Marco J. Bruno

International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer.

Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. Conclusions Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.

High Prevalence of Pancreatic Cysts Detected by Screening Magnetic Resonance Imaging Examinations

BACKGROUND & AIMS The prevalence of pancreatic cysts is not known, but asymptomatic pancreatic cysts are diagnosed with increasing frequency. We investigated the prevalence of pancreatic cysts in individuals who were screened by magnetic resonance imaging (MRI) as part of a preventive medical examination. METHODS Data from consecutive persons who underwent abdominal MRI (n = 2803; 1821 men; mean age, 51.1 +/- 10.8 y) at an institute of preventive medical care were included from a prospective database. All individuals had completed an application form including questions about possible abdominal complaints and prior surgery. MRI reports were reviewed for the presence of pancreatic cysts. Original image sets of all positive MRI reports and a representative sample of the negative series were re-assessed by a blinded, independent radiologist. RESULTS Pancreatic cysts were reported in 66 persons (2.4%; 95% confidence interval, 1.9-3.0); prevalence correlated with increasing age (P < .001). There was no difference in prevalence between sexes (P = .769). There was no correlation between abdominal complaints and the presence of pancreatic cysts (P = .542). Four cysts (6%) were larger than 2 cm and 3 (5%) were larger than 3 cm. Review of the original image sets by the independent radiologist did not significantly change these findings. CONCLUSIONS The prevalence of pancreatic cysts in a large consecutive series of individuals who underwent an MRI at a preventive medical examination was 2.4%. Prevalence increased with age, but did not differ between sexes. Only a minority of cysts were larger than 2 cm.

The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer

OBJECTIVES:Approximately 10–15% of all pancreatic cancers (PCs) may be hereditary in origin. We investigated the use of endoscopic ultrasonography (EUS) for the screening of individuals at high risk for developing PC. In this paper the results of first-time screening with EUS are presented.METHODS:Those eligible for screening in this study were first-degree family members of affected individuals from familial pancreatic cancer (FPC) families, mutation carriers of PC-prone hereditary syndromes, individuals with Peutz–Jeghers syndrome, and mutation carriers of other PC-prone hereditary syndromes with clustering (≥2 cases per family) of PC. All individuals were asymptomatic and had not undergone EUS before.RESULTS:Forty-four individuals (M/F 18/26), aged 32–75 years underwent screening with EUS. Thirteen were from families with familial atypical multiple-mole melanoma (FAMMM), 21 with FPC, 3 individuals were diagnosed with hereditary pancreatitis, 2 were Peutz–Jeghers patients, 3 were BRCA1 and 2 were BRCA2 mutation carriers with familial clustering of PC, and 1 individual had a p53 mutation. Three (6.8%) patients had an asymptomatic mass lesion (12, 27, and 50 mm) in the body (n=2) or tail of the pancreas. All lesions were completely resected. Pathology showed moderately differentiated adenocarcinomas with N1 disease in the two patients with the largest lesions. EUS showed branch-type intraductal papillary mucinous neoplasia (IPMN) in seven individuals.CONCLUSIONS:Screening of individuals at a high risk for PC with EUS is feasible and safe. The incidence of clinically relevant findings at first screening is high with asymptomatic cancer in 7% and premalignant IPMN-like lesions in 16% in our series. Whether screening improves survival remains to be determined, as does the optimal screening interval with EUS.

The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis.

BACKGROUND The OLGA (operative link on gastritis assessment) staging system is based on severity of atrophic gastritis (AG). AG remains a difficult histopathologic diagnosis with low interobserver agreement, whereas intestinal metaplasia (IM) is associated with high interobserver agreement. OBJECTIVE The aim of this study was to evaluate whether a staging system based on IM is preferable to estimate gastric cancer risk. DESIGN AND SETTING Prospective multicenter study. PATIENTS A total of 125 patients previously diagnosed with gastric IM or dysplasia. INTERVENTIONS Surveillance endoscopy with extensive biopsy sampling. MAIN OUTCOME MEASUREMENTS Three pathologists graded biopsy specimens according to the Sydney classification. Interobserver agreement was analyzed by kappa statistics. In the OLGA, AG was replaced by IM, creating the OLGIM. RESULTS Interobserver agreement was fair for dysplasia (kappa = 0.4), substantial for AG (kappa = 0.6), almost perfect for IM (kappa = 0.9), and improved for all stages of OLGIM compared with OLGA. Overall, 84 (67%) and 79 (63%) patients were classified as stage I-IV according to OLGA and OLGIM, respectively. Of the dysplasia patients, 5 (71%) and 6 (86%) clustered in stage III-IV of OLGA and OLGIM, respectively. LIMITATION Prospective studies should confirm the correlation between gastric cancer risk and OLGIM stages. CONCLUSION Replacement of AG by IM in the staging of gastritis considerably increases interobserver agreement. The correlation with the severity of gastritis remains at least as strong. Therefore, the OLGIM may be preferred over the OLGA for the prediction of gastric cancer risk in patients with premalignant lesions.

Feasibility and yield of a new EUS histology needle: results from a multicenter, pooled, cohort study

BACKGROUND EUS-guided FNA is an efficacious technique for sampling intraintestinal and extraintestinal mass lesions. However, cytology has limitations to its final yield and accuracy, which may be overcome if histological specimens are provided to the pathologist. OBJECTIVE To evaluate feasibility, yield, and diagnostic accuracy of a newly developed 19-gauge, fine-needle biopsy (FNB) device. DESIGN Multicenter, pooled, cohort study. SETTING Five medical centers. PATIENTS This study involved 109 consecutive patients with 114 intraintestinal or extraintestinal mass lesions and/or peri-intestinal lymph nodes. INTERVENTION EUS-guided FNB (EUS-FNB) with a newly developed, 19-gauge, FNB device. MAIN OUTCOME MEASUREMENTS Percentage of cases in which pathologists classified the sample quality as optimal for histological evaluation and the overall diagnostic accuracy compared with a composite criterion-standard diagnosis. RESULTS We evaluated 114 lesions (mean [± standard deviation] size 35.1 ± 18.7 mm; 84 malignant [73.7%] and 30 [26.3%] benign). EUS-FNB was technically feasible in 112 lesions (98.24%). Sample quality was adequate for full histological assessment in 102 lesions (89.47%). In 98 cases (85.96%), diagnosis proved to be correct according to criterion-standard diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for diagnosis of malignancy were 90.2%, 100%, 100%, 78.9%, and 92.9%, respectively. LIMITATIONS Use of a surrogate criterion-standard diagnosis, including clinical follow-up when no surgical specimens were available, mainly in benign diagnoses. CONCLUSION Performing an EUS-FNB with a new 19-gauge histology needle is feasible for histopathology diagnosis of intraintestinal and extraintestinal mass lesions, offering the possibility of obtaining a core sample for histological evaluation in the majority of cases, with an overall diagnostic accuracy of over 85%.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

BACKGROUND AND AIMS Clarification of the position of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the interventional options available for treating patients with chronic pancreatitis. METHODS Systematic literature search to answer explicit key questions with levels of evidence serving to determine recommendation grades. The ESGE funded development of the Guideline. SUMMARY OF SELECTED RECOMMENDATIONS For treating painful uncomplicated chronic pancreatitis, the ESGE recommends extracorporeal shockwave lithotripsy/endoscopic retrograde cholangiopancreatography as the first-line interventional option. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patients case should be discussed again in a multidisciplinary team. Surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy (Recommendation grade B). For treating chronic pancreatitis associated with radiopaque stones ≥ 5 mm that obstruct the main pancreatic duct, the ESGE recommends extracorporeal shockwave lithotripsy as a first step, combined or not with endoscopic extraction of stone fragments depending on the expertise of the center (Recommendation grade B). For treating chronic pancreatitis associated with a dominant stricture of the main pancreatic duct, the ESGE recommends inserting a single 10-Fr plastic stent, with stent exchange planned within 1 year (Recommendation grade C). In patients with ductal strictures persisting after 12 months of single plastic stenting, the ESGE recommends that available options (e. g., endoscopic placement of multiple pancreatic stents, surgery) be discussed in a multidisciplinary team (Recommendation grade D).For treating uncomplicated chronic pancreatic pseudocysts that are within endoscopic reach, the ESGE recommends endoscopic drainage as a first-line therapy (Recommendation grade A).For treating chronic pancreatitis-related biliary strictures, the choice between endoscopic and surgical therapy should rely on local expertise, patient co-morbidities and expected patient compliance with repeat endoscopic procedures (Recommendation grade D). If endoscopy is elected, the ESGE recommends temporary placement of multiple, side-by-side, plastic biliary stents (Recommendation grade A).

Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis

BACKGROUND & AIMS A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. METHODS Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. RESULTS During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. CONCLUSIONS In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.

Proton Pump Inhibitors Reduce the Risk of Neoplastic Progression in Patients With Barrett's Esophagus

BACKGROUND & AIMS Acid exposure contributes to the development of Barretts esophagus (BE) and its progression toward esophageal adenocarcinoma. Patients with BE are frequently treated with acid suppressants, but it is unclear whether these prevent the development of BE-related cancer. We investigated whether acid suppression reduces the risk of neoplastic progression in patients with BE. METHODS We performed a multicenter prospective cohort study of 540 patients with BE. We collected information on medication use at each surveillance visit, which was cross-checked with pharmacy records. Patients also completed a questionnaire about their use of over-the-counter medication. Incident cases of high-grade dysplasia and esophageal adenocarcinoma were identified during a median follow-up period of 5.2 years. Time-dependent Cox regression models were used to investigate the effect of acid suppression on the risk of neoplastic progression. RESULTS Forty patients (7%) developed high-grade dysplasia or esophageal adenocarcinoma during the follow-up period. Use of histamine-2 receptor antagonists did not affect the incidence of neoplastic progression. However, use of proton pump inhibitors (PPIs) at inclusion in the study or during the follow-up period reduced the risk of neoplastic progression (hazard ratio, 0.41; 95% confidence interval, 0.18-0.93 and hazard ratio, 0.21; 95% confidence interval, 0.07-0.66). Prolonged use of PPIs and good adherence were associated with an additional protective effect. The prevalence of esophagitis decreased during PPI use, but length of BE was not affected. CONCLUSIONS In a multicenter prospective cohort study, PPI use was associated with a reduced risk of neoplastic progression in patients with BE.

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus

Objective The value of surveillance for patients with Barretts oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO. Design We conducted a case–control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome. Results During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RRa) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RRa 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression. Conclusions Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

Efficacy of Endoscopic Closure of Acute Perforations of the Gastrointestinal Tract

BACKGROUND & AIMS Acute perforations of the gastrointestinal tract are rare, severe complications of endoscopy that usually require surgical repair. Endoscopic repair of perforations would reduce the need for surgeries; we evaluated the efficacy and safety of endoscopic closure of acute perforations of the gastrointestinal tract by using a new clip device. METHODS We conducted a prospective, international, multicenter study of 36 consecutive patients (15 male) with acute iatrogenic perforations (5 esophageal, 6 gastric, 12 duodenal, and 13 colonic perforation). Endoscopic repair was performed by using the Over-the-Scope-Clip according to a standardized operating procedure. Primary end point was successful closure, which was determined as endoscopic successful closure without leakage (detected by water-soluble contrast x-ray analysis), and absence of adverse events within 30 days after the procedure. RESULTS Immediate closure was endoscopically successful in 33 patients (92%). One patient developed an esophageal perforation while the cap was introduced, and in 2 patients the perforations did not close; these 3 patients were successfully treated with surgery. None of the patients had leakage of soluble contrast on the basis of contrast x-ray. One patient with a closed colonic perforation deteriorated clinically within 6 hours after the procedure. Despite surgery, the patient died within 36 hours. The remaining 32 patients had successful endoluminal closures; the overall success rate was 89% (95% confidence interval, 75%-96%). The mean endoscopic closure time was 5 minutes 44 seconds ± 4 minutes 15 seconds. CONCLUSIONS The Over-the-Scope-Clip is effective for endoluminal closure of acute iatrogenic perforations. It allows patients to avoid surgery, and 89% of patients had successful closures without adverse events.