Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

[Subjective grading of Barrett's neoplasia by pathologists: correlation with objective histomorphometric variables]. / Subjektive Graduierung von Barrett-Neoplasien durch den Pathologen: Korrelation mit objektiven histomorphometrischen Variablen.

Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia.

Outcome and complications of colonoscopy: a prospective multicenter study in northern Israel.

Background. Colonoscopy for screening the population at an average risk of colorectal cancer (CRC) is recommended by many leading gastrointestinal associations. Objectives. The objective was to assess the quality, complications and acceptance rate of colonoscopy by patients. Methods. We prospectively gathered data from colonoscopies which were performed between October 2003 and September 2006. Patients were asked to return a follow-up form seven days after the procedure. Those who failed to do so were contacted by phone. Results. 6584 patients were included (50.4% males). The average age of subjects was 57.73 (SD 15.22). CRC screening was the main indication in 12.8%. Cecal intubation was achieved in 92% of patients and bowel preparation was good to excellent in 76.2%. The immediate outcome after colonoscopy was good in 99.4%. Perforations occurred in 3 cases-1 in every 2200 colonoscopies. Significant bleeding occurred in 3 cases (treated conservatively). 94.2% of patients agreed to undergo repeat colonoscopy in the future if indicated. Conclusions. The good quality of examinations, coupled with the low risk for complications and the good acceptance by the patients, encourages us to recommend colonoscopy as a primary screening test for CRC in Israel.

A novel device to improve colon cleanliness during colonoscopy.

BACKGROUND AND STUDY AIM: Effective colonoscopy depends on adequate visualization of the intestine, which might be ensured by intraprocedural use of a cleansing device. We investigated the performance of a novel endoscopic device with regard to cleanliness, safety, and tolerability during colonoscopy, compared with standard cleansing. PATIENTS AND METHODS: At a single center, colonoscopy patients in whom the cecum was accessed and at least one bowel segment was inadequately cleansed were assigned to either use of a disposable catheter cleansing device (JetPrep), used through the endoscope working channel, or standard manual cleansing using a 50-ml syringe. The cleansing quality, for each segment and before and after irrigation, was recorded using a 4-point scale ranging from excellent (grade 1, no more than small bits of adherent feces) to poor (grade 4, large amount of fecal residue). RESULTS: 38 patients were included, 19 in each group. Reasons for referral included colorectal cancer screening (52 %), or blood loss (31 %). Each segment showed improvement after cleansing with JetPrep. Overall cleansing grade improved by a mean of 0.74 points (standard deviation [SD] 0.82) in the investigation group compared with 0.19 (0.40) in the control group (P < 0.0001), and right colon cleansing improved by 1.59 points (0.71) versus 0.31 (0.48) in the controls (P < 0.0001). There was no significant difference in procedure time between the groups. No adverse events or side effects were encountered. CONCLUSIONS: The JetPrep disposable catheter device is safe and efficient for intraprocedural cleansing of a suboptimally prepared colon, allowing higher quality colonoscopy.

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.

BACKGROUND AND STUDY AIMS: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Evaluation of the PillCam Colon capsule in the detection of colonic pathology: results of the first multicenter, prospective, comparative study.

BACKGROUND AND STUDY AIMS: Population-based screening for colorectal cancer is widely recommended, with conventional colonoscopy considered to be the preferred diagnostic modality. However, compliance with screening colonoscopy is low and manpower capacity is limited. Capsule endoscopy might therefore represent a desirable alternative strategy. PATIENTS AND METHODS: The PillCam Colon capsule endoscope was prospectively tested in a multicenter setting. The indications for endoscopy in the enrolled patients included colorectal cancer screening (43 %), postpolypectomy surveillance (26 %), and lower gastrointestinal signs and symptoms (31 %). Study subjects underwent colon preparation and then ingested the capsule on the morning of the examination, with conventional colonoscopy being performed the same day. The PillCam Colon capsule findings were reviewed by three experts in capsule endoscopy who were blinded to the conventional colonoscopy findings. RESULTS: A total of 91 subjects were enrolled in three Israeli centers (55 men, 36 women; mean age 57), and the results were evaluable in 84 cases. The capsule was excreted within 10 hours in 74 % of the patients and reached the rectosigmoid colon in the other 16 %. Of the 84 evaluable patients, 20 (24 %) had significant findings, defined as at least one polyp of 6 mm or more in size or three or more polyps of any size: 14/20 (70 %) were identified with the capsule and 16/20 (80 %) were identified by conventional colonoscopy. Polyps of any size were found in 45 patients, 34/45 (76 %) found by the capsule and 36/45 (80 %) by conventional colonoscopy. In comparison with conventional colonoscopy, false-positive findings on PillCam Colon capsule examination were recorded in 15/45 cases (33 %). There were no adverse events related to the capsule endoscopy. CONCLUSIONS: PillCam Colon capsule endoscopy appears to be a promising new modality for colonic evaluation. Further improvements in the procedure will probably increase capsule examination completion and polyp detection rates. Additional studies are needed to evaluate the accuracy of PillCam Colon endoscopy in other patient populations with different prevalence levels of colonic disease.

Outcome and early complications of ERCP: a prospective single center study.

BACKGROUND/AIMS: ERCP has been used since 1968 both as a diagnostic and as a therapeutic procedure. In the last ten years several less invasive imaging methods have developed which allow visualization of bile ducts and pancreatic ducts; therefore ERCP has become mainly a therapeutic tool. The aim of the study was to prospectively evaluate the early outcome of ERCP when used essentially as a therapeutic tool. METHODOLOGY: All patients referred to our unit between April 1 1998 and March 31 2000 were included in the study. The indication for the procedure, number of cannulations, duration of procedure, performance of endoscopic sphinterotomy or pre-cut, insertion of stent and the final outcome were recorded. All patients were visited (in-patients) or contacted by phone (outpatients) 24 hours and one week after the procedure. If a complication occurred the patient was followed until it was resolved. RESULTS: 722 ERCP procedures were performed on 534 patients (59% females), mean age 63.4 years (range 3 to 98 years). The procedure was performed with a therapeutic intention in 95% of cases because of suspicion of: cholelithiasis (58%), tumor of pancreas/bile ducts (30%), post-cholecystectomy bile leak or bile duct stenosis (6%) or treatment of chronic pancreatitis (1%). The overall success rate of selective duct cannulation was 92%. Endoscopic sphincterotomy was performed in 375 procedures (52%), pre-cut in 152 (21%) and stent inserted in 180 (25%). Among the 701 procedures with complete information 76 complications occurred in 73 patients (10.8%): pancreatitis 4.3%, perforation 1.3%, sepsis 3.7%, bleeding 1.4%. Most of the complications (63/701, 9%) were mild to moderate. Procedure-related mortality was 0.6% due to perforation (1 patient), and sepsis (3 patients). The main factors influencing the complication rate were the difficulty of the examination, performance of an invasive procedure or the operator. CONCLUSIONS: In the era of therapeutic ERCP, the risk of severe complication from the procedure is low--1.8% (including a mortality rate of 0.6%) when using the appropriate technique in experienced and skilled hands.

Carcinoma of Papilla Vateri presenting as recurrent acute pancreatitis.

Tumors of the Papilla of Vater can cause several clinical symptoms, the most prominent being jaundice, weight loss, anorexia, fever, abdominal pain and itching (1). Acute pancreatitis as a presenting symptom of ampullary carcinoma is rare. Few previous cases have been described in the literature (2,3). The prognosis of patients with jaundice is unfavorable in comparison with non icteric patients at the time of diagnosis (4) due to different staging, hence more complications, but not due to different histology. We report here a case of recurrent pancreatitis that was the only presentation of Vater ampullary carcinoma diagnosed by endoscopic ultrasound followed by duodenoscopy with guided biopsy. Recurrent pancreatitis without identifiable cause, particularly in elderly patients, could suggest tumor of the head of pancreas or the periampullary region among other causes such as intraductal papillary mucinous tumor, microlithiasis etc. An endoscopic ultrasound can allow earlier diagnosis and mandates biopsy in these cases.

[Undiagnosed celiac disease in adults unmasked by endoscopy].

BACKGROUND: Celiac disease may be present in many patterns other than the classical manifestations of diarrhea and malabsorption. The prevalence of celiac disease is greater than usually reported as mild cases are often undiagnosed. Diagnosing celiac disease may have major health significance. AIMS: The aim of our study was to determine the prevalence of celiac disease in adults appearing for endoscopy with abdominal pain, in an open access setting. METHODS: Two hundred and seventy consecutive, non-selected adult patients undergoing upper endoscopy for abdominal pain were included in the study. Three biopsies were routinely taken from the second part of the duodenum. In those cases with flattened villi on histology, antiendomysial antibody (AEA) was tested. RESULTS: The prevalence of celiac disease among Israeli patients undergoing endoscopy for abdominal pain was high (1:23), greater than its highest reported prevalence in general populations (1:200-300). CONCLUSIONS: Routine small bowel biopsies should be considered in patients undergoing upper endoscopy for otherwise unexplained pain.

Managing obesity: a survey of attitudes and practices among Israeli primary care physicians.

OBJECTIVES: To document and assess Israeli family physicians' (FPs) knowledge, attitudes and practices regarding the management of overweight and obesity. METHODS: Anonymous questionnaires were completed by 510 family physicians (82% compliance rate). The questionnaires were distributed in various continuous medical education sites of FPs in Israel. The measures included attitudes to and resources of knowledge on weight management, views regarding the prescription of drugs, approaches to and strategies recommended for weight loss. RESULTS: In all, 73% of FPs viewed weight management as important and reported that they often treated cases of overweight and obesity, including for patients without concomitant risk factors. The medical advice most frequently offered is: increase physical activity, decrease number of total calories (eat less) and consultation with a dietitian (95, 81 and 58% respectively). However, most responders (72%) believed that they had limited efficacy in treating obesity and considered themselves not well prepared by medical school to treat overweight patients. Some 60% reported feeling that they have insufficient knowledge regarding nutritional issues. Regarding pharmacotherapy for treating obesity, only 66% knew the drugs' prescription indications. However, the vast majority (87%) knew about the gradual increase of weight after stopping drug treatment. CONCLUSIONS: Knowledge gaps and ambivalent attitudes toward obesity management were found. More education focusing on obesity, from medical school to post-graduate learning, seems warranted based on these findings.

Linear EUS for bile duct stones.

BACKGROUND: Radial scanning endoscopic ultrasonography (EUS) has been shown, in experienced hands, to be a safe and accurate means of detecting bile duct stones. We compared linear array EUS with endoscopic retrograde cholangiopancreatography (ERCP), in our first 50 cases, to evaluate efficacy of this examination as well as the learning curve for this indication. METHODS: A retrospective study was conducted on 50 patients with suspected choledocholithiasis. We compared results of EUS with those of ERCP as a reference. First a linear EUS examination was performed followed by ERCP, at a median interval of 31 days (range 3 to 162 days). RESULTS: The average age of patients was 56 years (range 26 to 76); 48% were women. Fifteen (30%) had undergone cholecystectomy, a mean of 8.5 years (range 1 to 22) before the EUS. EUS compared with ERCP had a 97% sensitivity, 77% specificity, and 90% accuracy. In 14% of patients EUS provided an additional or alternative diagnosis: chronic pancreatitis (n = 3), duodenitis (2), bile duct stricture (1), chronic gastritis (1). No complications were encountered due to EUS. CONCLUSIONS: We found in this early experience that linear array EUS is a reasonably safe and accurate means of detecting choledocholithiasis. Linear array EUS, despite the learning curve, seems to be about equivalent to radial EUS in accuracy. Appropriate use of this less invasive technique may possibly replace the use of diagnostic ERCP.

Severe pulmonary disease in association with Crohn's disease in a 13-year-old girl.

Pulmonary manifestations of Crohn's disease are infrequent in adults and even less common in children. Our literature search found only a few cases of Crohn's disease causing pulmonary manifestations in children. We report on the case of a 13-year-old girl in whom severe pulmonary disease was found four years after the onset of Crohn's disease. Open lung biopsy uncovered bronchiolitis obliterans and granulomatous lung disease. Aggressive treatment has yielded gradual improvement. This case emphasizes the importance of recognizing the association, the differential diagnosis, and treatment implications.

Severe cholestatic jaundice induced by Epstein-Barr virus infection in the elderly.

Infectious mononucleosis due to Epstein-Barr virus (EBV) is almost always a self-limited disease, most commonly seen in young adults. Hepatitis is a well-recognized complication of EBV infection that usually resolves spontaneously. Jaundice occasionally results from the unusual complication of autoimmune haemolytic anaemia rather than hepatitis. We report a 60-year-old man with severe cholestatic jaundice whose history, liver histology and laboratory findings suggested EBV infection. He also developed significant jaundice related to his hepatitis, but not to autoimmune haemolysis, a situation that led to diagnostic delay. Costly diagnostic laboratory tests and invasive procedures were performed to rule out a malignant extrahepatic biliary obstruction. Physicians need to be aware of this complication and EBV infection should be included in the differential diagnosis of cholestatic jaundice in the elderly.

A 1000 cc Intragastric Balloon for Weight Reduction.

OBJECTIVE: To examine the efficiency of a 1000 cc intragastric balloon as an aid for weight reduction. SUBJECT: Thirty-three morbidly obese persons, after multiple attempts for weight loss. DESIGN: Intragastric 1000 cc balloons were endoscopically inserted into the stomachs of subjects. The balloons were left in place for six months. During that period the patients received dietary therapy. Hormone levels were measured prior to insertion and upon withdrawal of balloons. RESULTS: After a brief initial weight loss, most patients regained the weight initially lost. Mean weight loss after six months was only 8 kg (range 0-22 kg). We found that Bombesin levels, but not Gastrin levels, were significantly lower at the end of therapy than before insertion of the balloon. CONCLUSION: We conclude that a large intragastric balloon for a prolonged time did not assist in weight loss. Our preliminary results show Bombesin levels change significantly, a finding which warrants further study.