[Correlation between histological and molecular mechanisms of carcinogenesis in stomach cancer]. / Korrelation zwischen Histologie und molekularen Mechanismen der Karzinogenese beim Magenkarzinom.

Since gastric cancer is an exceptional heterogeneous tumor conflicting results have been obtained about the relationship between genotype and phenotype. From the molecular point of view gastric carcinoma diffuse type forms a distinct entity which is microsatellite stable, has almost no p53 mutations and exhibits in at least half of the cases mutations in the E-cadherin gene. In contrast, all other gastric carcinomas comprise a heterogeneous group of which about one third exhibits microsatellite instability (MSI) but no p53 protein stabilization or gene mutations. These tumors are either of pure intestinal (glandular) type or show large solid (medullary) tumor cell clusters. Thereby, in sporadic gastric cancer MSI is caused by loss of hMLH1 expression due to hypermethylation of the promotor region rather than by mutation of the gene itself. Tumors that are microsatellite stable (MSS) and show p53 alterations are either intestinal (about 70%) or a mixed-type encompassing at least 5% glandular and poorly differentiated diffuse components (about 30%). Whereas pure diffuse type gastric cancer is unlikely to develop from intestinal type carcinoma, this may, however, be the case in some advanced mixed-type gastric cancers.

Pathogenesis determines late morbidity of axillosubclavian vein thrombosis.

The late consequences of axillosubclavian vein thrombosis were evaluated through a clinical follow-up of 41 patients (45 limbs) treated from July 1975 to December 1985. The causes of the obstruction were classified into two main groups: Intrinsic damage, consisting of thrombophlebitis due to intravenous drug abuse (11 patients), central venous catheterization (10 patients), and hypercoagulability state (2 patients); and extrinsic obstruction, involving effort-induced or thoracic outlet obstruction (9 patients), underlying neoplastic disease (5 patients), trauma (3 patients), and congenital venous malformation (1 patient). Clinical diagnosis was confirmed by upper arm venography in all 41 patients, and all were initially treated by anticoagulation with heparin for 1 to 2 weeks, usually followed by oral warfarin for a variable period of 1 week to 5 years. Only three patients had an operation (rib resection for thoracic outlet obstruction, thrombectomy and clavicle fixation, and repair of a congenital venous malformation). Major early morbidity consisted of a documented pulmonary embolus in five patients, two in Group I and three in Group II, for an overall incidence of 12 percent. Clinical follow-up of up to 5 years revealed that chronic morbidity was related to our classification. Thrombosis secondary to intrinsic damage rarely caused persistent symptoms and responded well to anticoagulation alone. Conversely, when extrinsic obstruction was the cause, only 50 percent of patients were symptom-free, whereas many had disabling intermittent arm swelling and pain. Repeat venography in severely symptomatic patients revealed persistent obstruction with no recanalization. We conclude that patients with axillosubclavian venous thrombosis due to intrinsic damage do not require treatment other than anticoagulants, whereas patients with extrinsic obstruction often have poor long-term results from conventional therapy and therefore should be considered for adjunctive treatment with thrombolysins or operative intervention.