Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of ...methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.
Background
The optimal treatment for liver metastasis from gastric cancer (LMGC) remains uncertain. The relevance of surgical resection is controversial. We conducted a prospective multicenter ...interventional study of surgical resection for LMGC.
Patients and Methods
Patients with synchronous or metachronous LMGC who were surgically fit were registered. The primary endpoint was 3-year overall survival (OS) of patients who underwent R0 resection. Secondary endpoints were R0 resection rate, operative morbidity and mortality, 3-year recurrence-free survival (RFS) of R0 patients, and OS in all registered patients.
Results
Seventy patients were registered from 24 institutions between December 2011 and November 2019 and received preoperative chemotherapy. Three patients were ineligible, and 19 patients discontinued treatment, with disease progression in 12, adverse events in 4, and consent withdrawal in 3 before surgery. Of the 48 patients eventually undergoing surgery, R0 resection of the primary and/or metastatic GC was accomplished in 43 patients, while 1 patient discontinued treatment for positive peritoneal lavage cytology and 4 patients were considered ineligible based on postoperative pathological findings other than GC. The R0 resection rate of all eligible patients was 68.3% 95% confidence interval (CI) 55.3–79.4%, 43/63 patients, while that of all resected patients was 89.6% (95% CI 77.3–96.5%, 43/48 patients). Postoperative complications were identified in 12 out of 43 patients (27.9%), and Clavien–Dindo grade III or higher complications occurred in seven patients (16.3%). No hospital mortality was observed.
Conclusions
R0 resection for LMGC could be performed in approximately two-thirds of all eligible patients, with acceptable surgical morbidity and mortality.
Background
It has been reported that both fibrinogen and the neutrophil–lymphocyte ratio (NLR) are related to the degree of malignancy in various types of cancer. This study compared the combined ...index of fibrinogen and NLR (F-NLR) with NLR alone for predicting the prognosis of patients with resectable gastric cancer.
Methods
We collected data on 666 patients with resectable gastric cancer. Patients were divided into three F-NLR score groups based on the following criteria: score 2, both hyperfibrinogenemia (≥350 mg/dl) and high NLR (≥2.5); score 1, either hyperfibrinogenemia or high NLR; and score 0, neither abnormality. The association between prognosis and NLR alone or F-NLR was evaluated using the Kaplan–Meier method and Cox multivariate analysis.
Results
The high-NLR group had significantly worse overall survival (OS) than the low-NLR group (hazard ratio 1.62; 95% confidence interval CI 1.07–2.45; log-rank
P
= 0.022), but there was no significant difference between the high- and low-NLR groups after adjusting for the fibrinogen level. F-NLR groups showed significantly different OS (log-rank
P
< 0.001) and recurrence-free survival (log-rank
P
< 0.001). The 5-year OS rate for the groups with F-NLR scores of 2, 1, and 0 was 72.6%, 81.4%, and 90.4%, respectively. A Cox multivariate analysis of OS revealed that a high F-NLR score (1 or 2) was an independent prognostic factor (
P
= 0.007).
Conclusions
F-NLR was an independent prognostic factor in patients with gastric cancer and a more useful prognostic indicator than NLR alone.
A new strategy for catalytic functionalization of C−H bonds by means of electrochemical oxidation is described. Combination of palladium-catalyzed aromatic C−H bond cleavage and halogenation with ...electrochemically generated halonium ions enables highly efficient, selective halogenations of aromatic compounds in a green-sustainable manner. The required reagents for this reaction are an arene and an aqueous hydrogen halide as substrates, a palladium salt as a catalyst, and an organic solvent. No further additives such as electrolytes, oxidants, or ligands are necessary to achieve effective catalytic activity. Several remarkable advantages of the use of the electrochemical method are also described.
Abstract Background Reports on health-related quality of life (HRQOL) of Asian populations after acute myocardial infarction (AMI) and its predictors are rare. We describe the longitudinal HRQOL ...course after AMI, hypothesizing that post-discharge depressive symptoms predict poor recovery of HRQOL in Japan. Methods AMI survivors participated in a prospective cohort study of AMI patients admitted to 5 hospitals in Japan. Data from 218 consecutive male patients were analyzed. HRQOL was measured with Short-Form Health Survey-36 at 1, 6, and 12 months post-discharge. Five-question Mental Health Inventory (MHI-5) assessed presence of depressive symptoms. Multiple linear regression analyzed the relationship between depressive symptoms at 1 month and recovery of HRQOL at 6 months. Results AMI patients at 12 months after discharge had lower HRQOL in physical function (47.8), role-physical (44.1), general health (46.4), social function (47.4), and role-emotional (45.8) than the Japanese national norm. Impairment of each domain of HRQOL was seen in 36%–71% of patients. Multivariate analysis showed that depressive symptoms at 1 month post-discharge adversely affected recovery of physical function ( β = − 2.62; CI: − 5.00 to − 0.23), role-physical ( β = − 3.50; CI: − 6.94 to − 0.06) and bodily pain ( β = − 2.92; CI: − 5.26 to − 0.59) at 6 months. Conclusions Despite good prognosis for survival of discharged AMI patients, HRQOL did not recover to the national norm. Post-discharge depressive symptoms were significantly associated with poor recovery of the physical component of HRQOL. Increasing awareness of depressive symptoms in discharged AMI patients may improve survivor HRQOL.
Alagille syndrome (AGS, MIM 118450) is an autosomal dominant inherited disease. Paucity of interlobular bile ducts is one of the major abnormalities. To explore the molecular mechanism by which ...mutation in the human Jagged 1 gene (JAG1, MIM 601920) causes liver defects, we investigated the gene regulation of JAG1 to hepatocyte growth factor gene (HGF). By transfecting wild-type and mutant JAG1 into COS-7 cells
in vitro, we found that HGF is a target gene of JAG1 downstream. Wild-type JAG1 is inhibitory for HGF expression and mutant JAG1s relieve the inhibition. Several domain disruptions in mutant JAG1 protein reveal a reduced inhibition to HGF expression at different levels. JAG1 mutations actually result in HGF overexpression. Furthermore, JAG1 controls HGF expression by a dosage-dependent regulation and Notch2 signaling seems to mediate JAG1 function. Given that HGF plays a critical role in differentiation of hepatic stem cells, overexpression of HGF acts on off-balanced cell fate determination in AGS patients. Hepatic stem cells may differentiate towards more hepatocytes but less biliary cells, thus causing the paucity of interlobular bile ducts in liver development of AGS. Our novel findings demonstrated that dosage-dependent regulation by mutations of JAG1 is a fundamental mechanism for liver abnormality in AGS.
Abstract only
397
Background: In locally advanced, resectable gastric or gastro-oesophageal junction (EGJ) adenocarcinoma, perioperative the docetaxel-based triplet FLOT (fluorouracil plus ...leucovorin, oxaliplatin and docetaxel) is the standard chemotherapy in Europe. However, there is no evidence of neoadjuvant chemotherapy for resectable gastric cancer in Japan. Therefore, we conducted a phase II trial of neoadjuvant chemotherapy with docetaxel plus oxaliplatin, and S-1 (DOS) for locally advanced, resectable gastric or EGJ adenocarcinoma. Methods: Eligible patients had histologically confirmed gastric or EGJ adenocarcinoma of a clinical Stage III according to the 14th Edition of Japanese Classification of Gastric Carcinoma. DOS was administered for two or three preoperative cycles followed by eight postoperative cycles of S-1. Each 3-week cycle of DOS consisted of docetaxel 40 mg/m
2
and oxaliplatin 100 mg/m
2
on day 1 plus S-1 80-120 mg/body on days 1 to 14. Primary endpoint was 3-year progression-free survival rate, and secondary endpoints included overall survival, progression-free survival, response rate, histological response rate, R0 resection rate, and adverse events. Results: Of 50 enrolled patients, 48 (37 gastric and 11 EGJ) were eligible for the analysis. 42 (88%) patients completed two or three preoperative cycles of DOS. The most common grade 3-4 adverse events of DOS were neutropenia (69%), leukopenia (56%), diarrhea (19%), and febrile neutropenia (13%). Of 45 patients who underwent gastrectomy, postoperative morbidities (Clavien-Dindo ≥Grade II) occurred in 12 (27%) patients. R0 resection could be achieved in 43 (90%) patients. 12 (27%) and 30 (67%) of 45 patients achieved pathological response rate of Grade2-3 and Grade1b-3, respectively. There was no treatment-related death. Conclusions: Neoadjuvant DOS for locally advanced, resectable gastric or EGJ adenocarcinoma might be favorable. Long-term results will be published in two years. Clinical trial information: 000017652.
A 54-year-old female was admitted to hospital complaining of oppressive anterior chest pain during exercise. Treadmill exercise ECG testing showed significant ischemic ECG changes, and electron-beam ...computed tomography demonstrated patchy calcifications in the coronary artery. Coronary angiography revealed a significant stenotic lesion of the right coronary artery. On routine investigations, no classical coronary risk factors were found, although a very high concentration (209 mg/dl) of high-density lipoprotein cholesterol (HDL-C) was detected. The serum concentration of cholesteryl-ester transfer protein (CETP), which plays a central role in the reverse cholesterol transport system, was measured and found to be less than the measurable minimum. The patient showed one of the typical genetic CETP mutations (intone 14 splicing defect), and her lipid profile was improved by administration of probucol for 3 months. A very high concentration of HDL-C with a defect of CETP activity may be a specific biochemical indicator pointing to an increased risk of premature coronary artery disease, and the lipid profile can be improved by use of lipid-lowering drugs. (Circ J 2005; 69: 609 - 612)
Background: Since the 1980s, the number of foreign residents in Japan has continuously been on the rise. In order to improve the foreign resident support services infrastructure and effectiveness, a ...survey was conducted at a national level from February to August 2002. The survey was done via a mailed questionnaire to all municipalities in Japan.
Methods: For the purpose of the study, municipalities were divided into four groups based on level of urbanization and numbers of foreign residents in the area. The situation of the foreign maternal and child support programs were compared and the municipal administrations were evaluated. In addition, the attribution analysis and evaluation of the foreigner support program was conducted in each municipality group.
Results: The evaluation of the current service support program for foreigner was not judged positively in the majority (95%) of the municipalities. In the non‐urbanized municipalities with a low composition of foreigners, the foreigner mother and child support program were not functional compared with other regions. Additionally, various factors were highlighted based on attribution analysis among each group. Although most of the municipalities recognized the importance of the foreign resident support program, the evaluations showed a wide gap between intention and reality.
Conclusion: It is recommended that the barriers as identified in the research results are rectified, and the current situation improved based on municipality characteristics, local demands and the needs of the population. The efficient use of limited fiscal and human resources is also advocated by strengthening of cooperation with other official bodies and also employing foreign residents to work in public offices for facilitating the foreign residents support programs.
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