Adjuvant chemotherapy for colorectal hepatic metastases: role of route of administration and timing.

Improved results in the adjuvant and therapeutic treatment of colon cancer has led to renewed interest in the role of adjuvant chemotherapy following liver resection for colorectal hepatic metastases. However, little is known about the most effective method or timing of delivery of adjuvant chemotherapy. Sixty-nine BD-IX rats underwent a right hepatic lobectomy following tumour inoculation via a splenic injection of 10(7) K12/TRb colon cancer cells. The rats were then randomized to receive systemic FUdR (1 mg kg-1 d-1 for 7 d) or regional (hepatic artery or portal vein) FUdR (2 mg kg-1 d-1 for 7 d) immediately or 72 h following tumour injection. On Day 28, a laprotomy was performed, and tumour nodules in the liver were counted. The animals were followed to death, and at autopsy the cause of death from hepatic or extrahepatic metastases was determined. All methods of FUdR infusion were superior to no treatment. Immediate portal vein (PV) FUdR infusion delayed the appearance of hepatic tumour (P = 0.003), changed the cause of death from hepatic to extrahepatic disease (P = 0.019), and prolonged survival (P < 0.05). Infusion of FUdR via the PV 72 h later did not delay the appearance of hepatic tumours nor prolong survival. In contrast, delayed HA FUdR infusion controlled hepatic metastases (P = 0.04) and improved survival (P < 0.05).

Management of large malignant rectal polyps with transanal endoscopic microsurgery. Is there anything better for the patient?

The authors report their experience with transanal endoscopic microsurgery (TEM), a technique that allows all the standard surgical manoeuvres such as tissue excision, suction, control of bleeding and suturing in the entire length of the rectal cavity. Main indications for TEM are the removal of large sessile polyps and early rectal cancers' (T1, G1-G2). Out of 50 patients submitted to TEM the authors consider in this study 24 cases with a preoperative diagnosis of benign large sessile polyps. The procedures included: 14 (58.3%) total wall excision, four (16.6%) total wall excision with perirectal fat, three (12.5%) mucosectomy, one mucosectomy + total wall excision, one partial wall excision + total wall excision, and the remaining case was converted to laparotomy due to a large intraperitoneal perforation. There was no operative mortality and an 8.3% rate of major complications. With a median follow up of 19 months there was no evidence of local or distant recurrence. The authors compare their results with those of alternative endoscopic and surgical techniques and highlight the advantages of TEM in the management of large and giant rectal polyps.

Lactitol in the treatment of chronic hepatic encephalopathy--a randomized cross-over comparison with lactulose.

The effect of lactitol, a new non-absorbable disaccharide, in the treatment of chronic hepatic encephalopathy was assessed in 14 cirrhotic patients with non-selective portosystemic anastomosis in a randomized, cross-over study. At the time of inclusion, all patients showed alterations in mental state, and/or psychometric performance, and in the electroencephalogram. Moreover, 10 out of 14 patients suffered from recurrent episodes of hepatic encephalopathy in the 12 months prior to the study. Patients were randomly treated for two consecutive periods of six months with either lactitol or lactulose. The PSE index was calculated to quantify the neuro-psychiatric impairment. Twelve patients completed the study. The patients required a daily dose of 38.2 g +/- 19 of lactulose or 36.3 g +/- 5 of lactitol to produce two semi-soft stools per day. No deterioration in the mental state or in the other neuro-psychiatric parameters were observed, neither during lactitol nor during lactulose therapy. During the study, mild episodes of recurrent encephalopathy occurred in 60% of the patients taking lactulose, and in 25% of the patients taking lactitol, the difference not being significant (X = 1.54, p = 0.21). Flatulence, the major side-effect noted during the study, was present in 7 of the 12 patients during lactulose treatment, and in 2 patients during lactitol treatment; one patient on lactitol complained of nausea. The side effects which occurred during lactitol of the dosage, while those occurring during lactitol appeared when the dosage was higher than 40 g. Lactitol may be considered at least as effective as lactulose in the treatment of chronic hepatic encephalopathy.

[The surgical treatment of gastric carcinoma. Evolution in surgical technique and staging in a series of 194 patients]. / Trattamento chirurgico del carcinoma dello stomaco. Evoluzione della tecnica chirurgica e della stadiazione in una serie di 194 pazienti.

AIM: Surgery is, at present, the only potentially curative treatment for gastric carcinoma. The curability depends upon the extension and localization of the tumor and, particularly, the lymphatic involvement and the presence of distant metastases. The aim of this paper is to describe the personal experience during the last 2 decades and analyze the results of the surgical approach which has changed over the time. METHODS: One-hundred and ninety-four consecutive patients have been reported (127 male and 67 female, with a median age of 65.8 years), affected by gastric carcinoma and subjected to surgical procedures from 1987 to 2000. Because of the wide period of time which it refers to, this study is overlapped by a radical change in the staging rules of gastric carcinoma, according to the publication, in 1997, of the 5th edition of the TNM. This has made necessary to divide the series into 2 different groups. The 1st group is composed of 123 patients (63.4%), staged according to TNM-1987; the 2(nd) group is composed of 71 patients (36.6%) staged according to the TNM-1997. A D1 lymphadenectomy was used as treatment protocol until 1995. Subsequently, a D2 lymphadenectomy was performed in the most part of potentially curable patients. The reconstruction after total gastrectomy was carried out in all cases with Roux technique. In distal gastrectomies a Billroth 2 technique was performed in 89.3% of the cases and a Billroth 1 technique in 10.7% of the cases. RESULTS: The operative mortality observed on the total of patients was 1.5% (3 cases). With a median follow-up of 83 months (minimal 24, maximum 180 months), 134 patients were died, 50 are alive and 10 have been lost. The total median survival, in the 2 groups, was 24 months. We have observed a trend to improvement of survival for patients with carcinoma in stage II and III operated after 1997. CONCLUSION: The treatment of unresectable gastric cancer, i.e. palliative surgery, is the best choice when possible in comparison to other surgical procedures (gastroenteronastomosis, jejunostomy), endoscopic procedures (dilatation, endoprosthesis, laser, percutaneous endoscopic gastrostomy) and medical therapies. In order to choose the best palliative treatment, a careful evaluation of the non-curability signs is necessary to avoid high risk surgical interventions in patients with a low expectation of life.

Systemic specific active immunotherapy for solid tumors. An overview about cancer vaccinetherapy.

Augmentation of specific immunity is one of the most promising immunotherapeutical approaches against solid tumors. Protocols using autologous tumor cells or tumor associated antigens are easily performed and not charged by severe side effects. Recently some clinical trials suggested good results from immunotherapeutical protocols applied as an adjuvant to surgery in terms of disease free interval, survival and progression time in different stages. In this review the authors report the results of the most important clinical trials of vaccinetherapy in solid tumors. Little is known about the possibility of this new approach to oncology since we are at the real beginning of a new clinical treatment but in the considered trial its effectiveness seems to suggest a future wider application.

[Infections in surgery]. / Le infezioni in chirurgia.

In this paper the authors review current concepts on surgical infections. Topics covered are: hospital-acquired surgical infections, prognostic indexes, antibiotic prophylaxis, surveillance and control measures.

[Endoscopic retrograde transparietojejunal approach in hepatico-jejunostomy. An experimental model using fibrin glue]. / L'accesso endoscopico retrogrado transparietodigiunale all'epatico-digiunostomia. Un modello sperimentale con utilizzo della colla di fibrina.

The Authors describe an experimental model that makes feasible to endoscopically approach a Roux-en Y hepatico-jejunostomy through a percutaneous transjejunal route. Potentials for its clinical application are briefly discussed.

Prognosis of node-positive colon cancer.

The most recent American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system subgroups patients into one to three and four or more positive nodes. However, the Gastrointestinal Study Group and the National Surgical Adjuvant Breast and Bowel Project divides node-positive patients into one to four and five or greater. A Cox multi-variate retrospective analysis was done of the overall survival of node-positive colon cancer patients with the specific objective of determining the most appropriate subcategorization. Data on 306 patients with node-positive colon cancer who underwent potentially curative surgery from 1970 to 1984 were analyzed retrospectively. No patient received adjuvant chemotherapy. Also excluded were patients with synchronous resected metastatic disease or those with rectal primaries. The median follow-up was 6 years, and the median survival for the entire group was 8.6 years. By univariate analysis, the following were significant prognostic features: number of positive nodes (P less than 0.0001), degree of differentiation (P less than 0.0001), colon primary site (P = 0.009), tumor stage (P = 0.001), and tumor size (P less than 0.0001). Lymphatic/blood vessel invasion and a mucinous histology were not significant. By Cox multivariate analysis the number of positive lymph nodes remained the best discriminant of survival (P = 0.0001). The number of positive nodes was related inversely to prognosis with the optimal dichotomization between one to three (66% 5-year survival) and four or greater nodes (37% 5-year survival).

Regional chemotherapy for colorectal hepatic metastases: evidence for improved survival with new drug combinations.

BACKGROUND: In patients with colorectal hepatic metastases, response rates with hepatic arterial infusion (HAI) FUdR (5-Fluoro-2-deoxyuridine) are significantly higher than with systemic fluoropyrimidines. We report a novel animal model of intrahepatic therapy for hepatic metastasis for the study of methods to increase response rates and improve survival. METHODS. BD-IX rats are injected intrasplenically with K12/TRb cells. When hepatic metastases are established, animals are treated with hepatic or systemic chemotherapy, and the response to treatment, survival, and cause of death is determined. RESULTS: Significant responses were observed with low- and high-dose HAI FUdR (p = 0.03 and 0.001, respectively). Only high-dose FUdR controlled hepatic disease. HAI FUdR alone did not prolong survival compared with control, but combination systemic FUdR and HAI FUdR did (p = 0.04). Continuous HAI of either 5-fluorouridine or mitomycin C has not previously been reported. There was no significant difference in response to FUdR, 5-fluorouridine, or mitomycin C. However, combination HA bolus mitomycin C plus either HAI 5-fluorouridine or HAI mitomycin C showed synergy with improved survival compared with all treatment groups (p < 0.0001). CONCLUSIONS: The combination of bolus hepatic artery mitomycin C with either HAI mitomycin C or HAI 5-fluorouridine yields significant response rates, and survival is improved by this novel combination therapy.

Anti-tumor effect of combined treatment with thymosin alpha 1 and interleukin-2 after 5-fluorouracil in liver metastases from colorectal cancer in rats.

We studied the effect of combined chemo-immunotherapy, 5-FU followed by thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/K12 cells (1,2-dimethylhydrazine-induced colon adenocarcinoma) in syngeneic BDIX rats. The presence of liver metastases was checked by laparotomy 14 days after tumor-cell injection. Evaluable rats were assigned randomly to 5 experimental groups designated as control, 5-FU, IL-2, 5-FU/IL-2 and 5-FU/T alpha 1/IL-2. 5-FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. T alpha 1 and IL-2 were administered for 4 days and repeated after 11 days. Combined chemo-immunotherapy was shown both to significantly reduce the growth of liver metastases and to prevent extra-hepatic spread. 5-FU/T alpha 1/IL-2 also improved survival rate. Combined immunotherapy after 5-FU restored NK activity of the peripheral-blood-mononuclear-cell (PBMC) in tumor and/or 5-FU immunodepressed rats and enhanced PBMC cytotoxic activity against the DHD/K12 autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases.

Lactitol in prevention of recurrent episodes of hepatic encephalopathy in cirrhotic patients with portal-systemic shunt.

Recurrent episodes of hepatic encephalopathy (HE) frequently occur in surgically shunted cirrhotic patients. The prevention of these episodes is based mainly on the long-term use of lactulose. Recently, lactitol, a nonabsorbable disaccharide similar to lactulose, has been proposed as an alternative in the management of HE. It has the advantage of being better tolerated and producing a more predictable catharsis. The effects of the two agents were compared in a controlled randomized study lasting six months involving 31 cirrhotic patients with portal-systemic shunt, of whom 40% experienced HE. The PSE index (mental state, EEG, asterixis, Raitan test, and ammonia) was assessed in each patient on entry to the study and every three months during treatment. Episodes of HE, side effects, and the patients' comments on efficacy, tolerability, and palatability were recorded. The dose required to induce two bowel movements per day was 48 +/- 25 ml of lactulose syrup and 36 +/- 7 g of lactitol. During the study, the number of patients who had an episode of HE and the PSE index was similar in both groups. The patients judged lactitol better from the point of view of palatability. Meteorism and flatulence, experienced by patients treated with lactulose, was not reported by the lactitol group. We concluded that lactitol is as effective as lactulose in the long-term prevention of episodes of HE in cirrhotics with portal-systemic shunt and may be better tolerated.