The prevention of deep venous thromboses after radical or modified mastectomy interventions

With the aim of preventing deep vein thrombosis after radical or modified mastectomy, 100 patients were randomly assigned to one of two different groups: the first group was treated with defibrotide (400 mg b.i.d. e.v.) starting from the day before the operation and continuing for the following seven days. The second group was given calcium heparin (5,000 IU b.i.d. by s.c. route) from day 0 to the 7th post-operative day. Neither side effects nor DVT or PE were observed. The quantity of fluids from the drainages rapidly decreased in both groups from the first day to the third one, while the quantity of blood cells was negligible starting from the second post-operative day. On this basis defibrotide may be considered an effective and well tolerated drug for the prevention of DVT.     

Predictive indices for the identification of high-risk patients

In this article, the predictive indices which have been developed during the last decade to assess the risk of complications during hospitalization are reviewed. These indices are based on the evaluation of nutritional and immunological parameters and are particularly suitable for the identification of the surgical patient at risk for postoperative septic complications. The authors also review the methods which have been proposed for the classification of the severity of disease in critically ill subjects and the sepsis score method for the prediction of clinical outcome in severely septic surgical patients.     

Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences

Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.     

Effect of Intralipid on some immunological parameters and leukocyte functions in patients with esophageal and gastric cancer

This study has been undertaken to investigate if the intravenous (i.v.) infusion of fat emulsions may be associated with impairment of some immunological functions thus increasing the risk of septic complications. Fifteen malnourished patients with advanced gastric or esophageal cancer received for 2 weeks preoperatively and 1 week after surgery an isocaloric and isonitrogenous TPN treatment with Intralipid (group A: n=8) or glucose alone (group B: n=7) as energy substrate. Cluster analysis of 11 nutritional parameters and some tests of the humoral and cellular immunity (IgG, IgM, C3c, Factor B; polymorphonuclear (PMN) cells, total lymphocytes, T and B lymphocyte counts; 'in vitro' PMN chemotaxis, adherence to nylon fibers, phagocytosis of latex particles) were sequentially determined. The incidence and severity of post-operative infections were investigated and a 'sepsis score' was calculated for each patient. Pre- and postoperative TPN were not associated with an improvement of the nutritional status. The humoral and cellular immune parameters showed the same behaviour in patients receiving Intralipid and in controls. The chemotactic activity of PMN cells was constantly normal, granulocyte adherence fluctuated below the normality range in controls, whereas phagocytosis of latex was similar in both groups. Post-operative infectious episodes were less severe in patients receiving Intralipid. Our results do not confirm that Intralipid adversely affects some aspects of the humoral and cellular immune response.     

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).     

Clinical-pharmacological aspects, application and effectiveness of total parenteral nutrition in surgical patients.

The term "total parenteral nutrition" (TPN) refers to the maintenance of an adequate nutritional status, normal body weight and positive nitrogen balance solely by intravenous means. It requires solutions providing calories, amino acids and other nutrients in amounts much greater than those indicated for maintenance of normal body weight. Nutrient solutions have been studied, selected and prepared in our Hospital Pharmacological Service utilizing a sterile closed system, which allows large-volume filtering, sterilizing and bottling devices. For maintenance of weight gain in adults, a basic formula is employed, which provides 1,100 Kcal/1 with pure crystalline amino acids mixed with 50% anhydrous dextrose in water in a ratio of 5.8:1 (160 Kcal:1 g nitrogen). Minerals and vitamins are added to the base solution prior to use and may be increased or decreased by simple addition or omission depending on the patient's condition. This paper is based on 192 surgical patients who received TPN and have been followed in strict cooperation between the Hospital Pharmacological Service and the Surgical Department. The patients, ranging from 23 to 79 years of age, with life threatening diseases and unable to maintain adequate nutrition by the oral route, received TPN through a central catheter inserted via subclavian puncture (146 cases) or through a surgically created internal A-V fistula (46 cases). The condition of the patients generally improved within a few days after starting TPN; and weight gain, wound healing, general improvement and a shorter period of hospitalization were observed. TPN could be efficiently combined with oncologic treatment, and a significant improvement of the patients' performance status and decrease of toxic side-effects due to chemotherapeutic agents were observed. TPN has been successfully applied also in patients with fistulas of the alimentary tract obtaining spontaneous closure and in patients with ulcerative colitis, showing its beneficial effect in allowing complete bowel rest for healing. No major complications or deaths could be attributed to TPN or to the route of administration.     

Detection of alkaline sphingomyelinase activity in human stool: proposed role as a new diagnostic and prognostic marker of colorectal cancer.

OBJECTIVES: Intestinal alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of messengers able to trigger the rapid turnover and apoptosis in intestinal epithelial cells. Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with human colorectal neoplasms. The aim of this study was to analyze the alkaline sphingomyelinase activity in feces from healthy subjects and colorectal adenocarcinoma patients and to correlate it with the enzyme activity in intestinal tissues. MATERIALS AND METHODS: The enzyme activity was measured both in the intestinal samples from 12 healthy controls and 51 patients with colorectal adenocarcinoma (tumoral and paratumoral tissue) and in the fecal samples of 34 healthy subjects and 29 patients with adenocarcinoma. The relation between sphingomyelinase activity and Dukes' stage, cell differentiation degree, age, and gender was also analyzed. RESULTS: Alkaline sphingomyelinase was significantly decreased (P < 0.001; mean reduction >90%) in tumoral intestinal mucosa of patients compared with controls independently of Dukes' stage and tumor differentiation grade. Interestingly, the enzyme activity in histologically normal paratumoral tissues was statistically lower than control samples (P < 0.001). As occurs in neoplastic tissues, a relevant mean reduction (P < 0.0001; almost 90%) of alkaline sphingomyelinase was revealed in stool samples from tumor patients when compared with controls. CONCLUSION: These findings may have implications for cancer biology and perhaps also for the design of clinical test, thus suggesting that the fecal sphingomyelinase activity could really reflect the human intestinal mucosa enzyme level and could represent a new marker for human colorectal adenocarcinoma, mainly taking into account its early appearance in intestinal neoplasms.