Longer Postoperative Survival Research Articles

Enhanced expression of transforming growth factor β isoforms in pancreatic cancer correlates with decreased survival

Background: Transforming growth factor βs (TGF-βs) constitute a family of bifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. Perturbations in TGF-β expression and function may lead to loss of negative constraints on cell growth. In this study, we examined TGF-β expression in human pancreatic cancer. Methods: The distribution of TGF-β isoforms in 60 human pancreatic cancers was examined using immunohistochemical, Northern blot, and in situ hybridization techniques. Results: Immunohistochemical analysis showed the presence of TGF-β1 (47% of tumors), TGF-β2 (42% of tumors), and TGF-β3 (40% of tumors) in the cancer cells. The presence of TGF-β2 was associated with advanced tumor stage (P < 0.05). Furthermore, there was a significant correlation between the absence of TGF-βs in the tumors and longer postoperative survival. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P < 0.001), 7- (P < 0.05), and 9-fold (P < 0.001) increases in the messenger RNA (mRNA) levels encoding TGF-β1, TGF-β2, and TGF-β3, respectively. By in situ hybridization, these mRNA moieties colocalized with their respective proteins in the cancer cells. Conclusions: These findings show that human pancreatic cancers show increased levels of TGF-β isoforms and enhanced TGF-β mRNA expression and suggest that the presence of TGF-βs in pancreatic cancer cells may contribute to disease progression.

Leptomeningeal metastasis from supratentorial malignant gliomas.

The clinical and diagnostic findings in 13 patients with leptomeningeal metastasis from supratentorial malignant gliomas are reported. Criteria for inclusion in this study were positive myelographic examination, positive cerebrospinal fluid cytology on two or more samples, or evidence of leptomeningeal seeding at autopsy. Eight patients had premortem symptoms of leptomeningeal metastasis, with the diagnosis confirmed during life in 5 patients. Average survival after the onset of symptoms was 3 months (range, 1 to 5 months). Comparison of the autopsied group with 10 concurrent autopsied patients without leptomeningeal gliomatosis did not reveal any significant differences in age, but leptomeningeal gliomatosis was more prevalent in patients with longer postoperative survival. Leptomeningeal involvement at autopsy was more extensive in symptomatic patients. Cerebrospinal fluid examination often gave nondiagnostic or nonspecific results. Computed tomography of the brain showed evidence of ventriculomegaly, periventricular contrast enhancement, or multifocal tumor involvement in every case. Iophendylate myelography was the most reliable diagnostic tool and established the diagnosis whenever performed. The natural history and clinical significance of leptomeningeal metastasis from supratentorial malignant gliomas are discussed.

Splenectomy in agnogenic myeloid metaplasia: factors of possible prognostic significance

Summary The available data of 338 cases of splenectomy in agnogenic myeloid metaplasia published since 1940 were retrieved from the literature and analysed. Postoperative survival was significantly shorter in patients with anaemia, massive splenomegaly or elevated serum alkaline phosphatase. Younger age or normal platelet counts were associated with a longer postoperative survival than that in older patients and in patients with low platelet counts respectively. The shortest median postoperative survival was found in: patients in whom serum alkaline phosphatase exceeded twice the upper limit of the normal; patients with anaemia (less than 10 g/dl haemoglobin) and massive splenomegaly (above 3 kg); and patients with anaemia and a splenic weight less than one kg.

Spinal cord transection: a quantitative analysis of elements of the connective tissue matrix formed within the site of lesion following administration of piromen, cytoxan or trypsin.

Long-Evans hooded rats were cordotomized at the T-5 level and given either (1) cyclophosphamide (cytoxan), an immunosuppressive, (2) piromen, a bacterial polysaccharide-nucleic acid complex, (3) topical and systemic trypsin, or (4) no further specific treatment. Because of past and present controversy surrounding the proposed ability of these agents to promote spinal cord regeneration, a systematic study, employing light and electron microscopy, and quantitative methods in a single animal model, was done in order to re-evaluate the effects of each treatment upon the connective tissue matrix which forms in the defect left by transection. After an initial inflammatory reaction during the first week after surgery, the lesion zone is characterized either by areas of dense collagenous connective tissue with occasional fibroblasts and macrophages, or a loose areolar tissue with numerous sheets and cords of mesodermal cellular elements but minimal collagen. By 45 days postoperatively (dpo), axons supported by Schwann cells invade and become entangled in the loose connective tissue matrix. With longer postoperative survival, cysts appear craniad and caudad to the lesion and erode much of the scar together with viable neural tissue. Giving cytoxan or piromen did not result in any qualitative alteration of the scar matrix as evidenced by electron microscopy. Quantitative analysis revealed a slight reduction in the fibrous connective tissue component of the scar at 45--90 dpo, but this was transient when longer postoperative periods were studied. Trypsin caused a significant reduction in the amount of fibrous connective tissue with a concomitant increase in loose connective tissue and the appearance of a few distinctive, compact bundles of unmyelinated axons lacking Schwann cells. Consistent behavioral changes were not observed in any group which could distinguish them from the controls. Our results appear to contradict the findings of Matinian and Andreasian (1976) who reported return of normal sensori-motor function in 80% of their animals treated with topical and systemic trypsin. It is concluded that a major impediment to whatever longterm regenerative potential exists within the spinal cord is the lack of axonal guiding elements within the scar, but more importantly, the severe erosion of the remaining spinal cord due to cyst enlargement.

AUTORADIOGRAPHIC AND HISTOLOGICAL INVESTIGATION OF CHANGES IN THE VISUAL SYSTEM OF RATS AFTER UNILATERAL ENUCLEATION.

AbstractFollowing surgical removal of one eye, rats were permitted to survive for three days, one, two and four months, and before killing them they were injected with 2 mc of leucine‐H3 intraperitoneally. The utilization of this radiochemical was investigated in the brain autoradiographically. In all groups of animals the uptake of radioleucine, as determined by microdensitometry, was significantly higher in the “degenerated” optic nerve and tract than in their “normal” counterparts, with the relative difference increasing with longer postoperative survival within the periods tested. This progressive net increase in the utilization of leucine‐H3 was associated with an absolute increase in the number of glia cells. Similar, but attenuated, density differences were also obtained with relatively large‐aperture measurements over the stratum griseum of the superior colliculus in which the optic tract fibers terminate. In contrast, small‐aperture measurements of grain density over single neurons in the lateral geniculate nucleus showed no difference in the utilization of leucine‐H3 between the normal and subtotally deafferented sides. This suggests an absence of transneuronal changes in protein metabolism in the visual system of the rat as long as four months after unilateral enucleation.