Valerio Di Carlo

Hepatocellular carcinoma in Italian patients with cirrhosis.

BACKGROUND AND METHODS Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months. RESULTS Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery. CONCLUSIONS In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors.

Vitamin D3 Affects Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

We studied the effects of 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) on differentiation, maturation, and functions of dendritic cells (DC) differentiated from human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days. Recovery and morphology were not affected by 1α,25-(OH)2D3 up to 100 nM. DC differentiated in the presence of 10 nM 1α,25-(OH)2D3 (D3-DC) showed a marked decrease in the expression of CD1a, while CD14 remained elevated. Mannose receptor and CD32 were significantly increased, and this correlated with an enhancement of endocytic activity. Costimulatory molecules such as CD40 and CD86 were slightly decreased or nonsignificantly affected (CD80 and MHC II). However, after induction of DC maturation with LPS or incubation with CD40 ligand-transfected cells, D3-DC showed marginal increases in MHC I, MHC II, CD80, CD86, CD40, and CD83. The accessory cell function of D3-DC in classical MLR was also inhibited. Moreover, allogeneic T cells stimulated with D3-DC were poor responders in a second MLR to untreated DC from the same or an unrelated donor, thus indicating the onset of a nonspecific hyporesponsivity. In conclusion, our data suggest that 1α,25-(OH)2D3 may modulate the immune system, acting at the very first step of the immune response through the inhibition of DC differentiation and maturation into potent APC.

Islet isolation assessment in man and large animals

SummaryRecent progress in islet isolation from the pancreas of large mammals including man, accentuated the need for the development of precise and reproducible techniques to assess islet yield. In this report both quantitative and qualitative criteria for islet isolation assessment were discussed, the main topics being the determination of number, volume, purity, morphologic integrity andin vitro andin vivo function tests of the final islet preparations. It has been recommended that dithizone should be used as a specific stain for immediate detection of islet tissue making it possible to estimate both the total number of islets (dividing them into classes of 50 µ diameter range increments) and the purity of the final preparation. Appropriate morphological assessment should include confirmation of islet identification, assessment of the morphological integrity and of the purity of the islet preparation. The use of fluorometric inclusion and exclusion dyes together have been suggested as a viability assay to simultaneously quantitate the proportion of cells that are intact or damaged. Perifusion of islets with glucose provides a dynamic profile of glucose-mediated insulin release and of the ability of the cells to down regulate insulin secretion after the glycemic challenge is interrupted. Although perifusion data provides a useful guide to islet viability the quantity and kinetics of insulin release do not necessarily predict islet performance after implantation. Therefore, the ultimate test of islet viability is their function after transplantation into a diabetic recipient. For this reason,in vivo models of transplantation of an aliquot of the final islet preparation into diabetic nude (athymic) rodents have been suggested. We hope that these general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers.

Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer

Expression of TSLP in pancreatic cancer correlates with Th2 deviation of antitumor immunity that is associated with decrease of patient survival.

Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition

ObjectiveTo evaluate the potential clinical, metabolic, and economic advantages of enteral nutrition over total parenteral nutrition. DesignProspective, randomized clinical trial. SettingDepartment of surgery in a university hospital. PatientsTwo hundred and fifty-seven patients with cancer of the stomach (n = 121), pancreas (n = 110), or esophagus (n = 26) were randomized to receive postoperative total parenteral nutrition (TPN group, n = 131) or early enteral nutrition (EEN group, n = 126). The nutritional goal was 25 kcal/kg/day. The two nutritional formulas were isocaloric and isonitrogenous, and they were continued until oral intake was at least 800 kcal/day. MeasurementsMorbidity, mortality, length of hospital stay, and treatment costs were evaluated in all patients. In 40 consecutive patients, selected nutritional, immunologic and inflammatory variables were studied. Moreover, intestinal oxygen tension was evaluated by micropolarographic implantable probes. Main Results The nutritional goal was reached in 100/126 (79.3%) patients in the EEN group and in 128/131 (97.7%) patients in the TPN group (p < .001). In the EEN group, hyperglycemia (serum glucose, >200 mg/dL) was observed in 4.7% of the patients vs. 9.1% in the TPN group (p = NS). Alteration of serum electrolyte levels was 3.9% in the EEN group vs. 13.7% in the TPN group (p < .01). No significant difference was found in nutritional, immunologic, and inflammatory variables between the two groups. The overall complication rate was similar (40.4% for TPN vs. 35.7%, for EEN;p = .52). No difference was detected for either infectious or noninfectious complications, length of hospital stay, and mortality. From postoperative day 5, intestinal oxygen tension recovered faster in the EEN group than in the TPN group (43 ± 5 mm Hg vs. 31 ± 4 mm Hg at day 7;p < .001). EEN was four-fold less expensive than TPN (

Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial

25 vs.

Altered microperfusion at the rectal stump is predictive for rectal anastomotic leak

90.60/day, respectively). ConclusionEEN represents a rational alternative to TPN in patients who undergo upper gastrointestinal tract surgery for cancer and who clinically require postoperative artificial nutrition.

Laparoscopic vs. Open Colectomy in Cancer Patients: Long-Term Complications, Quality of Life, and Survival

BACKGROUND Patients with advanced pancreatic adenocarcinoma have a poor response, progression-free survival, and overall survival with standard treatment. We aimed to assess whether a four-drug regimen could improve 4 month progression-free survival compared with gemcitabine alone. METHODS In a randomised multicentre phase III trial, 52 patients were randomly assigned to 40 mg/m2 cisplatin and 40 mg/m2 epirubicin both given on day 1, 600 mg/m2 gemcitabine given intravenously over 1 h on days 1 and 8, and 200 mg/m2 fluorouracil a day given by continuous infusion on days 1-28 of a 4-week cycle (PEFG regimen), and 47 were assigned to 1000 mg/m2 gemcitabine given intravenously over 30 min once a week for 7 of 8 consecutive weeks in cycle 1 and for 3 of 4 weeks thereafter. The primary endpoint was 4-month progression-free survival. Secondary endpoints were overall survival, objective response, safety, and quality of life. Analyses were by intention to treat. FINDINGS 51 patients assigned PEFG and 46 assigned gemcitabine alone had disease progression. 49 patients in the PEFG group and 46 in the gemcitabine group died from progressive disease. More patients allocated PEFG than gemcitabine alone were alive without progressive disease at 4 months (60% [95% CI 46-72] vs 28% [17-42]; hazard ratio [HR] 0.46 [0.26-0.79]). 1-year overall survival in the PEFG group was 38.5% (25.3-51.7) and in the gemcitabine group was 21.3% (9.6-33.0; HR 0.68 [0.42-1.09]). More patients assigned PEFG showed disease response than did those assigned gemcitabine (38.5% [25.3-51.7] vs 8.5% [0.5-16.5]; odds ratio 6.60 [2.11-20.60], p=0.0008). More patients in the PEFG group had grade 3-4 neutropenia and thrombocytopenia than in the gemcitabine group (p<0.0001). INTERPRETATION The PEFG regimen could be considered for treatment of advanced pancreatic adenocarcinoma.

A Prospective, Randomized Clinical Trial on Perioperative Feeding With an Arginine-, Omega-3 Fatty Acid-, and RNA-Enriched Enteral Diet: Effect on Host Response and Nutritional Status

PURPOSE: The aim of this study was to evaluate the reliability of intraoperative laser-Doppler measurements in predicting the occurrence of anastomotic leak in patients with colorectal cancer undergoing stapled straight anastomosis to the rectum. METHODS: A prospective study was undertaken on 55 patients with rectal cancer or distal sigmoid cancer programmed for elective curative surgery. In all patients transmural colonic blood flow was measured by laser-Doppler flowmetry technique before bowel manipulation (baseline measurement) and after vascular ligation and division. Comorbidities at admission, intraoperative events, associated surgical procedures, and clinical outcome were tested for any association with anastomotic leak. RESULTS: Postoperative mortality was 1.8 percent (1/55 patients), and the overall morbidity was 21.3 percent. Anastomotic leak occurred in eight patients (14.5 percent). After colonic division a blood flow reduction at the rectal stump was observed in 42 patients (76.3 percent) as compared with baseline measurement. The mean rectal stump flow reduction was 6.2 percent in patients without anastomotic leak, whereas in patients who developed anastomosis breakdown it was 16 percent (P<0.001). Mean proximal stump flow reduction was 5.1 percent in the uncomplicated patients, whereas in patients who had an anastomosis breakdown it was 12.9 percent (P<0.01). A positive linear correlation was found between decrease in blood flow and rate of anastomotic leak. CONCLUSION: Blood flow reduction at the rectal stump is associated with an increased risk of anastomotic leak.

Laparoscopic versus open colorectal surgery: cost-benefit analysis in a single-center randomized trial.

PURPOSEThis study was designed to evaluate long-term complications, quality of life, and survival rate in a series of colorectal cancer patients randomized to laparoscopic or open surgery.METHODSA total of 391 patients with colorectal cancer were randomly assigned to laparoscopic (n = 190) or open (n = 201) resection. Long-term follow-up was performed every six months by office visits. Quality of life was assessed at 12, 24, and 48 months after surgery by a modified version of Short Form 36 Health Survey questionnaire. All patients were analyzed on an intention-to-treat basis.RESULTSEight (4.2 percent) laparoscopic group patients needed conversion to open surgery. Overall long-term morbidity rate was 6.8 percent (13/190) in the laparoscopic vs. 14.9 percent (30/201) in the open group (P = 0.018). Overall quality of life was significantly better in the laparoscopic group in the first 12 months after surgery, whereas at 24 months, patients of the laparoscopic group reported a significant advantage only in social functioning. No difference was found in both overall and disease-free survival rates by comparing laparoscopic vs. open group.CONCLUSIONSLaparoscopic colorectal resection was associated with a lower incidence of long-term complications and a better quality of life in the first 12 months after surgery compared with open surgery. No difference between groups was found in overall and disease-free survival rates.