Clinical Features, Prognosis, Diagnostic Approaches and Treatment of Multiple Primary Malignancies in the Digestive System.

BACKGROUND/AIM: Additional primary malignancy (APM) risk is increasing with improved prognosis of cancer survivors. In order to clarify risk factors and patients susceptible to develop APMs, we investigated the clinical features, prognosis, and approaches for diagnosis and treatment in these patients. PATIENTS AND METHODS: Among 874 patients newly diagnosed with gastrointestinal tract (GIT) or hepato-biliary-pancreatic (HBP) cancers between 2011 and 2014, 124 with a synchronous and/or metachronous APM were identified. Patient characteristics, time interval between the malignancies, clue to detect APMs, treatment approaches, and prognosis were investigated. RESULTS: Patients with APMs were older and predominantly male. Half of the metachronous APMs were detected within 3 years after the first primary malignancy (PM). The main clue to detect synchronous and metachronous APMs was preoperative screening for current PM, and follow-up of prior PM, respectively. There was no significant difference in the overall survival between colon cancer patients with or without APMs. CONCLUSION: Multiple PMs were present in 14.2% of patients. Male and old age were identified to be risk factors for APM. Pre-operative screening and post-operative regular follow-ups are important for detecting synchronous or metachronous APMs.

Feasibility study of adjuvant chemotherapy of S-1 and carboplatin for completely resected non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer (NSCLC) of pathological stage IB-IIIB. METHODS: S-1 was given orally at a dose of 80 mg/m²/day for 2 weeks, followed by a 2-week period of no treatment. Carboplatin was given intravenously on day 8 at an area under the curve of 6. This regimen was repeated for four to six 28-day courses. RESULTS: Seventeen patients were enrolled in this study. Fourteen of them completed at least 4 cycles of chemotherapy. Nine patients had grade 2 and three patients had grade 3 thrombocytopenia, respectively. Severe nonhematologic toxicities were uncommon. Treatment was delayed in a few patients because of prolonged thrombocytopenia. CONCLUSION: We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy.

[Surgical treatment of oral cancer pulmonary metastases].

We examined the efficacy of surgical resection of oral cancer pulmonary metastases. Between April 2001 and October 2010, 12 patients with pulmonary metastases underwent thoracic operations. There were 8 men and 4 women with a median age of 66.5 years (range, 27~76). All tumors were squamous cell carcinomas and the most common primary site was tongue (7 patients). Overall survival rate after metastasectomy was 50% at 3 years. Overall survival rate at 2 years by lobectomy was greater than by partial resection. For patients with oral cancer pulmonary metastasis, surgical resection is the effective treatment option.

Pulmonary Artery Leiomyosarcoma Diagnosed without Delay.

A 63-year-old female presented with abnormal lung shadows but had, apart from this, few symptoms. Computed tomography (CT) revealed multiple nodules and blockage of the pulmonary artery. She was immediately diagnosed with pulmonary artery sarcoma based on a careful differential diagnosis and underwent surgery. Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma). Pulmonary artery sarcoma can be easily confounded with thromboembolism in a clinical setting and some cases are diagnosed post mortem only. In our case, clinical prediction scores (Wells score, Geneva score, and revised Geneva score) for the pulmonary embolism showed low probability. Moreover, chest CT showed uncommon findings for pulmonary thromboembolism, as the nodules were too big for thrombi. Because surgical resection can provide the only hope of long-term survival in cases of pulmonary artery sarcoma, clinicians should consider this possibility in the differential diagnosis of pulmonary embolism. Clinical prediction scores and CT findings might help to reach the correct diagnosis of pulmonary artery sarcoma.

Good syndrome with thymic adenosquamous carcinoma--report of a case.

A 68-year-old man with recurrent bilateral severe pneumonia and invasive thymic carcinoma was admitted to our hospital. An extended thymo-thymectomy with lymph nodes dissection was performed for an irregular shaped anterior mediastinum mass. The tumor was mainly composed of type C, adenosquamous carcinoma, and found to have a small area of types B2 and B3 thymoma. History and laboratory findings were compatible with the diagnosis of Good syndrome. Although there are some reports of thymic carcinoma arising from thymoma, this is the first report of co-existence of adenosquamous carcinomas and thymoma with Good syndrome as far as reviewed articles. Thymic carcinoma with severe infection should be examined carefully for co-existence of thymoma, and co-existence of thymoma and thymic carcinoma suggests a close histogenetic relationship between the 2 tumors.

Cytosolic phospholipase A2 inhibition attenuates ischemia-reperfusion injury in an isolated rat lung model.

BACKGROUND: Arachidonic acid metabolites and platelet-activating factor (PAF) are potentially involved in ischemia-reperfusion (IR) lung injury. A key enzyme regulating their metabolism is cytosolic phospholipase A2 (cPLA2). Arachidonyl trifluoromethyl ketone (AACOCF3) is reported to be a potent cPLA2 inhibitor. In the present study, we hypothesized that pharmacological inhibition of cPLA2 might ameliorate IR lung injury. METHODS: To test the hypothesis, we examined the effects of AACOCF3 in an isolated rat lung model. Three groups were defined (n=6, each): in the vehicle group, lungs were perfused for 2 hours without an ischemic period. In the ischemic groups, 20 mg/kg of AACOCF3 (AACOCF3 group) or saline (control group) was i.v. administered 15 min before lung harvest. Lungs were flushed with LPD solution, cold-stored 18 hours, and reperfused for 2 hours. RESULTS: IR increased cPLA2 activity mainly via alveolar macrophages, sPLA2 activity, thromboxane and leukotriene formation, and the expression of PAF receptor, whereas AACOCF3 treatment significantly reduced all of these. Compared to the vehicle group, the wet-to-dry ratio, proteins in BAL, and MPO activity increased significantly by twofold, fourfold, and threefold, respectively. Furthermore, the PO2 dropped from 615.7+/-31.2 to 452.1+/-30.9 mmHg at the end of reperfusion (P<0.001). AACOCF3 treatment maintained the PO2 at a level similar to the vehicle group throughout reperfusion and reduced significantly the alveolar-capillary leakage, edema formation, and neutrophil extravasation. CONCLUSION: Pharmacological inhibition of the cPLA2 cascade decreases bioactive lipid formation and attenuates IR-induced lung injury.

Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury.

RATIONALE: Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell-associated proteins in the lung. OBJECTIVES: To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury. METHODS: Rats were instilled intratracheally with 10 mg/kg lipopolysaccharide or hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL) and serum in the rats and in the pulmonary edema fluid and plasma from patients with acute lung injury (ALI; n = 22) and hydrostatic pulmonary edema (n = 11). MAIN RESULTS: In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized approximately 48 kD. The elevated levels of RAGE in the BAL correlated well with the severity of experimentally induced lung injury. In the human studies, the RAGE level in the pulmonary edema fluid was significantly higher than the plasma level (p < 0.0001). The median edema fluid/plasma ratio of RAGE levels was 105 (interquartile range, 55-243). The RAGE levels in the pulmonary edema fluid from patients with ALI were higher than the levels from patients with hydrostatic pulmonary edema (p < 0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p < 0.001) or patients with hydrostatic pulmonary edema (p < 0.05). CONCLUSION: RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats and in patients with ALI.

Aprotinin attenuated ischemia-reperfusion injury in an isolated rat lung model after 18-hours preservation.

OBJECTIVE: Ischemia-reperfusion injury is a major factor in the early phase of lung transplantation. We hypothesized that aprotinin, a nonspecific serine protease inhibitor, attenuates ischemia-reperfusion lung injury by inhibiting the inflammatory response and suppressing NADPH oxidase. METHODS: We used an isolated rat lung model to test the above. A Control group was immediately perfused with fresh heparinized allogeneic blood after lung harvest without an ischemic period. Study lungs were flushed with low-potassium dextran (LPD) solution and stored for 18h at 4 degrees C then divided into two groups: the LPD group was flushed with LPD solution only, and the LPD+A group was flushed with LPD solution +200KIU/ml aprotinin. Lungs in all three groups were then reperfused with fresh heparinized allogeneic blood for 120min at 37 degrees C. RESULTS: Throughout reperfusion, PO(2) levels in the LPD+A group were similar to those in the Control group; although in the LPD group, PO(2) levels were significantly lower (P<0.05). Tissue MDA levels were significantly higher in the LPD group than the Control and LPD+A groups (P<0.05). IL-8 levels were significantly higher in the LPD group than the Control group (P<0.05), while in the LPD+A group they were similar to those in the Control group. Histological evaluation showed interstitial edema accompanied by neutrophil extravasation in the LPD group, whereas this effect was modest in the LPD+A group. An additional study of ischemia-reperfusion in an alveolar macrophage culture showed that the activitvation of NADPH oxidase, and translocation of p47(phox) from the cytosol to the membrane were suppressed in aprotinin group. CONCLUSIONS: Aprotinin attenuates ischemia-reperfusion lung injury by inhibiting the early inflammatory response, neutrophil extravasation and the production of oxygen free radicals through inhibition of the activation of the NADPH oxidase. The inhibition of p47(phox) translocation in alveolar macrophage seemed involved in this mechanism of aprotinin.

Serum adiponectin concentrations during treatment with olanzapine or risperidone: a pilot study.

Adiponectin is a recently identified adipocyte-derived protein, which is associated with glucose metabolism, insulin sensitivity and adiposity. The aim of this study was to explore the alterations in serum adiponectin concentration during treatment with olanzapine or risperidone. Serum concentrations of adiponectin were investigated in body mass index (BMI, kg/m2)- and age-matched groups of non-diabetic, non-obese schizophrenic patients receiving a stable dose of olanzapine (n = 18) or risperidone (n = 15) for 4 weeks or more, and of mentally and physically healthy volunteers (n = 17). Patients undergoing treatment with olanzapine or risperidone had significantly higher adiponectin concentrations than the healthy volunteers, even after controlling for BMI. Adiponectin concentrations decreased with increasing BMI in patients taking olanzapine, while elevated levels were observed in patients taking risperidone, regardless of adiposity. This preliminary cross-sectional study indicates that adiponectin is involved in the regulation of glucose metabolism and weight in schizophrenic patients during treatment with olanzapine or risperidone, presumably showing a normalizing effect on metabolic abnormality.

Serum ghrelin concentrations in patients receiving olanzapine or risperidone.

RATIONALE: Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanism is poorly understood. OBJECTIVES: To test the hypothesis that ghrelin, a gastrointestinal hormone that enhances appetite, is involved in increased food intake and weight gain during treatment with antipsychotics. METHODS: Serum ghrelin concentrations were investigated in schizophrenic patients receiving olanzapine or risperidone, and in healthy volunteers. RESULTS: Serum ghrelin concentrations did not increase, but rather decreased, in patients treated with olanzapine or risperidone in comparison with healthy volunteers. No significant difference was found in serum ghrelin concentration between patients treated with olanzapine and risperidone. CONCLUSIONS: Our results indicate that ghrelin is not a direct cause of increased food intake and weight gain during treatment with olanzapine or risperidone, whereas ghrelin is associated with metabolic change in patients receiving these agents.