Andrzej Białek

Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

UNLABELLED This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. MAIN RECOMMENDATIONS 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barretts esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).

Endoscopic submucosal dissection for treatment of gastric subepithelial tumors (with video).

BACKGROUND Endoscopic submucosal dissection (ESD) is a well-accepted method for removing superficial mucosal tumors; however, there is limited data on the use of this method for removing subepithelial tumors. OBJECTIVE To investigate the efficacy, safety, and outcome of ESD for gastric subepithelial tumors and determine factors related to treatment success. DESIGN Retrospective analysis of a prospectively maintained database. SETTING Single tertiary academic center. PATIENTS AND INTERVENTIONS From April 2007 to November 2010, 37 patients with gastric subepithelial tumors were treated with ESD. MAIN OUTCOME MEASUREMENTS Macroscopically and microscopically complete en block resection rate (R0), complication rate, and endosonographic features predictive of R0 resection. RESULTS The median tumor diameter was 25.0 mm, (range 10-60 mm, IQR 17-37). The overall rate of R0 resections was 81.1% (30/37, 95%CI: 61.8-90.2%), including 100% (15/15, 95%CI: 78.2-100.0%) of tumors from the submucosa and 68.2% (15/22, 95%CI: 45.1-86.1%) of tumors from the muscularis propria. Seventeen patients had a final diagnosis of gastrointestinal stromal tumor. The severe complication (perforation) rate was 5.4% (2/37, 95%CI: 0.0-9.5%). One patient required surgery; the other was treated conservatively. No recurrence was observed in patients with R0 resections at a median follow up of 21.0 months (IQR 11-35). Successful R0 resections were predicted by the observation of no, or only narrow, tumor connections with the underlying muscle layer during EUS (OR=35.0, 95%CI: 3.7-334.4, p=0.001). LIMITATIONS Single-center, retrospective analysis, short follow-up. CONCLUSIONS ESD is an effective and relatively safe method for removing gastric subepithelial tumors. Endoscopic ultrasonography findings can predict complete tumor resections.

Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study

BACKGROUND Primary biliary cirrhosis and primary sclerosing cholangitis are two cholestatic diseases characterised by hepatic accumulation of bile acids. AIMS This study compares serum bile acid levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis and from age and sex-matched non cholestatic donors. METHODS Seventeen bile acids were quantified using liquid chromatography coupled to tandem mass spectrometry. Serum samples from cholestatic patients were compared with those of non-cholestatic donors. RESULTS The concentration of total bile acids, taurine and glycine conjugates of primary bile acids was elevated in both patients with primary biliary cirrhosis and primary sclerosing cholangitis when compared to non-cholestatic donors. Samples from primary sclerosing cholangitis patients displayed reduced levels of secondary acids, when compared to non cholestatic and primary biliary cirrhosis sera. The ratio of total glycine versus total taurine conjugates was reduced in patients with primary biliary cirrhosis, but not in primary sclerosing cholangitis. CONCLUSION The present study suggests that circulating bile acids are altered differentially in primary biliary cirrhosis and primary sclerosing cholangitis patients.

Profiling Circulating and Urinary Bile Acids in Patients with Biliary Obstruction before and after Biliary Stenting

Bile acids are considered as extremely toxic at the high concentrations reached during bile duct obstruction, but each acid displays variable cytotoxic properties. This study investigates how biliary obstruction and restoration of bile flow interferes with urinary and circulating levels of 17 common bile acids. Bile acids (conjugated and unconjugated) were quantified by liquid chromatography coupled with tandem mass spectrometry in serum and urine samples from 17 patients (8 men and 9 women) with biliary obstruction, before and after biliary stenting. Results were compared with serum concentrations measured in 40 age- and sex-paired control donors (20 men and 20 women). The total circulating bile acid concentration increases from 2.7 µM in control donors to 156.9 µM in untreated patients with biliary stenosis. Serum taurocholic and glycocholic acids exhibit 304- and 241-fold accumulations in patients with biliary obstruction compared to controls. The enrichment in chenodeoxycholic acid species reached a maximum of only 39-fold, while all secondary and 6α-hydroxylated species –except taurolithocholic acids – were either unchanged or significantly reduced. Stenting was efficient in restoring an almost normal circulating profile and in reducing urinary bile acids. Conclusion These results demonstrate that biliary obstruction affects differentially the circulating and/or urinary levels of the various bile acids. The observation that the most drastically affected acids correspond to the less toxic species supports the activation of self-protecting mechanisms aimed at limiting the inherent toxicity of bile acids in face of biliary obstruction.

Treatment of large colorectal neoplasms by endoscopic submucosal dissection: a European single-center study.

Objective Endoscopic submucosal dissection (ESD) has a high curative resection rate for gastrointestinal mucosal lesions, but is not used widely in Europe because of a high complication rate and a long learning curve. This study analyzed the ESD learning curve at a single European treatment center. Materials and methods ESD and hybrid-ESD (hESD) procedures were used to treat large colonic lesions that could not be resected in one piece by other endoscopic methods. Procedure duration and speed, and en-bloc, complete (R0) resection, and complication rates were analyzed. Results Fifty-three patients underwent ESD (37 pure ESD, 16 hESD), most with rectal lesions (n=34, 64.2%). The mean lesion diameter was 3.7±1.1 cm (range 2.0–7.0 cm), the median procedure duration was 70.0 min [interquartile range (IQR) 31.0–113.0 min], and the median treatment speed was 0.086 cm2/min (IQR 0.055–0.152). En-bloc and R0 resection rates were 86.5% (32/37) and 81.1% (30/37), respectively. Procedure speed increased significantly after about 25 cases (P=0.0313). The median hESD procedure treatment speed was 0.159 cm2/min (n=16, IQR 0.094–0.193), which was better than with classical ESD (P=0.04). The hESD en-bloc and R0 resection rates were comparable to those of classical ESD (P>0.05). The only complication was bleeding, 5.7% (3/53); no perforation occurred. Recurrence was detected during follow-up (median 30.0 months, IQR 12–48) in one patient (1.7%). Conclusion ESD is useful and safe for resection of large colorectal polyps, and procedure speed increased considerably after 25 procedures. hESD was faster than ESD, with a high therapeutic resection rate.

Role of Glucuronidation for Hepatic Detoxification and Urinary Elimination of Toxic Bile Acids during Biliary Obstruction

Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G), glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.

Liver transplantation as an ultimate step in the management of iatrogenic bile duct injury complicated by secondary biliary cirrhosis.

BACKGROUND This report summarizes a single centers experience with liver transplantation (LT) performed for secondary biliary cirrhosis resulting from iatrogenic bile duct injury (BDI) sustained during cholecystectomy. MATERIAL/METHODS Secondary biliary cirrhosis was the indication for LT in 5 (1.7%) out of 300 LTs performed in our center between Feb 2002 and April 2011. We analyzed the medical history of the patients, perioperative course and outcome following LT. RESULTS The BDI was classified as Strasberg A in 1 case, B in two cases, and E in 2 cases. There was no hepatic arterial or portal vein injury in any patient. All of the surgical repairs prior to the development of cirrhosis were performed in general surgical units. The median time between BDI and listing the patient for LT was 11 years. The cadaveric whole-organ LT was done in all patients using the Piggy-Back technique. All patients are alive with a median follow-up of 53 months. CONCLUSIONS Liver transplantation in patients with secondary biliary cirrhosis appears to result from a series of inadequate multiple surgical repairs following BDI. The immediate referral of such patients to centers with bile duct surgery experience is crucial.

Prevalence of ‘deep’ rectal varices in patients with cirrhosis: an EUS‐based study

Background: Endoscopic ultrasound (EUS) permits identification of dilated veins of the intrinsic rectal venous system (deep varices) in portal hypertension. The aim of this cross‐sectional study was to assess the prevalence of, and risk factors for, deep rectal varices, using EUS.

Endoscopic submucosal dissection for the treatment of neoplastic lesions in the gastrointestinal tract.

AIM To investigate the indications, resection rate, and safety of endoscopic submucosal dissection (ESD) for neoplastic lesions in the gastrointestinal tract at a European referral center. METHODS We carried out a retrospective analysis of the ESD procedures performed in our center for mucosal neoplastic and submucosal lesions of the gastrointestinal tract. The duration of the procedure, en bloc and complete (R0) resection rates, and complication rates were evaluated. Variables were reported as mean ± SD or simple proportions. Univariate analysis and comparisons of procedure times and resection rates were performed using Mann-Whitney U tests, or χ(2) tests for dichotomous variables. RESULTS Between 2007 and 2011, ESD was performed in a total of 103 patients (46.7% male, mean age 64.0 ± 12.7 years). The indications for the procedure were epithelial tumor (n = 54), submucosal tumor (n = 42), or other (n = 7). The total en bloc resection rate was 90.3% (93/103) and R0 resection rate 80.6% (83/103). The median speed of the procedure was 15.0 min/cm(2). The complete resection rate was lower for submucosal tumors arising from the muscle layer (68%, 15/22, P < 0.05). Resection speed was quicker for submucosal tumors localized in the submucosal layer than for lesions arising from the muscularis propria layer (8.1 min/cm(2) vs 17.9 min/cm(2), P < 0.05). The R0 resection rate and speed were better in the last 24 mo (90.1%, 49/54 and 15.3 min/cm(2)) compared to the first 3 years of treatment (73.5%, 36/49, P < 0.05 and 22.0 min/cm(2), P < 0.05). Complications occurred in 14.6% (n = 15) of patients, including perforation in 5.8% (n = 6), pneumoperitoneum in 3.9% (n = 4), delayed bleeding in 1.9% (n = 2), and other in 2.9% (n = 3). Only one patient with delayed perforation required surgical treatment. During the mean follow-up of 26 ± 15.3 mo, among patients with R0 resection, recurrence occurred in one patient (1.2%). CONCLUSION ESD is an effective and safe method for resection of neoplastic lesions with low recurrence. Speed and the R0 resection rate increased after 50 procedures.

Reduction of biliary complication rate using continuous suture and no biliary drainage for duct-to-duct anastomosis in whole-organ liver transplantation.

Biliary complications (BC) following orthotopic liver transplantation (OLT) are related to various factors including surgical technique and use of biliary drains for a duct-to-duct (DD) anastomosis. Herein we have reported the influence of changes in surgical technique on BC following OLT in our center. From February 2002 to February 2007, we performed 101 whole-organ OLT with a DD anastomosis in 99 adults, of whom we analyzed 84 subjects. We excluded recipients who died within 30 days of OLT without any evidence of BC and 1 patient with a biliary stricture secondary to a hepatic artery thrombosis. Until late 2004, a DD anastomosis with interrupted sutures over an external biliary drain (DD/BD) was performed in 35 patients (Group I). Subsequently, no biliary drain was used for the DD anastomosis (DD/non-BD), using a continuous suture in 49 patients (Group II). The DD anastomosis with interrupted sutures over a biliary drain was associated with a higher incidence of both total (31% vs 8%; P = .008) and late BC (>30 days; 20% vs 2%; P = .008) with a trend toward more leaks (17% vs 4%; P = .06). All biliary leaks in patients with DD/BD reconstruction occurred at the exit site of the biliary drain following its removal. No significant differences were observed when we compared the incidence of biliary strictures and the necessity for surgical intervention. One patient died due to a BC. Our results indicated that a DD anastomosis performed with a continuous suture technique and no external biliary drainage reduced the incidence of BC after whole-organ OLT.