Search

Background: Pulmonary tumor thrombotic microangiopathy is a special type of tumor thromboembolism. We report the case of a patient who developed pulmonary tumor thrombotic microangiopathy with alveolar hemorrhage. Almost all patients with pulmonary tumor thrombotic microangiopathy die within 1 week of the onset of dyspnea; however, the prognosis in this case was better, with 10 weeks of survival from presentation.Case Presentation: A 62-year-old Japanese man was referred to our hospital with a 4-week history of dyspnea on exertion and severe pulmonary hypertension. Five years previously, he had undergone distal gastrectomy for gastric cancer. He was afebrile, normotensive, and hypoxemic. A physical examination was unremarkable except for purpura on his upper extremities and trunk. Blood tests showed anemia and disseminated intravascular coagulation. Chest computed tomography revealed diffuse ground-glass opacities with emphysema in his upper lungs, moderate pleural effusions, mediastinal lymphadenopathy, and enlargement of the right ventricle and main pulmonary artery. A computed tomography pulmonary angiogram showed no evidence of pulmonary embolism. Lung perfusion scintigraphy showed multiple segmental defects. Although recurrence of gastric cancer was confirmed from the results of bone marrow biopsy, bronchoscopy was not performed due to bleeding diathesis. He was treated with corticosteroids, antibiotics, and platelet transfusion, following which resolution of the abnormal lung shadows and right ventricular pressure overload along with partial alleviation of respiratory failure was observed. Because of his poor performance status, he was eventually transited to palliative care and died 6 weeks after admission. Necropsy of the lung confirmed the diagnosis of pulmonary tumor thrombotic microangiopathy with alveolar hemorrhage.Conclusions: Pulmonary tumor thrombotic microangiopathy should be considered in the differential diagnosis of patients with cancer who present with severe pulmonary hypertension. In pulmonary tumor thrombotic microangiopathy, local inflammation in pulmonary microvasculature may contribute to pulmonary hypertension, and regulation of inflammation using corticosteroids may help improve the prognosis. [ABSTRACT FROM AUTHOR]

Activating mutations of RAS gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. However, several studies have shown a frequent loss of the wild-type KRAS allele in the tumors of murine models and an inhibition of oncogenic phenotype in tumor cell lines by transfection of wild-type RAS, indicating that wild-type RAS may have oncosuppressive properties. To determine whether loss of wild-type KRAS is involved in the development of human lung cancer, we investigated the mutations of KRAS, NRAS and BRAF in 154 primary non-small cell lung cancers (NSCLCs) as well as 10 NSCLC cell lines that have been shown to have KRAS mutations. We also determined the loss of heterozygosity status of KRAS alleles in these tumors. We detected point mutations of KRAS in 11 (7%) of 154 NSCLCs, with 10 cases at codon 12 and 1 at codon 61, but no mutations of NRAS or BRAF were found. Using the laser capture microdissection technique, we confirmed that 9 of the 11 tumors and 7 of the 10 NSCLC cell lines retained the wild-type KRAS allele. Among the cell lines with heterozygosity of mutant and wild-type KRAS, all of the cell lines tested for expression were shown to express more mutated KRAS than wild-type mRNA, with higher amounts of KRAS protein also being expressed compared to the cell lines with a loss of wild-type KRAS allele. In addition, among 148 specimens available for immunohistochemical analysis, 113 (76%) showed positive staining of KRAS, indicating that the vast majority of NSCLCs continue to express wild-type KRAS. Our findings indicate that the wild-type KRAS allele is occasionally lost in human lung cancer, and that the oncogenic activation of mutant KRAS is more frequently associated with an overexpression of the mutant allele than with a loss of the wild-type allele in human NSCLC development., (Copyright 2003 Wiley-Liss, Inc.)

Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen representing more than 90% of organic substances in bone and expected to be one of the markers reflecting bone resorption. We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis from primary lung cancer by comparing serum alkaline phosphatase (ALP), a bone formation marker, which was simultaneously measured. In addition, using the receiver operating characteristic (ROC) curve, we calculated the cut-off value of ICTP from which the diagnostic accuracy serves as best. The subjects were 87 patients with primary lung cancer including 21 patients with bone metastasis. ICTP was significantly higher in patients with bone metastasis than in the group without bone metastasis. On the other hand, in the serum ALP there was no significant difference between the two group. The result suggested that measurement of serum ICTP is worthwhile as a diagnosis method of bone metastasis from lung cancer. The calculated cut-off value was 6.4 ng/ml, higher than the 4.5 ng/ml indicated by the appending document which was from patients with lung, breast and prostate cancer. It is possible that the reason for the style of bone metastasis from lung cancer is mainly a osteolytic process.