Biomedical subjects

R Manzi

Publications and source records attributed to R Manzi.

11 recordsLinked to original sources

PubMed2003

Cytoreductive surgery followed by intra peritoneal hyperthermic perfusion in the treatment of peritoneal surface malignancies: morbidity and mortality with closed abdomen technique.

AIMS: The purpose of this phase II study was to analyze the morbidity and mortality of cytoreductive surgery (CRS) + intraperitoneal hyperthermic perfusion (IPHP) in the treatment of peritoneal surface malignancies. PATIENTS AND METHODS: One hundred and sixty four patients (36 ovarian cancer, 32 abdominal sarcomatosis, 34 peritoneal mesothelioma, 36 pseudomyxoma peritonei, 12 gastric cancer, 8 colon adenocarcinoma and 8 from other origins) underwent 166 procedures. Two patients underwent the intervention twice due to disease relapse. The mean follow-up was 20.6 months (range: 0.4 - 91.3). The mean age was 52 years (range: 24-76). CRS was performed with peritonectomy procedures. IPHP through Closed abdominal technique was conducted with preheated (42.5 degrees) perfusate containing cisplatin+mitomycin C or cisplatin+doxorubicin for 60/90 minutes. RESULTS: grade 3/4 morbidity rate was 12.0%. Some frequent post-operatory complications were intestinal fistulas (17), respiratory (5) and abdominal bleeding (4). Multivariate analysis with logistic regression model with the backward elimination method identified carcinomatosis extension (OR: 5.3, CI95%: 1.2-24.5) as the best predictor of morbidity grade 3/4. Four patients presented grade 3/4 toxicity. Operative mortality rate was 0.6%. CONCLUSIONS: CRS+ IPHP presented acceptable morbidity 3/4 toxicity and mortality rates what support the need to be tested in prospective phase III clinical trial.

Adult↗

PubMed1995

Pulmonary toxicity of alpha tumor necrosis factor in patients treated by isolation perfusion.

We studied pulmonary function in 22 patients affected by in-transit metastases from cutaneous melanoma and metastases from soft tissue sarcoma of the limbs who were treated with isolation perfusion in extracorporeal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild hyperthermia. Seventeen patients suffered from respiratory insufficiency which required assisted ventilation (7 mechanical ventilation for 1 day, 8 for 2 days and 2 patients on synchronized intermittent mandatory ventilation). Spirometric parameters recorded 7 to 15 days after treatment did not change from baseline values; in contrast, lung transfer factor for carbon monoxide significantly declined in a dose dependent fashion. These data confirm that rTNF alpha administered by isolation perfusion technique induces pulmonary side effects. Further studies are required to better define time course and reversibility of impairment in pulmonary function.

Adult↗

PubMed1994

Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan.

BACKGROUND: Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation. METHODS: From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature). RESULTS: Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6). CONCLUSIONS: The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.

Adult↗

PubMed1994

Treatment of in-transit metastases from cutaneous melanoma by isolation perfusion with tumour necrosis factor-alpha (TNF-alpha), melphalan and interferon-gamma (IFN-gamma). Dose-finding experience at the National Cancer Institute of Milan.

From December 1991 to July 1993, 22 consecutive patients with grade IIIA-IIIAB melanoma underwent isolation perfusion with TNF-alpha (0.5-4 mg), melphalan (10 mg/l perfused limb) and, in the first 12 cases, IFN-gamma (1.5 x 10(6) U). The first series of 12 patients received a total dosage TNF-alpha of 2-4 mg, and the second series of 10 cases received an escalating dosage of TNF-alpha (1.5-1.0-0.5 mg) and no IFN-gamma before or during surgery. The perfusion lasted 90 min and was conducted in mild hyperthermia (39-39.5 degree C muscle temperature). The results of the first series included seven patients in complete remission, four with stable disease and one case not evaluable for local toxicity. Fifty per cent of cases developed a regional relapse from 3 to 4 months after surgery. Presently with a median follow up of 10 months, five patients of this group have no evidence of disease, four are alive with disease, two died from melanoma and one died of complications likely due to treatment (multi-organ failure syndrome). In the second series, the immediate responses included seven patients in complete remission and three in partial remission; with a median follow up of 3 months, two patients developed a regional relapse, respectively, 3 and 5 months after surgery. So far our experience of perfusion with TNF-alpha has not reproduced the data reported by other investigators. Further clinical and biological findings and a longer follow-up period are needed to draw any conclusion, and a decreasing TNF-alpha dose should be carefully evaluated.

Adult↗

PubMed1993

Reappraisal of the role of liver transplantation in the treatment of hepatocellular carcinoma arising in cirrhosis.

Several retrospective analyses have recently shown the advantage of liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) at early tumor stages. Preliminary results of a prospective series of OLT for unresectable small HCC arising in cirrhosis are reported. Eighteen out of 22 patients (82%) are alive without evidence of HCC recurrence after a median follow-up of 11 months.

Carcinoma, Hepatocellular↗

PubMed1993

Pulmonary toxicity of recombinant interleukin-2 plus lymphokine-activated killer cell therapy.

The aim of the present investigation was to evaluate lung toxicity in 15 patients affected by metastatic melanoma of different sites, and treated with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells The treatment regimen included a first and a second course of rIL-2, separated by four consecutive daily leukaphereses. Autologous LAK cells were reinfused during the second course. Lung function was monitored before and after each rIL-2 administration. In the 12 patients who could be followed until completion of the therapy, spirometric parameters and transfer factor of the lungs for carbon monoxide (TLCO) decreased significantly during the first rIL-2 course, remained stable during leukapheresis, and declined significantly further during the second rIL-2 course. In the second phase, chest radiography documented some degree of pulmonary oedema, ranging from interstitial oedema to frank pulmonary oedema. A significant dose-dependent correlation was found between the cumulative rIL-2 dose and the decline in TLCO in the first course of therapy. Moreover, patients who developed symptomatic respiratory insufficiency (World Health Organisation grade III or IV) during the second course of therapy received a higher number of LAK cells than those who did not. The data support the hypothesis that LAK cells have an additional toxic effect on the lung.

Adult↗

PubMed1991

[Use of buprenorphine after right hepatectomy].

Ten patients who underwent surgery (5 right hepatectomy and 5 colectomy) for cancer participated in a clinical controlled study. They were treated with buprenorphine (i.v. slow infusion) to relieve postsurgical pain. We found an increased urinary excretion of this drug in patients who underwent hepatectomy as compared with patients who underwent colectomy. However no differences in the occurrence of side-effects and/or in the therapeutic effect were observed between the two groups. We conclude that buprenorphine can be effectively and safely used also in patients with a resection of liver parenchyma.

Adenocarcinoma↗

PubMed1990

[Functional changes in the biliary system following extrahepatic biliary obstruction].

To assess the potential structural changes of the biliary tree and liver in patients with extrahepatic biliary obstruction, the resected specimens of 20 patients operated for benign biliary stricture were evaluated by means of immunocytochemical and histological methods. Furthermore, liver biopsies were taken for the same purposes. The results showed that in the dilated segment of the hepatic duct proximal to the stricture, innervation was greatly reduced or completely absent with associated advanced morphological and histological changes and high intrabiliary pressure levels. Similar findings were observed in the liver biopsies, too. These biopsies showed advanced morphological and histological changes associated with reduced innervation. By contrast, the nondilated segment of the hepatic duct, distal to the obstruction, showed normal innervation, normal morphology and histology and normal levels of intrabiliary pressure. The present study provides evidence that in cases of extrahepatic biliary obstruction, there are advanced pathological changes in the biliary tree associated with innervation impairment. These structural changes are associated with functional changes in both the liver and the biliary tree. Such functional changes represent a threat to the patient, particularly if major surgery is required. Increased biliary pressure appears to be a major cause of the development of these changes. Biliary drainage, either surgical or endoscopic, is indicated as the only alternative to reduce intrabiliary pressure and to contribute to a reversal of these structural and functional changes.

Bile↗

PubMed1990

[Muciparous cells and endocrine cells of the gallbladder epithelium in patients with uncomplicated cholelithiasis].

In this study the authors have investigated the different morphofunctional features of the gallbladder mucosa in patients with uncomplicated cholelithiasis. Histological changes, type and distribution of endocrine and mucin-producing cells were characterized by immunocytochemistry and mucin histochemistry. The authors attempted to correlate these findings to the number and size of gallbladder stones as well as type of bacteria present in the bile. The results indicate that, despite similar clinical parameters, a wide range of histological changes may occur in the gallbladder mucosa of these patients. Moreover, the presence of some endocrine and mucin-producing cell types in the so called "pyloric metaplasia" led the Authors to hypothesize that the latter may be a trivial event.

Cholelithiasis↗

PubMedDate not supplied

Cardiac and pulmonary effects of alpha tumor necrosis factor administered by isolation perfusion.

AIMS: We studied cardiac and pulmonary function in 22 patients affected by in transit metastases from cutaneous melanoma and metastases from soft tissue sarcoma of the limbs and treated with isolation perfusion in extracorporeal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild hyperthermia. PATIENTS AND METHODS: All patients experienced a septic-like shock syndrome of variable severity: this feature lasted from 24 to 72 h and was controlled by the infusion of dopamine. Seventeen patients suffered from respiratory insufficiency, which required assisted ventilation (7 cases mechanical ventilation for 1 day, 8 cases for 2 days, and 2 cases synchronized intermittent mandatory ventilation). RESULTS: Spirometric parameters recorded 7-15 days after treatment did not change from baseline values. In contrast, lung transfer factor for carbon monoxide significantly declined in a dose dependent fashion. CONCLUSIONS: Our data confirm that rTNF alpha administered by isolation perfusion technique induces systemic cardiovascular and pulmonary side effects. Further studies are required to better define time course and reversibility of impaired pulmonary function.

Adult↗

PubMedDate not supplied

Treatment of recurrent sarcoma of the extremities by isolated limb perfusion using tumor necrosis factor alpha and melphalan.

BACKGROUND: 24-60% of patients with soft tissue sarcoma shows local recurrences after treatment of the primary tumor. The event is associated with a high incidence of macroscopic or microscopic metastases and a poor survival. Our goal is to preserve a patient's functional limb by treating such cases with isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rHu TNF-alpha) and melphalan, which have demonstrated a potent antitumor activity in vivo and in vitro studies. METHODS: During the period November 1991 to November 1995, 10 patients with unresectable recurrent soft tissue sarcoma of the limb were treated by ILP at intermediate hyperthermia (40-40.5 degrees C) with rHu TNF-alpha and melphalan. Two patients also received recombinant interferon gamma (rIFN-gamma) before and during ILP. We used a range of 2-4 mg for rHu TNF-alpha and 50-100 mg of melphalan. rIFN-gamma was administered on days -2 and -1 (15 x 10(6) IU) subcutaneously and the same dose was injected in the arterial line during ILP. RESULTS: No perioperative surgical complication was observed. Local toxicity was moderate (grade I or II); general toxicity was observed in 6 patients (2 grade I and 4 grade III). Complete response was obtained in 7 cases; 2 patients had a partial response and finally 1 was a nonresponder and showed local progression, which required surgical amputation. Tumor necrosis (observed in 5 cases) was maximal in 4 patients (80-100%) and absent in the patient who had local progression. CONCLUSIONS: The results we obtained with the treatment of soft tissue sarcoma confirm the efficacy of ILP as a limb-sparing methodology for unresectable recurrences. Furthermore, rHu TNF-alpha and melphalan confirmed their antitumor activity when associated with hyperthermia. Amputation or disarticulation may be reliable as a second-choice treatment for these patients.

Adult↗