Takuma Tsukioka

Iron restriction improves type 2 diabetes mellitus in Otsuka Long-Evans Tokushima fatty rats

Accumulating evidence suggests that alcohol, hepatitis C virus infection, steatosis with obesity, and insulin resistance are accompanied by iron overload states. Phlebotomy and oral iron chelators are effective treatments for these conditions and for hemochromatosis. However, the mechanisms by which iron depletion improves clinical factors remain unclear. We examined the effect of iron depletion in a model of type 2 diabetes, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Age-matched Long-Evans Tokushima Otsuka (LETO) rats were used as controls for all experiments. Iron restriction was performed by eliminating iron in the diet from 15 wk of age or by phlebotomy. Phlebotomy was commenced at 29 wk of age by removing 4 and 3 ml of blood from the tail vein every week in OLETF and LETO rats, respectively. Rats were euthanized at 43 wk of age, and detailed analyses were performed. The plasma ferritin concentration was markedly higher in OLETF rats and decreased in iron-deficient (ID) diet and phlebotomy rats. Hemoglobin A(1c) (Hb A(1c)) was decreased significantly in OLETF rats fed the ID diet and in the phlebotomy group. Increased levels of triglycerides, glucose, free fatty acids, and total cholesterol were found in ID OLETF rats. Plasma, liver, and pancreas lipid peroxidation and hepatic superoxide production decreased in both groups. Pancreatic fibrosis and insulin levels improved in both groups of OLETF rats. Pancreatic levels of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands and hypoxia-inducible factor (HIF)-1alpha were decreased significantly in OLETF rats. These factors were normalized in both rats fed ID and phlebotomy groups of OLETF rats. In conclusion, iron depletion improved diabetic complications by inhibition of oxidative stress and TGFbeta signal pathways and the maintenance of pancreatic PPARbeta/delta and HIF-1alpha pathways.

Supplementation of α-tocopherol improves cardiovascular risk factors via the insulin signalling pathway and reduction of mitochondrial reactive oxygen species in type II diabetic rats

This study determined the effects of α- and γ-tocopherol supplementation on metabolic control and oxidative stress in type 2 diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Blood glucose, haemoglobin A1c (HbA1c), urinary protein, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) levels in OLETF rats were significantly higher than in non-diabetic control Long–Evans Tokushima Otsuka (LETO) rats. α-Tocopherol inhibited the increase in urinary protein, blood glucose, HbA1c and PAI-1 levels, but γ-tocopherol did not. Plasma and hepatic lipid peroxidation and hepatic steatosis were increased in OLETF rats. α-Tocopherol decreased lipid peroxidation. Mitochondrial reactive oxygen species production and uncoupling protein 2 (UCP2) expression were significantly increased in the heart and aorta of OLETF rats compared with LETO rats. Endothelial NO synthase and aortic nitrotyrosine were increased in OLETF rats. In contrast, the expression of phosphorylated vasodilator-stimulated phosphoprotein and glucose transporter 4 in the aorta was significantly decreased in OLETF rats. These abnormalities were reversed by α-tocopherol. These findings suggest that α-tocopherol may prevent cardiovascular tissues from oxidative stress and insulin signalling disorder resulting from diabetes mellitus.

High Serum Concentrations of Sialyl Lewisx Predict Multilevel N2 Disease in Non–Small-Cell Lung Cancer

BackgroundThe purpose of this study was to analyze the clinical significance of serum Sialyl Lewisx (SLX) concentrations as a predictor of N2 disease in patients with non–small-cell lung cancer.MethodsThe study included 272 patients with non–small-cell lung cancer who underwent pulmonary resection in our institution between January 1998 and December 2003. Of 272 patients, the serum concentrations of SLX were measured by using a commercially available radioimmunoassay kit.ResultsThe 5-year survival rates of patients with concentrations of SLX > 38 U/mL and those with lower concentrations were 32% and 69%, respectively (P < .0001). The median serum concentration of SLX in patients with multilevel N2 or N3, single-level N2, and N0/1 disease were 44, 30, and 27 U/mL, respectively. The concentrations of serum SLX in patients with multilevel N2 disease were significantly higher than those in patients with single-level N2 or those with N0/1 disease (Mann-Whitney U-test; P < .0001). Although the sensitivity of SLX for identifying patients with non–small-cell lung cancer was only 24% in all patients, the sensitivity of SLX increased as the N-factor increased; the sensitivity of N0/1 disease was 15%, that of single-level N2 disease was 22%, and that of multilevel N2 or N3 disease was 71%.ConclusionsHigh serum concentrations of SLX predicted multilevel N2 disease and the associated poor outcome. Although the sensitivity of serum SLX is not acceptable for use as a screening tumor marker, we suggest that the serum concentration of SLX is useful as a staging marker to determine the strategy of treatment.

Role of pulmonary resection in the diagnosis and treatment of limited-stage small cell lung cancer: revision of clinical diagnosis based on findings of resected specimen and its influence on survival

PurposeOur aims were to evaluate (1) the result of surgical treatment of limited-stage small cell lung cancer (SCLC) by examining long-term survival and prognostic factors, (2) the diagnostic role of surgery by comparing clinical and histopathological diagnoses and staging, and (3) the impact of preoperative diagnostic accuracy on survival.MethodsWe retrospectively reviewed the clinical profiles of 37 patients treated at our institution between January 1990 and December 2007 for SCLC diagnosed using surgical specimens.ResultsThe median follow-up period was 41.2 months, and the 5-year survival rate was 57.5%. Lobectomy or wider resection was performed alone in 33 cases and with mediastinal dissection in 29 cases. Fifteen patients did not receive chemotherapy. SCLC was diagnosed preoperatively or intraoperatively in 75% and non-SCLC in 25%. Clinical stage 1 disease was diagnosed in 29 patients; however, pathological stage 1 was seen in only 20. Patients at pathological stage 1 disease showed better survival than those at stage 2, but a similar result was not obtained in the case of clinical stage of the disease. Tumor size and nodal stage were the only significant factors influencing survival in a multivariate analysis. The adequacy of preoperative clinical diagnosis of tumor extensiveness, nodal involvement, and clinical stage did not significantly influence survival.ConclusionSurgery for limited-stage SCLC was associated with a favorable survival rate and provided important pathological information that can help predict survival. Accuracy of preoperative diagnoses showed no apparent impact on survival for surgically treated SCLC patients.

Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer

OBJECTIVE Impacts of mediastinal lymph node dissection on a patients course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. METHODS Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. RESULTS Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. CONCLUSION Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.

Primary Pulmonary Meningioma Presenting with Hemoptysis on Exertion

An 18-year-old woman presented with hemoptysis during long-distant running. A chest computed tomographic scan revealed a well-demarcated, round-shaped, solitary mass (3.0 cm in diameter) in the left pulmonary hilum. The bleeding was getting more often and a left upper lobectomy was carried out to avoid critical airway bleeding. A solid proliferation of short spindle cells with a remarkable whorl pattern was demonstrated histologically. Immunohistochemical studies showed positive for vimentin and S-100, and focally positive for epithelial membrane antigen. Primary pulmonary meningioma was thus diagnosed. The patient is well without recurrent disease 15 months after surgery.

Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer

Objectives Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patients physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. Methods We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Results Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Conclusion Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease.

Extended resection of primary lung cancer directly invading the liver

Abstract:  A 61‐year‐old woman presented with chest pain. Chest CT revealed a mass of 6 cm diameter in the right lower lobe. Bronchoscopic biopsy showed squamous cell carcinoma. Video‐assisted thoracotomy revealed that the main tumour was directly invading the liver through the diaphragm. To alleviate local symptoms and for possible cure with adjuvant chemotherapy and radiotherapy, standard right lower lobectomy and mediastinal dissection were carried out, followed by combined resection of the diaphragm and posterior superior segmentectomy of the liver. Eleven months postoperatively, the patient was alive but had a metastatic lesion in the other lobe of the liver which reduced in size following chemotherapy.

Preoperative serum value of sialyl Lewis X predicts pathological nodal extension and survival in patients with surgically treated small cell lung cancer

We investigated various tumor markers in patients with surgically treated small cell lung cancer (SCLC) to identify the markers closely correlated to pathological staging and to predict survival by retrospective analyses.

Lung metastases from various malignancies combined with primary lung cancer

Various tumors metastasize to the lung, and they are often detected as multiple nodules. We report on two cases of such multiple lung metastases combined with primary lung cancer: a myxoid liposarcoma in the right thigh and a colon cancer. In each case, a pulmonary metastasectomy revealed that one of the tumors was primary lung cancer. Regardless of recent advances in computed tomography for detecting small pulmonary nodules and ground-glass opacity components, which indicate possible primary lung cancer, the preoperative differential diagnosis for either metastatic or primary lung cancers is usually difficult because they are too small to obtain enough tissue for diagnosis, except by surgery. When nodules are removed and diagnosed as lung metastasis combined with primary lung cancer, additional treatment should be considered depending on the prognosis of each disease.