Obstructive jaundice of a parasitic etiology.

We present the case of a patient with colic pain in the epigastrium and right hypochondrium, which was accompanied by choluria and acholia and slightly elevated levels of bilirubin and eosinophilia. Abdominal echography and magnetic resonance imaging identified a biliary obstruction and endoscopic retrograde cholangiopancreatography was used to extract 3 adult worms identified as Fasciola hepatica. This case highlights the need to consider the suspicion of biliary obstruction caused by Fasciola hepatica in the presence of obstructive jaundice, with or without eosinophilia.

Laparoscopic transgastric ERCP in bariatric surgery patients: our experience.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the surgical treatment of choice for morbid obesity. Several therapeutic options to remove common bile duct (CBD) stones have been proposed in these patients. Laparoscopy-assisted transgastric ERCP (LATERCP) has a high success rate. However, the procedure is not fully standardized and some technical variations have been proposed. We introduce two cases in which laparoscopic transgastric ERCP has been used to treat choledocholithiasis after LRYGB.

Successive breaks in biliary stents.

A 64 year-old male, was diagnosed with obstructive jaundice due to a well-differentiated pancreatic neuroendocrine tumor with liver metastases. The patient underwent endoscopic placement of covered self-expanding biliary stent (10x60 mm, Hanaro) by ERCP. He was admitted with cholangitis one year later. The following ERCP revealed a fractured stent with loss of the distal end (duodenal) and partial migration of the remaining stent to the common bile duct. The fragmented stent was removed from the common bile duct and a new, similar one was inserted. Four months later the patient was admitted with cholangitis. A new ERCP was done and biliary stent was also fragmented. It was removed and an uncovered stent (Wallflex) was inserted.

Endoscopic ampullectomy: a technical review.

BACKGROUND AND AIM: This article provides a practical review to undertaking safe endoscopic ampullectomy and highlights some of the common difficulties with this technique as well as offering strategies to deal with these challenges. METHODS: We conducted a review of studies regarding endoscopic ampullectomy for ampullary neoplasms with special focus on techniques. RESULTS: Accurate preoperative diagnosis and staging of ampullary tumors is imperative for predicting prognosis and determining the most appropriate therapeutic approach. The optimal technique for endoscopic ampullectomy is dependent on the lesions size. En bloc resection is recommended for lesions confined to the papilla. There is no significant evidence to support the submucosal injection before ampullectomy. There is no consensus regarding the optimal current and power output for endoscopic ampulectomy. The benefits of a thermal adjunctive therapy remain controversial. A prophylactic pancreatic stent reduces the incidence and severity of pancreatitis post-ampullectomy. CONCLUSIONS: Endoscopic ampullectomy is a safe and efficacious therapeutic procedure for papillary adenomas in experienced endoscopist and it can avoid the need for surgical intervention.

Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.

Dissecting the genetic heterogeneity of gastric cancer.

BACKGROUND: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. METHODS: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. FINDINGS: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. INTERPRETATION: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. FUNDING: German Research Foundation (DFG).

Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype.

Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.

Stenosis in laparoscopic gastric bypass: management by endoscopic dilation without fluoroscopic guidance.

OBJECTIVES: gastric bypass is the surgical procedure that is carried out most frequently in the treatment of morbid obesity. Stenosis of the gastro-jejunal anastomosis is a relatively frequent complication that requires endoscopic management. However, the optimal dilation technique is yet to be determined. The purpose of this study was to evaluate the safety and efficacy of dilation with a hydrostatic balloon (CRE) without radioscopic guidance in morbidly obese patients treated by laparoscopic bypass. MATERIAL AND METHODS: retrospective review of the data elicited from 525 patients treated against morbid obesity with laparoscopic gastric bypass from January, 2006 to November, 2010. RESULTS: a total of 22/525 patients (4.1%) developed stenosis of the anastomosis [20 women (91%), 2 men (9%)]. In four patients (18.2%), there was an associated anastomotic ulcer, and in one case, there was a history of bleeding of an ulcer treated with sclerosis one month earlier. The diagnosis of stenosis was done in most patient during the first 90 days after the bypass. All cases were resolved by means of endoscopic dilation without adioscopic guidance, 15 cases (68.1%) required a single session, 6 cases (27.2%) two sessions, and 1 case (4.5%) required four sessions. This last case had an associated anastomotic ulcer. The diameter of the balloons ranged from 12 to 20 mm, generally using diameters of 12-15 mm in the first session, and increasing them in the following sessions according to the previous result. One patient treated with a 20 mm balloon presented with a small tear, without showing any evidence of leak of contrast medium in the radioscopic guidance, and was thus managed conservatively. In the follow-up, no re-stenoses were detected. CONCLUSIONS: in our experience, stenosis of the anastomosis in the laparoscopic gastric bypass is an infrequent complication. When it happens, dilation with a hydrostatic balloon is an effective and safe treatment. Radioscopic guidance during dilation is not strictly necessary if norms of progressive dilation are followed.

Double-guidewire technique for difficult bile duct cannulation: a multicenter randomized, controlled trial.

BACKGROUND: ERCP can be associated with serious complications. Difficulty in common bile duct (CBD) cannulation is one of the main risk factors for post-ERCP pancreatitis. The double-guidewire technique (DGT) has been considered a promising alternative approach in difficult cannulation situations. OBJECTIVE: To compare the performance of DGT with the standard cannulation technique (SCT) in patients in whom CBD cannulation is difficult to perform. DESIGN: Multicenter randomized, controlled trial. SETTING: Six tertiary referral centers. PATIENTS: A total of 188 patients with difficult CBD cannulation defined by completion of 5 unsuccessful cannulation attempts were enrolled. INTERVENTIONS: Ninety-seven patients were assigned to the DGT group and 91 to the SCT group. Both techniques were compared for an extra 10 cannulation attempts. MAIN OUTCOME MEASUREMENTS: CBD cannulation rate, number of attempts required to cannulate, and ERCP-related complications. RESULTS: Successful CBD cannulation was achieved in 46 of 97 (47%) patients in the DGT group compared with 51 of 91 (56%) in the SCT group (OR 0.85; 95% CI, 0.64-1.12). The median number of attempts required for each group was 9 and 7, respectively (P = .128). The incidence of post-ERCP pancreatitis was 17% in the DGT group and 8% in the SCT group (OR 2.13; 95% CI, 0.89-5.05). LIMITATIONS: Reduced number of enrolled subjects and a lack of detailed information regarding the number and extent of pancreatic duct contrast injections. CONCLUSIONS: In patients with difficult CBD cannulation, DGT was not superior to SCT in achieving CBD cannulation. DGT might be associated with a higher risk of post-ERCP pancreatitis.

Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level.

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10-04 ) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10-09 ). On chromosome 5p13 we found cis-eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10-11 ). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10-47 ). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10-09 ). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms.

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype.

Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55-2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22-2.57), and family history of GC (OR: 2.87; 95% CI: 1.85-4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56-0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56-0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38-0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30-2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.

Treatment modalities for early gastric cancer.

Different treatment modalities have been proposed in the treatment of early gastric cancer (EGC). Endoscopic resection (ER) is an established treatment that allows curative treatment, in selected cases. In addition, ER allows for an accurate histological staging, which is crucial when deciding on the best treatment option for EGC. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become alternatives to surgery in early gastric cancer, mainly in Asian countries. Patients with "standard" criteria can be successfully treated by EMR techniques. Those who meet "expanded" criteria may benefit from treatment by ESD, reducing the need for surgery. Standardized ESD training system is imperative to promulgate effective and safe ESD technique to practices with limited expertise. Although endoscopic resection is an option in patients with EGC, surgical treatment continues to be a widespread therapeutic option worldwide. In this review we tried to point out the treatment modalities for early gastric cancer.

Endoscopic management of adenomatous ampullary lesions.

Lesions of the ampulla of Vater represent an uncommon group of gastrointestinal malignancies. The majority of lesions of the ampulla of Vater are either adenomas or adenocarcinomas. Ampullary lesions are often incidental findings. Accurate preoperative diagnosis and staging of ampullary tumors is imperative for predicting prognosis and determining the most appropriate therapeutic approach. Endoscopic ampullectomy is a safe and efficacious therapeutic procedure that can obviate the need for potentially major surgical intervention. This review will provide the framework for the diagnosis and management of ampullary lesions from the perspective of the practicing gastroenterologist. Strategies for safe and successful endoscopic ampullectomy with a focus on accurate preoperative diagnosis and staging, resection technique, and management of complications are presented.

Multiband mucosectomy for advanced dysplastic lesions in the upper digestive tract.

Endoscopic resection (ER) is at present an accepted treatment for superficial gastrointestinal neoplasia. ER provides similar efficacy to surgery; however, it is minimally invasive and less expensive. Endoscopic mucosal resection (EMR) is superior to biopsy for diagnosing advanced dysplasia and can change the diagnostic grade and the management. Several EMR techniques have been described that are alternatively used dependent upon the endoscopist personal experience, the anatomic conditions and the endoscopic appearance of the lesion to be resected. The literature suggests that EMR offers comparable outcomes to surgery for selected indications. EMR techniques using a cap fitted endoscope and EMR using a ligation device [multiband mucosectomy (MBM)] are the most frequently use. MBM technique does not require submucosal injection as with the endoscopic resection-cap technique, multiple resections can be performed with the same snare, pre-looping the endoscopic resection-snare in the ridge of the cap is not necessary, MBM does not require withdrawal of the endoscope between resections and up to six consecutive resections can be performed. This reduces the time and cost required for the procedure, while also reducing patient discomfort. Despite the increasing popularity of MBM, data on the safety and efficacy of this technique in upper gastrointestinal lesions with advanced dysplasia, defined as those lesions that have high-grade dysplasia or early cancer, is limited.