Endothelin receptor antagonists in a beagle model of pulmonary hypertension: Contribution to possible potential therapy?

Objectives.This study investigated the pharmacologic effect of endothelin receptor antagonists on cardiopulmonary hemodynamic variables in a beagle model of pulmonary hypertension.Background.We recently developed a beagle model of pulmonary hypertension that allows accurate determination of cardiopulmonary hemodynamic variables and is associated with elevated plasma endothelin-1 concentrations similar to those in pulmonary hypertension in humans.Methods.Twelve beagles (pulmonary hypertension, n = 6; control group, n = 6) were studied during baseline conditions and during right atrial infusion of FR139317 (an ETA receptor antagonist), RES-701-1 (an ETB receptor antagonist), nitroglycerin and prostaglandin E1. Pulmonary hypertension was induced in experimental beagles 8 weeks after injection with 3 mg/kg body weight of dehydromonocrotaline.Results.FR139317 lowered pulmonary artery and systemic arterial pressures in both pulmonary hypertensive and control beagles, with a significantly greater effect on pulmonary artery pressure in pulmonary hypertensive dogs. RES-701-1 tended to increase pulmonary artery pressure only in pulmonary hypertensive beagles. Nitroglycerin depressed pulmonary artery and systemic arterial tone equally well in control and pulmonary hypertensive animals. Prostaglandin E1produced a greater decrease in systemic arterial pressure in pulmonary hypertensive than in normal beagles despite having the same effect on pulmonary artery pressure in both.Conclusions.ETA receptor antagonists decrease pulmonary artery pressure in a beagle model and may therefore be clinically useful for treatment of pulmonary hypertension

Operative approach for multiple primary lung carcinomas

AbstractOf 908 patients who underwent operation for primary lung cancer between January 1985 and June 1996, we considered 57 (6.3%) to have a second primary lung cancer, which was synchronous in 28 cases (3.1%) and metachronous in 29 cases (3.2%). Five-year survival for patients with synchronous and metachronous disease from initial treatment of cancer was 70.3% and 66.0%, respectively. Survival after the development of a metachronous lesion was 32.9% at 5 years. Sixteen of the synchronous second tumors (57%) were detected on preoperative radiography or bronchoscopy and 11 (39%) at the time of operation. Survival of patients at stage I or II from treatment of a synchronous lesion (p = 0.002) and of a metachronous second lesion (p = 0.028) was significantly better compared with those at stage III or IV. Therefore it is important to carefully examine a synchronous lesion before and during the operation of a primary lung cancer and to perform close follow-up surveillance for early detection of a metachronous lesion. In treating multiple lung carcinomas consideration should always be given to performing precise staging, aggressive operative approach for early stage, and oncologically sound parenchymal sparing procedures. (J Thorac Cardiovasc Surg 1998;115:836-40

Leiomyosarcoma of the sigmoid colon with multiple liver metastases and gastric cancer: a case report

BACKGROUND: Leiomyosarcoma (LMS) of the gastrointestinal tract is an extremely rare high-grade neoplasm with poor prognosis. For advanced LMS with distant metastasis, the decision as to the choice of the most appropriate therapeutic strategy, including chemotherapy and surgery, is difficult. Here, we present an unusual case of LMS of the sigmoid colon with liver metastases and gastric cancer. The survival of this patient was prolonged by a combined modality therapy involving chemotherapy and surgery. CASE PRESENTATION: A 66-year-old woman who had been diagnosed with advanced gastric cancer and multiple liver metastases was referred to our hospital. The initial treatment with docetaxel and S-1 considerably reduced both the gastric cancer and liver tumors; consequently we performed surgical resection. Pathological examination revealed that no viable tumor cells remained in the stomach and chemotherapy resulted in complete remission of the gastric cancer. The liver tumors were immunohistochemically diagnosed as LMS. A tumor of the sigmoid colon was subsequently discovered and the liver tumors were found to have recurred. The surgically resected sigmoid colon and liver tumors were all immunohistochemically diagnosed as LMS. These findings indicated that the multiple liver metastases arose from the LMS in the sigmoid colon, and that they were accompanied by advanced gastric cancer. We performed another surgical resection and administered chemotherapy to treat the recurring liver metastases. The patient survived for 4 years and 10 months after initial presentation at our hospital. CONCLUSION: Colonic LMS is rare and its joint occurrence with gastric cancer is extremely unusual. Although LMS is a high-grade neoplasm, a multimodal therapeutic approach can increase patient survival time even when multiple liver metastases are present

Prediction of pathologic node-negative clinical stage IA lung adenocarcinoma for optimal candidates undergoing sublobar resection

ObjectivePatients with pathologic node-negative early lung cancer may be optimal candidates for sublobar resection. We aimed to identify predictors of pathologic lymph node involvement in clinical stage IA lung adenocarcinoma.MethodsThe data from a multicenter database of 502 patients with completely resected clinical stage IA lung adenocarcinoma were retrospectively analyzed to determine the relationship between the lymph node metastasis status and tumor size on high-resolution computed tomography (HRCT) or maximum standardized uptake value (SUVmax) on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). Revised SUVmax was used to correct interinstitutional discrepancies.ResultsIn multivariate analyses, either a solid tumor size on HRCT (P = .001) or an SUVmax on FDG-PET/CT (P = .049) was an independent predictor of lymph node metastasis. The predictive criteria of pathologic node-negative early lung cancer were a solid tumor size of less than 0.8 cm or an SUVmax of less than 1.5. Patients who met the predictive criteria of pathologic node-negative disease had less pathologic invasiveness, such as lymphatic, vascular, or pleural invasion (P < .001), and better disease-free survival (P < .0001) than those who did not, and 86 (40.4%) of the 213 patients with T1b (2-3 cm) tumors met the predictive criteria.ConclusionsEither a solid tumor size or an SUVmax was a significant independent predictor of nodal involvement in clinical stage IA lung adenocarcinoma. The pathologic node-negative status criteria of a solid tumor size of less than 0.8 cm on HRCT or an SUVmax of less than1.5 on FDG-PET/CT may be helpful for avoiding systematic lymphadenectomy for clinical stage IA lung adenocarcinoma, even in cases of T1b (2-3 cm) tumor

MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung

The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma and squamous cell carcinoma requires the positive and negative immunohistochemical markers of mesothelioma. The IMIG guideline has suggested the use of Calretinin, D2–40, WT1, and CK5/6 as mesothelial markers, TTF-1, Napsin-A, Claudin 4, CEA as lung adenocarcinoma markers p40, p63, CK5/6, MOC-31 as squamous cell markers. However, use of other immunohistochemical markers is still necessary. We evaluated 65 epithelioid mesotheliomas, 60 adenocarcinomas, and 57 squamous cell carcinomas of the lung for MUC4 expression by immunohistochemistry and compared with the previously known immunohistochemical markers. MUC4 expression was not found in any of 65 cases of epithelioid mesothelioma. In contrast, MUC4 expression was observed in 50/60(83.3%) cases of lung adenocarcinoma and 50/56(89.3%) cases of lung squamous cell carcinoma. The negative MUC4 expression showed 100% sensitivity, 86.2% specificity and accuracy rate of 91.2% to differentiate epithelioid mesothelioma from lung carcinoma. The sensitivity, specificity, and accuracy of MUC4 are comparable to that of previously known markers of lung adenocarcinoma and squamous cell carcinoma, namely CEA, Claudin 4 and better than that of MOC-31. In conclusion, MUC4 immunohistochemistry is useful for differentiation of epithelioid mesothelioma from lung carcinoma, either adenocarcinoma or squamous cell carcinoma.The authors thank Ms. Yukari Go of the Technical Center in Hiroshima University for excellent technical assistance and Ms. Naomi Fukuhara for administrative assistance. This work was supported by JSPS KAKENHI Grant Number 17K08742

Surgical Resection of Thoracic Esophageal Cancer with Interstitial Lung Disease : A Case Report

Patients with esophageal cancer often have various comorbidities, and these sometimes limit treatment choices. We describe a patient with stage IA esophageal cancer accompanied by interstitial lung disease (ILD). Endoscopic resection and radiotherapy were not appropriate because of clinically diagnosed submucosal invasion and the patient was at high risk of ILD exacerbation. We therefore selected transhiatal esophagectomy without a thoracotomy considering the risk of postoperative respiratory complications, and administered methylprednisolone and sivelestat in the perioperative period for the reduction of surgical stress. To our knowledge, this is the first report of surgical treatment for esophageal cancer with ILD. The patient was discharged without postoperative complications. Transhiatal esophagectomy is an appropriate choice for patients with early-stage esophageal cancer without lymph node metastasis who are at high risk for postoperative respiratory complications. The appropriate selection of treatment is important for patients with esophageal cancer considering the risk of complications

A Feasibility Study of Postoperative Adjuvant Therapy of Carboplatin and Weekly Paclitaxel for Completely Resected Non-small Cell Lung Cancer

IntroductionRecent clinical trials have shown significant survival benefits from postoperative adjuvant therapy for respectable nonsmall cell lung cancer (NSCLC). However, evaluation of adjuvant chemotherapy with carboplatin combination is still uncertain. The purpose of the study was to test the feasibility of adjuvant chemotherapy with carboplatin and separate weekly paclitaxel after complete resection of pStage IB, II, IIIA NSCLC in a multicenter study.MethodsThe study was conducted from 2001 to 2006 in the outpatient setting. A total of 61 patients were enrolled. Patients received adjuvant chemotherapy with 4 cycles of carboplatin (AUC 5) on day 1 and paclitaxel (70 mg/m2) on day 1, 8, and 15 every 4 weeks. Primary endpoints were toxicity and chemotherapy compliance. Secondary endpoints were disease-free survival and overall survival.ResultsMore than 65% of eligible patients had pStage IIIA. The median number of chemotherapy cycles was 4 (range 1–4). Grade 3 or 4 toxicities of neutropenia were 34% (grade 4: 2%). Other hematologic adverse effects were extremely less frequent. Regarding the nonhematologic adverse effect, hair loss was frequent; however, peripheral neuralgia was less frequent. Treatment-related death was not registered. During median follow-up of 21 months, 24 patients developed recurrent disease. Estimated disease-free survival and overall survival at 2 years was 51.2% and 84.6%, respectively.ConclusionsPostoperative carboplatin and weekly paclitaxel showed favorable feasibility and acceptable toxicity in comparison with the cisplatin-containing regimen. Consequently, it is desirable that this regimen would be validated in a phase III clinical trial for NSCLC after curative resection