Cancer of the cardia. Prognostic factors and treatment]

Pronostic of carcinoma of the esogastric junction is worsened by the potential two-way route of spread in case of lymph node metastasis: mediastinum and abdomen. During the last 10 years the authors observed 71 cases of adenocarcinoma of the gastric cardia, including 7 cases of linitis plastica. Histopathologic and clinical follow-up data are presented. The aims of the study were to evaluate prognostic factors and to define the best surgical treatment. There were mainly elderly patients with a poor physical status. Ten patients did not undergo surgery (14%). Among 57 patients undergoing radial resection (80.3%), total gastrectomy and upper polar esogastrectomy were performed in respectively 29 and 28 cases. The carcinomas were truly located to the gastric cardia in only 37 cases (65%). Operative mortality was 12.3%, not depending of the surgical technique. All patients five-year survival rate was 10.2%, improving to 15% in case of curative resection. The value of lymph node metastasis (80.7% of the patients) as a prognostic factor depended of the proximal or distal localization of the nodes. A positive surgical margin (15.7% of the patients) was a poor prognostic factor with a 6.9 months mean survival. The authors conclude that an aggressive surgical approach is worthwhile, because of the carcinoma invasion (nodes, margin), but not always possible (poor physical status).     

Characterization of persistent poliovirus mutants selected in human neuroblastoma cells

Six Sabin-derived persistent poliovirus mutants were selected in human neuroblastoma IMR-32 cells. The mutants had a titer 30 to 10⁵ times lower in nonneural HEp-2c cells than in IMR-32 cells. When the growth cycles of persistent viruses in the two cell lines were compared, the most striking feature was a delay of 2 to 4 hr in virus release from HEp-2c cells. In HEp-2c cells, type 1 mutants could spontaneously establish a persistent infection in the absence of any exogenous viral inhibitor. Mutations at a rate of 1 every 210 nucleotides had accumulated in the genome of the type 1 mutants selected in neuroblastoma cells, modifying cell specificity and conferring the ability to persist in some non-neural cells. These results indicate that mutants of poliovirus with highly modified biological properties can be selected in vitro in cells of neural origin.     

Aggressive fibromatosis of the neck: MR findings.

We present a case of aggressive fibromatosis of the scalene and longus colli muscles with surgically proved secondary involvement of the brachial plexus and carotid sheath in a 29-year-old woman in whom MR imaging failed to show involvement of the carotid sheath. The well-defined lesion was isointense on T1-weighted images and hyperintense on T2-weighted images relative to adjacent normal muscle and enhanced brightly.     

Transfection of pancreatic acinar cells (AR4-2J) by bFGF modifies cell morphology and biosynthesis of pancreatic secretory enzymes]

Basic fibroblast growth factor (bFGF or FGF-2) is present in the basal membrane of pancreatic cells during the pancreatic embryonic development. The expression of bFGF receptors has been described in normal pancreatic cells. By contrast, pancreatic cancer cells express not only the bFGF receptors but also the bFGF itself. With the aim of understanding the effects induced by the production of bFGF by pancreatic cancer cells, the pancreatic acinar cell line (AR4-2J) was used. AR4-2J cells do not produce bFGF but express bFGF receptors. These cells were transfected with a vector containing the bFGF cDNA encoding the three different forms of bFGF characterized in tumor cells. Results showed that the bFGF expression induced important phenotypic and enzymatic modifications. The transfected cells lost some morphological features of the acinar cells and expressed amylase and lipase at low levels (a 90% decrease for amylase activity, whereas lipase activity was barely detectable). These results suggest that bFGF could be involved in maintaining pancreatic cells in a slightly differentiated state.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

High-resolution x-ray computed tomography in lymphoid interstitial pneumonia

Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, "ground-glass" opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient present with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia.     

Human ventral mesencephalic xenografts to the catecholamine-depleted striata of athymic rats: ultrastructure and immunocytochemistry

On the basis of animal studies, grafts of fetal human dopaminergic cells have been suggested as a therapy for Parkinson's disease. The purpose of this study was to characterize the ultrastructure and immunocytochemistry of human ventral mesencephalic xenografts placed into the catecholamine-depleted striata of athymic "nude" rats. Human fetal tissue was obtained from tissue fragments derived from elective abortions during the first trimester of pregnancy. Small pieces of the basal mesencephalon were grafted into the catecholamine-depleted striata of four athymic nude rats. The rats were allowed to survive from 3 to 6 months after grafting; following fixation, the striatal tissue containing the grafts was labeled with antibodies against tyrosine hydroxylase and serotonin. Immunocytochemistry revealed tyrosine-hydroxylase-like-immunoreactive (THLI) and serotoninlike-immunoreactive (5HTLI) cell bodies within the human grafts. Both 5HTLI and THLI fibers crossed the graft-host interface and innervated the previously lesioned striatum. Both types of fibers also entered the host cortex from the adjacent human graft. At the ultrastructural level, THLI and 5HTLI fibers and synaptic terminals were observed in the host neuropil. THLI and 5HTLI dendrites and axon terminals were also observed in the neuropil of the grafts themselves. THLI axon terminals are not normally present in the substantia nigra. The results of our study indicate that human xenografts can survive in the neuropil of the host striatum and form morphologically appropriate synapses within the host brain.