Investigation of the usefulness of a bile duct biopsy and bile cytology using a hyperspectral camera and machine learning.

To improve the efficiency of pathological diagnoses, the development of automatic pathological diagnostic systems using artificial intelligence (AI) is progressing; however, problems include the low interpretability of AI technology and the need for large amounts of data. We herein report the usefulness of a general-purpose method that combines a hyperspectral camera with machine learning. As a result of analyzing bile duct biopsy and bile cytology specimens, which are especially difficult to determine as benign or malignant, using multiple machine learning models, both were able to identify benign or malignant cells with an accuracy rate of more than 80% (93.3% for bile duct biopsy specimens and 83.2% for bile cytology specimens). This method has the potential to contribute to the diagnosis and treatment of bile duct cancer and is expected to be widely applied and utilized in general pathological diagnoses.

Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

Suprapapillary placement of plastic versus metal stents for malignant biliary hilar obstructions: a multicenter, randomized trial.

BACKGROUND AND AIMS: The efficacy of the suprapapillary placement of inside plastic stents (iPSs) for unresectable malignant hilar biliary obstructions (MHOs) is unknown compared with that of uncovered inside metal stents (iMSs). This randomized controlled trial was designed to evaluate the outcomes of endoscopic placement of these stents for unresectable MHOs. METHODS: This open-label, randomized study was conducted at 12 Japanese institutions. The enrolled patients with unresectable MHOs were allocated to iPS and iMS groups. The primary outcome was defined as the time to recurrent biliary obstruction in patients for whom the intervention was both technically and clinically successful. RESULTS: Among 87 enrollments, 38 patients in the iPS group and 46 patients in the iMS group were analyzed. Technical success rates were 100% (38 of 38) and 96.6% (44 of 46), respectively (P = 1.00). After transferring 1 unsuccessful iMS-group patient to the iPS group (since iPSs were deployed), the clinical success rates were 90.0% (35 of 39) for the iPS group and 88.9% (40 of 45) for the iMS group from a per-protocol analysis (P = 1.00). Among the patients with clinical success, the median times to recurrent biliary obstruction were 250 (95% confidence interval, 85-415) and 361 (95% confidence interval, 107-615) days (log-rank test, P = .34). No differences were detected in rates of adverse events. CONCLUSIONS: This Phase II randomized trial did not show any statistically significant difference in stent patency between suprapapillary plastic versus metal stents. Considering the potential advantages of plastic stents for malignant hilar obstruction, these findings suggest that suprapapillary plastic stents could be a viable alternative to metal stents for this condition.

Clinical outcomes and predictors of technical failure of endoscopic transpapillary gallbladder drainage in acute cholecystitis.

BACKGROUND AND AIMS: Endoscopic transpapillary gallbladder drainage (ETGBD) has been performed as an alternative therapy against cholecystectomy in patients with acute cholecystitis. To date, few studies have reported the safety, efficacy, and factors affecting ETGBD. We evaluated the clinical outcomes and predictors of technical failure of ETGBD. METHODS: Patients with acute cholecystitis who underwent ETGBD were retrospectively reviewed, and consecutive patients were included in the study. The technical success rate, clinical success rate, adverse events, and the predictors associated with the technical failure of ETGBD were investigated. RESULTS: A total of 242 patients were enrolled in the study. The technical success rate of ETGBD and clinical success rate of technically successful ETGBD cases were 87% and 93%, respectively. We experienced cystic duct injury in 24 patients as an ETGBD-related adverse event, and pancreatitis in 12 patients as an endoscopic retrograde cholangiopancreatography-related adverse event. Multivariate analysis indicated that cystic duct injury was the independent predictor associated with the technical failure of ETGBD (odds ratio, 11; 95% confidence interval, 3.9-29; p < 0.001). CONCLUSIONS: ETGBD was a safe and effective treatment method for acute cholecystitis with acceptable adverse events. There was no predictor based on the information from patient characteristics; however, cystic duct injury was associated with the technical failure of ETGBD.

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in Japan.

BACKGROUND AND AIMS: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted ERCP has been reported as useful in patients with surgically altered anatomy, most studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy. METHODS: This multicenter, retrospective study was conducted at 8 tertiary referral care centers in Japan. The data of patients who underwent ERCP-related procedures using short SBE between September 2011 and August 2019 at each facility were analyzed. RESULTS: Overall, 1318 patients were included in this analysis. The enteroscopy (reaching the target site), cannulation, and total procedural success rates were 87.9% (95% confidence interval [CI], 86.1%-89.6%), 87.0% (95% CI, 84.9%-88.8%), and 74.9% (95% CI, 72.5%-77.2%), respectively. Adverse events occurred in 7.7% of patients (95% CI, 6.4%-9.3%). Multiple logistic regression analysis indicated that age (≥75 years), Roux-en-Y reconstruction, pancreatic indication, and malignancy were factors affecting the total procedural failure. CONCLUSIONS: This large-scale study proved that short SBE-assisted ERCP in patients with surgically altered anatomy was effective. Moreover, it clarified factors affecting procedure results. Proficiency with alternative treatment techniques is required in difficult cases. (Clinical trial registration number: UMIN00004045.).

Long-term outcomes of endoscopic transpapillary gallbladder drainage using a novel spiral plastic stent in acute calculus cholecystitis.

BACKGROUND: Endoscopic transpapillary gallbladder stenting (EGBS) is considered for patients with contraindications to early surgery for acute calculus cholecystitis. However, evidence regarding the long-term outcomes of EGBS is insufficient to date. The aim of the study was to evaluate the feasibility of EGBS as a bridge to or alternative to surgery when there are contraindications. METHODS: We reviewed the cases of patients who underwent EGBS using a novel spiral-shaped plastic stent for acute calculus cholecystitis between January 2011 and December 2019. We retrospectively evaluated the long-term outcomes of EGBS using a novel spiral-shaped plastic stent. RESULTS: Forty-nine patients were included. The clinical success rate of EGBS was 97%. After EGBS, 25 patients (surgery group) underwent elective cholecystectomy and 24 patients did not (follow-up group). In the surgery group, the median period from EGBS to surgery was 93 days. There was a single late adverse event with cholecystitis recurrence. In the follow-up group, the median follow-up period was 236 days. Late adverse events were observed in eight patients, including recurrence of cholecystitis (four patients), duodenal penetration by the distal stent end (two patients), and distal stent migration (two patient). In the follow-up group, the time to recurrence of biliary obstruction was 527 days. CONCLUSIONS: EGBS with a novel spiral-shaped plastic stent is safe and effective for long-term acute calculus cholecystitis. There is a possibility of EGBS to be a bridge to surgery and a surgical alternative for acute calculus cholecystitis in patients with contraindications to early cholecystectomy.

Incidence and management of cystic duct perforation during endoscopic transpapillary gallbladder drainage for acute cholecystitis.

BACKGROUND AND AIM: Evidence regarding the incidence and clinical outcome of cystic duct perforation (CDP) during endoscopic transpapillary gallbladder drainage (ETGBD) is inadequate. The present study aimed to evaluate the incidence and management of CDP during ETGBD. METHODS: Between March 2011 and December 2019, 249 patients underwent initial ETGBD for acute cholecystitis. The incidence of CDP was retrospectively examined and the outcomes between the CDP and non-CDP groups were compared. RESULTS: CDP during ETGBD occurred in 23 (9.2%) of 249 patients (caused by guidewire in 15 and cannula in 8). ETGBD was successful in 10 patients following CDP. In 13 patients who failed ETGBD, 11 underwent bile duct drainage during the same session; nine patients underwent gallbladder decompression by other methods, such as percutaneous drainage. Clinical resolution for acute cholecystitis was achieved in 20 patients, and no bile peritonitis was noted. ETGBD technical success rates (45.3% vs. 91.2%, p < 0.001), ETGBD procedure times (66.5 vs. 54.8 min, p = 0.041), and hospitalization periods (24.5 vs. 18.7 days, p = 0.028) were significantly inferior in the CDP group (n = 23) compared with the non-CDP group (n = 216). There were no differences in clinical success and adverse events other than CDP between both groups. CONCLUSIONS: Cystic duct perforation reduced the ETGBD technical success rate. However, even in patients with cystic duct perforation, an improvement of acute cholecystitis was achieved by subsequent successful ETGBD or additional procedures, such as percutaneous drainage.

Uncovered versus covered metallic stents for the management of unresectable malignant distal biliary obstruction: a randomized multicenter trial.

OBJECTIVE: The treatment result of the uncovered metallic stent (uncovered MS) and covered metallic stent (covered MS) for unresectable malignant distal biliary obstruction is controversial. This time, we conducted this study to compare the efficacies and complication rates of uncovered MS and covered MS in unresectable malignant distal biliary obstructions at a prospective randomized multicenter trial. MATERIALS AND METHODS: From April 2014 to September 2018, patients with unresectable malignant distal biliary obstruction were randomly assigned to 2 groups: the uncovered MS group and the covered MS group. RESULTS: 92 treatment results patients were discussed. 48 patients were assigned to the uncovered MS group and 44 cases were assigned to the covered MS group. Both groups showed a drainage effect. No significant difference was found in the drainage effect between the 2 groups. The number of stent occlusion was significantly greater (p = .0467) in uncovered MS (43.8%) comparing with those in covered MS (22.7%). As the cause of stent occlusion, tumor ingrowth was significantly greater (p < .001) in the uncovered MS group (35.4%) than in the covered MS group (2.3%). The median stent patency period was significantly longer (p = .0112) in the covered MS group (455 days) than that of the uncovered MS group (301 days). A significant difference in the median survival period was not found between the 2 groups. CONCLUSIONS: Covered MS showed the possibility of extending the stent patency period by suppressing tumor ingrowth more than uncovered MS does. The UMIN Clinical Trial Registry number is UMIN000015093.

Complete Lymphadenectomy Around the Entire Superior Mesenteric Artery Improves Survival in Artery-First Approach Pancreatoduodenectomy for T3 Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Artery-first approach pancreatoduodenectomy (AFA-PD) is an important technique for treating pancreatic ductal adenocarcinoma (PDAC). However, it remains unknown whether performing complete lymphadenectomy around the entire superior mesenteric artery (SMA) is associated with better outcomes. In this retrospective study, we aimed to investigate whether this approach improved overall and recurrence-free survival in patients with PDAC. METHODS: We identified 88 patients with T3 PDAC who underwent PD at St. Marianna University School of Medicine, Kawasaki, Japan, between April 2005 and October 2017. Two groups were defined: an "AFA-PD group" (n = 45) who had undergone AFA-PD in addition to complete lymphadenectomy around the entire SMA, and a "conventional PD group" (n = 43) in whom complete lymphadenectomy had not been performed (conventional group). Univariate and multivariate survival analyses were performed to identify risk factors for overall and disease-free survival. RESULTS: The AFA-PD group had a longer median survival time (40.3 vs. 22.6 months; p = 0.0140) and a higher 5-year survival rate (40.3% vs. 5.9%, p = 0.005) than the conventional PD group. Multivariate analysis showed that AFA-PD with complete lymphadenectomy around the entire SMA was an independent factor for improved overall survival (p = 0.022). Recurrences around the SMA were significantly less frequent in the AFA-PD group than in the conventional group (22.2% vs. 44.2%, p = 0.041). CONCLUSIONS: AFA-PD with complete lymphadenectomy around the entire SMA can prevent recurrences around the SMA and may prolong overall survival in patients with PDAC.

Pancreatic duct guidewire placement for biliary cannulation as a risk factor for stone residue after endoscopic transpapillary stone removal.

BACKGROUND: Recent improvements in stone extraction implements and apparatus have lessened the complexity of the endoscopic bile duct stone treatment. However, despite confirmation of complete removal, cases of residual stones have been reported, which can result in recurrent biliary symptoms, cholangitis, and pancreatitis and considerably increase cost given the need for repeat imaging and/or procedures. To date, risk factors for residual bile duct stones following endoscopic retrograde cholangiopancreatography (ERCP) extraction have not been thoroughly evaluated. This study retrospectively investigated the incidence and risk factors of residual bile duct stones following extraction via ERCP. METHODS: We retrospectively reviewed all ERCP cases that underwent endoscopic bile duct stone extraction between April 2014 and March 2019. A total of 505 patients were enrolled and evaluated for the incidence and risk factors of residual bile duct stones after ERCP. RESULTS: The rate of residual stones was 4.8% (24/505). Residual stones were detected by computed tomography (12/24) or magnetic resonance cholangiopancreatography (12/24). In univariate analyses, a large number of stones (P = 0.01), long procedure time (P = 0.005), and performance of the pancreatic duct guidewire placement method (P-GW) for selective bile duct cannulation (P = 0.01) were the factors involved in residual stones. In multiple logistic regression analysis, performing P-GW was retained as the only independent factor of residual stones (adjusted odds ratio, 3.44; 95% CI, 1.19-9.88; P = 0.02). CONCLUSIONS: When removing bile duct stones with a pancreatic guidewire in place, paying attention to residual stones is necessary.

Diagnostic Ability of Endoscopic Bile Cytology Using a Newly Designed Biliary Scraper for Biliary Strictures.

BACKGROUND: A new device with metallic wires for scrape cytology was developed. AIMS: To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures. METHODS: A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively. RESULTS: The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group. CONCLUSION: Scrape bile cytology for biliary strictures may be superior to conventional cytology.

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

A case of Ménétrier's disease seemingly caused by hilar cholangiocarcinoma.

A 54-year-old man presented to our department with abdominal discomfort and anorexia and was diagnosed as having Ménétrier's disease (MD) with hilar cholangiocarcinoma. Based on his clinical examination, there was no evidence of Helicobacter pylori or cytomegalovirus (CMV) infection. Although we administered proton pump inhibitor and high-calorie enteral nutrition, hypoproteinemia did not improve, and the refractory protein-losing enteropathy persisted. However, interestingly, MD improved immediately after resection of the hilar cholangiocarcinoma. Generally, the etiology of MD is unknown, but H. pylori and CMV infections have been implicated. To our knowledge, there has been no previous report indicating that a malignant tumor could be involved in the etiology of MD. Thus, we report an extremely rare case of MD which is seemingly caused by malignancy.