Biomedical subjects
Publications and source records attributed to F Izzo.
The Authors present their personal experience of circumscribed peritonitis of colic origin. They review some physiopathological aspects of these peritonitis and then emphasize the new therapeutic possibilities offered by percutaneous prick echo or TC guided.
The authors put forward a new and original classification of the clinical pictures of acute pseudo-abdomen. They separate the cases due to extra-abdominal causes which are not marked by the essential features of acuity and severity from those which do not require surgery.
We have cloned the fru operon of Salmonella typhimurium, coding for the enzymes of the phosphoenolpyruvate: fructose phosphotransferase system (Fructose PTS). The fruFKA operon consists of three genes: fruF coding for FPr, fruK for fructose 1-phosphate kinase and fruA for Enzyme IIFru. Insertions of Tn5 in the different genes were isolated and the activities of the gene products were measured. Expression of the plasmid-encoded fru operon in the maxicell system resulted in the synthesis of three proteins with molecular weights of 47 kDa (fruA), 39 kDa (fruF) and 32 kDa (fruK). We have sequenced the fruF gene and the regulatory region of the fru operon. In contrast to previously published results, we have found that the fruF gene codes for a 39 kDa protein, FPr, that combines Enzyme IIIFru and pseudo-HPr activities. The N-terminal part of FPr is homologous to the cytoplasmic domain of the Escherichia coli Enzyme IIMtl, as well as several Enzymes IIIMtl from gram-positive bacteria. The C-terminal domain shows homology to HPr of E. coli and several gram-positive organisms. The fru operon is regulated by a repressor, FruR. We have constructed an operon fusion between fru and the galK gene and shown that regulation of the fru operon by FruR takes place at the level of transcription.
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It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32% and 41% respectively; P <0.05 vs. other groups). With a median follow-up of 30 months, a significantly decreased local disease-free survival (LDFS) was seen in HBV-positive (5-year LDFS 26%) or HCV-positive (5-year LDFS 38%) patients compared to those with negative serology (5-year LDFS 79%; P <0.05). There was also a trend toward a decreased overall survival in patients with positive hepatitis serology compared to patients with negative serology (37% vs. 79%; P = 0.12). Univariate analysis revealed that only satellitosis was related to local recurrence and overall survival. Patients with positive serology for hepatitis B or C undergoing resection for hepatocellular carcinoma have a trend toward worse overall prognosis and a significantly decreased LDFS when compared to patients with negative serology.
Pancreatic carcinoma is an aggressive disease and its prognosis is dismal. Patients present with an advanced stage of disease and only a small number of patients undergo resection with a curative intent; thus the 5 years survival rate is very low. Several improvements have been made in the surgical approach with a decrease in perioperative morbidity and mortality. Results offered by chemotherapy and radiotherapy remain unsatisfactory despite a number of new drugs and considerable advancements in irradiation techniques. Jaundice, pain and gastrointestinal obstruction are the main clinical problems to be dealt with in advanced patients. Surgical palliation still represents a widely preferred option but non surgical approaches appear promising. The Authors analyse the possible options in palliation for pancreatic carcinoma. The various surgical procedures for biliary by-pass are described. Hepaticojejunostomy is the operation of choice and offers the best results in terms of quality of life and time of palliation. A possible role for resective operation also in advanced cases has been proposed by some groups and is gaining wide acceptance in referral centres where low morbidity and mortality are now routine. Percutaneous and endoscopic approaches to jaundice represent a valid alternative in some patients with a low life expectancy and in those centres with a high experience. Gastrointestinal by-pass in symptom-free patients or advanced cases only is an unsolved dilemma. New approaches such as locoregional chemotherapy with curative or neoadjuvant intent are also described in this paper. Many chemotherapic agents have been tested in various settings and appear to offer promising results in palliation and also, in some cases, in downstaging tumors then amenable to resection. Pain control is a major aspect in management of advanced pancreatic carcinoma. Appropriate pain therapy has to be established in all patients in order to obtain a better quality of life. Various options are available such as intraoperative alcohol injection or CT guided percutaneous splanchnicectomy. Palliation in patients with pancreatic carcinoma is a major aspect of management because of the high percentage of non curable cases; multimodality approach is mandatory and all possible problems have to be dealt with in order to increase survival and, more importantly, quality of life.
Chemotherapy has been proposed for patients with hepatocellular carcinoma (HCC) associated with well-compensated cirrhosis who are unsuitable for locoregional treatments. Anthracyclines are the most active agents against HCC, although their toxicity is often unpredictable; thus, there is a need for new active drugs with a safe toxicity profile. The liposomal formulation of the anthracycline daunorubicin has low systemic toxicity and is taken up strongly by the liver. We started a phase I study with liposomal daunorubicin (starting dose 80 mg/m2 every 21 days) in patients with hepatocellular carcinoma and Child-Pugh stage A or B liver cirrhosis. At the starting dose, we recorded dose-limiting toxicities (1 hyperbilirubinemia, 1 prolonged prothrombin time, 1 persisting grade 3 neutropenia) in 3 out of 4 patients. Thus, according to protocol, we went down to the dose level of 60 mg/m2 but still 2 out of 3 patients had unacceptable toxicity (1 hypertransaminasemia, 1 hyperbilirubinemia with encephalopathia). Finally, we treated 4 more patients at the dose level of 40 mg/m2 and again we recorded liver toxicity in three of them. Overall haematological toxicity was mild and significant non-haematologic toxicities, other than hepatic, were not recorded. The toxicity profile observed warns against further assessment of liposomal daunorubicin in patients with hepatocellular carcinoma and liver cirrhosis.
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BACKGROUND AND PURPOSE: Preoperative chemoradiation allows downstaging of locally advanced rectal cancer and in selected patients also a sufficient downsizing to ensure sphincter preservation. Selection of patients warranting a preoperative approach is improved by magnetic resonance imaging (MRI) which is able to define the involvement of mesorectal circumferential margin. Similarly it would be crucial to define the response to chemoradiation during the treatment but traditional morphologic imaging techniques may fail in differentiating neoplastic tissue from scarring. PET-FDG has been successfully used in the detection of metastatic colorectal cancer allowing imaging of deposits as small as 0.5 cm and may have a role in evaluating early response to chemoradiation. METHODS: In the present study, in patients with T3-T4 rectal cancer undergoing preoperative chemoradiation PET-FDG and flow cytometry analysis on endoscopic biopsy specimen have been performed before, during and after preoperative chemoradiation. RESULTS: Chemoradiation treatment has been successful in terms of downsizing and downstaging of the tumor. PET-FDG was able to demonstrate local response at only ten-fifteen days after the beginning of neoadjuvant therapy, also identifying non responding patients. CONCLUSIONS: FDG-PET may have a role in defining the response to chemoradiation and modulate the treatments strategy in patients with advanced rectal cancer.
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BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.
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Ex novo Kaposi's Sarcoma 4 months after renal transplantation in a young patient is described. Progression of the tumoral lesions has been observed during combined immunosuppressive treatment with Prednisone, Azathioprine and Cyclosporin. Stopping Azathioprine and Cyclosporin as well as reducing Prednisone prevented new lesions and made the preexistent skin lesions less extensive. Clinical case, possible pathogenesis and therapeutic strategies are discussed.
The authors intended verifying the effectiveness of natural beta-interferon in the treatment of metastatic pleural effusion from breast's cancer. 24 patient, with an average age of 54, were studied. The objective responses were: 2 Complete Responses, 8 Partial Responses, 6 Stationarity and 5 Progression. The responses seem independent from the association of systemic treatment. Clinical response has been observed in patients with initial pleural effusion less than or equal to 1000 cc.
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