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.     

INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA

1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.     

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.