[Surgical drainage of the pancreatic duct in patients with chronic pancreatitis is more effective than endoscopic drainage: randomized trial]. / Chirurgische drainage van de ductus pancreaticus bij patiënten met chronische pancreatitis effectiever dan endoscopische drainage: gerandomiseerde trial.

OBJECTIVE: To compare endoscopic and surgical drainage of the pancreatic duct for ductal decompression in patients with severe pain due to chronic pancreatitis and a dilated pancreatic duct. DESIGN: Randomized clinical trial. METHOD: All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct, but without an inflammatory mass, were eligible for this study. Patients were randomized to endoscopic transampullary pancreatic duct drainage or to operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score, measured during 2 years of follow-up. The secondary endpoints were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, hospital stay and number of procedures performed. RESULTS: Of 118 patients who were evaluated between January 2000-October 2004 39 patients were randomized; 19 were treated endoscopically (16 of whom underwent lithotripsy) and 20 by operative pancreaticojejunostomy. During 24 months of follow-up, compared with endoscopic drainage, surgery was associated with lower Izbicki pain scores (51 versus 25; p < 0.001) and better SF-36 physical health summary scores (p = 0.003). Furthermore, at the end of follow-up, pain relief was achieved in 32% of patients randomized to endoscopic drainage and 75% of patients randomized to surgical drainage (p = 0.007). Complication rates and hospital stay were similar, but endoscopic treatment required more procedures (median 8 versus 3; p < 0.001).

Endoscopic drainage of pancreatic pseudocysts: long-term outcome and procedural factors associated with safe and successful treatment.

BACKGROUND AND STUDY AIMS: Endoscopic drainage is a widely used treatment modality for pancreatic pseudocysts and has challenged more traditional drainage techniques. This retrospective study evaluates the short-term and long-term results with this technique and aims to identify procedural modifications that may improve its safety and efficacy. PATIENTS AND METHODS: All consecutive patients who underwent endoscopic drainage of pancreatic pseudocysts in our hospital between 1983 and 2000 were included in the study. The patients' charts were reviewed, and long-term follow-up data were obtained by written questionnaires sent to the patients at the end of the follow-up period in November 2002. RESULTS: A total of 92 patients were included (66 men, 26 women; median age 49 years). The technical success rate of the drainage procedure was 97 % and the mortality rate was 1 %. Complications occurred in 31 patients (34 %), eight of which (9 %) were major and required surgery: hemorrhage in four cases (three of which were caused by erosion of a straight endoprosthesis through the cyst wall), secondary infection in three, and perforation in one. During a median follow-up period of 43 months, 10 patients (11 %) underwent additional (nonendoscopic) treatment for a persistent cyst and five (5 %) for a recurrent cyst. Overall, endoscopic drainage was successful in 65 patients (71 %). CONCLUSIONS: Endoscopic drainage is an effective treatment for pancreatic pseudocysts and offers a definitive solution in almost three-quarters of the cases. The majority of major complications might have been prevented by using pigtail stents instead of straight stents and by taking a more aggressive approach to the prevention and treatment of secondary cyst infection.

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.

Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.

BACKGROUND AND STUDY AIMS: Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS: Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS: Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS: Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.

Impaired quality of life 5 years after bile duct injury during laparoscopic cholecystectomy: a prospective analysis.

OBJECTIVE: To assess the impact of bile duct injury (BDI) sustained during laparoscopic cholecystectomy on physical and mental quality of life (QOL). SUMMARY BACKGROUND DATA: The incidence of BDI during laparoscopic cholecystectomy has decreased but remains as high as 1.4%. Data on the long-term outcome of treatment in these patients are scarce, and QOL after BDI is unknown. METHODS: One hundred six consecutive patients (75 women, median age 44 +/- 14 years) were referred between 1990 and 1996 for treatment of BDI sustained during laparoscopic cholecystectomy. Outcome was evaluated according to the type of treatment used (endoscopic or surgical) and the type of injury. Objective outcome (interventions, hospital admissions, laboratory data) was evaluated, a questionnaire was filled out, and a QOL survey was performed (using the SF-36). Risk factors for a worse outcome were calculated. RESULTS: Median follow-up time was 70 months (range 37-110). The objective outcome of endoscopic treatment (n = 69) was excellent (94%). The result of surgical treatment (n = 31) depended on the timing of reconstruction (overall success 84%; in case of delayed hepaticojejunostomy 94%). Five patients underwent interventional radiology with a good outcome. Despite this excellent objective outcome, QOL appeared to be both physically and mentally reduced compared with controls (P <.05) and was not dependent on the type of treatment used or the severity of the injury. The duration of the treatment was independently prognostic for a worse mental QOL. CONCLUSIONS: Despite the excellent functional outcome after repair, the occurrence of a BDI has a great impact on the patient's physical and mental QOL, even at long-term follow-up.

Long-term follow-up after biliary stent placement for postoperative bile duct stenosis.

BACKGROUND: The outcome of temporary biliary stent placement for postoperative bile duct stenosis was retrospectively evaluated with the main aim of assessing long-term complications after stent removal. METHODS: ERCP was performed between 1981 and 1991 in 74 patients with postoperative bile duct stenoses. Two 10F stents were inserted for a maximum of 12 months with stent exchange every 3 months to avoid cholangitis caused by clogging. RESULTS: Stent insertion failed in 11 patients with complete and 4 patients with incomplete biliary obstruction. Early complications occurred in 14 patients (19%) including 2 deaths. Therefore 57 patients were included in the stent phase of the study. In 10 patients the referring physician did not adhere to the treatment protocol, and nonelective stent exchange for jaundice and/or cholangitis was necessary in 7 (70%). Of the 47 patients treated according to protocol, complications developed in 40% during the period with stents in situ. Stents were eventually removed in 44 patients who were subsequently followed for a median of 9.1 years. Late complications developed in 15 patients (34%) including recurrent stenosis in 9 (20%). All cases of recurrent stenosis occurred within 2 years of stent removal. CONCLUSIONS: Endoscopic treatment is feasible in 80% of patients who undergo an ERCP for postoperative bile duct stenosis. After stent insertion and during the time with stents in situ, complications occur at a significant rate but are usually mild or reflect the patient's underlying condition. After stent removal, recurrent stenosis develops in 20% of patients within 2 years of stent removal. Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis.

Improved gene transfer efficiency to primary and established human pancreatic carcinoma target cells via epidermal growth factor receptor and integrin-targeted adenoviral vectors.

In this study we analyzed two ways of retargeting of Ad-vectors to human pancreatic carcinoma with the aim of enhancing the gene transfer efficiency. First, we analyzed the expression of the epidermal growth factor receptor (EGFR) on primary, as well as established pancreatic carcinoma cells by flow cytometry which revealed high expression levels of EGFR on the surface of these cells. We showed that EGFR-retargeted entry pathway using a bispecific fusion protein formed by a recombinant soluble form of truncated Coxsackie and Adenovirus Receptor (sCAR) genetically fused with human EGF (sCAR-EGF) redirects them to the EGFR leading to an enhanced gene transfer efficiency to pancreatic carcinoma cells. Since flow cytometry revealed absence of CAR expression, but the presence of at least one of both alphav integrins on the pancreatic carcinoma cells, a second way of targeting was investigated using a genetically modified Ad vector which has an RGD (Arg-Gly-Asp)-containing peptide inserted into the HI-loop of the fiber knob. This RGD targeted Ad (AdlucRGD) revealed efficient CAR-independent infection by allowing binding to cellular integrins resulting in a dramatic enhancement of gene transfer. These findings have direct relevance for Ad-vector based gene therapy strategies for pancreatic carcinoma.

The effect of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.

BACKGROUND: The benefit of preoperative biliary drainage in jaundiced patients undergoing pancreaticoduodenectomy for a suspected malignancy of the periampullary region is still under debate. This study evaluated preoperative biliary drainage in relation to postoperative outcomes. STUDY DESIGN: At the Academic Medical Center, Amsterdam, the Netherlands, a cohort of 311 patients undergoing pancreaticoduodenectomy from June 1992 up to and including December 1999 was studied. Of this cohort 21 patients with external or surgical biliary drainage were excluded and 232 patients who had received preoperative internal biliary drainage were divided into three groups corresponding with severity of jaundice according to preoperative plasma bilirubin levels: < 40 microM (n = 177), 40 to 100 microM (n = 32), and > 100 microM (n = 23) were designated as groups 1, 2, and 3, respectively. These groups were compared with patients who underwent immediate surgery (n = 58) without preoperative drainage. RESULTS: The median number of stent (re)placements was 2 (range 1 to 6) with a median drainage duration of 41 days (range 2 to 182 days) and a stent dysfunction rate of 33%. Although patients in group 1 were better drained than patients in groups 2 and 3 (median reduction of bilirubin levels 82%, 57%, and 37%, respectively, p < 0.01), there was no difference in overall morbidity among the drained groups (50%, 50%, and 52%, respectively). There was no significant difference in overall morbidity between patients with and without preoperative biliary drainage (50% and 55%, respectively). CONCLUSIONS: Preoperative biliary drainage did not influence the incidence of postoperative complications, and although it can be performed safely in jaundiced patients it should not be used routinely.

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.

Precut sphincterotomy: indications, pitfalls, and complications.

Precut sphincterotomy is a technique employed to gain access to the common bile duct (CBD) when standard methods using catheters, cannulatomes, and guidewires have failed. It is particularly useful in cases of distal biliary strictures or distal impacted stones and in patients with Billroth II gastrectomies who require papillotomy. It significantly improves the overall success rate of CBD access. This technique should only be used, however, when a therapeutic maneuver is anticipated, and it has no place in diagnostic imaging. In the hands of experienced, skillful endoscopists, the complication rate is comparable with that of standard sphincterotomy.

A randomized trial of endoscopic balloon dilation and endoscopic sphincterotomy for removal of bile duct stones in patients with a prior Billroth II gastrectomy.

BACKGROUND: A prior Billroth II gastrectomy renders endoscopic sphincterotomy (EST) more difficult in patients with bile duct stones. Endoscopic balloon dilation (EBD) is a relatively easy procedure that potentially reduces the risk of bleeding and perforation. METHODS: Thirty-four patients with bile duct stones and a previous Billroth II gastrectomy were randomized to EST or EBD. Complications were graded in a blinded fashion. Results were compared with those for a group of 180 patients with normal anatomy from a previously reported randomized trial of EBD versus EST. RESULTS: All stones were removed in 1 endoscopic retrograde cholangiopancreatography in 14 of 16 patients who underwent EBD versus 14 of 18 who had EST (p = 1.00). Mechanical lithotripsy was used in 3 EBD procedures versus 4 EST procedures (p = 1.00). Early complications occurred in 3 patients who had EBD versus 7 who underwent EST (p = 0.27). Three patients had bleeding after EST; 1 patient had mild pancreatitis after EBD. The median time required for stone removal was 30 minutes in both groups. Compared with patients with a normal anatomy, patients with a previous Billroth II gastrectomy had a significantly increased risk of bleeding after EST (17% vs. 2%, relative risk = 7.25, p < 0.05). CONCLUSIONS: A prior Billroth II gastrectomy renders EST more difficult and increases the risk of a complication. EBD in these patients is easy to perform and is not associated with an increased need for mechanical lithotripsy or a longer procedure time. The risk of bleeding is virtually absent after EBD and the risk of pancreatitis after EBD seems not significantly increased in these patients.

Midkine and cyclooxygenase-2 promoters are promising for adenoviral vector gene delivery of pancreatic carcinoma.

Midkine (MK), a heparin binding growth factor, and cyclooxygenase-2 (COX-2), a key enzyme in the conversion of arachidonic acid to prostaglandin, are both up-regulated at the mRNA or protein level in many human malignant tumors. Here, we investigated the tumor specificity of both MK and COX-2 promoters in human pancreatic cancer, with the aim to improve the selectivity of therapeutic gene expression. We constructed recombinant adenoviral (Ad) vectors containing either the luciferase (Luc) reporter gene under the control of the COX-2 or MK promoter or the herpes simplex virus thymidine kinase (HSV Tk) gene under the control of the COX-2 promoter and compared the expression with the cytomegalovirus (CMV) promoter. AdMKLuc achieved moderate to relatively high activity upon infection to both primary and established pancreatic carcinoma cells. Of the two COX-2 promoter regions (COX-2M and COX-2L), both revealed a high activity in primary pancreatic carcinoma cells, whereas in the established pancreatic carcinoma cell lines, COX-2L has an approximately equal high activity compared to CMV. In addition, both AdCOX-2M Tk and AdCOX-2L Tk induced marked cell death in response to ganciclovir (GCV) in three of four established pancreatic carcinoma cell lines. From these results, and because it has been reported that AdMKTk and AdCOX-2L Tk in combination with GCV did not reveal significant liver toxicity, we conclude that the MK as well as the COX-2 promoters are promising tumor-specific promoters for Ad vector-based gene therapy of pancreatic cancer.

Endoscopic stent placement for pancreaticocutaneous fistula after surgical drainage of the pancreas.

BACKGROUND: Spontaneous closure of an external pancreatic fistula is unlikely when a concomitant downstream obstruction of the pancreatic duct inhibits downstream flow. Early endoscopic retrograde pancreatography (ERP) and stent insertion may enhance fistula closure in these patients. METHODS: The results of endoscopic stenting of the pancreatic duct were evaluated in 15 patients with an external pancreatic fistula that developed after operative necrosectomy and debridement of the pancreas (seven men and eight women, median age 45 (range 25-68) years). RESULTS: Median drainage before ERP was 50-800 ml/day, with an amylase content of 210,00-493,000 units/l. ERP was performed after a median time of 35 days and revealed leakage of the duct and a downstream obstruction in all patients. An endoprosthesis was inserted beyond the site of obstruction. Within a median time of 10 (range 2-64) days drainage stopped in all patients. In one patient ERP failed and pancreaticojejunostomy was performed. During follow-up (median 24 (range 2-55) months) three patients required resection of the pancreatic tail because of pseudocyst formation, all of whom originally had leakage from the tail area. CONCLUSION: Based on these data, an active approach for external pancreatic fistula seems warranted. Early ERP and stent insertion enhances fistula resolution, facilitates wound care and surgery is postponed or even avoided.

Systemic inflammatory response in acute cholangitis and after subsequent treatment.

OBJECTIVE: To measure the concentrations of endotoxin and inflammatory mediators during an attack of acute cholangitis and see what effect endoscopic treatment had on these mediators. DESIGN: Prospective study. SETTING: University teaching hospital The Netherlands. SUBJECTS: Ten patients with acute cholangitis. INTERVENTIONS: Measurements were made during the attack and 1 week after endoscopic treatment. MAIN OUTCOME MEASURE: Changes in clinical variables, and severity of biliary obstruction. Concentrations of endotoxin, cytokines, and endotoxin binding proteins, in plasma. RESULTS: The causes of cholangitis were obstructed endoprosthesis (n = 4) and stones (n = 6). The median bilirubin concentration during the attack was 70.0 micromol/L (range 14-156) and 14.5 micromol/L (range 9-80) after treatment (p < 0.05). Median (range) plasma endotoxin concentrations were 3.6 pg/ml (3.2-107) and 3.6 (2.4-5), respectively. Concentrations of cytokines were high during the acute attack and significantly lower after treatment: median tumour necrosis factor (TNF) fell from 44.6 pg/ml (range 1.2-403) to 7.3 (0-53); soluble TNF receptor p55 from 4.9 ng/ml (2.7-13.8) to 3.6 (1.4-8.2) and TNF receptor p75 from 11.6 ng/ml (7.1-40.6) to 8.1 (2.9-31.3); interleukin 6 (IL-6) fell from 690 pg/ml (34.1-4594) to 8.2 (0-39.3), IL-8 from 226.2 pg/ml (31.6-712.7) to 21.4 (4.2-63.5) and IL-10 from 33.4 pg/ml (2.7-5605) to 4.7 (0-16.7) (p < 0.03). Values for lipopolysaccharide binding protein and soluble CD14 also fell significantly (p < 0.01) from 86.5 (43.4-200) to 21.5 (11.3-37.5) and from 200 (59-200) to 47.8 (0.47-200), respectively. The concentration of bactericidal permeability increasing protein did not change significantly, being 7.1 (2-18.9) during the acute attack and 4.6 (0.8-17.7) a week later. CONCLUSION: There is a considerable systemic inflammatory response during cholangitis, which is dramatically reduced one week after endoscopic treatment.

Analysis of a positional candidate gene for inflammatory bowel disease: NRAMP2.

Genome scans have identified a region spanning 40 cM on the long arm of chromosome 12 as a susceptibility locus for inflammatory bowel disease (IBD). This locus contains several candidate genes for IBD, one of which is the gene for the natural resistance associated macrophage protein 2 (NRAMP2). This protein is a divalent cation transporter and is expressed in many cells and tissues. The putative role of this protein in innate immunity prompted us to investigate a possible relationship between NRAMP2 and IBD. We assessed the frequency of four restriction fragment length polymorphisms (IVS2+11A/G, IVS4+44C/A, 1254T/C, and IVS15Ex16-16C/G) in a group of 155 Crohn's disease (CD) patients, 114 ulcerative colitis (UC) patients, and 189 healthy controls. Linkage analysis was performed in a group of 70 families with multiple members suffering from IBD. We searched for additional intragenic markers and mutations by sequence analysis of the natural resistance-associated macrophage 2 gene of 33 CD patients, with a positive family history for IBD. We identified one novel restriction fragment length polymorphism in intron 15 of the gene. The frequency of the rare allele is: 0.08 in our control population. An increased frequency of this allele was found in CD patients but this difference did not reach statistical significance. A weak association between CD and homozygosity for the G allele of the IVS2+11A/G was found (OR [odds ratio] = 2.2, CI [confidence interval] = 1.3-3.9, chi2 = 8.4, p = 1.013). Nonparametric linkage analysis and transmissions disequilibrium tests did not provide evidence for linkage of NRAMP2 to IBD, UC, or CD. Sequence analysis of the exons and the iron-responsive element in a panel of 33 CD patients did not reveal any mutations in NRAMP2. Our association, linkage, and sequence analysis in IBD shows that the putative genetic risk factor on chromosome 12 likely is not NRAMP2. The weak association between the G/G genotype of IVS2+11A/G and CD may be due to linkage disequilibrium with a nearby disease-causing gene.

Long-term outcome of endoscopic stent placement for chronic pancreatitis associated with pancreas divisum.

BACKGROUND AND STUDY AIMS: In pancreas divisum (PD), endoscopic drainage of the minor papilla is beneficial for patients presenting with acute recurrent pancreatitis, but in cases of chronic pancreatitis, surgery is claimed to be indicated. The aim of this study was to evaluate the efficacy of endoscopic stent placement in patients with PD presenting with chronic pancreatitis. PATIENTS AND METHODS: The outcome of endoscopic treatment was evaluated in 16 patients with PD presenting with chronic pancreatitis, who underwent stenting as a first line of treatment. Chart reviews and patient interviews by mail and telephone were conducted. Median follow-up time was 51 months (range 6-120). RESULTS: After one episode of stenting and subsequent stent extraction, five of 16 patients remained pain-free (i.e., for a median time of 45 months, range 12-64). Six patients had temporary pain relief (14 months), and five patients experienced no effect of stent therapy. A total of five patients underwent surgery after failure of stenting. CONCLUSIONS: Patients with chronic pancreatitis and a PD should undergo trial stenting, since every third patient remains symptom-free after one episode of stenting.

Altered pharmacokinetics and metabolism of CPT-11 in liver dysfunction: a need for guidelines.

Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction treated with CPT-11 at two different dose levels (100 mg/m2 and 30 mg/m2, single dose, administered as a 90-min i.v. infusion). The lactones and carboxylates of CPT-11 and SN-38 were determined by high-performance liquid chromatography. SN-38 glucuronide was determined after deglucuronidation. The procedures allowed intrapatient comparison of pharmacokinetics and metabolism of the drug. Severe side effects were encountered, which could be explained by the reduced clearance of CPT-11 and its metabolites. These included neutropenic fever with culture-proven septicemia, thrombocytopenia, somnolence, diarrhea, and signs and symptoms of transient hepatic failure. Our findings offer important data for the further development of guidelines for dose reduction of CPT-11 in patients with liver dysfunction.