Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma

Background@#/Aim: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated. @*Methods@#Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay. @*Results@#CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2. @*Conclusions@#CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.

Single institute experience of pancreatico-enteric anastomosis failure after pancreaticoduodenectomy

PURPOSE: We have summarized the experience of our institution related to what treatment has been performed in patients with pancreatic fistula and their outcome.METHODS: Seventy-eight pancreatico-enteric anastomosis failure (PEAF) patients of 403 pancreaticoduodenectomy (PD) were included for this retrospective study. PEAF was defined by the presence of rich amylase (over 10,000 IU/L) in drainage fluid at postoperative day 5 to 7 and radiographic demonstration of the anastomotic breakdown and associated local fluid collection. The management was analyzed by observation group (O group), intervention (I group) and surgery group (S group).RESULTS: Preoperative clinical status of the PEAF group and non-PEAF group was similar. Bile duct cancer was the highest risk subgroup of the PEAF (P=0.001) and the pancreatic adenocarcinoma showed the least risk for the PEAF (P<0.001). Among the 78 PEAF patients, 50 were managed as a conservative treatment, 15 patients were received radiologic intervention and 13 patients performed rescue surgery. Among these three subgroups, there was no statistical significance in the patient's demographics, clinical status, surgical factors and disease nature. However, mortality was significantly higher in the S group (P<0.001). The mortality cases were developed one and six patients in O and S group, respectively. Surgical procedures in S group were completion total pancreatectomy with or without splenectomy (n=12) and pancreatectomy preserving spleen in four (28.6%). Pancreaticogastrostomy repair and Roux-en-Y pancreaticojejunostomy reconstruction were performed each case, respectively.CONCLUSION: Proper drainage catheter indwelling during the PD or postoperative radiological intervention can effectively manage the PEAF without surgical interventional treatment.

Operative Management of the Endoscopic Retrograde Cholangiopancreatography Injury / 한국간담췌외과학회지

BACKGROUND/AIMS: Diagnostic or thepapeutic endoscopic retrograde cholangiopancreatography (ERCP) is the mainstream for the pancreaticobiliary disease. However, the ERCP related complications are serious and sometimes fatal to the patients. We have reviewed our experiences of the operative management for the ERCP injury. METHODS: Medical records of 13 patients who underwent laparotomic surgical intervention for various ERCP injuries from March 1996 to August 2002 at Department of Surgery, the Catholic University of Korea were reviewed. RESULTS: The age range of the patients was from 28 to 85 years. There were 5 females and 8 males. 6 patients showed the duodenal perforations and 4 patients suffered from bleedings around the ampulla of Vater. One of the 4 bleeding patients had huge expanding submucosal hematomas throughout the entire duodenum. We found massive retroperitoneal extraluminal air density in one patient but we could not find any leakage of the contrast media during the upper gastrointestinal series, however, this patient complained aggravated peritoneal irritation sign, so we explored the abdomen. Most of the patients had free abdominal or retroperitoneal air shadows (n=7) on plain chest or abdominal X-ray. We diagnosed the uncontrolled bleeding from the sphincterotomy site using the gastroduodenal fiberscopes in 3 patients. On the computed tomogaphic images, one patient showed a huge duodenal hematoma, another one had a retroperitoneal fluid collection and another one revealed a retroperitoneal air shadow. One patient showed aggravated pancreatitis on the serial CT scan and finally the patient developed a hemorrhagic necrotizing pancreatitis, then we explored the abdomen and tried peripancreatic drainage but we lost the patient in 19 postoperative day due to sepsis. The other 12 patients survived by the various surgical procedures. For the 6 patients, we performed duodenotomic sphincteroplasty, tube duodenostomy and biliary drainage with T-tube. One patient survived with Whipple's procedure, one patient improved by the pyloric exclusion and one patient cured with the duodenal diverticulization. Other procedures were primary repair of the duodenum, transduodenal sphincteroplasty and just cholecystectomy and T-tube choledochostomy. CONCLUSION: There was tendency to uneventful improvement of patients by the early detection and urgent laparotomic surgical intervention of the ERCP complication.

Choledochoscopic Electrohydraulic Lithotripsy for the Retained Bile Duct Stones / 한국간담췌외과학회지

Choledochoscopic lithotomy with the aid of electrohydraulic lithotripsy ( EHL ) was performed in 12 patients at the Department of Surgery, College of Medicine, the Catholic University of Korea, St. Vincent Hospital between January 1996 and March 1998. This retrospective analysis include 4 patients with common bile duct (CBD) stones, 5 patients with intrahepatic duct (IHD) stones, and 3 patients with CBD & IHD stones. The male to female ratio was 1 to 2. The peak incidence of age was the fifty. As a route for the choledochoscopy, a T-tube tract was used in 9 patients, while percutaneous biliary drainage followed by dilatation of the tract was established in 3 patients. The largest stones measured 22mm (by 5mm), the average is 10.3mm. Average number of session which performed for IHD stones was 3.7, while that of CBD stones was 2.7. Complete removal of the stones was achieved in 7 of 12 patients. Retained stones of CBD were removed completely in all cases. We could not removed retained stones completely in cases of multiple, impacted stones in peripheral ducts, associated stricture and acute angulation of IHD & CHD which choledochoscopic manipulation make difficult. Minor complications were bleeding from the bile duct mucosa in 1 patient and postprocedure chills and fever in 1 patient. In conclusion, choledochoscopic lithotomy with electrohydraulic lithotripsy is efficient and will be useful to remove biliary calculi in patients who have poor surgical risks.

Percutaneous Cholecystostomy / 한국간담췌외과학회지

BACKGROUND/AIMS: Cholecystectomy remains the best treatment for acute cholecystitis but may cause high morbidity or mortality in critically ill or elderly patients. METHODS: We performed ultrasonography-guided percutaneous cholecystostomy under local anesthesia in 18 elderly or critically ill patients with suspected acute cholecystitis between 1996 and 1999. RESULTS: Among the 18 patients, 16 had cholecystitis(11 calculous and 5 acalculous); in 2 patients, the procedure was only diagnostic. In 13 of 16 patients with acute cholecystitis, immediate relief of symptoms and significant improvement of laboratory signs of cholecystitis occurred. Persistent signs of cholangitis due to combined common bile duct and intrahepatic duct stones lead to laparotomy in 2 patients. One of these patients died due to pneumonia. Among 13 patients with cholecystitis, 5 patients underwent elective cholecystectomy(4: calculous, 1: acalculous) in 5 and 7 postprocedure days. One laparoscopic cholecystectomy was performed in these patients in 3 months. There was no any operative complication in elective cholecystectomy for these patients. The other 8 patients are symptom-free with an intact gallbladder after mean follow-up period of 17 months. In 2 patients, postprocedure radiologic signs of right pleural effusion were noted but resolved in 10 days in both patients. In one patient minor bleeding was noted but improved by observation only. Mortality rate of a patient with cholecystitis, treated by percutaneous cholecystostomy, was 12.5 percent( 2 of 16). CONCLUSION: These results indicate that percutaneous cholecystostomy is an effective temporary measure in elderly or critically ill patients.