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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.

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.

Objectives: To evaluate the prevalence of abdominal aortic aneurysms (AAA) in a general population and to compare the results with those of similar studies in other countries., Design: Ultrasound screening study and collection of clinical and biochemical data., Setting: An urban Health Service District in Genoa, Italy., Materials: A general population, aged 65-75 years, invited by personal letter between 1991-1994., Results: 1601 subjects (741 males and 860 females) out of 2734 invited (58.5%) were evaluated. According to the ultrasound findings, 27 patients (1.7%) had an aortic dilatation of 26-29 mm; an AAA of 30-39 mm was found in 37 (2.3%) and an AAA > or = 40 mm in 33 (2.1%). The overall prevalence for AAA was 4.4% (8.8% in males and 0.6% in females respectively). The prevalence of smoking, alcohol consumption, coronary heart disease, chronic obstructive pulmonary disease and arterial disease were significantly higher in patients with AAA (p < 0.01)., Conclusions: Ultrasound screening for AAA is a reliable and useful method and should be focused on men, regardless of concurrent disease.

Twenty-two patients with recurrent melanoma of the limbs, underwent Hyperthermic Antiblastic Perfusion (HAP). HAP lasted 60 min, with maximal local temperature of 40.5-42 degrees C and melphalan 10 mg/L limb volume as antiblastic agent. Fourteen patients had in-transit metastases and 8 local recurrences. Regional nodes were involved in 6 patients. Systemic leakage monitored with 125I or 99Tc ranged between 5 and 30% (mean 19%). No operative mortality nor major complications occurred. Local toxicity scored Wieberdink grade I in 6 patients, grade II in 11 and III in 5. Response rate (UICC) in the 9 patients treated with unexcised lesions was 88% (55% complete responses). After a median follow-up of 27 months (1-92) 9 patients relapsed after a median time of 17 months, and 15 patients are currently disease free, 4 of them being re-excised and one reperfused. Actuarial 5 year survival is 67%, with 45% 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.

Since January 1992 a feasibility study was set up to establish the possible role of pelvic hyperthermochemotherapy for the local control of rectal cancer. Patients with resectable rectal cancer (clinical stage III-IV) are eligible for the study. Only patients submitted to abdominoperineal resection with or without extended pelvic linfoadenectomy (PLND) and/or resection of contiguous organs are included in the initial pilot phase of the study. Until now, two patients with stage III rectal cancer submitted to abdominoperineal resection and PLND have been treated. A single (40 mg) push of MMC was injected in the circuit with median local temperature of 46.0 +/- 0.3 and 45.9 +/- 0.5 degrees C and the pelvis was perfused for 60 min. There were no local or systemic complications. The ratio between the pelvis and plasma AUCs showed a high local pharmacokinetic advantage. The treatment can contribute to complete the standard protocols of adjuvant therapy. Since the simple decrease of local recurrence could represent an important clinical aim, this experience, even initial, supports us to continue the study.

Purpose: The increased risk of pelvic recurrence in patients with locally advanced rectal cancer seems to justify a more aggressive regional therapeutic approach. In this attempt a feasibility study has been recently activated on hyperthermochemotherapeutic pelvic wash in patients with resectable, locally advanced, cancer of the distal rectum., Methods: Two alternative methods of hyperthermochemotherapeutic pelvic wash have been used in sequence. In the first method 3000 ml of warm (45 degrees C) saline solution containing 30 mg of mitomycin C were injected into the pelvis both intraoperatively and in the immediate postoperative period. In the second method a 60-minute perfusion of the pelvic space with 2000 ml of heated (45 degrees C) saline solution with 40 mg of mitomycin C was provided intraoperatively using an extracorporeal circuit., Results: Four patients submitted to abdominoperineal amputation with pelvic lymph node dissection have been treated following one of the two methods. No complications related to the treatment occurred. Either the first or the second hyperthermochemotherapeutic pelvic wash method showed a high regional pharmacokinetic advantage with a perfusate/blood "AUCs" ratio of 576 and 374, respectively., Conclusions: The potential role of hyperthermochemotherapeutic pelvic wash as an additional regional treatment in locally advanced rectal cancer and the differences between the two methods, in our limited experience, are discussed.

Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.

A basic requirement for arterial chemotherapy of liver tumors is complete catheter perfusion of the liver. In cases with atypical anatomy of the hepatic artery, it is frequently impossible to obtain this goal by means of a single catheter. In a patient with a right replaced hepatic artery, the aberrant vessel was ligated and the left hepatic artery was perfused through a catheter inserted into the gastroduodenal artery. Perfusion scans performed through the catheter 14 and 135 days after arterial ligation showed a fall in the arterial flow to the right liver (right/left ratio 0.43 and 0.60). In contrast, a nearly complete perfusion of the liver (0.91 right/left ratio) was obtained 28 days after ligation, when the perfusion scan was performed immediately after catheter infusion of 90,000,000 degradable starch microspheres (DSM: diameter = 40 m). DSM administration is supposed to increase back pressure in the lobe receiving native circulation, thus activating intrahepatic collateral flow to the ischemic lobe. As regards regional treatment of liver tumors, obvious conclusions are to be drawn.

The role of vascularity as a prognostic factor was investigated in 35 patients undergoing arterial chemotherapy for liver tumours. Compared with parenchyma, tumour vascularity was classified as hot (18 cases), cold (12 cases), and mixed (12 cases) using 99mTc-macroaggregated albumin (MAA) hepatic arterial scans. The proportion of patients showing complete and partial responses to treatment was higher in the hot group (56 per cent) than in the combined cold and mixed group (12 per cent). In 15 cases (six hot, six cold and three mixed lesions), additional MAA scans were performed immediately after arterial embolization with degradable starch microspheres (DSMs). Either complete or partial reversal of tumour vascularity was observed after DSM-embolization in five and seven cases respectively, two and two of them respectively showing native cold lesions. As tumour vascularity appears to be a prominent prognostic factor, DSM-embolization should improve the efficacy of treatment by improving liver extraction of drugs and causing flow redistribution towards hypovascular areas.