Chemosensitivity and Survival in Gastric Cancer Patients with Microsatellite Instability

Introduction  Conflicting data exist regarding the relevance of high-frequency microsatellite instability (MSI-H) for predicting the prognosis and benefits of 5-fluorouracil (5-FU)-based chemotherapy. This study investigated the usefulness of MSI as either a prognostic indicator or predictor of distinct clinical attributes regarding the use of adjuvant chemotherapy with 5-FU and its analogues in gastric cancer. Materials and methods  Data and tumor specimens were collected from 240 gastric cancer patients from 1993 to 2002. Five microsatellite loci were analyzed using a high-intensity microsatellite analysis reported previously. A Cox proportional hazard model was used to compare the clinical data and survival as well as any associations between MSI and 5-FU treatment status of patients with MSI or microsatellite stability (MSS) gastric cancers. A 3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted in 168 cases to investigate chemosensitivity to 5-FU. Results  This analysis identified 22 MSI-H (9.4%), 25 MSI-L (10.7%), and 193 MSS (79.9%) tumors. Gastric cancer with MSI-H tended to have increased likelihood to show higher age, antral location of the tumor, and lymph vessel involvement (P < 0.05). Univariate analyses failed to show any difference between the MSI-H and MSS/MSI-L groups with respect to overall survival. Furthermore, survival after the administration of 5-FU did not correlate with MSI status, and MSI was not associated with 5-FU sensitivity by MTT assay. Conclusion  The results of this study indicate that MSI status has no clear influence on overall survival or response to 5-FU in gastric cancer.     

Three-dimensional CT image analysis of a tracheal bronchus in a patient undergoing cardiac surgery with one-lung ventilation

The incidence of a tracheal bronchus—that is, a congenitally abnormal bronchus originating from the trachea or main bronchi–is 0.1%–2%. Serious hypoxia and atelectasis can develop in such patients with intubation and one-lung ventilation. We experienced a remarkable decrease in peripheral oxygen saturation () and a rise in airway pressure during placement of a double-lumen endobronchial tube in a patient with patent ductus arteriosus and tracheal bronchus. Substitution of the double-lumen tube with a bronchial blocker tube provided secure isolation of the lung intraoperatively. A type I tracheal bronchus and segmental tracheal stenosis were identified on postoperative three-dimensional (3D) computed tomographic (CT) images. Preoperative examination of chest X-rays, CT images, and preoperative tracheal 3D images should preempt such complications and assist in securing safe and optimal one-lung ventilation.     

Real-time endobronchial ultrasound-guided transbronchial needle aspiration is useful for diagnosing sarcoidosis

BACKGROUND AND OBJECTIVE: Several studies of real-time endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) have reported a sensitivity of approximately 90% in the diagnosis of mediastinal and hilar malignancies. However, few studies have addressed its role in the diagnosis of sarcoidosis. The aim of the present study was to assess the utility of EBUS-TBNA in confirming a pathological diagnosis of sarcoidosis. METHODS: Fifteen consecutive patients with suspected sarcoidosis and mediastinal and/or hilar lymphadenopathy were investigated prospectively. EBUS-TBNA with an echo-bronchoscope and a dedicated echogenic 22-gauge needle was carried out in patients under conscious sedation, followed by conventional TBNA of the same lesion using a 19-gauge needle. RESULTS: EBUS-TBNA and/or TBNA demonstrated non-caseating epithelioid cell granulomas in 14 of 15 patients (93%). All 14 patients with a pathological diagnosis of sarcoidosis were considered to have sarcoidosis based on subsequent clinical assessments. The single patient with a negative EBUS-TBNA and TBNA had a malignant melanoma diagnosed following surgical biopsy. EBUS-TBNA confirmed a diagnosis of sarcoidosis in 13 of the 14 patients (93%) by identifying non-caseating epithelioid cell granulomas in 18 of 23 lymph nodes (78%) sampled. When two needle aspirates of one or two lymph nodes were carried out, the percentage positive pathological diagnosis for sarcoidosis for (i) EBUS-TBNA; (ii) TBNA; and (iii) the combination of EBUS-TBNA and TBNA were 93% (13 of 14 patients), 93% (13 of 14 patients) and 100% (14 of 14 patients), respectively. There were no complications associated with the procedures. CONCLUSION: EBUS-TBNA is less invasive and acceptably sensitive as a method for obtaining pathological confirmation of sarcoidosis.     

The relationship between acute phase serum amyloid A (SAA) protein concentrations and left ventricular systolic function in acute myocardial infarction patients treated with primary coronary angioplasty

BACKGROUND: Our study was planned to investigate the relationship between plasma levels of serum amyloid A protein (SAA) concentrations and the subsequent left ventricular systolic function in patients with acute myocardial infarction (AMI) treated with primary coronary angioplasty. METHODS AND RESULTS: Reperfusion by primary percutaneous coronary intervention was successful in 486 consecutive AMI patients who were admitted within 12 hours of onset. Plasma SAA concentrations were evaluated 24 hours after onset. Left ventricular (LV) function was serially determined by left ventriculography performed in the acute (soon after recanalization) and chronic phases (6 months after onset). (I) There was no significant correlation between SAA concentration and acute phase left ventricular ejection fraction (LVEF) or regional wall motion (RWM). (II) The SAA concentration was significantly correlated with both highly sensitive C-reactive protein (hs-CRP) and the peak-CK value (hs-CRP: r = 0.69, P < 0.0001, peak-CK: r = 0.21, P = 0.0003). (III) SAA was significantly negatively correlated with both LVEF and RWM in the chronic phase (LVEF: r = -0.42, P = 0.001; RWM: r = -0.41, P = 0.007). (IV) The plasma level of SAA also showed a significant negative correlation with the differences in LVEF between the 2 stages (delta-LVEF) (r = -0.43, P = 0.02). CONCLUSION: In the setting of AMI, plasma SAA concentrations may be closely related to subsequent left-ventricular systolic dysfunction.     

Anti-oxidative effect of Klotho on endothelial cells through cAMP activation

Klotho, a regulatory factor implicated in countering the aging process, has been reported to ameliorate endothelial dysfunction in vivo. To clarify whether Klotho protein directly affects endothelial cell function, we studied the effects of membrane-form Klotho on manganese superoxide dismutase (Mn-SOD) expression and nitric oxide production in human umbilical vein endothelial cells (HUVEC). We incubated HUVEC with conditioned medium from COS-1 cells transfected with expression vector, pCAGGS-klotho (Klotho-CM) or a recombinant, purified 6His-tagged Klotho protein. Both Klotho-CM and 6His-tagged Klotho protein enhanced Mn-SOD expression by approximately two-fold, partially via activation of the cAMP signaling pathway. Furthermore, Klotho-CM increased nitric oxide production, which also contributed to the up-regulation of Mn-SOD. Using the oxidation-sensitive dye dihydroethidium, we found that Klotho inhibited angiotensin II-induced reactive oxygen species production in HUVEC. These findings provide new insights into the mechanisms of Klotho action and support the therapeutic potential of membrane-form Klotho to regulate endothelial function. Hiromi Rakugi and Naomichi Matsukawa contributed equally to this work.     

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma （BSC） of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil （5-FU） and cisplatin （CDDP）. A 57-year-old woman was diagnosed as having SCluamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.