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In a series of 279 hepatectomies performed for cancer between June 1984 and March 1992, 46 were repeat operations, for metastases in 41 patients. The primary tumour was in the colon and rectum (28 patients), APU Doma (five) and miscellaneous (eight). Repeat hepatectomies were performed in 26 per cent of patients who had recurrence after the first liver resection and in 40 per cent of those who had liver recurrence. An unsuspected extrahepatic recurrence was discovered and resected in eight instances and in two other cases a known extrahepatic recurrence was resected during the second hepatectomy. The hospital mortality rate was 2 per cent (one patient); the death was from nosocomial pneumonia. The total morbidity rate including minor complications was 32 per cent, with a higher frequency of haemorrhagic problems after secondary liver resection (12 per cent) than after primary hepatectomy (5 per cent). The rate of postoperative complications after repeat hepatectomy was related significantly to operative blood loss greater than 1500 ml(P = 0·04). The technical problems of repeat hepatectomy were: (1) re-exposure of the liver, considered to be difficult in 67 per cent of second liver resections and 80 per cent of third procedures; (2) the liver parenchyma, which often had histological modifications between first and second resections and was more difficult to ‘work’ as shown by the mean duration of clamping of the hepatic pedicle (54 min for secondary versus 36 min for primary liver resection); and (3) modification of the intraparenchymal vasculobiliary anatomy following liver regeneration after major hepatectomy. Intraoperative ultrasonography was of great benefit. Rates of crude and recurrence-free survival were relatively encouraging at 47 and 33 per cent 3 years after the second liver resection for the whole group. These values were lower for colorectal cancer (37 and 21 per cent 3 years after the second hepatectomy). These figures do not, however, convey the complete picture of the outcome for these patients. During the same follow-up period, 143 recurrences were detected and a mean of 2·9 resections per patient were performed. The indications for repeat hepatectomy are still to be clarified, although the surgical technique is safe.

Nonhistone nucleoproteins associated with the nucleolar organizer region (NOR) can be visualized by a silver-staining technique on paraffin-embedded tissues. The number of black dots (Ag NORs) appearing on the nuclei are thought to reflect cell differentiation of certain tumors and can be used as an adjunct in predicting their evolution. We applied this method to determine if Ag NORs counts could be used as a diagnostic aid in borderline tumors of the ovary. Thirty-two cases of adenocarcinomas, 25 cases of borderline tumors, and 14 cases of adenomas were selected from Bouin-fixed archival material after histological examination. Both mean values of Ag NORs counts demonstrated a progressive increase from adenomas to borderline tumors and to carcinomas; the differences were statistically significant. Using discriminant analysis, all cases of benign and malignant tumors except one adenoma and one carcinoma were discriminated as belonging to an individualized group. No difference was found between borderline tumor with peritoneal implants and those without peritoneal implants. The results indicate that the Ag NORs counting procedure may be useful in distinguishing borderline tumors from carcinomas and adenomas. Ag NORs counts cannot, however, predict the clinical behavior of borderline tumors of the ovary.

Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies.

Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.