The fate of patients who undergo "preoperative" ERCP to clear known or suspected bile duct stones.

BACKGROUND: There is debate as to whether recurrent biliary complications are more common in patients who do not have elective cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) management of common bile duct (CBD) stones. The aim of this study was to determine the fate of patients with intact gallbladders who have had CBD stones removed at ERCP, and to assess their risk of recurrent biliary symptoms. METHODS: We retrospectively identified all patients in our large tertiary center population with intact gallbladders who had an ERCP for CBD stones from December 1999 to March 2002. We determined which patients had subsequent elective cholecystectomy, and the outcomes of patients who did not have elective surgery. RESULTS: 309 patients had CBD stones at ERCP during the study period, of which 139 had intact gallbladders at the time of ERCP. Of these 139 patients 59 had subsequent elective cholecystectomy, 11 by open operation and 48 laparoscopically. Of these 139 patients, 27 had cholecystectomy planned; 47 patients were managed with a wait-and-see strategy, 30 of whom were poor surgical candidates. Of these 47 patients in whom a wait-and-see policy was adopted, 9 (19%) developed complications including recurrent pain and/or abnormal liver function tests (LFTs), recurrent biliary colic, and pancreatitis. Eight of these nine patients were from the poor surgical candidate group. Sphincterotomy had been performed at initial ERCP in all patients. CONCLUSIONS: Over half of our population of 139 patients with CBD stones at ERCP and intact gallbladders had actual or planned elective cholecystectomy. For those patients in whom a decision to wait-and-see was made, almost 20% developed complications. Elective cholecystectomy after a finding of choledocholithiasis is supported by many and is a common strategy in our experience. Recurrent biliary complications are relatively common in those who do not undergo elective cholecystectomy, especially those patients who represent a high operative risk.

Endoscopic ultrasound and computer tomography are inaccurate methods of classifying cystic pancreatic lesions.

BACKGROUND: Despite advances in imaging modalities, preoperative diagnosis of pancreatic cystic lesions remains difficult. AIM: To assess the accuracy of endoscopic ultrasound and computer tomography to preoperatively distinguish benign from potentially malignant and malignant pancreatic cystic lesions. METHODS: Photograph series obtained from endoscopic ultrasound examinations of 66 patients with cystic pancreatic lesions were blindly reviewed by three endoscopic ultrasonographers. Forty-one of those 66 patients also underwent a computer tomography scan at our institution, which was blindly reviewed by a single radiologist. Computer tomography and endoscopic ultrasound classification into benign and malignant and potentially malignant pancreatic cystic lesions was correlated with the final diagnosis, which was established by surgical pathology (n = 43), diagnostic fine needle aspiration (n = 13) or follow-up imaging (n = 10). Interobserver agreement was measured using kappa statistics. RESULTS: Endoscopic ultrasound classification by the three examiners into benign versus malignant or potentially malignant cystic lesions was correct in 65-67%. Interobserver agreement was 50%. Kappa values for pairs of endoscopic ultrasound examiners were 0.16, 0.43 and 0.53. Computer tomography classification was correct in 71% and in agreement with the endoscopic ultrasound classification in 56-61% (kappa 0.12 to 0.27). CONCLUSIONS: Endoscopic ultrasound and computer tomography cannot accurately distinguish between benign pancreatic cystic lesions and malignant or potentially malignant ones. There is poor-to-modest interobserver agreement in classifying these lesions.

Yield of endoscopic ultrasound-guided fine-needle aspiration of bile duct lesions.

BACKGROUND AND STUDY AIMS: It is still difficult to differentiate reliably between benign and malignant biliary tract lesions. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has added to the diagnostic power of EUS for other gastrointestinal tumors. A retrospective analysis of experience with FNA sampling of bile duct lesions was therefore carried out. PATIENTS AND METHODS: All EUS-FNA procedures for bile duct masses or strictures were analyzed at our tertiary referral center from May 2000 through October 2002. Data for EUS findings, the results of EUS-FNA, and tissue sampling at surgery were included. EUS-FNA procedures were carried out using a 22-gauge needle. An experienced cytopathologist was present during FNA in all but three cases. Clinical follow-up details were recorded when available for patients in whom a suitable diagnostic gold standard was not available for comparison. RESULTS: A total of 35 patients underwent EUS-FNA of bile duct lesions during the study period. There were no complications. Data for EUS-FNA of bile duct masses or strictures and tissue obtained at surgery were available for 23 patients. If positive cytology at surgical pathology is taken as the gold standard, EUS-FNA has a diagnostic yield for cancer of 100 % (if atypia/inconclusive findings in the FNA sample are regarded as benign). Eleven patients had a definite malignancy on surgical pathology. Of these 11 patients, five had a finding of malignancy on EUS-FNA, giving a sensitivity of 45 % (if FNA cytology reported as atypia/inconclusive is regarded as benign). Twelve patients had findings of no malignancy from tissue obtained at surgery. Of these 12 patients, nine had benign pathology and three had atypia/inconclusive findings in the EUS-FNA sample (specificity of 100 % if atypia/inconclusive findings are considered benign). A further 12 patients did not have surgical specimens for comparison with EUS-FNA results. Four patients had definite findings of malignancy on EUS-FNA alone, and one patient had FNA findings suspicious for malignancy. Seven patients had negative or equivocal EUS-FNA results. These 12 patients are described but excluded from further analysis, as a gold standard was not available for comparison. However, clinical follow-up data were available for eight of these 12 patients, and in each case the follow-up findings were compatible with previous benign or malignant EUS-FNA findings. CONCLUSIONS: The practice of EUS-FNA has improved the diagnostic yield of EUS. These results suggest that it is a safe and useful procedure for investigating biliary masses or strictures that have hitherto caused considerable diagnostic confusion, especially in patients with negative brush cytology findings. The possibility of false-negative findings remains, but core biopsy needles may improve the situation. The results of further studies are awaited.

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Predictors of successful clinical and laboratory outcomes in patients with primary sclerosing cholangitis undergoing endoscopic retrograde cholangiopancreatography.

UNLABELLED: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with primary sclerosing cholangitis (PSC) can be a challenging and sometimes gratifying opportunity for therapeutic intervention. Although there often appears to be initial radiological improvement after ERCP, the benefit as measured by serial estimations of subsequent liver enzymes is questionable. The fluctuating course of the inflammatory process makes the interpretation of serology even more difficult. OBJECTIVES: To document and compare the liver profile and clinical status of patients before and after diagnostic and therapeutic ERCP; to determine predictors of clinical and laboratory success in patients with PSC; and to assess the complication rate of diagnostic and therapeutic ERCP in these patients. METHODS: All patients with PSC who underwent ERCP at the authors' medical centres between January 6, 1987 and January 12, 1998 were identified using a computerized database. Presenting symptoms, liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase) and bilirubin were recorded before ERCP. Clinical success was defined as resolution of the presenting symptoms. Laboratory success was defined as improvement in two of three liver enzymes by at least 50%, or resolution of jaundice. RESULTS: One hundred four patients underwent 204 ERCPs of which 56 ERCPs were diagnostic. Clinical improvement was seen in 35% of the patients after diagnostic ERCP and in 70% after therapeutic procedures (chi 2=18.4, P=0.001). Laboratory improvement was seen in 35% of patients undergoing diagnostic ERCP and in 52% of the patients undergoing therapeutic ERCP (P=0.04). The reductions in liver enzymes were significant in both the diagnostic and therapeutic groups. Serum bilirubin level decreased significantly in the therapeutic ERCP group only. In a univariate analysis, patients with common bile duct strictures, any dominant stricture and those who underwent a therapeutic procedure were most likely to have clinical and laboratory improvement. In multivariable logistic regression, the presence of a dominant stricture, endoscopic therapy and high serum bilirubin were all independent predictors of a successful clinical outcome. There was no difference in total complication rates (18% versus 14%) when comparing the diagnostic and therapeutic ERCP groups. However, all seven severe complications occurred in the therapeutic ERCP group. CONCLUSIONS: First, in PSC, clinical and laboratory improvement is more common in patients undergoing therapeutic ERCP than diagnostic ERCP. Second, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase improve following both diagnostic and therapeutic ERCP, and should therefore not be relied upon to determine the success of the procedure. Third, bilirubin levels decreased in the therapeutic group but remained unchanged in the diagnostic group, suggesting that the serum bilirubin level may be a more sensitive indicator of successful therapeutic intervention than transaminases. Fourth, common bile duct strictures, dominant strictures and bilirubin levels are important variables in determining the success of an ERCP in PSC. Finally, complication rates after therapeutic ERCP are similar to those after diagnostic ERCP in PSC patients. However, severe complications occur more commonly in the therapeutic group.

ERCP-related perforations: risk factors and management.

BACKGROUND AND STUDY AIMS: Perforations during endoscopic retrograde cholangiopancreatography (ERCP) are rare, and the management of these perforations is variable, with some patients requiring immediate surgery and others only conservative management. We reviewed all ERCP-related perforations at our institution to determine: a) their incidence; b) clinical outcomes; c) which management approaches gave the best results; and d) which factors predict a perforation. PATIENTS AND METHODS: All patients who underwent ERCP and suffered perforation were reviewed. To compare the length of hospital stay of the perforation group with that of patients suffering a different complication, patients who developed post-ERCP pancreatitis were also reviewed. To evaluate predictors of ERCP-related perforations, three groups were compared: group 1 (n = 49), normal ERCP/no complications; group 2 (n = 52), ERCP complicated by pancreatitis; and group 3 (n = 33), ERCP with perforation. RESULTS: Of 33 patients with confirmed ERCP-related perforations, only seven patients required surgical intervention. The overall length of hospital stay (6.5 +/- 3.5 days) was significantly longer (P = 0.003) than that of a random group of patients with the complication of post-ERCP pancreatitis (4.7 +/- 2.6 days). According to univariate analysis, risk factors included: sphincterotomy (odds ratio [OR] 9.0, 95 % confidence interval [CI] 3.2 - 28.1); sphincter of Oddi dysfunction (OR 3.8, 95 % CI 1.4 - 11.0); and dilated common bile duct (OR 4.07, 95 % CI 1.63 - 10.18, P = 0.003). In the multivariate logistic regression analysis, additional predictive factors included the duration of procedure (OR 1.021, 95 % CI 1.006 - 1.036), and biliary stricture dilation (OR 7.2, 95 % CI 1.84 - 28.11). CONCLUSIONS: (i) The incidence of ERCP-related perforations is very low (0.35 %). (ii) Esophageal, gastric and duodenal perforations usually require surgery, but sphincterotomy- and guide wire-related perforations rarely do so. (iii) Factors which carry increased risk of an ERCP-related perforation include suspected sphincter of Oddi dysfunction, greater age, a dilated bile duct, sphincterotomy, and longer duration of the procedure.

Yield of colonoscopy in patients with nonacute rectal bleeding: a multicenter database study of 1766 patients.

OBJECTIVE: There are few data to guide the choice between colonoscopy and flexible sigmoidoscopy in patients with nonacute rectal bleeding, especially in younger age groups. Our aim was to determine the yield of colonoscopy for significant proximal large bowel disease in the absence of significant distal disease, with special reference to young patients. METHODS: This was a retrospective study of data collected prospectively in 1766 patients (median age 57 yr, 711 women). The endoscopic database (GI-Trac) contained 152 discrete fields for data input. Multiple logistic regression analysis was performed to identify variables independently associated with the presence of isolated significant proximal disease. RESULTS: Young patients had a higher percentage of normal examinations than did older patients. The incidence of diverticular disease, small polyps, large polyps, and cancer rose with increasing age. No patient aged <40 yr had an isolated proximal cancer, but 7% had other significant isolated proximal disease. There was no overall association between age and significant proximal disease in the absence of significant distal disease (p = 0.66). The only variable associated with isolated proximal disease was anemia (odds ratio = 1.81; 95% CI = 1.11-2.93; p = 0.02). CONCLUSION: The yield of colonoscopy (beyond the range of sigmoidoscopy) for neoplasia is low in patients aged <40 yr, but other significant disease may be missed if age is the only criterion determining colonoscopy use.

Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations.

BACKGROUND & AIMS: Nonalcoholic chronic pancreatitis is usually idiopathic and often associated with cystic fibrosis gene (CFTR) mutations. It is unknown whether pancreatitis risk correlates with having 1 or 2 CFTR mutations, abnormal epithelial ion transport, or mutations of other genes. METHODS: We tested 39 patients with idiopathic chronic pancreatitis (mean age at diagnosis, 33 years) for common mutations of CFTR and of genes encoding a trypsin inhibitor (PSTI) and trypsinogen (PRSS1). To exclude hereditary pancreatitis, we initially relied on family history and subsequently tested for PRSS1 mutations. Twenty subjects were tested for rare CFTR mutations (DNA sequencing) and 11 were tested for extrapancreatic CFTR function (clinical and physiologic evaluation). RESULTS: Mutations were identified in 24 of 39 subjects. Nine patients had cystic fibrosis-causing mutations, 8 of whom also had mild-variable mutations. Eight others had only mild-variable mutations. Nine subjects had the N34S PSTI mutation and 1 had hereditary pancreatitis (R122H, PRSS1). Pancreatitis risk was increased approximately 40-fold by having 2 CFTR mutations (P < 0.0001), 20-fold by having N34S (P < 0.0001), and 900-fold by having both (P < 0.0001). Subjects with 2 CFTR mutations had abnormal nasal epithelial ion transport and clinical findings suggesting residual CFTR function between that in cystic fibrosis and in carriers. By contrast, subjects with only PSTI mutations had normal CFTR function. CONCLUSIONS: CFTR-related pancreatitis risk correlates with having 2 CFTR mutations and reduced extrapancreatic CFTR function. The N34S PSTI mutation increased risk separately. Testing for pancreatitis-associated CFTR and PSTI genotypes may be useful in nonalcoholic pancreatitis.

Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study.

INTRODUCTION: Symptoms of dyspepsia are common but most patients do not have major upper gastrointestinal pathology. Endoscopy is recommended for dyspeptic patients over the age of 45, or those with certain "alarm" symptoms. We have evaluated the effectiveness of age and "alarm" symptoms for predicting major endoscopic findings in six practising endoscopy centres. METHODS: Clinical variables of consecutive patients with dyspepsia symptoms undergoing upper endoscopy examinations were recorded using a common endoscopy database. Patients who had no previous upper endoscopy or barium radiography were included. Stepwise multivariate logistic regression was used to identify predictors of endoscopic findings. The accuracy of these for predicting endoscopic findings was evaluated with receiver operating characteristic analysis. The sensitivity and specificity of age thresholds from 30 to 70 years were evaluated. RESULTS: Major pathology (tumour, ulcer, or stricture) was found at endoscopy in 787/3815 (21%) patients with dyspepsia. Age, male sex, bleeding, and anaemia were found to be significant but weak independent predictors of endoscopic findings. A multivariate prediction rule based on these factors had poor predictive accuracy (c statistic=0.62). Using a simplified prediction rule of age > or =45 years or the presence of any "alarm" symptom, sensitivity was 87% and specificity was 26%. Increasing or decreasing the age cut off did not significantly improve the predictive accuracy. CONCLUSIONS: Age and the presence of "alarm" symptoms are not effective predictors of endoscopic findings among patients with dyspepsia. Better clinical prediction strategies are needed to identify patients with significant upper gastrointestinal pathology.

Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience.

OBJECTIVE: To examine clinical outcomes in patients receiving neoadjuvant chemoradiation for locally advanced rectal adenocarcinoma. SUMMARY BACKGROUND DATA: Preoperative radiation therapy, either alone or in combination with 5-fluorouracil-based chemotherapy, has proven both safe and effective in the treatment of rectal cancer. However, data are lacking regarding which subgroups of patients benefit from the therapy in terms of decreased local recurrence and increased survival rates. METHODS: A retrospective chart review was performed on 141 consecutive patients who received neoadjuvant chemoradiation (5-fluorouracil +/- cisplatin and 4,500-5,040 cGy) for biopsy-proven locally advanced adenocarcinoma of the rectum. Surgery was performed 4 to 8 weeks after completion of chemoradiation. Standard statistical methods were used to analyze recurrence and survival. RESULTS: Median follow-up was 27 months, and mean age was 59 years (range 28-81). Mean tumor distance from the anal verge was 6 cm (range 1-15). Of those staged before surgery with endorectal ultrasound or magnetic resonance imaging, 57% of stage II patients and 82% of stage III patients were downstaged. The chemotherapeutic regimens were well tolerated, and resections were performed on 140 patients. The percentage of sphincter-sparing procedures increased from 20% before 1996 to 76% after 1996. On pathologic analysis, 24% of specimens were T0. However, postoperative pathologic T stage had no effect on either recurrence or survival. Positive lymph node status predicted increased local recurrence and decreased survival. CONCLUSIONS: Neoadjuvant chemoradiation is safe, effective, and well tolerated. Postoperative lymph node status is the only independent predictor of recurrence and survival.

Staging of pancreatic cancer before and after neoadjuvant chemoradiation.

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine the utility of staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT. Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT. Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT.

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

BACKGROUND: The use of neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. METHODS: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy (EBRT; median, 4500 cGy) with 5-flourouracil-based chemotherapy. Tumors were defined as potentially resectable (PR, n = 53) in the absence of arterial involvement and venous occlusion and locally advanced (LA, n = 58) with arterial involvement or venous occlusion by CT. RESULTS: Five patients (4.5%) were not restaged due to death (n = 3) or intolerance of therapy (n = 2). Twenty-one patients (19%) manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors (53%) and 11 patients with initially LA tumors (19%) were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. CONCLUSIONS: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant (postoperative) CRT.

Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival.

BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.

A double-blind, randomized, dose response study testing the pharmacological efficacy of synthetic porcine secretin.

BACKGROUND: Biologically derived porcine secretin has been used as a diagnostic agent in clinical gastrointestinal practice for many years. Pure synthetic porcine secretin is now available for investigational clinical use. AIM: To compare the pharmacology of synthetic porcine secretin and biologically derived porcine secretin in healthy volunteers. METHODS: Secretin stimulation tests were performed in 12 volunteer subjects in a double-blind, randomized, Latin square crossover design study comparing three doses of synthetic porcine secretin (0.05, 0.2, and 0.4 microgram/kg) with a standard dose of biologically derived porcine secretin (1 CU/kg). Duodenal aspirates were analysed for total volume and for bicarbonate concentration. Total bicarbonate output was calculated. RESULTS: Twelve subjects completed four dosing regimens. A multiple comparison test was used to compare dosing regimens. The 0.2 and 0.4 microgram/kg doses of synthetic porcine secretin were not different from the 1 CU/kg dose of biologically derived porcine secretin for volume, bicarbonate concentration and total output from 0 to 60 min. Only one patient had an adverse event, which was mild, transient flushing after the 0.2 and 0.4 microgram/kg doses of synthetic porcine secretin and after the 1 CU/kg dose of biologically derived porcine secretin. CONCLUSIONS: Synthetic porcine secretin has identical pharmacologic effects to biologically derived porcine secretin in normal subjects. Both drugs were safe and well-tolerated. This study validates synthetic porcine secretin as a substitute for biologically derived porcine secretin.

A pilot study of preoperative continuous infusion 5-fluorouracil, external microwave hyperthermia, and external beam radiotherapy for treatment of locally advanced, unresectable, or recurrent rectal cancer.

PURPOSE: To determine the feasibility of combining external beam radiotherapy, continuous infusion 5-fluorouracil (5-FU), and external microwave hyperthermia in patients with locally advanced, unresectable, or recurrent adenocarcinoma of the rectum. METHODS AND MATERIALS: From 7/95 through 2/99, 15 patients were enrolled in the study. The treatment regimen consisted of continuous infusion 5-FU 250 mg/m(2)/d 7 days/week beginning on day 1, external beam radiotherapy to the pelvis, 4500 cGy, 180 cGy/d 5 days/week using a 3 or 4-field technique, and external microwave hyperthermia on days 3, 8, 15, 22, and 29. Chemotherapy was stopped on the last day of radiotherapy. Surgical resection, if feasible, was scheduled 3-6 weeks after completing thermochemoradiotherapy. For this regimen to be considered feasible, no more than 2 of the 15 patients should fail to complete therapy due to life-threatening toxicity. Toxicity was scored using National Cancer Institute Criteria. RESULTS: All patients completed the chemoradiotherapy portion of the protocol. Eleven of the 15 patients completed all 5 hyperthermia treatments. Of the 4 patients who did not receive the full course of hyperthermia, only 1 patient had treatment stopped due to life-threatening toxicity. The other 3 patients did not complete hyperthermia due to scheduling errors (n = 2) or patient request (n = 1). Five of 15 patients required a treatment interruption due to toxicity > or = Grade 3. Seven patients experienced lesser degrees of toxicity which did not require treatment interruption. Three patients experienced no side effects. The most common toxicities were dermatitis and diarrhea. Of the 14 patients in whom surgery was planned, 11 (79%) were resectable. There was one pathologic complete response. CONCLUSIONS: It is feasible to deliver thermochemoradiotherapy, as prescribed in this study, to patients with locally advanced, unresectable, or recurrent rectal cancer. The therapy is moderately toxic, with one-third of patients requiring temporary treatment interruptions. The regimen appears active against rectal cancer, and appears to warrant further consideration as a treatment option for this patient population.

Cystic fibrosis mutations and genetic predisposition to idiopathic chronic pancreatitis.

Idiopathic chronic pancreatitis is a leading cause of chronic pancreatitis. Work from this and other groups has shown that idiopathic chronic pancreatitis is associated with mutations of the cystic fibrosis gene (CFTR). Many idiopathic pancreatitis patients have compound heterozygote genotypes in which both copies of the CFTR gene are abnormal. In these patients, the pancreatic disease can be viewed as a mild variant of cystic fibrosis, in which there is sufficient residual CFTR function to prevent lung disease. This article summarizes the evidence associating these abnormal CFTR genotypes with idiopathic chronic pancreatitis and reviews the implications of this association for the pathogenesis, classification, and prevention of pancreatitis.