The in situ near-total pancreatectomy (LIVOCADO procedure) for end-staged chronic pancreatitis

PURPOSE: Total pancreatectomy for severe pain in end-stage chronic pancreatitis may be the only option, but with vascular involvement, this is usually too high risk and/or technically not feasible. The purpose of the study was to present the clinical outcomes of a novel procedure in severe chronic pancreatitis complicated by uncontrollable pain and vascular involvement. METHODS: We describe an in situ near-total pancreatectomy that avoids peripancreatic vascular dissection (Livocado procedure) and report on surgical and clinical outcomes. RESULTS: The Livocado procedure was carried out on 18 (3.9%) of 465 patients undergoing surgery for chronic pancreatitis. There were 13 men and 5 women with a median (IQR) age of 48.5 (42.4–57) years and weight of 60.7 (58.0–75.0) kg. All had severe pain and vascular involvement; 17 had pancreatic parenchymal calcification; the median (IQR) oral morphine equivalent dose requirement was 86 (33–195) mg/day. The median (IQR) maximal pain scores were 9 (9–10); the average pain score was 6 (IQR 4–7). There was no peri-operative or 90-day mortality. At a median (IQR) follow-up of 32.5 (21–45.75) months, both maximal and average pain scores were significantly improved post-operatively, and at 12 months, two-thirds of patients were completely pain free. Six (33%) patients had employment pre-operatively versus 13 (72%) post-operatively (p = 0.01). CONCLUSIONS: The Livocado procedure was safe and carried out successfully in patients with chronic pancreatitis with vascular involvement where other procedures would be contraindicated. Perioperative outcomes, post-operative pain scores, and employment rehabilitation were comparable with other procedures carried out in patients without vascular involvement

StellaTUM: current consensus and discussion on pancreatic stellate cell research

The field of pancreatic stellate cell (PSC) biology is very young, as the essential in-vitro tools to study these cells (ie, methods to isolate and culture PSC) were only developed as recently as in 1998. Nonetheless, there has been an exponential increase in research output in this field over the past decade, with numerous research groups around the world focusing their energies into elucidating the biology and function of these cells. It is now well established that PSC are responsible for producing the stromal reaction (fibrosis) of two major diseases of the pancreas—chronic pancreatitis and pancreatic cancer. Despite exponentially increasing data, the methods for studying PSC remain variable. Although within individual laboratories methods are consistent, different methodologies used by various research groups make it difficult to compare results and conclusions. This article is not a review article on the functions of PSC. Instead, members of the Pancreatic Star Alliance (http://www.pancreaticstaralliance.com) discuss here and consolidate current knowledge, to outline and delineate areas of consensus or otherwise (eg, with regard to methodological approaches) and, more importantly, to identify essential directions for future research

Post cholecystectomy bile duct injury: early, intermediate or late repair with hepaticojejunostomy – an E-AHPBA multi-center study

Background: Treatment of bile duct injuries (BDI)during cholecystectomy depends on the severity of injury and the timing of diagnosis. Standard of care for severe BDIs is hepaticojejunostomy. The aim of this retrospective multi-center study was to assess the optimal timing for repair of BDI with hepaticojejunostomy. Methods: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients with hepaticojejunostomy after BDI from January 2000 to June 2016. Patients were stratified according to the timing of biliary reconstruction with hepaticojejunostomy: early (day 0–7), intermediate (1–6 weeks)and late (6 weeks–6 months). Primary endpoint was re-intervention >90 days after the hepaticojejunostomy and secondary endpoints were severe 90-day complications and liver-related mortality. Results: In total 913 patients from 48 centers were included in the analysis. In 401 patients (44%)the bile duct injury was diagnosed intraoperatively, and 126 patients (14%)suffered from concomitant vascular injury. In multivariable analysis the timing of hepaticojejunostomy had no impact on postoperative complications, the need for re-intervention after 90 days nor liver-related mortality. The rate of re-intervention more than 90 days after the hepaticojejunostomy was significantly increased in male patients but decreased in older patients. Severe co-morbidity increased the risk for liver-related mortality (HR 3.439; CI 1.37–8.65; p = 0.009). Conclusion: After BDI occurring during cholecystectomy, the timing of biliary reconstruction with hepaticojejunostomy did not have any impact on severe postoperative complications, the need for re-intervention or liver-related mortality. Individualised treatment after iatrogenic bile duct injury is still advisable. © 2019 International Hepato-Pancreato-Biliary Association Inc

Treatment of esophageal leakages with the Microtech-VAC-Stent: a monocentric early experience of three cases

Background: Endoscopic approaches in the treatment of transmural esophageal defects, either after esophageal resection or due to perforation, have demonstrated convincing feasibility. Surgical options are limited and associated with high morbidity and mortality rates. Currently, internal endoscopic drainage with pigtail stents, self-expanding metal stent (SEMS), or endoscopic vacuum therapy (EVT) are options for first-line treatment. Here, we report the outcome of the recently developed combination of SEMS and EVT using the endoscopic Microtech ® -VAC-Stent (EVS). Methods: Between June and July 2022, three consecutive patients (one female and two males) with esophageal transmural defects were treated with the Microtech ® -VAC-Stent. Two patients suffered from an anastomotic leak after oncologic gastroesophageal surgery, and one patient presented with esophageal perforation due to Boerhaave syndrome. Results: Three consecutive patients were successfully treated with EVS. In one patient, one EVS treatment was sufficient, whereas the other two patients needed two and six EVS exchanges. Exchanges were scheduled every 7 days and no procedural adverse events were observed. Conclusion: In line with the former case series, EVS therapy is a promising new approach for the treatment of esophageal leaks. Exchange of the EVS seems feasible every 7 days reducing interventions for the individual patient. Prospective studies comparing EVS with other endoscopic therapies are needed to define the best therapeutic approach

Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a cancer of the exocrine pancreas with unmet medical need and is strongly promoted by tumor-associated macrophages (TAM). The presence of TAMs is associated with poor clinical outcome, and their overall role, therefore, appears to be protumorigenic. The "don't eat me" signal CD47 on cancer cells communicates to the signal regulatory protein-α on macrophages and prevents their phagocytosis. Thus, inhibition of CD47 may offer a new opportunity to turn TAMs against PDAC cells, including cancer stem cells (CSC), as the exclusively tumorigenic population. EXPERIMENTAL DESIGN: We studied in vitro and in vivo the effects of CD47 inhibition on CSCs using a large set of primary pancreatic cancer (stem) cells as well as xenografts of primary human PDAC tissue. RESULTS: CD47 was highly expressed on CSCs, but not on other nonmalignant cells in the pancreas. Targeting CD47 efficiently enhanced phagocytosis of a representative set of primary human pancreatic cancer (stem) cells and, even more intriguingly, also directly induced their apoptosis in the absence of macrophages during long-term inhibition of CD47. In patient-derived xenograft models, CD47 targeting alone did not result in relevant slowing of tumor growth, but the addition of gemcitabine or Abraxane resulted in sustained tumor regression and prevention of disease relapse long after discontinuation of treatment. CONCLUSIONS: These data are consistent with efficient in vivo targeting of CSCs, and strongly suggest that CD47 inhibition could be a novel adjuvant treatment strategy for PDAC independent of underlying and highly variable driver mutations

Chloroquine targets pancreatic cancer stem cells via inhibition of CXCR4 and hedgehog signaling.

Pancreatic ductal adenocarcinoma is one of the deadliest carcinomas and is characterized by highly tumorigenic and metastatic cancer stem cells (CSC). CSCs evade available therapies, which preferentially target highly proliferative and more differentiated progenies, leaving behind CSCs as a putative source for disease relapse. Thus, to identify potentially more effective treatment regimens, we screened established and new compounds for their ability to eliminate CSCs in primary pancreatic cancer (stem) cells in vitro and corresponding patient-derived pancreatic cancer tissue xenografts in vivo. Intriguingly, we found that in vitro treatment with the antimalarial agent chloroquine significantly decreased CSCs, translating into diminished in vivo tumorigenicity and invasiveness in a large panel of pancreatic cancers. In vivo treatment in combination with gemcitabine was capable of more effectively eliminating established tumors and improved overall survival. The inhibitory effect of chloroquine was not related to inhibition of autophagy, but was due to inhibition of CXCL12/CXCR4 signaling, resulting in reduced phosphorylation of ERK and STAT3. Furthermore, chloroquine showed potent inhibition of hedgehog signaling by decreasing the production of Smoothened, translating into a significant reduction in sonic hedgehog-induced chemotaxis and downregulation of downstream targets in CSCs and the surrounding stroma. Our study demonstrates that via to date unreported effects, chloroquine is an effective adjuvant therapy to chemotherapy, offering more efficient tumor elimination and improved cure rates. Chloroquine should be further explored in the clinical setting as its success may help to more rapidly improve the poor prognosis of patients with pancreatic cancer

Expression and significance of FXYD-3 protein in gastric adenocarcinoma

Objective: FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down-regulated in other types of cancers (such as colon and kidney cancer). No study has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma. Patients and methods: FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n = 29) and gastric adenocarcinoma (n = 51), obtained from surgical resection of gastric cancer patients. Results: FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X-2=13.210, p andlt; 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X-2 = 5.765, p = 0.016). However, FXYD-3 expression was not correlated with patients gender, age, tumor size, lymph node status and histological grade (p andgt; 0.05). Conclosion: Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma.Original Publication:Zhen-Long Zhu, Zeng-Ren Zhao, Yu Zhang, Yan-Hong Yang, Zheng-Min Wang, Dong-Sheng Cui, Ming-Wei Wang, Joerg Kleeff, Hany Kayed, Bao-Yong Yan and Xiao-Feng Sun, Expression and significance of FXYD-3 protein in gastric adenocarcinoma, 2010, DISEASE MARKERS, (28), 2, 63-69.http://dx.doi.org/10.3233/DMA-2010-0669Copyright: Ios Presshttp://www.iospress.nl