| 1. |
- Månsson, Christopher
(författare)
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Irreversible electroporation of pancreatic adenocarcinoma
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 2. |
- Regnér, Sara
(författare)
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Protease Activation and Inflammation in Acute Pancreatitis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Approximately 10—20 % of patients with acute pancreatitis (AP) develop a severe disease with high mortality and morbidity. Activation of pancreatic proteases, the inflammatory response and impaired pancreatic circulation are pathophysiological events that are important in order for the disease to develop. There is no specific treatment for severe AP, and no useful marker for predicting the severity of the disease upon admission to the hospital. In this thesis, markers of early pathophysiological events in AP are investigated, with emphasis on protease activation and inflammation. ProCarboxypeptidase B (proCAP) is a pancreatic proenzyme which, particularly in severe AP, is activated by trypsin thereby forming Carboxypeptidase B (aCAP ) and the activation peptide of proCarboxypeptidase B (CAPAP). An ELISA method for measurement of serum aCAP in patients with AP was developed, and aCAP was shown to inhibit fibrinolysis in vitro. This may contribute to formation of necrosis in AP. The prediction of severity and pathophysiology was studied in patients with mild (n=124) and severe (n=16) AP. Markers of protease activation (aCAP, CAPAP) and inflammation (Monocyte Chemoattractant protein-1 (MCP-1) and CRP) were found to be elevated within 24 hours in patients with severe AP. Protease activation decreased after 48 hours, yet inflammation persisted for a longer period of time. Markers of pancreatic leakage (proCAP) decreased with time without differences in patients with mild and severe AP. MCP-1 exhibited a good capacity at predicting severe AP upon hospital admission. CAPAP and aCAP may also be useful in predicting the degree of severity.
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| 3. |
- Sanjeevi, Srinivas
(författare)
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Advances in the Perioperative Management of Pancreatic Cancer
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgery is currently the only form of curative treatment for pancreatic cancer, yet five-year survival rates following resection are just 15-20%. Improved hospital care has decreased postoperative mortality to 2% yet morbidity remains high at 50%. Poor survival and high morbidity are driven by several perioperative factors. The aims of this thesis were to (I) understand the impact of waiting times between imaging and surgery, (II) evaluate the best strategy for patients deemed unresectable at surgery, (III) explore novel pancreaticojejunal anastomotic techniques and (IV) to evaluate systemic treatment options for patients with borderline resectable pancreatic cancer. In paper I, the time between diagnosis and surgical treatment was evaluated with regards to cancer progression at the time of surgery. The rate of unresectable disease at surgery was significantly lower with a waiting of time of 32 days or less compared with longer waiting times (13.9 vs 32.5%). Tumor size and vascular involvement also increased the risk of unresectable disease at surgery. In paper II, the palliative double bypass (PDB) and just an exploratory laparotomy were compared in cases of unresectable disease at surgery. Perioperative mortality and initiation of chemotherapy were similar between the groups. Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival compared to patients undergoing chemotherapy following a PDB (16.3 versus 10.3 months).In paper III, an end-to-end invaginated pancreaticojejunostomy was compared to the traditional duct to mucosa anastomosis in the setting of a randomized controlled trial. Patients at high risk for developing a post-operative pancreatic fistula (POPF) were selected The results showed no difference in clinically significant pancreatic leaks. There were however significantly fewer cases of grade C POPF associated with the invaginated pancreaticojejunostomy. In paper IV the role of neoadjuvant chemotherapy (NACT) and upfront resection was retrospectively evaluated for patients with borderline resectable pancreatic tumors. Patients who underwent upfront resection versus NACT had comparable median overall survival rates when drop-outs were included in an intention-to-treat principle (9 vs 10.9 months respectively). Per-protocol analysis of patients that completed their intended therapy revealed no difference in the upfront surgery group (9.5 months) and a significantly longer survival in the NACT group (21.8 months).
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