Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology.

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Laparoscopic ultrasonography as an alternative to intraoperative cholangiography during laparoscopic cholecystectomy.

AIM: To assess the role of laparoscopic ultrasound (LUS) as a substitute for intraoperative cholangiography (IOC) during cholecystectomy. METHODS: We present a MEDLINE and PubMed literature search, having used the key-words "laparoscopic intraoperative ultrasound" and "laparoscopic cholecystectomy". All relevant English language publications from 2000 to 2016 were identified, with data extracted for the role of LUS in the anatomical delineation of the biliary tract, detection of common bile duct stones (CBDS), prevention or early detection of biliary duct injury (BDI), and incidental findings during laparoscopic cholecystectomy. Data for the role of LUS vs IOC in complex situations (i.e., inflammatory disease/fibrosis) were specifically analyzed. RESULTS: We report data from eighteen reports, 13 prospective non-randomized trials, 5 retrospective trials, and two meta-analyses assessing diagnostic accuracy, with one analysis also assessing costs, duration of the examination, and anatomical mapping. Overall, LUS was shown to provide highly sensitive mapping of the extra-pancreatic biliary anatomy in 92%-100% of patients, with more difficulty encountered in delineation of the intra-pancreatic segment of the biliary tract (73.8%-98%). Identification of vascular and biliary variations has been documented in two studies. Although inflammatory disease hampered accuracy, LUS was still advantageous vs IOC in patients with obscured anatomy. LUS can be performed before any dissection and repeated at will to guide the surgeon especially when hilar mapping is difficult due to fibrosis and inflammation. In two studies LUS prevented conversion in 91% of patients with difficult scenarios. Considering CBDS detection, LUS sensitivity and specificity were 76%-100% and 96.2%-100%, respectively. LUS allowed the diagnosis/treatment of incidental findings of adjacent organs. No valuable data for BDI prevention or detection could be retrieved, even if no BDI was documented in the reports analyzed. Literature analysis proved LUS as a safe, quick, non-irradiating, cost-effective technique, which is comparatively well known although largely under-utilized, probably due to the perception of a difficult learning curve. CONCLUSION: We highlight the advantages and limitations of laparoscopic ultrasound during cholecystectomy, and underline its value in difficult scenarios when the anatomy is obscured.

A scoring system for the prediction of choledocholithiasis: a prospective cohort study.

BACKGROUND: Techniques for diagnosing choledocholithiasis pose significant morbidity and mortality risks. OBJECTIVES: We aimed to develop and validate a clinical scoring system for predicting choledocholithiasis. DESIGN: Data from a prospectively maintained database of all patients with gallstones. SETTING: Patients were admitted to the general surgery department of a military hospital. PATIENTS AND METHODS: We enrolled consecutive patients with symptomatic gallstones, biliary pancreatitis, obstructive jaundice, or cholangitis, who subsequently underwent biochemical testing and ultrasonography. A predictive model was developed from a scoring system using their imaging and laboratory data. Endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography were used for confirmatory diagnoses. The predictive efficacy of the scoring system was validated using a retrospective cohort of 272 patients. MAIN OUTCOME MEASURES: Predictive accuracy of the scoring system. RESULTS: We enrolled 155 patients in the development group. The common bile duct diameter, alkaline phosphatase of >=200 IU, elevated bilirubin levels, alanine transaminase of >=220 IU, and male age of >=50 years were significantly associated with choledocholithiasis and were included in the scoring system. Ninety-six patients (35%) had scores of >=8 (high risk), 86 patients (32%) had scores of 4-7 (intermediate risk), and 27 patients (10%) had scores of 1-3 (low risk). In the validation cohort, the positive predictive value for a score of >=8 was 91.7%, and the scoring system had an area under the curve of 0.896. CONCLUSION: Scores of >=8 were strongly correlated with choledocholithiasis in the developmental and validation groups, which indicates that our scoring system may be useful for predicting the need for therapeutic ERCP. However, prospective validation in a large multicenter cohort is needed to fully understand the benefits of the system. LIMITATIONS: The retrospective validation cohort might have introduced selection and observational biases. The study may have been underpowered because of the sample size of the developmental cohort. The delay between admission and the time of ERCP theoretically may have increased the number of negative ERCP results, but our false negative rate for ERCP was consistent with the previously reported rates.

Initial cholecystectomy vs sequential common duct endoscopic assessment and subsequent cholecystectomy for suspected gallstone migration: a randomized clinical trial.

IMPORTANCE: The optimal management of treatment for patients at intermediate risk of a common duct stone (including increased liver function tests but bilirubin <4 mg/dL and no cholangitis) is a matter of debate. Many stones migrate spontaneously into the duodenum, making preoperative common duct investigations unnecessary. OBJECTIVE: To compare strategies of cholecystectomy first vs a sequential endoscopic common duct assessment and cholecystectomy for the management of patients with an intermediate risk of a common duct stone. The main objective was to reduce the length of stay and the secondary objectives were to reduce the number of common duct investigations, morbidity, and costs. DESIGN, SETTING, AND PARTICIPANTS: Interventional, randomized clinical trial with 2 parallel groups performed between June 2011 and February 2013, with a patient follow-up of 6 months. The trial comprised a random sample of 100 adult patients admitted to Geneva University Hospital, Geneva, Switzerland, for acute gallstone-related conditions with an intermediate risk of a common duct stone. Fifty patients were randomized to each group. INTERVENTIONS: Cholecystectomy first with intraoperative cholangiogram for the study group and endoscopic common duct assessment and clearance followed by cholecystectomy for the control group. MAIN OUTCOMES AND MEASURES: Length of initial hospital stay (primary end point), number of common duct investigations and morbidity and mortality within 6 months after initial admission, and quality of life at 1 and 6 months after discharge (EQ-5D-5L [EuroQol Group, 5-level] questionnaire). RESULTS: Patients who underwent cholecystectomy as a first step had a significantly shorter length of hospital stay (median, 5 days [interquartile range {IQR}, 1-8] vs median, 8 days [IQR, 6-12]; P < .001), with fewer common duct investigations (25 vs 71; P < .001), no significant difference in morbidity or quality of life. CONCLUSIONS AND RELEVANCE: Among patients at intermediate risk of a common duct stone, initial cholecystectomy compared with sequential common duct endoscopy assessment and subsequent surgery resulted in a shorter length of stay without increased morbidity. If these findings are confirmed, initial cholecystectomy with intraoperative cholangiogram may be a preferred approach. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01492790.

Does on-site adequacy assessment by cytotechnologists improve results of EUS guided FNA of solid pancreaticobiliary lesions?

CONTEXT: Rapid onsite adequacy assessment is stated to improve the diagnostic performance of EUS-FNA. OBJECTIVES: The aim of this study was to establish if the introduction of adequacy assessment performed by a biomedical scientist (cytotechnologist) to an established EUS service improved the diagnostic accuracy of EUS guided FNA of solid pancreaticobiliary lesions. DESIGN AND PATIENTS: This retrospective study includes all patients with solid pancreaticobiliary lesions who underwent EUS-FNA from April 2009 to September 2010. An in room cytotechnologist was present for 2 out of the 4 weekly EUS lists and therefore there were two groups identified: Group 1, cytotechnologist absent; and Group 2, cytotechnologist present. RESULTS: There were 82 patients in Group 1 and 97 patients in Group 2. There was no statistically significant difference in the number of passes (4.1 vs. 4.3), the inadequate aspirate rate (7.3% vs. 5.1%) or the mean size of the lesions (34.7 vs. 32.6 mm) between the groups. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value in Group 1 were 89%, 88%, 100%, 100% and 50% respectively. The results in Group 2 were 91%, 90%, 100%, 100% and 69% respectively. There was no statistically significant difference between the two groups. CONCLUSIONS: In this study the adequacy assessment performed by a cytotechnologist did not improve the diagnostic accuracy of EUS-FNA. In an established EUS-FNA service with low inadequate aspirate rates, onsite adequacy assessment may not improve results of the test.

Multimedia article. Sphincterotome stricturoplasty for long ampullary stenoses and benign biliary strictures (with video).

BACKGROUND: Long ampullary stenoses and fibrotic distal biliary strictures are not infrequently encountered during endoscopic retrograde cholangiopancreatography (ERCP). Instead of balloon dilation and stenting, we propose that these strictures can be managed with sphincterotome stricturoplasty (SS) during the initial ERCP. OBJECTIVE: To report our clinical experience with SS for benign distal biliary strictures. DESIGN: Review on prospectively collected data. PATIENTS: All (consecutive) patients who underwent ERCP and SS performed by the authors in a 12-month period. Long ampullary stenosis and/or distal biliary stricture is defined as significant narrowing of CBD from the level of duodenal wall into the common bile duct (CBD) after initial sphincterotomy. The upstream CBD is dilated. Despite adequate ES, contrast drainage is poor due to the downstream stricture. SS was performed using the same sphincterotome in slightly bowed position under endoscopic and fluoroscopic guidance. The cutting wire was placed parallel to the superior border within the stricture and incising the stenosis. In cases of relatively long strictures, during initial SS the majority of the cutting wire was inside the biliary opening. This differs from ES, where about one-third to one-half of the length of cutting wire is outside the ampulla. MEASUREMENTS: Clinical data, hospital course, procedure-related complication rates, and outcomes were prospectively collected in a database. RESULTS: During the study period, 308 ERCPs were performed. Benign and short (≤15 mm in length) distal biliary strictures were observed in 25 patients. Mean ± SD stricture length was 7.4 ± 3.0 mm. The presumed etiologies for these strictures were choledocholithiasis (n = 22) and postsphincterotomy stenosis (n = 3). There was no perforation, post-ERCP pancreatitis, postsphincterotomy bleeding, or cholangitis. To date, none of these patients who had SS have needed follow-up ERCP. LIMITATIONS: Single-operator experience, limited follow-up period. CONCLUSIONS: Compared with balloon stricturoplasty ± biliary stenting, SS is a simple and cost-effective alternative option in managing long ampullary stenosis and/or distal fibrotic biliary stricture during the initial ERCP.

IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater's ampulla and the bile duct.

BACKGROUND AND AIM: Autoimmune pancreatitis is commonly associated with immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC). The discrimination between IgG4-SC and pancreatobiliary malignancies or primary sclerosing cholangitis (PSC) is now an important issue. The present study was carried out to examine the usefulness of endoscopic biopsies from Vater's ampulla and the bile duct to diagnose IgG4-SC. METHODS: The present study included 29 IgG4-SC patients (26 with both pancreatitis and cholangitis, and 3 with cholangitis only), 6 PSC patients, and 27 pancreatobiliary carcinoma patients. All patients underwent endoscopic biopsies from Vater's ampulla and the common bile duct. Biopsied specimens were histologically examined using immunostaining for IgG4. RESULTS: For the ampullary and bile duct biopsies, the IgG4-SC samples had a significantly greater number of IgG4-positive plasma cells than the PSC or pancreatobiliary carcinoma specimens. In addition, bile duct biopsies from five patients (17%) with IgG4-SC showed diffuse inflammatory cell infiltration with irregular fibrosis corresponding to the histological features of lymphoplasmacytic sclerosing pancreatocholangitis. Based on the threshold of 10 IgG4-positive plasma cells per high power field, the diagnostic rates of the ampullar and bile duct biopsies were both 52% (15/29 cases). Twenty-one patients (72%) had more than 10 IgG4-positive plasma cells in at least one biopsy. The bile duct biopsy was significantly valuable for IgG4-SC patients with swelling of the pancreatic head. CONCLUSION: The present study suggested that ampullar and bile duct biopsies are useful for diagnosing IgG4-SC.

Physical and histopathological assessment of the effects of metallic stents on radiation therapy.

To evaluate whether simultaneous metallic stent (MS) placement and radiotherapy are feasible, phantom and animal experiments were performed. The interface dose by external irradiation (EI) or intracavity irradiation (II) to 5 kinds of MS was measured using the charge-coupled device (CCD) camera with a thermoluminescent (TL) sheet, and backscatter and absorption were evaluated using composite method. Lineac 10 MV X-ray irradiated the MS in close contact with the TL sheet. II was performed using (192)Ir, and the irradiation dose transmitted through the MS was measured using the TL sheet. The ratio of the CCD value of the MS wire region to that of the MS non-wire region was defined as the dose perturbation factor (DPF). Furthermore, the effects of a combination of (60)Co gamma-ray EI and MS placement in the normal common bile duct were histopathologically evaluated in dogs. In the phantom experiments of EI, in backscatter by the MS, the DPF was 1.09 for CZ, and 1.03 for Pal, but no backscatter was detected in the remaining 3 MS. In absorption by the MS, the DPF was 0.92, 0.97, 0.97, and 0.98 for CZ, Wall, Pal, and Vel, respectively, but no absorption was detected in U. Flex. In those of II, the DPF of absorption was 0.91, 0.98, and 0.98 for CZ, U. Flex, and Wall, respectively, but no absorption was detected in Pal and Vel. The animal experiments showed infiltration of inflammatory cells and fibrosis in the case of both MS placement and EI. These changes were marked in EI treating after MS placement, but neither severe ulcer nor perforation was found. In conclusion, these results suggested that the effect of MS should be considered carefully when simultaneous MS placement and EI is performed clinically.

An economic analysis of hospital charges for choledocholithiasis by different treatment strategies.

The ideal management of presumed choledocholithiasis is controversial. We hypothesized that patients admitted with presumed choledocholithiasis would be better served financially to undergo laparoscopic cholecystectomy (LC) with possible intraoperative intervention versus preoperative endoscopic retrograde cholangiopancreatography followed by LC. A chart review was performed from September 1, 2000 to August 31, 2003. One hundred seventy-one consecutive patients identified with presumed choledocholithiasis were reviewed. Six patients were excluded because of missing charge data. Professional and technical fees from the total hospital charges were used for comparison. Three groups of patients were compared for charge analysis. Group 1 underwent LC with laparoscopic common bile duct exploration. Group 2 underwent LC with preoperative or postoperative endoscopic retrograde cholangiopancreatography. Group 3 was a control group of LC only. Student's t test was used for statistical analysis with a P value of <0.05 defined as statistically significant. P values reflect comparisons with Group 1. Group 1 charges were $13,026, Group 2 charges were $15,303, and Group 3 charges were $9,122. For suspected choledocholithiasis, LC with intraoperative intervention is the most economically advantageous approach.

Bile duct strictures after hepatobiliary surgery: assessment with MR cholangiography.

PURPOSE: To establish the accuracy of magnetic resonance (MR) cholangiography for diagnosis of postsurgical bile duct strictures. MATERIALS AND METHODS: Sixty-seven patients suspected of having bile duct strictures after liver transplantation (n = 54), cholecystectomy (n = 8), hepatic resection (n = 4), or pancreaticoduodenectomy (n = 1) underwent MR cholangiography. Thick-slab single-shot fast spin-echo (repetition time msec/echo time msec, 4,500/940) imaging was performed in the coronal through sagittal planes with rotation in 10 degrees increments, and contiguous thin-section images were obtained in the transverse and the optimal coronal oblique planes by using half-Fourier rapid acquisition with relaxation enhancement (1,900/96). Three blinded observers independently reviewed the MR images and recorded diagnostic features including presence of biliary stricture by using a five-point confidence scale. Receiver operating characteristic analysis was used to measure the accuracy of MR cholangiography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Final diagnosis was established at surgery (n = 29) and direct cholangiography (23 of 29) or at direct cholangiography, liver biopsy, and/or serial liver function tests (n = 38). RESULTS: Thirty-three of 67 patients had strictures confirmed with the reference standard. MR cholangiography enabled correct diagnosis and depicted the site of strictures in all cases. Findings of stricture at MR cholangiography were false-positive in five patients with moderate duct dilatation and caliber change at the level of the anastomosis. Mean accuracy, sensitivity, specificity, PPV, and NPV were 94%, 97%, 74%, 86%, and 96%, respectively. CONCLUSION: MR cholangiography is as sensitive as direct cholangiography for the assessment of bile duct strictures after hepatobiliary surgery but may lead to overestimation of the importance of duct dilatation and caliber change.

Intraductal ultrasonographic assessment of coagulation depth during endoscopic microwave coagulation therapy in a canine model.

In order to examine the feasibility of endoscopic microwave coagulation therapy (MCT) for the treatment of common bile duct cancer in humans, we investigated the safety and effectiveness of endoscopic MCT with the assistance of intraductal ultrasonography (IDUS). We performed MCT in the canine small intestine as a model because of its similarity in size to the obstructed human common bile duct. Multiple coagulation lesions were made in anesthetized dogs, with the endoscope inserted through a jejunostomy. Under condition "A", the tip of the MCT probe was kept in a fixed position in contact with the mucosa of the intestine, and coagulation was performed with an output of 30 or 50 W for 30 or 10 s, respectively. Under condition "B", the tip of the MCT probe was moved along the intestinal mucosa, and coagulation was performed with an output of 50, 40, or 30 W, all for 10 s. After coagulation, a thin-caliber ultrasonic probe was inserted endoscopically for observation of the effects of coagulation. Each coagulation under condition "A" resulted in degeneration of all layers of the intestine. Coagulation under condition "B" resulted in more localized degeneration, extending from the mucosal layer to the proper muscle layer. By comparison with histologic observations, the accuracy of IDUS in assessing depth of degeneration was 87.5%. Endoscopic microwave coagulation was considered safe and effective, and IDUS was able to accurately assess the effects of microwave coagulation.

Laparoscopic common bile duct exploration: evolution of a new technique.

Laparoscopic exploration of the common bile duct (CBD) with a choledochoscope or a stone basket during laparoscopic cholecystectomy was attempted in 60 patients and was successful in 56. The cystic duct was used for entry to the CBD in 46 patients and in 14 a choledochotomy was performed. Of 51 patients with confirmed common duct stones, 38 had complete laparoscopic clearance (75 per cent). In 13 patients the duct was not cleared or was only partially cleared, of whom four went on to have clearance by postoperative percutaneous choledochoscopy down a cystic duct or T-tube track. Two patients with cystic duct tubes passed their remaining stones spontaneously. One patient had open exploration and six required endoscopic retrograde cholangiopancreatography. Of nine patients without stones, choledochoscopy was impossible in three patients whose cholangiogram was later considered to be normal. In five patients stones were excluded by choledochoscopy and in one patient laparoscopic choledochoscopy was undertaken to better define abnormal biliary anatomy; this helped to avoid major bile duct injury. Choledochoscopy was easier with the smaller 3.6-mm ureteroscope but stone removal was more difficult when the basket was too small for the stones, the cystic duct too small relative to stone size or the number of stones was too great. Successful stone clearance was proportional to the level of effort expended, and was limited by operating time and equipment.

Choledochoscopy. A cost-minimization analysis.

Although choledochoscopy for the prevention of retained bile duct stones has been postulated as cost effective, no economic evaluation exists to substantiate this claim. We performed a cost-minimization analysis on 287 patients who underwent choledochoscopy during operations for biliary tract calculi between 1981 and 1987 to assess the economic impact of choledochoscopy versus noncholedochoscopic alternatives in obtaining a stone-free duct. Common duct exploration was positive for calculi in 75% of patients. Choledochoscopy-detected residual stones after duct exploration in 10% of patients. Residual stones were more frequent after positive (12.5%) than negative (2.7%) duct explorations. retained stones occurred in 4.5% of patients after operation. Sensitivity, specificity, and negative predictive values of choledochoscopy were 67%, 100%, and 95%, respectively. Cost-minimization analysis showed that total cost of either selective ($75,250) or routine ($110,450) choledochoscopy significantly exceeded the total cost of obtaining a stone-free duct for patients with retained stones via either extraction through a T-tube tract ($17,545) or by endoscopic papillotomy ($45,675). Because choledochoscopy was not economically competitive with noncholedochoscopic, nonoperative alternatives, reduction of choledochoscopy fees was implemented to economically justify continued use of choledochoscopy. We conclude that choledochoscopy is clinically efficacious in obtaining a stone-free duct, but endorsement of either routine or selective choledochoscopy by cost-minimization analysis requires careful assessment of fee structure to make choledochoscopy competitive economically.

A quantitative assessment of the structural changes the rat's liver following obstruction of the common bile duct.

A study has been made of sequential changes in the rat's liver from 1 to 40 days after obstruction of the common bile duct. The qualitative changes have been described and illustrated. The volume proportions of hepatocytes, bile duct epithelium and biliary stroma have been quantified by histological analysis using a point counting technique. The proliferation of hepatocytes and bile duct cells have been measured by labelling with tritiated thymidine. The absolute quantity of hepatocytes in each liver has been estimated and expressed as a percentage of body weight. Over 40 days there is a relative fall in the volume proportion of hepatocytes and an increase in bile duct cells and biliary stroma. These changes in volume proportions are related directly to the period of jaundice. Biliary stroma increases in support of new bile duct tissue and there is no excessive fibrosis. Hepatocytes proliferate at a greater rate than normal after obstruction of the common bile duct and the degree of proliferation reaches a maximum of 24 times that of normal 4 days after obstruction. Similarly, the proliferation of bile duct epithelium is increased in obstructive jaundice but in this instance it reaches a maximum of 50 times that of normal 24 h after ligation of the common bile duct. The absolute quantity of hepatocytes in the liver probably falls during the period of jaundice. However, the fall is less than anticipated from the volume proportion of hepatocytes because of the overall increase in liver size.