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  • 1.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Enblad, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Artursson, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Patients with colorectal peritoneal metastases and high peritoneal cancer index may benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy2020In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 46, no 12, p. 2283-2291Article in journal (Refereed)
    Abstract [en]

    Background: Peritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI <= 20 treated with CRS and HIPEC to those having open-close/debulking procedure only.

    Methods: All patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004-2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI <= 20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking.

    Results: Of 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI <= 20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14-27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI <= 20 the median survival was 33 months (95%CI 30-39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4-10 months), no one survived >5years.

    Conclusion: Patients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken.

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    FULLTEXT01
  • 2.
    Bushati, M.
    et al.
    Catharina Hosp, Dept Surg, POB 1350, NL-5602 ZA Eindhoven, Netherlands;Univ Padua, Surg Clin 1, Dept Surg Oncol & Gastroenterol, Padua, Italy.
    Rovers, K. P.
    Catharina Hosp, Dept Surg, POB 1350, NL-5602 ZA Eindhoven, Netherlands.
    Sommariva, A.
    Veneto Inst Oncol IOV IRCCS, Unit Surg Oncol Esophagus & Digest Tract, Castelfranco Veneto, TV, Italy.
    Sugarbaker, P. H.
    MedStar Washington Hosp Ctr, Ctr Gastrointestinal Malignancies, 106 Irving St NW,Suite 3900, Washington, DC 20010 USA.
    Morris, D. L.
    St George Hosp, Dept Surg, Gray St Kogarah, Sydney, NSW 2217, Australia.
    Yonemura, Y.
    Kishiwada Tokushukai Hosp, Peritoneal Surface Malignancy Ctr, 4-27-1 Kamori Cho, Kishiwada, Osaka 5968522, Japan.
    Quadros, C. A.
    Sao Rafael Hosp, Surg Oncol Unit, Ave Sao Rafael 2152, BR-41253190 Salvador, BA, Brazil.
    Somashekhar, S. P.
    Manipal Hosp, Manipal Comprehens Canc Ctr, Dept Surg Oncol & Robot Surg, 98 HAL Airport Rd, Bengaluru 560017, Karnataka, India.
    Ceelen, W.
    Ghent Univ Hosp Belgium, Dept Gastrointestinal Surg, Ghent, Belgium.
    Dube, P.
    Univ Montreal, Hosp Maisonneuve Rosemont, Dept Surg, Montreal, PQ, Canada.
    Li, Y.
    Capital Med Univ, Beijing Shijitan Hosp, Dept Peritoneal Canc Surg, Beijing, Peoples R China.
    Verwaal, V. J.
    Aarhus Univ Hosp, Dept Surg, Norrebrogade 44, DK-8000 Aarhus, Denmark.
    Glehen, O.
    Hosp Civils Lyon, Dept Surg Oncol, Lyon, France;Lyon Sud Hosp, Lyon Fac Med, Lyon, France.
    Piso, P.
    Hosp Barmherzige Bruder, Dept Gen & Visceral Surg, Regensburg, Germany.
    Spiliotis, J.
    European Interbalkan Med Ctr, Thessaloniki, Greece.
    Teo, M. C. C.
    Natl Canc Ctr Singapore, Singapore, Singapore.
    Gonzalez-Moreno, S.
    Univ Texas MD Anderson Canc Ctr, Surg Oncol, Madrid, Spain.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Lehmann, K.
    Univ Hosp Zurich, Dept Visceral & Transplantat Surg, Zurich, Switzerland.
    Deraco, M.
    Fdn IRCCS Ist Nazl Tumori, Peritoneal Surface Malignancies Unit, Milan, Italy.
    Moran, B.
    Hampshire Hosp Fdn Trust, Peritoneal Malignancy Inst Basingstoke, Adelmaston Rd, Basingstoke RG24 9NA, Hants, England.
    de Hingh, I. H. J. T.
    Catharina Hosp, Dept Surg, POB 1350, NL-5602 ZA Eindhoven, Netherlands.
    The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI)2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 12, p. 1942-1948Article in journal (Refereed)
    Abstract [en]

    Background: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice.

    Methods: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and country wide practice.

    Results: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies.

    Conclusion: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

  • 3.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Akad Sjukhuset, S-75185 Uppsala, Sweden..
    A new technique to improve surgery for peritoneal colorectal metastases?2016In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 1, no 4, p. 263-264Article in journal (Other academic)
  • 4.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Esquivel, Jesus
    Beebe Healthcare, Div Surg Oncol, Lewes, DE USA..
    Larsen, Stein G.
    Oslo Univ Hosp, Dept Gastroenterol Surg, Sect Surg Oncol, N-0372 Oslo, Norway..
    Liauw, Winston
    UNSW Australia, St George & Sutherland Clin Sch, Sydney, NSW, Australia.;St George Hosp, Dept Med Oncol, Sydney, NSW, Australia..
    Alzahrani, Nayef A.
    St George Hosp, Dept Surg, Sydney, NSW, Australia..
    Morris, David L.
    St George Hosp, Dept Surg, Sydney, NSW, Australia..
    Kepenekian, Vahan
    Hosp Civils Lyon, Hosp Lyon Sud, Lyon, France.;Univ Lyon 1, CICLY, Lyon, France..
    Sourrouille, Isabelle
    Inst Gustave Roussy, Dept Surg, Villejuif, France..
    Dumont, Frederic
    Inst Cancerol lOuest, Dept Oncol Surg, St Herblain, France..
    Tuech, Jean-Jacques
    Ctr Hospitalo Univ Rouen, Dept Digest Surg, Rouen, France..
    Ceribelli, Cecilia
    Ctr Hospitalo Univ Archet II, Dept Surg, Nice, France..
    Doussot, Beranger
    Ctr Hosp Univ Dijon Bourgogne, Dept Digest Surg, Dijon, France..
    Sgarbura, Olivia
    Univ Montpellier, Canc Inst Montpellier, Dept Surg Oncol, Montpellier, France..
    Quenet, Francois
    Univ Montpellier, Canc Inst Montpellier, Dept Surg Oncol, Montpellier, France..
    Glehen, Olivier
    Hosp Civils Lyon, Hosp Lyon Sud, Lyon, France.;Univ Lyon 1, CICLY, Lyon, France..
    Fisher, Oliver M.
    St George Hosp, Dept Med Oncol, Sydney, NSW, Australia.;St George Hosp, Dept Surg, Sydney, NSW, Australia.;Notre Dame Univ, Sch Med, Sydney, NSW, Australia..
    Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study2023In: eClinicalMedicine, E-ISSN 2589-5370, Vol. 55, article id 101746Article in journal (Refereed)
    Abstract [en]

    Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM.

    Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed.

    Findings: Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy.

    Interpretation: Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting.

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    FULLTEXT01
  • 5.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Enblad, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Morris, David L.
    Univ New South Wales, Dept Surg, Sydney, NSW 2217, Australia..
    Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study2020In: World Journal of Gastrointestinal Oncology, E-ISSN 1948-5204, Vol. 12, no 5, p. 549-558Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment have never been investigated. AIM To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival. METHODS All patients with colorectal peritoneal metastases (1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a bi-institutional database (Uppsala and Sydney) were included in the study. Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs non-neutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for disease-free survival were implemented. RESULTS Two hundred and forty-six patients were identified - 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the non-neutropenia group (66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P = 0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02. Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio: 0.58, 95% confidence interval: 0.36-0.95, P = 0.03. CONCLUSION 13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity.

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  • 6.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sequential postoperative intraperitoneal chemotherapy for colorectal cancer with peritoneal metastases: a narrative review2021In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 12, p. S131-S135Article, review/survey (Refereed)
    Abstract [en]

    Sequential postoperative intraperitoneal chemotherapy (SPIC) is a chemotherapy abdominal infusion given as a postoperative adjuvant treatment for 6 months after cytoreductive surgery (CRS) for peritoneal surface malignancies. It has most commonly been used in conjunction with ovarian cancer where the SPIC treatment has been integrated with adjuvant systemic chemotherapy. This review investigates the role of SPIC in the setting of colorectal cancer with peritoneal metastases. The focus is on the CRS+SPIC combination treatment with no systemic chemotherapy component. Several cohort studies, several comparative studies, and one randomized trial have been reported with several important endpoints. The following aspects will be covered in this review: overall survival, disease-free survival, morbidity, quality-of-life, and cost-effectiveness. In comparison to systemic chemotherapy alone for isolated resectable colorectal peritoneal metastases, CRS+SPIC is superior concerning overall survival, has no difference in morbidity, is similar in quality-of-life, and SPIC is cast-effective. In comparison to HIPEC, results are conflicting in multivariate analysis; but in a univariate analysis HIPEC (most often combined with systemic adjuvant therapy) appears superior to SPIC alone (no systemic component). The future of SPIC is uncertain. However, a combination of HIPEC and SPIC +/- a systemic chemotherapy component is a possible direction to explore further.

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  • 7.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Considerations on the Selection Process for Cytoreductive Surgery and Hyperthermic IntraPeritoneal Chemotherapy for Colorectal Carcinomatosis Reply2015In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 262, no 2, p. e48-e49Article in journal (Refereed)
  • 8.
    Cashin, Peter H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy in Patients with Peritoneal Metastases from Colorectal Cancer: Aspects of loco-regional treatment outcome, patient selection, and chemo-sensitivity 2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Previously, peritoneal metastases(PM) from colorectal cancer(CRC) have been considered a terminal and generalised form of cancer. A new treatment strategy combining cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) has recently shown promising results. The aim of this thesis was to investigate different aspects of this treatment in order to optimise the treatment and to clarify its potential as a new treatment option. Treatment outcome, patient selection, method of IPC (hyperthermic intraperitoneal chemotherapy-HIPEC vs. sequential postoperative intraperitoneal chemotherapy-SPIC) and choice of drugs for IPC were the aspects covered in this thesis.

    The treatment outcome of CRS and IPC according to the median overall survival ranged from 24 to 34 months with 5-year overall survival ranging from 20 to 40% depending on the IPC treatment administered. Furthermore, the 5-year disease-free survival was impressive at 32% for patients receiving HIPEC. This establishes the curative potential of this treatment. Due to current inadequacies of radiological imaging, a score (Corep score) was developed for patient selection purposes. This score had a sensitivity of 80% and specificity of 100% in identifying patients with short cancer-specific survival after the treatment (<12 months). Further studies are needed to elucidate the clinical usefulness of the Corep score. HIPEC was associated with better survival than the SPIC method at similar morbidity and mortality rates, suggesting that HIPEC be the method of preference. Concerning the choice of drugs, the last study investigated the chemo-sensitivity of different PM tumour-types with a special focus on CRC. While CRC samples were generally more resistant, the ratio of the in vivo concentration compared to the ex vivo concentration giving a 50% tumour cell death showed that oxaliplatin had the best profile across all PM tumour types as well as for CRC. This needs further confirmation in a clinical trial.

    List of papers
    1. Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    Open this publication in new window or tab >>Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    2012 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed) Published
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

    Keywords
    HIPEC, Intraperitoneal chemotherapy, Colorectal cancer, Peritoneal carcinomatosis, Cytoreductive surgery, Recurrences
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-169544 (URN)10.1016/j.ejso.2012.03.001 (DOI)000304510600008 ()
    Available from: 2012-03-05 Created: 2012-03-02 Last updated: 2017-12-07Bibliographically approved
    2. Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    Open this publication in new window or tab >>Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    2012 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed) Published
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

    Keywords
    colorectal cancer, corep score, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, HIPEC, patient selection, serum tumour markers, peritoneal carcinomatosis, peritoneal metastases
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-169548 (URN)10.1097/SLA.0b013e318254f281 (DOI)000312261000038 ()
    Available from: 2012-03-05 Created: 2012-03-02 Last updated: 2017-12-07Bibliographically approved
    3. Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    Open this publication in new window or tab >>Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    2012 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

    Place, publisher, year, edition, pages
    Oxford University Press, 2012
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-165543 (URN)10.1093/annonc/mdr301 (DOI)000300733300016 ()21685413 (PubMedID)
    Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2017-12-08Bibliographically approved
    4. Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Open this publication in new window or tab >>Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Show others...
    2013 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 435-Article in journal (Refereed) Published
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-172441 (URN)10.1186/1471-2407-13-435 (DOI)000325079100001 ()
    Available from: 2012-04-10 Created: 2012-04-10 Last updated: 2017-12-07Bibliographically approved
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  • 9.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Dranichnikov, Faoz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland.
    Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy Treatment of Colorectal Peritoneal Metastases: Cohort Analysis of High Volume Disease and Cure Rate2014In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 110, no 2, p. 203-206Article in journal (Refereed)
    Abstract [en]

    Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) treatment of colorectal peritoneal metastases (PM) is an established treatment alternative. The study aim was, first, to investigate the outcome of high-volume disease defined by the peritoneal cancer index (PCI) 20; second, to report the long-term disease-free survival of patients with >5 years observation. Methods: Consecutive patients with colorectal PM from a prospective HIPEC database between 2004 and 2010 were included, 67 patients. Clinicopathological and outcome parameters were compared between low PCI (n = 40) and high PCI (n = 27). A subgroup analysis on patients with >5 years observation was performed (n = 32). Disease-free survival after 5 years defined cure. Results: Median overall survival (OS) was 28 months, low PCI-group 33 months versus high PCI-group 17 months (P = 0.03). Median OS of patients with complete CRS (n = 56) was 30 months, low PCI-group 37 months versus high PCI-group 27 months (P = 0.2), with 5-year survival of 31% and 21%, respectively. No difference in morbidity/mortality. The cure rate was 22% in the subgroup (7/32) and 28% in those with complete CRS (7/25). Two patients in the cured group had PCI 29 and 34. Discussion: Treatment of high-volume disease may result in long-term survival and even cure. The key is to reach a complete CRS. The overall cure rate is 22%. 

  • 10.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ehrsson, H
    Wallin, I
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis2013In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, no 3, p. 533-540Article in journal (Refereed)
    Abstract [en]

    Purpose

    Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has not previously been measured with a selective technique. The primary aims were to examine the pharmacokinetics of active cisplatin and its monohydrated complex (MHC) during HIPEC using a specific measuring technique, to compare cisplatin’s systemic absorption with oxaliplatin, and to compare active cisplatin levels to that of total platinum.

    Methods

    Ten patients treated with cytoreductive surgery and HIPEC (cisplatin 50 mg/m2,doxorubicin 15 mg/m2) were recruited. Blood and perfusate samples were drawn during and after HIPEC. Cisplatin analysis was conducted using liquid chromatography (LC) with post-column derivatization with diethyldithiocarbamate and compared with inductively coupled plasma-mass spectrometry (ICP-MS).

    Results

    The mean half-life (t1/2) of perfusate cisplatin was 18.4 min, with area under the time-concentration curve (AUC) 0–90 min of 2.87 mM·min and estimated 0–60 min of 2.45 mM·min. The absorption t1/2 was 9.0 min for cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active cisplatin increased in a linear manner by time of perfusion.

    Conclusions

    Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60 min does not significantly change the pharmacokinetics of cisplatin, and is therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS technique does not adequately reflect active cisplatin levels in the perfusate

  • 11.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Comparison of Prognostic Scores for Patients with Colorectal Cancer Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2013In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 20, no 13, p. 4183-4189Article in journal (Refereed)
    Abstract [en]

    Background. There are three prognostic scores for the cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer peritoneal metastases: the newly introduced COREP (colorectal peritoneal) score, the peritoneal surface disease severity score (PSDS), and the prognostic score (PS). The aim was to determine which prognostic score had the best prognostic value. Methods. Between 2006 and 2010, a total of 77 patients with peritoneal metastases fromcolorectal cancer underwent CRS/HIPEC treatment. The COREP, PSDS, and PS scores were successfully applied to 56 patients (73 %) having sufficient data. The end points were prediction of open-and-close cases (n = 9), R1 resections (n = 41), and survival of <12 months (n = 18). Area under the receiver operating characteristic curves (accuracy) was compared. Subgroup analysis was performed on patients not previously used for the development of the COREP score (n = 24). Multivariable logistic regressions of the three end points were performed as well as Cox regression for overall survival. Furthermore, COREP and peritoneal cancer index were compared. Results. For open-and-close case prediction, accuracy for the whole group (n = 56) and subgroup (n = 24) was 87 and 88 %, respectively for COREP; 66 and 77 % for PSDS; and 68 and 78 % for PS. For R1 resection prediction, accuracy was 81 and 81 %, 76 and 78 %, and 75 and 77 %, respectively. For prediction of survival of <12 months, accuracy was 83 and 84, 54 and 67 %, and 55 and 56 %, respectively. The COREP score was the only independent prognostic factor in all four multivariable analyses. A COREP score of >= 6 identified patients with poor survival more accurately than a PCI of >20. Conclusions. The COREP score predicted open-and-close cases, R1 resections, and poor survival better than PSDS and PS. COREP better identifies patients with poor survival than intraoperative PCI.

  • 12.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed)
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

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  • 13.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

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  • 14.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study2012In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed)
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

  • 15.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Response to comments on 'Cytoreductive surgery and intraperitoneal chemotherapy'2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 10, p. 1012-1012Article in journal (Refereed)
  • 16.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlsson, Henning
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 435-Article in journal (Refereed)
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

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  • 17.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala Canc Clin, Uppsala, Sweden..
    Spang, N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Syk, I.
    Skane Univ Hosp, Dept Surg, S-21428 Malmo, Sweden..
    Frodin, J. E.
    Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Torkzad, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial2016In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 53, p. 155-162Article in journal (Refereed)
    Abstract [en]

    Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).

  • 18.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lundberg, Lars Göran
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ejerblad, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Acquired haemophilia A and Kaposi's sarcoma in an HIV-negative, HHV-8-positive patient: a discussion of mechanism and aetiology2010In: Acta Haematologica, ISSN 0001-5792, E-ISSN 1421-9662, Vol. 124, no 1, p. 40-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acquired haemophilia A (AHA) is a rare bleeding disorder caused by an imbalance in the immune system leading to the production of factor VIII antibodies. In half of the cases, the underlying cause is not known. CLINICAL HISTORY: We report on a patient with AHA and Kaposi's sarcoma (KS), which is caused by the human herpes virus 8 (HHV-8). The patient presented with appendicitis and developed several severe post-operative haemorrhages. He spent 3 months in intensive care due to long and difficult infections. While recuperating on the ward, the patient developed KS in the lower extremities. He had a positive HHV-8 infection. DISCUSSION/CONCLUSION: Due to its latency and replication in the lymphoid system, HHV-8 is an ideal candidate for causing an imbalance in the immune system in susceptible patients. Our conclusion is that AHA was caused or prompted by the HHV-8 infection. Since HHV-8 viral infection is often subclinical, viral testing might be an important tool in acquired haemophilia diagnostics even when viral symptoms are absent.

  • 19.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala Canc Clin, Uppsala, Sweden.
    Syk, I.
    Lund Univ, Sect Surg, Dept Clin Sci, Malmo, Sweden.
    Frodin, J. E.
    Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 7, p. 983-990Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

  • 20.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andréasson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Appendiceal Adenocarcinoids with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy: a retrospective study of in vitro drug sensitivity and survival2011In: Clinical Colorectal Cancer, ISSN 1533-0028, Vol. 10, no 2, p. 108-112Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to present results on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of appendiceal adenocarcinoid (MC) with peritoneal carcinomatosis (PC), to assess drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report any discordant histopathology.

    Methods: Ten patients were treated with CRS and HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data were recorded and matched with potential prognostic indicators. Drug sensitivity was assessed with short-term fluorometric microculture cytotoxicity assay and compared with peritoneal metastases from CRC.

    Results: Patients with completeness of cytoreduction score (CC) 1 (16.4 months). In the CC 1 group. For standard drugs, tumor cells from MC and CRC were equally sensitive; except for docetaxel, to which MC was more sensitive than CRC.

    Conclusion: The CC-score correlated with overall survival. Candidates for this type of treatment should be referred early for evaluation in order to reach a better CC score. Drugs used for CRC also seem adequate for treatment of MC, although other drugs, eg, docetaxel, might be more active.

  • 21.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Palmer, Gabriella Jansson
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Asplund, Dan
    Univ Gothenburg, Sahlgrenska Univ Hosp Ostra, Sahlgrenska Acad, Dept Surg,Inst Clin Sci, Gothenburg, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Syk, Ingvar
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden.
    Peritoneal mesothelioma in Sweden: A population-based study2019In: Cancer Medicine, E-ISSN 2045-7634, Vol. 8, no 14, p. 6468-6475Article in journal (Refereed)
    Abstract [en]

    The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.

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  • 22.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sugarbaker, Paul H.
    Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, USA.
    Hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases: lessons learned from PRODIGE 72021In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 12, no S1, p. S120-S128Article, review/survey (Refereed)
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  • 23.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Söderström, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Blom, Kristin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Artursson, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Andersson, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ex vivo assessment of chemotherapy sensitivity of colorectal cancer peritoneal metastases2023In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 110, no 9, p. 1080-1083Article in journal (Refereed)
    Abstract [en]

    Patients with peritoneal metastasis from colorectal cancer (PMCRC) may have a chance of cure when treated with cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC)1–5.

    Choice of chemotherapy for HIPEC has been based on knowledge of its systemic effects, pharmacokinetics, technical feasibility, hyperthermic efficacy enhancement, and tolerance6–8. Selection of cancer drugs for treatment based on phenotypical assessment of patient cancer cell drug sensitivity ex vivo is one approach to personalized cancer treatment. One technique for this is the fluorometric microculture cytotoxicity assay (FMCA) that has been used in drug development and for the development of personalized cancer medicine9–16.

    This study investigated whether ex vivo assessment of drug sensitivity by the FMCA provides predictive information in terms of peritoneal recurrence-free survival (PRFS) and overall survival (OS) in patients treated with CRS and HIPEC for isolated PMCRC.

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  • 24. Castro, J
    et al.
    Ericsson, C
    Cashin, Peter H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Preliminary Finding: Detection of Circulating Cancer Cells in Blood from a Patient with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy2012In: Surgery: Current Research, Vol. 2, no 3Article in journal (Refereed)
  • 25.
    Dranichnikov, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Sciences, Department of Colorectal Surgery, Uppsala University Hospital, S-751 85, Uppsala, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Sciences, Department of Colorectal Surgery, Uppsala University Hospital, S-751 85, Uppsala, Sweden..
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Sciences, Department of Colorectal Surgery, Uppsala University Hospital, S-751 85, Uppsala, Sweden..
    Morbidity following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases with or without early postoperative intraperitoneal chemotherapy: A propensity score matched study2022In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 48, no 7, p. 1598-1605Article in journal (Refereed)
    Abstract [en]

    Background: Combining hyperthermic intraperitoneal chemotherapy (HIPEC) treatment with early postoperative intraperitoneal chemotherapy (EPIC) may increase postoperative morbidity. This study aims to investigate postoperative morbidity after HIPEC+EPIC compared with HIPEC alone in patients with peritoneal metastases (PM).

    Materials and methods: This is a retrospective propensity score matched cohort study. All patients undergoing PM treatment at Uppsala University Hospital between February 2004 and December 2014 were included. Propensity score matching with a 1:1 ratio was performed using sex, primary tumor site, preoperative chemotherapy, peritoneal cancer index, completeness of cytoreduction score, and HIPEC regimen. Length of hospital stay, morbidity, reoperation rate, and readmission rate within 6 months were selected as endpoints.

    Results: A total of 390 consecutive patients were divided in two arms: HIPEC+EPIC (n = 115) and HIPEC alone (n = 275). The propensity score matching (n = 190) was successful with balanced covariates: 95 patients/arm. The length of stay (LOS) was longer in the HIPEC + EPIC group in the total cohort (30 vs 24 days, p < 0.001), with a trend towards significance in the propensity matched group (29 vs 25 days, p = 0.062). No other differences in endpoints were found.

    Conclusion: HIPEC+EPIC is associated with a prolonged hospital stay, but with no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission.

  • 26.
    Dranichnikov, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Readmissions after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy-a national population-based study2020In: World Journal of Surgical Oncology, E-ISSN 1477-7819, Vol. 18, no 1, article id 67Article in journal (Refereed)
    Abstract [en]

    Background Comprehensive readmission morbidity studies after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are scarce. This study aimed to investigate readmissions and in-hospital morbidity after CRS and HIPEC. Methods The national in-hospital patient register was used to identify patients via the HIPEC ICD code JAQ10 2004-2014. Data were retrieved from the index CRS/HIPEC treatment and from all HIPEC-related readmissions within 6 months. Univariate/multivariate logistical analyses were performed to identify risk factors for reinterventions and readmissions. Results A total of 519 patients (mean age 56 years) had a mean hospital stay of 27 days. Within 6 months, 150 readmissions for adverse events were observed in 129 patients (25%) with 67 patients requiring an intervention (13%). Totally 179 patients (34%) required a reintervention during the first 6 months with 85 (16%) requiring a reoperation. Of these 179 patients, 83 patients (46%) did not undergo the intervention at the HIPEC centre. Gastric resection was the only independent risk factor for in-hospital intervention, and advanced age for readmission. Conclusion Morbidity causing HIPEC-related readmission was higher than expected with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and high age are independent predictors of morbidity and readmission.

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  • 27.
    Dranichnikov, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Coagulopathy and Venous Thromboembolic Events Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2021In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 28, no 12, p. 7772-7782Article in journal (Refereed)
    Abstract [en]

    Background Coagulopathy after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recognized but few details have been studied.

    Objectives The aim of this study was to investigate changes in coagulation biomarkers and their predictive ability for venous thromboembolism (VTE).

    Methods Patients undergoing CRS and HIPEC at Uppsala University Hospital, Sweden, from 2004 to 2014 were included in a prospective study of coagulation biomarkers. Prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, D-dimer, and platelets were sampled on postoperative days 1, 2, 5, and 10. Logistic regression analysis was used to evaluate predictive capacity for coagulation-related complications.

    Results Overall, 380 patients were included (214 females, mean age 56 years); 38 patients had a history of thromboembolism and 57 were active smokers. Mean perioperative blood loss was 1228 mL and 231 (61%) received perioperative blood transfusions. PT-INR and APTT were elevated directly after surgery but returned to normal levels on postoperative day 5. Conversely, fibrinogen, platelet count, D-dimer, and antithrombin increased by postoperative day 5 and continued to increase up to day 10. There were 23 radiologically verified cases of VTE within 6 months. The multivariate analysis identified a completeness of cytoreduction score of 2-3 (p = 0.047) and day 2 D-dimer (p = 0.0082) as independent risk factors for postoperative VTE.

    Conclusion Significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery and elevated D-dimer on day 2 were independent risk factors for postoperative VTE.

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  • 28.
    Dranichnikov, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala Univ Hosp, Dept Surg Sci, Dept Colorectal Surg, Uppsala, Sweden..
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala Univ Hosp, Dept Surg Sci, Dept Colorectal Surg, Uppsala, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala Univ Hosp, Dept Surg Sci, Dept Colorectal Surg, Uppsala, Sweden..
    Coagulopathy and Venous Thromboembolic Events Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: ASO Visual Abstract2021In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 28, no SUPPL 3, p. 440-440Article in journal (Other academic)
  • 29.
    Dranichnikov, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Science, Section of Colorectal Surgery, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    Semenas, Egidijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Science, Section of Colorectal Surgery, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgical Science, Section of Colorectal Surgery, Uppsala University Hospital, 751 85, Uppsala, Sweden.
    The Impact on Postoperative Outcomes of Intraoperative Fluid Management Strategies During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2023In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 49, no 8, p. 1474-1480Article in journal (Refereed)
    Abstract [en]

    Background 

    The impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to investigate the impact of intraoperative fluid management strategy on postoperative outcomes and survival focusing on postoperative hemorrhage. 

     Methods 

    509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004-2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluids management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed.

     Results

    The pre-GDT group received higher intraoperative fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p<0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p=0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10-3.10, p=0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p=0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64-2.95, p=0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p=0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p<0.0001). Survival did not differ between the groups.

    Conclusion

    While GDT management increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did.  

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  • 30.
    Duraj, Frans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal and hepatic metastases: a case-control study2013In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 4, no 4Article in journal (Other academic)
    Abstract [en]

    Background:

    Concomitant treatment of colorectal peritoneal metastases (PM) and hepatic metastases (HM) remains controversial. This study compares the cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal metastases (PM) with the CRS/IPC/hepatic resection treatment of colorectal PM and HM.

    Methods:

    All patients from a prospective PM registry at the Uppsala institution treated concomitantly for PM/HM with CRS/IPC/hepatic resections were included in a PM/HM-group, n=11. They were matched 1:2 with patients from the registry being treated only for PM with CRS/IPC, n=22. Overall survival (OS), disease-free survival (DFS), morbidity, mortality, and recurrences were compared.

    Results:

    The PM/HM-group had median OS of 15 months (95% CI: 6-46 months) and the PM-group had a median OS of 34 months (95% CI: 19-37 months), P=0.2. The DFS was 10 months (95% CI: 3-14 months) and 24 months (95% CI: 10-32 months) respectively, P=0.1. Morbidity was 27% in both groups and one postoperative death in the PM/HM-group. Currently, 1/10 (10%) patients with an R1 resection are disease-free in the PM/HM group while 9/20 (45%) are disease-free in the PM group (P=0.05).

    Conclusions:

    Concomitant treatment of PM and HM with CRS/IPC/hepatic resections is feasible with no significant increase in morbidity compared to CRS/IPC. The risk of recurrences is higher in the PM/HM group with a tendency towards worse DFS.

  • 31.
    Enblad, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Prognostic scores for colorectal cancer with peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy2018In: International Journal of Hyperthermia, ISSN 0265-6736, E-ISSN 1464-5157, Vol. 34, no 8, p. 1390-1395Article in journal (Refereed)
    Abstract [en]

    Background: Selecting colorectal patients for HIPEC-surgery needs improvement. The study aim was to improve the colorectal peritoneal score (COREP) and to compare it with three other scores: peritoneal-surface disease-severity score (PSDS), colorectal-peritoneal metastases prognostic-surgical-score (COMPASS), and the CEA/PCI ratio.

    Method: Twelve preoperative factors were chosen to evaluate for COREP score modification. Criteria from logistical analyses were set to qualify for the modified COREP score (mCOREP). Odds ratios were used to assign score points for the eligible factors with open/close laparotomy prediction as endpoint. mCOREP was applied internally and compared with the original COREP, PSDS, COMPASS, and CEA/PCI ratio. Odds ratios, hazard ratios, and Kaplan-Meier curves were used for comparison.

    Results: Seven factors qualified for mCOREP: CEA, CA 19-9, CA-125, C-reactive protein, albumin, platelet count and signet-cell histology. mCOREP was superior to the original COREP. mCOREP and COMPASS scores were the only scores with independent prognostic value. The mCOREP had the best discriminatory ability between its prognostic groupings. mCOREP 11+had 9months survival with half of patients being open/close surgery.

    Conclusion: The mCOREP has successfully been simplified while still improving its prognostic ability. The mCOREP and COMPASS scores have independent prognostic value. Patients with mCOREP 11+may not benefit from treatment.

  • 32.
    Farrokhnia, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Benoni, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Validating the PSOGI classification of peritoneal disease from non-carcinoid epithelial appendiceal neoplasms in the curative and palliative setting: an observational retrospective study2022In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 13, no 2, p. 859-870Article in journal (Refereed)
    Abstract [en]

    Background: Few studies on long-term survival have been published since the new updated pseudomyxoma peritonei (PMP) classification was published in 2016. The aim was to investigate long-term survival according to the Peritoneal Surface Oncology Group International (PSOGI) classification and compare prognostic factors. Methods: From Uppsala University Hospital, consecutive patients referred for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from 2004 to 2017 with peritoneal disease from non-carcinoid mucinous epithelial appendiceal neoplasms were included in the study. The peritoneal disease was divided into four groups: mucin only, low-grade mucinous carcinoma peritonei (MCP-1), high-grade (MCP-2), and high-grade with signet ring cells (MCP-3). Survival curves were rendered, and prognostic factors were compared. Results: The study included 223 patients: 36 with mucin only, 112 with MCP-1, 70 with MCP-2, and 5 with MCP-3. Thirty-eight patients had a palliative debulking or open/close procedure. The 5-and 10-year overall survival was 97% and 97% for mucin only, 83% and 70% for MCP-1, 69% and 49% for MCP-2, with no patients still under follow-up after 5 years in the MCP-3 group. In a multivariable analysis, completeness of cytoreduction (CC) score 2-3 and PSOGI class MCP-3 were significantly associated with lower survival. The 5-year overall survival in the palliative setting was 40% vs. 44% (MCP-1 vs. MCP-2, P>0.05) with median survival 51 vs. 53 months, respectively. Conclusions: The PSOGI classification of PMP provides a solid differentiation of prognostic groups after CRS/HIPEC treatment, but not in the palliative setting.

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  • 33.
    Fisher, Oliver M.
    et al.
    St George Hosp, Dept Surg, Sydney, NSW, Australia.;UNSW Australia, St George & Sutherland Clin Sch, Kogarah, NSW, Australia.;Notre Dame Univ, Sch Med, Sydney, NSW, Australia..
    Brown, Chris
    NHMRC Clin Trials Ctr, Sydney, NSW, Australia..
    Esquivel, Jesus
    Frederick Mem Hosp, Div Surg Oncol, Frederick, MD USA..
    Larsen, Stein G.
    Oslo Univ Hosp, Norwegian Radium Hosp, Dept Surg Oncol, Oslo, Norway..
    Liauw, Winston
    UNSW Australia, St George & Sutherland Clin Sch, Kogarah, NSW, Australia.;St George Hosp, Dept Med Oncol, Sydney, NSW, Australia..
    Alzahrani, Nayef A.
    St George Hosp, Dept Surg, Sydney, NSW, Australia.;King Abdul Aziz Med City, Minist Natl Guard Hlth Affairs, Dept Surg, Riyadh, Saudi Arabia..
    Morris, David L.
    St George Hosp, Dept Surg, Sydney, NSW, Australia..
    Kepenekian, Vahan
    Hosp Civils Lyon, Hop Hosp Lyon Sud, Dept Digest Surg, Lyon, France.;Univ Lyon 1, EA CICLY 3738, Lyon, France..
    Sourrouille, Isabelle
    Inst Gustave Roussy, Dept Surg, Villejuif, France..
    Dumont, Frederic
    Inst Cancerol Ouest Rene Gauducheau, Dept Oncol Surg, St Herblain, France..
    Tuech, Jean-Jacques
    Ctr Hosp Univ Rouen, Dept Digest Surg, Rouen, France..
    Ceribelli, Cecilia
    Ctr Hosp Univ Archet II, Dept Surg, Nice, France..
    Doussot, Beranger
    Ctr Hosp Univ Dijon Bourgogne, Dept Digest Surg, Dijon, France..
    Sgarbura, Olivia
    Univ Montpellier, Inst Reg Canc Montpellier, INSERM, IRCM,Inst Rech Cancerol Montpellier,U1194, Montpellier, France.;Inst Reg Canc Montpellier, Dept Chirurg Oncol, Montpellier, France..
    Alhosni, Mohammed
    Sultan Qaboos Univ Hosp SQUH, Dept Surg, Surg Oncol Div, Muscat, Oman. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. Akad Sjukhuset, Dept Surg, Uppsala, Sweden. St George Hosp, Dept Surg Upper Gastrointestinal & Hepatobiliary, Gray St, Sydney, Australia..
    Quenet, Francois
    Inst Reg Canc Montpellier, Dept Chirurg Oncol, Montpellier, France..
    Glehen, Olivier
    Hosp Civils Lyon, Hop Hosp Lyon Sud, Dept Digest Surg, Lyon, France.;Univ Lyon 1, EA CICLY 3738, Lyon, France..
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Department of Surgery, Akademiska Sjukhuset, Uppsala, Sweden..
    Hyperthermic intraperitoneal chemotherapy in colorectal cancer2024In: BJS Open, E-ISSN 2474-9842, Vol. 8, no 3, article id zrae017Article in journal (Refereed)
    Abstract [en]

    Background: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients.

    Patients and Methods: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed.

    Results: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period.

    Conclusions: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

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  • 34.
    Frühling, Petter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Dranichnikov, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Enblad, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Oxaliplatin-based hyperthermic intraperitoneal chemotherapy with single drug versus multiple drug treatment for colorectal cancer with peritoneal metastases: an observational cohort study2021In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 12, no 2, p. 516-526Article in journal (Refereed)
    Abstract [en]

    Background: Long-term survival for selected patients with peritoneal metastases (PM) from colorectal cancer (CRC) is possible when treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The objective of this study was to compare three different oxaliplatin-based (OX)-HIPEC regimens. Primary end-point was disease-free survival (DFS), and secondary endpoints, morbidity and overall survival (OS).

    Methods: This is a retrospective study of all patients with colorectal PM treated with CRS and HIPEC between 2004 and 2015 from the prospectively maintained Uppsala HIPEC database. One hundred and thirty-three patients were identified. Three HIPEC regimens were included: OX-HIPEC, OX-HIPEC + post-operative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil (5-FU), and oxaliplatin-irinotecan-based (OXIRI)-HIPEC. Multivariable Cox regression for DFS was performed.

    Results: Sixty-one patients received OX-HIPEC, 24 patients received OX-HIPEC + 5-FU EPIC, and 48 patients received OXIRI-HIPEC. The DFS for the OX-HIPEC group was 10.5 months, OX-HIPEC + EPIC 11.9 months, and OXIRI-HIPEC 13.4 months (OX-HIPEC vs. OXIRI HIPEC, P=0.049). The morbidity and OS did not differ between the groups. In the multivariable analysis, low peritoneal cancer index (PCI), absence of liver metastases, low completeness of cytoreduction (CC) score, and multiple drug (EPIC or OXIRI) HIPEC regimen were independent prognostic factors for DFS.

    Conclusions: This study showed improved DFS with an intensification of HIPEC by adding irinotecan or EPIC compared to oxaliplatin alone without an increase in morbidity or mortality.

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  • 35.
    Ghanipour, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ Hosp, Uppsala, Sweden.
    Jansson Palmer, Gabriella
    Karolinska Univ Hosp, Dept Pelv Canc, GI Oncol & Colorectal Surg Unit, Stockholm, Sweden..
    Nilsson, Per J.
    Karolinska Univ Hosp, Dept Pelv Canc, GI Oncol & Colorectal Surg Unit, Stockholm, Sweden..
    Nordenvall, Caroline
    Karolinska Univ Hosp, Dept Pelv Canc, GI Oncol & Colorectal Surg Unit, Stockholm, Sweden..
    Frödin, Jan-Erik
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden..
    Bexe Lindskog, Elinor
    Sahlgrens Univ Hosp, Inst Clin Sci, Dept Surg, Gothenburg, Sweden..
    Asplund, Dan
    Sahlgrens Univ Hosp, Inst Clin Sci, Dept Surg, Gothenburg, Sweden..
    Swartling, Torbjörn
    Sahlgrens Univ Hosp, Inst Clin Sci, Dept Surg, Gothenburg, Sweden..
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ Hosp, Uppsala, Sweden.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ Hosp, Uppsala, Sweden.
    Syk, Ingvar
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Malmö, Sweden..
    Verwaal, Victor
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Malmö, Sweden..
    Brändstedt, Jenny
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Malmö, Sweden..
    Cashin, Peter H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ Hosp, Uppsala, Sweden.
    Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer: A phase I and III open label randomized controlled registry-based clinical trial protocol2024In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 3, article id e0294018Article in journal (Refereed)
    Abstract [en]

    Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

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  • 36.
    Graf, Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Enblad, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Terman, Alexei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Prognostic Impact of BRAF and KRAS Mutation in Patients with Colorectal and Appendiceal Peritoneal Metastases Scheduled for CRS and HIPEC2020In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 27, no 1, p. 293-300Article in journal (Refereed)
    Abstract [en]

    Background

    KRAS and BRAF mutations are prognostic and predictive tools in metastatic colorectal cancer, but little is known about their prognostic value in patients scheduled for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Therefore, we analyzed the prognostic impact of KRAS and BRAF mutations in patients with peritoneal metastases scheduled for CRS and HIPEC.

    Patients and Methods

    In a consecutive series of 399 patients scheduled for CRS and HIPEC between 2009 and 2017, 111 subjects with peritoneal metastases from primaries of the appendix, colon, or rectum were analyzed for KRAS mutation and 92 for BRAF mutation.

    Results

    Mutation in KRAS was present in 51/111 (46%), and mutated BRAF was found in 10/92 (11%). There was no difference in overall survival between KRAS mutation tumors and KRAS wild type, whereas BRAF mutation was associated with short survival. No subject with BRAF mutation survived 2 years. On multivariate analysis, completeness of cytoreduction score (CCS, p = 0.000001), presence of signet cell differentiation (p = 0.000001), and BRAF mutation (p = 0.0021) were linked with poor prognosis.

    Conclusions

    BRAF mutation is a marker of poor prognosis in patients with appendiceal and colorectal peritoneal metastases scheduled for CRS and HIPEC, whereas survival outcome in subjects with mutated KRAS does not differ from wild-type KRAS. This finding suggests that those with BRAF mutation should be considered for alternative treatment options.

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  • 37.
    Graf, Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ, Akad Sjukhuset, Inst Surg Sci, Dept Surg, SE-75185 Uppsala, Sweden..
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ, Akad Sjukhuset, Inst Surg Sci, Dept Surg, SE-75185 Uppsala, Sweden..
    Birgisson, Helgi
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ, Akad Sjukhuset, Inst Surg Sci, Dept Surg, SE-75185 Uppsala, Sweden..
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Uppsala Univ, Akad Sjukhuset, Inst Surg Sci, Dept Surg, SE-75185 Uppsala, Sweden..
    Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal Cancer-An Overview of Current Status and Future Perspectives2024In: Cancers, ISSN 2072-6694, Vol. 16, no 2, article id 284Article, review/survey (Refereed)
    Abstract [en]

    Simple Summary The concept of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy perfusion for the treatment of colorectal cancer peritoneal metastases has been debated based on the results of recent controlled trials. In this review, we describe the development of this "package" treatment and discuss various aspects of the selection and indications, as well as future fields of research.Abstract Peritoneal metastases (PM) are observed in approximately 8% of patients diagnosed with colorectal cancer, either synchronously or metachronously during follow-up. PM often manifests as the sole site of metastasis. PM is associated with a poor prognosis and typically shows resistance to systemic chemotherapy. Consequently, there has been a search for alternative treatment strategies. This review focuses on the global evolution of the combined approach involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of PM. It encompasses accepted clinical guidelines, principles for patient selection, surgical and physiological considerations, biomarkers, pharmacological protocols, and treatment outcomes. Additionally, it integrates the relevant literature and findings from previous studies. The role of CRS and HIPEC, in conjunction with other therapies such as neoadjuvant and adjuvant chemotherapy, is discussed, along with the management of patients presenting with oligometastatic disease. Furthermore, potential avenues for future development in this field are explored.

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  • 38.
    Kozman, Mathew A.
    et al.
    St George Hosp, Dept Surg, Hepatobiliary & Surg Oncol Unit, Kogarah, NSW, Australia.;St George Hosp, Canc Care Ctr, Kogarah, NSW, Australia..
    Fisher, Oliver M.
    St George Hosp, Dept Surg, Hepatobiliary & Surg Oncol Unit, Kogarah, NSW, Australia.;Univ New South Wales, St George Hosp Clin Sch, Sydney, NSW, Australia.;Univ Notre Dame, Sch Med, Sydney, NSW, Australia..
    Liauw, Winston
    St George Hosp, Canc Care Ctr, Kogarah, NSW, Australia.;Univ New South Wales, St George Hosp Clin Sch, Sydney, NSW, Australia..
    Morris, David L.
    St George Hosp, Dept Surg, Hepatobiliary & Surg Oncol Unit, Kogarah, NSW, Australia.;Univ New South Wales, St George Hosp Clin Sch, Sydney, NSW, Australia..
    Cashin, Peter H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Akad Sjukhuset, Uppsala, Sweden.
    External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy2023In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 128, no 7, p. 1150-1159Article in journal (Refereed)
    Abstract [en]

    Background and Objectives

    Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy.

    Methods

    Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open–close laparotomy—those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility—those who underwent open–close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS).

    Results

    Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open–close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open–close prediction was 0.78 (95% confidence interval, CI: 0.68–0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52–0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination.

    Conclusion

    While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

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  • 39.
    Liu, Yang
    et al.
    NPO Support Peritoneal Surface Malignancy Treatme, Kyoto, Japan;Kishiwada Tokushukai Hosp, Peritoneal Disseminat Ctr, Osaka, Japan.
    Yonemura, Yutaka
    NPO Support Peritoneal Surface Malignancy Treatme, Kyoto, Japan;Kishiwada Tokushukai Hosp, Peritoneal Disseminat Ctr, Osaka, Japan;Kusatsu Gen Hosp, Peritoneal Disseminat Ctr, Shiga, Japan.
    Levine, Edward A.
    Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA.
    Glehen, Olivier
    Hosp Civils Lyon, Ctr Hosp Univ Lyon Sud, Pierre, France.
    Goere, Diane
    Inst Gustave Roussy Canc Ctr, Villejuif, France.
    Elias, Dominique
    Inst Gustave Roussy Canc Ctr, Villejuif, France.
    Morris, David L.
    Univ New South Wales, St George Hosp, Sydney, NSW, Australia.
    Sugarbaker, Paul H.
    Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
    Tuech, Jean J.
    Ctr Hosp Rouen, Rouen, France.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Spiliotis, John D.
    Metaxa Canc Mem Hosp, Dept Surg Oncol, Piraeus, Greece.
    de Hingh, Ignace
    Catharina Hosp, Eindhoven, Netherlands.
    Ceelen, Wim
    Ghent Univ Hosp, Dept Gastrointestinal Surg, Ghent, Belgium.
    Baumgartner, Joel M.
    Univ Calif San Diego, Div Surg Oncol, Moores Canc Ctr, San Diego, CA 92103 USA.
    Piso, Pompiliu
    Krankenhaus Barmherzige Brueder Regensburg, Regensburg, Germany.
    Katayama, Kanji
    Univ Fukui, Med Sch Hosp, Canc Care Promot Ctr, Fukui, Japan.
    Deraco, Marcello
    Natl Canc Inst, Dept Surg, Milan, Italy.
    Kusamura, Shigeki
    Natl Canc Inst, Dept Surg, Milan, Italy.
    Pocard, Marc
    Hop Lariboisiere, AP HP, Paris, France.
    Quenet, Francois
    Ctr Val DAurelle, Montpellier, France.
    Fushita, Sachio
    Kanazawa Univ, Kanazawa Univ Hosp, Dept Surg, Kanazawa, Ishikawa, Japan.
    Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience2018In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 25, no 5, p. 1184-1192Article in journal (Refereed)
    Abstract [en]

    The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA). A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC. Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS. The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

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  • 40.
    Mercier, Frederic
    et al.
    Univ Montreal, Dept Surg Oncol, CHU Montreal, 1000 St Denis, Montreal, PQ H2X 0C1, Canada.;Univ Lyon, Hosp Civils Lyon, Dept Surg Oncol, CHU Lyon Sud, Lyon, France.
    Passot, Guillaume
    Univ Lyon, Hosp Civils Lyon, Dept Surg Oncol, CHU Lyon Sud, Lyon, France.;Lyon 1 Univ, EMR 37 38, Lyon, France.
    Bonnot, Pierre-Emmanuel
    Jean Mermoz Hosp, Dept Digest Surg, Lyon, France.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ceelen, Wim
    Ghent Univ Hosp, Dept Gastrointestinal Surg, Ghent, Belgium.
    Decullier, Evelyne
    Hosp Civils Lyon, Unite Rech Clin, Pole Sante Publ, Lyon, France.
    Villeneuve, Laurent
    Lyon 1 Univ, EMR 37 38, Lyon, France.;Hosp Civils Lyon, Unite Rech Clin, Pole Sante Publ, Lyon, France.
    Walter, Thomas
    Univ Lyon, Hosp Civils Lyon, Dept Gastroenterol & Oncol, Edouard Herriot Hosp, Lyon, France.
    Levine, Edward A.
    Wake Forest Sch Med, Dept Gen Surg, Sect Surg Oncol, Winston Salem, NC 27101 USA.
    Glehen, Olivier
    Univ Lyon, Hosp Civils Lyon, Dept Surg Oncol, CHU Lyon Sud, Lyon, France.;Lyon 1 Univ, EMR 37 38, Lyon, France.
    An International Registry of Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2022In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 46, no 6, p. 1336-1343Article in journal (Refereed)
    Abstract [en]

    Purpose Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry.

    Methods A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed.

    Results The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p < 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications.

    Conclusion CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology.

  • 41.
    Sand, Olivia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Andersson, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Arakelian, Erebouni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Semenas, Egidijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Severe pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are common and contribute to decreased overall survival.2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 12, article id e0261852Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Extensive abdominal surgery is associated with the risk of postoperative pulmonary complications. This study aims to explore the incidence and risk factors for developing postoperative pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and to analyze how these complications affect overall survival.

    METHODS: Data were collected on 417 patients undergoing surgery between 2007 and2017 at Uppsala University Hospital, Sweden. Postoperative pulmonary complications were graded according to the Clavien-Dindo classification system where Grade ≥ 3 was considered a severe complication. A logistic regression analysis was used to analyze risk factors for postoperative pulmonary complications and a Cox proportional hazards model to assess impact on survival.

    RESULTS: Seventy-two patients (17%) developed severe postoperative pulmonary complications. Risk factors were full thickness diaphragmatic injury and/or diaphragmatic resection [OR 5.393, 95% CI 2.924-9.948, p = < 0.001]. Severe postoperative pulmonary complications, in combination with non-pulmonary complications, contributed to decreased overall survival [HR 2.285, 95% CI 1.232-4.241, p = 0.009].

    CONCLUSIONS: Severe postoperative pulmonary complications were common and contributed to decreased overall survival. Full thickness diaphragmatic injury and/or diaphragmatic resection were the main risk factors. This finding emphasizes the need for further research on the mechanisms behind pulmonary complications and their association with mortality.

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  • 42.
    Soucisse, Mikael L.
    et al.
    Univ Montreal, Dept Surg, Hop Maisonneuve Rosemont, 5415 Boul Assompt, Montreal, PQ H1T 2M4, Canada..
    Fisher, Oliver
    Univ New South Wales, Dept Surg, St George Hosp, Sydney, NSW, Australia..
    Liauw, Winston
    Univ New South Wales, Dept Med Oncol, St George Hosp, Sydney, NSW, Australia..
    Ghanipour, Lana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without early post-operative intraperitoneal chemotherapy for appendix neoplasms with peritoneal metastases: A propensity score analysis2021In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 47, no 1, p. 157-163Article in journal (Refereed)
    Abstract [en]

    Introduction: Early post-operative intraperitoneal chemotherapy (EPIC) can be used after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with resectable peritoneal metastases (PM). Whether EPIC adds any benefit is debatable.

    Methods: We performed a retrospective case-control analysis of patients with PM of appendiceal origin treated by CRS + HIPEC +/- EPIC at Uppsala University Hospital between 2004 and 2012. The 206 patients were divided into two groups depending on if they received EPIC or not. The two groups were propensity-matched with a 1:1 ratio. The patients in the EPIC group were mostly operated in the first three years of the unit's experience.

    Results: After matching, 76 patients were left in each group. The groups were similar, except for the proportion of histological subtypes (p = 0.021) and chemotherapy agents used for HIPEC (0.017). Survival outcomes were stratified by histology. The patients who received EPIC had a longer hospital and ICU length of stay (15.71 vs 14.28 days, p = 0.049), (1.45 vs 1.05 days, p = 0.002), respectively. Post-operative complications were similar in both groups. Overall Survival (OS) and recurrence-free survival (RFS) did not differ for the patients with low-grade histology. The patients with high-grade tumors who received EPIC had a significantly worse OS (p = 0.0088) while having the same RFS as the patients who did not receive EPIC.

    Conclusion: Our results suggest there is no benefit of EPIC in patients with advanced appendiceal tumors while increasing hospital and ICU length of stays. A suboptimal group matching might influence our results. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  • 43.
    Söderqvist, Erik V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Surgical treatment of rectovaginal fistula-predictors of outcome and effects on quality of life2022In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 37, no 7, p. 1699-1707Article in journal (Refereed)
    Abstract [en]

    Purpose

    To determine the results after rectovaginal fistula (RVF) repair and find predictors of outcome. Primary objective was fistula healing. Secondary outcomes were morbidity and patient health-related quality of life (HRQoL).

    Method

    An observational study of 55 women who underwent RVF repair including both local procedures and tissue transposition 2003-2018 was performed. Baseline patient and fistula characteristics were registered, combined with a prospective HRQoL follow-up and a general questionnaire describing fistula symptoms.

    Results

    Healing rate after index surgery was 25.5% (n = 14) but the final healing rate was 67.3% (n = 37). Comparing the etiologies, traumatic fistulas (iatrogenic and obstetric) had the highest healing rates after index surgery (n = 11, 45.9%) and after repeated operations at final follow-up (n = 22, 91.7%) compared with fistulas of inflammatory fistulas (Crohn's disease, cryptoglandular infection, and anastomotic leakage) that had inferior healing rates after both index surgery (n = 7, 7.1%) and at final follow-up (n = 13, 46.4%). Fistulas of the category others (radiation damage and unknown etiology) included a small amount of patients with intermediate results at both index surgery (n = 1, 33.3%) and healing rate at last follow-up (n = 2, 66.7%). The differences were statistically significant for both index surgery (p = 0.004) and at final follow-up (p = 0.001). Unhealed patients scored lower than both healed patients and the normal population in 6/8 Rand-36 domains, but the differences were not statistically significant.

    Conclusions

    Most traumatic rectovaginal fistulas closed after repeated surgery whereas inflammatory fistulas had a poor prognosis. Low healing rates after local repairs suggest that tissue transfer might be indicated more early in the treatment process. Unhealed fistulas were associated with reduced quality of life.

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  • 44.
    van de Vlasakker, Vincent C. J.
    et al.
    Catharina Hosp, Dept Surg, Eindhoven, Netherlands..
    Lurvink, Robin J.
    Catharina Hosp, Dept Surg, Eindhoven, Netherlands..
    Cashin, Peter H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ceelen, Wim
    Ghent Univ Hosp Belgium, Dept Gastrointestinal Surg, Ghent, Belgium..
    Deraco, Marcello
    Fdn IRCCS Inst Nazl Tumori Milano, Dept Surg, Peritoneal Surface Malignancy Unit, Milan, Italy..
    Goéré, Diane
    Gustave Roussy, Dept Surg, Villejuif, France..
    González-Moreno, Santiago
    MD Anderson Canc Ctr, Dept Surg Oncol, Madrid, Spain..
    Lehmann, Kuno
    Univ Hosp Zurich, Dept Visceral & Transplantat Surg, Zurich, Switzerland..
    Li, Yan
    Capital Med Univ, Dept Peritoneal Canc Surg, Beijing Shijitan Hosp, Beijing, Peoples R China..
    Moran, Brendan
    Hampshire Hosp Fdn Trust, Peritoneal Malignancy Inst Basingstoke, Basingstoke, Hants, England..
    Morris, David L.
    St George Hosp, Dept Surg, Sydney, NSW, Australia..
    Piso, Pompiliu
    Hosp Barmherzige Bruder, Dept Gen & Visceral Surg, Regensburg, Germany..
    Quadros, Claudio A.
    Sao Rafael Hosp, Dept Surg Oncol, Salvador, BA, Brazil..
    Rau, Beate
    Charite Univ Med Berlin, Dept Surg, Campus Virchow Klinikum, Berlin, Germany.;Charite Univ Med Berlin, Charite Campus Mitte, Berlin, Germany..
    Somashekhar, S. P.
    Manipal Comprehens Canc Ctr, Dept Surg Oncol & Robot Surg, Bengaluru, India..
    Sommariva, Antonio
    Veneto Inst Oncol IOV IRCCS Padova, Adv Surg Oncol Unit, Surg Oncol Esophagus & Digest Tract, Padua, Italy..
    van der Speeten, Kurt
    Ziekenhuis Oost Limburg, Dept Surg Oncol, Genk, Belgium..
    Spiliotis, John
    European Interbalkan Med Ctr, Dept Surg Oncol, Thessaloniki, Greece..
    Sugarbaker, Paul H.
    MedStar Washington Hosp Ctr, Ctr Gastrointestinal Malignancies, Washington, DC USA..
    Teo, Melissa C. C.
    Natl Canc Ctr, Dept Surg, Singapore, Singapore..
    Verwaal, Vic J.
    Hosp South West Jutland, Dept Surg, Esbjerg, Denmark..
    Yonemura, Yutaka
    Kishiwada Tokushukai Hosp, Peritoneal Surface Malignancy Ctr, Dept Surg, Kishiwada, Japan..
    Glehen, Olivier
    Lyon Sud Hosp, Hosp Civils Lyon, Dept Surg Oncol, Lyon, France.;Lyon Sud Hosp, Lyon Fac Med, Lyon, France..
    de Hingh, Ignace H. J. T.
    Catharina Hosp, Dept Surg, Eindhoven, Netherlands.;Maastricht Univ, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands..
    The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI)2021In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 47, no 11, p. 2888-2892Article in journal (Refereed)
    Abstract [en]

    Introduction

    The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.

    Materials and methods

    CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.

    Results

    The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.

    Conclusion

    The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.

  • 45.
    Wang, Meijuan
    et al.
    Tongji Univ, Shanghai Peoples Hosp 10, Dept Psychiat, Sch Med, Shanghai, Peoples R China..
    Xu, Yuanhong
    Tongji Univ, Shanghai Peoples Hosp 10, Dept Psychiat, Sch Med, Shanghai, Peoples R China..
    Shi, Jingqing
    Tongji Univ, Shanghai Peoples Hosp 10, Dept Psychiat, Sch Med, Shanghai, Peoples R China..
    Zhuang, Chengle
    Tongji Univ, Shanghai Peoples Hosp 10, Dept Gastrointestinal Surg, Sch Med, Shanghai, Peoples R China.;Tongji Univ, Shanghai Peoples Hosp 10, Colorectal Canc Ctr, Sch Med, Shanghai, Peoples R China..
    Zhuang, Ying
    Tongji Univ, Shanghai Maternity Infant Hosp 1, Dept Nursing, Sch Med, Shanghai, Peoples R China..
    Li, Jiyu
    Fudan Univ, Huadong Hosp, Geriatr Canc Ctr, Shanghai, Peoples R China..
    Cashin, Peter H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    The effect of cognitive behavioral therapy on chemotherapy-induced side effects and immune function in colorectal cancer patients undergoing chemotherapy: study protocol for a randomized controlled trial2023In: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 14, no 4, p. 1869-1877Article in journal (Refereed)
    Abstract [en]

    Background: Colorectal cancer (CRC) was one of the most widely diagnosed cancers in the United States in 2021. CRC patients may experience significant psychological stress and are susceptible to depression and anxiety. Previous studies have shown that cognitive behavioral therapy (CBT) can reduce fatigue and improve quality of life among breast cancer patients. However, as a non-pharmaceutical treatment, it remains unclear whether CBT improves chemotherapy-induced side effects and immune function in CRC patients. In this study, we will conduct a randomized controlled trial (RCT) among CRC patients undergoing chemotherapy to determine whether CBT can reduce the side effects of chemotherapy and improve the immune function of CRC patients. Methods: The study will be a single-center RCT. CRC patients undergoing chemotherapy will receive either eight sessions of group-based CBT (every 2-3 weeks) or usual care (usual oncology care). Each participant will undergo assessments at baseline (T0), immediately post-intervention (T1), 3 months postintervention (T2), and 6 months post-intervention (T3). The primary outcome will include chemotherapyinduced side effects in CRC patients. The secondary outcome will be immune function (measured by levels of inflammatory cytokines). Other outcomes will include the levels of tumor markers, assessments of psychological status (perception of stress, depression and anxiety, self-efficacy, sleep quality, quality of life, social support condition, and cognitive function), and necessary laboratory examinations (biochemical index and blood cell counts) among CRC patients undergoing chemotherapy. Discussion: Our study will provide clinical evidence regarding whether CBT should be generalized in clinical treatment and the extent to which CBT reduces chemotherapy- induced side effects for CRC patients.

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