Migration of biliary plastic stents: experience of a tertiary center

Background and study aims  Stent migration occurs in about 5–10% of patients undergoing biliary stenting. The aim of this study was to analyze the risk factors for stent migration in patients with benign and malignant strictures. Patients and methods  We retrospectively analyzed records of 524 biliary plastic stent placement procedures. Details noted included the cause and localization of stricture, characteristics and number of stents, direction of stent migration, presentation of patient with migrated stent, and the methods used for retrieval of migrated stents. Results  Two hundred and four (38.9%) of the procedures were performed for benign biliary strictures (BBS) and 320 (61.1%) for malignant biliary strictures (MBS). Thirty-four patients had 45 migrated biliary stents. The rate of migration was 8.58% (proximal 4.58% and distal 4.00%). Migration frequency was higher in BBS compared with MBS (13.7% versus 5.3%, p = 0.001). In BBS, the rate of stent migration was higher in cases with one (19.3%) and two stents (20.9%) when compared with cases with multiple stents (2.7%) (p = 0.001; p = 0.001, respectively). Migration occurred more frequently (10.9%) in cases with two stents when compared both to cases with one stent (3.0%) and those with multiple stents (0%) in MBS (p = 0.008; p = 0.020, respectively). In BBS, short stents migrated more frequently proximally (77%) and long stents more frequently distally (73%) (p = 0.008). In BBS, migration in cases with proximal stricture occurred more frequently distally (76.9%), while in those with distal stricture, migration was more frequently proximal (73.3%) (p = 0.008). All of the proximally migrated stents could be successfully retrieved endoscopically. Conclusions  The risk of stent migration is higher in BBS compared with in MBS. The cases with multiple stents had significantly lower stent migration. In BBS, long stent, proximal and postcholecystectomy strictures were associated with distal migration, while short stent, distal and non-postcholecystectomy strictures were associated with proximal migration.     

Second-Look Operation for Unresectable Pancreatic Ductal Adenocarcinoma at a High-Volume Center

Background The value of re-exploration for pancreatic ductal adenocarcinoma after the initial diagnosis of unresectability is unclear. Methods In this study, we analyzed 33 patients who were re-explored after an initial diagnosis of unresectability. Results At the time of reoperation, a resectable tumor was found in 18 patients: therefore, 15 pancreaticoduodenectomies, two total pancreatectomies and one left resection were performed with three vascular resections. Morbidity and mortality rates for the cohort were 6/33 and 1/33, without significant differences between resectable and nonresectable patients. Length of stay, duration of operation, and blood loss were significantly increased in the resection group. Kaplan–Meier survival analysis demonstrated increased median survival for resected patients (1078 days after the initial operation versus 547 days in the group of unresectable patients; p = 0.018). Analysis of the reasons against initial resection showed that, if the patients had been sent to a tertiary referral center for pancreatic surgery, a different decision in favor of resection would probably have been made in 14 out of 33 patients. A review of 10 published reports on reoperation for pancreatic cancer revealed results comparable to our study in terms of low morbidity and mortality as well as a survival benefit. Conclusions Reoperation for pancreatic ductal adenocarcinoma that is initially deemed unresectable can be safely performed in a selected group of patients by experienced surgeons, supporting the concept of patient centralization in pancreatic surgery. Resection at the second operation may confer a survival benefit even when the initial findings preclude a potentially curative approach.     

Effect of fish oil, olive oil, and vitamin E on liver pathology, cell proliferation, and antioxidant defense system in rats subjected to partial hepatectomy

The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.     

The role of pancreatic stellate cells in pancreatic cancer

Since conventional and targeted therapies aiming at cancer cells have largely failed to prolong survival in pancreatic cancer, targeting the infrastructure of the tumor, hence its stroma is a novel strategy. It is believed that fibrotic and hypovascular stroma forms a barrier around cancer cells, hindering effective delivery of chemotherapy. Theoretically, antifibrotic therapy should reduce the compactness of the stroma and reduce the interstitial pressure, allowing better delivery of chemotherapy. This approach has worked successfully in a genetically engineered mouse model but failed in humans, paradoxically increasing mortality in the treatment arm. Normally, stromal cells deposit extracellular matrix as an innate defensive reaction to form a barrier between what is harmful and the rest of the body. Despite the significant amount of in vitro data suggesting the pro-tumorigenic roles of activated stellate cells, there is no reason to believe that stellate cells around genetically mutated cells are from the beginning there to support carcinogenesis. Such a stromal activation is also observed around PanIN lesions (which harbor genetically mutated cells) in chronic pancreatitis, where no cancer develops. In pancreatic cancer, the selection pressure created by the fibrotic and hypoxic stroma eventually leads to the evolution of more aggressive clones, indirectly contributing to the aggressiveness of the tumor. Here, the main problem is the late diagnosis of pancreatic cancer, which gives cancer cells enough time for malignant evolution. Therefore, applying antifibrotic therapy at a late stage can be counterproductive. It may increase delivery of chemotherapy, but also lead to the escape of cancer cells.     

The role of hypoxia in pancreatic cancer: a potential therapeutic target?

One of the key factors that correlates with poor survival of patients with pancreatic cancer is the extent of hypoxic areas within the tumor tissue. The adaptation of pancreatic cancer cells to limited oxygen delivery promotes the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development, which resist in most cases adjuvant therapies following tumor resection. In this article, the authors summarize the evidence demonstrating the significance of hypoxia in pancreatic cancer pathogenesis and discuss the possible hypoxia-induced mechanisms underlying its aggressive nature. We then conclude with promising strategies that target hypoxia-adapted pancreatic cancer cells.