Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial.

BACKGROUND: Patients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer. METHODS: The PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6-10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients' medical records; (v) explorative outcomes of patients' experience of the exercise program which will be evaluated using focus group/individual interviews. DISCUSSION: It is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

Impact of the serum creatinine and cystatin C ratio for prediction of sarcopenia and prognosis in biliary tract cancer.

BACKGROUND: Sarcopenia is a poor prognostic factor in cancer patients. In recent years, there have been reports that serum creatinine and cystatin C (Cr/CysC) ratio is associated with sarcopenia. However, the prognostic value of the Cr/CysC ratio in biliary tract cancer is unclear. We evaluated the impact of the Cr/CysC ratio on sarcopenia and prognosis in biliary tract cancer. METHODS: We retrospectively reviewed the records of 190 patients with biliary tract cancer who had undergone surgical resection from January 2017 to March 2023. Frozen serum samples collected at the time of surgery were used to measure CysC. We calculated the Cr/CysC ratio and investigated the relationship with sarcopenia and the prognostic significance. RESULTS: We calculated the cutoff value of the Cr/CysC ratio for low skeletal muscle index (SMI) (< 42 cm2/m2 for males and < 38 cm2/m2 for females). The optimal cutoff value of the Cr/CysC ratio was 0.848. The low Cr/CysC ratio group was significantly associated with higher preoperative CRP and lower albumin, lower SMI, lower handgrip strength, and higher intramuscular adipose tissue content. In multivariate analysis, patients with a low Cr/CysC ratio showed poorer overall survival (hazard ratio 2.60, 95% confidence interval 1.07-6.29, p = 0.033), which was significantly worse than in those with a high Cr/CysC ratio. CONCLUSIONS: In patients with biliary tract cancer, the Cr/CysC ratio showed weak correlation with sarcopenic indicators. However, the Cr/CysC ratio could be strong prognostic factor in biliary tract cancer.

Prognostic Significance of Sarcopenia and Systemic Inflammatory Markers in Biliary Tract Cancer: A Retrospective Cohort Study.

PURPOSE: To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC). METHODS: Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant. RESULTS: Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m2), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively). CONCLUSION: Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI.

Long-term risk of venous thromboembolism among patients with gastrointestinal non-neoplastic and neoplastic diseases: A prospective cohort study of 484 211 individuals.

We conducted a prospective cohort study to examine the associations of 21 gastrointestinal diseases with the risk of incident venous thromboembolism (VTE). The study included 485 936 UK Biobank participants free of baseline VTE. The gastrointestinal diseases were defined by the International Classification of Disease (ICD)-9 and 10 codes with data from the nationwide inpatient data set, the primary care data set, and the cancer registries. Incident VTE cases were defined by ICD-9 and 10 codes with data from the nationwide inpatient data set. Cox proportional hazards regression was used to estimate the associations of baseline gastrointestinal diseases with incident VTE risk. During a median follow-up of 12.0 years, 13 646 incident VTE cases were diagnosed. Eleven gastrointestinal diseases (nine non-neoplastic and two neoplastic) were associated with an increased risk of incident VTE after Bonferroni corrections. The risk of VTE was >50% higher among patients with gallbladder and biliary tract cancer (hazard ratio [HR] 3.15, 95% confidence interval [CI] 95% CI 1.74-5.70), pancreatic cancer (HR 2.84, 95% CI 1.65-4.91), cirrhosis (HR 2.34, 95% CI 1.96-2.79), Crohn's disease (HR 1.61, 95% CI 1.33-1.95), or pancreatitis (HR 1.57, 95% CI 1.31-1.88) compared with individuals without each of these diseases. We observed multiplicative interactions of age, sex, and body mass index with some gastrointestinal diseases (p < .05). A more pronounced, increased risk of VTE was found among younger, female, or obese patients. The study suggests a 50% higher risk of developing VTE among patients with gallbladder and biliary tract cancer, pancreatic cancer, cirrhosis, Crohn's disease, or pancreatitis.

Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.

The impact of osteosarcopenia in patients with unresectable or recurrent biliary tract cancer receiving palliative chemotherapy.

BACKGROUND: Osteosarcopenia is a newly described syndrome that has been reported to be associated with worse outcomes in various types of cancer. However, its impact on survival in biliary tract cancer remains unclear. This study evaluated the impact of osteosarcopenia on survival in patients with unresectable or recurrent biliary tract cancer. METHODS: A total of 306 patients with unresectable or recurrent biliary tract cancer who initiated chemotherapy at our institution between 2015 and 2021 were retrospectively investigated. Skeletal muscle index and bone mineral density were measured using pretreatment cross-sectional computed tomography images. Baseline characteristics and survival outcomes were compared between patients with osteosarcopenia and those without. The Cox proportional hazards regression model was used to identify factors associated with survival. RESULTS: Osteosarcopenia was present in 66 patients (22%) and was associated with older age (74 vs. 69 years, P < 0.001) and female sex (58 vs. 37%, P = 0.003). Patients with osteosarcopenia tended to have worse performance status (P = 0.098), higher modified Glasgow prognostic score (P = 0.082), higher neutrophil to lymphocyte ratio (P = 0.058) and were significantly less likely to receive combination chemotherapy (68 vs. 80%, P = 0.044) than those without. Osteosarcopenia was associated with reduced survival (8.9 vs. 14.0 months, P < 0.001) and was identified as an independent factor predicting shorter survival in multivariate analysis. CONCLUSIONS: Osteosarcopenia was associated with poor survival in unresectable or recurrent biliary tract cancer treated with chemotherapy. This study highlights the potential importance of screening for osteosarcopenia in patients with biliary tract cancer.

Impact of cholangitis on survival of patients with malignant biliary obstruction treated with percutaneous transhepatic biliary drainage.

PURPOSE: To evaluate the impact of cholangitis on survival of patients with gastrointestinal cancer and malignant biliary obstruction treated with percutaneous transhepatic biliary drainage (PTBD). METHODS: A retrospective registry study was performed at a tertiary center from 2000 to 2016 in Northern Finland. RESULTS: The study included 588 patients, 258 (43.9%) patients with pancreatic cancer, 222 (37.7%) with biliary tract cancer, and 108 (18.4%) with metastasis from gastrointestinal cancers. Patient mean age was 70 years, range 26 - 93 years. There were 288 [49.0%] women. The 30-day mortality rate was 30.8% for 156 patients with cholangitis before PTBD, 19.5% for 215 patients with cholangitis after PTBD and 25.8% for 217 patients without cholangitis (P = 0.039). The median survival was 1.8 months for patients with cholangitis before PTBD, 3.0 months for patients with cholangitis after PTBD, and 3.2 months for patients without cholangitis (P = 0.002). The hazard ratio (HR) for 1-year mortality for patients with cholangitis before PTBD was 1.3 (95% CI 1.06 - 1.67, P = 0.015) compared to patients with cholangitis after PTBD. After successful PTBD, 54 out of 291 patients received chemotherapy; the median survival was 5.2 months with cholangitis before PTBD, 9.4 months with cholangitis after PTBD and 15.3 months without cholangitis. CONCLUSION: In gastrointestinal cancers with malignant biliary obstruction, survival is poorer if cholangitis occurs before PTBD compared to cholangitis after PTBD. An oncologist's consultation is essential for assessing the possibility of chemotherapy in successfully treated PTBD patients, because of the notable survival benefit.

Associations between cigarette smoking and biliary tract cancer by anatomic subsite and sex: a prospective cohort study in Japan.

PURPOSE: Biliary tract cancer (BTC) has not been considered a tobacco-related cancer, largely because of inconclusive results from epidemiological studies. We herein evaluate the association between cigarette smoking and risk of death from BTC by anatomic subsite and sex using data from a large, prospective cohort study in Japan. METHODS: The present study included 97,030 Japanese individuals who were enrolled in 1988-1990 and followed until 31 December 2009. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association of BTC with cigarette smoking, including smoking status, number of cigarettes smoked per day, and pack-years of smoking. RESULTS: During a mean follow-up of 16.2 years, we documented 484 deaths (187 from gallbladder cancers and 297 from cancers of other and unspecified biliary tract parts). After adjustment for sex, age, body mass index, alcohol consumption, and history of gallstones, current smokers had a higher risk of death due to BTC (RR = 1.35, 95% CI = 1.01-1.79) than never smokers. In the analyses by anatomic subsite, current smoking was associated with an increased risk of death from gallbladder cancer (RR = 1.89 95% CI = 1.19-3.02), whereas no evidence of an association was noted for cancers of other and unspecified biliary tract parts (RR = 1.10, 95% CI = 0.77-1.58). Moreover, mortality risk increased with an increasing number of cigarettes smoked per day and pack-years of smoking, particularly for gallbladder cancer in men. CONCLUSION: Cigarette smoking is associated with an increased risk of death from BTC, particularly gallbladder cancer, in Japanese men.

Sarcopenia Predicts Relevant Clinical Outcomes in Biliary Tract Cancer Patients: A Systematic Review and Meta-Analysis.

The purpose of this meta-analysis was to analyze the influences of sarcopenia on clinical outcomes in patients with biliary tract cancer (BTC). A systematic literature search was performed in November 2021. Some studies that reported the impacts of sarcopenia on the prognosis of patients with BTC were included. The overall hazard ratios (HRs), overall survival (OS), recurrence-free survival (RFS), and odds ratio (OR) for major postoperative complications were calculated using a fixed- or random effects. In the 18 studies, 3261 patients were enrolled for analysis. Based on defining sarcopenia by muscle mass, sarcopenia predicted OS, and based on defining sarcopenia by muscle density, HR was 2.10 (95% CI 1.72-2.56) and HR was 2.12 (95% CI 1.46- 3.10). Patients with sarcopenia had poorer RFS, and HR was 2.18 (95% CI 1.75-2.71). The incidence rate of major postoperative complication increased compared with those without sarcopenia (OR, 1.45; 95% Cl, 1.07-1.96). Sarcopenia is an independent risk factor for poor OS and RFS in patients with BTC. Sarcopenia is associated with the occurrence of major postoperative complications. This study provides advice that clinicians should provide importance to the assessment of skeletal muscle status and provide suitable nutritional supports and exercise program to reduce the sarcopenia in patients with BTC.

Body composition assessment and sarcopenia in patients with biliary tract cancer: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia, as assessed by body composition, can affect morbidity and survival in several gastrointestinal cancer. However, the impact of sarcopenia, referring to both quantity and quality of skeletal muscle, in biliary tract cancer (BTC) is debatable. We aimed to investigate the impact of sarcopenia on morbidity and mortality in patients with BTC. METHODS: Electronic databases and trial registries were searched through July 2021 to perform random-effects meta-analyses. Study selection, data abstraction and quality assessment were independently performed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Twenty-nine studies (4443 patients) were included; 28 used computed tomography and one used dual-energy X-ray absorptiometry to assess body composition. Eighteen studies reported the impact of pre-operative sarcopenia on postoperative outcomes; namely, sarcopenia increased postoperative complications (risk ratio = 1.23, 95% confidence interval [CI] = 1.07 to 1.41; I2 = 2%), and decreased recurrence-free survival (hazard ratio [HR] = 2.20, 95% CI = 1.75 to 2.75; I2 = 0%) in multivariable analyses. Low muscle quantity (HR = 2.26, 95% CI = 1.75 to 2.92; I2 = 66%) and quality (HR = 1.75, 95% CI = 1.33 to 2.29; I2 = 50%) decreased overall survival in multivariable analyses. The certainty of the evidence was low because of heterogeneity and imprecision. CONCLUSIONS: In sarcopenia, low muscle quantity and quality by body composition conferred an independent risk of morbidity and mortality in patients with BTC. Further studies are needed to confirm these findings and mitigate risk.

Irradiation stent insertion for distal biliary obstruction secondary to primary common biliary cancer.

PURPOSE: To assess the effectiveness and safety of irradiation stent insertion for patients with distal biliary obstruction (DBO) secondary to primary common biliary cancer. MATERIAL AND METHODS: Eighty-two consecutive patients with DBO secondary to primary common biliary cancer were treated via either normal (n = 45) or irradiation stenting (n = 37) between January 2013 and December 2019. The instant and long-term outcomes were compared. RESULTS: Technical success rates of normal and irradiation stenting were both 100%. Clinical success rates of normal and irradiation stenting were 91.1 and 100%, respectively (p = .179). Stent reobstruction was observed in 13 and 7 patients in the normal and irradiation stenting groups, respectively (p = .295). The median stent patency was 162 and 225 days in the normal and irradiation stenting groups, respectively (p < .001). The median survival was 178 and 250 days in the normal and irradiation stenting groups, respectively (p < .001). Cholangitis was, respectively, observed in 8 and 12 patients in normal and irradiation stenting groups (p = .124). CONCLUSION: Irradiation stenting is effective and safe for patients with DBO secondary to primary common biliary cancer and can prolong stent patency and survival.

Artificial intelligence for automatic diagnosis of biliary stricture malignancy status in single-operator cholangioscopy: a pilot study.

BACKGROUND AND AIMS: The diagnosis and characterization of biliary strictures (BSs) is challenging. The introduction of digital single-operator cholangioscopy (DSOC) that allows direct visual inspection of the lesion and targeted biopsy sampling significantly improved the diagnostic yield in patients with indeterminate BSs. However, the diagnostic efficiency of DSOC remains suboptimal. Convolutional neural networks (CNNs) have shown great potential for the interpretation of medical images. We aimed to develop a CNN-based system for automatic detection of malignant BSs in DSOC images. METHODS: We developed, trained, and validated a CNN-based on DSOC images. Each frame was labeled as a normal/benign finding or as a malignant lesion if histopathologic evidence of biliary malignancy was available. The entire dataset was split for 5-fold cross-validation. In addition, the image dataset was split for constitution of training and validation datasets. The performance of the CNN was measured by calculating the area under the receiving operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: A total of 11,855 images from 85 patients were included (9695 malignant strictures and 2160 benign findings). The model had an overall accuracy of 94.9%, sensitivity of 94.7%, specificity of 92.1%, and AUC of .988 in cross-validation analysis. The image processing speed of the CNN was 7 ms per frame. CONCLUSIONS: The developed deep learning algorithm accurately detected and differentiated malignant strictures from benign biliary conditions. The introduction of artificial intelligence algorithms to DSOC systems may significantly increase its diagnostic yield for malignant strictures.

Benign Finding or Malignancy: von Meyenburg Complexes Found during Laparoscopic Cholecystectomy.

Von Meyenburg complexes are benign bile duct hamartomas that arise as cystic nodules of the liver. Von Meyenburg complexes are often asymptomatic and thus typically discovered incidentally on imaging or autopsy. They can also be encountered at the time of surgery where they often appear as scattered white liver lesions concerning for malignancy. Here, we present a case in which white hepatic nodules were found incidentally during laparoscopic cholecystectomy in a 36 -year-old female. Pathologic analysis confirmed the diagnosis of von Meyenburg complexes. The operating surgeon proceeded with laparoscopic cholecystectomy without complication. We report this case to encourage awareness of this benign entity. The finding of scattered hepatic lesions found intra-operatively can create concern for metastatic neoplastic processes. An awareness of von Meyenburg complexes and their gross appearance can better guide surgeons' intraoperative decision-making when encountering these characteristic hepatic lesions.

Prognostic Impact of Sarcopenia in Patients With Biliary Tract Cancer Undergoing Chemotherapy.

AIM: Sarcopenia affects the treatment of various cancer types but its impact on chemotherapy efficacy and prognosis in biliary tract cancer remains unclear. Thus, we evaluated whether sarcopenia independently affects the outcome of chemotherapy for biliary tract cancer. PATIENTS AND METHODS: Data of 50 patients who underwent chemotherapy for biliary tract cancer at two affiliated centres were retrospectively analysed. The association of clinical factors, including sarcopenia, with overall survival and time to treatment failure was analysed. RESULTS: Sarcopenia was an independent factor negatively influencing overall survival and time to treatment failure in univariate and multivariate analyses (median overall survival, sarcopenic vs. non-sarcopenic patients: 10.6 vs. 16.6 months; hazard ratio=2.19, p=0.018; time to treatment failure: 5.3 vs. 13.1 months, hazard ratio=2.50, p=0.019). CONCLUSION: Sarcopenia may affect the efficacy of chemotherapy and prognosis in biliary tract cancer. Thus, improving sarcopenia may improve the prognosis of patients with biliary tract cancer undergoing chemotherapy.

Association of prediabetes, diabetes, and diabetes duration with biliary tract cancer risk: A nationwide cohort study.

BACKGROUND & AIMS: Population-based evidence of the association between diabetes and biliary tract cancer (BTC) risk is lacking. We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with subsequent risk of BTC, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), in the Korean general population. METHODS: This nationwide cohort study included 9,697,773 adults aged ≥20 years without cancer who underwent national health screening between January and December 2009. Subjects' glycemic status was categorized as normoglycemic, impaired fasting glucose (IFG), newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Incident BTC was identified using claims data. Follow-up continued until December 2017. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% CIs of BTC. RESULTS: During a median follow-up of 7.2 years, 13,022 patients were newly diagnosed with BTC. Compared with the normoglycemic group, the IFG, newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years groups showed the following adjusted hazard ratios (95% CIs) for BTC: 1.08 (1.04-1.12), 1.31 (1.22-1.41), 1.35 (1.27-1.43), and 1.47 (1.39-1.55), respectively. BTC risk significantly increased with deteriorating glycemic status (P for trend <0.001). These results were consistent with those of CCA and GBC analyses. CONCLUSIONS: Both IFG and diabetes were independently associated with an increased risk of BTC, including CCA and GBC. A longer diabetes duration was associated with a further increase in BTC risk. Diabetes and even IFG may be modifiable risk factors for BTC.

Chemotherapy Improves Survival After Percutaneous Biliary Drainage in Patients With Pancreatic or Biliary Tract Cancer With Biliary Obstruction.

BACKGROUND: The survival benefit of chemotherapy compared to best supportive care (BSC) after percutaneous transhepatic biliary drainage (PTBD) was evaluated in patients with pancreatic or biliary tract cancer. PATIENTS AND METHODS: A retrospective registry study was conducted at a tertiary-level university hospital. The endpoint was survival measured from the PTBD and the initiation of chemotherapy. RESULTS: Among 158 patients (mean age=74 years, range=43-93 years; 51.9% women), 82 (51.9%) had pancreatic cancer and 76 (48.1%) had biliary tract cancer. After PTBD, 32 (20.3%) patients received chemotherapy and had a median survival of 11.7 months; 126 (79.7%) patients received only BSC resulting in a median survival of 1.7 months. The hazard ratio for survival at 1 year for patients who received chemotherapy compared to BSC was 0.22 (95% confidence interval=0.12-0.41, p<0.001). CONCLUSION: After PTBD, patients with pancreatic or biliary tract cancer should be critically evaluated by an oncologist to determine whether chemotherapy is possible, as it seems to significantly improve survival compared to BSC.

Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113.

JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504-0.937) in the low CCr group. Although the total number of incidences of all Grade 3-4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.

Stent insertion with high-intensity focused ultrasound ablation for malignant biliary obstruction: A protocol of systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted in order to understand the clinical efficacy of stent insertion with high-intensity focused ultrasound (HIFU) ablation for the treatment of malignant biliary obstruction (MBO). METHODS: The Pubmed, Embase, and Cochrane Library databases were searched for all relevant studies published through July 2020. The meta-analysis was conducted using RevMan v5.3, with analyzed study endpoints including the rate of stent dysfunction, time to stent dysfunction, stent patency, complication rate, and overall survival (OS). RESULTS: In total, 35 potentially relevant studies were initially identified, of which 6 were ultimately included in the present meta-analysis. These 6 studies included 429 MBO patients that were treated either only via stenting (n = 221) or via stenting in combination with HIFU ablation (n = 208). Pooled stent dysfunction rates in the stent and stent with HIFU groups were 25.9% and 18.0%, respectively (OR: 1.59; 95% CI: 0.88, 2.84, P = .12). The average time to stent dysfunction was significantly longer in the stent with HIFU group relative to the stent group (MD: -3.15; 95% CI: -3.53, -2.77, P < .0001). Pooled complication rates in the stent and stent with HIFU groups were 17.1% and 19.6%, respectively (OR: 0.88; 95% CI: 0.49, 1.58, P = .67). Stent patency and OS were both significantly longer in the stent with HIFU group relative to the stent group (P < .0001 and.0001, respectively). Funnel plot analyses did not reveal any significant evidence of publication bias linked to the selected study endpoints. CONCLUSIONS: This meta-analysis found that a combined stenting and HIFU ablation approach can achieve better stent patency and OS in MBO patients relative to stent insertion alone.

Intraductal papillary mucinous neoplasm of the biliary tract with cardiac metastasis: A case report.

INTRODUCTION: Intraductal papillary mucinous neoplasm of the biliary tract (IPNB) is a rare, low-grade neoplasm limited to the bile duct mucosa. The malignant transformation rate is low, and there have been limited reports of metastasis to other organs. Herein, we presented a rare case of a patient who was diagnosed with IPNB concurrent with invasive adenocarcinoma after surgery and was diagnosed with cardiac metastasis 6 months later. PATIENT CONCERNS: A 61-year-old male patient presented with abdominal pain to a local clinic. He was diagnosed with intrahepatic cholangiocarcinoma with pancreatitis and transferred to our hospital. DIAGNOSIS: Diagnostic testing (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography) revealed a papillary neoplasm and invasive adenocarcinoma with papillary neoplasm in the periampullary lesion. INTERVENTIONS: Pancreaticoduodenectomy, right hemihepatectomy, and left lateral sectionectomy of the liver were performed. After surgery, we planned gemcitabine-based adjuvant chemotherapy. OUTCOMES: Upon completion of the sixth gemcitabine chemotherapy cycle, a hyperechoic, oval-shaped mass (1.3 × 2.6 cm) was found on the outer wall of the right atrium. Resection of a cardiac tumor in the right atrium and patch repair were performed. CONCLUSION: To our knowledge, no other case of cardiac metastasis found during observation after surgery for an IPNB has been described. IPNBs are known to be less aggressive and to have a lower metastasis rate than intraductal papillary mucinous neoplasms; therefore, the number of case reports describing metastasis after surgery is relatively low. Our case suggests that close observation is necessary in patients diagnosed with an IPNB.

Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy for advanced biliary tract cancers with biliary obstruction: a multicentre, retrospective, controlled study.

OBJECTIVE: To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). METHODS: We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. RESULTS: Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1-9.3) than in the control group (4.3 months, 95% CI: 3.6-5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1-16.5; control: 8.5 months, 95% CI: 7.6-9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. CONCLUSIONS: Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. KEY POINTS: • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.