[Six Cases of Esophagogastric Junctional Cancer Successfully Treated with Neoadjuvant Chemotherapy].

Neoadjuvant chemotherapy(NAC)is prescribed for resectable esophagogastric junctional cancer on the basis of esophageal invasion length, lymph node metastasis, and pathological diagnosis. Due to a lack of consensus in Japan, however, discussion regarding its use is necessary. This study comprised 6 patients who underwent surgical resection after receiving NAC in our department from 2018 to 2022. All the patients were male, with a median age of 67 years. Three patients underwent SP therapy, 2 received SOX therapy, and 1 received both SOX and HER therapy. A total gastrectomy was performed in 3 cases, a fundectomy in 1 case, and a subtotal esophagectomy with gastric tube reconstruction in 2 cases. The histological types were tub2 in 3 cases; and tub1 plus pap, por1 plus pap, and NEC in 1 case each, respectively. One case was ypStage ⅠA, 2 cases were ⅠB, 1 was ⅡA, 1 was ⅡB and 1 was pCR. Currently, all the patients remain alive and without recurrence. NAC has, therefore, been demonstrated to be an effective therapeutic strategy for esophagogastric junctional cancer in this study. However, further research with a larger sample size is required.

Gender and age variations in the association between multigenerational cohabitation and self-rated health among middle-aged and older adults in Japan.

Despite encouraging multi-generational cohabitation, the population of Japanese people living alone has increased. However, little is known about the association between health and multigenerational cohabitation. This study examined the relationship between self-rated health and living arrangements among Japanese adults using data from the Japan Multi-Institutional Collaborative Cohort Study (2013-2017). The analysis employed multivariate logistic regression to examine the associations. Our results showed no association between living arrangements and self-rated health when stratified by gender. Living alone was found to be associated with poor self-rated health among women aged 65 and above. A similar association may exist among men in the same age group. Among women aged < 65 years, two-generation cohabitation was associated with a good self-rated health, similar to those living alone. Among men aged < 65 years, neither living alone nor two-generation cohabitation was significantly associated with good self-rated health. We found no association between three- or plus-generation cohabitation and self-rated health. Therefore, our findings indicate associations between multigenerational cohabitation and self-rated health, but they vary by gender and age. Invested stakeholders in the public health field should consider the potential impact of living arrangements on health based on gender and age.

Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis.

Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.

Positive association between blood glucose in physical examinations and self-reported fractures among middle-aged and elderly Japanese men: a prospective cohort study.

The association between blood glucose and fractures is not consistent across populations. Blood glucose was associated with fractures five years later in middle-aged and elderly men who underwent health examinations in Japan, respectively. Blood glucose-targeted fracture alerts are crucial for middle-aged and elderly individuals. OBJECTIVES: The evidence on blood glucose as a fracture risk marker has not been adequately examined in various populations, and there are no studies in middle-aged Japanese. We aimed to determine the association between blood glucose status and self-report fractures among middle-aged and elderly Japanese men. METHODS: The data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Okazaki Study were used. Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) measured at baseline physical examinations were examined for association with fractures questioned five years later. Analyses were performed for the middle-aged and elderly respondents. RESULTS: The HbA1c was dichotomized into 290 (11.8%) with HbA1c ≥ 6.5% and 2165 (88.2%) with HbA1c < 6.5%. Compared to the group with an HbA1c < 6.5, the odds ratio for the risks of fracture among the group with an HbA1c ≥ 6.5% were 3.46 (95% confidence interval (CI), 1.75-6.84) in Model 1 (adjusted for age) and 3.60 (95% CI, 1.77-7.34) in Model 2 (adjusted for various confounding factors). These associations were also observed in both middle-aged and elderly generations, whereas no association was observed for FPG. CONCLUSIONS: Among Japanese men who have undergone physical examinations, those with an HbA1c of 6.5% or higher are at higher risk for fractures, and HbA1c-targeted fracture alerts are crucial for middle-aged and elderly individuals.

[A Case Report of Successful Treatment with Dose-controlled mFOFOX6+Bevacizumab for Metastatic Colorectal Cancer in Patient Receiving Hemodialysis].

A 65-years-old man undergoing hemodialysis for chronic kidney disease was diagnosed with ascending colon cancer and 3 hepatic metastases. He was administered mFOLFOX6 (reducing the dose to 50%) plus bevacizumab (BEV) therapy. Hemodialysis was performed 4 h after administration of oxaliplatin on day1 and repeated three times a week. No serious adverse events were observed. After 4 courses of chemotherapy, a computer tomography scan showed that the hepatic metastases had reduced. 2 courses of mFOLFOX6 (increasing the dose to 75%) plus BEV therapy were added, he was operated by laparoscopic right hemicolectomy and laparoscopic patrial hepatectomy. He has been in remission for 2 years and 4 months since the surgery. Dose-adjusted chemotherapy with hemodialysis was effective and improve the prognosis of the patient.

Common and rare genetic variants predisposing females to unexplained recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10-10; odds ratio [OR] = 1.51 [95% CI: 1.33-1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10-10, 1.5 × 10-10, and 1.2 × 10-9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10-10; OR = 0.65 [95% CI: 0.57-0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10-4; OR = 3.29 [95% CI: 1.78-5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.

Tumor diameter and enhancing capsule, as well as previous interventional treatments, as potential predictors of vascular lake phenomenon in hepatocellular carcinoma patients treated with drug-eluting beads transarterial chemoembolization.

Objectives: The initial drug-eluting bead (DEB)-transarterial chemoembolization (TACE) are often performed after multiple sessions of transarterial infusion chemotherapy (TAI) or conventional TACE. The purpose of our study was to evaluate the factors associated with the occurrence of vascular lake phenomenon (VLP) during DEB-TACE, considering the previous interventional treatments. Material and Methods: Forty-nine initial DEB-TACE procedures in 49 patients between November 2010 and April 2024 were included in this retrospective study. VLP was defined as a localized pooling of contrast agents within the tumor in the venous phase of digital subtraction angiography. The laboratory data, pre-treatment imaging findings such as the maximum tumor diameter (≥3 cm or <3 cm) and the presence of enhancing capsule obtained from computed tomography or magnetic resonance imaging, size of DEBs, and loading drugs, the total number of previous interventional treatments were recorded and compared between VLP occurrence and VLP non-occurrence groups. The multivariate logistic regression analysis was performed to explore the association of factors in predicting VLP occurrence. Results: VLP was observed in 16 patients (32.65%) out of 49 patients. The maximum tumor diameter (≥3 cm) and the presence of the enhancing capsule were significantly higher, and the total number of previous interventional treatments was significantly smaller in the VLP occurrence group than in the VLP non-occurrence group (P = 0.0006, 0.0007, and 0.0003). In multivariate analysis, the maximum tumor diameter, the presence of the enhancing capsule, and the total number of previous interventional treatments were significantly associated with the occurrence of VLP (P = 0.0048, 0.0093, and 0.047). Conclusion: Our study confirmed that the reported risk factor, the maximum tumor diameter, and the enhancing capsule were significantly related to the occurrence of VLP in DEB-TACE. Further, the occurrence of VLP might be carefully considered when the number of previous interventional treatments is small.

Characterisation of colorectal cancer by hierarchical clustering analyses for five stroma-related markers.

Evidence for the tumour-supporting capacities of the tumour stroma has accumulated rapidly in colorectal cancer (CRC). Tumour stroma is composed of heterogeneous cells and components including cancer-associated fibroblasts (CAFs), small vessels, immune cells, and extracellular matrix proteins. The present study examined the characteristics of CAFs and collagen, major components of cancer stroma, by immunohistochemistry and Sirius red staining. The expression status of five independent CAF-related or stromal markers, decorin (DCN), fibroblast activation protein (FAP), podoplanin (PDPN), alpha-smooth muscle actin (ACTA2), and collagen, and their association with clinicopathological features and clinical outcomes were analysed. Patients with DCN-high tumours had a significantly worse 5-year survival rate (57.3% versus 79.0%; p = 0.044). Furthermore, hierarchical clustering analyses for these five markers identified three groups that showed specific characteristics: a solid group (cancer cell-rich, DCNLowPDPNLow); a PDPN-dominant group (DCNMidPDPNHigh); and a DCN-dominant group (DCNHighPDPNLow), with a significant association with patient survival (p = 0.0085). Cox proportional hazards model identified the PDPN-dominant group (hazard ratio = 0.50, 95% CI = 0.26-0.96, p = 0.037) as a potential favourable factor compared with the DCN-dominant group. Of note, DCN-dominant tumours showed the most advanced pT stage and contained the lowest number of CD8+ and FOXP3+ immune cells. This study has revealed that immunohistochemistry and special staining of five stromal factors with hierarchical clustering analyses could be used for the prognostication of patients with CRC. Cancer stroma-targeting therapies may be candidate treatments for patients with CRC.