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Biomedical subjects

G Canavese

Publications and source records attributed to G Canavese.

At least 37 records · Page 2Linked to original sources

Surgical complications related to peri-operative adjuvant chemotherapy in breast cancer. Results of a prospective, controlled, randomized clinical trial.

From May 1985 to June 1992, 375 patients were enrolled in a prospective controlled randomized clinical trial of peri-operative adjuvant chemotherapy (PAC) associated with long-term adjuvant chemo-endocrinotherapy in order to test the effectiveness of reducing the time interval between surgery and chemotherapy. The short-term surgical complications related to PAC are reported in order to verify whether such treatment might negatively affect the results of breast cancer surgery. One hundred and eighty-nine patients were randomly assigned to the peri-operative treatment, and 186 to the control group. Patients undergoing PAC received one course of cyclophosphamide (600 mg/sqm), epidoxorubicin (60 mg/ sqm), and 5-fluorouracil (600 mg/sqm) (CEF) within 48-72 h following surgery. Pathologically node-positive (N+) patients, who were given peri-operative CEF, had five further cycles of CEF alternated with six cycles of CMF (cyclophosphamide 600 mg/sqm, methotrexate 40 mg/sqm, and 5-fluorouracil 600 mg/sqm). All the other N+ patients received six cycles of CEF alternated with six cycles of CMF, starting within 30 days of surgery. No significant difference in post-operative morbidity was observed as regards median hospital stay (8 days), number of outpatient dressings (3.5 vs 3), seroma (51 (26.9%) vs 45 (24.2%)), lymphatic drainage (400 ml vs 409 ml), and post-operative infections, both local (10 vs 9) and in extraoperative foci (6 vs 7), in the study and control group, respectively. The toxicity of the peri-operative CEF was mainly gastrointestinal (nausea and vomiting, 55%; stomatitis, 3%), with only a small percentage (9%) reaching grades III-IV. Hair loss was the other main side effect (55%) with baldness in only 3%. Post-operative complications following radical breast cancer surgery seem to be primarily related to operative details (type of incision, accurate nerve-sparing technique, bleeding control, closure of subcutaneous and skin, drainage, aseptic technique) rather than to the one course of PAC.

Adult↗

Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I.

In recent classifications of gastric endocrine tumors, tumors arising in patients with multiple endocrine neoplasia type 1 (MEN-1) are regarded to be regulated by the concomitant hypergastrinemia resulting from to pancreatic or, most commonly, duodenal gastrinomas and to have a benign behavior. In this article, we report on two cases of MEN-1 gastric neuroendocrine tumors having a fatal course. Case 1 was a young male with hyperparathyroidism and Zollinger-Ellison syndrome and with florid development of multiple gastric carcinoids and multiple duodenal gastrinomas. Metastases occurred in the liver, of exclusive gastric origin, in periduodenal lymph nodes, of exclusive duodenal origin, and in perigastric lymph nodes, of mixed origin. The patient died 48 months after diagnosis. Case 2 was an adult female patient with hyperparathyroidism, adrenocortical disorders, and gastric tumors but no hypergastrinemia. The patient died 3 months after tumor diagnosis. At autopsy, the stomach showed multiple benign carcinoids and two independent neuroendocrine carcinomas not reported before in MEN-1 and massively metastatizing to lymph nodes, liver, and peritoneum. Multiple islet cell tumors mostly producing pancreatic polypeptide were found, whereas gastrinomas were seen in neither the pancreas nor the duodenum. Allelic losses at the MEN-1 gene locus in chromosome 11q13, the mechanism responsible for tumor development in MEN-1 syndrome, were demonstrated in the carcinoid tumors of case 1 and in the neuroendocrine carcinoma of case 2. We conclude that gastric neuroendocrine tumors in patients with MEN-1 may have a poor outcome, they have the same genetic mechanism as MEN-1 tumors in other organs, and they may be independent of the trophic effect of hypergastrinemia.

Adult↗

Breast intraductal masses: US-guided fine-needle aspiration after galactography.

PURPOSE: To evaluate ultrasonographic (US)-guided fine-needle aspiration (FNA) of intraductal masses performed immediately after galactography and to compare cytologic findings from US-guided FNA with those from nipple discharge. MATERIALS AND METHODS: In 36 patients with nipple discharge from a single duct in one breast and intraductal masses diagnosed at galactography, US was performed to detect intraductal lesions and perform FNA before removal of the galactographic catheter. Cytologic analysis of nipple discharge, excisional biopsy, and histopathologic evaluation were performed in all patients. RESULTS: Cytologic analysis revealed 23 nonpapillary benignancies, seven papillomas, five indeterminate cases, and one carcinoma. US-guided FNA cytologic analysis revealed 16 papillomas, 10 nonpapillary benignancies, five indeterminate cases, and three carcinomas. The two carcinomas misdiagnosed as papillomas at US-guided FNA cytologic analysis were papillary in situ carcinomas, while the three carcinomas correctly identified were invasive (only one was detected with cytologic analysis of nipple discharge). With cytologic analysis of nipple discharge, nine (25%) of 36 diagnoses were correct, and with US-guided FNA, 18 (50%) were correct (P = .0352). CONCLUSION: Compared with cytologic analysis of nipple discharge, US-guided FNA cytologic analysis seems to add useful information for tailored surgical planning.

Adolescent↗

Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia.

PURPOSE: Although erythropoietin (EPO) is known to be useful in treating chemotherapy-induced anemia, few data are available on its potential preventive role. The aim of this study was to evaluate the ability of EPO in preventing the development of clinically significant anemia in patients treated with chemotherapy. PATIENTS AND METHODS: Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were randomized to receive EPO 150 U/kg three times a week or no additional treatment. Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF) intravenously on day 1, every 2 weeks with the support of granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously from day 4 to day 11. RESULTS: Throughout the six cycles of chemotherapy, EPO-treated patients maintained stable values of hemoglobin, whereas control patients developed a progressive anemia. At the end of chemotherapy, the mean (+/- SD) hemoglobin decrease in the control group was 3.05 g/dL (+/- 1.0; 95% confidence interval [CI], 2.6 to 3.5), whereas in the EPO group it was 0.8 (+/- 1.4; 95% CI, 0.3 to 1.4). Clinically significant anemia (hemoglobin < or = 10 g/dL) occurred in 16 patients (52%; 95% CI, 33 to 69) in the control arm and in no patient (0%; 95% CI, 0 to 14) in the EPO arm (P = .00001). CONCLUSION: EPO prevents anemia in patients undergoing chemotherapy. Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective.

Adult↗

[The surgery of breast carcinoma. 10 years of activity].

From 1981 to 1990, 1003 stage I-II breast cancers underwent surgery at the Division of Surgical Oncology of National Institute for Cancer Research of Genoa. This study described the clinical and pathologic features of these breast cancers. Radical mastectomy was performed in 73.8% of cases and conservative surgery in 26.2% of cases. In the last years the number of conservative treatment has increased. Related to size of tumour, in 1991 80.4% of pT1 performed a conservative surgery. The choice of type of surgery for pT2 tumours depended on the choice of patient and the ratio breast size and tumour size. The five-year overall survival was 85.8% in the group of conservative surgery and 65.3% in the group of radical surgery. The overall survival and relapse free survival have been calculated by Kaplan-Meyer method. Actuarial survival curves were computed according to type of surgery, tumor size, nodal status, hormonal receptors. In our experience the size of tumour was an important prognostic factor. The five years, overall survival was 80.7% in pT1 tumours and 67% in pT2-pT3 tumours (p = 10(-6)). The five-year overall survival in negative nodes patients was 80.5%. Conversely in patients with more than ten nodal metastases was 29.5%. The data reported in the present study were no different as in previous studies.

Adult↗

Carcinoid tumor associated with vascular malformation as a cause of massive gastric bleeding.

Massive gastric bleeding in a 28-yr-old woman requiring emergency surgical treatment was found to originate from a polypoid carcinoid tumor 1.3 cm in diameter. Histologically, the tumor was found to be associated with a complex vascular malformation apparently originating from the underlying submucosa, crossing the tumor and ending in large mucosal sinusoids that opened on the mucosal surface. A similar clinical presentation was reported in three previous cases of small gastric carcinoids, one of which revealed an anomalous intratumoral bleeding artery. We recommend that in the absence of more common causative lesions of gastric bleeding, gastric carcinoid be considered in cases of focal massive hemorrhage requiring emergency treatment.

Adult↗

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

Aged↗

Locally advanced non-metastatic breast cancer: analysis of prognostic factors in 125 patients homogeneously treated with a combined modality approach.

125 stage III breast cancer patients, including 51 cases of inflammatory carcinoma, were treated with the following combined modality approach: three courses of primary 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) chemotherapy followed by locoregional treatment and subsequent adjuvant chemotherapy consisting of three courses of FAC alternating with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Clinical response to primary FAC was 65% (complete 10%). Residual tumour mass in the mastectomy specimen was > 1 and < or = 1 cm in 82 and 18% of cases, respectively. Complete pathological response following primary chemotherapy was achieved in only 3.5% of cases. After primary FAC and local treatment, 97% of patients were disease-free. Overall survival (S) and progression-free survival (PFS) at 5 years were 56 and 34%, respectively. Univariate analysis showed that age, receptor status and clinical and pathological response to primary chemotherapy did not appear to influence treatment outcome significantly, whereas stage, presence of inflammatory disease and number of involved nodes had a significant impact on both S and PFS.

Adenocarcinoma↗

Pre-operative localization of non-palpable lesions in breast cancer by charcoal suspension.

The use of preoperative localization procedures for non-palpable breast lesions (NPBL) is becoming more and more widespread, increasing the detection of early breast cancers. From October 1987 to July 1992, at our Institution, 253 patients (pts) with clinically non-palpable lesions underwent surgical treatment. Of the 253 pts, the lesions have been localized in 95 cases by a needle system, and in the other 158 cases by a dye injection of a 3% sterile charcoal suspension using stereotactic method (118 cases) or sonography (40 cases). The patients' mean age was 53 years (range 30-75). Mammography revealed regular opacities in 133 cases, clustered microcalcification in 75, diffuse microcalcification in 24, opacities with irregular borders in nine and opacities with internal microcalcifications in 12. The histological findings showed benign breast disease in 175 cases (69.2%), borderline breast disease in 23 (9.1%) and malignancy in 55 (21.7%). The benign/malignant/borderline lesions ratio was 3.2:1. The majority (70%) of these malignant lesions were small cancers (less than 1 cm in diameter) and without lymph-node involvement. The biopsy cost (benign/malignant/borderline ratio, patients discomfort and cosmetic result) has been acceptable.

Adult↗

A pilot study of accelerated cyclophosphamide, epirubicin and 5-fluorouracil plus granulocyte colony stimulating factor as adjuvant therapy in early breast cancer.

32 consecutive early breast cancer patients were treated to evaluate the feasibility of an accelerated CEF regimen (cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2 and 5-fluorouracil 600 mg/m2) given intravenously every 2 weeks for six cycles together with granulocyte colony stimulating factor, 5 micrograms/kg/day subcutaneously from day 4 to day 11. One hundred and eighty two out of 192 planned cycles (95%) were administered. Toxicity was mild: no cases of grade IV non-haematological toxicity and only one episode of grade IV granulocytopenia were observed. Delays or dose reductions of anti-neoplastic drugs occurred in 14 cycles (7.7%). The mean duration of six cycles of treatment was 71 days (planned 70) and 93% of average planned dose intensity was actually administered. The short course CEF therapy is a feasible, well tolerated outpatient chemotherapy regimen, allowing a 46% increase in dose intensity compared with a standard CEF regimen given every 3 weeks. A randomised study comparing this regimen to a standard CEF regimen is now in progress in early breast cancer patients.

Adult↗

Monoclonal antibodies to keratan sulfate immunolocalize ramified microglia in paraffin and cryostat sections of rat brain.

We used six monoclonal antibodies (MAb) recognizing epitopes within keratan sulfate (KS) chains for an immunocytochemical study of adult rat brain. One of the MAb selectively stained microglia and their ramified processes. KS-positive cells were found throughout the CNS in both paraffin-embedded and cryostat sections; the greatest number were present in hippocampus and brainstem. In the cortex the positive processes of some cells surrounded neuronal somata. In the white matter the processes were both parallel and perpendicular to the axon bundles. Double staining showed that KS-positive cells did not express astrocytic or oligodendroglial markers. By immunoelectron microscopy, the positivity was localized around the perikarya and cell processes of small cells with peripheral chromatin clumps and dark cytoplasm, which often contained secondary lysosomes. The KS-positive cells did not contribute to myelin sheaths and were not surrounded by a basal membrane. In addition to the cellular staining, three other MAb stained the white matter diffusely. Anti-KS MAb are therefore proposed as immunohistochemical markers for ramified microglia in both paraffin and cryostat sections of adult rat brain.

Animals↗

Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas.

A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials.

Adolescent↗

[Merkel's tumor. Some comments and the authors' personal cases].

The clinical features of 7 cases of primary neuroendocrine carcinoma of the skin (Merkel cell tumor) are reported. This cancer arises in the dermis and subcutaneous tissues of elderly individuals. Natural history is characterized by local recurrences (30%), regional lymph node metastases (65%) and distant metastases (40%). Surgery is the elective treatment, chemotherapy and radiotherapy resulted in only short-term palliative response.

Aged↗

Surgery for disseminated abdominal sarcoma.

Seventy-two consecutive patients with disseminated soft tissue sarcoma in the abdomen were prospectively placed in a program of debulking surgery. The tumor was completely resectable in 64% of the patients. Following the first exploration, the median survival was 23 months for those with resection of metastases and 9 months for those without resection (p less than or equal to 0.01); the former group had a survival rate of 28% at 3 years, 18% at 4 years, and 4% at 5 years (44%, 37%, and 10%, respectively, for low-grade sarcomas, i.e., grade I or II sarcomas), whereas in the latter group, none survived for 3 years. In the group with resection, patients with grade III tumors had a median survival longer by 6 months, and those with low-grade tumors by 28 months (p less than or equal to 0.001), over the respective median survival of patients with unresectable tumors. Metastasectomy appeared to prolong survival in all patients and significantly so in patients with low-grade tumors and those with long disease-free intervals.

Abdominal Neoplasms↗

Chondroitin sulfate proteoglycan surrounds a subset of human and rat CNS neurons.

Chondroitin sulfate proteoglycan (CS-PG) bearing glycosaminoglycan (GAG) chains containing unsulfate (COS) and 6-sulfate (C6S) disaccharides was immunolocalized in rat and human CNS by using monoclonal antibodies (MAb) specific for the two disaccharides. The immunostaining with both MAb was restricted to the periphery of a neuronal subset in rat and human CNS. Double immunofluorescence showed codistribution of the antigens around the same neuronal population. The staining with anti-COS MAb was stronger than with anti-C6S MAb, suggesting that the proteoglycan (PG) contains mainly COS disaccharides. In different rat cortical areas, 40-60/mm2 positive interneurons were found, the visual cortex showing the highest value. In human cortex, positivity was also observed around the soma of some pyramidal cells. In the rat, positive neurons were also localized in deep cerebellar nuclei, reticular nucleus of the thalamus, and other structures of the midbrain and hindbrain. CA3 region of hippocampus and the external layer of pyriform cortex were characterized by positivity of the neuropil. Immunoelectronmicroscopy showed the antigens in the extracellular space around the neuronal soma, the synaptic elements and the cell processes of the neuropil. The neuronal surface of the soma and of the proximal dendrites were positive, but the pre- and postsynaptic membranes and clefts were negative.

Aged↗

Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas.

We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.

Adolescent↗