Low-dose gemcitabine plus nab-paclitaxel versus standard-dose gemcitabine plus nab-paclitaxel in elderly patients with metastatic pancreatic cancer: A randomized Phase II trial.

Background and Aim: A multicenter, open-label randomized Phase II trial was conducted to determine whether low-dose gemcitabine plus nab-paclitaxel (GnP) could improve tolerability and show equivalent efficacy to the standard-dose GnP for elderly patients with metastatic pancreatic cancer. Methods: Consecutive patients aged ≥65 years with metastatic pancreatic cancer who presented at one of four Japanese referral centers between November 2016 and January 2021 were enrolled. The 60 patients were randomly assigned to low- or standard-dose groups with a 1:1 ratio. Patients in the low-dose GnP group received gemcitabine at a dose of 250 mg/m2 and nab-paclitaxel at 125 mg/m2. Results: Low-dose GnP significantly decreased the rate of cases requiring dose reduction (16.7% vs 63.3%). The response rate (36.7% vs 33.3%) and progression-free survival (7.3 vs 8 months) were comparable between the low- and standard-dose groups as determined by independent review. The difference in the median overall survival between the two groups was not significant (7.9 vs 12 months). The proportion of patients with hematologic and non-hematologic treatment-related adverse events was comparable between the two groups. Conclusion: Low-dose GnP had an equivalent efficacy to conventional therapy; however, it did not reduce adverse events.

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma.

Background and Aim: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). Methods: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. Results: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin-bilirubin (ALBI) grade and low level of des-gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log-rank tests with the Kaplan-Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. Conclusion: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.

Significance of post-progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma.

Background and Aim: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. Methods: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. Results: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan-Meier analysis revealed no significant differences in progression-free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). Conclusion: The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.

[A case of upper gastrointestinal bleeding due to a ruptured gastric aneurysm caused by arteriosclerosis derived from primary aldosteronism-induced hypertension].

A 77-year-old woman with a history of hypertension underwent upper gastrointestinal endoscopy for hematemesis, and vasodilation with erosion was detected. Contrast-enhanced computed tomography and abdominal angiography revealed a gastric aneurysm penetrating the stomach wall. Endoscopic hemostasis was thought to be not applicable to a ruptured aneurysm. Transcatheter arterial embolization was not performed because of technical difficulties. Therefore, local gastric resection was performed. It was later determined that the cause of the persistent hypertension was primary aldosteronism, which was thought to cause arteriosclerotic obstruction of the celiac, common hepatic, and splenic arteries, resulting in the formation of the gastric arterial aneurysm. In the case of upper gastrointestinal bleeding, keeping primary aldosteronism in mind as a differential diagnosis is important to make a precise diagnosis and suitable treatment selection.

Efficacy of Over-The-Scope Clip Method as a Novel Hemostatic Therapy for Colonic Diverticular Bleeding.

Colonic diverticular could bleed recurrently, and, sometimes, fatal massive bleeding could occur. However, the choice of endoscopic hemostasis remains controversial. Although the over-the-scope clip (OTSC) method has been reported to be effective, it has not been fully evaluated due to the small number of cases. This study aimed to evaluate the efficacy of the OTSC method for colonic diverticular bleeding. Between August 2017 and December 2020, 36 consecutive patients, including those who could not be treated using endoscopic band ligation (EBL) and those in whom re-bleeding had occurred after EBL, underwent the OTSC method for hemostasis of colonic diverticular bleeding at Hyogo Prefectural Awaji Medical Center. The procedure success rate, adverse events rate, early phase re-bleeding rate (within 30 days following primary hemostasis), and the requirement rate for additional transcatheter arterial embolization (TAE) or surgery were the outcomes assessed. The outcomes were procedure success rate 100%, adverse events rate 0%, early phase re-bleeding rate 8.3%, and additional TAE or surgery rate 0%. These results suggest that the OTSC method is a safe and effective treatment for managing colonic diverticular bleeding.

Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation.

BACKGROUND: Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery. METHODS: This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features. RESULTS: Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003). CONCLUSIONS: The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.

Low-dose rectal diclofenac does not prevent post-ERCP pancreatitis in low- or high-risk patients.

BACKGROUND AND AIM: The most common adverse event following an endoscopic retrograde cholangiopancreatography (ERCP) procedure is post-ERCP pancreatitis (PEP). Rectal nonsteroidal anti-inflammatory drug (NSAID) administration has shown promise to reduce the risk of PEP in high-risk patients. However, in contrast to high-risk patients, the role of NSAID administration in patients with low risk remains controversial. METHODS: We performed a prospective, single-center, single-blinded, two-arm parallel group, randomized controlled trial to clarify the efficacy of low dose (50 mg) rectal NSAID administration for preventing PEP in at-risk patients. Patients scheduled to undergo ERCP were randomized into two groups, those with and without rectal administration of diclofenac. Patients in the diclofenac group received 50 mg of rectal diclofenac 30 min before undergoing ERCP. The primary endpoint was rate of PEP. RESULTS: A total of 303 were randomized into the study groups. Four patients declined participation following randomization, and another two were withdrawn. As a result, a total of 147 patients were assigned to the diclofenac group and 150 to the control group. The baseline and procedural characteristics were similar in both groups. The primary endpoint of PEP occurrence was seen in 13 of 297 patients (4.4%), including eight (5.4%) in the diclofenac group and five (3.3%) in the control group (P = 0.286). Additionally, those results were not significantly different when patients were classified as low or high risk. CONCLUSIONS: Prophylactic low-dose rectal diclofenac did not reduce the incidence of PEP following ERCP in patients classified as low or high risk.

Antibiotic prophylaxis in transcatheter treatment of hepatocellular carcinoma: an open randomized prospective study of oral versus intravenous administration.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) and transcatheter arterial infusion chemotherapy (TAI) are increasingly used to treat inoperable liver malignancies. It has not been determined whether standard oral and intravenous administration of antibiotics have different prophylactic effects against post-TACE/TAI infection. We compared the efficacy of oral levofloxacin (LVFX) and intravenous cephazolin (CEZ) in patients receiving TACE/TAI for hepatocellular carcinoma (HCC) using a prospective design. PATIENTS AND METHODS: One hundred twenty-nine eligible subjects with HCC treated by TACE/TAI were analyzed in this study. Patients were randomly assigned by the envelope method to groups who received either intravenous infusion of CEZ at 2 g/day or oral administration of LVFX at 300 mg/day for 5 days. Laboratory data, changes in antibiotic administration from the standard ones, duration of hospital stay, side effects of antibiotics, and infectious complications were assessed. RESULTS: There were no significant differences in the WBC counts and serum CRP levels between the groups; there were also no significant inter-group differences in the numbers of infectious and other adverse events. CONCLUSION: Our study findings suggest that the results of peroral administration of LVFX for the prevention of post-procedure infectious complications in patients receiving TACE/TAI for HCC are not inferior to those of intravenous administration of CEZ.