Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi-Institutional Collaborative Cohort Study.

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.

Characterization of colorectal cancer by hierarchical clustering analyses of five immune cell markers.

The present study analyzed the expression of five independent immunohistochemical markers, CD4, CD8, CD66b, CD68, and CD163, on immune cells within the colorectal cancer (CRC) tumor microenvironment (TME). Using hierarchical clustering, patients were successfully classified according to significant associations with clinicopathological features and/or survival. Patients with mismatch repair-proficient (pMMR) CRC were categorized into four groups with survival differences (p = 0.0084): CD4Low , CD4High , MΦHigh , and CD8Low . MΦHigh tumors showed significantly higher expression of CD47 (p < 0.0001), a phagocytosis checkpoint molecule. These tumors contained significantly greater numbers of PD-1+ (p < 0.0001), TIM-3+ (p < 0.0001), and SIRPA+ (p < 0.0001) immune cells. Notably, 10% of the patients with pMMR CRC expressed PD-L1 (CD274) on tumor cells with significantly worse survival (p = 0.00064). The Cox proportional hazards model identified MΦ High (hazard ratio [HR] = 2.02, 95%, p = 0.032), CD8Low (HR = 2.45, p = 0.011), and tumor PD-L1 expression (HR = 2.74, p = 0.0061) as potential risk factors. PD-L1-PD-1 and/or CD47-SIRPA axes targeting immune checkpoint therapies might be considered for patients with pMMR CRC according to their tumor cells and tumor immune microenvironment characteristics.

Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-cholesterol Levels in J-MICC Study Participants.

BACKGROUND: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, of which seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex, and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSION: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Coffee and metabolic phenotypes: A cross-sectional analysis of the Japan multi-institutional collaborative cohort (J-MICC) study.

BACKGROUND AND AIMS: To date, the relationship between coffee consumption and metabolic phenotypes has hardly been investigated and remains controversial. Therefore, the aim of this cross-sectional study is to examine the associations between coffee consumption and metabolic phenotypes in a Japanese population. METHODS AND RESULTS: We analyzed the data of 26,363 subjects (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Coffee consumption was assessed using a questionnaire. Metabolic Syndrome (MetS) was defined according to the Joint Interim Statement Criteria of 2009, using body mass index (BMI) instead of waist circumference. Subjects stratified by the presence or absence of obesity (normal weight: BMI <25 kg/m2; obesity: BMI ≥25 kg/m2) were classified by the number of MetS components (metabolically healthy: no components; metabolically unhealthy: one or more components) other than BMI. In multiple logistic regression analyses adjusted for sex, age, and other potential confounders, high coffee consumption (≥3 cups/day) was associated with a lower prevalence of MetS and metabolically unhealthy phenotypes both in normal weight (OR 0.83, 95% CI 0.76-0.90) and obese subjects (OR 0.83, 95% CI 0.69-0.99). Filtered/instant coffee consumption was inversely associated with the prevalence of MetS and metabolically unhealthy phenotypes, whereas canned/bottled/packed coffee consumption was not. CONCLUSION: The present results suggest that high coffee consumption, particularly filtered/instant coffee, is inversely associated with the prevalence of metabolically unhealthy phenotypes in both normal weight and obese Japanese adults.

[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.

The Impact of Marital Transitions on Vegetable Intake in Middle-aged and Older Japanese Adults: A 5-year Longitudinal Study.

BACKGROUND: Marital transitions are associated with adverse health events, such as mortality and cardiovascular disease. Since marital transitions (eg, becoming widowed) are unavoidable life events, it is necessary to identify modifiable intermediate outcomes. Thus, we examined the association between marital transitions and vegetable intake among middle-aged and older Japanese adults. METHODS: This longitudinal study included Japanese adults aged 40-79 years who received an annual health checkup between 2007 and 2011 (baseline) and 5 years later (follow-up). Marital transitions were classified as whether and what type of transition occurred during the 5-year period and comprised five groups: consistently married, married to widowed, married to divorced, not married to married, and remained not married. Changes in total vegetable, green and yellow vegetable, and light-colored vegetable intake from baseline to follow-up were calculated using the Food Frequency Questionnaire. RESULTS: Data from 4,813 participants were analyzed (mean age, 59.4 years; 44.1% women). Regarding marital transitions, 3,960 participants were classified as "consistently married," 135 as "married to widowed," 40 as "married to divorced," 60 as "not married to married," and 529 as "remained not married." Multivariable linear regression analysis revealed that compared to consistently married, married to widowed was inversely associated with the change in total vegetable intake (ß = -16.64, SE = 7.68, P = 0.030) and light-colored vegetable intake (ß = -11.46, SE = 4.33, P = 0.008). CONCLUSION: Our findings suggest that being widowed could result in a reduced intake of vegetables. Hence, dietary counseling according to marital situation is necessary.

Long-Term Trends in Respiratory Function After Esophagectomy for Esophageal Cancer.

BACKGROUND: Esophagectomy for esophageal cancer is known to lead to deterioration in respiratory function (RF). The aim of this study was to assess long-term trends in RF after esophagectomy and the impact of different operative procedures. METHODS: A total of 52 patients with thoracic esophageal cancer who were scheduled for esophagectomy from 2003 to 2012 were enrolled. We prospectively evaluated patients for vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and 6-min walk distance (6MWD) before and after esophagectomy at 3, 6, 12, 24, and 60 mo. RESULTS: Patients had mostly recovered their VC and FEV1.0 after 12 mo. After that point, VC and FEV1.0 declined again, reaching levels lower than baseline at 60 mo, with a median change ratio of 0.85 and 0.86, respectively. Although the 6MWD after open esophagectomy declined, patients treated with transhiatal esophagectomy and minimally invasive esophagectomy maintained above baseline levels throughout the follow-up period. Furthermore, we identified transhiatal esophagectomy (odds ratio [OR] = 0.03, 95% confidence interval [CI] 0.002-0.43, P = 0.01) and minimally invasive esophagectomy (OR = 0.14, 95% CI 0.02-0.94, P = 0.04) as favorable factors and postoperative pulmonary complication (OR = 9.14, 95% CI 1.22-68.6, P = 0.03) as an unfavorable factor for RF after 12 mo. Operative procedures had no significant impact on RF after 60 mo. CONCLUSIONS: Our results support the notion that RF does not recover to the baseline level, and operative procedures have no significant impact on RF at late phase after esophagectomy.

Tic Movement of Thyroid Cartilage as a Cause for Localized Cerebral Embolism: Mimics of Embolic Stroke of Undetermined Source with Non-Stenotic Carotid Plaque.

Several studies have suggested that non-stenotic carotid plaque was a risk factor for embolic stroke of undetermined source in some patients. However, individual backgrounds of these patients is unclear. We encountered a 64-years-old female with cerebral emboli, from an apparently stable non-stenotic carotid plaque (only 1.42mm thick) at the distal left common carotid artery, caused by violent tic movement of thyroid cartilage under well controlled dyslipidemia. Even though the plaque appeared thin and stable, mechanical stimulation could cause multiple, unnaturally localized emboli by stimulation-induced atherogenesis and plaque rupture, resulting in a misdiagnose of embolic stroke of undetermined source with non-stenotic carotid plaque.

[A Case of Pathological Complete Response of Colon Cancer after Systemic Chemotherapy with mFOLFOX6].

Neoadjuvant chemoradiotherapy is a standard mode of therapy for rectal cancer but not colon cancer. A 74-year-old man undergoing treatment for prostate cancer was found to have a tumor in both the sigmoid colon and liver. Colonoscopy showed a type 2 tumor of the sigmoid colon, with a biopsy confirming a diagnosis of well differentiated tubular adenocarcinoma. Computed tomography demonstrated a tumor of the sigmoid colon with metastasis to the liver. As there was a high suspicion of invasion of the left ureter, we decided to administer mFOLFOX6 as neoadjuvant chemotherapy prior to tumor resection. After 8 courses of mFOLFOX6, both the primary lesion and liver metastasis significantly decreased in size. Subsequently, the patient underwent a sigmoidectomy and partial hepatectomy. Histopathological examination revealed pathological complete response(Grade 3). It is important to reveal effective cases of neoadjuvant chemotherapy, the appropriate treatment regime and timing of surgical intervention so as to advance therapeutic strategies for the treatment of colon cancer.

[Staged Laparoscopy-Assisted Surgery Including Hand-Assisted Laparoscopic Surgery for Rectal Cancer with Synchronous Liver Metastases-A Case Report].

Here, we reported a case of a 39-year-old woman having rectal cancer with multiple liver metastases who underwent staged laparoscopic resection. She was diagnosed with low rectal cancer and multiple liver metastases; thus, she underwent low anterior resection and diverting colostomy. Following the neoadjuvant chemotherapy, she underwent colostomy closure and subsequent hand-assisted laparoscopic partial hepatectomy using the operative site during the colostomy closure. The postoperative course was uneventful, and adjuvant chemotherapy with CapeOX was performed 3 weeks post-surgery. Minimally invasive surgery was performed using hand-assisted laparoscopy.

[Chemoresistance in Microsatellite Instability-High Gastric Cancer-A Case Report].

A 74-year-old woman with cT4aN2M0, cStage ⅢB gastric cancer underwent neoadjuvant chemotherapy comprising 2 courses of S-1 plus cisplatin, and the clinical response was determined as non-CR/non-PD according to RECIST ver 1.1. Although distal gastrectomy with D2 lymphadenectomy was planned, the tumor was considered as unresectable with peritoneal metastases during laparotomy. After the subsequent chemotherapy with 1 course of capecitabine plus cisplatin, tumor bleeding, and obstruction due to rapid tumor progression occurred. We performed palliative distal gastrectomy; however, the patient died 17 days after gastrectomy. A comprehensive genomic analysis using cancer-gene panel identified the tumor as a microsatellite instability-high(MSI-H). Recently post hoc analysis of the large-scale clinical trials showed no clinical benefit of perioperative chemotherapy in MSI-H gastric cancer. MSI status has a potential to optimize the perioperative treatment strategy in gastric cancer.

[Two Episodes of Colostomy-Associated Intestinal Perforation during Chemotherapy for Metastatic Rectal Cancer].

A 77-year-old woman with rectal cancer and synchronous liver metastasis underwent a Hartmann operation with D3 lymph node dissection in June 2014. mFOLFOX6 plus bevacizumab(bev)was then administered to treat the liver metastasis.In February 2015, multiple liver metastases were detected and the regimen was changed to FOLFIRI plus bev.After 3 courses, peritonitis due to intestinal perforation around the descending colostomy occurred, and an emergency operation(partial resection of the descending colon and transverse colostomy)was performed.FOLFIRI was then administered from 2 months after the operation.After 3 courses of this regimen, a CT scan showed progression of the hepatic metastases.The regimen was therefore changed to mFOLFOX6.Five months later, another CT scan showed an intestinal perforation of the transverse colostomy at the abdominal wall, and an emergency cecostomy was performed.At this stage, chemotherapy was ceased.This case highlights the risk of intestinal perforation during chemotherapy, regardless of the use of bev.

[Surgical Resection after Gemcitabine plus Cisplatin Chemotherapy for Intrahepatic Cholangiocarcinoma with Multiple Lymph Node Metastases - Report of a Case].

An 82-year-old man with upper abdominal pain was referred to our hospital because of an elevated serum CEA level and dilatation of the intrahepatic bile ducts on ultrasonography.Computed tomography revealed a hypovascular mass measuring 5.0 cm in size in the lateral section, dilatation of the peripheral intrahepatic bile ducts, and swollen lymph nodes around the lesser curvature of the stomach, the common hepatic artery, and the paraaorta.He was diagnosed with unresectable intrahepatic cholangiocarcinoma, and he received chemotherapy with biweekly gemcitabine plus cisplatin.After 33 courses of the chemotherapy, computed tomography revealed that the tumor size decreased over 63%, and all swollen lymph nodes had almost resolved.He underwent a left hemihepatectomy 1 year 6 months after the start of the chemotherapy.He remains alive and well with no evidence of recurrence, 11 months after resection.

[A Case of Advanced Gastric Cancer with Portosystemic Shunt Successfully Treated with Percutaneous Transvenous Coil Embolization].

A 57-year-old man with advanced gastric cancer and multiple liver metastases was referred to our hospital. He underwent a palliative gastrectomy to treat hemorrhage, and S-1 and cisplatin therapy was administered. After 7 courses of chemotherapy, a new liver metastatic lesion and a tumor thrombus in the right portal vein appeared. Moreover, the serum level of ammonia was elevated(296 mg/dL)following a consciousness disorder. Enhanced CT revealed an inferior mesenteric vein to left renal vein shunt, which led to the diagnosis of portal systemic encephalopathy due to portosystemic shunt. Percutaneous transvenous coil embolization was performed. The serum ammonia level decreased, and the encephalopathy disappeared. As a result, he was able to continue chemotherapy.

[A Case of Advanced Gastric Cancer Resected for Rebleeding after Palliative Radiotherapy for Hemostasis].

We report a case of advanced gastric cancer(AGC)that was resected for rebleeding after palliative radiotherapy for hemostasis. A 74-year-old man with Stage IV gastric cancer received chemotherapy and achieved stable disease. After 23 months, he experienced continuous bleeding from the tumor due to regrowth. Palliative radiotherapy was conducted to control the bleeding, and the tumor successfully achieved hemostasis. However, 6 weeks later, the patient experienced rebleeding and developed hemostatic shock. We then performed a successful emergency gastrectomy. Bleeding negatively affects quality of life in patients with AGC and is potentially lethal. Although palliative radiotherapy for bleeding of gastric cancer is a safe and useful treatment within a short time frame in cases of rebleeding, emergency gastrectomy may be necessary. Therefore, when we select this treatment, the possibility of subsequent surgical treatment must be considered.

[A Case of Simultaneous Multiple Gastric Cancers Showing Differences of Response after Neoadjuvant Chemotherapy with Docetaxel, CDDP, and S-1].

A 63-year-old man with epigastralgia was referred to our hospital and diagnosed with simultaneous multiple gastric cancers. One lesion was type 2 advanced and the other was type 0- II c early gastric cancer. CT examination revealed 4 regional lymph node metastases. Neoadjuvant chemotherapy(NAC)with docetaxel/CDDP/S-1was administered. After 2 courses of NAC, total gastrectomy with D2(-No. 10), lymphadenectomy was performed. The pathological response to NAC was judged to be Grade 3 for advanced gastric cancer and Grade 0 for early gastric cancer. The patient is alive with no evidence of disease during the 10 months after the operation.

[A Case of Long-Term Survival of a Patient with Liver Metastasis of Colon Cancer and Suspected Inferior Vena Cava Invasion].

A 58-year-old woman was diagnosed with a sigmoid colon cancer and synchronous liver metastasis. Because an obstruction of the sigmoid colon was identified, the patient underwent sigmoidectomy. Computed tomography(CT)findings suggested possible vena cava and hepatic vein invasion. Therefore, the decision was made to offer systemic chemotherapy. The patient underwent 6 courses of chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6). After 4 courses of chemotherapy, CT scans showed a significant reduction of the liver metastasis (reduction rate of 5 0%; a partial response) and demonstrated improved exclusion of the inferior vena cava and hepatic vein. After 6 courses of chemotherapy, we performed right trisegmentectomy of the liver and resection of the inferior vena cava and diaphragm. Postoperative pathological findings revealed negative margins, and no invasion of the inferior vena cava. The pathological response grade of the tumor after chemotherapy was determined to be Grade 2. Adjuvant chemotherapy was not performed because of the patient 's poor performance status. The patient was alive with no recurrence 8 years after resection of the liver metastasis.

[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.

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.