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Biomedical subjects

L Gennari

Publications and source records attributed to L Gennari.

At least 91 records · Page 5Linked to original sources
PubMed1991

Changes in alpha-1 and beta-2 adrenoceptor density in human hepatocellular carcinoma.

Catecholamines are involved critically in the mechanisms of liver cell proliferation by acting on hepatic alpha-1 and beta-2 adrenoceptors. To identify the role of these receptors in human hepatocellular carcinoma (HCC), the density was examined of alpha-1 and beta-2 adrenoceptors with their affinity and coupling of beta-2 adrenoceptors to adenylate cyclase in HCC tissue and in nonadjacent/nontumor tissue from the same livers. Studies were also done on healthy livers from age-matched and sex-matched patients undergoing abdominal surgery for nonhepatic diseases. Twenty-two HCC had a decrease of about 72% in alpha-1 adrenoceptor density compared with their nonadjacent/nontumor tissue and a decrease of about 40% compared with healthy controls. Nonadjacent/nontumor tissue from HCC patients had a 125% increase in alpha-1 adrenoceptor density compared with healthy livers. Twenty-three of 24 HCC had an increase of about 180% in beta adrenoceptor density compared with their nonadjacent/nontumor tissue and healthy controls. Beta adrenoceptors were coupled to adenylate cyclase, as evidenced by a guanosine triphosphate-mediated right shift in (-)-isoproterenol competition isotherms and by cyclic adenosine monophosphate (cAMP) production after stimulation with (-)-isoproterenol. The HCC tissue yielded a larger increase in cAMP than nonadjacent/nontumor tissue and healthy controls. The authors conclude that a higher density of alpha-1 adrenoceptors in nonadjacent/nontumor tissue from HCC characterizes the "healthy" part of the liver in HCC patients and that an increase in beta-2 and a decrease in alpha-1 adrenoceptor densities characterize the tumor part of the liver in human HCC.

Adenylyl Cyclases↗
PubMed1991

One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants.

One hundred patients with hepatic metastases from colorectal cancer underwent 'radical' liver resection from 1980 to 1989. At least 1 cm of normal parenchyma surrounded the tumour and no microscopic invasion of resection margins was evident. The disease was staged according to our own staging system. Lobectomy was performed in 50 patients and non-anatomical resection in the remainder. The postoperative mortality rate was 5 per cent and the major morbidity rate was 11 per cent. The actuarial 5-year survival rate for patients in stages I, II and III was 42 per cent, 34 per cent and 15 per cent respectively (P less than 0.001). The overall actuarial 5-year survival rate was 30 per cent. The prognostic importance of various patient and tumour variables was evaluated by univariate analysis and then by multivariate analysis. Age of patient, site of primary, disease-free interval between treatment of primary and of hepatic metastases, preoperative carcinoembryonic antigen levels, and number of metastases, did not relate to prognosis, while sex (P = 0.024), stage of primary (P = 0.026), extent of liver involvement (P less than 0.001), distribution of metastases (P = 0.01) and type of surgery (P = 0.028) significantly affected prognosis as single factors. Multivariate analysis revealed that only the extent of liver involvement and stage of the primary tumour were independent predictors of survival. We conclude that liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not yet possible to formulate a clear prognosis based on clinical factors. The extent of liver involvement and the staging system used may be significant, although not absolute, indicators of outcome.

Adenocarcinoma↗
PubMed1991

Hepatic resections for colorectal metastases: the Italian multicenter experience.

In 1989 there were 151,000 new cases of colorectal carcinoma in the United States. Approximately 50% of these patients will be at risk of developing liver metastases together with other sites of recurrence. However, the liver will be the main site of relapse in only 14,000 patients with colorectal cancer. Approximately 25% of patients with colorectal carcinoma have technically resectable hepatic metastases at the time of operation for primary lesion, and an additional 8-25% will develop metachronous hepatic metastases after primary resection. Recent reported experiences with surgical treatment of metastatic colorectal cancer in the liver seem to indicate that hepatic resection has become more acceptable, safe and effective therapy, and offers today when technically possible, the best prospect of survival in a conspicuous number of patients. For these reasons, although a prospective randomized trial has not been done comparing resection with nonresection, resection seems to give the best hope for cure and actually is the treatment of choice for selected patients. In fact in these patients is reported a significant prolongation of survival compared with those patients with unresectable liver metastases treated only with adjuvant therapy in the form of chemotherapy or radiation therapy. Median survival of resected patients with hepatic metastases has been reported to range from 6-12 months, and for patients with single metastases is reported to range from 4.5-6.2 months to 11 and 21 months. The benefits of surgical therapy have been emphasized by different experience, with a 5-year overall survival rate ranging from 20-40%. In a recent multicenter survey a 33% 5-year survival rate was demonstrated in 859 patients resected for hepatic metastases.

Adenocarcinoma↗
PubMed1991

Role of estrogens and epidermal growth factor in hepatocellular carcinoma (HCC).

Estrogen (E) and epidermal growth factors (EGF) receptors were assayed in the liver of nine patients with hepatocellular carcinoma (HCC). Total E and nuclear E receptors were decreased significantly in neoplastic tissue as compared to the levels found in surrounding nonneoplastic tissue. The EGF receptor was decreased also in neoplastic tissue. On the basis of binding data, a decrease in the number but not in affinity of both the E and EGF receptors was found.

Carcinoma, Hepatocellular↗
PubMed1991

Quantitation of estrogen and androgen receptors in hepatocellular carcinoma and adjacent normal human liver.

Sex hormones have been shown to influence the development and course of several liver diseases. The worldwide predominance of hepatocellular carcinoma (HCC) in males has led to the suggestion that this disease might be hormone-responsive. Therefore, the hepatic estrogen (ER) and androgen receptor (AR) status of liver specimens from such patients was investigated. Samples were obtained from three female and six males patients undergoing liver resection; in each case, a small sample of both the tumor and adjacent normal tissue was collected. All patients had primary hepatocellular carcinoma without cirrhosis. In most cases, the tumor and the normal specimen had an equivalent content of cytosolic ER; however, three of the tumor samples (one female and two male) displayed considerably elevated cytosolic ER levels as compared to that of the normal tissue. In every sample, the tumor contained less nuclear ER than did the normal liver. When AR was measured, tumors of three patients (one female and two male) demonstrated a twofold elevation in cytosolic AR as compared to adjacent normal tissue. In the two male patients, an approximately twofold greater nuclear AR was found. Two other samples from male patients showed a modest elevation of cytosolic AR in the tumors. The patients whose tumors showed elevations in ER were not the same patients as those in whom the AR was elevated. Thus, these studies indicate that certain, but not all, specimens of HCC demonstrate either elevated ER or AR and suggest that a determination of receptor content might be useful prior to initiation of certain antihormone therapies.

Adult↗
PubMed1990

A feasibility study of high-dose cisplatin and 5-fluorouracil with glutathione protection in the treatment of advanced colorectal cancer.

On the basis of previous studies supporting that glutathione (GSH) reduced cisplatin nephrotoxicity we have designed a new regimen in the treatment of advanced colorectal cancer, which included GSH as a modulator of cisplatin-induced toxicity. Eleven untreated patients with measurable metastatic colorectal cancer received 5-fluorouracil (750 mg/m2, daily continuous infusion for days 1-5) and cisplatin (40 mg/m2 1 hour-infusion for days 6-8) given every 4 weeks. Reduced glutathione (2.5 g) was delivered i.v. prior to each cisplatin infusion. Toxicity was minimal and reversible and included nausea/vomiting (11 cases), mild neurotoxicity (4 cases) and leukopenia (2 cases); only 2 patients showed moderate and transient increases of serum creatinine (less than 2 mg/dl) and BUN. Renal function impairment was also monitored by magnesemia levels and urinary marker enzymes indicating minimal cumulative nephrotoxicity. Out of 10 evaluable patients, only 2 partial responses were observed. The median survival was 9 months (range 5-26). The study was closed, since the preliminary results do not suggest any therapeutic advantage in adding cisplatin to 5-fluorouracil in the present schedule, even using an intensive regimen. Indirect evidence suggests that these disappointing results are not the consequence of interference of GSH on the cytotoxic efficacy of cisplatin. The lack of incidence of severe toxicity of this regimen supports the role of reduced glutathione as a potential protective against cisplatin nephrotoxicity. Although these preliminary results suggest that further studies with the present regimen in this disease are not warranted, in view of its safety this program deserves evaluation in the treatment of neoplastic diseases responsive to 5-fluorouracil/cisplatin.

Adult↗
PubMed1990

A clinicopathologic study of primary hepatic carcinoid tumors.

Six cases of primary hepatic carcinoid tumors were studied with combined immunocytochemical and electron microscopic techniques. Positive tumor immunostaining with PHE5, LK2H10, neuron-specific enolase (NSE), serotonin, gastrin, and insulin antibodies was observed. At the ultrastructural level, cytoplasmic dense granules were seen in all the cases tested. This finding supports a putative origin of these carcinoids found in the liver from a pluripotential stem cell. The clinical course and follow-up of these cases suggests that this unusual hepatic neoplasm has a more favorable prognosis than other forms of hepatic cancer.

Adult↗
PubMed1990

Early and late results of extended surgery for cancer of the stomach.

The experience of the Istituto Nazionale Tumori of Milan of 143 patients who underwent extended surgery for cancer of the stomach from 1965 to 1980 is reviewed. They represent 16.3 per cent of the patients who underwent curative surgery. The operative mortality rate was 15.4 per cent but this significantly decreased in recent years to 8 per cent and the morbidity rate to 17.5 per cent. The overall 5-year survival rate was 19 per cent. Survival was analysed according to tumour penetration (pT) and nodal status (N). It was found that patients without tumour penetration of adjacent structures and nodal involvement (pT3N-) had a better 5-year survival rate (21 per cent) than patients with nodal involvement (pT3N+) (2 per cent). Patients with tumour penetration of adjacent structures and without nodal involvement (pT4N-) had a better 5-year survival rate (29 per cent) than patients with nodal involvement (pT4N+) (5 per cent). These differences were significant on log rank test (P less than 0.000001 and P less than 0.001 respectively) and suggest that nodal status is a stronger prognostic variable than pT level. The role of extended surgery is discussed from the viewpoint of the oncological surgeon who has to weigh up the difficulty of a preoperative diagnosis of tumour infiltration of adjacent structures (predictive positive value 0.39), with the operative mortality rate of at least 8 per cent and long-term results which are strongly affected by the nodal status.

Digestive System Neoplasms↗
PubMed1990

Cell kinetics of hepatic metastases as a prognostic marker in patients with advanced colorectal carcinoma.

Cell kinetics was determined, as 3H-thymidine labeling index (LI), in hepatic lesions from 36 patients with primary colorectal carcinoma: LI values ranged from 0.9% to 23.5% and were normally distributed. Cell kinetics was not related to sex or age of the patient, or to liver function. For clinical studies the median LI value of 10% was used to separate slowly and rapidly proliferating lesions. Univariate analysis showed that patients radically resected and with a low LI tumor have a longer disease-free interval and a better probability of 12-month survival than those non-radically resected and with a high LI tumor. When treatment and cell kinetics were taken into consideration, the probability of 12-month survival was 100% for patients with slowly proliferating and radically resected hepatic metastases. Patients with rapidly proliferating tumors, regardless of type of treatment, had the worst prognosis.

Adenocarcinoma↗
PubMed1990

The role of CEA and liver function tests in the detection of hepatic metastases from colo-rectal cancer.

Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyltranspeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallible imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases.

Carcinoembryonic Antigen↗
PubMed1988

Abnormal pattern of mucin secretion at the resection margin of colorectal carcinomas.

In a retrospective study, we investigated 56 consecutive patients who had undergone radical intestinal resection for colorectal adenocarcinoma and who had developed local or distant recurrences of the disease. We found that the presence of a predominant sialomucin pattern at the margins of resection of the surgical specimen was correlated with a high percentage of local, endoluminal recurrence in the anastomotic mucosa. In contrast, no correlation could be found when the recurrences occurred in the outer tissues around the anastomosis or at some distance from it.

Adenocarcinoma↗
PubMed1988

Intrahepatic chemotherapy for unresectable hepatocellular carcinoma.

From 1976 to 1983, 28 patients (24 male and four female) with unresectable hepatocellular carcinoma (HCC) were treated by intraarterial chemotherapy at the Istituto Nazionale Tumori of Milan, Milan, Italy. Tumors were retrospectively classified by a previously proposed staging system. Two patients were classified as Stage I and 26 as Stage II. Liver cirrhosis was present only in the males (in 50% of them). Nineteen patients were treated with doxorubicin (Adriamycin [Adria Laboratories, Columbus, OH]) and nine with 5-fluorouracil. Systemic toxicity was mild, but the treatment induced hepatic toxicity (ascites, clinical jaundice, or biochemical impairment) in 18% of noncirrhotic and 66% of cirrhotic patients. Clinical reduction of hepatomegaly was observed in 50% of noncirrhotic versus 16% of cirrhotic patients. Doxorubicin was effective in 66% of noncirrhotic patients and 20% of cirrhotic patients, with an overall response rate of 42%. 5-fluorouracil was effective only in patients without cirrhosis, with an overall response rate of 22%. Overall median actuarial survival was 3.5 months, with a significant difference between noncirrhotic and cirrhotic patients (6 versus 2 months, respectively). Overall median survival of patients who responded to the treatment was 13 versus 2 months for nonresponders (P less than 0.001). Liver cirrhosis was the most important prognostic factor in terms of liver toxicity, response rate, and survival. This study emphasized the negative impact of the treatment on cirrhotic patients. Also, the real value of intraarterial administration of doxorubicin was investigated.

Adult↗
PubMed1988

Chordoma: natural history and treatment results in 33 cases.

Thirty-three chordomas were observed at the Istituto Nazionale Tumori of Milan from 1933 to 1983: 27 sacrococcygeal, 3 spheno-occipital, and 3 vertebral. The male:female ratio was 2.7, and the median age was 63 yr for patients with sacrococcygeal and 35.2 yr for those with nonsacral chordomas. After pathologic reassessment, distinct cytologic patterns were found: physaliphorous, syncytial, and mixed subtypes, with variable degrees of cytologic atypia. However, no evident difference in survival was documented in relation to these cytohistologic features. Four cases had a prior traumatic fracture, and the pathogenetic role of trauma is stressed. Eight cases were operated with adequate surgery and only three recurred, whereas of 11 inadequate operations, 10 developed local relapse. However, follow-up for recent adequate operations is short. Radiation therapy seemed to be effective with adjuvant or palliative aims. No chemotherapeutic regimen achieved any result; one case had a short complete remission after cis-dichlorodiammineplatinum + vinblastine + bleomycin (PVB). This analysis confirms the possibility of achieving radicality with high resection of the sacrum for lesions confined below the second sacral vertebra. Nonsacral chordomas were all unresectable. The best treatment for unresectable lesions seems to be palliative surgery plus radiotherapy.

Adolescent↗