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Biomedical subjects

N Colombo

Publications and source records attributed to N Colombo.

At least 55 records · Page 3Linked to original sources

[Neuroradiologic study of partial temporal epilepsy].

MR imaging is considered the neuroradiological procedure of choice for the study of intractable partial epileptic patients. The role of CT-scan is limited to the demonstration of calcific components of the lesion and of bony abnormalities of the adjacent skull. In this chapter we describe an MR protocol for the evaluation of temporal lobe epilepsy patient; moreover, here there are described neuroradiological characteristics (MR and CT) of the more frequent temporal lobe lesions.

Astrocytoma↗

The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery. METHODS: Eligible patients had residual lesions measuring more than 1 cm in diameter after primary surgery. After three cycles of cyclophosphamide and cisplatin, these patients were randomly assigned to undergo either debulking surgery or no surgery, followed by further cycles of cyclophosphamide and cisplatin. The study end points were progression-free and overall survival. At surgery 65 percent of the patients had lesions measuring more than 1 cm. In 45 percent of this group, the lesions were reduced surgically to less than 1 cm. RESULTS: Of the 319 patients who underwent randomization, 278 could be evaluated (140 patients who underwent surgery and 138 patients who did not). Progression-free and overall survival were both significantly longer in the group that underwent surgery (P = 0.01). The difference in median survival was six months. The survival rate at two years was 56 percent for the group that underwent surgery and 46 percent for the group that did not. In the multivariate analysis, debulking surgery was an independent prognostic factor (P = 0.012). Overall, after adjustment for all other prognostic factors, surgery reduced the risk of death by 33 percent (95 percent confidence interval, 10 to 50 percent; P = 0.008). Surgery was not associated with death or severe morbidity. CONCLUSIONS: Debulking surgery significantly lengthened progression-free and overall survival. The risk of death was reduced by one third, after adjustment for a variety of prognostic factors.

Adult↗

Peripheral neurotoxicity of taxol in patients previously treated with cisplatin.

BACKGROUND: Taxol is a new anticancer drug that acts as a tubulin polymeration enhancer. Its major toxicities are myelosuppression, hypersensitivity, and mucositis, but it also induces peripheral nerve damage. The use of taxol has recently been proposed for platinum-resistant cancers, but in these cases there is a possibility of cumulative toxicity in the peripheral nervous system. METHODS: Twenty-two patients affected by a relapse of cisplatin-treated ovarian cancer were examined clinically and neurophysiologically to determine the evolution of taxol-induced peripheral somatic and autonomic neurotoxicity and the possible cumulative effect of a combination of taxol and cisplatin. Each patient was examined before, during, and after taxol treatment (using a dose of 135 or 175 mg/m2 in 3 hours every 3 weeks). RESULTS: No patients were excluded from the study because of unacceptable toxicities of any kind. The serial examinations demonstrated that taxol induced onset of (or worsening of preexisting) neuropathic symptoms and signs in almost all the patients. The features were those of a distal, symmetrical, sensory polyneuropathy due to an axonopathy. Motor nerves and the autonomic nervous system were unaffected. Taxol neurotoxicity appeared early in the course of the treatment (i.e., after three courses) and was not severely disabling. In most cases after the early onset of peripheral neuropathy, stabilization of this side effect occurred. CONCLUSIONS: Considering the low doses of taxol used in this study, the sensory nerve damage was unexpectedly severe. It appears that a cumulative, but not dose-limiting, neurotoxic effect occurs using taxol in patients previously treated with cisplatin.

Adult↗

Effects of granulocyte-monocyte colony-stimulating factor (GM-CSF) on expression of adhesion molecules and production of cytokines in blood monocytes and ovarian cancer-associated macrophages.

The present study was aimed at characterizing the effects of in vitro exposure to GM-CSF on blood monocytes and tumor-associated macrophages (TAM) in human ovarian cancer. Purified populations of TAM from ovarian cancer patients were studied in terms of expression of surface molecules, cytokine production and tumor cytotoxicity after overnight incubation with GM-CSF or IFN gamma and LPS, used as reference activators. GM-CSF augmented the surface expression of ICAM-I and CD18 in TAM and in blood monocytes. Stimulation was more prominent in monocytes than in TAM, which showed higher baseline expression of this adhesion molecule. ICAM-3 was not influenced by GM-CSF or by IFN gamma/LPS. GM-CSF-augmented ICAM-I expression was associated with higher levels of mRNA transcripts. The protein synthesis inhibitor cycloheximide super-induced basal and GM-CSF-induced ICAM-I transcripts, thus excluding a role for secondary polypeptide mediators. In the absence of stimuli, TAM produced higher levels, compared to monocytes, of IL-6 and IL-8 but not of IL-1 and TNF. GM-CSF augmented the production of IL-6 and IL-8 (but not that of IL-1 and TNF) in TAM, whereas it had little effect on blood monocyte. Tumoricidal activity was tested against two ovarian tumor cell lines (OVCAR3 and SW626). GM-CSF more prominently augmented monocyte cytotoxicity, while only 2 of 6 TAM preparations were stimulated by GM-CSF. These results suggest that GM-CSF selectively regulates the function of blood monocytes and TAM, the effect of this cytokine varying with the parameter and cell population examined. These data provide a rational and biological endpoint for further studies with GM-CSF as an activator of mononuclear phagocyte function in ovarian cancer.

Adenocarcinoma↗

Surgical management of malignant ovarian germ-cell tumors: 10 years' experience of 129 patients.

OBJECTIVE: To evaluate the surgical management of ovarian germ-cell tumors treated at a single institution during the last decade. METHODS: One hundred twenty-nine patients affected by ovarian germ-cell tumors were studied retrospectively for their surgical management. Fifty-seven patients were affected by dysgerminoma, 39 by non-dysgerminoma, and 33 by pure immature teratoma. Seventy-nine patients were stage I according to International Federation of Gynecology and Obstetrics criteria, with five first referred at recurrence, 11 at stage II, 35 at stage III, and four at stage IV. RESULTS: Fertility-sparing surgery was performed in 108 of 129 patients. Eighty-five of 100 referred patients underwent surgical or radiologic restaging, with an increase in staging in 16 cases. Three patients with immature teratoma underwent second laparotomy for a growing mass. Thirty-one patients underwent second-look surgery, with positive findings in four cases. Three patients did not respond to chemotherapy, and ten had a recurrence after complete response or surveillance. Six patients died of tumor, with an overall survival of 96% (mean follow-up time 55 months). CONCLUSION: Fertility-sparing surgery is warranted in all ovarian germ-cell tumors because it does not affect recurrence rate or survival. Extensive tumor-reductive surgery is advisable only in immature teratoma patients and is not necessary for other histologic types. Restaging can be useful in selected cases, but the administration of effective chemotherapy, when needed, seems to be more important. The usefulness of second-look surgery is marginal.

Adolescent↗

Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica.

BACKGROUND: From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients. METHODS: Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. RESULTS: With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. CONCLUSION: Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.

Adult↗

[Kinetics of hepatic enzymes in anorexia nervosa].

Nervous anorexia in advanced stage causes a generalized deterioration of organs' and apparatuses' functions. In particular, well-known are disorders of both CNS and PNS, changes of the haematic crasis and worsening of the metabolic-endocrine axis. Less well-known, however, is the compromission of function. Analysis of the data obtained in this trial points out a statistically significant correlation between the loss of weight and the variation of level of some liver enzymes (SGPT, SGOT, LDH). These indexes of hepatic necrosis in our opinion, can therefore, be regarded as sound markers not only for a more careful evaluation of the clinical evolution of the anorexic patient, but also for a better monitoring of the effectiveness of diet therapy.

Adult↗

Controversial issues in the management of early epithelial ovarian cancer: conservative surgery and role of adjuvant therapy.

The feasibility of conservative surgery and the role of postoperative adjuvant therapy are still controversial issues in the management of early ovarian cancer. Data on 99 patients below the age of 40 with stage I ovarian cancer are reported and conservative surgery was performed in 56 (56%) patients (36 stage Ia, 1 stage Ib, and 19 stage Ic). Relapse occurred in 3 stage Ia (grades 1, 2, and 3) patients, but only 1 occurrence was in the residual ovary and the patient was rescued by surgery. The other 2 patients who relapsed in distant sites died as a result of their tumors. Seventeen patients who desired to become pregnant did so for a total of 25 conceptions. These data support the possibility of some extension of the traditional conservative approach. Only two randomized studies so far have tested cisplatin as an adjuvant treatment of early disease. A Norwegian trial compared cisplatin to 32P in stage I-III ovarian cancer without residual tumor after primary surgery and found no difference in survival. An Italian study compared cisplatin to observation in stage Ia and Ib grade 2 and 3 tumors and cisplatin to 32P in stage Ic patients. While disease-free survival was statically longer in cisplatin-treated patients of both groups, no difference in survival could be detected. These results supported the design of a currently ongoing multicenter trial testing platinum-based therapy soon after surgery or at time of relapse.

Adult↗

Options for primary chemotherapy in advanced ovarian cancer: the European perspective.

Primary chemotherapy for ovarian cancer has evolved over the past 30 years from the use of single alkylating agent to several combination regimens. Treatment strategies, however, vary greatly both nationally and internationally, since no firm results can be derived from available data. Five questions can be identified: (1) Should primary chemotherapy consist of single agent or combination? (2) Should it include doxorubicin? (3) Is cisplatin or carboplatin preferred? (4) Which is the role of cisplatin dose intensity? (5) Should it include taxol? Available data from the European experience are discussed. Final considerations include: (1) Platinum combinations are more effective than single agent platinum when this drug is used at the same dose (now considered lower than current standard). (2) CAP offers a survival benefit of 7% at 6 years compared to CP. However, in most trials dose intensity was higher in CAP than in CP. (3) Cisplatin and carboplatin are equally effective. (4) There is no survival benefit when doubling the dose intensity of cisplatin over 25 mg/m2/week. (5) A confirmatory study will help define the contribution of Taxol in the first-line treatment of ovarian cancer, when administered at 175 mg/m2 over a 3-hr infusion in association with cisplatin.

Antineoplastic Agents↗

Leptomeningeal dissemination of juvenile pilocytic astrocytoma: case report.

The authors report a case of leptomeningeal spinal metastasis of chiasmatic juvenile pilocytic astrocytoma. A 7-year-old boy underwent surgery and radiation therapy for a chiasmatic pilocytic astrocytoma. Three years later he experienced a syndrome of medullary compression. A lumbosacral intradural extra-axial tumor was discovered and subtotally excised. Pathologic examination revealed a metastasis of the chiasmatic tumor without any evidence of malignant transformation. Only five cases of leptomeningeal spinal dissemination of pilocytic astrocytoma have been previously reported. The authors review and discuss the clinical and pathologic features of these cases.

Astrocytoma↗

Spared and impaired cognitive abilities after bilateral frontal damage.

We report on a patient (PG) with a severe behavioural disorder following massive bilateral prefrontal damage due to herpetic encephalitis. The lesion involves also the mesial and polar regions of the temporal lobes; the frontal dorso-lateral cortices were relatively spared. The patient's inattentiveness and alternating impulsive and apathetic behaviour led to her social alienation. The only self-motivated activities we observed were those initiated to satisfy her enhanced urge to eat and play games. She did not react to surprise stimuli that consistently elicit a reaction of surprise in healthy people. She also presented "adynamic aphasia" associated with anomia and episodic amnesia. A striking feature of the syndrome was the patient's consistent "utilization behaviour". Her motor behaviour was marked by constant akathisia. She performed surprisingly well on intelligence, "frontal", and visuo-spatial tests. This non-demented patient exhibited a clear dissociation between her relatively spared cognitive abilities and grossly impaired behaviour. In the discussion we explore the extent to which a defect of the supervisory control may be held responsible for the inconsistencies in the patient's coping skill performances.

Adolescent↗

European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion.

PURPOSE: Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. METHODS: Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. RESULTS: Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. CONCLUSION: The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.

Adult↗

Pure ovarian immature teratoma, a unique and curable disease: 10 years' experience of 32 prospectively treated patients.

OBJECTIVE: To report and evaluate a conservative and individualized treatment policy in a homogeneously selected series of patients affected by pure ovarian immature teratoma. METHODS: This prospective trial, with specific treatment policies according to stage and grade, was planned and started in 1982. The study population consisted of 32 patients affected by pure immature teratoma, with the exclusion of mixed germ cell tumors. Fertility-sparing surgery was performed whenever possible. Surgery alone, with careful follow-up, was adopted for stage I or II according to the International Federation of Gynecology and Obstetrics (FIGO) and grade 1 or 2 tumors. The other patients, with stage III or with grade 3 stage I or II tumors, or those referred at relapse, were treated with platinum-based chemotherapy regimens. RESULTS: Thirty of 32 patients underwent fertility-sparing surgery. Ten of 32 patients received chemotherapy after surgery, either as adjuvant treatment or in the presence of visible tumor. All 32 patients are alive and disease-free, with a median follow-up from surgery of 47 months (range 11-138). In six patients, regardless of the administration of chemotherapy, the tumor either spontaneously differentiated toward mature glia or increased in volume, mimicking progression but still remaining completely mature. Five of six patients wishing to procreate had a total of seven normal pregnancies. CONCLUSIONS: Pure ovarian immature teratoma is a potentially curable disease with a unique natural history. Our data substantiate the hypothesis that low-grade and low-stage tumors do not require chemotherapy, and that a fertility-sparing surgical approach is warranted in all cases.

Adolescent↗

Analytical-physical profile of the novel macrolide antibiotic flurithromycin ethylsuccinate.

Data are reported on the structural characterization of flurithromycin ethylsuccinate (FE, CAS 82730-23-2), a novel macrolide antibiotic. UV, IR, NMR and MS spectra confirmed the structure; in particular the presence of ketonic-hemiketalic equilibrium, already described for flurithromycin A, is supported by NMR and HPLC studies. Moreover physico-chemical properties and stability were studied; the product exhibits a good stability at solid state, whereas degradation products are present both in acidic and basic solution. Microbiological activity and principal pharmaceutical features were carried out.

Animals↗

MR of corticotropin-secreting pituitary microadenomas.

PURPOSE: To assess the accuracy of MR in the preoperative identification of corticotropin-secreting pituitary microadenomas. METHODS: Twenty-six patients with clinical and biochemical evidence of pituitary-driven Cushing disease in whom MR of the seller region was performed were selected for this study. The MR examinations were retrospectively evaluated by a neuroradiologist who was aware of the presence of an adenoma at surgery but not of location and size of the lesion. RESULTS: Considering the whole group of MR examinations performed either without (n = 26) or without and with intravenous injection of gadopentetate dimeglumine (n = 16), overall 20 MR studies were judged to show disease. Seventeen of 26 microadenomas were adequately shown and located by MR (true-positive, 65.4%). In three cases the sides of the microadenomas were misjudged (false-positive, 11.5%). Six patients had negative MR studies (false-negative, 23%). Twelve of the 16 patients studied after gadopentetate dimeglumine injection had true-positive MR findings (75%). CONCLUSIONS: In our experience the accuracy of MR in detecting corticotropin-secreting microadenomas as small as 2 to 3 mm is 65% to 75%. Although precontrast images provide diagnostic information, the microadenoma can be better seen with administration of contrast material.

Adenoma↗

Low-dose oral etoposide in epithelial cancer of the ovary.

AIMS: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of low-dose oral etoposide (E) in patients (pts) with epithelial cancer of the ovary previously treated with cisplatin. PATIENTS AND METHODS: Eighteen pts receiving 50 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of bioavailability and weekly 24-hour drug concentrations. RESULTS: Among 17 evaluable pts, 1 partial remission of 9 months. Dose-limiting neutropenia of high inter-patient variability. Mean bioavailability value of 75%, ranging from 44% to 100%. No correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC during the first cycle. CONCLUSIONS: Low-dose oral E is ineffective as salvage treatment in epithelial cancer of the ovary. The large variability of neutropenia requires a careful hematological monitoring to avoid severe myelosuppression.

Administration, Oral↗

Overexpression of p185 is not related to erbB2 amplification in ovarian cancer.

BACKGROUND: While in breast cancer the amplification and overexpression of the erbB2 gene has been reported in numerous studies and found to be correlated to poor prognosis, information about this oncogene with respect to ovarian cancer is still limited. A recent study reported that approximately 30% of tumor biopsies from ovarian cancer patients exhibited erbB2 amplification and overexpression and suggested that the overexpression of this oncogene is an indicator of bad prognosis in ovarian cancer. The purpose of our studies was to investigate amplification of the erbB2 gene, the levels of erbB2 m-RNA and the erbB2 product (p185) in ovarian cancer, and the correlation between these findings and the pathological and clinical features. RESULTS: Amplification of the erbB2 gene was investigated by Southern blot analysis in 75 samples from 62 patients; mRNA levels were evaluated by Northern blot analysis in 58 samples from 48 patients; and p185 was determined by immunohistochemistry in 65 samples from 65 patients. The erbB2 gene was amplified in only one case (1.6%), and a marked increase in erbB2 mRNA was found only in the same case. Staining for p185 was positive in 12 cases (18.5%). The staining was always confined to the cytoplasm except in the case that showed amplification of erbB2 in which p185 was localized in the membrane. No correlation was found between p185 positivity and pathological and clinical features or response to chemotherapy. Western blot analysis showed that the molecular weight of p185 in positive ovarian cancer cells was approximately 10 KDa lower than in breast cancer. CONCLUSION: In contrast to breast cancer, in ovarian cancer the amplification of erbB2 appears infrequent. The levels of p185 detected by immunohistochemistry were not related to the amplification of the gene or to the increase in mRNA, suggesting the possibility of a longer half-life of the protein in the positive cases. The finding that erbB2 product in ovarian cancer is mostly localised in cytoplasm and not in the membrane as in breast cancer and that it has a lower molecular weight than the p185 in breast cancer suggest that this oncogene plays a different biological role in these two neoplasms.

ErbB Receptors↗