Older Age as a Worrisome Feature in Patients With Intraductal Papillary Mucinous Neoplasms: a Long-Term Surveillance Study.

INTRODUCTION: Aging has been implicated in the development of various cancer types. No study has specifically investigated age at the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) in relation to the long-term risk of pancreatic carcinogenesis. METHODS: Within a prospective cohort of 4,104 patients diagnosed with pancreatic cysts, we identified 3,142 IPMN patients and examined an association of age at IPMN diagnosis with the incidence of pancreatic carcinoma. Utilizing the multivariable competing-risks proportional hazards regression model, we estimated subdistribution hazard ratios (SHRs) and 95% confidence intervals (CIs) for pancreatic carcinoma incidence according to age at IPMN diagnosis. RESULTS: During 22,187 person-years of follow-up, we documented 130 patients diagnosed with pancreatic carcinoma (64 with IPMN-derived carcinoma and 66 with concomitant ductal adenocarcinoma). Older age at IPMN diagnosis was associated with a higher risk of pancreatic cancer incidence (Ptrend = 0.002). Compared to patients aged < 55 years, patients aged 55-64, 65-74, and ≥ 75 years had adjusted SHRs of 1.80 (95% CI, 0.75-4.32), 2.56 (95% CI, 1.10-5.98), and 3.31 (95% CI, 1.40-7.83), respectively. Patients aged ≥ 70 years had a numerically similar adjusted SHR compared to patients aged < 70 years with worrisome features defined by the international consensus guidelines (1.73 [95% CI, 1.01-2.97] and 1.66 [95% CI, 0.89-3.10], respectively). DISCUSSION: Older patients with IPMNs were at a higher risk of developing pancreatic carcinoma during surveillance. Surgically fit elderly patients may be good candidates for periodic surveillance aimed at a reduction of pancreatic cancer-related deaths.

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.

Body mass index and survival among patients with advanced biliary tract cancer: a single-institutional study with nationwide data-based validation.

BACKGROUND: Excess body weight may modulate the progression of various cancer types. The prognostic relevance of body mass index (BMI) has not been fully examined in patients with biliary tract cancer. METHODS: Using a single-institutional cohort of 360 patients receiving gemcitabine-based chemotherapy for advanced biliary tract cancer, we examined the association of BMI with overall survival (OS). Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for OS according to BMI. The findings were validated using a Japanese nationwide inpatient database including 8324 patients treated at 201 hospitals. RESULTS: In the clinical cohort, BMI was not associated with OS (Ptrend = 0.34). Compared to patients with BMI = 18.5-24.9 kg/m2, patients with BMI < 18.5 kg/m2 and ≥ 25.0 kg/m2 had adjusted HRs for OS of 1.06 (95% CI, 0.78-1.45) and 1.01 (95% CI, 0.74-1.39), respectively. There was no evidence on a non-linear relationship between BMI and OS (Pnonlinearity = 0.63). In the nationwide cohort, the null findings were validated (Ptrend = 0.18) with adjusted HRs of 1.07 (95% CI, 0.98-1.18) for BMI < 18.5 kg/m2 and 1.05 (95% CI, 0.96-1.14) for BMI ≥ 25.0 kg/m2 (vs. BMI = 18.5-24.9 kg/m2). In the clinical cohort, BMI was not associated with progression-free survival (Ptrend = 0.81). CONCLUSIONS: BMI was not associated with survival outcomes of patients with advanced biliary tract cancer. Further research is warranted incorporating more detailed body composition metrics to explore the prognostic role of adiposity in biliary tract cancer.

The Revised Kyoto Criteria and Risk of Malignancy Among Patients With Intraductal Papillary Mucinous Neoplasms.

BACKGROUND & AIMS: The revised Kyoto guidelines have a new catalog of high-risk stigmata and worrisome features for the risk stratification of intraductal papillary mucinous neoplasms (IPMNs). We aimed to validate the stratification system in terms of short- and long-term risks of pancreatic carcinoma. METHODS: We included 3336 patients diagnosed with IPMNs in 2000-2021 and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma diagnosis. We used the multivariable competing-risks proportional hazards regression model to calculate subdistribution hazard ratios for long-term incidence of pancreatic carcinoma with adjustment for potential confounders. RESULTS: In short-term analyses, pancreatic carcinomas were prevalent predominantly in IPMNs with high-risk stigmata (49% vs 1.3% and 0.05% in IPMNs with worrisome features and no risk factors, respectively). In long-term analyses of worrisome features, the main pancreatic duct diameter of 5-9.9 mm, acute pancreatitis, and IPMN growth rate of 2.5 mm/y were associated with a high incidence with multivariable subdistribution hazard ratios of 3.46 (95% confidence interval [CI], 2.04-5.89), 5.65 (95% CI, 1.86-17.2), and 3.83 (95% CI, 2.14-6.86), respectively. An increasing number of worrisome features at baseline was associated with a higher prevalence and incidence of pancreatic carcinoma (Ptrend < .001). Patients with 1, 2, and 3-4 worrisome features had multivariable subdistribution hazard ratios for pancreatic cancer incidence of 1.43 (95% CI, 0.93-2.19), 2.17 (95% CI, 1.17-4.05), and 10.1 (95% CI, 4.20-24.5), respectively (vs no positive feature). CONCLUSIONS: The revised Kyoto criteria stratify IPMN patients well in terms of the short- and long-term risks of pancreatic carcinoma diagnosis, potentially informing personalized patient management.

Controversies in endoscopic ultrasonography-guided management of walled-off necrosis.

Walled-off necrosis (WON) develops as local complications after acute necrotizing pancreatitis. Although less invasive interventions such as endoscopic ultrasonography (EUS)-guided drainage and endoscopic necrosectomy are selected over surgical interventions, delayed and step-up interventions are still preferred to avoid procedure-related adverse events. However, there is a controversy about the appropriate timing of drainage and subsequent necrosectomy. The advent of large-caliber lumen-apposing metal stents has also brought about potential advantages of proactive interventions, which still needs investigation in future trials. When step-up interventions of necrosectomy and additional drainage are necessary, a structured or protocoled approach for WON has been reported to improve safety and effectiveness of endoscopic and/or percutaneous treatment, but has not been standardized yet. Finally, long-term outcomes such as recurrence of WON, pancreatic endocrine, and exocrine function are increasingly investigated in association with disconnected pancreatic duct syndrome. In this review we discuss current evidence and controversy on EUS-guided management of WON.

Computed tomography-based prediction of pancreatitis following biliary metal stent placement with the convolutional neural network.

Background and study aims Pancreatitis is a potentially lethal adverse event of endoscopic transpapillary placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction (MBO). Deep learning-based image recognition has not been investigated in predicting pancreatitis in this setting. Patients and methods We included 70 patients who underwent endoscopic placement of a SEMS for nonresectable distal MBO. We constructed a convolutional neural network (CNN) model for pancreatitis prediction using a series of pre-procedure computed tomography images covering the whole pancreas (≥ 120,960 augmented images in total). We examined the additional effects of the CNN-based probabilities on the following machine learning models based on clinical parameters: logistic regression, support vector machine with a linear or RBF kernel, random forest classifier, and gradient boosting classifier. Model performance was assessed based on the area under the curve (AUC) in the receiver operating characteristic analysis, positive predictive value (PPV), accuracy, and specificity. Results The CNN model was associated with moderate levels of performance metrics: AUC, 0.67; PPV, 0.45; accuracy, 0.66; and specificity, 0.63. When added to the machine learning models, the CNN-based probabilities increased the performance metrics. The logistic regression model with the CNN-based probabilities had an AUC of 0.74, PPV of 0.85, accuracy of 0.83, and specificity of 0.96, compared with 0.72, 0.78, 0.77, and 0.96, respectively, without the probabilities. Conclusions The CNN-based model may increase predictability for pancreatitis following endoscopic placement of a biliary SEMS. Our findings support the potential of deep learning technology to improve prognostic models in pancreatobiliary therapeutic endoscopy.

Drainage for fluid collections post pancreatic surgery and acute pancreatitis: similar but different?

Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.

Feasibility of comprehensive genomic profiling using endoscopic ultrasound-guided tissue acquisition with a 22-gauge Franseen needle.

Aim: Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are often submitted for tissue-based CGP test. In this study, we evaluated the feasibility of EUS-TA using a 22-gauge Franseen needle for the CGP test. Methods: Consecutive patients with solid tumors who underwent EUS-TA using a 22-gauge Franseen needle, and whose tissue samples were pre-checked for suitability for CGP test, were included in this single-center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS-TA slides were evaluated for the tissue area and tumor area content, using the image software. Results: A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS-TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS-TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis. Conclusions: The present study demonstrated the feasibility of EUS-TA using a 22-gauge Franseen needle for CGP test.

Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography for hepatolithiasis in patients with hepaticojejunostomy.

BACKGROUND AND AIM: Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is an emerging procedure for pancreatobiliary diseases in patients with surgically altered anatomy. However, data on BE-ERCP for hepatolithiasis after hepaticojejunostomy (HJS) are still limited. METHODS: Stone removal success, adverse events and recurrence were retrospectively studied in consecutive patients who underwent BE-ERCP for hepatolithiasis after HJS between January 2011 and October 2022. Subgroup analysis was performed to compare clinical outcomes between patients who had undergone HJS over 10 years before (past HJS group) and within 10 years (recent HJS group). RESULTS: A total of 131 patients were included; 39% had undergone HJS for malignancy and 32% for congenital biliary dilation. Scope insertion and complete stone removal were successful in 89% and 73%, respectively. Early adverse events were observed in 9.9%. Four patients (3.1%) developed gastrointestinal perforation but could be managed conservatively. Hepatolithiasis recurrence rate was 17%, 20% and 31% in 1-year, 3-year, and 5-year after complete stone removal. The past HJS group was the only risk factor for failed stone removal (odds ratio 10.4, 95% confidence interval 2.99-36.5) in the multivariable analysis. Failed scope insertion (20%) and failed guidewire or device insertion to the bile duct (22%) were two major reasons for failed stone removal in the past HJS group. CONCLUSIONS: BE-ERCP for hepatolithiasis was effective and safe in cases with HJS but the complete stone removal rate was low in the past HJS group. Recurrent hepatolithiasis was common and careful follow up study is needed even after complete stone removal.

Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer.

OBJECTIVE: To examine whether long-term surveillance of intraductal papillary mucinous neoplasms (IPMNs) leads to early diagnosis and better clinical outcomes of pancreatic ductal adenocarcinomas (PDACs) developing concomitantly with IPMNs. SUMMARY BACKGROUND DATA: Long-term image-based surveillance is recommended for patients with low-risk IPMNs. However, it is unknown whether the surveillance can improve surgical and survival outcomes of patients with concomitant PDACs. METHODS: Using a prospective single-institutional cohort of 4,620 patients with pancreatic cysts including 3,638 IPMN patients, we identified 63 patients who developed concomitant PDAC during long-term surveillance. We compared overall survival (OS) of 46 cases with concomitant PDAC to that of 460 matched cases diagnosed with non-IPMN-associated PDAC at the same institution. Multivariable hazard ratios and 95% confidence intervals (CIs) for overall mortality were computed using the Cox regression model with adjustment for potential confounders. RESULTS: Concomitant PDACs were identified at an earlier cancer stage compared to non-IPMN-associated PDACs with 67% and 38% cases identified at stage 2 or earlier, respectively (P<0.001) and 57% and 21% cases with R0 resection, respectively (P<0.001). Compared to non-IPMN-associated PDACs, concomitant PDACs were associated with longer OS (P=0.034) with a multivariable hazard ratio of 0.61 (95% CI, 0.39-0.96). The 5-year survival rate of patients with concomitant PDAC was higher compared to patients with non-IPMN-associated PDAC (34% vs. 18%, respectively; P=0.018). CONCLUSIONS: The surveillance for patients with IPMNs was associated with early identification of concomitant PDACs and longer survival of patients diagnosed with this malignancy.

Skeletal muscle status and survival among patients with advanced biliary tract cancer.

BACKGROUND: Studies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes. METHODS: We identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change. RESULTS: Compared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15-2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07-2.14; Ptrend = 0.012), but not with PFS (Ptrend = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD. CONCLUSIONS: Skeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status.

Risk of recurrence with or without plastic stent after EUS-guided treatment of peripancreatic fluid collections: A systematic review and meta-analysis.

Background and study aims Recent advances in endoscopic transmural treatment have improved the clinical outcomes of patients with pancreatic fluid collections (PFCs). However, there is still a debate about the preventive effect of long-term placement of a transmural plastic stent (PS) on recurrence after successful endoscopic ultrasound (EUS)-guided treatment of PFCs. We conducted a systematic review and meta-analysis to evaluate PFC recurrence rates with and without a transmural PS after EUS-guided treatment. Patients and methods A systematic literature search of PubMed, Embase, and the Cochrane database was conducted to identify clinical studies comparing outcomes with and without transmural PS published until September 2022. Data on PFC recurrence and adverse events (AEs) were pooled using a random-effects model. Results Nine studies including 380 patients with long-term transmural PS and 289 patients without PS were identified. The rate of PFC recurrence was significantly lower in patients with transmural PS (pooled odds ratio [OR] = 0.23, 95% confidence interval [CI] [0.08-0.65], P = 0.005). In a subgroup analysis limited to studies focusing on patients with disconnected pancreatic duct syndrome, which has been reported to be a risk factor for PFC recurrence, the OR was numerically lower than that for the entire cohort (OR = 0.14, 95% CI [0.04-0.46]). The rate of AEs was significantly higher with long-term transmural PS (OR = 14.77, 95% CI [4.21-51.83]). Conclusions In this meta-analysis, long-term PS placement reduced the risk of PFC recurrence. Given the potential AEs of indwelling PS, further research is required to evaluate the overall benefits of long-term PS placement.

Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age.

OBJECTIVE: Current guidelines recommend long-term image-based surveillance for patients with low-risk intraductal papillary mucinous neoplasms (IPMNs). This simulation study aimed to examine the comparative cost-effectiveness of continued versus discontinued surveillance at different ages and define the optimal age to stop surveillance. DESIGN: We constructed a Markov model with a lifetime horizon to simulate the clinical course of patients with IPMNs receiving imaging-based surveillance. We calculated incremental cost-effectiveness ratios (ICERs) for continued versus discontinued surveillance at different ages to stop surveillance, stratified by sex and IPMN types (branch-duct vs mixed-type). We determined the optimal age to stop surveillance as the lowest age at which the ICER exceeded the willingness-to-pay threshold of US$100 000 per quality-adjusted life year. To estimate model parameters, we used a clinical cohort of 3000 patients with IPMNs and a national database including 40 166 patients with pancreatic cancer receiving pancreatectomy as well as published data. RESULTS: In male patients, the optimal age to stop surveillance was 76-78 years irrespective of the IPMN types, compared with 70, 73, 81, and 84 years for female patients with branch-duct IPMNs <20 mm, =20-29 mm, ≥30 mm and mixed-type IPMNs, respectively. The suggested ages became younger according to an increasing level of comorbidities. In cases with high comorbidity burden, the ICERs were above the willingness-to-pay threshold irrespective of sex and the size of branch-duct IPMNs. CONCLUSIONS: The cost-effectiveness of long-term IPMN surveillance depended on sex, IPMN types, and comorbidity levels, suggesting the potential to personalise patient management from the health economic perspective.