Enterovirga aerilata sp. nov. and Knoellia koreensis sp. nov., isolated from an automobile air conditioning system.

Two strictly aerobic and rod-shaped bacteria, labelled as DB1703T and DB2414ST, were obtained from an automobile air conditioning system. Strain DB1703T was Gram-stain-negative, while strain DB2414ST was Gram-stain-positive. Both strains were catalase-positive and oxidase-negative. Strains DB1703T and DB2414ST were able to grow at 18-42 °C. Strain DB1703T grew within a NaCl range of 0-3 % and a pH range of 6.0-8.0; while strain DB2414ST grew at 0-1 % and pH 6.5-8.5. The phylogenetic and 16S rRNA gene sequence analysis indicated that strains DB1703T and DB2414ST belonged to the genera Enterovirga and Knoellia, respectively. Strain DB1703T showed the closest phylogenetic similarity to Enterovirga rhinocerotis YIM 100770T (94.8 %), whereas strain DB2414ST was most closely related to Knoellia remsis ATCC BAA-1496T (97.7 %). The genome sizes of strains DB1703T and DB2414ST were 4 652 148 and 4 282 418 bp, respectively, with DNA G+C contents of 68.8 and 70.5 mol%, respectively. Chemotaxonomic data showed Q-10 as the sole ubiquinone in DB1703T and ML-8 (H4) in DB2414ST. The predominant cellular fatty acid in DB1703T was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), whereas iso-C16 : 0, C17 : 1 ω8c, and iso-C15 : 0 were dominant in DB2414ST. Overall, the polyphasic taxonomic comparisons showed that strains DB1703T and DB2414ST were distinct from their closest taxa and represent novel species within the genera Enterovirga and Knoellia, respectively. Accordingly, we propose the names Enterovirga aerilata sp. nov., with the type strain DB1703T (=KCTC 72724T=NBRC 114759T), and Knoellia koreensis sp. nov., with the type strain DB2414ST (=KCTC 49355T=NBRC 114620T).

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis.

Background: Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy. Methods: We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity. Results: A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression. Conclusion: PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea.

BACKGROUND: Intrahepatic duct (IHD) stones are among the most important risk factors for cholangiocarcinoma (CCC). Approximately 10% of patients with IHD stones develop CCC; however, there are limited studies regarding the effect of IHD stone removal on CCC development. AIM: To investigate the association between IHD stone removal and CCC development. METHODS: We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020. RESULTS: CCC occurred in 36 of the 397 enrolled patients. In univariate analysis, chronic hepatitis B infection (11.1% vs 3.0%, P = 0.03), carbohydrate antigen 19-9 (CA19-9, 176.00 vs 11.96 II/mL, P = 0.010), stone located in left or both lobes (86.1% vs 70.1%, P = 0.042), focal atrophy (52.8% vs 26.9%, P = 0.001), duct stricture (47.2% vs 24.9%, P = 0.004), and removal status of IHD stone (33.3% vs 63.2%, P < 0.001) were significantly different between IHD stone patients with and without CCC. In the multivariate analysis, CA19-9 > upper normal limit, carcinoembryonic antigen > upper normal limit, stones located in the left or both lobes, focal atrophy, and complete removal of IHD stones without recurrence were independent factors influencing CCC development. However, the type of removal method was not associated with CCC risk. CONCLUSION: Complete removal of IHD stones without recurrence could reduce CCC risk.

Sphingomonas flavescens sp. nov., isolated from soil.

An aerobic bacterium, designated as PT-12T, was isolated from soil collected from agriculture field, and its taxonomic position was validated through a comprehensive polyphasic methodology. The strain was identified as Gram-stain-negative, non-motile, rod-shaped, and catalase- and oxidase-positive. The yellow-colored colonies showed growth ability at temperature range of 18-37 °C, NaCl content of 0-1.0% (w/v), and at a pH of 6.0-8.0. The 16S rRNA gene and phylogenetic analysis showed that strain PT-12T affiliated with the genus Sphingomonas in the family Sphingomonadaceae, and displayed the highest 16S rRNA nucleotide sequence similarity with Sphingomonas limnosediminicola 03SUJ6T (98.4%). The genome size of strain PT-12T was 2,656,862 bp and the DNA G + C content estimated from genome was 63.5%. The highest values of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) were observed between strain PT-12T and Sphingomonas segetis YJ09T, accounting to 76.2% and 20.2%, respectively. In addition, both ANI and dDDH values between strain PT-12T and other phylogenetically related neighbors ranged between 69.6% and 76.2% and 18.4% and 20.2%, respectively. Chemotaxonomic features exhibited Q-10 as the only ubiquinone; homospermidine as the major polyamine; summed feature 8 (C18:1ω7c and/or C18:1ω6c), C16:0, and 10-methyl C18:0 as the notable fatty acids; and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, and sphingoglycolipid as dominating polar lipids. Overall, the comprehensive polyphasic data supported that strain PT-12T represents a novel bacterial species within the genus Sphingomonas. Accordingly, we propose the name Sphingomonas flavescens sp. nov. The type strain is PT-12T (= KCTC 92114T = NBRC 115717T).

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer.

BACKGROUND: Currently, there is no standard adjuvant therapy for patients with resected ampulla of Vater (AoV) cancer. AIM: To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy (CCRT) in patients with advanced AoV cancer who underwent curative resection. METHODS: This single-centered, retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018. The impact of CCRT on advanced AoV cancer was analyzed. RESULTS: The 1-, 3-, and 5-yr recurrence-free survival (RFS) rates for patients with advanced AoV cancer were 82.8%, 48.3%, and 40.8%, respectively, and the overall survival (OS) rates were 89.7%, 62.1%, and 51.7%, respectively. Lymphovascular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis, whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis. Compared to the patients who did not receive adjuvant CCRT, those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS, although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio. CONCLUSION: Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer. These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining.

BACKGROUND: The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS: Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS: Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS: Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

Anti-Neuroinflammatory Effects of Arecae pericarpium on LPS-Stimulated BV2 Cells.

Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways.

Side-by-side placement of fully covered metal stents versus conventional 7F plastic stents in malignant hilar biliary obstruction: Prospective randomized controlled trial.

OBJECTIVES: We aimed to evaluate the efficacy and safety of metal stents compared with plastic stents when bilateral side-by-side stents were deployed for malignant hilar biliary obstruction (MHBO). METHODS: Fifty patients with unresectable advanced MHBO were randomly assigned to the metal stent (MS, n = 25) or plastic stent group (PS, n = 25). Fully covered self-expandable metal stents with 6 mm diameter and plastic stents with either 7F straight or double pigtail were used for MS and PS groups, respectively. Time to recurrent biliary obstruction (TRBO) was evaluated as the primary outcome. RESULTS: Both groups had 100% technical success rates; 88% and 76% of clinical success rates were obtained in MS and PS, respectively. Although stent migrations were more frequent in MS than PS (48% vs. 16%, P = 0.02), the mean TRBO was significantly longer in MS (190 days; 95% confidence interval [CI] 121-260 days vs. 96 days; 95% CI 50-141 days, P = 0.02). The placement of plastic stents (hazard ratio 2.42; 95% CI 1.24-4.73; P = 0.01) was the only significant risk factor associated with TRBO in multivariable analysis. The rates of adverse events were similar between the two groups (difference 0%; 95% CI -25% to 25%; P > 0.99). CONCLUSIONS: During bilateral side-by-side deployment in MHBO, the use of metal stents appears to be preferable to plastic stents in terms of TRBO, despite a higher frequency of stent migration.

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Metastatic pancreatic solitary fibrous tumor: A case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that is most commonly found in the pleura but can also originate from non-pleural sites. Among the non-pleural localizations, the pancreas is extremely rare. In particular, metastasis to the pancreas from the central nervous system (CNS) is extremely rare, with only two cases reported so far. We report a case of recurrence in the pancreas 14 years after the initial complete surgical removal of a tumor in the CNS. CASE SUMMARY: A 68-year-old man with a past medical history of recurrent meningeal hemangiopericytoma, currently referred to as SFT, presented to the hospital with jaundice. The patient was first diagnosed with an 8cm-sized meningeal hemangiopericytoma fourteen years ago and underwent osteoplastic craniotomy. After 16 mo, imaging showed recurrence and he underwent gamma knife radiosurgery (GKRS). 2 years later, imaging showed recurrence again leading to a second GKRS. 5 years later, recurrence was again suspected leading to a second craniotomy. Since then 3 years had passed, and imaging showed a 3.5cm-sized mass lesion on the pancreatic head with obstruction of the pancreatic and bile ducts. Endosonography with fine-needle aspiration biopsy was done preoperatively and aided in the diagnosis of SFT. The patient underwent pylorus-preserving pancreaticoduodenectomy. Pathologic findings of the resected pancreatic specimen, consistent with the previously resected brain specimen, confirmed the diagnosis of SFT. CONCLUSION: The rarity and lack of knowledge about SFTs make suspecting and diagnosing this disease challenging. We believe that a report of metastatic pancreatic SFT from the CNS will contribute to a better understanding of this rare disease.

Clinicopathological characteristics of extrahepatic biliary neuroendocrine neoplasms in the gallbladder, extrahepatic biliary tract, and ampulla of Vater: A single-center cross-sectional study.

Backgrounds/Aims: In 2019, the grading and staging system for neuroendocrine neoplasms (NENs) was significantly changed. In this study, we report the clinicopathological characteristics and surgical outcomes of patients with extrahepatic biliary NENs who underwent curative resection with or without adjuvant treatment. Methods: We retrospectively reviewed a database of 16 patients who developed NENs, neuroendocrine carcinoma (NEC), and mixed endocrine non-endocrine neoplasms (MiNENs) after curative resection. Among them, eight patients had ampulla of Vater (AoV) tumors, and eight patients had non-AoV tumors. Results: G1 and G2 were more frequently observed in the AoV group than in the non-AoV group (12.5% and 62.5%, respectively). In contrast, NEC and MiNEN were more common in the non-AoV group (50.0%). High Ki-67 index (> 20%) and perineural invasion (PNI) were more frequently observed in the non-AoV group. Advanced age (> 65 years), mitotic count > 20 per 2 mm2, and Ki-67 index > 20% were strongly correlated with patient survival (p = 0.018, 0.009, and 0.044, respectively). Advanced age (> 65 years) and mitotic count > 20 per 2 mm2 were significantly correlated with disease recurrence (p = 0.033 and 0.010, respectively). Conclusions: AoV and non-AoV tumors had significant differences in the histologic grade, Ki67, and PNI. Patients with non-AoV tumors had an increased risk for survival and recurrence than those in the AoV group. For extrahepatic biliary NENs, early detection of tumors, adequate surgery, and aggressive adjuvant treatment for high-risk patients are important to achieve long-term survival and prevent disease recurrence.

Guggulsterone protects against lipopolysaccharide-induced inflammation and lethal endotoxemia via heme oxygenase-1.

Guggulsterone (GS) is a phytosterol used to treat inflammatory diseases. Although many studies have examined the anti-inflammatory activities of GS, the detailed mechanisms of GS in lipopolysaccharide (LPS)-induced inflammation and endotoxemia have not yet been examined. Therefore, we investigated the anti-inflammatory effects of GS on LPS-induced inflammation. In murine peritoneal macrophages, the anti-inflammatory activity of GS was primarily mediated by heme oxygenase-1 (HO-1) induction. HO-1 induction by GS was mediated by GSH depletion and reactive oxygen species (ROS) production. The ROS generated by GS caused the phosphorylation of GSK3ß (ser9/21) and p38, leading to the translocation of nuclear factor erythroid-related factor 2 (Nrf2), which ultimately induced HO-1. In addition, GS pretreatment significantly inhibited inducible nitric oxide synthase (iNOS), iNOS-derived NO, and COX-2 protein and mRNA expression, and production of COX-derived prostaglandin PGE2, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α). In a mouse model of endotoxemia, GS treatment prolonged survival and inhibited the expression of inflammatory mediators, including IL-1ß, IL-6, and TNF-α. GS treatment also inhibited LPS-induced liver injury. These results suggest that GS-induced HO-1 could exert anti-inflammatory effects via ROS-dependent GSK (ser21/9)-p38 phosphorylation and nuclear translocation of Nrf2.

Catechin hydrate ameliorates cerulein­induced chronic pancreatitis via the inactivation of TGF­ß/Smad2 signaling.

Chronic pancreatitis (CP) is a pancreatic inflammatory disease associated with histological changes, including fibrosis, acinar cell loss and immune cell infiltration, and leads to damage of the pancreas, which results in pain, weight loss and loss of pancreas function. Catechin or catechin hydrate (CH) has antioxidant, anticancer and immune­regulatory effects. However, unlike other catechins, the antifibrotic effects of (+)­CH have not been widely studied in many diseases, including CP. Therefore, the anti­fibrotic effects of (+)­CH against CP were evaluated in the present study. To assess the prophylactic effects of CH, (+)­CH (1, 5 or 10 mg/kg) or ethanol was administered 1 h before first cerulein (50 µg/kg) injection. To assess the therapeutic effects, (+)­CH (5 mg/kg) or ethanol was administered after cerulein injection for one or two weeks. In both methods, cerulein was injected intraperitoneally into mice once every hour, six times a day, four times a week, for a total of three weeks, to induce CP. The data showed that (+)­CH markedly inhibited glandular destruction and inflammation during CP. Moreover, (+)­CH prevented pancreatic stellate cell (PSC) activation and the production of extracellular matrix components, such as fibronectin 1 and collagens, which suggested that it may act as a novel therapeutic agent. Furthermore, the mechanism and effectiveness of (+)­CH on pancreatic fibrosis were investigated in isolated PSCs. (+)­CH suppressed the activation of Smad2 and fibrosis factors that act through transforming growth factor­ß (TGF­ß) or platelet­derived growth factor. These findings suggest that (+)­CH exhibits antifibrotic effects in cerulein­induced CP by inactivating TGF­ß/Smad2 signaling.

Clinical significance of C-reactive protein-to-prealbumin ratio in predicting early recurrence in resectable pancreatic cancer.

PURPOSE: Resectable pancreatic ductal adenocarcinoma (PDAC) has a high risk of recurrence after curative resection; despite this, the preoperative risk factors for predicting early recurrence remain unclear. This study therefore aimed to identify preoperative inflammation and nutrition factors associated with early recurrence of resectable PDAC. METHODS: From March 2021 to November 2021, a total of 20 patients who underwent curative resection for PDAC were enrolled in this study. We evaluated the risk factors for early recurrence within 1 year by univariate and multivariate analyses using Cox hazard proportional regression. The cutoff values for predicting recurrence were examined using receiver operating characteristic (ROC) curves. RESULTS: In our univariate and multivariate analyses, C-reactive protein (CRP), CRP-albumin ratio, and CRP-prealbumin ratio, as well as sex and age, were significant independent prognostic factors for early recurrence in PDAC. However, known inflammatory factors (neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios), nutritional factors (albumin, prealbumin, ferritin, vitamin D), and inflammatory-nutritional factors (Glasgow Prognostic Score, modified Glasgow Prognostic Score, albumin-bilirubin) showed no association with early recurrence. In addition, using cutoff values by ROC curve analysis, a high preoperative CRP level of >5 mg/L, as well as high CRP-to-albumin (>5.3) and CRP-to-prealbumin (>1.3) ratios showed no prognostic value. CONCLUSION: Our results showed that inflammatory and perioperative nutritional factors, especially CRP-to-prealbumin ratio, have significant associations with early recurrence after curative resection in resectable PDAC. Therefore, for such patients, a cautious approach is needed when inflammation and poor nutritional status are present.

Risk Factors for Early- and Late-Onset Cholecystitis after Y-Configured Metal Stent Placement in Patients with Malignant Hilar Biliary Obstruction: A Single-Center Study.

This study evaluated the prevalence and risk factors of early- (within 7 days of placement) and late-onset (after 7 days of placement) cholecystitis after Y-configured metal stent placement. Between June 2005 and August 2020, 109 patients who had been treated with Y-configured metal stents for malignant hilar obstruction were enrolled in the study. We retrospectively analyzed the potential risk factors for post-stent cholecystitis. The presence of diabetes (p = 0.042), the length of the common part of the Y-stent (p = 0.017), filling of the gallbladder with contrast medium during the procedure (p = 0.040), and tumor invasion of the cystic duct accompanied by filling the gallbladder with contrast medium during metal stent placement (p = 0.001) were identified as important risk factors. In cases of late-onset cholecystitis, stent obstruction (p = 0.004) and repeated endoscopic procedures due to stent malfunction (p = 0.024) were significant risk factors. In the multivariate logistic regression analysis, significant risk factors were the length of the common part of the Y-stent (p = 0.032) in early-onset cholecystitis and stent obstruction (p = 0.007) in late-onset cholecystitis. This study demonstrated that early-onset cholecystitis may occur in patients according to the length of the common portion of the Y-stent. In contrast, late-onset cholecystitis may occur in patients with stent obstruction.

Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study.

BACKGROUND: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer. METHODS: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment. FINDINGS: Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 [56%] were female and 35 [44%] were male; 52 [65%] were Asian; median age was 64 years [IQR 58-70]) and seven in cohort 2 (five [71%] were male and two [29%] were female; five [71%] were Asian; median age was 62 years [IQR 58-77]). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 [74%] patients). The median duration of follow-up was 12·4 months (IQR 9·4-17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4-52·8]). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four [5%] patients) and decreased ejection fraction (three [3%] patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer. FUNDING: Zymeworks, Jazz, and BeiGene.

Postoperative delirium after cholecystectomy in older patients: A retrospective study.

Backgrounds/Aims: Postoperative delirium (POD) is a common complication that increases mortality and morbidity in older patients. This study aimed to evaluate the clinical significance of post-cholecystectomy delirium in older patients. Methods: This retrospective study included 201 patients aged > 75 years who underwent cholecystectomy for acute or chronic cholecystitis between January 2016 and December 2019. Patients were divided into the POD (n = 21) and non-POD (n = 180) groups, and their demographic features and clinical results were compared. Results: The mean patient age was 78.88 years; the female/male ratio was 44.8%/55.2%. Laparoscopic surgery was performed in 93.5% of patients. The univariate analysis showed that lower body mass index (BMI), immobilized admission status, neuropsychiatric disease history, preoperative intervention (percutaneous drainage), high C-reactive protein, hypoalbuminemia, neutrophilia, hypo-/hyperkalemia, and longer operative time were more frequently observed in the POD group. The multivariate analysis showed that lower BMI (odds ratio [OR], 2.796; p = 0.024), neuropsychiatric disease history (OR, 3.019; p = 0.049), hyperkalemia (OR, 5.972; p = 0.007), and longer operative time (OR, 1.011; p = 0.013) were significant risk factors for POD. Conclusions: POD was associated with inflammation degree, general condition, poor nutritional status, electrolyte imbalance, and stressful conditions. Recognizing risk factors requiring multidisciplinary team approaches is important to prevent and treat POD.

Patient-derived Organoid Model for Predicting the Chemoresponse in Patients With Colorectal Cancer.

BACKGROUND/AIM: Cancer mortality has decreased due to the contribution of extensive research on cancer treatment, including chemotherapy, radiation, and immunotherapy. However, histopathologically similar tumors originating from the same organ are treated with identical or similar chemotherapeutic regimens regardless of patient characteristics or cancer subtypes. The aim of this study was to evaluate the utility of organoids in predicting responses to chemotherapeutic agents. PATIENTS AND METHODS: This study retrospectively reviewed patient-derived organoids (PDOs) from 10 colorectal cancer patients to compare chemotherapy responses. Drug sensitivities for 5-fluorouracil (5-FU), cisplatin, oxaliplatin, and irinotecan were compared using GI50 (concentration that inhibits cancer cell growth by 50%). RESULTS: When organoids were treated with 5-FU, GI50 was the lowest compared to the other three chemotherapeutic agents (cisplatin, oxaliplatin, and irinotecan). The responsiveness to chemotherapeutic agents differed depending on specific patient characteristics including age, tumor location, stage, and gross type. The response of the patients' organoids to chemotherapeutic agents was consistent with the response to chemotherapy actually performed in those patients with cancer recurrence after surgery. CONCLUSION: PDOs may be useful as a preclinical model in predicting chemotherapy responses in cancer patients.