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Biomedical subjects

F Bozzetti

Publications and source records attributed to F Bozzetti.

At least 55 records · Page 3Linked to original sources

Regulation of glucose homeostasis in humans with denervated livers.

The liver plays a major role in regulating glucose metabolism, and since its function is influenced by sympathetic/ parasympathetic innervation, we used liver graft as a model of denervation to study the role of CNS in modulating hepatic glucose metabolism in humans. 22 liver transplant subjects were randomly studied by means of the hyperglycemic/ hyperinsulinemic (study 1), hyperglycemic/isoinsulinemic (study 2), euglycemic/hyperinsulinemic (study 3) as well as insulin-induced hypoglycemic (study 4) clamp, combined with bolus-continuous infusion of [3-3H]glucose and indirect calorimetry to determine the effect of different glycemic/insulinemic levels on endogenous glucose production and on peripheral glucose uptake. In addition, postabsorptive glucose homeostasis was cross-sectionally related to the transplant age (range = 40 d-35 mo) in 4 subgroups of patients 2, 6, 15, and 28 mo after transplantation. 22 subjects with chronic uveitis (CU) undergoing a similar immunosuppressive therapy and 35 normal healthy subjects served as controls. The results showed that successful transplantation was associated with fasting glucose concentration and endogenous glucose production in the lower physiological range within a few weeks after transplantation, and this pattern was maintained throughout the 28-mo follow-up period. Fasting glucose (4. 55+/-0.06 vs. 4.75+/-0.06 mM; P = 0.038) and endogenous glucose production (11.3+/-0.4 vs. 12.9+/-0.5 micromol/[kg.min]; P = 0.029) were lower when compared to CU and normal patients. At different combinations of glycemic/insulinemic levels, liver transplant (LTx) patients showed a comparable inhibition of endogenous glucose production. In contrast, in hypoglycemia, after a temporary fall endogenous glucose production rose to values comparable to those of the basal condition in CU and normal subjects (83+/-5 and 92+/-5% of basal), but it did not in LTx subjects (66+/-7%; P < 0.05 vs. CU and normal subjects). Fasting insulin and C-peptide levels were increased up to 6 mo after transplantation, indicating insulin resistance partially induced by prednisone. In addition, greater C-peptide but similar insulin levels during the hyperglycemic clamp (study 1) suggested an increased hepatic insulin clearance in LTx as compared to normal subjects. Fasting glucagon concentration was higher 6 mo after transplantation and thereafter. During euglycemia/hyperinsulinemia (study 3), the insulin-induced glucagon suppression detectable in CU and normal subjects was lacking in LTx subjects; furthermore, the counterregulatory response during hypoglycemia was blunted. In summary, liver transplant subjects have normal postabsorptive glucose metabolism, and glucose and insulin challenge elicit normal response at both hepatic and peripheral sites. Nevertheless, (a) minimal alteration of endogenous glucose production, (b) increased concentration of insulin and glucagon, and (c) defective counterregulation during hypoglycemia may reflect an alteration of the liver-CNS-islet circuit which is due to denervation of the transplanted graft.

Adult↗

Surgical treatment of locally recurrent rectal carcinoma.

PURPOSE: This study was performed to analyze the outcomes of patients with local (pelvic) recurrence (following radical surgery for rectal cancer) who subsequently underwent a new operation. METHODS: Forty-five patients (19 percent of 213 local recurrences) were explored surgically because the disease was deemed to be confined to the pelvis with a limited extension and, therefore, amenable to surgical cure. RESULTS: Only 21 of the 45 patients who underwent surgical exploration had an oncologically radical operation (R0). In the remaining 24 patients, either a simple exploration or palliation or a nonradical procedure (R1-R2) was performed. In the R0 group, there was a 19 percent five-year survival rate vs. a 0 percent rate in the R1-R2 group (median survival, 4 months). Site of recurrence (anastomosis vs. other sites) was statistically associated with a higher chance of long-term survival for those who underwent an R0 operation. CONCLUSIONS: The prognosis of locally recurrent rectal cancer is dismal; less than 10 percent of all patients who underwent surgical treatment benefit from reoperation with an overall survival for five years. On the basis of these results, we no longer consider the surgical approach as the primary option for treating locally recurrent rectal cancer.

Adenocarcinoma↗

Renal-splenic shunt for infrahepatic caval occlusion after piggy-back liver transplantation.

Inferior vena cava thrombosis after liver transplantation is uncommon. We describe a case of this unusual complication occurring after piggy-back (end-to-side) graft implantation. Renal failure, lower limb edema, and hemodynamic instability were the presenting symptoms requiring immediate surgical correction with a left renal-to-splenic vein shunt over a ringed 2.5-cm prosthesis. The decision to go ahead with the shunt was preceded by an intraoperative confirmation of a 10-cm H2O pressure gradient between the caval and portal circulations. This gradient, unlike that observed in liver cirrhosis, ultimately turned a splenorenal shunt into a renal-splenic one. Six months after the procedure, the patient is alive and well with normal liver and renal function. The technique described may be useful in the management of other clinical conditions of acute infrahepatic caval hypertension.

Graft Occlusion, Vascular↗

Initial chemotherapy for primary resectable large-cell lymphoma of the stomach.

BACKGROUND: We aimed to evaluate the safety and effectiveness of a conservative approach with short-term chemotherapy with or without consolidation radiotherapy in primary resectable large-cell gastric lymphoma in patients not requiring emergency surgery at presentation. PATIENTS AND METHODS: Seventeen consecutive patients presenting with resectable primary large-cell lymphoma of the stomach not requiring immediate surgery were initially treated with chemotherapy with or without consolidation radiotherapy. Subtotal or total resection of the stomach was planned only as salvage treatment for those patients who failed locally, or as emergency surgery in instances of acute iatrogenic complications of treatment. Chemotherapy included four to six cycles of an anthracycline-containing regimen, and consolidation radiotherapy was planned on the entire stomach and surrounding lymph node areas for complete responders readily capable of compliance with a daily treatment schedule at our Institution. RESULTS: None of the patients in the present series experienced acute iatrogenic morbidity or mortality from local complications. After a median follow-up of almost six years, two patients failing first-line chemotherapy have died of progressive lymphoma, while 15 patients are well and currently disease-free. CONCLUSIONS: Up-front chemotherapy as initial treatment for primary gastric large-cell lymphoma appears to be a safe and effective treatment by which most patients can probably be spared surgical gastrectomy. Consolidation radiation therapy on the stomach can probably improve on the effectiveness of chemotherapy alone. More experience is needed to elucidate the prognostic factors, treatment-related long-term toxic effects and the feasibility of such a treatment administered outside of highly specialized institutions.

Adult↗

Total versus subtotal gastrectomy: surgical morbidity and mortality rates in a multicenter Italian randomized trial. The Italian Gastrointestinal Tumor Study Group.

OBJECTIVE: The purpose of this study was to analyze postoperative morbidity and mortality of patients included in a randomized trial comparing total versus subtotal gastrectomy for gastric cancer. SUMMARY BACKGROUND DATA: There is controversy as to whether the optimal surgery for gastric cancer in the distal half of the stomach is subtotal or total gastrectomy. Although only a randomized trial can resolve this oncologic dilemma, the first step is to demonstrate whether the two procedures are penalized by different postoperative morbidity and mortality rates. METHODS: A total of 624 patients with cancer in the distal half of the stomach were randomized to subtotal gastrectomy (320) or total gastrectomy (304), both associated with a second-level lymphadenectomy, in a multicenter trial aimed at assessing the oncologic outcome after the two procedures. The end points considered were the occurrence of a postoperative event, complication, or death and length of postoperative stay. RESULTS: Nonfatal complications and death occurred in 9% and 1% of subtotal gastrectomy patients and in 13% and 2% of total gastrectomy patients, respectively. Multivariate analysis of postoperative events showed that splenectomy or resection of adjacent organs was associated with a twofold risk of postoperative complications. Random surgery and extension of surgery influenced the length of stay. The mean length of stay, adjusted for extension of surgery, was 13.8 days for subtotal gastrectomy and 15.4 days for total gastrectomy. CONCLUSIONS: Our data show that subtotal and total gastrectomies, with second-level lymphadenectomy, performed as an elective procedure have a similar postoperative complication rate and surgical outcome. A conclusive long-term evaluation of the two operations and an accurate estimate of the oncologic impact of surgery on long-term survival, not penalized by excess surgical risk of one of the two operations, are consequently feasible.

Aged↗

Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.

BACKGROUND: The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. METHODS: We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation. RESULTS: The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival. CONCLUSIONS: Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

Adult↗

Cancer of the low and middle rectum: local and distant recurrences, and survival in 350 radically resected patients.

The purpose of this study was to compare local recurrence, distant metastases, and survival rate in 350 patients with cancer of the middle and low rectum who underwent a radical abdominoperineal resection (APER) or a sphincter-saving resection (SSR) in our Institute. There were 257 APER patients and 93 SSR patients, with a median follow-up of 77 months. At 5 years, the estimates in APER and SSR patients were respectively 11% and 30% for the incidence of pelvic recurrence, 18% and 8% for the incidence of distant metastases, and 64% and 73% for overall survival. In the multivariate analysis it was found that Dukes' stage significantly affected pelvic recurrences, distant metastases rate and overall survival; histologic type affected only the pelvic recurrence rate. However, the final outcome of patients following APER or SSR was similar, suggesting that local failure per se does not affect long-term survival.

Adult↗

Preoperative radiotherapy for resectable cancer of the middle-distal rectum: its effect on the primary lesion as determined by endorectal ultrasound using flexible echo colonoscope.

20 patients with rectal cancer within 8 cm of the anal verge were studied. Endoscopic endosonography was carried out before and after pre-operative radiotherapy (45 Gy over three weeks). The local extent (tumour stage and diameter) was compared with the results of histopathological examination of the resected specimen after anterior resection or total rectal excision. The Tumour Regression Grade (TRG) and lymph node status were also estimated. Two patients were not evaluated endosonographically. Two (11%) of the remaining 18 patients showed ultrasound evidence of down staging (14/18 uT3/4 pre-radiotherapy: 12/18 uT3/4 after) and tumour diameter was significantly reduced. Tumour Regression Grade estimation showed evidence of response to treatment, showing regression of more than 50% in 13 (65%) of cases. Involved nodes were less than 5 mm in diameter in 45% of cases. Histopathological evidence of nodal metastatic regression was seen in 13 (28%) of all involved nodes found. The ultrasonically determined response to radiotherapy may offer useful information in predicting outcome and possibly in selecting surgery.

Adenocarcinoma↗

Total nutritional manipulation in humans: report of a cancer patient.

We report here on a patient requiring home total parenteral nutrition (TPN) for a huge intra-abdominal desmoid associated with chronic small bowel pseudo-obstruction who was kept on a special lipid-based calorie regimen for 5 months. The rationale was to attempt to feed the host with a minimal stimulation of tumour growth by using lipid as caloric substrate instead of glucose which is utilized by the tumour. Gluconeogenesis was tentatively inhibited at the level of phosphoenolpyruvate-carboxy-kinase through the oral intake of hydrazine sulphate. The regimen consisted of 28 non-protein lipid Kcal/kg/day plus 1.5 g amino acid per kg/day. Only a small amount of glucose (approx. 40 g/day) was allowed. Tolerance to the regimen was good and body weight maintained. Liver enzymes remained within the normal range and liver sonography was normal throughout the 5 months' therapy and there were no episodes of symptomatic hypoglycaemia. The tumour volume did not substantially change.

Journal Article↗

Guidelines on artificial nutrition versus hydration in terminal cancer patients. European Association for Palliative Care.

Whether a terminally ill cancer patient should be actively fed or simply hydrated through subcutaneous or intravenous infusion of isotonic fluids is a matter of ongoing controversy among clinicians involved in the care of these patients. Under the auspices of the European Association for Palliative Care, a committee of experts developed guidelines to help clinicians make a reasonable decision on what type of nutritional support should be provided on a case-by-case basis. It was acknowledged that part of the controversy related to the definition of the terminal cancer patient, since this is a heterogeneous group of patients with different needs, expectations, and potential for a medical intervention. A major difficulty is the prediction of life expectancy and the patient's likely response to vigorous nutritional support. In an attempt to reach a decision on the type of treatment support (artificial nutrition vs. hydration) which would best meet the needs and expectations of the patient, we propose a three-step process: Step 1: define the eight key elements necessary to reach a decision; Step II: make the decision; and Step III: reevaluate the patient and the proposed treatment at specified intervals. Step I involves assessing the patient concerning the following: 1) oncological/clinical condition; 2) symptoms; 3) expected length of survival; 4) hydration and nutritional status; 5) spontaneous or voluntary nutrient intake; 6) psychological profile; 7) gut function and potential route of administration; and 8) need for special services based on type of nutritional support prescribed. Step II involves the overall assessment of pros and cons, based on information determined in Step I, in order to reach an appropriate decision based on a well-defined end point (i.e., improvement of quality of life; maintaining patient survival; attaining rehydration). Step III involves the periodic reevaluation of the decision made in Step II based on the proposed goal and the attained result.

Fluid Therapy↗

Comparing reconstruction with Roux-en-Y to a pouch following total gastrectomy.

BACKGROUND: Although more than 50 methods of gastric replacement after total gastrectomy have been used, none of them has demonstrated a substantial nutritional advantage. The Roux-en-Y esophagojejunostomy is still the preferred type of reconstruction, more because of its simplicity than the lack of postprandial disturbances. STUDY DESIGN: A randomized controlled trial was conducted to compare two reconstructive procedures, Roux-en-Y esophagojejunostomy (n = 24) and Hunt-Rodino-Lawrence pouch (HRL, n = 24), by evaluating nutritional status (body weight, arm circumference, and serum nutritional parameters), nutritional habits (number of meals, energy intake, and postprandial disturbances), and emptying time of the jejunal loop. RESULTS: Twenty-seven patients were studied two years after operation (12 had undergone Roux-en-Y and 15 had undergone HRL). No difference was found in either postoperative morbidity or mortality, emptying time, frequency of meals, or variation of body weight. Postprandial disturbances were more frequent in patients having Roux-en-Y. In a subset of patients, there was a correlation between nutrient intake and change of body weight, but not between nutrient intake and type of reconstruction. CONCLUSIONS: The simple use of a reservoir such as the HRL pouch after total gastrectomy is of no benefit to the patient as compared with the Roux-en-Y reconstruction.

Anastomosis, Roux-en-Y↗

Morbidity and mortality after hepatic resection of metastases from colorectal cancer.

A review was carried out of morbidity and mortality after hepatic resection for metastatic colorectal cancer in 208 consecutive patients who underwent this procedure between 1980 and 1992. Overall postoperative morbidity and mortality rates were 35 and 2.4 per cent respectively. The major morbidity rate was 18 per cent, the main complications being intra-abdominal sepsis, biliary fistula and haemorrhage. Of the different factors examined, morbidity was significantly related to the extent of liver resection (53 versus 21 per cent after major and minor resections respectively), amount of blood transfused (18 versus 52 per cent for no transfusion and more than 300 ml transfused respectively) and the date of the operation (53 versus 24 per cent before and after 1986 respectively). Multivariate analysis showed that only the extent of hepatic resection and the period at which surgery was performed retained their statistical significance. These data support the opinion that surgical treatment of hepatic metastases from colorectal cancer is an effective procedure with acceptable mortality and morbidity rates. An extensive experience of hepatic surgery is, however, necessary to optimize results.

Adenocarcinoma↗

Restorative effect of total parenteral nutrition on natural killer cell activity in malnourished cancer patients.

Decreased natural killer cell activity (NKCA) is associated with malnutrition in both cancer and non-cancer patients. We have studied the effect of total parenteral nutrition (TPN) on NKCA in 9 malnourished cancer patients, candidates for surgery. TPN was administered for a median of 10 days (range 7-11), providing 1.5-fold the estimated resting energy expenditure, with 30% as fat. Calorie:nitrogen ratio was 150:1. Basal human recombinant interferon-alpha 2a (rIFN-alpha 2a) and human recombinant IL-2 rIL-2) activated NKCA were measured, as were the main nutritional parameters, prior to and after TPN. NKCA increased in all patients and reached the normal range in 5, 3 and 4 subjects, respectively, for basal, rIFN-alpha 2a and rIL-2 activated NKCA. As regards nutritional assessment, body weight and IgM levels significantly increased from 47.7 to 50.1 kg and from 174 to 237 mg/dl, respectively. This study demonstrates that a 10-day TPN course increases and sometimes restores normal NKCA. Such effect was constant and preceded nutritional changes.

Aged↗