Confirmation of graft-versus-host disease after liver transplantation by PCR HLA-typing.
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Biomedical subjects
Publications and source records attributed to F Bozzetti.
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The survival of two groups of patients, affected by liver metastases (Stage I and II by Gennari et al.) from a previously operated colorectal cancer and treated by surgical resection (Group 1, 39 patients) or chemotherapy with various cytotoxic drugs (Group 2, 31 patients) at the Istituto Nazionale Tumori, Milan, is reported. In comparison with Group 2, Group 1 included more patients with metachronous lesions, with high level of serum bilirubin and with primary tumour originating from the colon. A univariate analysis (log rank test) identified a statistically significant prognostic role of type of treatment (surgery vs chemotherapy) and of the level of serum bilirubin. However the multivariate analysis by the Cox's regression model showed that the only independent statistically significant prognostic factor was type of treatment, since the hazard ratio of surgery vs chemotherapy was 0.490 with a 95% confidence interval of 0.256-0.936. The survival probabilities at 24 and 36 months were respectively 60% and 47% in surgical patients, vs 30% and 23% in those receiving chemotherapy, the difference between the curves being statistically different (P = 0.001). The median survival of Group 1 patients was 30 months whereas the median survival of Group 2 patients was 19 months, a value quite similar to that published in literature for untreated patients with limited metastatic disease-thus indicating that this patients' population was not selected according to unfavourable criteria. These findings suggest a beneficial role of surgical resection in patients with colorectal metastases confined to the liver in Stages I and II.
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Since 1980 120 patients with hepatic metastases from colorectal cancer underwent surgery at the Istituto Nazionale Tumori of Milan. Of these, 34 developed recurrence in the liver only and 11 underwent repeat surgery. The median interval between the two resections was 10 months and operative morbidity and mortality rates were 40 per cent and 9 per cent respectively. Nine patients with adequate follow-up were evaluated and after a median follow-up of 17 months four were alive and disease-free, two were alive with lung metastases and hepatic relapse and three had died. The overall median survival of these patients was 23 months.
Right and left paracardial dissection represents an obligatory step in gastrectomy for gastric cancer of the lower half of the stomach because a second-level lymphadenectomy is part of the radical surgery for malignancy at this site. Whereas right and left paracardial dissection is easily accomplished during total gastrectomy, there is doubt as to whether subtotal gastrectomy achieves the same radical clearance of these groups of lymph nodes. This study therefore compared the number of lymph nodes dissected and the frequency of metastases in these compartments in 14 patients undergoing total gastrectomy and 22 submitted to subtotal gastrectomy. The mean number of lymph nodes dissected in the right paracardial compartment was 7.1 per patient undergoing total gastrectomy and 6.7 per patient in subtotal gastrectomy (P = 0.7). The mean numbers of left paracardial lymph nodes dissected in total and subtotal gastrectomy were 3.4 and 4.1 per patient respectively (P = 0.3). These data show that the same degree of radical clearance can be achieved in these nodal compartments, irrespective of the extent of gastric resection.
A retrospective analysis to compare the single vs double stapled technique for rectal anastomosis was carried out on patients that underwent radical surgical resection between January 1986 and January 1989 at the Istituto Nazionale Tumori of Milan. In 143 patients anastomotic integrity had been checked both intraoperatively with air insufflation and postoperatively by water soluble contrast enema. A single stapled anastomosis (SST) was performed using the EEA instrument in 94 patients, and in 49 patients a double stapled (DST) using the EEA and TA instruments was performed. The level of the anastomosis was less than or equal to 10 cm from the anal margin in 94 patients (54 SST, 40 DST). In 52 patients it was greater than 10 cm (40 SST, 12 DST) (SST vs DST ns). The presence of anastomotic dehiscence occurred in 29 (20%) patients (17 SST, 12 DST). This was not related either to the anastomotic site or to the suture technique used. The dehiscence was located on the posterior wall in 79% of cases and in 58% the size was less than 1 cm. In 78% clinical symptoms were evident. There was no difference between SST and DST patients. Further surgery (colostomy) was necessary in six patients (2 SST, 4 DST). Two patients died through complications (1 SST, 1 DST); making an overall mortality rate of 1.0% and 2.0% in each group. There was no difference in infection rate and length of postoperative stay in the two groups. Our data demonstrate that both methods give similar results.(ABSTRACT TRUNCATED AT 250 WORDS)
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In order to assess whether the gastric wall undergoes some change in length during gastrectomy operation for cancer, we measured the variation in length of the anterior gastric wall in 25 patients. The first measurement was made at the beginning of laparotomy by placing two stitches on the anterior gastric wall and registering the distance between them. A second and a third measurement were recorded when the stomach was fully isolated just before its transection and subsequently on the anatomic table. The results indicate that the usual recommendations made by pathologists to maintain a 6 cm margin of tissue clearance proximally to the cephalic edge of the tumour, can be safely followed by the surgeons who can correctly assess, during operation, the distance between tumour and the desirable line of transection since no misleading reduction in size of the resected specimen takes place.
The purpose of this review is to analyse critically the pros and cons of 'en principle' total gastrectomy for cancers of the distal stomach. The theoretical advantages of total gastrectomy would be the guarantee of no infiltration of the margin of proximal transection owing to multicentric cancers or to a microscopical intramural spreading of tumoral cells beyond the macroscopically detectable boundaries of the lesion. However, these expectations are not substantiated since multicentric tumours are rare, a safe margin of resection can be achieved maintaining a proximal clearance of 6 cm from the cranial edge of the tumour. Moreover, recurrences confined to the gastric stump, after subtotal gastrectomy (and originally preventable with a total gastrectomy) are extremely rare according to literature. Furthermore, current experience suggests that the extent of lymph node dissection is not affected by the extent of the resection of the stomach. Analysis of the published series of patients undergoing an en principle total gastrectomy fails to demonstrate any advantage for long-term survival compared with patients treated by subtotal gastrectomy. A recent randomized trial comparing these two procedures is in keeping with the above-mentioned conclusions. It is true, however, that the gap in surgical mortality for total and subtotal gastrectomy tends to disappear when total gastrectomy is electively performed in patients with tumours of the distal stomach. So, whereas the long-term oncological results of the two surgical procedures seem to be similar, the main disadvantage of total gastrectomy is the onset of malnutrition, which is common, but incapacitating only in a few patients. This condition is likely to be of relevance should the patients be selected for aggressive postoperative adjuvant treatments which require good general status and nutritional integrity. The main disadvantage of subtotal gastrectomy is that the patients are exposed to the risk of a gastric stump cancer. However, this risk, owing to the advanced median age of the resected patients and the actual reconstructive procedures which minimize the biliary reflux, cannot be quantified. We think that when two surgical procedures are compared, if the oncological results are the same, the operation which is associated with least discomfort and impairment of the quality of life, should be chosen.
Two hundred and twenty-nine resections of hepatic tumors were performed over the past 10 years. The intraoperative death rate, 30-day operative mortality and major complication rate were 1.3%, 8.3% and 20%, respectively. Both morbidity and mortality were significantly related to the type of surgery and to the extent of the resection to contiguous organs and/or structures. Cirrhotic patients (40% in hepatocellular carcinoma) had a higher mortality rate (19%). Intraoperative blood loss was related to the extent of the resection and was significantly higher in patients with major complications and/or death. The main problem was postoperative liver failure in cirrhotic patients, which is difficult to predict and to treat.
One hundred patients with hepatic metastases from colorectal cancer underwent 'radical' liver resection from 1980 to 1989. At least 1 cm of normal parenchyma surrounded the tumour and no microscopic invasion of resection margins was evident. The disease was staged according to our own staging system. Lobectomy was performed in 50 patients and non-anatomical resection in the remainder. The postoperative mortality rate was 5 per cent and the major morbidity rate was 11 per cent. The actuarial 5-year survival rate for patients in stages I, II and III was 42 per cent, 34 per cent and 15 per cent respectively (P less than 0.001). The overall actuarial 5-year survival rate was 30 per cent. The prognostic importance of various patient and tumour variables was evaluated by univariate analysis and then by multivariate analysis. Age of patient, site of primary, disease-free interval between treatment of primary and of hepatic metastases, preoperative carcinoembryonic antigen levels, and number of metastases, did not relate to prognosis, while sex (P = 0.024), stage of primary (P = 0.026), extent of liver involvement (P less than 0.001), distribution of metastases (P = 0.01) and type of surgery (P = 0.028) significantly affected prognosis as single factors. Multivariate analysis revealed that only the extent of liver involvement and stage of the primary tumour were independent predictors of survival. We conclude that liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not yet possible to formulate a clear prognosis based on clinical factors. The extent of liver involvement and the staging system used may be significant, although not absolute, indicators of outcome.
Natural killer (NK) cell activity was measured in the peripheral blood mononuclear cells (PBMC) from malnourished (MN) and well-nourished (WN) cancer patients and in healthy controls. A marked depression of NK activity was observed in MN cancer patients with moderate protein-calorie malnutrition (PCM), but not in WN cancer patients nor in the healthy controls. The depression of NK activity did not correlate with the localisation of the tumour, patient's age or body weight reduction. The defective NK activity of PBMC from MN cancer patients was restored to normal by rIL-2, but not by alfa-rIFN. Parenteral nutrition of MN patients with the proper amount of proteins and calories quickly corrected the depressed NK activity, indicating a central role of malnutrition in the genesis of their immune disfunction. PBMC from MN cancer patients produced lower amounts of IL-2, as compared with healthy controls, when stimulated in vitro; the most frequently affected were the responses to recall antigens such as influenza virus vaccine (FLU), while those to allogeneic PBMC (ALLO) and phytohaemagglutinin (PHA) were less affected. However, for each patient the ability to produce IL-2 in vitro did not correlate with NK activity, thus showing how the impairment of NK activity is not subsequent to a decreased production of endogenous IL-2. In summary, it can be concluded that malnutrition, rather than malignancy, plays a major role in the immune dysfunction of cancer patients.
The experience of the Istituto Nazionale Tumori of Milan of 143 patients who underwent extended surgery for cancer of the stomach from 1965 to 1980 is reviewed. They represent 16.3 per cent of the patients who underwent curative surgery. The operative mortality rate was 15.4 per cent but this significantly decreased in recent years to 8 per cent and the morbidity rate to 17.5 per cent. The overall 5-year survival rate was 19 per cent. Survival was analysed according to tumour penetration (pT) and nodal status (N). It was found that patients without tumour penetration of adjacent structures and nodal involvement (pT3N-) had a better 5-year survival rate (21 per cent) than patients with nodal involvement (pT3N+) (2 per cent). Patients with tumour penetration of adjacent structures and without nodal involvement (pT4N-) had a better 5-year survival rate (29 per cent) than patients with nodal involvement (pT4N+) (5 per cent). These differences were significant on log rank test (P less than 0.000001 and P less than 0.001 respectively) and suggest that nodal status is a stronger prognostic variable than pT level. The role of extended surgery is discussed from the viewpoint of the oncological surgeon who has to weigh up the difficulty of a preoperative diagnosis of tumour infiltration of adjacent structures (predictive positive value 0.39), with the operative mortality rate of at least 8 per cent and long-term results which are strongly affected by the nodal status.
The purpose of this investigation was to evaluate in a randomised crossover study the effects on nutritional status of two isonitrogenous-isocaloric regimens of total parenteral nutrition (TPN) in 12 severely cachectic cancer patients. The regimens consisted of (1) G: 50 kcal of glucose.kg(-1).day(-1) + 2g amino-acids.kg(-1).day(-1) (2) GL: 30 kcal glucose and 20 kcal lipids.kg(-1) + 2g amino-acids.kg(-1).day(-1). Regimens G and GL were delivered sequentially for a period of 10 days each. Six patients (Group A) were randomised to receive regimen G first and regimen GL subsequently. In Group B patients the regimens alternated in the opposite way. The following nutritional variables were measured before TPN, after regimen G and after regimen GL: weight, arm circumference, arm muscle circumference, triceps skin fold, serum proteins, serum albumin, cholinesterase, transferrin, pre-albumin, retinol-binding protein, peripheral lymphocytes, cumulative nitrogen balance and mean urinary excretion of creatinine and 3-methylhistidine. The data showed that body weight and retinol-binding protein significantly increased with both G and GL regimens. No difference was found in the remaining variables, not even when comparing regimen G to GL. Increase in retinol-binding protein and in nitrogen balance were significantly better in the first period of treatment than in the second. These results show that the two regimens had a similar impact on the nutritional status of the cachectic cancer patients and choice between a glucose or a glucose-fat TPN should depend mainly on tolerance of the patients, duration and cost of therapy.
The effect of infusion of branched chain amino-acids (BCAA) on post-operative protein metabolism was analysed in 19 elective surgical patients treated for the first 5 post-operative days with a nutritional regimen of 30 kcal kg(-1) day(-1) and 2 g of amino-acids kg(-1) day(-1). The patients were divided into three groups whose only difference was the amount of BCAA delivered. Our results showed that an increased BCAA input improved nitrogen balance and reduced protein catabolism as estimated by the excretion of 3-methyl-histidine. Since nitrogen retention was maximal during the first 3 post-operative days and the reduction in 3-methylhistidine excretion was observed only on post-operative days 4 and 5, a dual action of BCAA on improving protein synthesis and reducing catabolism is postulated, even though the reduction in catabolism seems to be the main action. This dual action may reflect the unique role of BCAA, which is both 'nutritional' (as they constitute 40% of total amino-acid daily requirements of the healthy subject) and 'pharmacological (as they reduce protein catabolism and improve synthesis in muscle and liver with a dose-dependent effect). Of the three BCAA, isoleucine and leucine seemed to have an 'anticatabolic' effect, whereas an analysis of literature data showed that valine probably has none.
Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyltranspeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallible imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases.
Ten patients harboring an indwelling CVC with contamination of the infusate are described. Six patients developed sepsis, which was resolved in all patients except one who died from misdiagnosed septic shock. The majority of microorganisms responsible for the infusate contamination were opportunistic pathogens and in five cases were S. epidermidis. There was no apparent correlation between contamination rate of the infusate and subsequent sepsis of the patients. Reasons for the high prevalence of Staphylococcus epidermidis include ubiquitous diffusion of this microorganism, marked affinity for prosthetic devices, especially by the slime-producing strains, and increased susceptibility of debilitated cancer patients to infection. Recognition that the possibility exists for infusate contamination during compounding should alert all members of the Nutritional Support Team to use aseptic technique when preparing and handling the intravenous solutions. Infusate-related sepsis is a potentially lethal but preventable event.
In this work we investigated the effects of malnutrition on the immune response in neoplastic patients. We studied the basal NK activity of 34 neoplastic malnourished patients and 10 neoplastic not malnourished patients and a control group of blood donors, by a standard 51 Cr release assay against K562 cells. We observed that the neoplastic malnourished patients have a defective NK activity in spite of a normal number of NK cells, as ascertained by HNK-1 monoclonal antibodies. The reduced NK activity of the neoplastic malnourished patients is only partially restored by rIFN alpha 2a but is normalized by rIL-2 stimulation. We also found that the endogenous IL-2 production from some of these patients is slightly reduced as compared to controls. On the contrary, there are no significative differences between the neoplastic not malnourished patients and blood donors, as concerns the NK activity. These results suggest that nutritional status plays a very important role in the maintenance of an efficient immune response in neoplastic patients.