Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Completion pancreatectomy or a pancreas-preserving procedure during relaparotomy for pancreatic fistula after pancreatoduodenectomy: a multicentre cohort study and meta-analysis.

BACKGROUND: Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy. METHODS: This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84). CONCLUSION: Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.

Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial.

BACKGROUND: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. METHODS: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. DISCUSSION: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. TRIAL REGISTRATION: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004.

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

High mortality rates after nonelective colon cancer resection: results of a national audit.

AIM: Colon cancer resection in a nonelective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on nonelective resection. METHOD: Data were obtained from the Dutch Surgical Colorectal Audit. Patients undergoing colon cancer resection in the Netherlands between January 2009 and December 2013 were included. Patient, treatment and tumour factors were analysed in relation to the urgency of surgery. The primary outcome was 30-day postoperative mortality. RESULTS: The study included 30 907 patients. A nonelective colon cancer resection was performed in 5934 (19.2%) patients. There was a 4.4% overall mortality rate, with significantly more deaths after nonelective surgery (8.5% vs 3.4%, P < 0.001). Older patients, male patients and patients with high comorbidity, advanced tumours, perforated tumours, a tumour in the right or transverse colon and postoperative anastomotic leakage were at risk of postoperative death. In nonelective resections, a right-sided tumour and postoperative anastomotic leakage were associated with high mortality. CONCLUSION: Nonelective colon cancer resection is associated with high mortality. In particular, right-sided resections and patients with tumour perforation are at particularly high risk. The optimization of patients prior to surgery and expeditious operation after diagnosis might prevent the need for a nonelective resection.

Identification of anastomotic leakage after colorectal surgery using microdialysis of the peritoneal cavity.

BACKGROUND: Early detection of colorectal anastomotic leakage (AL) may lead to better outcome. AL may be preceded by change in local metabolism and local ischaemia. Microdialysis of the peritoneal cavity is able to measure these changes in real-time and is minimally invasive. The aim of this prospective cohort study was to compare values of intraperitoneal microdialysis in patients with AL to patients without AL after open and laparoscopic colorectal surgery. METHODS: Twenty-four patients underwent surgery for left-sided, sigmoid and rectal carcinoma with creation of an anastomosis. Intraoperatively a juxta-anastomotical intraperitoneal and subcutaneous microdialysis catheter was placed. The levels of lactate, pyruvate, glucose and glycerol in the dialysate were measured every 4 h during the first 5 post-operative days, and mean values and area under the curve (AUC) were calculated. RESULTS: Mortality was 0 % and morbidity 38 %. In 3 patients (17 %), AL occurred. In patients with AL, post-operative peritoneal lactate level was 3.2 mmol/l (standard deviation (SD) 0.9) for patients without AL, compared to 4.4 mmol/l (SD 1.5) in case of AL (p = 0.03 for AUC). Intraperitoneal glucose levels were 8.1 mmol/l (SD 1.3), compared to 7.8 mmol/l (SD 2.2) in the complicated course (ns for AUC). Mean intraperitoneal lactate/pyruvate-ratio was 19.2 (SD 3) after colorectal surgery without AL compared to 25 (SD 4.7) in case of AL (non-significant (ns) for AUC). No significant differences were observed between patients who underwent laparoscopic resection and those who underwent open resection. CONCLUSIONS: Anastomotic leakage was preceded by a significantly higher AUC and mean value of lactate levels during the first 5 post-operative days. To identify cut-off values for clinical use, pooling of data is necessary.

Anastomotic leakage as an outcome measure for quality of colorectal cancer surgery.

INTRODUCTION: When comparing mortality rates between hospitals to explore hospital performance, there is an important role for adjustment for differences in case-mix. Identifying outcome measures that are less influenced by differences in case-mix may be valuable. The main goal of this study was to explore whether hospital differences in anastomotic leakage (AL) and postoperative mortality are due to differences in case-mix or to differences in treatment factors. METHODS: Data of the Dutch Surgical Colorectal Audit were used. Case-mix factors and treatment-related factors were identified from the literature and their association with AL and mortality were analysed with logistic regression. Hospital differences in observed AL and mortality rates, and adjusted rates based on the logistic regression models were shown. The reduction in hospital variance after adjustment was analysed with Levene's test for equality of variances. RESULTS: 17 of 22 case-mix factors and 4 of 11 treatment factors related to AL derived from the literature were available in the database. Variation in observed AL rates between hospitals was large with a maximum rate of 17%. This variation could not be attributed to differences in case-mix but more to differences in treatment factors. Hospital variation in observed mortality rates was significantly reduced after adjustment for differences in case-mix. CONCLUSIONS: Hospital variation in AL is relatively independent of differences in case-mix. In contrast to 'postoperative mortality' the observed AL rates of hospitals evaluated in our study were only slightly affected after adjustment for case-mix factors. Therefore, AL rates may be suitable as an outcome indicator for measurement of surgical quality of care.

Treatment of colorectal anastomotic leakage: results of a questionnaire amongst members of the Dutch Society of Gastrointestinal Surgery.

Anastomotic leakage after colorectal surgery is correlated with considerable morbidity and mortality. Although many studies focus on risk factors and detection, studies on the treatment strategy for colorectal anastomotic leakage are scarce. A national questionnaire amongst 350 members of the Dutch Society for Gastrointestinal Surgery was undertaken on the current treatment of colorectal anastomotic leakage. The response was 40% after two anonymous rounds. 27% of the respondents state that a leaking anastomosis above the level of the promontory should be salvaged in ASA 1-2 patients <80 years of age, for ASA 3 and/or >80 years of age this percentage is 7.3%. For an anastomosis under the promontory, 50% of the respondents choose preserving the anastomosis for ASA 1-2 compared to 17% for ASA 3 and/or >80 years of age. In ASA 1-2 patients with a local abscess after a rectum resection without protective ileostomy, 31% of the respondents will create an protective ileostomy, 40% break down the anastomosis to create a definite colostomy, in ASA 3 and/or >80 years of age 14% of the respondents create a protective ileostomy and 63% a definitive colostomy. In ASA 1-2 patients with peritonitis after a rectum resection with deviating ileostomy, 31% prefer a laparotomy for lavage and repair of the anastomosis, 25% for lavage without repair and 36% of the respondents prefer to break down the anastomosis. When the patient is ASA 3 and/or >80 years of age, 13% prefer repair, 9% a lavage and 74% breaking down the anastomosis. This questionnaire shows that in contrast to older people, more surgeons make an effort to preserve the anastomosis in younger people.

Results of surgery for perforated gastroduodenal ulcers in a Dutch population.

OBJECTIVE: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment. PATIENTS AND METHODS: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality. RESULTS: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class. CONCLUSIONS: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment.

Problems with technical equipment during laparoscopic surgery. An observational study.

BACKGROUND: This study was designed to investigate the incidence of technical equipment problems during laparoscopic procedures. METHODS: A video-capturing system was used, consisting of an analog video recorder with three camera image inputs and a microphone. Problems with all technical equipment used by the surgical team, such as the insufflator, diathermy apparatus, monitors, light source, camera and camera unit, endoscope, suction devices, and instruments, were registered. RESULTS: In total, 30 procedures were randomly videotaped. In 87% (26/30) of the procedures, one or more incidents with technical equipment (49 incidents) or instruments (9 incidents) occurred. In 22 of those incidents (45%) the technical equipment was not correctly positioned or not present at all; in the other 27 (55%), the equipment malfunctioned as a result of a faulty connection (9), a defect (5), or the wrong setting of the equipment (3). In 10 (20%) cases the exact cause of equipment malfunctioning was unclear. CONCLUSIONS: The incidence of problems with laparoscopic technical equipment is high. To prevent such problems, improvement and standardization of equipment is needed, combined with the incorporation of checklist use before the start of a surgical procedure. Future research should be aimed at development, implementation, and evaluation of these measures into the operating room.

Bacterial translocation from the biliary tract to blood and lymph in rats with obstructive jaundice.

BACKGROUND: The disruption of the hepatocyte tight junctions observed in biliary obstruction suggests altered permeability of the blood-bile barrier. In this study the role of biliary obstruction and increased biliary pressure on the translocation of bacteria from biliary tract to bloodstream and lymphatic system were evaluated. MATERIALS AND METHODS: Rats underwent distal bile duct ligation (BDL, n = 33) for two weeks or a sham celiotomy (n = 21). Seventeen of the 33 BDL rats underwent subsequent biliary decompression by a choledochojejunostomy (CJ). Two weeks after the final operation, a laparotomy was performed again and the CBD, the thoracic duct, and the caval vein were canulated. Next, a suspension containing 10(8) Escherichia coli/ml was retrogradely infused in the CBD for 5 min at 5 or 20 cm H2O above the secretory biliary pressure. RESULTS: A higher biliary infusion pressure resulted in a significant increase of cfu E.coli per milliliter of blood in all the three groups (Sham, BDL, CJ). BDL rats showed significantly more bacterial translocation to the bloodstream than the shams. After biliary decompression, translocation normalized to the control levels. At 5 cm H2O infusion pressure only one lymph culture was positive (CJ group). At 20 cm H2O overpressure, nine lymph cultures were E.coli positive (P = 0.03). These were found mainly in groups with a nonobstructed bile duct (Sham and CJ 40% vs BDL 10%). CONCLUSION: Translocation of bacteria from biliary tract to bloodstream increased at higher intrabiliary pressures. Longstanding bile duct obstruction was an independent determinant for cholangiovenous reflux. Bacterial translocation to the lymphatic system did not parallel translocation to the bloodstream, although in the nonobstructed biliary tract, increased bacterial translocation to the lymphatic system was pressure related.

Preoperative biliary drainage, colonisation of bile and postoperative complications in patients with tumours of the pancreatic head: a retrospective analysis of 241 consecutive patients.

OBJECTIVE: To analyse the outcome of preoperative biliary drainage in patients being operated on for a tumour in the pancreatic head. DESIGN: Retrospective study. SETTING: University hospital, The Netherlands. SUBJECTS: Consecutive series of 241 patients. MAIN OUTCOME MEASURES: Decline in bilirubin concentrations and bacterial contamination of bile as a result of preoperative drainage. Incidence of postoperative complications in patients who underwent preoperative drainage and those who did not. RESULTS: 184/241 patients underwent preoperative biliary drainage. Endoscopic drainage was the most effective, shown by a median reduction in bilirubin concentrations of 82%, 74%, and 50% after endoscopic drainage (n = 149), papillotomy (n = 25) and external drainage (n = 10), respectively. Bacterial contamination of bile was significantly more common when an endoprosthesis was used, but did not result in a higher rate of infective complications. 163 Whipple's resections, 33 total pancreatectomies, and 45 biliary-enteric bypasses were performed. 137/241 (57%) patients had postoperative complications. There was no significant difference in the incidence of postoperative complications between patients who had preoperative biliary drainage and those who did not (p = 0.4).

Outcome of microscopically nonradical, subtotal pancreaticoduodenectomy (Whipple's resection) for treatment of pancreatic head tumors.

From 1983 to 1992 a total of 240 patients with a pancreatic head tumor underwent laparotomy to assess the resectability of the tumor. In 44 patients the tumor was not resected because of distant metastases (n = 20) or major vascular involvement or local tumor infiltration (n = 24) not detected during the preoperative workup. A palliative biliary and gastric bypass was performed in these patients. All other patients underwent a subtotal (Whipple's resection, n = 164) or total (n = 32) pancreaticoduo-denectomy. However, in 56 cases after Whipple's resection, microscopic examination of the specimen showed tumor invasion in the dissection margins. For this reason, these resections were considered palliative. We compared hospital mortality, morbidity, and long-term survival of patients who had undergone a biliary and gastric bypass for a locally advanced tumor (group A, n = 24) with a matched group of patients who had undergone a macroscopically radical Whipple's resection that on microscopic examination proved to be nonradical (group B, n = 36). Both groups were comparable with regard to age (mean 61 years in both groups), duration of symptoms (8 weeks in group A and 10 weeks in group B), and tumor size (mean 4.25 cm in group A and 4.30 cm in group B). Median postoperative hospital stay was 18 days in group A and 25 days in group B. Postoperative complications (intraabdominal abscess, gastrointestinal hemorrhage, anastomotic leakage, delayed gastric emptying) occurred in 33% of patients in group A and in 44% of patients in group B. Hospital mortality was 0% and 3% in group A and group B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of biliary endoprostheses on the extrahepatic bile ducts in relation to subsequent operation of the biliary tract.

Despite the widespread use of transpapillary biliary endoprostheses, little is known about their effect on the extrahepatic bile ducts. In an experimental study in dogs, we induced inflammatory changes in the bile ducts by stent insertion and studied the reversibility of these changes after stent removal. In addition, the consequences of a period of preoperative stenting for subsequent operation of the biliary tract and the eventual detrimental effects of stenting on the histologic factors of the liver were studied. Twenty-six mongrel dogs were randomly divided into four groups: group 1, stenting during four weeks; group 2, after four weeks stenting, construction of a hepaticojejunostomy; group 3, four days of common bile duct (CBD) ligation, four weeks stenting and hepaticojejunostomy, and group 4, four days of CBD ligation and hepaticojejunostomy. All dogs were sacrificed two months after the last procedure. Hepatic biopsies were obtained during each procedure and bile duct biopsies during hepaticojejunostomy and upon sacrifice. Four weeks of stenting of a normal or obstructed CBD resulted in fibrosed bile ducts, showing severe chronic inflammation with papillary hyperplasia of the epithelium. All bile cultures grew fecal bacteria. Two months after stent removal, inflammation was still present, albeit less severe. Stenting and subsequent surgical treatment resulted in a higher incidence of postoperative complications (54 percent) compared with the control group (14 percent), although this did not reach statistical significance. Hepatic histologic factors were not markedly changed after transpapillary endoprosthesis placement, but after hepaticojejunostomy cholangiolitis was observed. Whenever transpapillary biliary endoprostheses are used, the local effects on the extrahepatic bile ducts and the subsequent bacterial contamination of the bile should be considered.

Morphologic changes of extrahepatic bile ducts during obstruction and subsequent decompression by endoprosthesis.

The morphologic changes of the extrahepatic biliary tract during obstruction and the effects of biliary decompression by means of an endoprosthesis on the bile duct wall were studied by light microscopy and scanning electron microscopy. Common hepatic duct biopsy specimens and bile cultures were obtained during surgery from 30 patients with a distal common bile duct obstruction caused by a tumor. Thirteen patients had obstructed bile ducts of 3 weeks' duration (group A). Seventeen patients had had jaundice for a period of 4 weeks and had subsequently undergone preoperative endoscopic biliary stenting for a period of 4 weeks (group B). Three autopsy specimens from patients without hepatobiliary disease served as controls. The results showed that the initial dilatation and thickening of the obstructed ducts in group A were associated with a mild inflammation, a moderate degree of fibrosis, and local epithelial disintegration. The presence of an endoprosthesis, however (group B), induced severe inflammatory changes with considerable fibrosis and ulcerative lesions, resulting in markedly thickened ducts with lumina approximating the diameter of the stent. Three of 13 (24%) bile cultures in group A were positive and 14 of 17 (82%) in group B were positive.