Biliary tract complications after orthotopic liver transplantation. Endoscopic approach to diagnosis and therapy

This study was undertaken to further define the role of endoscopic methods in the evaluation and treatment of biliary tract complications after liver transplantation and to determine the efficacy and safety of this approach. Fifty liver transplant patients were referred for endoscopic evaluation of a suspected biliary tract complication. Two patient groups were identified based on the indication for the endoscopic retrograde cholangiopancreatography (ERCP): Group 1 was suspected of having biliary fistula and group 2 was suspected of having bile duct obstruction. Group 1 consisted of 35 patients who developed bile peritonitis after inadvertent migration of the T-tube or intentional T-tube removal. Group 2 consisted of 15 patients who developed cholestatic hepatic chemistries in the absence of allograft rejection on liver biopsy. ERCP identified a biliary fistula at the T-tube insertion site into the bile duct in 32 (91%) group 1 patients. Twenty-six of 26 treated with a nasobiliary tube had fistula closure at a mean 5.2 days. Five of 6 treated with a stent, with or without sphincterotomy, had no leak at the time of stent removal (mean, 45 days). ERCP identified a cause for the cholestatic hepatic chemistries in 11 (73.5%) group 2 patients, including bile duct stones (n = 4), anastomotic (n = 3) or intrahepatic (n = 2) strictures, bile duct necrosis (n = 1), and hemobilia (n = 1). Five of the 5 patients undergoing endoscopic therapy were treated successfully. The endoscopic complication rate was 4% and the 30-day mortality rate was 2%. During a mean follow-up of 15 months, 94% of the patients who were treated successfully had no recurrent biliary tract disease. The results of this study suggest that ERCP is an effective modality in the evaluation of patients with suspected biliary tract complications after liver transplantation. In selected patients, endoscopic therapy obviates the need for additional surgical or percutaneous intervention

Hybrid natural orifice transluminal endoscopic surgery (NOTES) for Roux-en-Y gastric bypass: an experimental surgical study in human cadavers

BACKGROUND AND STUDY AIMS: The advantages of a hybrid natural orifice transluminal endoscopic surgery approach to Roux-en-Y gastric bypass (hNOTES-RYGBP) might include: easier access to the peritoneal cavity, reduced number of ports and related complications, improved cosmesis, and others. However, currently available conventional endoscopic and laparoscopic instruments might be unsuitable for complex surgical procedures using transluminal access. The aim of this study was to investigate the feasibility and limitations of a NOTES RYGBP. METHODS: hNOTES-RYGBP was performed in human cadavers. Pouch creation was achieved by needle-knife dissection using a transvaginal, flexible scope. Articulating linear staplers were placed transumbilically to transect the stomach. Measurements of the small bowel were accomplished intraluminally or with flexible and rigid graspers. New methods were tested to create the gastro-jejunal anastomosis. A linear laparoscopic stapler was used to form the jejuno-jejunal anastomosis. RESULTS: Stapler manipulation and anvil docking, bowel manipulation and measurement, and tissue dissection presented the main obstacles for hNOTES-RYGBP. Conventional instruments were too short for some transvaginal manipulations. The time to complete the procedure was 6 - 9 hours. It was feasible to perform a complete hNOTES-RYGBP in four out of seven cadavers. Two cadavers were unsuitable due to anatomical abnormalities or advanced decay. One procedure was terminated before completion because of time constraints. Combinations of flexible and rigid visualization and manipulation were helpful, especially for dissection and gastric pouch creation. CONCLUSIONS: Several factors made hNOTES-RYGBP very challenging and time-consuming. A lack of proper instrumentation resulting in insufficient tissue traction, countertraction, and instrument manipulation complicated several steps during the procedure. A combination of flexible with rigid endoscopic techniques offers specific advantages for components of this type of surgery. Changes in instrument design are required to improve more complex endosurgical procedures

Access fistulotomy: technical tips for success

Background and Aims: Biliary cannulation, although critical to procedural success in ERCP, can be difficult and, if unsuccessful, can lead to longer hospital stays, repeat procedures, and increased costs. Expertise in adjunct techniques, including access fistulotomy, can increase success rates and potentially avoid these issues. The aim of this case series is to describe the technique of access fistulotomy and illustrate key points that are important for successful biliary access. Methods: Three cases are reviewed in which access fistulotomy was used to achieve biliary access. The steps for the procedure are reviewed, and key technical tips and anatomic landmarks are illustrated in the video. Results: Successful biliary access is obtained using fistulotomy in 3 cases. In each case, the anatomic landmarks of the papilla and intraduodenal biliary segment are reviewed. The first case illustrates a large papilla in which initial incision followed by careful exposure reveals a clear “onion ring” structure corresponding to the bile duct. The second case requires stepwise incision, each guided by anatomic landmarks before the biliary adventitia is identified, leading to biliary cannulation. In the third case, the utility of fistulotomy in a duodenal diverticulum is illustrated. Recognition of the distorted anatomy allowed precise, careful incision leading to biliary access. Conclusions: Access fistulotomy is an invaluable technique to aid in biliary access. Knowledge of key landmarks and careful evaluation of the incision are critical to successful biliary access when performing fistulotomy

Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study

Characterization of indeterminate biliary strictures remains problematic. Tissue sampling is the criterion standard for confirming malignancy but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed excellent sensitivity in a registry; however, it has not been validated in a prospective study

Reply: To PMID 25616752

Reply: To PMID 2561675

Response

We would like to thank Dr Balderramo for his interest in our study, and we thank the editors for an opportunity to preview and respond to his letter. Dr Balderramo brings up several important points and questions, which we can respond to. The first question raised relates to the isolated accuracy of probe-based confocal laser endomicroscopy (pCLE) compared with the accuracy of tissue sampling. Previous studies have examined the \u201cisolated\u201d performance of pCLE to diagnose cholangiocarcinoma by consensus and individual review of edited images in a blinded fashion.1 and 2 In this study, we recognized that the treating physician is never unbiased when performing pCLE, having met and examined the patient and reviewed all previous studies. We therefore chose to study the clinical impression of the physician at the time of pCLE and after tissue sampling returned because these are the metrics that drive decision making. Thus, the performance of pCLE alone cannot be determined in this study design because it cannot be isolated from the clinical impression of the treating physician at the time of pCLE, as we have done in prior studies. We apologize for any confusion generated by Table 3 in our article, where the last column shows the performance of ERCP plus tissue sampling of the blinded reviewer (second investigator), who had access only to single images of ERCP, CT, and a brief clinical vignette along with the tissue sampling results. Dr Balderramo asks for the clinical ERCP impression of the second investigator, which we had chosen not to present. This blinded investigator\u2019s impression of ERCP underperformed compared with the primary investigator, with accuracy, sensitivity, and specificity of 69%, 78%, and 53%, respectively. This is not surprising, given the limited data that were transmitted by electronic packages. We did this analysis to estimate routine clinical care without pCLE. Dr Balderramo also asked whether prior stenting of the common bile duct has an impact on the performance of pCLE. This was previously addressed in a separate study that showed slightly better performance in unstented patients.3 For the purposes of this response, we calculated the performance of ERCP plus pCLE in patients with prior stents (accuracy 80%, sensitivity 89%, specificity 71%) and in patients without prior stents (accuracy 85%, sensitivity 88%, specificity 79%) and found a nonsignificant trend toward better accuracy of pCLE in patients who had not been previously stented. Finally, we agree with Dr Balderramo that the accuracy of ERCP with pCLE should be compared with the accuracy of ERCP and tissue sampling. In our study, this could be done only by comparing data obtained from the treating physician who performed pCLE with data from the blinded second investigator, as shown in Table 3 of our article. This difference in accuracy between these 2 groups was not significant (82% for ERCP plus pCLE vs 79% for ERCP plus tissue sampling). We stand by our conclusion that the addition of pCLE to clinical impression and tissue sampling may allow for more accurate assessment of patients with indeterminate biliary strictures

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

Background: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript "liquid biopsy" (NETest) in BPC for diagnosis and monitoring of the disease status. Aim: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. Material and Methods: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. Results: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood. samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25-0.31). Conclusions: Elevated NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression