PubMed Health⌕ Search

Biomedical subjects

D Nitti

Publications and source records attributed to D Nitti.

At least 55 records · Page 3Linked to original sources
PubMed1995

Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.

PURPOSE: In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS: Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS: Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION: FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.

Adenocarcinoma↗
PubMed1994

Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas.

BACKGROUND: Locoregional control of soft tissue sarcomas of the limbs is achieved generally using a multidisciplinary approach consisting of conservative surgery combined with radiation therapy, intraarterial chemotherapy, or hyperthermic antiblastic perfusion (HAP). Before surgery, HAP seems to be the more suitable tool in decreasing tumor mass and allowing limb-sparing surgery. The authors' aim was to ascertain the activity of HAP with doxorubicin against intermediate or high grade limb tumors. METHODS: In 23 patients with limb sarcomas (2 patients International Union Against Cancer Stage IIA, 4 stage IIB, 1 stage IIIA, 11 stage IIIB, and 5 stage IVB) doxorubicin was administered via HAP 4-6 weeks before surgery. The drug (bolus, 0.7-1.4 mg/kg) was perfused for 60 minutes with a tumor temperature of at least 40.5 degrees C (range, 40.5-42.6 degrees). Tumor necrosis was then assessed radiologically and pathologically. RESULTS: Systemic toxicity was hematologic grade (G) 2 in 2 patients, gastrointestinal (hepatic) in 6, G1 in 2, G2 in 3, and G3 in 1; 2 patients had alopecia; locoregional toxicity (graded according to Wieberdink) was G1 or G2 in 18, G3 in 4, and G4 in 1. Tumor necrosis was more than 50% in 17 patients (74%). Limb-sparing surgery was feasible in 20 patients (91%). At present, 14 patients are alive. Six had local recurrences, and eight had distant metastases. CONCLUSIONS: Our findings show that HAP with doxorubicin is an active and well-tolerated procedure within a multidisciplinary approach to treatment of limb sarcomas.

Adult↗
PubMed1994

Pathology and ploidy in the prognosis of gastric cancer with no extranodal metastasis.

BACKGROUND: The prognostic relevance of morphology in advanced gastric cancer is well known. Data on tumor cell DNA content are still inadequate and contradictory. METHODS: Morphologic parameters and DNA ploidy were evaluated in 76 gastric cancer patients with no extranodal metastases (Stage I, 10 cases; Stage II, 20 cases; and Stage III, 46 cases), using formalin-fixed paraffin-embedded tissue. All cases were followed for at least 6 years after surgery or until death. RESULTS: Among the potential prognostic factors analyzed by Mantel-Cox and generalized Wilcoxon statistics, male sex (P = 0.02), cardiac location of neoplasia (P = 0.02), deeper infiltration of the gastric wall (P = 0.001), vascular neoplastic invasion (P = 0.006), metastatic lymph nodes (P = 0.001), pathologic stage (P = 0.0001), and aneuploidy (P = 0.01) were significantly associated with lower survival rate. Testing of all of the above-mentioned variables by the Cox stepwise multiple regression model disclosed that factors independently associated with survival were stage (P = 0.0001), ploidy (P = 0.0006), and vascular carcinomatous invasion (P = 0.01). CONCLUSIONS: In gastric cancer with no extranodal metastases, DNA ploidy was found to be the most significant prognostic parameter after pathologic stage.

Aged↗
PubMed1994

Functional role of IL-2 receptors on tumour-infiltrating lymphocytes.

This study was undertaken to investigate the pathways involved in the interleukin 2 (IL-2)-driven growth of tumour-infiltrating lymphocytes (TILs). For this purpose, TIL lines and freshly isolated TILs obtained from 16 patients with solid cancer (three melanoma, seven primary colorectal carcinoma, four hepatic metastases from colorectal cancer and two lung cancer) were evaluated for (a) expression of IL-2 receptor (IL-2R) both at the RNA level and on the cell surface by flow cytometric analysis and (b) their proliferative activity in response to IL-2 and the role of IL-2R subunits in the IL-2-driven TIL growth. Northern blot analysis showed that TILs express a strong message for both the p55 and the p75 IL-2R. Accordingly, flow cytometric analysis demonstrated that TILs bear both IL-2R chains. TILs cultured in vitro in the presence of rIL-2 were able to proliferate in response to different concentrations of this cytokine. Monoclonal antibodies (MAbs) specifically recognising the p55 and p75 IL-2R chains (anti-Tac and TU27 respectively) exhibited a marked inhibitory effect on IL-2-driven growth when added individually or in appropriate combinations. Our results demonstrated that TILs are equipped with a fully functional IL-2 receptor system, thus suggesting the involvement of this structure in the activation and expansion of TILs following immunotherapy with IL-2.

Antibodies, Monoclonal↗
PubMed1993

Reverse transcription-polymerase chain reaction phenotyping of metalloproteinases and inhibitors involved in tumor matrix invasion.

The matrix metalloproteinase enzymes have been implicated in tumor invasion and metastasis by a series of correlative immunohistochemical studies. In addition, direct evidence for the role of these enzymes in this pathologic process comes from studies using specific metalloproteinase inhibitors to block tumor invasion and metastasis formation, both in vitro and in vivo. Synthetic oligonucleotide primers for four metalloproteinases (MMP-1, MMP-2, MMP-9, MMP-10) and their tissue inhibitors (TIMP-1, TIMP-2) were selected, synthesized, and optimized in the reverse transcriptase-polymerase chain reaction (RT-PCR) to study the qualitative profile of these enzymes and inhibitors in cultured human tumor cells and tumor tissues. These primers are specific and generate unique amplification products for each appropriate enzyme and inhibitor. Slight enhancement in the amplification of cDNA products was achieved by adding dimethylsulfoxide to the reaction mixture, but commercial enhancement reagents were ineffective. Using this RT-PCR method, cDNA amplification was successful with RNA from as few as 20 cultured tumor cells. The RT-PCR analysis was done on three invasive human colon adenocarcinomas and their paired adjacent normal mucosa. The results show MMP-1 and MMP-2 products in all three tumors, and MMP-2 detected in one of the three normal mucosa samples; TIMP-2 expression was present in two of three patients and awaits quantitative assessment of RT-PCR products.

Base Sequence↗
PubMed1993

Management of primary sarcomas of the retroperitoneum.

We here report on our 10-year experience of surgery in 25 patients with primary retroperitoneal sarcoma and make an appraisal of the more effective available clinical approach. Ten patients had leiomyosarcoma, eight liposarcoma, and seven had other tumor types. Histological grading was G1 in seven patients, G2 in six patients and G3 in 12. Ten patients (40%) underwent wide tumor excision, five (20%) marginal excision, four (16%) partial excision and six (24%) wedge biopsy at laparotomy. Adjacent organ resection was required in 10 of the 15 patients who underwent wide or marginal resection, seven of whom had adjuvant chemoradiotherapy. After wide resection, local recurrences were observed in 2/10 patients; the 10-year survival rate was 33%. Three out of five patients who underwent marginal resection had local recurrences; one is alive 10 years after surgery and chemo-radiotherapy. Histological grading was the most important prognostic factor. Radical resection is the only effective available treatment for retroperitoneal sarcomas, and patients with low-grade tumors benefit most from it with respect to survival and local recurrence rate. The efficacy of adjuvant treatment has yet to be clarified.

Adult↗
PubMed1992

Adriamycin in hyperthermic perfusion for advanced limb sarcomas.

From February 1989 to April 1991, 12 hyperthermic limb perfusions (HLP) with adriamycin (ADR) were performed in 12 patients with high grade soft tissue sarcomas (9 in the leg and 3 in the arm); two were at A.J.C. stage IIb, eight stage IIIb and two stage IV. ADR (0.7-1.5 mg/kg) was administered in bolus at a mean temperature of 41.5 degrees C and perfused for 60 min. No systemic toxicity was reported; seven patients had grade II locoregional toxicity, another four grade III and one grade IV. Tumor necrosis (radiological evaluation) was less than 25% in two patients, 25% to 50% in two, 50% to 75% in five and greater than 75% in three. Limb sparing surgery was feasible in ten patients. At present eight patients are alive; three had local recurrence and four distant metastases.

Adult↗
PubMed1991

CA 50 determination in body fluids: can we screen patients at risk for gastric cancer?

CA 50 (a tumor-associated gangliosidic antigen) levels have been determined by an RIA test in serum, gastric juice and urine of patients undergoing upper gastrointestinal tract endoscopy: 22 control subjects (no macroscopic or microscopic lesions), 29 patients with chronic atrophic gastritis, 20 with epithelial dysplasia and 16 with gastric cancer entered the study. Gastric juices were also tested for pH, protein concentration and specific gravity, urines for protein concentration and osmolarity. Serum and gastric juices were also tested for CEA levels and the results obtained with the two markers compared. In patients with gastric cancer, CA 50 gastric juice levels were statistically higher than in controls; a wide overlap was however present among groups, and sensitivity and specificity were respectively 38% and 85% for serum and 69% and 82% for gastric juice. Sensitivity and specificity were respectively 23% and 89% for CA 50 determination in urines. In this case, no statistically significant difference was observed between gastric cancer and control patients. A trend toward higher median values was observed in advanced with respect to early gastric cancer. A correlation was found between gastric juice and serum CA 50 levels, as well as between serum and urine levels of the marker. A correlation was also observed between CA 50 values and protein concentration in gastric juice and with osmolarity in urines. Overall, CA 50 levels were statistically higher in patients with intestinal metaplasia than in those who did not present the lesion. Increased CA 50 gastric juice levels are also observed in patients with chronic atrophic gastritis and epithelial dysplasia. CA 50 gastric juice and urine levels appear to be dependent, at least in part, on the concentration of the fluid.

Adult↗
PubMed1991

Colorectal metastases to the liver: present results and future strategies.

In recent years, wide agreement has been expressed on the value of surgical resection for liver metastases from colorectal cancer, while for unresectable patients different types of locoregional treatment have been attempted. One hundred seventy-one patients with hepatic metastases from colorectal cancer were treated by us over a period of 15 years. Sixty-four underwent hepatic resection, and 107 underwent various forms of locoregional treatment. Our experience confirms the opinion that hepatic resection can be performed with a "curative" aim in patients with colorectal liver metastases: a 5-year survival rate can be achieved in about 30% of resectable cases. Adjuvant chemotherapy after hepatic resection should be tested in prospective randomized trials. Patients with diffuse liver metastases can benefit from locoregional infusion chemotherapy. Symptoms improve in most patients and objective responses are higher than those reported for systemic chemotherapy. Survival benefit with respect to untreated patients, has not yet been demonstrated by prospective randomized studies. Future improvements may be achieved by using new treatment modalities, such as new drug combinations, repeat arterial ischemia, and local tumor destruction. As these types of treatment are still experimental they should be employed only in prospective clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Adjuvant treatment for gastric cancer.

In spite of progress made in surgical techniques and intensive care, only a slight improvement in the therapeutic control of gastric carcinoma has been achieved in the last 20 years. In this paper we present a review of controlled clinical trials on adjuvant chemotherapy and chemo-immunotherapy for gastric cancer and this topic is discussed in the light of our experience and that of the Gastrointestinal Group of the European Organization for Research and Treatment of Cancer. The results of adjuvant therapy are less satisfactory in Western countries than in Japan. The efficacy of the 5-fluorouracil + adriamycin + mitomycin C regimen in advanced gastric cancer has not been confirmed in an adjuvant setting. The therapeutic benefit reported in Japanese studies may be due to a chemotherapy started intraoperatively or during the immediate postoperative period and should also be considered in the light of a standardized surgical treatment. The new therapeutic trends, using recent chemotherapeutic associations tested in Phase I and II clinical trials or combining traditional chemotherapy with different types of immunostimulators, are discussed. Only when large-scale clinical studies have been made will it be possible to confirm their therapeutic efficacy.

Antineoplastic Agents↗
PubMed1991

Direct involvement of human gastric mucosa in the activation of alimentary pro-carcinogens.

Exposure to N-nitroso-compounds and aromatic amines, xenobiotics which require an activation in order to exert their genotoxic potential, is causally associated with gastric cancer. We evaluated the capacity of microsome-containing fractions from human gastric mucosa to activate two model carcinogenic compounds. A 9,000 x g supernatant (S9) was obtained from gastric mucosal specimens and, for comparison, from human liver and aroclor-induced and non induced rat liver. The capacity of the S9 to activate N-nitrosopyrrolidine (NPY) and 2-aminofluorene (2AF) to mutagenic metabolites was tested in the Ames/Salmonella reversion assay, while dimethylnitrosamine (DMN) and aminopyrine (AP) demethylation activities were spectrophotometrically evaluated by using an enzymatic assay of the amount of formaldehyde released following the enzymatic demethylation of the corresponding substrates. Results indicate that human gastric S9 fractions may activate 2AF to a genotoxic derivative and are characterized by DMN and AP demethylase activities higher (p < 0.05) than those of human liver, when expressed in mg/protein (p < 0.05). Although the parameters evaluated can only be considered as a partial measure of the general activating capacity toward dietary and environmental procarcinogens, these results suggest that human gastric mucosa may be directly involved in the metabolic activation of these compounds to mutagenic/carcinogenic species.

Aminopyrine N-Demethylase↗
PubMed1991

Hepatic artery ligation with and without portal infusion of 5-FU. A randomized study in patients with unresectable liver metastases from colorectal carcinoma. The E.O.R.T.C. Gastrointestinal Cancer Cooperative Group (G.I. Group).

The aim of this multicentric prospective randomized clinical trial was to study the efficacy of hepatic artery ligation (HAL) with and without portal infusion (PI) of 5-FU in patients with liver metastasis of colorectal origin. Seventy-four patients were randomized. Sixty-seven were fully evaluable. Thirty-five patients were eligible in the HAL + PI of 5-FU group and 32 in the HAL alone group. The 5-FU infusion had to be discontinued for technical reasons in 13 patients. Complications of HAL were relatively high, including four hepatic failures (WHO grading greater than 2). Side effects of chemotherapy were limited. Five patients out of 30 had a partial response (WHO criteria) and one patient had a complete response in the group treated by HAL and PI of 5-FU. Only one patient had a partial response in the HAL alone group. Median survival for both groups was 12 months. Median time to progression for both groups was 6 months. This study did not show any advantage of delivery using the portal route in addition to hepatic artery ligation in terms of progression nor in survival of patients.

Adenocarcinoma↗
PubMed1990

Colorectal metastases to the liver: present status of management.

The management of patients with hepatic metastases from colorectal carcinoma is controversial. While a "no treatment" attitude still persists, other patients undergo systemic chemotherapy with very limited results. Other possible options are hepatic resection and locoregional treatments. One hundred twenty-three patients with hepatic metastases from colorectal cancer were treated at the authors' institution over a period of 15 years. Thirty-nine patients underwent hepatic resection while 84 underwent various forms of locoregional treatment. Several patients in the latter group were registered in one national (RNSI) Phase 2 study and one international (EORTC) Phase 3 trial. The authors' experience confirms the opinion that hepatic resection can be performed with the aim of curing in patients with isolated metastases. A five-year survival rate can be achieved in 25 to 30 percent of the resectable patients. Patients with unresectable extrahepatic disease or multiple bilateral metastases are usually excluded from resection. In other cases, hepatic resection should be carried out when technically possible. The value of adjuvant chemotherapy to the remaining liver has to be tested in prospective randomized trials. Patients with diffuse metastases can benefit from locoregional infusion of chemotherapeutic agents. Symptoms improve in most patients; objective responses vary from 53 to 83 percent of the cases, which is a higher rate than that reported for systemic chemotherapy. Survival may be prolonged in respect to untreated patients but this has not been demonstrated yet by prospective randomized studies. Current trends are continuous infusion of chemotherapeutic agents and experimentation of new drugs or drug combinations. Future improvements may be achieved by adding hepatic arterial ischemia, hyperthermia, or radiation therapy. As these kinds of treatments are still experimental, they should be applied to the patients only in the context of prospective clinical trials.

Adult↗
PubMed1990

[Malfunctioning of linear staplers as a cause of gastro-gastric fistula in vertical gastroplasty].

The Authors reviewed their series of patients submitted to VBG in order to investigate the rate and cause of gastric partition disruption. This complication was found only in patients who had the gastric partition done by means of a double application of TA-90. No gastric partition disruption was found in those patients in which TA-90-B was used. The partition breakdown might be due to occasionally defective closure mechanism in the traditional staplers.

Adult↗
PubMed1989

Laparoscopy in the abdominal staging of melanoma.

A retrospective study on laparoscopic results in the abdominal staging of 297 patients with melanoma, is reported. In 195 (99.3%) of patients, laparoscopy was technically feasible, and in 10% the clinical stage was changed on the basis of the findings. In 34% of patients with metastasis of the liver and peritoneum, the tumor had a diameter of under 1 cm and therefore was not detectable with non-invasive techniques. In the light of these results laparoscopy is advisable in patients with Stage I melanoma at a high risk of metastatization (Clark IV-V; Breslow greater than 0.76 mm) and in Stage II patients. In Stage III patients, laparoscopy seems indicated for an evaluation of the efficacy of systemic treatment.

Adolescent↗