A phase-I study of second-line S-IROX for unresectable pancreatic cancer after gemcitabine plus nab-paclitaxel failure.

Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. This phase-I study used the "3 + 3" dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1-7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80 mg/m2; oxaliplatin, 85 mg/m2; and irinotecan, 120 mg/m2), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150 mg/m2), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77-422) days, and 414 (101-685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80 mg/m2; oxaliplatin, 85 mg/m2; and irinotecan, 150 mg/m2).

Diagnosis of pancreatic malignancies using an overnight-stored pancreatic juice cell block specimen.

BACKGROUND AND AIMS: Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease. METHODS: This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB. RESULT: An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry. CONCLUSION: The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment.

Evaluating optimal bilateral biliary stenting in endoscopic reintervention after initial plastic stent dysfunction for unresectable malignant hilar biliary obstruction: Retrospective cross-sectional study.

OBJECTIVES: The placement of plastic stents (PS), including intraductal PS (IS), is useful in patients with unresectable malignant hilar biliary obstruction (UMHBO) because of patency and ease of endoscopic reintervention (ERI). However, the optimal stent replacement method for PS remains unclear. METHODS: This retrospective study included 322 patients with UMHBO. Among them, 146 received PS placement as initial drainage (across-the-papilla PS [aPS], 54; IS, 92), whereas 75 required ERI. Eight bilateral aPS, 21 bilateral IS, and 17 bilateral self-expandable metallic stent (SEMS) placements met the inclusion criteria. Rates of technical and clinical success, adverse events, recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival, and secondary ERI were compared. RESULTS: There were no significant intergroup differences in rates of technical or clinical success, adverse events, RBO occurrence, or overall survival. The median TRBO was significantly shorter in the aPS group (47 days) than IS (91 days; P = 0.0196) and SEMS (143 days; P < 0.01) groups. Median TRBO did not differ significantly between the IS and SEMS groups (P = 0.44). On Cox multivariate analysis, the aPS group had the shortest stent patency (hazard ratio 2.67 [95% confidence interval 1.05-6.76], P = 0.038). For secondary ERI, the median endoscopic procedure time was significantly shorter in the IS (22 min) vs. SEMS (40 min) group (P = 0.034). CONCLUSIONS: Bilateral IS and SEMS placement featured prolonged patency after first ERI. Because bilateral IS placement is faster than SEMS placement and IS can be removed during secondary ERI, it may be a good option for first ERI.

One-stage versus two-stage endoscopic management for acute cholangitis caused by common bile duct stones: A retrospective multicenter cohort study.

BACKGROUND: One-stage endoscopic management, where papillary interventions and stone removal are simultaneously performed, has been reported to be an effective treatment for acute cholangitis caused by common bile duct stones (CBDS). However, there have been few reports comparing it with two-stage management, and there is no established strategy for the indication of one-stage management. The aim of the present study was to compare the short- and long-term outcomes between one- and two-stage management for acute cholangitis caused by CBDS. METHODS: We retrospectively studied 577 patients who underwent one- or two-stage endoscopic management for acute cholangitis between May 2010 and December 2020. The patients were divided into one- and two-stage groups by endoscopic management. The clinical outcomes were compared between groups. RESULTS: The technical and clinical success were similar in both groups, although the length of hospital stay was significantly shorter in the one-stage group. Although there was no difference in the early adverse event (AE) between two groups, post-ERCP pancreatitis was recognized in 3.4% and 10.0%, which was significantly higher in the two-stage group. The cumulative late AE rate was 22.6% and 14.1%, which was significantly higher in the one-stage group. In the multivariate analyses, intervention (one-stage), number of CBDS ≥2, biliary drainage, the use of ML, and gallbladder stone were identified as significant factors associated with the recurrence of CBDS. CONCLUSION: Although one-stage endoscopic management is useful and safe with reducing hospital stays, diligent postoperative follow-up with consideration to recurrence of CBDS is essential.

Development of Pancreatic Cancer during the Follow-up of Autoimmune Pancreatitis: A Report of Two Cases.

Autoimmune pancreatitis (AIP) is considered to have a good steroid response and is recognized as a disease with a favorable prognosis. However, it has been reported that patients with AIP have malignant diseases. We herein report two cases of pancreatic cancer during the follow-up of AIP, in which both patients died of pancreatic cancer. Patients with AIP may be at a high risk of malignant diseases, including pancreatic cancer, and medium- to long-term follow-up may be necessary.

Gastric Varices Rupture due to Splenic Vein Obstruction Associated with Autoimmune Pancreatitis.

A 60-year-old man with a high IgG4 level was found to have pancreatic tail enlargement on computed tomography (CT), and autoimmune pancreatitis (AIP) was confirmed by a histological diagnosis. He was treated with prednisolone for one year and seven months, at which point his treatment finished. Four months later, however, he had hematemesis from gastric varices. CT showed recurrence of pancreatic tail enlargement with obstruction of the splenic artery and vein and formation of collateral blood vessels to the gastric fornix. Endoscopic injection sclerotherapy was performed, and he underwent splenectomy. This case highlights the importance of paying attention to peripancreatic vascular abnormalities during follow-up of AIP patients.

The evaluation of bilateral stenting using braided or laser-cut self-expandable metallic stent for malignant hilar biliary obstruction.

OBJECTIVES: Bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage with long-term stent patency. Laser-cut and braided SEMS can be used for bilateral SEMS placement. This study aimed to clarify any differences in the clinical features and proper use of the laser-cut and braided SEMS placement using the stent-in-stent method for UMHBO. METHODS: In this study, 78 patients who underwent bilateral stent-in-stent SEMS placement for UMHBO were included. The patients were divided into the laser-cut (n = 33) and braided groups (n = 45). Both groups were compared for technical and clinical success, adverse events (AEs), time to recurrent biliary obstruction (TRBO), overall survival, and endoscopic reintervention (ERI). RESULTS: There were no significant differences in technical and clinical success rates (laser-cut vs. braided group, 97% vs. 95.6%, P = 1.0), AEs (21.2% vs. 15.6%. P = 0.56), median TRBO (242 days vs. 140 days, P = 0.36), and median overall survival (654 days vs. 675 days, P = 0.58). ERI was required in 15 patients in the laser-cut group and in 20 patients in the braided group. The technical and clinical success rates of ERI (60% vs. 85%) were not significantly different (P = 0.13); however, the median ERI procedure time was significantly longer in the laser-cut group (38 min) than in the braided group (22 min; P = 0.02). CONCLUSION: No significant difference in initial SEMS placement was noted between the laser-cut and braided groups; however, the laser-cut group required a longer ERI procedure time than that required by the braided group. The use of braided SEMS may be a convenient option for ERI.

Utility of bilateral intraductal plastic stent for malignant hilar biliary obstruction compared with bilateral self-expandable metal stent: a propensity score-matched cohort analysis.

BACKGROUND AND AIMS: Intraductal plastic stent (IS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage. However, the effectiveness of bilateral IS placement compared with bilateral self-expandable metal stent (SEMS) placement remains unclear. METHODS: Overall, 301 patients with UMHBO were enrolled; 38 patients underwent bilateral IS placement (IS group) and 38 patients underwent SEMS placement (SEMS group) in the propensity score-based cohort. Both groups were compared for technical and clinical success, adverse events (AEs), recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival (OS), and endoscopic reintervention (ERI). RESULTS: No significant differences were observed between the groups regarding technical and clinical success, AEs and RBO occurrence rates, TRBO, or OS. The median initial endoscopic procedure time was significantly shorter in the IS group (23 vs 49 minutes, P < .01). ERI was performed on 20 and 19 patients in the IS and SEMS groups, respectively. The median ERI procedure time was significantly shorter in the IS group (22 vs 35 minutes, P = .04). Median TRBO after ERI with plastic stent placement tended to be longer in the IS group (306 vs 56 days, P = .068). A Cox multivariate analysis showed that the IS group was the significant related factor for TRBO after ERI (hazard ratio, .31; 95% confidence interval, .25-.82; P = .035). CONCLUSIONS: Bilateral IS placement can reduce the duration of the endoscopic procedure and provide sufficient stent patency both initially and after ERI stent placement, and the stents are removable. Bilateral IS placement is considered a good option for initial UMHBO drainage. (Clinical trial registration number: UMIN000050546.).

Long- and short-term outcomes of balloon dilation for benign choledochojejunal anastomotic stricture using balloon endoscopy-assisted ERCP: a multi-center retrospective cohort study.

BACKGROUND: Benign choledochojejunal anastomotic stricture (CJS) is a common complication of pancreaticoduodenectomy and choledochojejunostomy. CJS is generally treated with balloon dilation, using balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP); however, its long- and short-term outcomes have not been fully evaluated. Therefore, we evaluated the treatment outcomes of balloon dilation with BE-ERCP for CJS. METHODS: We retrospectively analyzed 40 patients who had undergone balloon dilation with BE-ERCP for CJS between January 2009 and December 2022. The primary outcomes were technical and clinical success, and adverse event rates of balloon dilation using BE-ERCP for CJS. The secondary outcomes were long-term treatment outcomes for CJS recurrence, and evaluation of risk factors for recurrence. RESULT: Technical and clinical success rates were 93% (37/40) and 100% (37/37), respectively. CJS recurrence occurred in 32% (20/37). No procedure-related adverse events were observed. The significant risk factors of CJS after balloon dilation were its early occurrence after surgery (unit hazard ratio [HR] for month, 0.87; 95% confidence interval [CI], 0.76-0.99; p-value = 0.04) and residual waist during balloon dilation (HR, 5.46; 95% CI, 1.18-25.1; p-value = 0.03). Receiver operating characteristic curve analysis of time from surgery to balloon dilation revealed an area under the curve of 0.80 (95% CI, 0.65-0.94) and the cut-off value was 13.2 months. CONCLUSION: Treatment of CJS with balloon dilation was effective, although CJS recurrence occurred in one-third of the patients. The risk factors for recurrence were early occurrence of CJS after surgery and remaining waist circumference during balloon dilation.

Comparing endoscopic ultrasound-guided antegrade treatment and balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography in the management of bile duct stones in patients with surgically altered anatomy: A retrospective cohort study.

BACKGROUND: Endoscopic ultrasound-guided antegrade treatment (EUS-AG) and balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) have emerged as useful procedures for managing bile duct stones (BDS) in patients with surgically altered anatomy. However, the comparison between these two procedures has not been well studied. The aim of our study was to compare the clinical outcomes of EUS-AG and BE-ERCP for managing BDS in patients with surgically altered anatomy. METHODS: The database was retrospectively evaluated at two tertiary care centers to identify patients with surgically altered anatomy who underwent either EUS-AG or BE-ERCP for BDS. Clinical outcomes were compared between the procedures. The success rate of each procedure was evaluated in three steps: endoscopic approach, biliary access, and stone extraction. RESULTS: Among the 119 identified patients, 23 had EUS-AG, and 96 had BE-ERCP. The overall technical success rates of EUS-AG and BE-ERCP were 65.2% (15/23) and 69.8% (67/96), respectively (P = .80). The comparison of each step between the procedures EUS-AG versus BE-ERCP was as follows: endoscopic approach, 100% (23/23) versus 88.5% (85/96) (P = .11); biliary access, 73.9% (17/23) versus 80.0% (68/85) (P = .57); stone extraction, 88.2% (15/17) versus 98.5% (67/68) (P = .10). The overall adverse event rate was 17.4% (4/23) versus 7.3% (7/96) (P = .22). CONCLUSIONS: Both EUS-AG and BE-ERCP are effective and relatively safe procedures in the management of BDS in patients with surgically altered anatomy. The challenging steps of each procedure might be different, which could help decide which one to use to manage BDS in patients with surgically altered anatomy.

Current status of endoscopic ultrasound-guided antegrade intervention for biliary diseases in patients with surgically altered anatomy.

Endoscopic management of biliary diseases in patients with surgically altered anatomy can be challenging because the altered anatomy makes it difficult to insert an endoscope into the biliary orifice. Even if insertion is feasible, the worse maneuverability of the endoscope and the restriction in available devices and techniques could complicate the procedure. Recently, endoscopic ultrasound-guided antegrade intervention (EUS-AG) has been reported as a useful management method for biliary diseases, especially in patients with surgically altered anatomy. In EUS-AG, the biliary disease is managed in an antegrade fashion through a temporal fistula created under EUS guidance between the intrahepatic biliary duct and upper intestine. In this article, we reviewed the current status of EUS-AG for each biliary diseases, malignant biliary obstruction, bile duct stones, and benign biliary stricture in patients with surgically altered anatomy.

Effect of ursodeoxycholic acid after self-expandable metal stent placement in malignant distal biliary obstruction: a propensity score-matched cohort analysis.

BACKGROUND AND AIMS: Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS occlusion remains unexplored to date. This study aimed to evaluate the efficacy of UDCA after SEMS placement for malignant distal biliary obstruction (MDBO). METHODS: Three hundred fifty-four patients were included, of which 60 received UDCA. Additionally, we conducted a propensity score-matched cohort analysis on 110 patients with SEMS placement for MDBO to reduce selection bias. Patients were categorized into 2 groups of 55 each, based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) after SEMS placement. The secondary endpoint was to evaluate SEMS occlusion rate and early adverse events (AEs). RESULTS: The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P = .0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs 154 days, P = .0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio, 2.28; 95% confidence interval, 1.06-4.88; P = .0348). The overall early AE rate showed insignificant differences between groups. CONCLUSIONS: Administering UDCA after SEMS placement was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion. (Clinical trial registration number: UMIN000046862.).

The efficacy and safety of modified FOLFIRINOX for unresectable advanced pancreatic cancer in elderly versus young patients: A multicenter retrospective cohort study.

In the treatment of advanced pancreatic cancer (APC), FOLFIRINOX (FX), including its dose-modified regimen (mFX), is considered an effective regimen; however, FX is also known to be associated with a high incidence of adverse events due to its multi-agent combination regimen. The efficacy and safety in elderly patients with APC have not been well studied. AIM: To compare the safety and efficacy of first-line mFX for unresectable APC in elderly and young patients. METHODS: This was a multicenter retrospective cohort study included patients who received first-line mFX for unresectable APC. A total of 151 patients were included and divided into the elderly (≥65 years old; 76 patients) and young (<65 years old; 75 patients) groups. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and adverse events (AEs). RESULTS: The median OS and PFS were similar between the two groups (OS: 14.4 months versus 13.9 months, p = 0.42; PFS: 7.4 months versus 6.6 months, p = 0.65). Although severe AEs (≥ grade 3) were observed frequently in both groups (80% versus 84.2%, p = 0.53), there was no significant difference in any of the events between the groups. In the multivariate analysis evaluating the factors affecting OS and febrile neutropenia, age was not significant factors in both analyses. CONCLUSION: First-line mFX for APC in elderly patients was as safe and effective as in younger patients if performance status was good. Further evaluation in a larger cohort is required to confirm our findings.

Evaluation of the Cell Block Method Using Overnight-Stored Bile for Malignant Biliary Stricture Diagnosis.

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) (p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

[Non-surgical management using pancreatic duct drainage for a traumatic pancreatic injury with main pancreatic rupture: a case report].

After an abdominal injury, a woman in her 20s presented to our hospital with abdominal pain. Pancreatic trauma was discovered on computed tomography, along with a pancreatic duct injury and pancreatic juice leakage. Endoscopic retrograde pancreatography revealed a 10-mm rupture of the pancreatic body's main pancreatic duct (MPD) and intraperitoneal leakage of contrast enzyme from the MPD. The pancreatic injury was treated with the placement of a 5-Fr endoscopic nasopancreatic drainage tube in the ruptured distal side of the pancreatic duct;however, 3 months later, the MPD stenosis occurred. The MPD stenosis was improved using a 7-Fr pancreatic stent, and finally, placement of the pancreatic stent was not required for MPD drainage.

Covered self-expandable metallic stent versus plastic stent for preoperative endoscopic biliary drainage in patients with pancreatic cancer: a multi-center retrospective cohort study.

BACKGROUND: Expanding indications for neoadjuvant chemotherapy (NAC) for resectable pancreatic cancer prolong the period from diagnosis to surgery. In resectable pancreatic cancer with malignant biliary obstruction (MBO), the biliary drainage method without any biliary events is ideally required to safely perform NAC as planned. Plastic stents (PS) have been traditionally used for preoperative biliary drainage; however, recently, covered self-expandable metallic stents (CSEMS) have emerged as a tool for preoperative biliary drainage. AIMS: To compare CSEMS with PS for preoperative biliary drainage in the management of resectable pancreatic cancer with MBO. METHODS: In this multicenter retrospective cohort study, we compared CSEMS with PS for preoperative biliary drainage in patients with pancreatic cancer at three tertiary care centers between 2008 and 2019. RESULTS: Of the 120 enrolled patients, 45 underwent CSEMS and 75 underwent PS. No significant difference was observed in the basic characteristics between the groups. The rate of recurrent biliary obstruction (RBO) was significantly lower and the time to RBO was significantly longer in the CSEMS group. In multivariate analysis, CSEMS was an independent factor for a longer RBO. However, pancreatitis and cholecystitis were more common in the CSEMS group. The surgery-related adverse events were not significantly different between the two groups, except for longer surgery time and time to discharge in the CSEMS group. CONCLUSIONS: CSEMS for preoperative endoscopic biliary drainage in patients with pancreatic cancer reduced RBO, although the risk for pancreatitis or cholecystitis could be increased.

Electrohydraulic lithotripsy under the mother-baby cholangioscope system using a colonoscope for large common bile duct stones in a patient with Roux-en-Y reconstruction.

Video 1After insertion of the cholangioscope into the common bile duct, electrohydraulic lithotripsy was performed. All common bile duct stones were shattered and successfully removed using a basket and balloon catheter.

Preoperative perihilar cholangiocarcinoma assessment using virtual endoscopic imaging magnetic resonance cholangioscopy.

Background and study aims Preoperative assessment of the superficial ductal spread (SDS) of perihilar cholangiocarcinoma (PCCA) is important for determining its resectability. A virtual endoscopic imaging method, magnetic resonance cholangioscopy (MRCS), wherein a three-dimensional image is created from magnetic resonance imaging (MRI) data, can evaluate all aspects of arbitrary bile ducts. Patients and methods Overall, 15 patients with PCCA who underwent preoperative MRI were enrolled. All patients underwent surgical treatment. Results MRCS could be performed based on preoperative MRI data in all patients. MRCS could not be used in one patient due to debris in the obstructed bile duct. The remaining 14 patients (93 %) were diagnosed with obstructed bile duct or irregular surface of the bile duct, signifying tumor invasion. The accuracy rate of diagnosing the SDS was 93 % (14/15). Seven patients underwent preoperative peroral cholangioscopy; the scope could not pass through the tumor in three patients. In these three patients, MRCS was able to be use dtoevaluate the obstructed side of the bile duct and faciliated accurate diagnosis of SDS. Conclusions MRCS can be used to noninvasively evaluate the bile duct in all directions. This novel method makes it easy to create virtual images and can be useful for diagnosing the preoperative SDS of PCCA.