Ibaraki Prefectural Central Hospital

Metastatic colorectal cancer (mCRC) differs clinically based on RAS and BRAF mutations or DNA methylation. However, in mCRC, the prognostic value and biological characteristics of genome-wide DNA methylation status (GWMS) in each RAS/BRAF genotype is unknown. To clarify this, primary tumor samples from patients with informed consent in the phase III TRICOLORE study were collected, and RAS and BRAF mutations, immunohistochemical staining of mismatch repair-related proteins, comprehensive gene expression, and genome-wide DNA methylation were analyzed. The tumor samples were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Gene set enrichment analysis (GSEA) was conducted using microarray data. A total of 226 patients were included and classified into the RAS/BRAF wild-type (wt) (n = 125), RAS mutant (mt) (n = 87), and BRAF mt (n = 14), of whom 22 (17.6%), 30 (34.5%), and 14 (100%) had HMCC. HMCC exhibited significantly worse overall survival (OS) than that of LMCC in the RAS/BRAF wt group but not in the RAS mt group. In GSEA, RAS/BRAF wt HMCC was associated with microsatellite instability and BRAF V600E mutation. The poor prognosis of RAS/BRAF wt HMCC may be attributed to gene expression patterns associated with microsatellite instability and BRAF V600E mutation.

Pulmonary vascular invasion is a well-recognized feature of advanced lung cancer and is associated with poor prognosis. Vascular invasion usually refers to either microscopic invasion into small vessels or direct invasion of great vessels; however, longitudinal subintimal spread within the pulmonary artery has not been reported. We describe the case of a 77-year-old woman with a pulmonary nodule followed for two years, which enlarged to 23 mm with cavitation. A right upper lobectomy with mediastinal lymph node dissection was performed. Histopathology showed that the tumor was predominantly adenocarcinoma. In addition, longitudinal invasion was identified beneath the intima of the pulmonary artery, located between the lumen and elastic fibers without extension into the lumen or outside the vessel wall. Notably, in this subintimal invasive area, the central portion consisted of adenocarcinoma, whereas squamous differentiation was confined to the surrounding margins. The primary nodule measured 2.5 cm, but the total extent of subintimal invasion was 6 cm. The pathological stage was pT3N0, stage IIB. This case demonstrates a previously unreported pattern of pulmonary artery invasion by lung adenocarcinoma with characteristic marginal squamous differentiation, expanding the spectrum of vascular invasion in lung cancer.

164 Background: BRAF inhibitor combination therapies, triplet (encorafenib, binimetinib and cetuximab) and doublet (encorafenib and cetuximab), have been approved for BRAF -mutated metastatic colorectal cancer (mCRC) in Japan. The treatment with triplet is recommended for patients (pts) with clinical prognostic factors according to the sub-group analysis of the BEACON CRC trial. However, it is unclear whether the treatment strategy is useful. We therefore conducted a study on the use of combination therapy with triplet or doublet based on observational study that accumulated real world data. Methods: The BEETS trial was a multicenter observational study to prospectively evaluate the efficacy and safety of BRAF inhibitor combination therapy as a 2nd- or 3rd-line treatment in pts with BRAF -mutated mCRC in clinical practice [UMIN000045530]. Two hundred pts were assigned to either triplet or doublet therapy based on the physician’s choice. The primary endpoint was overall survival (OS). The secondary endpoints included overall response rate (ORR), disease control rate, progression-free survival (PFS), and safety. The exploratory analysis was performed to evaluate the efficacy of triplet and doublet therapies in all pts and pts with clinical prognostic factors (PS1, 3 or more metastatic sites, elevated CRP value, or primary tumor present) using inverse probability weighting (IPW) analysis based on propensity scores to account for potential cofounding factors. Results: Among 203 pts enrolled from Oct 2021 to Nov 2023, 195 pts were evaluable (median age 67 years old, 52% male, ECOG PS 0/1/2 55%/39%/6%, no. of prior regimens 1/2 85%/15%, right-sided primary 61%, MSI-high 7%, triplet regimen 57%). Median OS was 13.2 months (95%CI 11.4-17.4) with 1y-survival rate of 53%, and median PFS was 4.9 months. Comparing the triplet and doublet using IPW, the median OS and PFS were comparable between the two treatments (triplet vs. doublet; 16.0 months vs. 13.6 months [HR 0.88, 95%CI 0.53-1.48] and 5.7 months vs. 4.8 months [HR 0.87, 95%CI 0.59-1.28]). In 139 pts with any prognostic factors, median OS and 1y-survival rate were 13.2 months vs. 9.6 months [HR 0.80, 95%CI 0.45-1.43] and 54% vs. 42%, median PFS and ORR were 5.3 months vs. 4.2 months [HR 0.75, 95%CI 0.48-1.19] and 34% vs. 42%, in the triplet vs. doublet therapy, respectively. Conclusions: Our study demonstrated that BRAF inhibitor doublet therapy is a reasonable treatment for BRAF -mutated mCRC. However, triplet therapy may be a clinically useful for pts with clinical prognostic factors. Clinical trial information: UMIN000045530 .

ABSTRACTINTRODUCTIONBile duct injury is a rare but serious complication of laparoscopic cholecystectomy (LC), particularly in patients with biliary anomalies such as accessory hepatic ducts (AHDs). Indocyanine green (ICG) fluorescence imaging has recently been recognized as a valuable tool for intraoperative visualization of biliary anatomy. However, its application in Type I AHDs, as classified by Hisatsugu, has not been previously reported.CASE PRESENTATIONA 35-year-old male was referred for elective LC following successful conservative treatment for mild acute cholecystitis. Preoperative magnetic resonance cholangiopancreatography revealed that the cystic duct drained into a posterior AHD arising from segment 6, consistent with a Type I anomaly according to the Hisatsugu classification. At anesthesia induction, 2.5 mg of ICG was administered intravenously, and near-infrared fluorescence imaging enabled clear identification of the biliary anatomy, including the AHD. Despite mild chronic inflammation, Calot’s triangle was safely dissected, and the gallbladder was successfully removed. Post-resection ICG imaging confirmed the integrity of the AHD, with no evidence of injury or stricture. The operative time was 3 h and 30 min, and the patient was discharged without complications on POD 3.CONCLUSIONSIntraoperative ICG fluorescence imaging allowed for safe and accurate identification of biliary anatomy in a patient with a Type I AHD anomaly. This technique may help reduce the risk of bile duct injury during LC in patients with complex biliary variations.

This study aimed to investigate prognostic factors for predicting the survival of patients with extensive-disease-stage small-cell lung cancer treated with chemoimmunotherapy. Patients were classified according to overall survival (OS): favorable corresponded to an OS ≥ 24 months, moderate corresponded to an OS of 6-24 months, and poor corresponded to an OS < 6 months. Multivariate Cox regression analyses were used to evaluate prognostic factors. Of 130 patients, the proportions of performance status decline and liver metastasis were significantly higher in the poor-prognosis group. With regard to the laboratory findings, neutrophil/lymphocyte ratios and albumin levels differed significantly among the groups. Multivariate analysis showed that the independent prognostic factors for OS were liver metastasis and decreased albumin levels (<3.5 mg/dL). After classifying the patients into three groups according to the quantities of these prognostic factors, the OS differed significantly among the groups (18.3 vs. 13.5 vs. 3.8 months; p < 0.001). The incidence of immune-related adverse events (irAEs) was higher in patients without these prognostic factors than in those with both (36% vs. 5%; p = 0.01). Liver metastasis and decreased albumin levels are independent unfavorable prognostic factors. Patients with both prognostic factors showed unfavorable OS; however, patients without these factors may have a favorable prognosis but be at greater risk of irAEs.

BackgroundLifestyle modifications by educational sessions are an important component of multidisciplinary treatment for chronic kidney disease (CKD). We attempted to identify the best method to teach these modifications in order to ensure their acceptance by patients and investigated its effectiveness in CKD practice.MethodsThis study is a post-hoc analysis of the FROM-J study. Subjects were 876 CKD patients in the advanced care group of the FROM-J study who had received lifestyle modification sessions every 3 months for 3.5 years. Two-hundred and ten males (32.6%) and 89 females (38.2%) showed success in sodium restriction. In this study, we examined factors affecting sodium restriction in these subjects.ResultsSubjects received three or more consecutive educational sessions about improvement of salt intake. The median salt-intake improvement maintenance period was 407 days. The number of dietary counseling sessions (OR 1.090, 95%CI: 1.012–1.174) in males and the number of dietary counseling sessions (OR 1.159, 95%CI: 1.019–1.318), CKD stage progression (OR 1.658, 95%CI: 1.177–2.335), and collaboration with a nephrologist (OR 2.060, 95%CI: 1.073–3.956) in females were identified as significant factors improving salt intake. The only factor contributing to the maintenance of improved salt intake was the continuation of dietary counseling (p = 0.013).ConclusionAn increased number of educational sessions was the only successful approach for males to implement and maintain an improved salt intake. Providing the resources for continuous counseling is beneficial for lifestyle modifications and their maintenance in the long-term management of CKD. Continuous counseling for lifestyle modifications is highly cost-effective.Trial registrationThe FROM-J study was registered in UMIN000001159 on 16/05/2008.

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.