A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals.

OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. DESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. RESULTS: Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. CONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.

Dutch Chronic Pancreatitis Registry (CARE): design and rationale of a nationwide prospective evaluation and follow-up.

BACKGROUND: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. METHODS: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. RESULTS: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. DISCUSSION: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.

Management of pancreatic cysts: a review of the current guidelines.

The number of patients diagnosed with cystic pancreatic neoplasms (CPN) has increased significantly during the last decade due to the widespread use of cross-sectional imaging. These CPN consist of a heterogeneous group of neoplastic and non-neoplastic lesions with variable histopathological features, clinical presentation, and outcome. Until now we are not able to reliably identify all CPNs that require additional analysis, surgical resection or surveillance. Hence, physicians and surgeons are confronted with a difficult dilemma as they do not want to miss a diagnosis of pancreatic carcinoma, but this often leads to the risk of over- or misuse of diagnostic examinations with a risk of complications and increased health care costs. Currently, four expert consensus guidelines on cystic lesions of the pancreas are available. Unfortunately, recommendations vary considerably between these guidelines. The purpose of this review therefore was to compare the different guidelines and elaborate upon the topics where these guidelines disagree.

Serum level of Ca 19-9 increases ability of IgG4 test to distinguish patients with autoimmune pancreatitis from those with pancreatic carcinoma.

BACKGROUND: Autoimmune pancreatitis (AIP) is often difficult to distinguish from pancreatic carcinoma or other pancreatobiliary diseases. High serum levels of carbohydrate antigen 19-9 (Ca 19-9) are indicative of malignancies, whereas high levels of immunoglobulin (Ig)G4 (>1.4 g/l) are characteristic of AIP. We investigated whether serum levels of these proteins can differentiate between these diseases. METHODS: We measured levels of Ca 19-9 and IgG4 in serum samples from 33 patients with AIP, 53 with pancreatic carcinoma, and 145 with other pancreatobiliary disorders. We determined cut-off levels for each assay. Logistic regression analysis was used to evaluate combined data on Ca 19-9, IgG4, and bilirubin levels. RESULTS: Low levels of Ca 19-9 were independently associated with AIP, compared with pancreatic adenocarcinoma [odds ratio (OR) 0.28; 95% confidence interval (CI) 0.13-0.59; p = 0.0001]. Using an upper level of 74 U/ml, the assay for Ca 19-9 identified patients with AIP with 73% sensitivity and 74% specificity. Using a lower level of 2.6 g/l, the assay for IgG4 identified these patients with 70% sensitivity and 100% specificity. Combining data, levels of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l identified patients with AIP with 94% sensitivity and 100 % specificity. CONCLUSIONS: Patients with AIP have lower levels of Ca 19-9 than those patients with pancreatic carcinoma. Measurement of either the Ca 19-9 or the IgG4 level alone are not accurate enough for diagnosis. However, the combination of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l distinguishes patients with AIP from those patients with pancreatic carcinoma with 94% sensitivity and 100% specificity.

Clinical outcome of progressive stenting in patients with anastomotic strictures after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: Anastomotic strictures are an important cause of morbidity after orthotopic liver transplantation (OLT). Endoscopic treatment is the primary treatment modality for biliary complications after OLT. The outcome and complications of a progressive stenting protocol are largely unknown. PATIENTS AND METHODS: A longitudinal cohort study of OLTs was conducted. Only patients with late strictures were included. Treatment success was defined as cholangiographic stricture resolution and liver enzymes returning to normal with follow-up of at least 12 months. RESULTS: Between May 2000 and June 2009, 375 OLTs were performed. A duct-to-duct anastomosis was created in 304 cases (81 %). In 63 patients (21 %; 95 % confidence interval [CI] 16.5 % - 25.6 %) an anastomotic stricture developed and progressive stenting was started in 35. During treatment two patients died of a non-treatment-related cause and two patients underwent a second OLT during stent therapy. Therefore 31 patients were available for analysis (male : female 21:10; median age 61 years, range 28 - 75 years). Progressive stenting required a median number of 5 endoscopic retrograde cholangiopancreatography (ERCP) procedures (range 4 - 11). A median maximum of 4 stents (range 2 - 8) were inserted. A total of 21 patients (67.7 %; 95 %CI 50.1 % - 81.4 %) developed a treatment-related complication. In 33 out of a total of 155 ERCPs (21.3 %) a complication occurred: cholangitis (n = 12), transient cholestasis (n = 11), post-ERCP pancreatitis (n = 7), and treatment-related pain (n = 3). The median follow-up time after stent removal was 28 months (range 12 - 92). Treatment was successful in 25 patients (80.6 %; 95 %CI 63.7 % - 90.8 %). CONCLUSION: Progressive stenting for anastomotic strictures after OLT is demanding and burdensome, necessitating a median of 5 ERCP procedures with complications occurring in one out of five procedures. Its success rate however is high (81 %), avoiding surgery in the large majority of patients.

PTEN in colorectal cancer: a report on two Cowden syndrome patients.

Heterozygous germline PTEN mutations cause Cowden syndrome. The risk of colorectal cancer in Cowden patients, however, remains a matter of debate. We describe two patients presenting with colorectal cancer at a young age (28 and 39 years) and dysmorphisms fitting the Cowden spectrum. Heterozygous germline mutations in PTEN were found in both patients. Moreover, analysis of the resected colorectal cancer specimens revealed loss of heterozygosity at the PTEN locus with retention of the mutated alleles, and greatly reduced or absent PTEN expression. Histologically and molecularly, the tumours showed resemblance with sporadic colorectal cancers, although they had prominent fibrotic stroma. Our data indicate that PTEN loss was involved in carcinogenesis in the two patients, supporting that colorectal cancer is part of the Cowden syndrome-spectrum. This is in line with data on sporadic colorectal cancer, mice studies and emerging epidemiological data on Cowden syndrome. Although the exact role of germline PTEN mutations in the carcinogenesis of colorectal cancer remains unclear, we think that Cowden syndrome should be in the differential diagnosis of colorectal cancer certainly in view of the possible prognostic and therapeutic consequences. Prospective follow-up and surveillance of PTEN mutation carriers from the age of 25 to 30 years in a study setting should clarify this issue.

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 patient's 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).

New developments in endoscopic treatment of chronic pancreatitis.

The aim of endoscopic therapy of chronic pancreatitis (CP) is to treat pain by draining the pancreatic duct or managing loco-regional complications. Recent decennia were characterized by continuous improvement of endoscopic techniques and devices, resulting in a better clinical outcome. Novel developments now also provide the opportunity to endoscopically treat refractory CP-related complications. Especially suboptimal surgical candidates could potentially benefit from these new developments, consequently avoiding invasive surgery. The use of fully covered self-expandable metal stents (SEMS) has been explored in pancreatic and CP-related biliary duct strictures, resistant to conventional treatment with plastic endoprotheses. Furthermore, endosonography-guided transmural drainage of the main pancreatic duct via duct-gastrostomy is an alternative treatment option in selected cases. Pancreatic pseudocysts represent an excellent indication for endoscopic therapy with some recent case series demonstrating effective drainage with the use of a fully covered SEMS. Although results of these new endoscopic developments are promising, high quality randomized trials are required to determine their definite role in the management of chronic pancreatitis.

Endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions provides inadequate material for cytology and laboratory analysis: initial results from a prospective study.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is considered a valuable and safe technique for further investigation of pancreatic cystic lesions. In the framework of a prospective study on the accuracy of EUS-FNA we report our initial technical results regarding puncture access, sample adequacy, and complications PATIENTS AND METHODS: Consecutive patients with indeterminate pancreatic cystic lesions underwent EUS and EUS-FNA. Pancreatic cyst fluid was collected for cytopathological analysis and measurement of amylase, carcinoembryonic antigen (CEA), and carbohydrate antigen 19.9 (CA 19.9) levels. Main outcome parameter for this analysis was the percentage of samples adequate for cytologic and laboratory analysis. RESULTS: Of 143 patients (median age 63 years; median cyst size 2.8 cm) who underwent EUS, FNA was performed in 128 (90 %). The various reasons for not doing FNA included large distance between transducer and cystic lesion (n = 9), cyst not seen or too small (n = 2), and evident diagnosis not requiring FNA (n = 3). FNA was not possible in four patients (technical failures). Cyst fluid sent for cytology provided adequate cellular material in 44 cases only, accounting for an intention-to-diagnose yield of 31 % (44/143). Sufficient fluid for biochemical analysis was obtained in 68 cases (49 %). Complications occurred in three patients (2.4 %). CONCLUSIONS: Although EUS-guided FNA was technically feasible in the majority of patients with pancreatic cystic lesions (87 %), it was possible to obtain a classifying cytopathologic diagnosis and a chemical analysis in only a third and a half of cases, respectively.

Interobserver agreement for endosonography in the diagnosis of pancreatic cysts.

BACKGROUND AND STUDY AIMS: Endosonography is considered a valuable technique in the evaluation of pancreatic cysts. The aim of the present study is to assess interobserver agreement, in three different observer groups, regarding EUS for characterization of pancreatic cysts. PATIENTS AND METHODS: Video sequences of 40 EUS procedures for pancreatic cysts were prepared. Three groups of observers had different levels of EUS experience: group 1 comprised four experts with extensive EUS experience, group 2 had four "semi-experts" with limited EUS experience, and group 3 (novices) comprised four non-expert resident physicians without EUS experience. Features scored included septations, nodules, solid components, and pancreatic duct communication. A presumptive diagnosis had to be specified. The intraclass correlation coefficient (ICC) was used, with agreement classed as excellent (> 0.80), good (0.61 - 0.80), moderate (0.41 - 0.60), fair (0.20 - 0.40), and poor (< 0.20). RESULTS: Agreement regarding nodules was good among experts (ICC 0.65) and fair in the semi-expert and novice groups (ICC 0.32 and 0.37, respectively). For presence of solid components there was significantly higher agreement among experts (ICC 0.52) compared with the other two groups (semi-experts 0.09, and novices 0.03). Agreement regarding specific diagnosis was moderate in the expert group (0.43), poor among the semi-experts (0.09), and fair among the novices (0.30). CONCLUSIONS: Interobserver agreement among expert endosonographers was mostly moderate for characteristics of pancreatic cysts. However, interobserver agreement for experts was equal to or higher than that in the semi-expert and in the novice groups.

Complicated systemic lupus erythematosus pancreatitis: pseudocyst, pseudoaneurysm, but real bleeding.

We report the case of a 25-year-old patient with systemic lupus erythematosus (SLE) pancreatitis which was complicated by pseudocyst and pseudoaneurysm formation. The pseudoaneurysm progressed to intra-abdominal bleeding requiring endovascular coil embolization of the gastroduodenal artery. The pseudocyst and hematoma formed two large abdominal fluid collections causing symptoms due to a mass effect. These fluid collections were treated conservatively, while active SLE was treated with steroids, azathioprine, and immunoglobulins. She finally made a full recovery. To the best of our knowledge, this is the first report of a bleeding pseudoaneurysm complicating SLE pancreatitis. Although anecdotal, this case may serve as a useful example of the possible complications of SLE pancreatitis, including considerations on optimal management.

Predictors of complications after endoscopic retrograde cholangiopancreatography: a prognostic model for early discharge.

BACKGROUND: Several studies have evaluated predictors for complications of endoscopic retrograde cholangiopancreatography (ERCP), but their relative importance is unknown. In addition, currently used blood tests to detect post-ERCP pancreatitis are inconsistent. The aim of this study was to determine predictors of post-ERCP complications that could discriminate between patients at highest and lowest risk of post-ERCP complications and to develop a model that is able to identify patients that can safely be discharged shortly after ERCP. METHODS: In a single-center, retrospective analysis over the period 2002-2007, predictors of post-ERCP complications were evaluated in a multivariable analysis and compared with those identified from a literature review. A prognostic model was developed based on these risk factors, which was further evaluated in a prospective patient population. RESULTS: From our retrospective analysis and literature review, we selected the eight most important risk factors for post-ERCP pancreatitis and cholangitis. In the prognostic model, the risk factors (precut) sphincterotomy, sphincter of Oddi dysfunction, younger age, female gender, history of pancreatitis, pancreas divisum, and difficult cannulation accounted for a score of 1 each, whereas primary sclerosing cholangitis (PSC) accounted for a score of 2. A sum score of 4 or more in the prognostic model was associated with a high risk of developing pancreatitis and cholangitis (27%; 6/22) in the prospective patient population, whereas a sum score of 3 or less was associated with a low to intermediate risk (8%; 20/252). CONCLUSIONS: We identified specific patient- and procedure-related factors that are associated with post-ERCP complications. The prognostic model based on these factors is able to identify patients who can be safely discharged the same day after ERCP.

Is early diagnosis of pancreatic cancer fiction? Surveillance of individuals at high risk for pancreatic cancer.

Pancreatic cancer represents one of the most deadly human malignancies with an overall 5-year survival of less than 5%. Despite improvements in imaging techniques and surgical techniques, survival statistics have hardly improved over the past decades. To improve the dismal outlook it would be highly desirable to develop a program to detect precursor lesions or small asymptomatic early cancers at the time when the disease is still at a curable stage. Screening the general population for disease presence is not feasible at present because of the relatively low disease incidence and the lack of a noninvasive, reliable and cheap screening tool. Targeted surveillance programs, however, in individuals at high risk for developing pancreatic cancer, like mutation carriers of pancreatic cancer prone hereditary (tumor) syndromes or individuals with a strong family history of pancreatic cancer without a known underlying genetic defect, might be feasible. Careful consideration of the criteria put forward by Wilson and Jungner as published by the World Health Organization on the principles and practice of screening for disease, indicate that surveillance in this high-risk population by means of endosonography (EUS) and/or magnetic resonance imaging (MRI) represents a promising development, though experimental. It nicely points out which open questions need to be addressed. Among others, these include how to acquire a better understanding of the natural behavior and progression of precursor lesions towards invasive cancer, how to firmly establish the performance characteristics of EUS and MRI for the detection of (early) lesions in individuals at high risk for pancreatic cancer, and how to determine which lesions can be safely observed with continued surveillance and which lesions justify resection.

Preliminary report on the safety and utility of a novel automated mechanical endoscopic tissue resection tool for endoscopic necrosectomy: a case series.

Background and study aims Endoscopic drainage of walled-off necrosis and subsequent endoscopic necrosectomy has been shown to be an effective step-up management strategy in patients with acute necrotizing pancreatitis. One of the limitations of this endoscopic approach however, is the lack of dedicated and effective instruments to remove necrotic tissue. We aimed to evaluate the technical feasibility, safety, and clinical outcome of the EndoRotor, a novel automated mechanical endoscopic tissue resection tool, in patients with necrotizing pancreatitis. Methods Patients with infected necrotizing pancreatitis in need of endoscopic necrosectomy after initial cystogastroscopy, were treated using the EndoRotor. Procedures were performed under conscious or propofol sedation by six experienced endoscopists. Technical feasibility, safety, and clinical outcomes were evaluated and scored. Operator experience was assessed by a short questionnaire. Results Twelve patients with a median age of 60.6 years, underwent a total of 27 procedures for removal of infected pancreatic necrosis using the EndoRotor. Of these, nine patients were treated de novo. Three patients had already undergone unsuccessful endoscopic necrosectomy procedures using conventional tools. The mean size of the walled-off cavities was 117.5 ± 51.9 mm. An average of two procedures (range 1 - 7) per patient was required to achieve complete removal of necrotic tissue with the EndoRotor. No procedure-related adverse events occurred. Endoscopists deemed the device to be easy to use and effective for safe and controlled removal of the necrosis. Conclusions Initial experience with the EndoRotor suggests that this device can safely, rapidly, and effectively remove necrotic tissue in patients with (infected) walled-off pancreatic necrosis.

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 (> or =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.

High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis.

BACKGROUND AND STUDY AIM: Duodenal polyposis occurs in approximately 90 % of patients with familial adenomatous polyposis (FAP) and 5 % - 10 % develop duodenal cancer. Novel imaging techniques may improve evaluation of duodenal polyposis using the Spigelman classification. We aimed to analyze the value of high resolution endoscopy (HRE) and the additional value of chromoendoscopy in the evaluation of duodenal polyposis in FAP. PATIENTS AND METHODS: 43 FAP patients scheduled for surveillance endoscopy in two academic centers underwent gastroduodenoscopy with HRE forward- and side-viewing devices. After number and size of adenomas had been scored, indigo carmine 0.5 % was sprayed onto the mucosa, polyps were scored again and biopsies taken from the larger lesions. Subsequently, Spigelman classifications were assessed for pre- and post-staining. RESULTS: Before staining, a median of 16 adenomas per patient were detected compared with 21 adenomas after staining ( P = 0.02). Staining led to upgrading of Spigelman stage in 5/43 patients (12 %). Using the side-viewing endoscope, ampullary enlargement was detected in 22 patients (51 %) of whom 18 (42 %) had histologically confirmed ampullary adenomas. CONCLUSION: HRE has raised the quality of endoscopic imaging considerably. Consequently, re-evaluation of the original Spigelman classification system seems advisable. Chromoendoscopy further increases detection of duodenal adenomas in FAP but without considerable change in Spigelman stage. Ampullary adenomas are commonly found in FAP and are best visualized using a side-viewing endoscope. Therefore, a combination of forward-viewing HRE and chromoendoscopy with side-viewing endoscopy for the periampullary region seems useful for surveillance of duodenal adenomatosis in FAP.

Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: the Rotterdam experience.

Multimodality treatment is increasingly used in the treatment for esophageal cancer. We determined the tumor regression grade after preoperative chemoradiation and correlated the effect of specific pathologic and clinical findings to overall survival. For this purpose esophageal biopsies and surgical specimens of 67 patients treated with neoadjuvant paclitaxel and carboplatin concurrent with radiotherapy were reviewed. Neoadjuvant chemoradiotherapy led to a significant downstaging. Complete tumor regression was found in 24% of the patients resulting in a trend towards better survival. It was found more frequently in poorly differentiated tumors. Patients with pre-treatment nodal involvement, assessed by endoscopic ultrasound, had a significantly worse survival compared to patients without. Contrastingly, this was not found for post-treatment nodal involvement, as determined by pathological examination, speculating that survival is more determined by (submicroscopic) distant disease, than by locoregional tumor cells.

Eosinophilic oesophagitis: an enigmatic, emerging disease.

Eosinophilic oesophagitis is a disease that has emerged in recent years. It is often associated with dysphagia and oesophageal food impaction in adults. The disease is characterised by infiltration of eosinophilic granulocytes into the oesophageal mucosa. This infiltrate may be responsible for the subtle peristaltic abnormalities that can be found in these patients. Endoscopic findings are usually absent or nonspecific, although a discrete circular ring pattern of the mucosa may be noticed. Occasionally, overt endoscopic abnormalities (such as exudative changes and shearing of the mucosa) can be found. The presence of at least 15 intraepithelial eosinophilic granulocytes per high-power field in random biopsies from the whole length of the oesophagus is considered to be diagnostic. Gastro-oesophageal reflux needs to be excluded as it may lead to eosinophilic infiltration as well. Adequate diagnosis is relevant for treatment and the prevention of unnecessary further investigations. The disease responds well to the ingestion of fluticasone propionate and its long-term prognosis is generally good. But when fluticasone is discontinued recurrent symptoms are common, and some cases are severe, needing treatment with systemic corticosteroids.

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.

Publication bias does not play a role in the reporting of the results of endoscopic ultrasound staging of upper gastrointestinal cancers.

BACKGROUND AND STUDY AIM: An overestimation of the accuracy of endoscopic ultrasound (EUS) results in rectal cancer staging has been reported recently, which was found to be caused by the selective reporting of more positive results. In this study, we assessed whether publication bias was also present in the reporting of EUS staging results in upper gastrointestinal cancer. METHODS: A Medline literature search was performed. English-language articles containing information on the accuracy of EUS for T staging and/or N staging of esophageal, gastric, and pancreatic cancer were included. Articles published in abstract form only, case reports, and reviews were excluded. Studies reporting EUS results of patients who had undergone preoperative radiation and/or chemotherapy were also excluded. EUS results were plotted against numbers of patients, year of publication, journal type, and journal impact factor. RESULTS: The plots of the numbers of patients against accuracies for T stage and N stage and the statistical analyses showed no evidence of publication bias with regard to upper gastrointestinal cancer. The reported accuracy of EUS for the T stage of esophageal, gastric, and pancreatic cancer declined slightly over the years, but this was statistically significant only in the case of esophageal cancer (P = 0.01). No statistically significant correlations were found for N staging for any of the three types of cancer. In addition, no correlations were found between EUS results and journal type or journal impact factor. CONCLUSION: No evidence was found for the selective reporting of more positive EUS results for esophageal, gastric, and pancreatic cancer staging, which suggests that publication bias was not present.