Surgical Management of Cholecystoenteric Fistula in Patients With and Without Gallstone Ileus: An Experience of 29 Cases.

Background: Cholecystoenteric fistula (CEF) is an uncommon complication of cholelithiasis. Here, we report our experience on diagnostic methods and surgical management of CEF patients with and without gallstone ileus (GI). Methods: This is a retrospective cases series over an 11-year period (2011-2022). Data analyzed included preoperative characteristics, ultrasound, imaging features, operation findings and postoperative course. Results: A total of 29 patients diagnosed with CEF were enrolled, 51.7% (15/29) of whom were female, with a median age of 66 years (range: 35-96 years). With regards to subtype distribution, seventeen patients had cholecystoduodenal fistula (CDF), six had cholecystoconlonic fistula (CCF), three exhibited cholecystogastric fistula (CGF), one CDF combination with CCF and two CDF combination with type I Mirizzi syndrome. Twelve patients presented with gallstone ileus, and received one stage procedure or simple Enterolithotomy. The median operation time and blood loss of 157 min (range: 65-360 min) and 40 ml (range: 10-450 ml), respectively. Surgical complications, evidenced by fistula recurrence, were recorded in three patients (3/22; 13.6%), while four (4/29; 13.8%) and one patient (1/29; 3.4%) presented with wound infection and residual stone in common bile duct, respectively. No deaths were reported in our study. Conclusion: CEF is a rare complication of gallstone disease that is occasionally found during operation. To date, no consensus has been reached regarding efficacious treatment therapies for CEF patients. For a CEF patient with GI, one stage procedure should be selected prudently, while simple Enterolithotomy would be a mainstream choice for relieving bowel obstruction.

Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer.

Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been identified in the blood circulation of patients with cancer metastasis, and metastatic cancer cells can recruit circulating CAFs. However, primary carcinoma sites usually regulate the behavior of metastatic cancer cells through exosomes. Here, we hypothesized that cancer-derived exosomes could enhance CAF recruitment. Exosomes secreted by pancreatic cancer cells (PANC-1 and MIA PaCa-2) were isolated and characterized. The ability of pancreatic cancer to recruit pancreatic stellate cells (PSCs) was assessed with Transwell assays in vitro and bioluminescent imaging in a mouse model in vivo, and the underlying molecular mechanism was also investigated. The results showed that pancreatic cancer cell-derived exosomes (Exo-Pan and Exo-Mia) promoted the pancreatic cancer recruitment of PSCs. This effect was mediated partially by the transfer of the exosomal protein Lin28B to the recipient cells to activate the Lin28B/let-7/HMGA2/PDGFB signaling pathway. These results suggested that exosomes derived from local cancer could promote the formation of distant metastases through transferring the exosomal protein Lin28B to the metastatic cancer cells.