[Surgical resection of gastrointestinal stromal tumor after treatment with imatinib: clinical case]. / Resezione chirurgica di un tumore stromale gastrointestinale dopo trattamento con imatinib: un caso clinico.

The stromal tumor is the most common mesenchymal tumor of the gastrointestinal tract. Surgical resection is the first-line therapy for operable lesions, however for inoperable imatinib is an effective therapy. In this setting a patient has been operated after a remarkable response to imatinib, used as both neoadjuvant and adjuvant. This approach led to a disease-free condition without toxicity and complications.

Anterior tension-free repair under local anesthesia of abdominal wall hernias in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: A 10-year experience of abdominal wall hernia repair performed with anterior tension-free mesh or plug technique under local anesthesia in end-stage renal failure patients submitted to continuous ambulatory peritoneal dialysis (CAPD) is described in order to assess the safety and effectiveness of this approach. METHODS: Between January 1993 and December 2002, 18 hernia repairs were performed under local anesthesia in 16 patients (14 males and two females) with a mean age of 70 years (48-78). One umbilical and three unilateral inguinal hernias were observed and repaired before starting peritoneal dialysis (PD), while two umbilical, eight unilateral, and two bilateral groin hernias developed and were then treated during PD. Repairs were performed electively in all but one case, which was an emergency operation for strangulation. An ipsilateral scrotal swelling was also present in two indirect unilateral inguinal hernias. In these cases, the hernia sac was ligated before entering, while in the others it was simply dissected and inverted. RESULTS: Patients were discharged the same day or the day after surgery. No local or general immediate or late complications occurred. CAPD in subjects operated on during PD treatment was resumed the same day of surgery. In no instance was hernia recurrence or leak of dialysis solution observed at follow-up examinations. CONCLUSIONS: The absence of surgical and general complications and the nearly immediate resumption of PD indicate the anterior tension-free repair under local anesthesia as a safe and effective technique for CAPD patients even in an ambulatory or day-surgery setting.

Intraperitoneal mitoxantrone: a feasibility and pharmacokinetic study.

Fractionated doses have been advocated to prevent chemoperitonitis after intraperitoneal infusion of mitoxantrone. Patients with peritoneal carcinomatosis of various origin underwent surgery, including intestinal resections, with minimal residual disease. Peritoneal mitoxantrone in 1000 ml/m(2) saline was planned on the first post-operative day in groups of four patients (5 mg/m(2) for 3 and 5 days, 7.5 mg/m(2) for 3 and 4 days, 10 mg/m(2) for 2-4 days, if possible). Due to dose-limiting myelosuppression, only one and three patients received the 7.5-mg 4-day and 10-mg 3-day regimens, respectively. A total of 20 patients were consequently treated. Neither major complications nor severe pain were observed. Pharmacokinetics were completed on the 1st day in five 5-mg and five 10-mg patients, on the 5th day in three 5-mg patients, and on the 3rd day in one 10-mg patient. On the 1st day, mean peritoneal peak concentrations of mitoxantrone resulted 1.45 +/-0.56 (range 0.48-1.9) and 1.9+/-0.85 (range 1.27-3.13) microg/ml in the 5-mg and 10-mg patients, respectively. Mean dialysate/plasma exposure (AUC) ratio was 115. Even in patients with sutures, early post-operative fractionated intraperitoneal mitoxantrone appears feasible and safe, with a high local advantage, for up to 5 days of treatment and a maximum tolerated total dose of 20-25 mg/m(2).

Reduction of cisplatin nephrotoxicity by procainamide: does the formation of a cisplatin-procainamide complex play a role?

Procainamide protects mice bearing P388 leukemic cells against the toxicity of cisplatin without diminishing antitumor activity. The mechanism of action of procainamide protection was investigated both in vitro and in vivo. HPLC studies showed that procainamide forms a complex with cisplatin in vitro that has a UV spectrum similar to that of DPR, a triamine platinum complex that contains procaine as ligand. We report here the effect of the reaction product of cisplatin and procainamide on both cisplatin-induced DNA interstrand cross-links (ISCLs) and on the total DNA platination of isolated DNA. Total DNA platination in vitro of isolated DNA was increased by 113% (P <.01) and 17% (P <.05) after incubation times of 1.75 and 6 h, respectively, compared with products from the reaction of cisplatin with water. Furthermore, the reaction product of cisplatin and procainamide was bound to DNA to a significantly greater extent than was cisplatin itself. ISCLs were decreased by 41% when this drug combination was incubated with DNA for 1.75 h, but no changes were observed after incubation for 6 h. We also examined the influence of the time interval between administration of cisplatin and procainamide on normal kidney injury, the renal distribution and urinary excretion of platinum, and the formation of cisplatin-DNA adducts in renal tissue of Sprague-Dawley rats after i.p. administration of 7.5 mg/kg cisplatin either with or without procainamide. The plasma concentrations of urea and creatinine and kidney histology demonstrated that procainamide provided effective protection in vivo in the rat when administered either simultaneously or at 0.5 and 1 h before or after cisplatin. The protection was accompanied by both higher renal levels of platinum and cisplatin-DNA adducts and by an increase in the formation of ISCLs. Moreover, a dose-dependent reduction of urinary excretion and concentration of platinum was also observed. We propose that procainamide, after accumulation in the kidney, may coordinate with cisplatin to form a less toxic DPR-like complex that renders rats less susceptible to cisplatin-induced toxicity.

Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.

INTRODUCTION: Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior. METHODS: This study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41. 5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia. RESULTS: The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were greater after pleurectomy/decortication than after pleuropneumonectomy (P =.006). The local tissue/perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion. CONCLUSION: This multimodality approach is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.

[Pancreatic cancer. Analysis of 149 cases in our 17-year experience]. / Il carcinoma del pancreas. Analisi di 149 casi in 17 anni di esperienza.

The Authors analyse a series of 149 consecutive patients with carcinoma of the pancreas or the periampullary region. Curative surgical treatment was achievable in 55 patients, palliative procedures included surgery in 68 patients; biliary decompression with endoscopic or percutaneous procedure in 25 patients and chemotherapy in one patient with lymphoma. Perioperative complications consisted in gastroplegia (33%), pancreatic fistula (22%), biliary fistula (7.3%), abdominal abscess (5.5%) and hemoperitoneum (1.8%). Five patients died within 30 days after surgery (9%). The overall median postoperative survival was 37, 29 and 21 months in papillary, choledochal and pancreatic cancer, respectively.

Differential device performances for hepatic arterial chemotherapy: a technical report on totally implantable pumps and ports for both continuous and bolus infusion.

Performances of totally implantable infusion systems were analyzed in patients with colorectal liver metastases undergoing intra-arterial treatment. It consisted of 14-day continuous infusion of 5-fluor-2'deoxyuridine with pumps (pump14, 44 patients) or ports fed by external pumps (port14, 34 patients), or bolus infusion of cisplatin (port21, 57 patients) or epirubicin (port7, 22 patients) every 3rd week and weekly, respectively. Toxicity and disease progression were the most common causes of treatment interruption. System failure occurred in 2 pump14, 9 port14, 6 port21 and 2 port7 cases. Pocket problems were most frequent in the pump14 group (30%), whereas catheter- and infusion-related problems were mostly observed in the port14 group (109%). The devices were still functional after 12 months in 92% of pump14, 24% of port14, 65% of port21 and in 78% of port7 patients. Although implantable ports allow adequate infusion periods, in most cases they appear especially suitable for bolus infusions.

[Lipiodol with and without Gelfoam in primary liver tumors. Plasma levels of Mitoxantrone and clinical results]. / Lipiodolizzazione associata o meno a Gelfoam in pazienti con tumore epatico primitivo. Livelli plasmatici di Mitoxantrone e risultati clinici.

Transcatheter chemoembolization with various drugs is employed for palliative treatment of hepatocellular carcinoma. Thirty-seven patients (33 with Child A or B cirrhosis) were treated with 14 mg/m2 of Mitoxantrone and up to 20 ml of Lipiodol, followed by Gelfoam embolization as indicated. Sixty-nine cycles were given, with mean (+/-SD) Lipiodol and emulsified Mitoxantrone doses of 11.3 +/- 3.8 ml and 11.8 +/- 5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123 +/- 60 days. Thirty patients had Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. At the first cycle, 10 patients underwent serial measurements of serum Mitoxantrone up to two hours after a full dose of emulsified drug. Drug levels resulted much lower than those reported after plain arterial infusion, with AUC levels (+/-SE) of 5924 +/- 1015 and 4381 +/- 429 ng/ml x 120 min in 6 and 4 cases treated with and without Gelfoam, respectively. No treatment related deaths occurred. Complications were mild and transient, including nausea vomiting in most cases, fever > 38 degrees C 67%, pain 74%, ascites 8% jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor response) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with Mitoxantrone deserves further evaluation in randomized studies.

[Severe infections after orthotopic hepatic transplant]. / Infezioni gravi dopo trapianto epatico ortotopico.

METHODS: The authors analysed severe infections in 43 consecutive patients undergoing orthotopic liver transplant. Prophylaxis and full anti-infection monitoring was performed in all cases. Immunosuppressive therapy was administered in the form of primary cyclosporine in 27 cases and primary OKT3 in 16 cases. RESULTS: Twenty-seven patients are still alive (median 8 months, range 2-40) and 16 died (median 22 days, range 10-92) of whom 4 without and 12 with infection, including two deaths owing to non-correlated causes with infection after recovery. Twenty-three patients underwent 33 episodes of severe infection (plus four with inconclusive positive cultures) without any case of protozoal or viral infection. All episodes occurred within two months of surgery and affected the lung (10), abdomen (7), lung + abdomen (1), urinary tract (1), lung + urinary tract (1), as well as two diffused cases and 7 cases of isolated bacteremia deriving from the donor (1), venous catheters (3), mild otorhinolaryngeal infection (1) and two unknown sources (2). Eighteen infective agents were identified in 45 cases. The bacteria involved in single-agent episodes were: 11 Gram+, 9 Gram- and five fungi. Polymicrobic and bacterial/fungal episodes were repeatedly observed in two and two cases. Postoperative renal insufficiency significantly influenced both the incidence of and mortality due to infection. Overall mortality was also influenced by early graft function, postoperative complications and reoperations, and the incidence of infections by the portal clamping stage, reject and prolonged coma. CONCLUSIONS: The absence of severe viral infections and the gradual reduction of mortality caused by infection appear to be parallel to the aggressive antiviral prophylaxis, the gradual improvement of intra- and postoperative management and primary immunosuppression with OKT3.

[Effects of adjuvant hyaluronidase in tumors refractory to chemotherapy. Review of the literature and pharmacokinetics of cisplatin after regional administration in animals and humans]. / Effetto della ialuronidasi adiuvante in tumori refrattari alla chemioterapla. Revisione della letteratura e farmacocinetica del cisplatino dopo somministrazione regionale nell'animale e nell'uomo.

Several clinical studies have recently suggested that topical or systemic adjuvant hyaluronidase may increase the therapeutic index of anticancer drugs. In cases of disease progression, further objective responses have been observed after the association of hyaluronidase to the previously employed drugs. Some evidences suggest that hyaluronidase improves local diffusion as well as tissue and tumor uptake of the associated drugs. Hence, plasma and tissue concentrations of platinum following administration of cisplatin alone and associated with hyaluronidase have been investigated in 20 rats after intraperitoneal injection and in 10 patients with colorectal liver metastases and local progression of the disease after regional and systemic chemotherapy with intraarterial cisplatin and intravenous 5-fluorouracil. Three out of six refractory patients treated with hepatic intraarterial cisplatin + hyaluronidase showed one minor response and two stable diseases, respectively, without any apparent increase of treatment related toxicity. In turn, adjuvant hyaluronidase increased both the extent distribution and lasting time of cisplatin in the body and reduced plasma levels of total and free platinum originating from cisplatin, without any modification of either unbound fraction of platinum or total body clearance. Hence, adjuvant hyaluronidase seems to increase tissue extraction of cisplatin and, particularly, liver extraction after intraarterial administration in man. These results encourage further studies aimed to determine the clinical role of adjuvant hyaluronidase in patients refractory to regional chemotherapy.

[Performance and complications of totally implantable port device in bolus hepatic intra-arterial chemotherapy]. / Funzionalità e complicanze dei "port" totalmente impiantabili per la chemioterapia intraarteriosa epatica in bolo.

The performances of totally implantable ports were analyzed in patients with colorectal metastases undergoing intraarterial treatment. Seventy-nine patients received bolus infusion of Cisplatin (DDP, 57 cases) or Epirubicin (EPI, 22 cases) every 21 and 7 days, respectively. Disease progression or toxicity were the most common causes of interruption of treatment, whereas failure of ports occurred in six and two patients out of DDP and EPI groups, respectively. The incidence of single problems for each port was 65% in DDP group and 64% in EPI group, whereas rate of complications for each patient was 30% and 32%, respectively. The 12-months device duration rate in the two groups was 65% (median 17 months) in DDP group and 78% (median 18 months) in EPI group. The implantable ports employed for bolus arterial infusion, allowed adequate treatment periods in most cases, without any difference as far as intervals between cycles is concerned.

[Lacking effect of timing of surgery in relation to the menstrual cycle on prognosis of breast cancer in premenopausal women]. / Mancato effetto della temporizzazione della chirurgia in relazione con il ciclo mestruale sulla prognosi del cancro della mammella nelle donne in premenopausa.

The influence of timing of surgery in relation to menstrual period on survival of breast cancer patients has been both advanced advocated and disputed. A meta-analysis on published series showed a statistically significant overall odds reduction when surgery is performed in the luteal phase. The records of 165 premenopausal M- breast cancer women, not on hormonal therapies, consecutively operated on from 1977 to 1991 were reviewed. All patients underwent modified radical mastectomies or quadrantectomies plus operative radiotherapy, Node-positive patients received standard adjuvant chemotherapy. Cox regression analysis was used to estimate the relative risk (RR) of death in three models including timing of surgery, age, histology, pathological T and N. In each model, patients were divided into two groups according to the criteria proposed by Badwe, Hrushesky, and Senie. Multivariate analysis showed a significant association between pT and pN and survival, whereas no association with survival was observed for timing of surgery according to Badwe or Hrushesky or Senie criteria (RR = 1.26, RR = 0.91, and RR = 0.88 respectively). Up-to-date agreement on the menstrual phase and relative expected better prognosis is still lacking.

Timing of surgery related to menstrual cycle and prognosis of premenopausal women with breast cancer.

The influence of the timing of surgery in relation to the menstrual cycle on the survival of breast cancer patients has been both advocated and disputed. The records of 165 premenopausal M- breast cancer women consecutively operated from 1977 to 1991 were reviewed. All patients underwent modified radical mastectomies or quadrantectomies plus postoperative radiotherapy. Node-positive patients received adjuvant chemotherapy. Cox regression analysis was used to estimate the relative risk (RR) of death in three models including timing of surgery, age, histology, pT and pN. In each model, patients were divided into two groups according to the criteria proposed by Badwe, Hrushesky, and Senie. Multivariate analysis showed a significant association between pT and pN and survival, whereas no association with survival was observed for the timing of surgery according to either Badwe or Hrushesky or Senie (RR = 1.26, RR = 0.91 and RR = 0.88 respectively). Consensus on the menstrual phase related to the expected best prognosis is still required.

Helical CT for the study of abdominal aortic aneurysms in patients undergoing conventional surgical repair.

OBJECTIVES: To evaluate the reliability of helical computed tomography (CT) as sole preoperative diagnostic technique for abdominal aortic aneurysms (AAA) and to compare these results with the surgical findings. MATERIALS: Thirty-three patients undergoing elective surgical repair. METHODS: Helical CT, Doppler exam of lower limbs, digital angiography, in case of peripheral vascular disease, and intraoperative evaluation. RESULTS: Helical CT correctly detected, in all cases, the proximal and distal extent of the AAA. The coeliac axis and its branches, the superior mesenteric artery and renal vessels as well as the inferior vena cava were always clearly depicted, showing anatomical variants or pathological involvement in 14 patients (42.4%). CONCLUSIONS: Helical CT can be used as the sole method for preoperative imaging of AAA. It allows a complete and precise evaluation of size, extent and relationship of the AAA, the surrounding vessels and other abdominal structures.

Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas.

A multimodality approach including operation and isolated lung perfusion with platinum was used in six patients with lung metastases from soft tissue sarcomas. Staged thoracotomies were used in two patients with bilateral lesions. The inclusion criteria generally applied for surgical excision were adopted in this study. The pulmonary artery and a portion of the left atrium were isolated from systemic circulation and cannulated. The cannulas were then connected to a perfusion circuit and normothermic isolated lung perfusion was done for 60 minutes. The lung was then flushed and metastasectomy was done. Serial blood (systemic and pulmonary), tissue (normal lung and tumor), and urine samples were obtained for platinum content measurement by flameless atomic absorption spectroscopy. Lung damage was assessed by light and electron microscopy examination and by serial respiratory tests. Isolated lung perfusion was accomplished in all patients without any death, operative complication, or systemic toxicity. After operation, interstitial and alveolar edema developed in two patients (48 hours after treatment), necessitating respiratory support in one case. Total platinum concentrations in pulmonary plasma were about 43 times greater than those in systemic plasma. No differences in platinum concentrations between normal lung and metastatic tissue were found. Thus the proposed isolated lung perfusion technique is feasible and safe enough to be offered as a valid model to study combined chemosurgical approaches in the treatment of lung metastases.

Screening study of abdominal aortic aneurysm in a general population: lipid parameters.

The level of blood lipids and apolipoproteins in subjects being screened for abdominal aortic aneurysms have been investigated. As part of an ultrasound screening programme in a population of 65- to 75-year-olds, blood samples were collected from 1460 of 1504 subjects with a normal aorta (97.1%) and 69 of 70 patients with an abdominal aortic aneurysm > 29 mm (99%). Samples were also taken from 22 of 27 patients (81%) with an ectatic aorta (26-29 mm). Total cholesterol, HDL-cholesterol, LDL-cholesterol, Apo-AI and Apo-B levels were significantly higher in women than in men (P < 0.01). Levels of HDL-cholesterol and Apo-AI were significantly lower in patients with an abdominal aortic aneurysm than in normal subjects (P < 0.001). The mean(s.d.) body mass index was 25.1(3.9) in women and 25.5(3.2) in men with aneurysms and not significantly greater than that of normal subjects (25.2(3.61) and 25.2(3.38) respectively).

Conventional isolated hyperthermic antiblastic perfusion in the treatment of recurrent limb melanoma.

Hyperthermic Antiblastic Perfusion (HAP) is a widely used method for the treatment of recurrent limb melanoma. In terms of tumor response, locoregional control and survival HAP has led to better results than those achieved with any other treatment. The aim of this report is to analyze our own experience with HAP in locally advanced limb melanoma. Thirty-two patients were submitted to HAP. HAP lasted 60 minutes, with maximal local temperature of 40.5-42 degrees C using melphalan 10 mg/L limb volume as antiblastic agent. Twenty patients had in-transit metastases and 12 local recurrence. Regional nodes were involved in 12 patients. Systemic leakage monitored with 125I or 99Tc ranged between 5-30% (mean 14%). No operative mortality nor major complications occurred. Local toxicity scored Wieberdink grade I in 8 patients, grade II in 17, grade III in 6 and grade IV in 1 case. Response rate (UICC) in the 16 patients treated with unexcised lesions was 94% (56% complete responses). With a median follow-up of 29 months (2-126) 14 patients relapsed after a median time of 10 months, and 17 patients are currently disease free, 3 of these are being reexcised and 3 re-perfused. Actuarial 5 years survival was 64%, with 39% disease free to the first relapse. Our results are consistent with the literature indicating HAP as a safe procedure with a high evidence of clinical responses.

[Function and complications of diverse totally implantable systems for continuous intra-arterial infusion of FUdR in colorectal hepatic metastases]. / Funzionalità e complicanze di diversi sistemi totalmente impiantabili per l'infusione intraarteriosa continua di FUdR nelle metastasi epatiche colo-rettali.

Different totally implantable arterial infusion systems were compared in patients with liver metastases from colorectal cancer undergoing continuous intra-arterial infusion. Seventy-eight patients received continuous FUdR infusion using either totally implantable pumps (group a = 44 pts.) or ports fed by external portable pumps (group b = 34 pts.), and 57 patients received bolus infusion of Cisplatin (group c). Devices were cared for patency even after interruption of treatment, commonly caused by disease progression. Pocket problems most frequently occurred in group a (30%) compared to groups b (9%) and c (7%), whereas a higher incidence of catheter and infusion related problems was observed in group b (109%). System failure was recorded as a cause of interruption of treatment in two, 9, and 6 cases in groups a to c, respectively. The 12-months patency rate was 92% in group a, 24% in group b (median 9 months), and 65% in group c (median 17 months). Though implantable ports allow adequate infusion periods in most cases they seem more adequate for bolus infusions.

Palliative chemoembolization of hepatocellular carcinoma with mitoxantrone, Lipiodol, and Gelfoam. A phase II study.

Transcatheter chemoembolization, in conjunction with various drugs, has been widely used for palliative treatment of hepatocellular carcinoma. A phase II study was carried out on mitoxantrone chemoembolization. High risk cirrhotic patients were excluded from this study. Fourteen mg/m2 mitoxantrone and up to 20 ml Lipiodol were injected, followed by Gelfoam embolization as indicated. Thirty-seven patients (33 with cirrhosis) were treated. Sixty-nine cycles were delivered, with mean (+/-SD) Lipiodol and emulsified mitoxantrone doses of 11.3+/-3.8 ml and 11.8+/-5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123+/-60 days. Thirty patients received Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. No treatment-related deaths occurred. Complications were mild and transient, including nausea/vomiting in most cases, fever over 38 degrees C 67%, pain 74%, ascites 8%, jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor responses) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with mitoxantrone appears to be a promising method for the palliation of advanced hepatocellular carcinoma, and deserves to be evaluated in well controlled randomized studies.