Prognostic implications of patterns of failure for gastrointestinal leiomyosarcomas.

One hundred ninety-one patients with gastrointestinal leiomyosarcomas were analyzed to determine the prevalence in patterns of failure and the factors predicting those at higher risk of relapse at specific sites. Of 100 assessable patients who died of disease, 89% were found to have peritoneal tumor, 78% had liver metastases, and 32% had extraabdominal metastases. Of 132 patients (69%) with initial complete resection of the primary tumor, only 10% (n = 13) remained free of disease as of the last follow-up. The median interval to recurrence was 18 months; 60% of all recurrences occurred within 2 years after surgery. Half of these patients (n = 61) had metastases (predominantly in the liver) as the initial recurrence. Factors significantly associated with improved survival after relapse were initial disease-free interval of 18 months or more, recurrences either isolated to the peritoneal cavity or within the liver, or complete resection of peritoneal recurrences or liver metastases. In contrast, those patients with recurrences at multiple sites or unresectable disease had significantly shorter survival times. The presence of extraabdominal metastases also heralded an equally poor outcome. In conclusion, a multimodality approach is necessary to improve outcome from this disease because the liver and peritoneal cavity represent predominant sites of failure. Complete resection of isolated peritoneal or hepatic metastases improves survival and should be attempted when feasible.     

5-HT3 Receptor-independent Inhibition of the Depolarization-induced 86Rb Efflux from Human Neuroblastoma Cells,TE671, by Ondansetron

The 5-HT₃-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an ⁸⁶Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT₃-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT₃ agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT₃ receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.     

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.     

ELECTROHYDRAULIC LITHOTRIPSY: AN EFFECTIVE AND ECONOMICAL MODALITY OF ENDOSCOPIC URETERIC LITHOTRIPSY

Background : Electrohydraulic lithotripsy (EHL) has been available for endoscopic treatment of urinary calculi since 1960, but the large probe size and concerns regarding safety had previously restricted its use to the treatment of bladder calculi. However, recent refinements have made it particularly suitable for the treatment of ureteric calculi. Methods : The authors report their initial experience using EHL in conjunction with mini-ureteroscopy in the treatment of 94 ureteric calculi in 89 patients. The size of the calculi ranged from 3 to 19 mm in diameter, with a mean of 8.2 mm. The mean operating time was 29 min, ranging from 10 to 120 min. Results : A complete fragmentation rate of 91.5% of the calculi was achieved. There were no major complications and a low incidence of minor complications: haematuria (2.2%), urinary tract infection (3.4%) and postoperative ureteric colic (2.2%). There were four cases of minor ureteric perforations (4.5%); all were successfully treated using conservative measures. Conclusions : It is concluded that EHL is a safe and effective method of treating ureteric calculi.     

Adeno-associated virus vector-mediated systemic delivery of IFN-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models.

PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression.     

Cerebral amyloid angiopathy and spontaneous intracerebral haemorrhage. Report of a sporadic case in a young Chinese.

A 49-year-old Chinese male with spontaneous intracerebral haemorrhage due to cerebral amyloid angiopathy is presented. This is the first case reported in the Chinese population, and the youngest patient described without a family history or associated mental disorder.     

Colposcopic assessment in microinvasive carcinoma of the cervix

Forty of the 87 patients with microinvasive carcinoma (MIC) of the uterine cervix who underwent surgery were diagnosed colposcopically and the results were compared with the cytological and histological diagnoses. The cytology showed preinvasive carcinoma in 20 (50.0%) patients and invasive carcinoma in 19 (47.5%) patients. A correct colposcopic diagnosis was made in nine (22.5%) patients as having microinvasive carcinoma, 21 (52.5%) patients preinvasive carcinoma and eight (20%) patients invasive carcinoma, to sum up accuracy rate as 32.1%. The abnormalities most commonly observed in colposcopy were mosaic, punctuation and white epithelium. In microinvasive carcinoma, the triad co-existed in 43% of the patients. Atypical vessels, characteristic of invasion, were found in only one third of the patients. Microinvasion, therefore, may not be evident on colposcopy alone. It is therefore necessary to apply cone biopsy, prior to definite therapy, to make an accurate assessment of the maximum depth and extent of the invasion prior to definitive therapy.