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Irreversible electroporation of pancreatic adenocarcinoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pancreatic cancer (PC) is a severe diagnosis with poor prognosis. Radical surgery is the only treatment that can possibly lead to a cure, and even with surgery, the 5-year survival is only 20%–25%. The majority of patients cannot be resected due to metastases or having a tumour that is too advanced locally (LAPC) with encasement of blood-vessels.

Short electrical pulses can change the cell membrane, creating reversible pores in it. With a higher current, the pores become permanent, resulting in irreversible electroporation (IRE). This leads to specific cell death, with the chance to save surrounding scaffold material, such as the walls of blood vessels and bile ducts. This led to the theory that IRE might be suitable for treating LAPC.

In Paper I, we found that IRE can be safely performed percutaneously with ultrasound guidance in humans with PC, with promising efficacy, since one of the five patients included was downstaged due to the IRE and could be surgically resected. In Paper II, which is an extension of Paper I, we treated 24 patients with LAPC (3 were also included in Paper I) who had received chemotherapy and, after IRE, stable disease was seen. Median overall survival was 17.9 months. Eleven patients had some form of complication, but we still concluded that IRE is reasonably safe in LAPC patients, with promising efficacy. In Paper III, we chose to treat LAPC with IRE followed by adjuvant chemotherapy. We compared the overall survival of our patients with those with LAPC in the National Quality Registry for Pancreatic and Periampullary Cancer. No significant survival gain could be seen in the group that received IRE compared to the registry group (13.3 months versus 9.9 months, p=0.511). In the IRE group, there were six major complications and we found no support for using IRE in this setting. Paper IV examines the response on the tumour marker CA19-9 in PC treated with IRE. We found 35 patients suitable for this analysis. The hypothesis that IRE would lower the CA19-9 value could not be proven. In fact, the CA19-9 was slightly higher one month after IRE (282 U/ml versus 315 U/ml). However, the 25th percentile of patients with the best CA19-9 response had a better survival (p=0.01) compared to the 25th percentile with the worst response, indicating that CA19-9 can be used as a prognostic marker after IRE in PC.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 69
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1516
Keywords [en]
Pancreatic Neoplasms, Electroporation, Interventional Ultrasonography, CA 19-9.
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-365203ISBN: 978-91-513-0504-2 (print)OAI: oai:DiVA.org:uu-365203DiVA, id: diva2:1262332
Public defence
2019-01-12, Hedstrandsalen, Ingång 70 bv, Akademiska sjukhuset, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2018-12-19 Created: 2018-11-11 Last updated: 2019-01-21
List of papers
1. Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer
Open this publication in new window or tab >>Safety and Preliminary Efficacy of Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Localized Pancreatic Cancer
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2014 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 1A, p. 289-293Article in journal (Refereed) Published
Abstract [en]

Background:

Irreversible electroporation (IRE) is a local tumor treatment. Thin needles are placed percutaneously around the tumor under ultrasound guidance. Short pulses of direct current sent through the tissue irreversibly increase cell membrane permeability leading to cell death. We report a phase I study assessing the safety of ultrasound guided percutaneous IRE in patients with localized pancreatic cancer (LPC).

Patients and Methods:

Five patients (three males) with LPC, judged unsuitable for surgery, chemotherapy, or non-resectable after standard oncological treatment, were treated with IRE. The treatment was given under general anesthesia with muscle relaxation.

Results:

No serious treatment-related adverse events were observed. There was no 30-day mortality. One patient went on to laparotomy and had a R0 pancreaticoduodenectomy with portal vein resection. Six months after the treatment, two patients had no signs of recurrence on computed tomography or contrast-enhanced ultrasound.

Conclusion:

IRE for LPC can be safely performed percutaneously under ultrasound guidance, with promising initial results regarding efficacy.

Keywords
Pancreatic cancer, tumor ablation, safety, irreversible electroporation, ultrasound guidance
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-218956 (URN)000329765300037 ()24403476 (PubMedID)
Available from: 2014-02-20 Created: 2014-02-20 Last updated: 2018-11-15Bibliographically approved
2. Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy
Open this publication in new window or tab >>Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy
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2016 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 9, p. 1401-1406Article in journal (Refereed) Published
Abstract [en]

Background: Irreversible electroporation (IRE) is a non-thermal based tumor ablation method used close to vessels and ducts and has the potential of treating locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the efficacy and safety of IRE in patients with LAPC after chemo- and/or radio-chemotherapy.

Method: Twenty-four patients with biopsy proven LAPC and who had received chemo- and/or radio-chemotherapy with no signs of metastases were included and treated with ultrasound guided percutaneous IRE under general anesthesia.

Results: The median overall survival from diagnosis of LAPC was 17.9 months; this included 7.0 months after IRE. Median time from IRE was 6.1 months to local progression and 2.7 months to observation of metastases. Local control was observed in nine patients. IRE related complications were observed in 11 patients, three of which were serious complications. There was no IRE related mortality.

Conclusion: Percutaneous IRE is reasonably safe in LAPC after chemo-/radio-chemotherapy and with promising results regarding efficacy.

Keywords
Pancreatic neoplasms, Electroporation, Interventional ultrasonography
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-305544 (URN)10.1016/j.ejso.2016.01.024 (DOI)000383005100020 ()26906114 (PubMedID)
Available from: 2016-10-20 Created: 2016-10-19 Last updated: 2018-11-15Bibliographically approved
3. Percutaneous Irreversible Electroporation as First Line Treatment of Locally Advanced Pancreatic Cancer
Open this publication in new window or tab >>Percutaneous Irreversible Electroporation as First Line Treatment of Locally Advanced Pancreatic Cancer
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). There is very limited experience from the use of IRE prior to chemotherapy in LAPC. The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy and the secondary aim was to examine complication rates.

Method: Twenty-four patients with biopsy-proven LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison.

Results: The median survival after diagnosis in the IRE group was 13.3 months compared to 9.9 months in the National Quality Registry for Pancreatic and Periampullary Cancer (p=0.511). Six patients had a severe complication after the IRE treatment.

Conclusion: No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting.

Keywords
Pancreatic Neoplasms, Electroporation, Interventional Ultrasonography
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-365201 (URN)
Available from: 2018-11-11 Created: 2018-11-11 Last updated: 2018-11-15
4. The Value of CA 19-9 after Irreversible Electroporation for Pancreatic Cancer
Open this publication in new window or tab >>The Value of CA 19-9 after Irreversible Electroporation for Pancreatic Cancer
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker used to monitor pancreatic cancer treatment. Irreversible electroporation (IRE) is a relatively new experimental treatment modality for surgically untreatable pancreatic cancer. The aim of this study was to evaluate whether percutaneous IRE lowers CA 19-9 levels in pancreatic cancer and whether this correlates with improved overall survival.

Method: We treated 71 patients with both locally advanced pancreatic cancer and recurrence after resection. Patients with missing data, metastatic disease and normal CA 19-9 before IRE were excluded. This left 35 cases to analyze.

Results: CA 19-9 did not decrease in the cohort after the percutaneous IRE treatment. The median CA 19-9 level before the IRE treatment was in fact slightly lower than after it, 282 U/ml versus 315 U/ml. The 25th percentile of patients with the best CA 19-9 response had an improved overall survival compared to the 25th percentile with the worst response, mean 13.1 versus 8.1 months respectively (p=0.01).

Conclusion: IRE did not lower CA 19-9 in pancreatic cancer cases. However, a response in CA 19-9 was correlated with improved survival.

Keywords
Pancreatic Neoplasms, Electroporation, Interventional Ultrasonography, CA 19-9
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-365202 (URN)
Available from: 2018-11-11 Created: 2018-11-11 Last updated: 2018-11-15

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