Potential of Anti-Leukotriene Drugs as New Therapeutic Agents for Inhibiting Cholangiocarcinoma Progression.

Cholangiocarcinoma (CCA) is a cancer with a poor prognosis due to difficulties in diagnosis and limited treatment options, highlighting the urgent need for new targeted therapies. In a clinical setting, we found that leukotriene levels in bile were higher than in serum. Immunohistochemical analysis of surgically resected samples also revealed that CysLT receptor 1 (CysLTR1) was more highly expressed in CCA than in normal bile duct tissue, prompting us to investigate leukotriene as a potential therapeutic target in CCA. In vitro studies using CCA cell lines expressing CysLTR1 showed that leukotriene D4, a major ligand of CysLTR1, promoted cell proliferation, with increased phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Additionally, treatment with two clinically available anti-allergic drugs-zileuton, an inhibitor of CysLT formation, and montelukast, a CysLTR1 inhibitor-had inhibitory effects on cell proliferation and migratory capacity, accompanied by the reduced phosphorylation of AKT and ERK1/2. Furthermore, the simultaneous administration of both drugs synergistically enhanced the inhibitory effect on cell proliferation. Our study suggests that use of these drugs may represent a novel approach to treat CCA through drug repositioning.

[Gastric metastasis of breast cancer treated as primary gastric cancer due to difficulty in differentiating primary and metastatic cancer:a case report].

A female patient in her 50s who underwent chemotherapy for left primary breast cancer presented with cancerous pleurisy and disseminated intravascular coagulation. Esophagogastroduodenoscopy and liver biopsy revealed gastric and liver cancer. Distinguishing between primary and metastatic cancer by pathological findings is difficult using hematoxylin and eosin staining. We diagnosed and treated simultaneous primary breast cancer (ER-positive) and gastric cancer with liver metastasis (ER-negative), based on differences in estrogen receptor expression. The patient lived for 10 months with chemotherapy. After death, an autopsy was performed because the endoscopic results were atypical for primary gastric cancer, and additional immunohistochemical studies indicated gastric metastasis of breast cancer.

Comparison of the long-term outcomes of EUS-guided gallbladder drainage and endoscopic transpapillary gallbladder drainage for calculous cholecystitis in poor surgical candidates: a multicenter propensity score-matched analysis.

BACKGROUND AND AIMS: Although long-term stent placement using endoscopic transpapillary gallbladder drainage (ETGBD) and EUS-guided gallbladder drainage (EUS-GBD) reportedly reduces cholecystitis recurrence, comparative evidence of their safety and efficacy is scarce. This study aimed to examine and compare the long-term utility of EUS-GBD versus that of ETGBD in poor surgical candidates. METHODS: A total of 379 high-risk surgical patients with acute calculous cholecystitis met the eligibility criteria for enrollment in this study. The technical success and adverse events (AEs) were compared between the EUS-GBD and ETGBD groups, and propensity score matching was performed to adjust for differences between the groups. Both groups underwent plastic stent placement, and scheduled stent exchange and removal were not performed in either group. RESULTS: The technical success rate of EUS-GBD was significantly higher than that of ETGBD (96.7% vs 78.9%, P < .001), whereas the early AE rate did not differ significantly between the 2 methods (7.8% vs 8.9%, P = 1.000). The rate of recurrent cholecystitis did not differ significantly (3.8% vs 3.0%, P = 1.000), but the rate of symptomatic late AEs, in addition to cholecystitis, was significantly lower with EUS-GBD than with ETGBD (1.3% vs 13.4%, P = .006). Consequently, the overall late AE rate was significantly lower with EUS-GBD (5.0% vs 16.4%, P = .029). Multivariate analysis revealed that EUS-GBD was associated with a significantly longer time to late AE (hazard ratio, .26; 95% confidence interval, .10-.67; P = .005). CONCLUSIONS: Long-term stent placement via EUS-GBD is a promising potential option for limiting late AEs, including recurrence, in poor surgical candidates with calculous cholecystitis.

Outcome of nucleos(t)ide analog cessation in patients with treatment for prevention of or against hepatitis B virus reactivation.

AIM: We retrospectively investigated patients with administration of nucleos(t)ide analogs (NAs) for prevention of or against hepatitis B virus (HBV) reactivation, and their clinical outcomes after cessation of the NA. METHODS: We enrolled 180 patients who were positive for HBsAg when they started immunosuppressive therapy or chemotherapy and an NA was administered to prevent HBV reactivation (HBV carrier group), and 82 patients with resolved HBV infection who started administration of an NA after HBV reactivation (de novo HBV group). Cessation of the NA depended on each physician's judgment without definite criteria. RESULTS: A total of 27 patients in the HBV carrier group and 22 in the de novo HBV group stopped NA therapy. In the HBV carrier group, 16 patients experienced virological relapse, which was defined as HBV DNA levels ≥20 IU/ml, and one with hematological disease had an alanine aminotransferase flare after cessation of NA. Of the 16 patients, the NA was reintroduced in three, whereas, the remaining 13 had low levels of HBV DNA and no alanine aminotransferase flare. In the de novo HBV group, virological relapse occurred in six patients, and one with hematological disease had an alanine aminotransferase flare after cessation of the NA. The NA was reintroduced in four of the six patients. CONCLUSIONS: We may be able to consider to cease NA therapy proactively in HBV carriers and resolved patients with non-hematological disease, if their primary diseases are under remission after completion of immunosuppressive therapy or chemotherapy. However, careful follow up is necessary after stopping NA therapy.

[A rare case of hepatosplenic cat scratch disease].

A female patient in her 60s, treated with oral corticosteroids for scleroderma diagnosed 11 years ago, visited our hospital complaining of a persistent fever and liver dysfunction. She was treated with antibiotics, but her fever continued. Abdominal ultrasonography revealed multiple hypoechoic splenic masses. Splenic masses revealed multiple masses with no contrast effect in arterial and portal phases and nuclear in equilibrium phase by contrast computed tomography study, as well as hyperintensity masses with low signal areas in magnetic resonance imaging T2-weighted images. Liver tissue was obtained by percutaneous liver biopsy, and histological findings showed epithelioid cell granulomas without tumor cells. Further interview and physical examination revealed scratch scars from domestic cats and left axillary lymph node swelling. Hence, a cat scratch disease was suspected. She was diagnosed with cat scratch disease by serum indirect immunofluorescence. Her fever was resolved with minocycline administration. Therefore, persistent fever with splenic masses should be suspected of hepatosplenic cat scratch disease.