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  • 1.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Andreasson, Håkan
    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.
    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.
    Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal Chemotherapy of Pseudomyxoma Peritonei2015In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 22, p. S810-S816Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is an established therapy for pseudomyxoma peritonei (PMP). However, the role of IPC is unclear. By ex vivo assessment of PMP tumor cell sensitivity to cytotoxic drugs, we investigated the basis for IPC drug selection and the role of IPC in the management of PMP.

    METHODS: Tumor cells were prepared by collagenase digestion of tumor tissue from 133 PMP patients planned for CRS and IPC. Tumor cell sensitivity to oxaliplatin, 5FU, mitomycin C, doxorubicin, irinotecan, and cisplatin was assessed in a 72-h cell-viability assay. Drug sensitivity was correlated to progression-free survival (PFS) and overall survival (OS).

    RESULTS: Samples from 92 patients were analyzed successfully. Drug sensitivity varied considerably between samples. Peritoneal mucinous carcinomatosis (PMCA), compared with PMCA intermediate or disseminated peritoneal adenomucinosis, was slightly more resistant to platinum and 5FU and tumor cells from patients previously treated with chemotherapy were generally less sensitive than those from untreated patients. Multivariate analysis showed patient performance status and completeness of CRS to be prognostic for OS. Among patients with complete CRS (n = 61), PFS tended to be associated with sensitivity to mitomycin C and cisplatin (p ≈ 0.06). At the highest drug concentration tested, the hazard ratio for disease relapse increased stepwise with drug resistance for all drugs.

    CONCLUSIONS: Ex vivo assessment of drug sensitivity in PMP provides prognostic information. The results suggest a role for IPC as therapeutic adjunct to CRS and for individualization of IPC by pretreatment assessment of drug sensitivity.

  • 2. Butt, Salma
    et al.
    Butt, Talha
    Jirstrom, Karin
    Hartman, Linda
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Zhou, Wenjing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Borgquist, Signe
    The Target for Statins, HMG-CoA Reductase, Is Expressed in Ductal Carcinoma-In Situ and May Predict Patient Response to Radiotherapy2014In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, no 9, p. 2911-2919Article in journal (Refereed)
    Abstract [en]

    Background. Patients with ductal carcinoma-in-situ (DCIS) are currently not prescribed adjuvant systemic treatment after surgery and radiotherapy. Prediction of DCIS patients who would benefit from radiotherapy is warranted. Statins have been suggested to exert radio-sensitizing effects. The target for cholesterol-lowering statins is HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway. The aim of this study was to examine HMGCR expression in DCIS and study its treatment predictive value. Methods. A population-based cohort including 458 women diagnosed with primary DCIS between 1986 and 2004 were followed until November 2011 to study long-term survival. Tumor tissue microarrays were constructed, and immunohistochemical analyses were performed to detect cytoplasmic protein expression of HMGCR. The association between DCIS HMGCR expression and invasive breast cancer recurrence-free survival (RFSinv) and overall survival (OS) was analyzed by Kaplan-Meier curves, log rank test, and Cox proportional hazard analysis. Results. HMGCR was strongly expressed in 24 % of the assessed DCIS samples, moderately expressed in 46 %, and weakly expressed in 23 %; no expression was detected in 7 % of the samples. During the follow-up time (median 13.8 years), 61 patients were diagnosed with an invasive breast cancer recurrence, and 80 patients died. A crude analysis showed no survival benefit from radiotherapy. However, patients with strong HMGCR expression showed an improved RFSinv (log rank, p = 0.03) and OS (log rank, p = 0.04) after radiotherapy. No statistically significant interaction was observed for HMGCR and radiotherapy (RFSinv p = 0.69 and OS p = 0.29). Conclusions. This study demonstrates HMGCR expression in DCIS and suggests HMGCR as a predictive marker of response to postoperative radiotherapy in DCIS, although the test for interaction was nonsignificant. Future DCIS studies addressing the potential of statin treatment targeting HMGCR are warranted.

  • 3.
    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.

  • 4.
    Crona, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Gustavsson, Tobias
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Edfeldt, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Somatic Mutations and Genetic Heterogeneity at the CDKN1B Locus in Small Intestinal Neuroendocrine Tumors.2015In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Until recently, the genetic landscape of small intestinal neuroendocrine tumors (SI-NETs) was limited to recurrent copy number alterations, most commonly a loss on chromosome 18. Intertumor heterogeneity with nonconcordant genotype in paired primary and metastatic lesions also is described, further contributing to the difficulty of unraveling the genetic enigma of SI-NETs. A recent study analyzing 55 SI-NET exomes nominated CDKN1B (p27) as a haploinsufficient tumor suppressor gene.

    METHODS: This study aimed to determine the frequency of CDKN1B inactivation and to investigate genotype-phenotype correlations. It investigated 362 tumors from 200 patients. All samples were resequenced for mutations in CDKN1B using automated Sanger sequencing. The expression of p27 was investigated in 12 CDKN1B mutant and nine wild type tumors.

    RESULTS: Some 8.5 % (17/200) of patients had tumors with pathogenic mutations in CDKN1B including 13 insertion deletions, four nonsense variants, and one stop-loss variant. All variants with available nontumoral DNA were classified as somatic. Inter- and intratumor heterogeneity at the CDKN1B locus was detected respectively in six of ten and two of ten patients. Patients with CDKN1B mutated tumors had both heterogeneous disease presentation and diverse prognosis. Expression of the p27 protein did not correlate with CDKN1B mutation status, and no differences in the clinical characteristics between CDKN1B mutated and CDKN1B wild type tumor carriers were found.

    CONCLUSION: This study corroborates the finding of CDKN1B as a potential haplo-insufficient tumor suppressor gene characterized by inter- and intratumor heterogeneity in SI-NETs.

  • 5.
    Dantonello, Tobias M
    et al.
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Lochbühler, Helmut
    Department of Pediatric Surgery, Olgahospital, Klinikum Stuttgart, Germany.
    Schuck, Andreas
    Department of Radiotherapy, University of Muenster, Münster, Germany.
    Kube, Stefanie
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Godzinski, Jan
    Department of Pediatric Surgery, University of Wroclaw, Poland.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kosztyla, Daniel
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Veit-Friedrich, Iris
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Hallmen, Erika
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Feuchtgruber, Simone
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Wessalowski, Ruediger
    Department of Pediatric Oncology, University of Duesseldorf, Germany.
    Franke, Markus
    Department of Pediatric Surgery, University of Freiburg, Germany.
    Bielack, Stefan S
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Klingebiel, Thomas
    Department of Pediatric Oncology, University of Frankfurt, Germany.
    Koscielniak, Ewa
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma2014In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, no 11, p. 3579-3586Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear.

    METHODS:

    We analyzed patients with LARME treated in four consecutive CWS trials. All diagnoses were confirmed by reference reviews. Treatment included multiagent chemotherapy and local treatment of the primary tumor with surgery and/or radiotherapy. The impact of primary debulking surgery (PDS) also was studied.

    RESULTS:

    One hundred patients <21 years with a median age of 4 years had LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was performed in 19 of 100 children. The outcomes of patients with PDS were similar to those of the other patients. In 36 children, the tumor was resected after induction chemotherapy; 60 RME were irradiated. The toxic effects of radiochemotherapy were not significantly increased compared with the nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and OS were 52 ± 10 and 65 ± 9 %, respectively. Significant risk factors in multivariate analysis were age >10 years; no achievement of complete remission; and inadequate secondary local treatment, defined as incomplete secondary resection or no radiation.

    CONCLUSIONS:

    Children with LARME have a fair prognosis, despite an often huge tumor size and unfavorable primary site, if the tumors can either be resected or irradiated following induction chemotherapy. PDS was only performed in a small subgroup. Radiation performed concomitantly with chemotherapy did not increase the acute toxicity significantly.

  • 6.
    Enblad, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sköldberg, Filip
    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.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2016In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 23, no 4, p. 1149-1156Article in journal (Refereed)
    Abstract [en]

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  • 7.
    Eriksson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Res Oncol, Canc Epidemiol Grp, Div Canc Studies, London, England..
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ihre-Lundgren, Catharina
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    The Influence of Preoperative Symptoms on the Death of Patients with Small Intestinal Neuroendocrine Tumors2017In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 24, no 5, p. 1214-1220Article in journal (Refereed)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) are uncommon tumors with an annual incidence of about 1 per 100,000. Usually, SI-NETs have a slow progression, and patients often present with generalized disease. Many patients do well, and the disease has a relatively favorable 5-year survival rate. Some SI-NETs, however, have a more negative prognosis. This study aimed to establish prognostic factors for death identifiable at primary surgery. A nested case-control study investigated 1150 patients from the cohort of all patients with a diagnosis of SI-NETs in Sweden between 1961 and 2001. The study cases consisted of all patients who died of SI-NETs during the study period. Each case was assigned a control subject matched by age at diagnosis and calendar period. Possible prognostic factors [gender, degree of symptoms, indication for surgery, World Health Organization (WHO) stage] were evaluated in uni- and multivariable analyses. The patients with symptomatic disease had an increased risk of dying. The indication for primary surgery influenced survival, showing a more negative prognosis for elective surgery. The WHO stage influenced survival, and stage 4 patients had an almost threefold risk of dying compared with stages 1 to 3b patients. This study showed that preoperative symptoms are important in prognostication for SI-NETs. Hormonal symptoms generally signify a patient with a more advanced disease stage and a worse prognosis. Including symptomatic disease together with the WHO stage and grade could possibly increase the accuracy of prognostication.

  • 8. Esquivel, J
    et al.
    Sticca, R
    Sugarbaker, P
    Levine, E
    Yan, T D
    Alexander, R
    Baratti, D
    Bartlett, D
    Barone, R
    Barrios, P
    Bieligk, S
    Bretcha-Boix, P
    Chang, C K
    Chu, F
    Chu, Q
    Daniel, S
    Debree, E
    Deraco, M
    Dominguez-Parra, L
    Elias, D
    Flynn, R
    Foster, J
    Garofalo, A
    Gilly, F N
    Glehen, O
    Gomez-Portilla, A
    Gonzalez-Bayon, L
    Gonzalez-Moreno, S
    Goodman, M
    Gushchin, V
    Hanna, N
    Hartmann, J
    Harrison, L
    Hoefer, R
    Kane, J
    Kecmanovic, D
    Kelley, S
    Kuhn, J
    Lamont, J
    Lange, J
    Li, B
    Loggie, B
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mann, G
    Martin, R
    Misih, R A
    Moran, B
    Morris, D
    Onate-Ocana, L
    Petrelli, N
    Philippe, G
    Pingpank, J
    Pitroff, A
    Piso, P
    Quinones, M
    Riley, L
    Rutstein, L
    Saha, S
    Alrawi, S
    Sardi, A
    Schneebaum, S
    Shen, P
    Shibata, D
    Spellman, J
    Stojadinovic, A
    Stewart, J
    Torres-Melero, J
    Tuttle, T
    Verwaal, V
    Villar, J
    Wilkinson, N
    Younan, R
    Zeh, H
    Zoetmulder, F
    Sebbag, G
    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement2011In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 18, no Suppl 3, p. 334-335Article in journal (Refereed)
  • 9. Esquivel, J.
    et al.
    Sticca, R.
    Sugarbaker, P.
    Levine, E.
    Yan, T. D.
    Alexander, R.
    Baratti, D.
    Bartlett, D.
    Barone, R.
    Barrios, P.
    Bieligk, S.
    Bretcha-Boix, P.
    Chang, C. K.
    Chu, F.
    Chu, Q.
    Daniel, S.
    deBree, E.
    Deraco, M.
    Dominguez-Parra, L.
    Elias, D.
    Flynn, R.
    Foster, J.
    Garofalo, A.
    Gilly, F. N.
    Glehen, O.
    Gomez-Portilla, A.
    Gonzalez-Bayon, L.
    Gonzalez-Moreno, S.
    Goodman, M.
    Gushchin, V.
    Hanna, N.
    Hartmann, J.
    Harrison, L.
    Hoefer, R.
    Kane, J.
    Kecmanovic, D.
    Kelley, S.
    Kuhn, J.
    LaMont, J.
    Lange, J.
    Li, B.
    Loggie, B.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Mann, G.
    Martin, R.
    Misih, R. A.
    Moran, B.
    Morris, D.
    Onate-Ocana, L.
    Petrelli, N.
    Philippe, G.
    Pingpank, J.
    Pitroff, A.
    Piso, P.
    Quinones, M.
    Riley, L.
    Rutstein, L.
    Saha, S.
    Alrawi, S.
    Sardi, A.
    Schneebaum, S.
    Shen, P.
    Shibata, D.
    Spellman, J.
    Stojadinovic, A.
    Stewart, J.
    Torres-Melero, J.
    Tuttle, T.
    Verwaal, V.
    Villar, J.
    Wilkinson, N.
    Younan, R.
    Zeh, H.
    Zoetmulder, F.
    Sebbag, G.
    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement2007In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 14, no 1, p. 128-133Article in journal (Refereed)
  • 10.
    Fraser, Sheila
    et al.
    Univ Sydney, Royal North Shore Hosp, Endocrine Surg Unit, St Leonards, NSW, Australia..
    Zaidi, Nisar
    Univ Sydney, Royal North Shore Hosp, Endocrine Surg Unit, St Leonards, NSW, Australia..
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Glover, Anthony
    Univ Sydney, Kolling Inst Med Res, St Leonards, NSW, Australia..
    Kruijff, Schelto
    Univ Med Ctr Groningen, Dept Surg Oncol, Groningen, Netherlands..
    Sywak, Mark
    Univ Sydney, Royal North Shore Hosp, Endocrine Surg Unit, St Leonards, NSW, Australia..
    Delbridge, Leigh
    Univ Sydney, Royal North Shore Hosp, Endocrine Surg Unit, St Leonards, NSW, Australia..
    Sidhu, Stan B.
    Univ Sydney, Royal North Shore Hosp, Endocrine Surg Unit, St Leonards, NSW, Australia.;Univ Sydney, Kolling Inst Med Res, St Leonards, NSW, Australia..
    Incidence and Risk Factors for Occult Level 3 Lymph Node Metastases in Papillary Thyroid Cancer2016In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 23, no 11, p. 3587-3592Article in journal (Refereed)
    Abstract [en]

    Papillary thyroid cancer (PTC) frequently disseminates into cervical lymph nodes. Lateral node involvement is described in up to 50 % patients undergoing prophylactic lateral neck dissection. This study aimed to assess this finding and identify which factors predict for occult lateral node disease. Patients with fine needle aspiration-confirmed PTC (Bethesda V or VI), without evidence of cervical lymph node metastases, underwent a total thyroidectomy with prophylactic ipsilateral central and level 3 dissection. Level 3 nodes were removed by compartmental dissection or by sampling the sentinel nodes overlying the jugular vein, according to surgeon preference. Data were collected prospectively from January 2011 to August 2014. Statistical analysis was performed by SPSS software. A total of 137 patients underwent total thyroidectomy with prophylactic ipsilateral central and level 3 dissection for PTC. The incidence of occult level 3 disease was 30 % (41/137 patients). A total of 48 % of patients (66/137) harbored occult central neck disease. A total of 80.5 % of patients with pN1b disease had macrometastases (aeyen2 mm), and 15 % exhibited skip metastases with central compartment sparing. In patients with pN1b disease, a median of 6 level 3 nodes were retrieved, with an average involved nodal ratio of 0.29. Multivariate regression demonstrated risk factors for occult lateral neck metastasis include tumor size (odds ratio 1.1), upper pole tumors (odds ratio 6.6), and vascular invasion (odds ratio 3.2) (p < 0.05). PTC is associated with a significant incidence of occult central and lateral nodal metastases. In patients undergoing prophylactic central neck dissection, inclusion of level 3 dissection should be considered in patients with large upper lobe cancers.

  • 11. Glover, Anthony R
    et al.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Gundara, Justin S
    Morris, Michael
    Sidhu, Stan B
    Use of the Nerve Integrity Monitor during Thyroid Surgery Aids Identification of the External Branch of the Superior Laryngeal Nerve.2015In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 22, no 6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The external branch of the superior laryngeal nerve (EBSLN) is at risk during thyroid surgery. Despite meticulous dissection and visualization, the EBSLN can be mistaken for other structures. The nerve integrity monitor (NIM) allows EBSLN confirmation with cricothyroid twitch on stimulation.

    AIMS: The aim of this study was to assess any difference in identification of EBSLN and its anatomical sub-types by dissection alone compared to NIM-aided dissection.

    METHODS: Routine intra-operative nerve monitoring (IONM) was used, when available, for 228 consecutive thyroid operations (129 total thyroidectomies, 99 hemi-thyroidectomies) over a 10-month period. EBSLN identification by dissection alone (with NIM confirmation of cricothyroid twitch) and by NIM-assisted dissection was recorded prospectively. Anatomical sub-types were defined by the Cernea classification.

    RESULTS: Of 357 nerves at risk, 97.2 % EBSLNs (95 % confidence interval [CI], 95.5-98.9) were identified by visualization and NIM-aided dissection compared to 85.7 % (95 % CI, 82.1-89.3) identified by dissection alone (<0.001). EBSLN frequency was 34 % for type 1, 55 % for type 2a, and 11 % for type 2b. All identified EBSLNs were stimulated to confirm a cricothyroid twitch after superior thyroid vessel ligation.

    CONCLUSION: Using the NIM and meticulous dissection of the upper thyroid pole improves EBSLN identification. As the EBSLN is at risk during thyroidectomy and can lead to voice morbidity, the NIM can aid identification of the EBSLN and provide a functional assessment of the EBSLN after thyroid resection.

  • 12.
    Haugvik, Sven-Petter
    et al.
    Oslo Univ Hosp, Rikshosp, Dept Hepatopancreatobiliary Surg, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Osterlund, Pia
    Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland..
    Langer, Seppo W.
    Univ Copenhagen, Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark..
    Falk, Ragnhild Sorum
    Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway..
    Labori, Knut Jorgen
    Oslo Univ Hosp, Rikshosp, Dept Hepatopancreatobiliary Surg, Oslo, Norway..
    Vestermark, Lene Weber
    Odense Univ Hosp, Dept Oncol, DK-5000 Odense, Denmark..
    Gronbaek, Henning
    Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, DK-8000 Aarhus, Denmark..
    Gladhaug, Ivar Prydz
    Oslo Univ Hosp, Rikshosp, Dept Hepatopancreatobiliary Surg, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway..
    Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma: A Nordic Multicenter Comparative Study2016In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 23, no 5, p. 1721-1728Article in journal (Refereed)
    Abstract [en]

    This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery is uncertain. Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan-Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate factors potentially influencing survival. The study registered 119 patients. The median survival period from the time of metastasis was 23 months for patients undergoing initial resection of localized nonmetastatic disease and chemotherapy at the time of recurrence (n = 14), 29 months for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor and metastatic disease was 69 %. Resection of the primary tumor was an independent factor for improved survival after occurrence of metastatic disease. Patients with resected localized nonmetastatic hgPNEC and later metastatic disease seemed to benefit from initial resection of the primary tumor. Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment.

  • 13.
    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.

  • 14. Modlin, Irvin M.
    et al.
    Gustafsson, Björn I.
    Moss, Steven F.
    Pavel, Marianne
    Tsolakis, Apostolos V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kidd, Mark
    Chromogranin A: Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease2010In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 17, no 9, p. 2427-2443Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Neuroendocrine tumors (NETs) are a form of cancer that differ from other neoplasia in that they synthesize, store, and secrete peptides, e.g., chromogranin A (CgA) and amines. A critical issue is late diagnosis due to failure to identify symptoms or to establish the biochemical diagnosis. We review here the utility of CgA measurement in NETs and describe its biological role and the clinical value of its measurement. METHODS: Literature review and analysis of the utility of plasma/serum CgA measurements in NETs and other diseases. RESULTS: CgA is a member of the chromogranin family; its transcription and peptide processing are well characterized, but its precise function remains unknown. Levels are detectable in the circulation but vary substantially (~25%) depending on which assay is used. Serum and plasma measurements are concordant. CgA is elevated in ~90% of gut NETs and correlates with tumor burden and recurrence. Highest values are noted in ileal NETs and gastrointestinal NETs associated with multiple endocrine neoplasia type 1. Both functioning and nonfunctioning pancreatic NETs have elevated values. CgA is more frequently elevated in well-differentiated tumors compared to poorly differentiated NETs. Effective treatment is often associated with decrease in CgA levels. Proton pump inhibitors falsely increase CgA, but levels normalize with therapy cessation. CONCLUSIONS: CgA is currently the best available biomarker for the diagnosis of NETs. It is critical to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy. Measurement of plasma CgA is mandatory for the effective diagnosis and management of NET disease.

  • 15.
    Norlén, Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Popadich, Aleksandra
    Kruijff, Schelto
    Gill, Anthony J.
    Sarkis, Leba M.
    Delbridge, Leigh
    Sywak, Mark
    Sidhu, Stan
    Bethesda III Thyroid Nodules: The Role of Ultrasound in Clinical Decision Making2014In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, no 11, p. 3528-3533Article in journal (Refereed)
    Abstract [en]

    Assessment for thyroid nodules includes ultrasound (US) and cytology according to the Bethesda classification. There is no firm consensus regarding clinical management for nodules classified as Bethesda III. Our aim was investigate the value of US to predict malignancy in these nodules. Patients with Bethesda III nodules who underwent thyroid surgery from July 2011 to July 2013 were included. Inclusion criteria mandated that US were available for review by two observers blinded to each other's results and histological outcome. The nodules were scrutinized with six US criteria: hypoechoic attenuation (HA), irregular margins (IM), taller than wide, microcalcifications (MC), loss of halo, and increased central vascularity. Disagreements between observers were solved by consensus. There were 141 patients (121 women) with a mean age of 55 years. Mean nodule size was 25 mm. The malignancy rate was 13 %. Interobserver ratios were moderate to very strong for all six predictors (kappa = 0.60-0.94). However, only HA, IM, and MC were predictors of malignancy by univariate analysis (all p < 0.002). Logistic regression revealed an odds ratio of malignancy versus no malignancy for HA 4.8, IM 3.3, and MC 4.0 (all p < 0.05). The positive and negative predictive value for malignancy when having one or more of these three criteria was 22 % and 98 %, respectively. HA, IM, and MC were predictors of malignancy in Bethesda III nodules. In addition, the negative predictive value for any of these three criteria was high; a nodule that lacks all of these three criteria is thus unlikely to be malignant.

  • 16. Sjövall, Annika
    et al.
    Granath, Fredrik
    Cedermark, Björn
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Holm, Torbjörn
    Loco-regional Recurrence from Colon Cancer: A Population-based Study2007In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 14, no 2, p. 432-440Article in journal (Refereed)
    Abstract [en]

    Background  The survival after colon cancer surgery has not improved to the same extent as after rectal cancer treatment and studies on loco-regional recurrence after colon cancer surgery are scarce. The aim of this study was to assess the problem of loco-regional recurrence after potentially curative resections for colon cancer, regarding incidence, risk factors, management, and outcome. Methods  All 1,856 patients submitted to potentially curative surgery for colon cancer in the Stockholm/Gotland region in Sweden between 1996 and 2000 were followed until January 2005 or until death. Follow-up data were prospectively collected. Risk factors for loco-regional recurrences were analyzed, treatment and outcome for patients with recurrence was studied. Results  The cumulative 5-year incidence of loco-regional recurrence was 11.5%. Tumor locations in the right flexure and in the sigmoid colon, bowel perforation and emergent surgery were identified as independent risk factors for loco-regional recurrence. The risk also increased with increasing T- and N-stage. The median survival for all 192 patients with loco-regional recurrence was 9 months. Surgery was performed in 110 (57%) patients. In 23 (12%) patients a complete tumor clearance was achieved and the estimated 5-year survival in this group was 43%. Conclusion  Loco-regional recurrence from colon cancer is a significant clinical problem. A multidisciplinary treatment approach, including preoperative staging, a complete resection of the recurrence and more effective adjuvant treatments may improve the outcome.

  • 17.
    Starker, Lee F
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery. Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
    Mahajan, Amit
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery. Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
    Sze, Gordon
    Udelsman, Robert
    Carling, Tobias
    4D parathyroid CT as the initial localization study for patients with de novo primary hyperparathyroidism2011In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 18, no 6, p. 1723-1728Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Preoperative localization of parathyroid tumors of primary hyperparathyroidism (pHPT) is required for minimally invasive parathyroidectomy (MIP). Parathyroid four-dimensional computed tomography (4DCT) has mainly been used as an adjunct to other imaging modalities in the remedial setting. 4DCT was evaluated as the initial localization study in de novo patients with pHPT.

    MATERIALS AND METHODS:

    A total of 87 consecutive patients underwent parathyroidectomy for pHPT from August 2008 to November 2009. 4DCT was introduced as the preferred imaging modality instead of sestamibi with SPECT (SeS) in April 2009. Results of the imaging studies [4DCT, SeS, and ultrasonography (US)], operative and, pathologic findings, and biochemical measurements were evaluated.

    RESULTS:

    In this study, 84% of patients (73 of 87) underwent an US, 59.8% (52 of 87) a SeS, and 38.0% (33 of 87) had a 4DCT. 4DCT had improved sensitivity (85.7%) over SeS (40.4%) and US (48.0%) to localize parathyroid tumors to the correct quadrant of the neck (P < 0.005) as well as to localize (lateralize) the parathyroid lesions to one side of the neck (93.9% for 4DCT vs. 71.2% for US and 61.5% for SeS; P < 0.005). 4DCT correctly predicted multiglandular disease (MGD) in 85.7% (6 of 7) patients, whereas US and SeS were unable to detect MGD in any case. All patients achieved cure based on intraoperative parathyroid hormone (PTH) measurements and normalization of intact PTH and S-Ca during follow-up.

    CONCLUSIONS:

    4DCT provides significantly greater sensitivity than SeS and US for precise localization of parathyroid tumors of pHPT. Additionally, it correctly predicted MGD in a majority of patients.

  • 18.
    Tiselius, Catarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Vastmanlands Hosp Vasteras, Dept Surg, Vasteras, Sweden..
    Kindler, Csaba
    Vastmanlands Hosp, Dept Pathol, Vasteras, Sweden..
    Shetye, Jayant
    Vastmanlands Hosp, Dept Pathol, Vasteras, Sweden..
    Letocha, Henry
    Vastmanlands Hosp, Dept Oncol, Vasteras, Sweden..
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Computed Tomography Follow-Up Assessment of Patients with Low-Grade Appendiceal Mucinous Neoplasms: Evaluation of Risk for Pseudomyxoma Peritonei2017In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 24, no 7, p. 1778-1782Article in journal (Refereed)
    Abstract [en]

    Low-grade appendiceal mucinous neoplasms are rare. Both classification and management vary. This study aimed to follow up on patients with a diagnosis of LAMN after primary surgery with computer tomography (CT) scans to examine the risk for the development of pseudomyxoma peritonei (PMP).

    This population-based prospective study investigated patients who underwent appendectomy between 2007 and 2013 and had histology results demonstrating the presence of LAMN. The patients were followed up with a CT scan every 6 months for 2 years, until December 2015.

    The study investigated 41 patients (20 females) with a median age of 65 years (range 20-87 years). The entire appendix was processed and examined, with results showing that 12 were perforated, and 3 had a positive margin. Extra-appendiceal mucin on the surface of the appendix was found in ten cases, and in two cases, extra-mucinous epithelial cells were detected. During a median follow-up period of 5.1 years (range 2-8.6 years), none of the patients experienced the development of PMP.

    These data suggest that for patients with LAMN confined to the appendix, involvement of the appendectomy margin or perforation with mucin locally, even with epithelial cells, did not predict the development of PMP, and a conservative approach seems justified. No reoperation was needed, and regular follow-up evaluation with CT scans was sufficient.

  • 19.
    Van der Speeten, Kurt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Stuart, O.A.
    Washington Cancer Institute, Washington D.C., USA.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sugarbaker, Paul H.
    Washington Cancer Institute, Washington D.C., USA.
    Pharmacokinetic Study of Perioperative Intravenous Ifosfamide2011In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, p. 185092-Article in journal (Refereed)
    Abstract [en]

    Background

    The use of cancer chemotherapy as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Various combinations of intraperitoneal and systemic chemotherapy used with moderate hyperthermia constitute the cytotoxic component of this therapy.  Ifosfamide, being a heat synergized drug, may be an important chemotherapy agent to use when attempting to optimize this treatment strategy. 

    Materials and methods

    16 Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5 - 42.5°C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy.  Using high pressure liquid chromatography (HPLC) the concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm.

    Results

    Urine ifosfamide and 4-hydroxyifosfamide concentrations exceeded those within the plasma and peritoneal fluid throughout the 90 minutes of drug infusion.  Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion; however, at 60 minutes after infusion ceased, the peritoneal fluid and plasma concentrations were equivalent.  Both ifosfamide and 4-hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations.

    Conclusions

    Clear understanding of the pharmacology of perioperative intraperitoneal hyperthermia combined with systemic chemotherapy may provide important information for the design of treatment regimens.  4-hydroxyifosfamide within cancerous tissue suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room. 

  • 20.
    van Leeuwen, Barbara L.
    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.
    Påhlman, Lars
    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.
    Swedish experience with peritonectomy and HIPEC: HIPEC in peritoneal carcinomatosis2008In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 15, no 3, p. 745-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Peritonectomy with heated intraperitoneal chemotherapy (HIPEC) has shown a survival benefit in selected patients with peritoneal carcinomatosis. This prospective non-randomized study was designed to identify factors associated with postoperative morbidity and survival after peritonectomy HIPEC in patients with this condition. METHOD: Data were prospectively collected from all patients with peritoneal carcinomatosis treated by means of peritonectomy and HIPEC at Uppsala University Hospital between October 2003 and September 2006. Depending on the primary tumor, mitomycin C or a platinum compound was used as a chemotherapeutic agent for perfusion. RESULTS: A total of 103 patients were treated. Primary tumors were pseudomyxoma peritonei (47 patients), colorectal cancer (38 patients), gastric cancer (6 patients), ovarian cancer (6 patients) and mesothelioma (5 patients). Postoperative morbidity was 56.3% and was significantly lower in patients treated with mitomycin C for pseudomyxoma peritonei (42%) than in those with another diagnosis treated with platinum compound (71%, P < 0.05). Postoperative mortality was less than 1%. At 2 years, overall survival was estimated to be 72.3%, and disease-free survival was 33.5%. Factors influencing overall and disease-free survival were tumor type and optimal cytoreduction. CONCLUSION: Postoperative morbidity is dependent mainly on a tumor type; however, the chemotherapeutic agent used might also influence morbidity. Survival is determined by optimal cytoreduction and tumor type. Irrespective of age, patients with good performance status benefit from this treatment.

  • 21.
    Wei, Qichun
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sheng, Liming
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Shui, Yongjie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Hu, Qiongge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Nordgren, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases2008In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 15, no 4, p. 1193-1201Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are several substances available to target members of the epidermal growth factor receptor (EGFR) family, both for imaging in nuclear medicine and for various forms of therapy. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as a target in systemic tumor therapy. To date, the expression of EGFR family members has only been determined in primary laryngeal carcinomas, and we have not found published data regarding the receptor status in corresponding metastatic lesions. METHODS: Expression of EGFR, HER2, and HER3 was investigated immunohistochemically in both lymph node metastases and corresponding primary laryngeal squamous carcinomas (n = 40). RESULTS: EGFR overexpression (2+ or 3+) was found in 87.5% (35/40) of the laryngeal primary tumors and 82.5% (33/40) of the corresponding lymph node metastases. There was a good agreement between the primary tumors and the paired metastases regarding EGFR expression. HER2 overexpression was found in only four cases (10.5%) of the studied primary tumors and in all cases the HER2 expression was retained in the paired metastases. Another two metastases gained HER2 status when compared to the corresponding primary tumors. Strong HER3 staining was found in 26.7% of both the primary tumors and the corresponding metastases. CONCLUSIONS: The high frequency and stability in EGFR expression is encouraging for efforts to use EGFR targeting agents (e.g. Iressa, Tarceva, Erbitux or radiolabeled antibodies) for therapy of laryngeal carcinoma. For a few laryngeal carcinoma patients with HER2 overexpression, anti-HER2 agents could possibly be used.

  • 22.
    Wärnberg, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stigberg, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Obondo, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Olofsson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wärnberg, Madeleine
    Karakatsanis, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery.2019In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 26, no 5, p. 1247-1253Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVE: SPIO is effective in sentinel node (SN) detection. No nuclear medicine department is needed, and no allergic reactions have occurred. This study aimed to compare retro-areolar and peri-tumoral SPIO injections regarding skin staining, detection rates and number of SNs.

    METHODS: Data on staining size, intensity and cosmetic outcome (0-5; 0 = no problem) were collected by telephone interviews with 258 women undergoing breast conservation. SN detection and the number of SNs were prospectively registered in 332 women.

    RESULTS: After retro-areolar and peri-tumoral injections, 67.3% and 37.8% (p < 0.001) developed skin staining, with remaining staining in 46.2 vs. 9.4% after 36 months (p < 0.001). Initial mean size was 16.3 vs. 6.8 cm (p < 0.001) and after 36 months, 6.6 vs. 1.8 cm2 (p < 0.001). At 75.1% of 738 interviews, staining was reported paler. After retro-areolar injections, cosmetic outcome scored worse for 2 years. The mean (median) scores were 1.3(0) vs. 0.5(0) points, and 0.2(0) vs. 0.1(0) points, at 12 and 36 months, respectively. Overall detection rates were 98.3% and 97.4% (p = 0.43) and the number of SNs 1.35 vs. 1.57 (p = 0.02) after retro-areolar and peri-tumoral injections. Injection, regardless of type, 1-27 days before surgery increased detection rates with SPIO, 98.0% vs. 94.2% (p = 0.06) ,and SN numbers, 1.56 vs. 1.27 (p = 0.003).

    CONCLUSION: SPIO is effective and facilitates planning for surgery. Peri-tumoral injection reduced staining with a similar detection rate. Staining was not considered a cosmetic problem among most women. Injecting SPIO 1-27 days before surgery increased the detection rate by 3.8% and increased the number of SNs by 0.3.

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