Early closure of a multicenter randomized clinical trial of endoscopic stenting versus surgery for stage IV left-sided colorectal cancer.

BACKGROUND AND STUDY AIMS: The introduction of self-expandable metal stents has offered a promising alternative for palliation of malignant left-sided colonic obstruction. This randomized clinical trial aimed to assess whether a nonsurgical policy, with endoluminal stenting, is superior to surgical treatment in patients with stage IV left-sided colorectal cancer and imminent obstruction. PATIENTS AND METHODS: Patients with incurable left-sided colorectal cancer who fulfilled the study criteria were randomly assigned to nonsurgical or surgical treatment. The primary outcome measure was survival in good health out of hospital (World Health Organization performance scores 0 or 1). RESULTS: A high number of serious adverse events in the nonsurgical arm led to premature closure of the trial. Ten patients were allocated to surgical treatment and 11 patients to nonsurgical palliation. The median survival in good health out of hospital during the first year was 56 days (interquartile range 7.5 - 338.5 days) in the surgical arm vs. 38 days (interquartile range 5.25 - 288.75 days) in the nonsurgical arm (P = 0.68). Eleven adverse events (six perforations) occurred in the nonsurgical arm vs. one adverse event in the surgical arm (P < 0.001). Of the six perforations, two were stent-related because they occurred at the proximal edge of the stent by erosion through a normal colon wall; one was probably stent-related (it was located in the region of the proximal half of the stent); one was a colon blowout; and two were late tumor perforations in patients on chemotherapy. CONCLUSIONS: The unexpected high rate of perforation in the nonsurgical arm might be specifically WallFlex-related or enteral stent-related in patients on chemotherapy and warrants attention.

Circumferential and axial distribution of esophageal mucosal damage in reflux disease.

The aim of this study was to evaluate the axial and radial distribution of histological markers including hyperplasia of the basal cell layer, elongation of the papillae and dilatation of the intercellular spaces of the squamous epithelium in patients with nonerosive reflux disease compared to controls and to relate this to the macroscopic topography in erosive reflux disease. Two different study populations were included in this report. Endoscopic esophageal biopsies were taken from 21 healthy control subjects and 21 nonerosive reflux disease patients before and after 4 weeks of esomeprazole therapy. Endoscopic still images from 50 erosive reflux disease patients were reviewed for the radial orientation of LA grade A and/or B esophagitis (Los Angeles criteria for grading of reflux esophagitis). The 3 o'clock position of the squamocolumnar junction showed significantly thicker basal cell layer (P=0.011) and more intercellular space dilatation (P=0.01) in nonerosive reflux disease patients compared to the 9 o'clock position. Only a significant difference in dilatation of the intercellular spaces (P=0.018) between nonerosive reflux disease patients and controls were observed in the 3 o'clock region at the squamocolumnar junction, whereas 1-2 cm orally, all three histological criteria differed significantly (P

Magnification endoscopy for diagnosis of nonerosive reflux disease: a proposal of diagnostic criteria and critical analysis of observer variability.

BACKGROUND AND STUDY AIMS: This study tested the diagnostic value of high-resolution endoscopy for the recognition of subtle diagnostic esophageal mucosal changes in nonerosive reflux disease. PATIENTS AND METHODS: Ten control subjects and eleven patients with nonerosive reflux disease confirmed by a validated questionnaire, standard endoscopy, and 24-hour pH-metry participated in the study. Still images were collected by high-resolution endoscopes from the distal esophagus in a standardized manner, incorporating iodine staining. Assessments were repeated in the patients with reflux disease after 4 weeks of esomeprazole therapy. Interobserver variability in the recognition of the proposed criteria was initially evaluated by 27 endoscopists using an Internet-based process. After optimisation of image quality the evaluation was repeated face-to-face with six expert endoscopists. RESULTS: No criterion was identified in either assessment that was sufficiently sensitive and specific to patients with reflux disease to be clinically useful. The kappa value, used to assess interobserver variation, was acceptably high only for invisibility of palisade vessels (0.59). Triangular indentations, apical mucosal breaks, and pinpoint blood vessels at the squamocolumnar junction were identified more frequently in the patients with reflux disease ( P < 0.05). These changes and the invisibility of the palisade vessels were significantly less prevalent in reflux patients after therapy ( P < 0.01). CONCLUSIONS: Though some distal esophageal mucosal appearances observed with the high-resolution endoscope appeared to be related to nonerosive esophageal mucosal injury, none of these changes proved to be sufficiently sensitive and specific to justify their use as a diagnostic criterion for nonerosive reflux disease.

Mechanisms of biliary stent clogging: confocal laser scanning and scanning electron microscopy.

BACKGROUND AND STUDY AIMS: Endoscopic insertion of plastic biliary endoprostheses is a well-established treatment for obstructive jaundice. The major limitation of this technique is late stent occlusion. In order to compare events involved in biliary stent clogging and identify the distribution of bacteria in unblocked stents, confocal laser scanning (CLS) and scanning electron microscopy (SEM) were carried out on two different stent materials - polyethylene (PE) and hydrophilic polymer-coated polyurethane (HCPC). PATIENTS AND METHODS: Ten consecutive patients with postoperative benign biliary strictures were included in the study. Two 10-Fr stents 9 cm in length, one made of PE and the other of HCPC, were inserted. The stents were electively exchanged after 3 months and examined using CLS and SEM. RESULTS: No differences were seen between the two types of stent. The inner stent surface was covered with a uniform amorphous layer. On top of this layer, a biofilm of living and dead bacteria was found, which in most cases was unstructured. The lumen was filled with free-floating colonies of bacteria and crystals, surrounded by mobile laminar structures of mucus. An open network of large dietary fibers was seen in all of the stents. CONCLUSIONS: The same clogging events occurred in both PE and HCPC stents. The most remarkable observation was the identification of networks of large dietary fibers, resulting from duodenal reflux, acting as a filter. The build-up of this intraluminal framework of dietary fibers appears to be a major factor contributing to the multifactorial process of stent clogging.

Self-expanding metal stents in benign biliary strictures due to chronic pancreatitis.

BACKGROUND AND STUDY AIMS: In selected patients with chronic pancreatitis in whom conventional plastic stenting fails and in whom surgery is contraindicated or declined, insertion of a biliary self-expanding metal stent (SEMS) may be a valuable treatment option. PATIENTS AND METHODS: Between 1994 and 1999, 13 patients with chronic pancreatitis received SEMS for benign biliary strictures (four women and nine men; mean age 56). The indications for SEMS placement were: contraindication to surgery (n = 10), presumed inoperable pancreatic carcinoma (n = 1), concomitant unresectable lung cancer (n = 1), and declined surgery (n = 1). The success of treatment was defined as adequate biliary drainage due to SEMS therapy. RESULTS: The mean follow-up period was 50 months (range 6 days - 86 months). Nine patients (69 %) were successfully treated with SEMS therapy: a patent first SEMS (n = 5); a patent second SEMS inserted through the first SEMS (n = 3); and one patent SEMS after balloon cleaning. SEMS treatment was not successful in four patients (due to stent migration in one case and occlusion in three ). The mean patency period of the SEMS was 60 months (95 % CI, 43 months - 77 months). At 33 months, the probability of adequate biliary drainage with SEMS therapy was 75 %. CONCLUSIONS: SEMS therapy was safe and provided successful and prolonged biliary drainage in a selected group of patients with benign biliary strictures due to chronic pancreatitis in whom surgical intervention was not possible or desirable.

A prospective randomized study of hydrophilic polymer-coated polyurethane versus polyethylene stents in distal malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Hydrophilic polymer-coated polyurethane (HPCP) stents have a low friction coefficient and a hydrophilic layer, which may reduce biofilm formation and increase the period of stent patency. We compared the patency rates with this new stent with the standard Amsterdam-type polyethylene (PE) stent in a prospective randomized trial. PATIENTS AND METHODS: One hundred patients with an unresectable distal malignant bile duct stricture without a previous drainage procedure were randomly assigned to receive either a HPCP stent or a PE stent. The diameter (10 Fr), length (9 cm) and stent design (Amsterdam type) were similar in both stents. Nine patients were excluded. Forty-four patients received an HPCP stent and 47 patients a PE stent. The diagnoses included carcinoma of the pancreas (n = 78), papilla (n = 1), bile duct (n = 10), and metastases (n = 2). RESULTS: Stent insertion was successful in all patients. Stent dysfunction occurred in 27 of the HPCP stents and 20 of the PE stents, with median stent patency periods of 77 days (95 % CI, 53-101 days) for HPCP stents and 105 days (95 % CI, 42-168 days) for PE stents. The patency period was significantly longer for the PE stent (P = 0.04). Early complications occurred in four patients (4%), one in the HPCP group and three in the PE group. CONCLUSION: Hydrophilic polymer-coated polyurethane stents do not prolong the patency period of biliary stents. In fact, the current standard treatment using polyethylene stents in patients with distal malignant biliary obstruction showed a significantly longer patency period.

Unexpected prolonged extreme hypocalcaemia and an inadequate PTH response in a patient with metastatic breast carcinoma.

Although hypercalcaemia is often encountered during the course of malignant disease, hypocalcaemia appears to be rather rare. We describe a 37-year-old patient with metastatic carcinoma of the breast, who developed extreme hypocalcaemia (as low as 0.75 mmol calcium per litre) after chemotherapy. This is caused by a combination of hungry-bone syndrome and an insufficient parathyroid response. The latter may be the result of a direct toxic effect of chemotherapy on parathyroid hormone (PTH) synthesis possibly in combination with microscopic tumour infiltration in the parathyroid glands. Correction of the extreme hypocalcaemia over a period of 100 days by oral and intravenous calcium supplementation, corresponding to a total of 352 gram elemental calcium (1/3 of the total body calcium), resulted in gradual symptomatic relief. The possible mechanisms for these findings are discussed and the literature is briefly reviewed.

Is endoscopic balloon dilation for removal of bile duct stones associated with an increased risk for pancreatitis or a higher rate of hyperamylasemia?

BACKGROUND AND STUDY AIMS: We studied the rate of pancreatitis and asymptomatic hyperamylasemia after endoscopic balloon dilation (EBD) and endoscopic sphincterotomy (EST) for removal of bile duct stones. PATIENTS AND METHODS: Patients with bile duct stones of all sizes were randomly allocated to undergo EBD (8-mm dilation balloon) or EST. Pancreatitis was defined as epigastric pain combined with at least a threefold rise in serum amylase at 24 hours after the endoscopic retrograde cholangiopancreatography (ERCP). Asymptomatic hyperamylasemia was defined as a threefold rise in serum amylase without epigastric pain. RESULTS: There were 180 patients (67 men, 113 women; mean age 67, SD 16.2) available for analysis. Complete stone removal after a single ERCP was achieved in 82 (88%) of 93 EBD patients and in 81 (93%) of 87 EST patients (P = 0.38). Mechanical lithotripsy was used more frequently in the EBD group (31% vs. 13%, P = 0.005). Early complications occurred in 16 EBD patients (17%) and in 19 EST patients (22%) (P = 0.46). Pancreatitis was observed in seven patients in each group (8%). Logistic regression identified no significant predictors for the occurrence of pancreatitis. Asymptomatic hyperamylasemia occurred in 21 EBD patients (23%) vs seven EST patients (8%) (P = 0.008). Logistic regression identified EBD as the only significant predictor for asymptomatic hyperamylasemia: odds ratio 2.9 (95% confidence interval (CI) 1.1 to 7.3, R2 = 0.02). CONCLUSIONS: We did not observe a difference in the rate of pancreatitis between EBD and EST. Asymptomatic hyperamylasemia was observed more frequently after EBD. Although asymptomatic hyperamylasemia is not a clinical entity, this finding may indicate that EBD causes more irritation of the pancreas than EST.

A scanning electron microscopic study of biliary stent materials.

BACKGROUND: Clogging of biliary stents remains an important problem. In vitro studies have shown less sludge formation in Teflon stents. Recently, clinical studies with Teflon stents have produced contradictory results. The aim of this study was to investigate whether the surface properties of the endoprostheses could explain the variation observed in clinical studies. METHODS: A total of 9 different types of unused 10F endoprostheses were examined by scanning electron microscopy (SEM): polyethylene Amsterdam-type, polyurethane Amsterdam-type, Teflon Amsterdam-type, Teflon Tannenbaum-type and a Tannenbaum-type stent with a thin stainless steel mesh between inner and outer layers. RESULTS: All polyethylene stents had a relief with tiny lumps. All Teflon stents had multiple shallow pits and ridges along the entire longitudinal axis. Both Tannenbaum-type stents also had multiple particles protruding into the stent lumen with adjacent holes in the wall of the stent. The polyurethane stent had an extremely smooth surface. CONCLUSION: SEM of Teflon made stents showed a markedly irregular inner surface, which may explain the controversial results of clinical studies. Our results indicate that the inner surface of a new stent should first be evaluated by SEM before clinical trials are initiated.

A prospective randomized trial of Teflon versus polyethylene stents for distal malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Clogging of biliary stents continues to be a major clinical problem. Different polymer materials may have different effects on clogging. In vitro studies have shown a direct relation between the frictional coefficient of a polymer and the amount of encrusted material. Teflon appeared to be the best polymer for biliary stents. Two different types of stents made of Teflon have been tested in clinical practice and showed favourable patency rates. However, a randomized trial has never been performed. We compared the patency of an Amsterdam-type polyethylene stent with a Teflon stent in a prospective randomized trial. PATIENTS AND METHODS: Between September 1995 and November 1996, 42 patients received a Teflon stent and 42 patients a polyethylene stent. All patients had a distal malignant biliary stricture without a previous drainage procedure. Diagnoses included carcinoma of the pancreas (n = 76), papilla (n = 1), bile duct (n = 5) and metastases (n = 2). The internal and external diameter (10 Fr), length (9 cm) and stent design (a straight stent with two side flaps and one side hole at each end) were similar for both stents. RESULTS: A reduction in bilirubin of more than 20% within one week was seen in 91% of the patients. Early complication rates were similar in both groups (10%). The median follow-up was 142 days. Stent dysfunction occurred in 28 Teflon and 29 polyethylene stents. The thirty-day mortality was 14% in both groups. Patient survival did not differ significantly between the groups (median survival: Teflon 165 days, polyethylene 140 days). The median stent patency was 83 days for Teflon and 80 days for polyethylene stents, and was not significantly different either. CONCLUSION: Teflon material did not improve patency in biliary stents with an Amsterdam-type design.

Biliary manometry, bacterial characteristics, bile composition, and histologic changes fifteen to seventeen years after endoscopic sphincterotomy.

AIM: To evaluate the function of the biliary sphincter 15 to 17 years after endoscopic sphincterotomy and to investigate if loss of sphincter function is associated with bacterial colonization, changes in bile composition, or inflammation of the biliary system. METHODS: Eight patients who had undergone endoscopic sphincterotomy for bile duct stones 15 to 17 years previously underwent ERCP with biliary manometry, bile sampling, and biopsy. Manometry was performed using a perfused triple-lumen manometry catheter and a station pull-through technique. Bile samples were cultured and analyzed for biliary lipids, bile salts, bacterial beta-glucuronidase, and phospholipase A2. Biopsy specimens were taken from the proximal common heptic duct for histologic examination. RESULTS: Manometry demonstrated absent basal sphincter pressure and no choledochoduodenal pressure gradient in all patients. Phasic contractions were observed in two patients. Cholangiography showed stones in one patient. Positive cultures were obtained in three patients, including the patient with stones. All bile samples showed a high content of biliary lipids and cholesterol. Some samples contained considerable amounts of hydrophobic bile salts. Five samples contained very high levels of phospholipase A2 activity. Significant bacterial beta-glucuronidase activity was found in one patient, the patient with stones. Biopsy specimens of the proximal common hepatic duct in three patients showed chronic inflammation with fibrosis and reactive epithelial changes. CONCLUSIONS: After endoscopic sphincterotomy for bile duct stones, the function of the biliary sphincter is permanently lost. This is associated with bacterial colonization, presence of cytotoxic components in the bile, and chronic inflammation of the biliary system.

Randomised trial of endoscopic balloon dilation versus endoscopic sphincterotomy for removal of bileduct stones.

BACKGROUND: Endoscopic sphincterotomy (EST) for the removal of bileduct stones is associated with acute complications and a permanent loss of biliary-sphincter function. Endoscopic balloon dilation (EBD) causes less trauma to the biliary sphincter, but may be less effective in allowing stone removal. METHODS: 218 consecutive patients with bileduct stones on endoscopic retrograde cholangiopancreatography (ERCP) were enrolled. 202 who met all eligibility criteria were randomly assigned EST or EBD. The patients were observed in hospital for at least 24 h and followed up at 1 month and 6 months. Complications were classified by an expert panel unaware of treatment allocation and outcome. Analysis was done by intention to treat. FINDINGS: After a single ERCP, all stones were removed from 92 (91%) of 101 patients assigned EST and 90 (89%) of 101 assigned EBD (p = 0.81); in nine of the latter, successful removal required additional EST. Mechanical lithotripsy was used to fragment stones in 31 EBD procedures and 13 EST procedures (p < 0.005). Early complications (before 15 days) occurred in 24 EST patients and 17 EBD patients (p = 0.29). One patient died of retroperitoneal perforation after EBD. Four patients had bleeding after EST. Seven patients in each group had pancreatitis. Complications during follow-up occurred in 23 EST patients and 18 EBD patients (p = 0.48). Acute cholecystitis was observed in seven EST patients and one EBD patient (p < 0.05). INTERPRETATION: The success rate of EBD was similar to that of EST. We found there is no evidence of the previously suggested higher risk of pancreatitis with EBD and suggest that EBD is preferred in patients at risk of bleeding after EST. Preservation of biliary-sphincter function after EBD may prevent long-term complications and reduce the risk of acute cholecystitis during follow-up. This procedure is a valuable alternative to EST in patients with bileduct stones.

Wallstents for metastatic biliary obstruction.

BACKGROUND AND STUDY AIMS: In patients with obstruction of the common bile duct caused by primary pancreaticoblliary tumors, Wallstents have been shown to remain patent for a median duration of 273 days (range: 14-363). However, in one study that included both patients with primary pancreaticobillary malignancies and patients with metastatic malignant disease, the reported median Wallstent patency was found to be significantly shorter. We have studied the patency of Wall-stents in patients with metastatic billary obstruction. PATIENTS AND METHODS: All patients who had received a Wallstent for metastatic biliary obstruction between January 1990 and August 1994 were analyzed retrospectively. Follow-up was achieved by contacting referring physicians and general practitioners, and lasted up to the end of the study period (November 1994) or death of the patient. Follow-up was discontinued if a polyethylene stent was inserted through the Wallstent for treatment of stent dysfunction. RESULTS: 28 patients were identified, including 14 men and 14 women, with a mean age of 61.3 years (range 24-87). Long-term follow-up was possible in 27 patients (96%), for a median duration of 140 days (range 29- 561). Eleven patients died during the study period, and there were three deaths related to Wallstent dysfunction. The median duration of Wallstent patency was 265 days (range 11-519). Wallstent obstruction occurred in 13 patients; seven patients presented with cholangitis, six patients had jaundice. The cause of obstruction was established at endoscopic retrograde cholangiopancreatography in ten patients: seven had tumor ingrowth, and three had tumor overgrowth. Treatment consisted of insertion of a polyethylene stent in seven and placement of a second Wallstent in three patients. CONCLUSION: In patients with metastatic obstruction of the common bile duct, the duration of patency of Wallstents is comparable to that reported in series of Wallstents for primary pancreaticobiliary malignancies.