Prospective Multicenter Interventional Study of Surgical Resection for Liver Metastasis from Gastric Cancer: R0 Resection Rate, and Operative Morbidity and Mortality.

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.

Anti-metastatic effect of methylprednisolone targeting vascular endothelial cells under surgical stress.

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.

Retrograde endoscopic submucosal dissection for early thoracic esophageal carcinoma.

Although the standard treatment for intramucosal esophageal cancer without lymph node metastasis is endoscopic submucosal dissection (ESD), we sometimes encounter patients who are not able to undergo a transoral endoscopic examination. Here, we report a surgical procedure consisting of transgastric retrograde ESD to treat early esophageal cancer (T1a-EP, N0, M0) because of a stricture after hypopharyngeal cancer surgery. This retrograde ESD procedure can be a safe and effective treatment option for early esophageal cancer. This is the first report of a surgical retrograde ESD method for esophageal cancer.

Prognostic Value of the Combined Index of Plasma Fibrinogen and the Neutrophil-Lymphocyte Ratio in Gastric Cancer.

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.

[Simultaneous Laparoscopic Sigmoid Colectomy and Malignant Lymphoma Biopsy-A Case Report].

The patient, a woman in her 70s, was diagnosed with occlusive ileus caused by sigmoid colon cancer.She underwent transanal stent placement to release the occlusion.Subsequent detailed testing revealed a 70×60mm mass on the dorsal side of the pancreas and PET-CT indicated an SUVmax 18.2 FDG uptake. EUS-FNA was performed twice.However, the mass was unable to be definitively diagnosed.The patient was then referred to our hospital.She underwent laparoscopic sigmoid colectomy and laparoscopic biopsy of the mass for sigmoid colon cancer.The patient progressed well postoperatively and was discharged home on postoperative day 9.The postoperative diagnosis was colon cancer(S, Type 2, 58×50 mm, tub2, pT4a [SE], pN1, Stage Ⅲa)and the biopsied mass was found to be a nodal marginal zone B-cell lymphoma according to histopathological testing.After undergoing chemotherapy at our hematology department, she has experienced no recurrence.

[A Case Report on Larynx-Preserving Surgery with Tracheal Resection of an Advanced Esophageal Cancer with Tracheal Invasion].

We present the case of a 69-year-old man who was diagnosed with ascending colon cancer. Preoperative CT revealed 2 advanced esophageal cancers, both at T4; thus, a diagnosis of esophageal cancer(Ut-Ce, cT4b[Tr]N2M0, Stage ⅣA/Mt, cT4b[Lt-Br]N2M0, Stage ⅣA)was made. The patient received chemotherapy(DTX/CDDP/5-FU), and as the second-line treatment, he received chemoradiotherapy(40 Gy with DTX/CDDP/5-FU). We performed transthoracoabdominal esophagectomy, laryngeal preservation with tracheal resection, 3-field lymph node dissection, posterior mediastinal gastric tube reconstruction, mediastinal tracheostomy, and pectoralis major myocutaneous flap filling. He had an anterior chest wall subcutaneous abscess without respiratory complications. Pathological examination indicated a complete response. Two months after the surgery for esophageal cancer, radical surgery was performed for the colon cancer. Fifty-five months after esophagus cancer surgery, no recurrence was observed.

[A Case of Pulmonary Embolism Developed during Combination Chemotherapy with S-1 and Cisplatin in a Young Female Patient with Type 4Gastric Cancer].

We report a case of a 23-year-old womanwho developed pulmonary embolism(PE)during chemotherapy for advanced gastric cancer following total gastrectomy(R1). She presented with type 4 gastric cancer with peritoneal dissemination and positive washing cytology. Palliative total gastrectomy was performed(R1)and first-line chemotherapy with S-1(80mg/m2, days 1 to 21) plus CDDP(60mg/m2, day 8)(SP; every 35 days)was administered. PE occurred on day 15 of the 3rd courses of SP. Computed tomography(CT)revealed massive PE in both the pulmonary arteries, and ultrasonography indicated an increase in right-sided pressure. Thrombolysis using urokinase and heparin was performed immediately, and she recovered after 10 days in intensive care. Dehydration caused by the adverse event, as well as nausea and the anticancer drug itself, are risk factors for DVT and PE. Risk stratification, prevention, and early treatment are very important for PE.

Post-discharge depressive symptoms can predict quality of life in AMI survivors: a prospective cohort study in Japan.

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 (ß = -2.62; CI: -5.00 to -0.23), role-physical (ß = -3.50; CI: -6.94 to -0.06) and bodily pain (ß = -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.

Clinical significance of awake oscillatory ventilation in patients with heart failure and effects of open-heart surgery.

BACKGROUND: Although sleep apnea has recently become a concern in patients with congestive heart failure (CHF), some patients with CHF exhibit characteristic oscillatory ventilation (OV) even when they are awake. We investigated the clinical significance of OV in patients with CHF, and effects of open-heart surgery on the OV. HYPOTHESIS: OV is an indicator of the severity of CHF, and this abnormal respiratory pattern improves with hemodynamic changes after open-heart surgery. METHODS: According to respiratory pattern in the cardiopulmonary exercise testing (CPX) before cardiac surgery, 50 patients with CHF were divided into 14 patients of OV-positive (OV+) and 36 patients of OV-negative (OV-). Then, the several indices of CPX before surgery, 1 week and 6 months after surgery were compared between the 2 groups. RESULTS: The peak VO2 before surgery was lower in OV+ patients than those in OV- patients (15.3 vs 18.8 m1/min/kg, p < 0.05). One week after surgery, anaerobic threshold (AT) and end-tidal C02 (ETC02) were lower in OV+ patients than those in OV- patients (AT: 9.5 vs 10,7 ml/min/kg, p < 0.05, ETCO2: 5.3 vs 5.6%, p < 0.05). However, 6 months after surgery, the statistical differences of these CPX parameters between the 2 groups were not found, and OV disappeared in 79% of OV+ patients. CONCLUSIONS: These data suggest that OV is an indicator of the severity of CHF, and gradually improved with the open-heart surgery.

Palladium-catalyzed aromatic C-H halogenation with hydrogen halides by means of electrochemical oxidation.

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.

Situational analysis of maternal and child health services for foreign residents in Japan.

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.

[Development of 64-channel magnetocardiography and clinical application].

A magnetocardiogram (MCG) can detect three-dimensional electric phenomena of the heart, because MCG does not influence the lung and torso form of the internal organs. In this symposium, we report the application of 64-channel MCG for the measurement of various arrhythmias (atrial flutter, atrial fibrillation), myocardial injury, and fetus arrhythmia. We composed function images of the conduction wave front and injured myocardium superimposed on a three-dimensional heart outline from the magnetic field. The injured myocardium was determined by a three-dimensional RT dispersion map. This algorithm allows the non-invasive determination of the space location of signal source and injured myocardium. In addition, 64-channel MCG can detect the fetal arrhythmias and autonomic nervous activity, which allows the diagnosis of fetus arrhythmia in detail before birth. Thus, MCG measurement is a useful non-invasive diagnostics procedure. However, there are several problems such as sealed room installation and the use of liquid helium. In the future, a newer technology that does not require liquid helium and a sealed room will be necessory.

Human Jagged 1 mutants cause liver defect in Alagille syndrome by overexpression of hepatocyte growth factor.

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.

[Coronary sinus ostial atresia with thrombus: a case report].

An 82-year-old woman presented with mitral regurgitation and atrial fibrillation. She was hospitalized for further examination of cardiac thrombus detected by transthoracic echocardiography. No definitive diagnosis could be made based on computed tomography and magnetic resonance imaging. Intravenous contrast echocardiography suggested a coronary sinus thrombus. Coronary angiography showed coronary sinus ostial atresia. Multislice computed tomography confirmed the presence of thrombus in the enlarged coronary sinus with coronary sinus ostial atresia and persistent left superior vena cava. Persistent left superior vena cava is present in 3% of patients with congenital heart disease. Persistent left superior vena cava is detected by chance during cardiac catheterization for other conditions in patients without cardiac malformations. The present case was detected at an advanced age, and in the absence of prior symptoms.

Effects of exercise training on left ventricular function evaluated by the Tei index in patients with myocardial infarction.

BACKGROUND: This study investigated the influence of exercise training on left ventricular (LV) function in patients with acute myocardial infarction (AMI) using a new index of cardiac function, the Tei index. METHODS AND RESULTS: The study enrolled 53 consecutive patients (36 males, 17 females; mean age: 65+/-10 years) with AMI. Exercise training was performed for 6 months; peak VO2 and the Tei index were measured at the start of the cardiac rehabilitation program and 1, 3, and 6 months later. The peak VO2 improved from 14.3+/-3.3 to 18.5+/-5.2 ml.min -1.kg-1 after 6 months (p<0.01). Although there were no significant changes in LV ejection fraction over the 6 months, the Tei index improved from 0.50+/-0.18 to 0.41+/-0.19 (p<0.05). When the DeltaTei index was compared among the 3 groups classified by the Tei index at baseline, the values improved in the groups with high/slightly high values compared with the normal group. CONCLUSION: Both cardiac function, as evaluated by the Tei index, and exercise capacity improved after exercise training in patients with AMI. The greater improvement was seen in the population with the higher value (lower cardiac function) according to this index.

Effort angina in a middle-aged woman with abnormally high levels of serum high-density lipoprotein cholesterol: a case of cholesteryl-ester transfer protein deficiency.

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.

Effects of exercise training after open heart surgery on quality of life and exercise tolerance in patients with mitral regurgitation or aortic regurgitation.

We conducted a questionnaire survey regarding quality of life (QOL) to evaluate the effects of exercise training on the QOL in patients with valvular heart disease after surgery. This study included 64 consecutive patients who underwent heart surgery. They were divided into two groups: exercise training could (EX(+) group, n = 31) and could not be performed (EX(-) group, n = 33) until 6 months after surgery. To evaluate the QOL and exercise tolerance, we employed "a questionnaire regarding disease and quality of life" developed for Japanese people and cardiopulmonary exercise testing. In our questionnaire survey, the improvement rating (Delta subjective/social index), which was calculated from the difference between the pre-and postoperative values, was greater in the EX(+) group than that in the EX(-) group (4.9 +/- 3.1 versus 1.1 +/- 4.0, P < 0.05). In the changes in exercise tolerance, Delta anaerobic threshold was greater in the EX(+) group (0.79 +/- 0.17 versus -0.02 +/- 0.28, P < 0.01). Moreover, there was a positive correlation between Delta subjective/social index and Delta peak VO(2) (r = 0.62, P < 0.05). We concluded that exercise training for patients after cardiac surgery improves the QOL and exercise tolerance. It is suggested that changes in subjective and social parameters contribute to an exercise training-related improvement in the QOL.

Factors affecting ST depression during cardiopulmonary exercise testing in patients with mitral stenosis without significant coronary lesions.

Symptom-limited cardiopulmonary exercise testing was performed in 37 patients with mitral stenosis (MS) without significant coronary artery stenosis to evaluate factors affecting ST depression in exercise electrocardiograms. The degree of ST depression was not associated with gender or exercise tolerance. The incidence of significant ST depression was higher in the patients receiving than in those not receiving digitalis (P < 0.05). In addition, the patients with atrial fibrillation and a higher heart rate response were more likely to have a high prevalence of significant ST depression than those with sinus rhythm and a lower response (P < 0.05). We concluded that atrial fibrillation, a higher maximum heart rate, and oral digitalis administration were involved in ST depression during exercise testing in patients with mitral stenosis without coronary heart disease.

Do the right precordial leads during exercise testing contribute to detection of coronary artery disease?

BACKGROUND: It is still unknown whether or not the additional right precordial leads (RPL) during exercise testing contribute to detection of coronary artery disease (CAD). HYPOTHESIS: The aim of this study was to evaluate the RPL during exercise testing for the detection of CAD. METHODS: The study included 157 consecutive patients (116 men and 41 women, mean age 66 years) suspected of having CAD, who underwent conclusive treadmill exercise testing (heart rate reached at least 85% of the predicted maximum or positive electrocardiogram [ECG] changes were exhibited) and coronary angiography. During exercise testing, the ECG was recorded with the standard 12 leads and 4 RPL (V3R, V4R, V5R, V6R). RESULTS: Of the 157 patients, 67 had CAD (> 75% stenosis in at least one major coronary artery), and 64 had positive ST changes in the standard ECG leads during exercise testing. Using the conventional 12-lead method, sensitivity and specificity were 76 and 86%, respectively. Only three patients exhibited positive changes in the RPL leads; all had > 0.1 mV ST elevation in one of the RPL leads with > 0.1 mV ST elevation in aVR. Two of these patients had significant right coronary artery lesions and the other had a lesion of the left anterior descending artery which perfused the inferior as well as the anteroseptal area. In the standard 12 leads, one of the patients with an abnormal RPL and a right coronary lesion was negative, while the other two patients were positive. Combining RPL with the conventional 12-lead method, sensitivity and specificity were 78 and 86%, respectively. Therefore, RPL did not improve the accuracy of the exercise ECG. CONCLUSION: The use of RPL during exercise testing may contribute to the detection of ischemia perfused by the right coronary artery; however, it does not improve the diagnostic accuracy of the exercise test.

A new method using pulmonary gas-exchange kinetics to evaluate efficacy of beta-blocking agents in patients with dilated cardiomyopathy.

BACKGROUND AND OBJECTIVES: The effects of beta-blocking agents on exercise tolerance in cardiopulmonary exercise testing (CPX) have not been fully identified. Because the negative chronotropic effects of these agents produce a sluggish increase in heart rate (HR) during CPX, exercise capacity is actually underestimated by methods that depend on HR-related variables such as peak oxygen uptake (O(2)) and anaerobic threshold (AT). The aim of this study was to clarify the efficacy of beta-blocking agents by means of O(2) kinetics, a parameter independent of HR, in patients with dilated cardiomyopathy (DCM). DESIGN AND PATIENTS: The exercise capacity of 12 patients (9 men and 3 women; mean +/- SD age, 54 +/- 12 years; New York Heart Association class I [n = 1], NYHA class 2 [n = 4], and NYHA class III [n = 6]) with DCM, who were treated with beta-blocking agents, was evaluated by CPX. O(2) was calculated from respiratory gas analysis on a breath-by-breath basis. Nine patients were treated with metoprolol (30 mg or 60 mg), two with carteolol (10 mg or 20 mg), and one patient with atenolol (25 mg). RESULTS: All patients showed a significantly favorable results (ie, improvement in symptoms of congestive heart failure). Peak O(2) (20.4 +/- 5.1 to 18.8 +/- 5.8 mL/min/kg), AT (12.7 +/- 3.5 to 12.1 +/- 2.1 mL/min/kg), and exercise time (4.8 +/- 2.2 to 4.5 +/- 2.1 s) were unchanged. The time constant of O(2) kinetics (tau) on response to constant low-dose work loading (warm up) decreased significantly (64 +/- 30 to 44 +/- 24 s; p < 0.01) and ejection fraction increased (30 +/- 14 to 44 +/- 15%, p < 0.01) significantly following treatment with beta-blocking agents. In spite of excluding two NYHA I patients, these changes were also statistically correlated. CONCLUSION: In the low level of exercise, tau was prolonged in patients with DCM. Although indexes of total exercise time and AT were not useful markers for clinical improvement in cardiac performance as assessed by echocardiography, measuring can validly assess the beneficial effects in heart failure treated with beta-blocking agents.