TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions.

BACKGROUND: Differences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. METHODS: Forty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. RESULTS: 1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). CONCLUSIONS: Because characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.

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.

Early and long-term clinical outcomes of endoscopic interventions for benign pancreatic duct stricture/obstruction-the possibility of additional clinical effects of endoscopic ultrasonography-guided pancreatic drainage.

OBJECTIVES: For benign pancreatic duct strictures/obstructions (BPDS/O), endoscopic ultrasonography-guided pancreatic drainage (EUS-PD) is performed when endoscopic transpapillary pancreatic drainage (ETPD) fails. We clarified the clinical outcomes for patients with BPDS/O who underwent endoscopic interventions through the era where EUS-PD was available. METHODS: Forty-five patients with BPDS/O who underwent ETPD/EUS-PD were included. We retrospectively investigated overall technical and clinical success rates for endoscopic interventions, adverse events, and clinical outcomes after successful endoscopic interventions. RESULTS: The technical success rates for ETPD and EUS-PD were 77% (35/45) and 80% (8/10), respectively, and the overall technical success rate using two drainage procedures was 91% (41/45). Among the 41 patients who underwent successful endoscopic procedures, the clinical success rates were 97% for the symptomatic patients (35/36). The rates of procedure-related pancreatitis after ETPD and EUS-PD were 13% and 30%, respectively. After successful endoscopic interventions, the cumulative 3-year rate of developing recurrent symptoms/pancreatitis was calculated to be 27%, and only two patients finally needed surgery. Continuous smoking after endoscopic interventions was shown to be a risk factor for developing recurrent symptoms/pancreatitis. CONCLUSIONS: By adding EUS-PD to ETPD, the technical success rate for endoscopic interventions for BPDS/O was more than 90%, and the clinical success rate was nearly 100%. Due to the low rate of surgery after endoscopic interventions, including EUS-PD, for patients with BPDS/O, EUS-PD may contribute to their good clinical courses as a salvage treatment for refractory BPDS/O.

Accurate endoscopic identification of the afferent limb at the Y anastomosis using the fold disruption sign after gastric resection with Roux-en-Y reconstruction.

In patients with Roux-en-Y (RY) reconstruction for gastric resection, the newly defined "fold disruption" (FD) sign can be useful to distinguish the afferent limb from the efferent limb at the Y anastomosis when balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is performed. The FD sign was defined as endoscopic findings of the internal folds disrupted toward the afferent limb and continued toward the efferent limb at the Y anastomosis. In this prospective observational study, the accuracy of the FD sign was evaluated for those who underwent BE-ERCP after gastric resection with RY reconstruction. Of 28 patients for whom the accuracy could be evaluated among 30 enrolled patients, the afferent limb was identified using the FD sign with 100% accuracy. For the other two patients, the scope could not reach the target lumen due to severe intestinal adhesion in one and reached the target lumen without recognition of the Y anastomosis in the other. There was no patient for whom the FD sign could not be judged for any reason, such as a blurred anastomosis line, unclear folds, sticky discharge and blood coating the surface, when the Y anastomosis was recognized. The FD sign was a highly accurate tool for distinguishing the afferent limb from the efferent limb in patients after gastric resection with RY reconstruction. This study was registered in UMIN (issued ID, UMIN000038326).

[Endoscopic mucosal resection of localized plasmablastic lymphoma with early rectal cancer:a rare case report and literature review].

A 79-year-old male with a positive fecal occult blood test result underwent total colonoscopy, which revealed a 15-mm-semipedunculated polyp in the rectum. The polyp appeared to be an adenoma using narrow-band imaging observation in magnifying endoscopy, although a 3mm reddish segment with a different surface structure was identified adjacent to the base of the polyp. En-bloc endoscopic mucosal resection (EMR) was performed. From the pathological evaluation using the specimen, the polyp was mainly a tubular adenoma with an adenocarcinoma component within the lesion. Additionally, a tiny plasmablastic lymphoma (PBL) component, which was positive for CD45, CD79a, CD30, CD38, MUM1, and lambda light chain;negative for CD3, CD5, CD20, CD56, CD138, cyclin D1, PAX5, IgG, IgA, IgM, IgE, HHV8, and kappa light chain, coexisted near the stalk. The proliferation index using Ki-67 immunohistochemistry was approximately 80%. Furthermore, Epstein-Barr virus-encoded RNAs were identified in in-situ hybridization, although the human immunodeficiency virus was not detected. The patient received contrast-enhanced computed tomography (CT) and positron emission tomography-CT (PET-CT) follow-ups after treatment without recurrence for two years. This is the first report of gastrointestinal PBL that could be treated using EMR.

Predictive Factors for Short-Term Survival after Non-Curative Endoscopic Submucosal Dissection for Early Gastric Cancer.

BACKGROUND/AIMS: For early gastric cancer (EGC) treated using endoscopic submucosal dissection (ESD) with poor curability defined by the Japanese Guidelines (non-curative EGC, N-EGC), additional gastrectomy has been recommended. However, N-EGC patients without additional gastrectomy often die of other diseases within a relatively short interval after ESD. It has been unclear whether additional gastrectomy is beneficial or not for such patients. The aim of this study was to clarify predictors for short-term survival of N-EGC patients without additional gastrectomy after ESD. METHODS: One hundred six N-EGC patients without additional gastrectomy were included in this study. Factors related to short-term survival, defined as death within 3 years after ESD, were evaluated using uni- and multivariate analyses by comparing patients with and without short-term survival (Groups S and C, respectively). RESULTS: During the mean follow-up period of 89 months, 39 patients died (14 patients died within 3 years, being Group S). The cause of death was gastric cancer for only 1 patient in the Group C. The 3- and 5-year overall survival rates were 86.8 and 81.8%, respectively, and the 3- and 5-years disease-specific survival rates were 100 and 98.9%, respectively. Univariate analyses showed that short-term survival was statistically associated with elevated morphology, high-risk status for lymph node metastases as defined by the eCura system, severe comorbidity (Charlson Comorbidity Index [CCI] ≥3), low level of activity in daily living (being unable to go out by oneself), habitation (a nursing home), and several poor nutritional prognostic indices (neutrophil to lymphocyte ratio ≥2.5, geriatric nutritional risk index <92, C-reactive protein ≥1.0). In the multivariate analysis, a high CCI (≥3) was the independent predictor for short-term survival after ESD (odds ratio, 8.1; 95% confidence interval, 1.53-43.0; p = 0.014). CONCLUSIONS: Severe comorbidity indicated by a high CCI score (≥3) was the independent predictor for short-term survival for EGC patients without additional gastrectomy after non-curative ESD. Since the cause of death for most patients was not gastric cancer, observational follow-ups without additional gastrectomy might be a reasonable option for patients with a poor general status indicated by a CCI ≥3.

Cholangioscopy- versus fluoroscopy-guided transpapillary mapping biopsy for preoperative evaluation of extrahepatic cholangiocarcinoma: a prospective randomized crossover study.

BACKGROUND: To evaluate the lateral extent of extrahepatic cholangiocarcinoma, the value of cholangioscopy-guided mapping biopsy (CMB) compared with that of fluoroscopy-guided mapping biopsy (FMB) remains unknown. The aim of this study was to compare these two techniques. METHODS: In this prospective, randomized, crossover study, both CMB and FMB techniques were performed for all patients in a randomized order. Target sites for the mapping biopsy were determined based on resection lines of possible surgical procedures. At least two biopsy strokes were attempted at each target site. The primary outcome was the rate of site-based successful biopsies, which was defined as acquisition of epithelium-containing material appropriate for diagnosing benignancy/malignancy from each site, regardless of amount of materials obtained from the same site. RESULTS: Between September 2016 and October 2018, 28 patients (16 distal bile duct cancer and 12 perihilar bile duct cancer) were enrolled and divided into two groups of 14 patients: CMB first and FMB first. Although all 118 target sites could be approached using CMB, FMB forceps reached only 71% of them with significantly poor accessibility to the B2/3 confluence. Since several materials were too small and did not contain epithelium, the overall rates of site-based successful biopsies were 78% (92/118) using CMB and 64% (76/118) using FMB (P = 0.031). CONCLUSIONS: The rate of site-based successful biopsies using CMB was significantly higher than that using FMB when evaluated using specimens obtained from several biopsy strokes.

Value of repeated cytology for intraductal papillary mucinous neoplasms of the pancreas with high risk potential of malignancy: Is it a promising method for monitoring a malignant transformation?

OBJECTIVES: The efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs. METHODS: Forty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study. RESULTS: Thirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size. CONCLUSION: Repeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology.

Efficacy of EUS-guided celiac plexus neurolysis compared with medication alone for unresectable pancreatic cancer in the oxycodone/fentanyl era: a prospective randomized control study.

BACKGROUND AND AIMS: The efficacy of celiac plexus neurolysis (CPN) with EUS guidance (EUS-CPN) has not been confirmed in the era of developed opioids. The aim of this study was to evaluate the efficacy of EUS-CPN for patients with pancreatic cancer-associated pain to compare medication using oxycodone and/or fentanyl with and without EUS-CPN. METHODS: In this randomized control study involving patients who underwent EUS-CPN and those who did not, pain, quality of life (QOL), and opioid consumption were compared. Standard medicinal treatment using oxycodone and/or fentanyl was performed for both groups. The primary endpoint was defined as the pain evaluated by using a visual analog scale (VAS) rated from a 0 to 10, 4 weeks after the baseline. RESULTS: For 48 registered patients, the outcomes of 24 patients in the EUS-CPN group and 22 patients in the control group were analyzed. EUS-CPN was successfully performed and did not induce severe procedure-related adverse events for all patients in the EUS-CPN group. Although the average pain VAS scores for both groups significantly decreased in comparison with baseline, scores were not statistically different between the groups at week 4 (1.3 ± 1.3 for the EUS-CPN group vs 2.3 ± 2.3 for the control group, P = .10). There was no statistical difference or tendency in favor of EUS-CPN at evaluation points of weeks 1, 2, 8, and 12. Moreover, the average VAS scores for QOL and the average opioid consumption between the groups were not different at all evaluation points. CONCLUSIONS: EUS-CPN for patients with pancreatic cancer-associated pain did not appear to improve pain, QOL, or opioid consumption compared with those who did not undergo EUS-CPN and medicated with oxycodone/fentanyl. Although EUS-CPN can be an option, it was not found to have a large enough impact to be routinely performed for all patients with pain. (Clinical trial registration number: UMIN 000037172.).

[Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 diagnosed using an endoscopic submucosal dissection specimen].

A 15-mm whitish, depressed lesion was observed in the stomach of a 39-year-old using screening esophagogastroduodenoscopy. The lesion had grown to a size of 40mm and had a cobblestone-like appearance at an 11-year endoscopic follow-up. Using endoscopic submucosal dissection (ESD) as a diagnostic therapy, gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 without Helicobacter pylori infection was detected. Although the patient did not undergo additional treatments, he remained alive without for recurrence 5 years after ESD.

[Synchronous double primary cancers of a mixed adenoneuroendocrine carcinoma of the distal bile duct and a carcinoma in situ in the perihilar bile duct].

We report the rare case of a 69-year-old man who underwent resection of a mixed adenoneuroendocrine carcinoma (MANEC) of the distal bile duct and a carcinoma in situ in the perihilar bile duct. The patient was admitted to our hospital for obstructive jaundice. Imaging studies revealed a mass in the distal bile duct, and an abnormal epithelium was detected in the perihilar bile duct using peroral cholangioscopy. Bile cytology and transpapillary biopsy of the tumor revealed adenocarcinoma. We diagnosed this patient with distal cholangiocarcinoma with extensive intraepithelial progression toward the perihilar bile duct and performed a subtotal stomach-preserving pancreaticoduodenectomy and left hepatectomy. According to the histological examination of the resected specimens, we found a MANEC in the distal bile duct and a carcinoma in situ in the perihilar bile duct. Together, they were diagnosed as synchronous double primary cancers due to the lack of pathological transition between them.

Should we regard all main duct type intraductal papillary mucinous neoplasms of the pancreas (MD-IPMN) as an indication of surgery? -A retrospective study in 29 patients with MD-IPMN showing mural nodules.

PURPOSE: To elucidate predictive factors for malignant main duct type IPMN (MD-IPMN). METHODS: All 29 subjects had mural nodules (MNs) in the main pancreatic duct (MPD) on preoperative endoscopic ultrasonography and underwent surgery (19, malignant; 10, benign). Possible predictive factors for malignancy such as background, imaging, and histological factors including histological subtype (HS), were evaluated. RESULTS: Multivariate analysis revealed an MPD diameter of ≥12 mm (p = 0.042) and non-gastric type (p = 0.001) to be the statistically significant predictive factors for malignancy. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to detect malignancy by using "an MPD diameter of ≥12 mm and/or non-gastric type" were 95%, 70%, 86%, 88%, and 86%, respectively. In 7 subjects in whom HS was preoperatively evaluated using pancreatic specimens obtained before surgery, the agreement rate of the preoperative HS with definitive HS evaluated using resected specimens was 86%. CONCLUSIONS: For MD-IPMNs with MNs, "an MPD diameter of ≥12 mm and/or non-gastric type" are indicated for surgery. On the other hand, careful surveillance without immediate pancreatic surgery may be an option for MD-IPMNs showing both an MPD diameter of <12 mm and gastric type.

[Detection of small pancreatic cancer during surveillance of the main pancreatic duct stenosis].

An 83-year-old man with main pancreatic duct (MPD) stenosis in the pancreatic body had undergone surveillance with semiannual imaging studies for 3 years. During surveillance, magnetic resonance cholangiopancreatography revealed gradual enlargement of a small cyst near the MPD stenosis and contrast-enhanced computed tomography revealed locally progressive atrophic parenchyma in the pancreatic body. On endoscopic retrograde pancreatography, the MPD stenosis was more severe than it had been at diagnosis 3 years earlier. Endoscopic ultrasonography (EUS) showed a 10-mm hypoechoic mass adjacent to the MPD stenosis. The mass was pathologically diagnosed as an adenocarcinoma using EUS-guided fine needle aspiration, and distal pancreatectomy was performed. On histopathological examination, the resected specimen was found to be a moderately differentiated 9-mm invasive ductal carcinoma. Additionally, multiple high-grade pancreatic intraepithelial neoplasms (i.e., carcinoma in situ) were detected in the MPD and branch ducts near the invasive carcinoma.

Pancreatic juice cytology with immunohistochemistry to detect malignancy and histologic subtypes in patients with branch duct type intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND AND AIMS: The aim of this study was to elucidate the efficacy of pancreatic juice cytology with the cell-block method (CB-PJC) for the determination of surgery in patients with branch duct intraductal papillary mucinous neoplasm (BD-IPMN). METHODS: In 138 patients with BD-IPMN from whom pancreatic juice was collected under ERCP for CB-PJC, we retrospectively evaluated the following: (1) the rate of successfully evaluated CB-PJC; (2) the ability of CB-PJC to diagnose malignancy and to identify pathologic subtypes in resected BD-IPMNs; (3) the rate of development into invasive cancer and progression of BD-IPMNs in patients with BD-IPMNs diagnosed as benignancy by CB-PJC; and (4) post-ERCP adverse events. RESULTS: (1) The success rate of CB-PJC was 89.9%. (2) The sensitivity and specificity of CB-PJC for preoperative diagnosis of malignancy were 50% and 100%, respectively, with only hematoxylin and eosin staining, whereas they were 79% and 100%, respectively, by adding immunohistologic staining. The agreement rate of the preoperative subtypes by CB-PJC with the subtypes of resected specimens was 93%. (3) The onset of invasive cancer was not detected at all on imaging studies, whereas the progression of IPMN was detected in 14 patients. Multivariate analysis revealed the risk factor of progression to be non-gastric type. The cumulative 5-year progression rate in this group was 89%. (4) Post-ERCP pancreatitis developed in 13 patients (7.7%). CONCLUSIONS: The diagnostic efficacy of preoperative CB-PJC for malignant BD-IPMN was excellent. The results may suggest the feasibility of applying preoperative subtyping by CB-PJC for decisions as to whether surgery is indicated.