Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions

Background: The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27^kip1 play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions. Methods: A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry. Results: P53 was expressed in 15% of cases with gastric dysplasia and not in the pre‐dysplastic stages of the gastric mucosa. All cases were concerning high‐grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27^kip1 protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27^kip1 protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27^kip1 protein. Conclusions: (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27^kip1 is a rather early event in gastric tumorigenesis, before dysplastic changes occur.     

Zur Casuistik der Hirntumoren

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Beiträge zur epidemischen Cerebrospinal-Meningitis

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Chemotherapy for patients with two favourable subsets of unknown primary carcinoma: active, but how effective?

Carcinoma of unknown primary (CUP) is characterized by dismal patient survival. The outcome of patients with two favourable risk CUP subsets was studied. Eighty patients diagnosed with either midline lymph node metastases (n=33) or peritoneal carcinomatosis (n=47) were analysed retrospectively. The majority had poorly differentiated adenocarcinoma or undifferentiated carcinoma, treated with platinum-taxane based chemotherapy from 1996 till 2002. Females with peritoneal carcinomatosis also underwent surgical debulking. Objective tumour regression was present in 44% of patients (nodal group 30% versus peritoneal group 53%, p=0.066). Complete responses were seen more often in peritoneal carcinomatosis patients (nodal group 9%, peritoneal group 36%, p=0.008). At a median follow up of 60 months, median progression-free and overall survival were 5 and 10 months respectively in the nodal group, 7 and 15 months in the peritoneal group. Five-year survival was 7% (nodal group 0% vs. peritoneal group 10%, p=0.05). Complete responders fared better than non-CR patients. Fewer than four metastatic sites, elevated CA 125, and normal CA 19-9 levels were favourable prognostic factors for survival. Modern combination chemotherapy has satisfactory activity, with a minority of CUP patients enjoying long-term responses. Research efforts towards complete remission consolidation and molecular profiling are imperative.     

The correlation between carotid plaque ulceration and cerebral infarction seen on CT scan

The purpose of the study was to determine the association between cerebral infarction seen on CT scan and macroscopic ulceration of atheromatous carotid plaques in patients undergoing carotid endarterectomy. Following carotid endarterectomy in 65 patients, specimens were examined for the presence of ulceration without knowing the result of the preoperative CT brain scan. The 65 patients thus investigated underwent 68 carotid endarterectomies: 36 for a history of transient ischemic attacks (TIAs), 13 for amaurosis fugax, and six for prior strokes; 13 asymptomatic patients had prophylactic carotid endarterectomy prior to coronary bypass. A macroscopic ulcer was present in 42 specimens. Twenty-six (62%) of the patients with ulceration had one or more ipsilateral cerebral infarcts on CT scan. Only two (8%) of the 26 patients without an ulcer had cerebral infarcts. Of the 36 patients who presented with TIAs, 26 (72%) had carotid plaque ulcers and 23 (88%) of these had cerebral infarcts on CT scan also. In contrast, only three of 13 asymptomatic patients had plaque ulcers and only one of these had a cerebral infarct. There is a high incidence of cerebral infarction seen on CT scan in patients presenting with TIAs. These infarcts occur predominantly in patients with ulcerated atheromatous carotid lesions. (J VASC SURG 1984;1:782-786.)     

Anuria due to acute bilateral renal vein occlusion after thrombolysis for pulmonary embolism

Severe hemorrhage is the more frequent complication of thrombolysis, with intracranial bleeding the most critical one. We report a 73-year-old woman with major pulmonary embolism (PE), yet haemodynamically stable, in whom thrombolysis resulted in severe complications with acute renal failure (ARF) due to bilateral renal vein occlusion, quite unexpected; this complication has never been reported, as yet. We believe that disrupture of peripheral vein clots by thrombolysis led to migration of thrombi particles upwards to the inferior vena cava (IVC) and bilateral renal vein occlusion. However, the large thrombus straddled to the bifurcation of the main pulmonary trunk and extending to the right pulmonary artery, as visualized by transthoracic (TTE) and transesophageal echocardiogram (TEE), was not affected by thrombolysis. Finally, endogenous fibrinolytic activity, under low molecular weight heparin, resulted in a slow dissolution of the pulmonary thrombus and restoration of kidney function.