Outcomes of 6-mm diameter fully covered self-expandable metal stents for preoperative biliary drainage in pancreatic cancer.

Background: 10-mm self-expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent-related adverse events (AEs). Methods: We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent-related non-event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent-related AEs). Secondary outcomes included stent-related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined. Results: A total of 76 patients were included (6-mm group: 23; 10-mm group: 53). Stent-related NER (57% vs. 64%, p = 0.610), stent-related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95-5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk-reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration. Conclusions: Stent-related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6-mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.

Current Status of Targeted Therapy for Biliary Tract Cancer in the Era of Precision Medicine.

First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such as fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), BRAF, human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI)-high, neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), and poly (adenosine diphosphate-ribose) polymerase (PARP). This review summarizes currently available options in precision medicine and clinical trials for patients with advanced BTC.

Bone loss over time and risk of osteoporosis in advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a high risk of developing osteoporosis. However, the impact of osteoporosis has not been well-studied. This study aimed to evaluate bone loss over time and risk of osteoporosis in patients with advanced pancreatic cancer. METHODS: We retrospectively examined consecutive patients with unresectable pancreatic cancer who had evaluable computed tomography before treatment and at 1-year follow-up. Bone mineral density at the first lumbar vertebra was measured on computed tomography, and osteoporosis was defined as bone mineral density < 135 Hounsfield units. The prevalence and risk factors for osteoporosis, changes in bone mineral density over time and incidence of bone fractures were analyzed. RESULTS: Three hundred eighty patients were included. Osteoporosis was associated with older age, female sex, low body mass index and poor performance status at baseline. A consistent decrease in bone mineral density was observed over time regardless of age, sex or disease status, resulting in an increase in the prevalence of osteoporosis over time (47% at baseline, 79% at 1 year, 88% at 2 years, 89% at 3 years, 95% at 4 years and 100% at 5 years). Changes in bone mineral density from baseline were greater in patients with locally-advanced pancreatic cancer, in those who received modified FOLFIRINOX or S-IROX for more than 3 months, and in those who received radiation therapy. Incident fractures developed in 45 patients (12%) during follow-up. CONCLUSIONS: Osteoporosis and osteoporotic fractures were highly prevalent in patients with advanced pancreatic cancer. This study highlights the importance of screening for osteoporosis in such patients.

Effects of different initial speeds on subsequent glide and underwater undulatory swimming.

This study aimed to investigate the effect of different initial speeds on the performance during underwater undulatory swimming (UUS). The study included 13 female swimmers. Each participant was asked to perform a 15-m maximum UUS, starting with four different push-off speeds. The experiment was recorded using three underwater cameras; subsequently, a two-dimensional motion analysis was conducted. Statistical parametric mapping (SPM) was employed to identify the position where the UUS velocity stabilised. The findings revealed a significant difference in the average swimming velocities during the first cycle of UUS, which was attributed to the variation in initial speed (p < 0.05) while there is no significant difference in the middle and final cycles. The results of SPM analysis suggested that differences in UUS velocity became negligible after approximately 6-m position from the pool wall, regardless of variations in push-off velocity. Furthermore, it was confirmed that swimmers can reach their maximum achievable UUS velocity at approximately 5-m position, even if they fail to execute an effective push-off from the wall. These findings offer valuable insights for future UUS studies, specifically in choosing suitable cycles for analysis.

Rotatable sphincterotome as a rescue device for endoscopic retrograde cholangiopancreatography cannulation: a single-center experience.

BACKGROUND/AIMS: Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. METHODS: We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. RESULTS: TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. CONCLUSION: The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Splenic Hilar Involvement and Sinistral Portal Hypertension in Unresectable Pancreatic Tail Cancer.

BACKGROUND: Pancreatic tail cancer (PTC) frequently displays splenic hilar involvement (SHI), but its impact on clinical outcomes remains unclear. We investigated the clinical impact of SHI in patients with unresectable PTC. METHODS: We retrospectively reviewed all patients with unresectable PTC who received first-line therapy at our institution from 2016 to 2020. RESULTS: Of the 111 included patients, 48 had SHI at diagnosis. SHI was significantly associated with younger age, liver metastasis, peritoneal dissemination, larger tumor size, modified Glasgow prognostic score of 1 or more, splenic artery involvement, gastric varices, and splenomegaly. Shorter median overall survival (OS; 9.3 vs. 11.6 months, p = 0.003) and progression-free survival (PFS; 4.3 vs. 6.3 months, p = 0.013) were observed in SHI patients. Poor performance status of 1 or 2, tumor size > 50 mm, hepatic metastasis, mGPS of 1 or 2, and SHI (hazard ratio: 1.65, 95% confidence interval: 1.08-2.52, p = 0.020) were independent predictors of shorter OS. Splenic artery pseudoaneurysm rupture and variceal rupture were rare and only observed in cases with SHI. CONCLUSIONS: Splenic hilar involvement is associated with worse outcomes in pancreatic tail cancer.

Safety and Effectiveness of Chemotherapy in Elderly Biliary Tract Cancer Patients.

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3-4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients.

Outcomes of lung oligometastasis in pancreatic cancer.

OBJECTIVE: Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases. METHODS: Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model. RESULTS: A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1 months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P = 0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3 months, P = 0.527) and polymetastasis (17.9 vs. 16.7 months, P = 0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7 months. CONCLUSIONS: Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival.

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.

Late-onset hemobilia due to pseudoaneurysm rupture after endoscopic ultrasound-guided hepaticogastrostomy.

We report the case of a 65-year-old man who experienced hemobilia due to rupture of a pseudoaneurysm of the left hepatic artery after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS). The patient was diagnosed with pancreatic cancer and underwent endoscopic retrograde cholangiopancreatography for obstructive jaundice. Biliary drainage was converted to EUS-HGS due to tumor invasion in the superior duodenal angle. A partially covered metal stent was placed in the B3 intrahepatic bile duct. The procedure was completed without early complications, but 50 days later, the patient developed fever, elevated hepatobiliary enzymes, and shock. Contrast-enhanced computed tomography (CT) showed that the hepatic end of the HGS stent had moved slightly toward the stomach compared to the previous CT. A 6-mm pseudoaneurysm was also observed near the A3 and A4 branches of the left hepatic artery, coinciding with the hepatic end of the EUS-HGS stent. Hemostasis was achieved with coil embolization. Biliary hemorrhage due to rupture of a pseudoaneurysm should be considered in the differential diagnosis of biliary obstruction accompanied by bleeding after EUS-HGS.

Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression.

Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09-1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10-1.46). Compared to cases with 0-2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09-1.51) and 1.47 (95% CI, 1.22-1.78), respectively (ptrend < 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (ptrend = 0.003) and to develop liver metastasis (ptrend = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer.

Clinical Efficacy of Neoadjuvant Chemotherapy with Gemcitabine plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma Compared with Upfront Surgery.

BACKGROUND: The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear. METHODS: In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 < 500 U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS. RESULTS: Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02). CONCLUSIONS: NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC.

Risk factors for recurrent stenosis after balloon dilation for benign hepaticojejunostomy anastomotic stricture.

Background/Aims: Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS. Methods: We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy-endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020. Results: Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01-7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85-6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively. Conclusions: Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

Outcomes of Intraductal Placement of Covered Metal Stents for Unresectable Distal Malignant Biliary Obstruction.

Intraductal self-expandable metal stent (SEMS) placement may prolong stent patency by reducing duodenobiliary reflux. This study aimed to evaluate the efficacy and safety of this biliary drainage method in patients with unresectable distal malignant biliary obstruction (MBO). Consecutive patients with unresectable MBO who underwent initial covered SEMS placement between 2015 and 2022 were retrospectively reviewed. We compared the causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates between two biliary drainage methods (SEMSs placed above and across the papilla). A total of 86 patients were included (above: 38 and across: 48). Overall RBO rates (24% vs. 44%, p = 0.069) and median TRBO (11.6 months vs. 9.8 months, p = 0.189) were not significantly different between the two groups. The frequency of overall AEs was similar between the two groups in the entire cohort, but was significantly lower in patients with non-pancreatic cancer (6% vs. 44%, p = 0.035). Reintervention was successfully performed in the majority of patients in both groups. Intraductal SEMS placement was not associated with a prolonged TRBO in this study. Larger studies are warranted to further evaluate the benefit of intraductal SEMS placement.

Prognostic impact of osteosarcopenia in patients with advanced pancreatic cancer receiving gemcitabine plus nab-paclitaxel.

BACKGROUND: Osteosarcopenia, defined as the combination of osteoporosis and sarcopenia, has recently gained attention as a novel prognostic factor for survival in patients with cancer. This study aimed to evaluate the prognostic impact of osteosarcopenia in metastatic pancreatic cancer (PC). METHODS: We retrospectively investigated consecutive metastatic PC patients receiving first-line gemcitabine plus nab-paclitaxel (GnP). Skeletal muscle index at the third lumbar vertebra and bone mineral density at the first lumbar vertebra were measured using pretreatment computed tomography. Treatment outcomes of osteosarcopenia and non-osteosarcopenia groups were compared and analyzed. Multivariate analysis was performed to identify variables associated with survival. RESULTS: Among 313 patients, osteosarcopenia was present in 59 patients (19%). The osteosarcopenia group was associated with older age, higher proportion of females, worse performance status, and higher modified Glasgow prognostic scores (mGPS). Response rates to chemotherapy, progression-free survival (3.5 months vs. 6.4 months, p < 0.001), and overall survival (5.6 months vs. 13.0 months, p < 0.001) were significantly better in the non-osteosarcopenia group. Osteosarcopenia, performance status of 1-2, mGPS score of 1-2, carcinoembryonic antigen ≥10 ng/mL, and carbohydrate antigen 19-9 ≥ 1000 IU/mL were identified as independent factors predicting shorter survival. Grade 3 or higher anemia and febrile neutropenia occurred more frequently in the osteosarcopenia group. CONCLUSIONS: Osteosarcopenia was associated with poor survival in metastatic PC treated with first-line GnP. Screening for osteosarcopenia may be helpful for better management of metastatic PC.

Removal of Duckbill-type laser-cut anti-reflux metal stents: Clinical evaluation and in vitro study.

Objectives: Duckbill-type metal stent (DMS) was the first laser-cut biliary metal stent with an anti-reflux valve. Removal of DMS is believed to be difficult and relevant reports are scarce. This study aims to investigate the feasibility of DMS removal. Methods: We retrospectively analyzed patients who underwent DMS removal between June 2019 and March 2022 to evaluate success rates and factors affecting outcomes. In addition, six different methods of DMS removal were reproduced in vitro, varying removal devices, angle of applied force, and grasped location. Extraction resistance, the distance of forceps stroke, and stent length after removal were compared. Results: Forty patients were enrolled, and DMS removal was successful in 31 cases (78%). No adverse events were observed. Tumor ingrowth was evident in 78% (7/9) of failed cases. Patients receiving biliary metal stents for the first time (naïve cases), long indwelling time, longer stent, and stent tearing during removal were associated with unsuccessful stent removal. In the in vitro study, a larger force was required to remove the stent at an extraction angle of 120° than at 0°. Among cases in which force was applied at 120°, the load tended to be lower when rat-tooth forceps were applied horizontally across the stent. Conclusions: Stent removal was possible in a majority of cases. Deployment of additional stents inside DMS may be preferable to forceful removal in the presence of factors associated with difficult stent removals, such as tumor ingrowth, naïve cases, longer stents, long indwelling time, and stent tearing during removal.

Treatment Outcomes and Prognostic Factors of Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy after Modified FOLFIRINOX in Unresectable Pancreatic Cancer.

Outcomes and prognostic factors of second-line gemcitabine plus nab-paclitaxel (GnP) after modified FOLFIRINOX (mFFX) for unresectable pancreatic cancer were unclear. We retrospectively analyzed consecutive patients with unresectable pancreatic cancer treated with GnP after first-line mFFX treatment between March 2015 and March 2022 at our hospital. A total of 103 patients were included. Median overall survival (OS) from the start of first-line and second-line treatments was 14.9 months and 7.2 months, respectively. Median progression-free survival (PFS) was 3.6 months. Performance status, modified Glasgow prognostic score, and neutrophil-to-lymphocyte ratio were independently associated with OS. Our prognostic model using these parameters classifies patients into good (n = 70) and poor (n = 33) prognosis groups. Median OS and PFS were longer in the good prognosis group than in the poor prognosis group (OS: 9.3 vs. 3.8 months, p < 0.01; PFS: 4.1 vs. 2.3 months, p < 0.01). Grade 3/4 adverse events were observed in 70.9% of patients, with neutropenia being the most frequent. While GnP as second-line treatment was well-tolerated, efficacy of second-line gemcitabine plus nab-paclitaxel was notably limited, particularly in the poor prognosis group.