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Gold particles labelling on ultrathin sections is extensively used for antigen localization in transmission electron microscopy. In establishing absolute or relative counts in tissue sections, it would be expedient to use stereologically based unbiased estimates for quantitative results. Nowadays, quantitative immunoelectron microscopy has achieved good and satisfactory results to test whether the gold labelling follows a non-random or a random pattern and then to draw statistical comparisons between cell subcompartments within a sample of cells or between experimental groups of cells. This brief informal review of literature focuses on the relative quantitative determinations of gold labelling of antigens as well as on the statistical distribution comparisons in transmission electron microscopy.

Liver is deeply involved in the metabolism of proteins, hormones, enzymes, cytokines, as well as in sex hormones catabolism. Gonadal function requires a normal liver function, and it is well known that clinical signs of hypogonadism are common in patients with liver cirrhosis. Few studies have focused on hypothalamic- pituitary-gonadal alterations in male cirrhotic patients or after orthotopic liver transplantation (OLT). The pathogenesis of hypogonadism in cirrhotic patients is complex and not well explained. It involves both a gonadal and a hypothalamic- pituitary dysfunction. After OLT the hypothalamic-pituitary-gonadal function partially improves, showing that the hepatic dysfunction before OLT is deeply involved in its pathogenesis. After OLT some alterations persist in some patients, both because of pre-existing gonadal alterations (toxic-metabolic damage) and immunosuppressive pharmacological side effects. Further studies will explain the relationship between hypogonadism and OLT outcome, and the role of androgen therapy in hypogonadism after OLT, in the early months and in the long term.

Background The distribution of lesions in the gastrointestinal tract in patients with sporadic telangiectasia is at present unknown. Patients and methods 75 patients with sporadic telangiectasia underwent esophagogastroduodenoscopy (EGD), capsule endoscopy, and colonoscopy. Endoscopic diagnosis of telangiectasia and gastrointestinal bleeding were required for enrollment in the study. Hemorrhagic diathesis, co-morbidity, number of blood transfusions, and subsequent management were also noted. Results 35 of the patients presented with gastroduodenal vascular lesions, 51 with small-bowel lesions, and 28 with colonic lesions. 67 % of patients in whom EGD found telangiectasia also presented small-bowel vascular lesions at capsule endoscopy and 43 % colonic lesions at colonoscopy. 54 % percent of patients with positive colonoscopy also presented gastroduodenal lesions and 48 % small-bowel lesions. Patients with known duodenal lesions were more likely to have small-bowel lesions at capsule endoscopy (odds ratio [OR] 10.19, 95 % CI 2.1 - 49.33, P = 0.003). Patients with associated diseases, such as liver cirrhosis, chronic renal failure, or heart valvulopathy, presented more severe disease requiring blood transfusions (OR 6.37, 95 % CI 1.39 - 29.2, P = 0.015). The number of blood transfusions correlated with the number of sites affected ( R = 0.35, P = 0.002). The detection of new lesions at capsule endoscopy allowed new treatment in 46 % of patients. Mean follow-up was 18 months. Conclusions Sporadic telangiectasia is a multifocal disease potentially involving the whole digestive tract. Patients with duodenal telangiectasia show a higher risk of jejunal or ileal lesions. Capsule endoscopy is a useful diagnostic tool for the detection of such small-bowel vascular lesions, indicating a more specific prognosis and treatment strategy.

The white-throated Dipper (Cinclus cinclus) is unique among passerine birds by its reliance on diving to achieve energy gain in fast-flowing waters. Consequently, it should have evolved behavioural adaptations allowing responding directly to runoff patterns (one of the assumptions of the Natural Flow Regime Paradigm-NRFP). In this study (October 1998-August 2001), we investigated how behavioural and energy use strategies in Dippers might vary under the natural flow regime of snowmelt-dominated streams in The Pyrénées (France) where natural flow regime is highly seasonal and predictable. We recorded time spent in each of 5 behavioural activities of ringed birds to estimate time-activity budgets and derive time-energy budgets enabling the modelling of daily energy expenditure (DEE). Annual pattern in 'foraging' and 'resting' matched perfectly the annual pattern of the natural regime flow and there was a subtle relationship between water stage and time spent 'diving' the later increasing with rising discharge up to a point where it fell back. Thus, time-activity budgets meet the main prediction of the NRFP. For males and females Dippers, estimates of feeding rates (ratio E(obs)/E(req)=observed rate of energy gain/required foraging rate) and energy stress (M=DEE/Basal Metabolic Rate) also partly matched the NFRP. Maximum value for the ratio E(obs)/E(req) was registered in May whilst M peaked in spring. These ratios indicated that Pyrenean Dippers could face high energy stress during winter but paradoxically none during high snowmelt spates when food is expected to be difficult to obtain in the channel and when individual birds were observed spending ca 75% of the day 'resting'. Annual pattern in DEE did not match the NFRP; two phases were clearly identified, the first between January to June (with oscillating values 240-280 kJ d(-1) ind(-1)) and the second between July and December (200-220 kJ d(-1) ind(-1)). As total energy expenditure was higher during the most constraining season or life cycle, we suggest that energy management by Dippers in Pyrenean mountain streams may fit the 'peak total demand' hypothesis. At this step of the study, it is not possible to tell whether Dippers use an 'energy-minimisation' or an 'energy-maximisation' strategy.

The aims of this cross-sectional study were to assess the long-term quality of life, the body image, and the cosmetic and functional results in patients who had laparoscopic-assisted for colorectal cancer. Forty-two patients were enrolled in this study: 21 consecutive patients who had undergone laparoscopic-assisted colonic resection and 21 patients who had open colonic resection, selected according to stage, gender, age, cancer site, and type of resection. The patients answered four questionnaires about their quality of life, body image, functional, and cosmetic results. Nonparametric tests were used for statistical analysis. Postoperative hospital stay was shorter in patients who had laparoscopic-assisted resection. The cosmetic score was significantly better in the laparoscopic-assisted group than in the open group (p

The aim of this retrospective study is to analyze the prognostic impact of Model for End-Stage Liver Disease (MELD) score in patients undergoing liver transplantation (OLT) with suboptimal livers.Between January 2002 and January 2006, 160 adult patients with liver cirrhosis received a whole liver for primary OLT at our institution including 81 with a suboptimal liver (SOL group) versus 79 with an optimal liver (group OL). The definition of suboptimal liver was: one major criterion (age60 years, steatosis20%) or at least two minor criteria: sodium155 mEq/L, Intensive Care Unit stay7 days, dopamine10 microg/kg/min, abnormal liver tests, and relevant hemodynamic instability.Baseline recipients characteristics were comparable in the two study groups. The SOL group had a significantly greater number of early graft deaths (30 days) than the OL group, while the 3-year Kaplan-Meier patient survivals were similar. Using logistic regression, MELD score was significantly related to patient death only in the SOL group (P = .01), and the receiver operator characteristics curve method identified 17 as the best MELD cutoff with the 3-year survival of 93% versus 85% for MELDor =7 versus17, respectively (P05). In comparison, it was 94% and 72% in the SOL group (P.05). Similarly, MELD17 was significantly associated with early graft death rates only in the SOL group.This study advised surgeons to not use suboptimal livers for patients with advanced MELD scores, thus supporting a donor-recipient matching policy.

Objective The objective of this study was to analyze experience on pediatric liver transplantation (LT) between June 1993 and September 2006, including split liver transplantation (SLT), living donor liver transplantation (LDLT), and auxiliary partial orthotopic liver transplantation (APOLT). Furthermore, hepatocyte transplantation (HT) had a role in one patient with metabolic disease. Methods From November 1990 to September 2006, 657 LTs were performed including 63 pediatric LTs (9.6%) in 57 patients (32 boys and 25 girls). Six were retransplantations (9.5%). Thirty-two patients (57%) were younger than 5 years. The types of graft included the following: 26 whole organs (41%), 32 in situ split organs (51%), 4 reduced-size organs (6%), and 1 graft from a living donor (2%). Two patients received an APOLT, 4 patients received a combined kidney-liver transplantation (CKLT), and 1 patient received HT. Of the 63 pediatric LTs, 16 were behaved to be highly urgent (25%). Results Overall 1-, 3-, 5-, and 10-year patient survival rates were 82%, 82%, 78%, and 78%, respectively. Overall 1-, 3-, 5-, and 10-year graft survival rates were 76%, 76%, 72%, and 72%, respectively. In patients younger than 1 year, the 5-year survival rate was 100%. Perioperative mortality was 8.8%. Vascular complications occurred in 4 patients (6.3%). Six children required retransplantation due to primary nonfunction (PNF) in 4 cases (7%) and vascular thrombosis in 2 cases (3.5%). Conclusions Cholestatic liver disease and age younger than 1 year were the best prognostic factors for excellent survival.

Liver transplantation still represents the only effective treatment for patients with liver failure, but many patients die while awaiting transplantation, even though many attempts have been made to increase the organ procurement rates and to partially support hepatic function in recent years. Our aim was to design an "open" ex vivo perfused liver model to simplify liver support using an isolated porcine liver perfused with arterial and portal blood from the recipient pig, while monitoring the metabolic capacity of the supporting graft. It was possible to perfuse the isolated liver for 6 hours as a bridging procedure with satisfactory hemodynamic homeostasis controlled by software biofeedbacks.

To evaluate the usefulness of double contrast small-bowel radiography (SBR) in the preoperative assessment of patients with Crohn's disease (CD).Thirty-nine consecutive patients who underwent surgery for CD between 2000 and 2004, preceded by a preoperative small-bowel series evaluation, were enrolled in our study. The radiologic findings were compared with the intraoperative findings.Small-bowel radiography was associated with good specificity and sensitivity for the detection of stenosis. Although its main limitation was a remarkable overestimation of stenosis, the main indications for surgery were always confirmed. Sensitivity and specificity were lower for the detection of internal fistulas and the correlation was significant only for SBR performed within 3 months of the operation; however, the concordance between radiological and operative findings was greater. No correlation was observed for the detection of an abdominal mass.Small-bowel radiography is still reliable for evaluating stenoses and internal fistulas. However, magnetic resonance imaging or computed tomography is mandatory to evaluate an abdominal mass.

B1a lymphocytes (CD5+) are the major contributors of natural antibodies (Ab) implicated in the initial protection against several infections. The aim of this study was to assess the expression of these cells in the peripheral blood of ulcerative colitis (UC) patients who underwent restorative proctocolectomy (RPC) and others who were not operated on.The blood concentration of CD5+ B cells was analysed by three-colour flow cytometry. Blood was collected from 38 UC patients, 20 of whom had undergone RPC and compared with the results in 18 healthy controls and in 12 familial adenomatous polyposis (FAP) patients who had undergone RPC. We were interested in evaluating if there was any correlation between B1a blood cell concentration and ESR and CRP levels, clinical, endoscopic and histological activity, perinuclear anti-neutrophil cytoplasmic antibody (pANCA) and extra-intestinal symptoms.B1a cell blood concentration was reduced in non-operated UC patients (20.7 +/- 4.6/microl) with respect to that in healthy controls (71.1 +/- 18.0/microl, p0.05). It was also lower in UC patients with RPC (24.9 +/- 1.0/microl) compared to RPC for FAP (48.2 +/- 6.2, p0.05). B1a cell rate correlated inversely in UC patients with ESR (R = -0.41, p0.05) and CRP levels (R = -0.47, p = 0.01).B1a cell concentration was reduced in the blood of patients with UC even after the diseased organ was surgically removed by proctocolectomy. As these cells play an important role in natural immunity against luminal stimuli, consistently lower levels that are found in UC patients could be responsible for the impaired immunologic response to gut antigens in this disease.

Background According to some researchers, health-related quality-of-life scores for patients who undergo restorative proctocolectomy (RPC) for ulcerative colitis (UC) are comparable to those of healthy control subjects. Other studies show evidence that patients who undergo RPC experience a health-related quality of life similar to patients with mild UC or UC in remission. Hypothesis The discrepancy in health-related quality-of-life scores among studies may be due to different health-related quality-of-life analyses. Design Cross-sectional study. Setting Outpatient clinic of a tertiary care center. Patients In the first phase of the study, we consecutively enrolled 24 patients with UC, 24 patients with Crohn disease, and 24 healthy controls. In the second phase of the study, 40 patients who underwent RPC, 43 patients with UC, and 44 controls were consecutively enrolled. Interventions We administered an Italian version of the Cleveland Global Quality of Life (CGQL) instrument, the Padova Inflammatory Bowel Disease Quality of Life instrument, and the Italian 36-Item Short-Form Health Survey. Main Outcome Measures We evaluated the construct validity, internal consistency, test-retest reliability, sensitivity to change, and discriminant ability of the Italian CGQL instrument. We compared its discriminative ability with that of the Padova Inflammatory Bowel Disease Quality of Life instrument. Results The Italian CGQL instrument obtained good construct validity, internal consistency, test-retest reliability, and sensitivity to change. The Italian CGQL score did not distinguish patients who underwent RPC from healthy controls and those with mild UC or UC in remission, while the Padova Inflammatory Bowel Disease Quality of Life instrument reported similar scores for patients who underwent RPC and those with mild UC or UC in remission, and showed a difference vs healthy controls. Conclusions We validated an Italian version of the CGQL score. The different results obtained with the CGQL and the Padova Inflammatory Bowel Disease Quality of Life instruments can be attributed to the different discriminative ability of the 2 questionnaires.

Background Ulcerative colitis and Crohn's disease are characterized by a chronic intestinal inflammation. Since the precise etiology is still unknown, current therapies are aimed at reducing or eliminating inflammation. Methods Endoscopy and histology on biopsy specimens remain the gold standard methods for detecting and quantifying bowel inflammation. These technique are expensive, invasive and not well tolerated by patients since the need of repeated examinations affects their quality of life. Although disease activity scores and laboratory inflammatory markers are widely used they showed unreliable relations with endoscopy and histology. Fecal markers have been investigated in inflammatory bowel disease (IBD) by many authors for diagnostic purposes, to assess disease activity and of risk of complications, to predict relapse or recurrence, and to monitor the effect of therapy. Many inflammatory mediators have been detected in the feces such as leukocytes, cytokines and proteins from neutrophil activation. Some of these, particularly lactoferrin and calprotectin, have been demonstrated to be useful in detecting active inflammatory bowel disease, in predicting recurrence of disease after surgery or monitoring the effects of medical therapy. Calprotectin and lactoferrin are remarkably stable and easily detect in stool using ELISA so they appear to be equally recommendable as inflammation markers in the lower gastrointestinal tract especially in IBD patients. Conclusion Fecal markers are non-invasive, simple, cheap, sensitive and specific parameters and are useful to detect strointestinal inflammation.

Background: Crohn’s disease (CD) is a chronic illness that interferes with the daily life of those affected. The aim of the present study was to evaluate long-term health-related quality of life (HRQL) outcome and its clinical predictors in CD patients who have had ileocolonic resection. Methods: Ninety-seven CD patients, with a mean follow-up of 47.1 months (95% CI, 40.7–53.5 months) after ileocolonic resection, were interviewed by telephone and responded to the generic Cleveland Global Quality of Life (CGQL) questionnaire, and 63 of them also agreed to come to our outpatient clinic to have a Crohn’s Disease Activity Index (CDAI) assessment and blood test and to answer the disease-specific Padova Inflammatory Bowel Diseases Quality of Life (PIBDQL) questionnaire. Control groups also were enrolled. Results: The CGQL scores of the 97 CD patients were similar to those of 69 healthy controls. Only the item on current quality of health was scored significantly lower by patients with CD. In contrast, the PIBDQL item and total scores of the CD patients were all significantly lower than those of the respective healthy controls (P 0.05). Multivariate analysis showed that the CGQL and PIBDQL scores both had a strong linear relationship with number of daily stools and with CDAI score (P 0.05). Conclusions: Despite CD patients who have undergone ileocolonic resection having an apparently normal quality of life with a good energy level, as shown by the CGQL, their long-term HRQL is still affected by a significantly impaired quality of health. In fact, the PIBDQL questionnaire showed significant impairment of bowel and systemic symptom domains with important consequences for emotional and social functions. HRQL seems to be significantly related only to current disease activity. (Inflamm Bowel Dis 2007;13:462– 469)

Objectives. To identify the most significant variables in determining if candidates with past or current addictions can be considered for liver transplantation. Methods. Data relating to 58 cases from January 2001 to December 2003 were collected and analyzed. Results. The decisional algorithm identified by discriminant analysis is based on the following variables: the duration of remission, treatment adherence, and the presence of a valid help relationship. Candidates undergoing initial remission (up to 12 months) must demonstrate both adherence and affective support; those with over 5 years of remission, however, are considered sufficiently reliable. A positive judgment is significantly correlated to overall survival and clinical improvement even without transplantation. Conclusions. In toxicological evaluation, treatment adherence and the presence of a valid help relationship for patients in remission from addictions can improve the selection criteria for liver transplantation, making it more dependable.

Background/Aim The main indications for combined liver and kidney transplantation (CLKT) are as follows: (1) cirrhosis with renal damage dependent or not upon liver disease, (2) renal failure with dialysis and concomitant liver end-stage disease, (3) congenital diseases, and (4) enzymatic liver deficiency with concomitant renal failure. The aim of this study was to evaluate our results with CLKT both in adult and pediatric patients. Methods From September 1995 to September 2006, 15 CLKT (2.8%) among 541 liver transplantations included 4 pediatric patients (27%). The main indications for CLKT were hepatitis C virus (HCV) and polycystic diseases in adult patients, and primary hyperoxaluria in pediatric patients. Results The double transplantation was performed from the same donor in all cases. All adult patients received whole liver grafts, whereas 3 split transplants and 1 whole liver graft were transplanted in the pediatric patients. Median liver and kidney cold ischemia times were 468 and 675 minutes, respectively. After a median follow-up of 36 months (range, 1–125), the overall survival rate was 80%. Five-year patient and graft survival rates were 100% for adult CLKT, whereas they were 50% for pediatric patients. We observed only 2 cases (18%) of delayed renal function, requiring temporary hemodialysis with progressive graft improvement. There was only 1 case of kidney retransplantation due to early graft nonfunction in a pediatric patient. Conclusion Although CLKT is related to major surgical risks, results after transplantation are satisfactory with an evident immunological advantage.

Whether beta-blockers (BB) or banding is the best therapy for primary prophylaxis of variceal bleeding is subject to debate. A randomized comparison between the 2 treatments was performed in candidates for liver transplantation (LT). A total of 62 patients with Child-Turcotte-Pugh B-C cirrhosis and high risk varices received propranolol (31) or variceal banding (31). The primary endpoint was variceal bleeding. There were 2 variceal hemorrhages (6.5%) in the banding group, related to postbanding ulcers, and 3 (9.7%) in the propranolol group (P = not significant [n.s.]). Deaths and bleeding related deaths were 3 and 1 for banding and 3 and 2 for BB, respectively (P = n.s.). A total of 14 patients underwent LT in the banding group and 10 in the propranolol group (P = n.s.). Adverse events were 2 postbanding ulcer bleedings in ligated patients (1 fatal) and 5 were intolerant to propranolol (P = n.s.). Mean costs per patient were higher with banding than with propranolol treatment (4,289 +/- 285 vs. 1,425 +/- 460 U.S. dollars, P < 0.001). In conclusion, propranolol and banding are similarly effective in reducing the incidence of variceal bleeding in candidates for LT, but ligation can be complicated by fatal bleeding and is more expensive. Our results suggest that banding should not be utilized as primary prophylaxis in transplant candidates who can be treated with BB.

Introduction Liver transplantation represents the gold standard for the treatment of chronic liver disease. The whole transplantation process was assessed using an intention-to-treat analysis and considering patients from the time of their inclusion on the list and throughout lengthy follow-up. Materials and methods From January 1, 1999 to June 1, 2004, 373 adults joined the waiting list for liver transplantation at our institution. The main variables analyzed were: age, gender, etiology, Model for End-stage Liver Disease score, Child-Pugh class, United Network for Organ Sharing (UNOS) status. Global survival was evaluated using intention-to-treat analysis from the time of patient inclusion in the list to the end of their late follow-up. Results The median waiting time was 20 months (range 0.1 to 70.2). By univariate analysis, the variables significantly influencing survival when patients joined the waiting list were: encephalopathy; ascites, poor nutritional status, Child-Pugh class C, UNOS 2, hepatitis C virus (HCV) and bilirubin > 2 mg/dL. By multivariate analysis, only HCV-related cirrhosis emerged as having an independent prognostic value. By intention-to-treat analysis, the 5-year survival rate was 67% and 79% for HCV-positive and HCV-negative patients, respectively (P = .0003). Conclusions HCV-related cirrhosis is an independent prognostic factor for survival according to an intention-to-treat analysis. Different inclusion criteria or treatments while on the waiting list and after transplantation need to be considered in the future for HCV-positive patients.

This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.

This study was designed to assess the role of fecal lactoferrin and calprotectin as markers of intestinal inflammation in patients with Crohn’s disease who have undergone ileocolonic resection. Sixty-three patients who had undergone ileocolonic resection for Crohn’s disease with a median follow-up of 40.5 (range, 5–102) months were enrolled. Clinical examination and blood test were performed, and fecal lactoferrin and calprotectin levels were dosed. The predictors for fecal lactoferrin and calprotectin levels that resulted to be significant at the univariate analyses were included in two multiple regression analysis models. The mean lactoferrin level was 21 ± 3.9 μg/g and the mean calprotectin fecal level was 247 ± 22.7 ng/ml. C-reactive protein levels (P

Background Ovarian metastases from primary colorectal cancer occur in 3–8% of female patients. The aim of this study was to assess the prognostic value of radical oophorectomy for ovarian metastasis from colorectal cancer. Patients and methods From our series of 859 patients operated for colorectal cancer from 1982 to 2005 ten patients with isolated ovarian metastasis were retrieved. Ovarian colorectal metastasis diagnosis was confirmed by pathology revision. Overall and disease-free survival after radical oophorectomy for metastases were assessed and compared with literature data. Results The median follow-up from ovarian metastases resection was 36 months (range 194–14). Survival analysis showed that survival rate after ovarian metastasectomy was 100% at 1 year and 80% at 5 years of follow up. Conclusion Our study, although limited by a relatively short follow-up and small sample size, shows that bilateral oophorectomy for ovarian metastasis from colorectal cancer has a good impact on disease-free and overall survival. J. Surg. Oncol. 2007;96:113–117. © 2007 Wiley-Liss, Inc.

Aim To assess the indications and results of endoscopic retrograde cholangio-pancreatography (ERCP) in patients who have undergone ortotopic liver transplantation (OLT). Methods We reviewed data from 42 consecutive patients who underwent ERCP for biliary complications after OLT over an 8-year period, in particular recording indications and success of the treatment after a mean of 17 months follow-up. Results Cholangiograms performed in 33/42 patients (79%) displayed anastomotic strictures in 17 patients (52%), bile duct stones in 8 (24%), both bile duct stones and an anastomotic stricture in 2 (6%), papillary stenosis in 1 (3%), and anastomotic biliary leakage in 1 (3%). In contrast, the contrastogram was normal in four patients (12%). Stone extraction was completed in 9/10 patients (90%) with a mean of 1.2 sessions, while stricture dilation was achieved in 12/19 patients (63%) after a mean of 1.7 sessions, by stent positioning ( n = 7), balloon dilation ( n = 4), or Soehendra dilator ( n = 1). Both biliary leakage and papillary stenosis were cured by ERCP. Only one procedure-related complication—severe pancreatitis (2.4%)—was observed and no mortality. Conclusion ERCP is a safe and effective mode of management of bile duct complications after OLT. It should be attempted before a surgical approach. Better results are obtained for treatment of biliary stones than of anastomotic strictures.

Antitumor necrosis factor alpha (anti-TNF-alpha) therapy in perianal Crohn's disease (CD) is widely established but recent studies suggest that the underlying fistula tract and inflammation may persist. Treatment with a monoclonal antibody against interleukin (IL)-12 was reported to induce clinical responses and remissions in patients with active CD. The aim of our study was to analyze the cytokine network (TNF-alpha, IL-12, IL-1beta, and IL-6) in 12 patients with chronic perianal CD and a Crohn's disease activity index (CDAI) score150 to exclude active intestinal disease, in 7 patients with indeterminate colitis (IC) after restorative proctocolectomy with perianal complications, in 7 patients with active intestinal CD without perianal manifestations, and in 19 healthy controls. Nonparametric Mann-Whitney U test and Spearman's rank correlation test were used. Serum TNF-alpha levels were significantly higher in patients with IC than perianal CD patients and healthy controls. Serum TNF-alpha levels significantly correlated with perianal CDAI score and with the presence of anal fistulas. Serum IL-12 levels correlated with the presence of anal strictures and were similar in all groups. Serum IL-6 levels were significantly higher in the presence of perianal fistulas and lower in the presence of anal strictures. Our study confirmed that TNF-alpha plays a major role in the perianal and intestinal CD. Furthermore, the significantly higher TNF-alpha serum levels in patients with IC suggest the use of anti-TNF-alpha in such patients. On the contrary, according to our results the efficacy of anti-IL-12 antibodies appears doubtful in chronic perianal CD or IC without anal strictures. The role of IL-6 as a systemic mediator for active chronic inflammation was confirmed and a possible role for its monoclonal antibody was suggested.

Background The number of orthotopic liver transplantation performed each year is increasing due to increased safety and logistic facilities. Therefore, the importance of reducing adverse events is progressively growing. Aim To review present knowledge on the neurological complications of orthotopic liver transplantation. Methods The epidemiology, the clinical features and the pathophysiology of the neurological complications of orthotopic liver transplants, resulting from a systematic review of the literature in the last 25 years, are summarized. Results and conclusions The review highlights that a relevant variety of neurological adverse events can occur in patients undergoing orthotopic liver transplantation. The knowledge of neurological complications of orthotopic liver transplantation is important for transplantation teams to reduce their prevalence and improve their management. In addition, the likelihood of neurological adverse effects provides evidence for the need of a careful cognitive and neurological work up of patients in the orthotopic liver transplantation waiting list, in order to recognize and interpret neurological dysfunction occurring after orthotopic liver transplantation.

Anastomotic recurrence after bowel resection is a major problem in Crohn’s disease (CD) surgery. The aims of this retrospective study are to assess the role of anastomotic configuration, the type of suture and the type of surgical approach (laparoscopy-assisted vs laparotomy) in CD recurrence. Secondary end points were to identify any possible predictor that would help the selection of patients for medical prophylaxis. In this retrospective study, we enrolled 141 consecutive patients who had undergone ileocolonic resection for CD. Univariate actuarial analysis was performed according to demographic, clinical and surgical predictors. Variables that resulted to be significant at the univariate analysis were included in two multivariate Cox proportional hazards models that analyzed symptomatic and surgical recurrence, respectively. In the long-term, handsewn side-to-side anastomosis reported a significantly lower surgical recurrence rate than stapled end-to-side (p

Background and Objectives This retrospective study was undertaken to evaluate if high resectability rate could improve the long-term outcome of patients with proximal bile duct cancer. Methods Between 1985 and 2001, 50 patients (34 male and 16 female) with proximal bile duct cancer were treated. Thirty-six patients (72%) were considered suitable for surgery, while 14 underwent nonsurgical palliative procedures. Twenty patients had bile duct resection only. Ten patients had Roux-en-Y cholangiojejunostomy with two or three divided segmental hepatic ducts; in 10 patients, the cholangiojejunostomy was performed with four or five divided segmental hepatic ducts. Three patients were treated by palliative transtumoral intubation with Kehr tube. Thirteen patients had bile duct resection plus hepatectomy. Despite the curative intention of the operation, only in 19 (52.7%) patients did the histopathological examination reveal tumor-free margins. Results There was no operative mortality. Postoperative morbidity was 25%. Overall 1-, 3-, and 5-year survival of the entire surgical group was 61%, 22.5%, and 9%, respectively. In the 19 patients treated with curative intent the survival at 1, 3, and 5 years was 63.1%, 31.5%, and 15.8%, respectively, while in the group that had palliative treatment it was 45%, 15%, and 0%, respectively. Conclusions Only margins free from tumor can guarantee an improvement in long-term outcome. Increasing resectability improves survival and could offer a chance of better long-term survival. J. Surg. Oncol. 2006;93: 199–205. © 2006 Wiley-Liss, Inc.

The aim of this prospective study was to validate a variant in the loop ileostomy construction to reduce peristomal pressure ulcers and, subsequently, the need of stoma therapist assistance and the frequency of changing the stoma appliance. We have enrolled 33 consecutive patients who underwent two stage restorative proctocolectomies. The first consecutive 13 patients operated on had their ileostomies constructed with a standard rod. In the following 20 patients, we placed a 5.3-mm suction catheter tube closed with a stitch to form a “ring” and without any stitches fixing it to the skin. In the “ring” rod group 40% of patients did not report any complication compared to the 8% of patients in the standard rod group (p = 0.046). Pressure ulcers were absent in this group, while it affected 61% of the patients in the standard rod group (p

Ulcerative colitis is an established risk factor for colorectal cancer but dysplasia reports are much more frequent than invasive neoplasm diagnosis. The effective activation of T lymphocytes that provide antitumor surveillance requires the presence of costimulation molecules such as CD80 and CD86 on the surface of antigen-presenting cells. The aim of our study was to verify the presence of an in vivo immunosurveillance mechanism in the early stages of colon tumorigenesis.Expression of CD80, CD86, and IFN-gamma in the colonic mucosa of 21 consecutive ulcerative colitis (UC) patients was quantified using reverse transcription polymerase chain reaction. After a 7-year follow-up period, we reviewed the histology of all surveillance colonoscopy specimens for colonic dysplasia. Correlation, frequency, and survival analyses were performed.CD80 was detectable in seven patients while expression of CD86 and IFN-gamma was evident in all patients. Histology confirmed the presence of dysplasia in eight patients. Patients who had dysplasia showed higher CD80 levels compared to those without dysplasia (p=0.02). Survival analysis demonstrated that cumulative dysplasia rates of CD80-positive patients were significantly higher than those of CD80-negative patients (p=0.04).Even if partially limited by a relatively small sample size, our study seems to show an association between CD80 expression and colonic dysplasia in UC patients that may suggest a role for CD80 in the immunosurveillance against colorectal cancer in this early stage of tumorigenesis. On the contrary, CD86 seems to be involved in the inflammatory pathogenesis of UC.

The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C–positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 μmol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline. Liver Transpl 12:1464–1472, 2006. © 2006 AASLD.

The use of hepatocytes that express liver-specific functions to develop an artificial liver is promising. Unfortunately, the loss of specialized liver functions (dedifferentiation) is still a major problem. Different techniques, such as collagen entrapment, spherical multicellular aggregates (spheroids), and coculture of hepatocytes with extracellular matrix, have been used to improve the performance of hepatocytes in culture. The aim of this study was to compare two different models of hepatocyte isolation in culture: isolated hepatocytes (G1) and hepatocyte spheroids (60% hepatocytes, 40% nonparenchymal cells, and extracellular matrix) (G2). To test functional activity of hepatocytes, both synthetic and metabolic, production of albumin and benzodiazepine transformation into metabolites was tested. G2 showed a high albumin secretion, while a decrease after 15 days of culture in G1 was noted. Diazepam metabolites were higher in G2 than in G1 in all samples, but had statistical significance at days 14 and 21 (p < 0.01). The glycogen content, after 30 days of culture, was very low in G1 (14.2 ± 4.4%), while in G2 it was 72.1 ± 2.6% (p < 0.01). Our study confirms the effectiveness of a culture technique with extracellular matrix and nonparenchymal cells. Maintenance of a prolonged functional activity has been related to restoration of cell polarity and close cell-to-cell contact. We showed that isolated hepatocytes maintain their functional activity for a period significantly reduced, when compared to the hepatocyte spheroids. We confirmed the role of extracellular matrix as a crucial component to promote hepatocyte homeostasis, and the close link between cellular architecture and tissue-specific functions.

Several studies showed that costimulatory signals on antigen presenting cells are up-regulated in inflammatory bowel disease. We quantified the expression of CD80, CD86, and IFNgamma in colonic mucosa of patients affected by ulcerative colitis and correlated it with clinical and biochemical parameters to identify the context of this up regulation. We enrolled 21 patients affected by ulcerative colitis and 6 healthy subjects. We evaluated for each patient gender, age, duration of disease, clinical, endoscopic and histologic disease activity index, medical therapy, ESR, serum CRP, WBC, and serum al-acid glycoprotein. CD80, CD86, and IFNgamma expression in the colonic mucosa was quantified using reverse transcription polymerase chain reaction. Statistical analysis was performed using Mann-Whitney U test and Spearman's rank correlation test. Significance was set at P < 0.05. CD80 was detectable in seven patients, while CD86 and IFNgamma expression was evident in all UC patients. CD80 and CD86 were not detectable in control specimens. Colonic CD80 expression was correlated to the age of the patients. CD86 expression showed an inverse correlation with duration of disease and a direct correlation with serum CRP levels and histologic grade of disease activity. IFNgamma was not correlated with any of the examined parameter. Our study confirms a major role in ulcerative colitis pathogenesis for CD86 which correlates with histologic grade of disease and with serum CRP levels, and its upregulation seems to be higher at the beginning of the disease. In "in vivo" conditions IFNgamma may not be the only factor responsible for CD86 up-regulation in the ulcerative colitis colonic mucosa.

The differential diagnosis of cystic neoformations in the pancreas is challenging. We report a case of a true solitary cyst of the pancreas in a 26-year old woman. Abdominal magnetic resonance imaging and computed tomography showed a unilocular neoformation in the head of the pancreas, without obstruction of Wirsung's duct. We excised the cyst and performed Roux-en-Y loop pancreaticojejunostomy, but the patient suffered recurrent acute pancreatitis from Wirsung's duct stenosis. Thus, a new Roux-en-Y loop pancreaticojejunostomy was successfully done 6 months later. Histologically, the cyst was lined by cuboidal epithelium, immunohistochemically positive to anti-carbohydrate antigen 19-9 antibodies. To our knowledge, only 11 cases of solitary true cyst of the pancreas in adults have been reported, so the characteristics of this unusual entity are not well known. We propose a scheme for the differential diagnosis of cystic neoformations of the pancreas, starting from the histopathological definition of a true solitary cyst.

We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF.

A simple and rapid method is described for staining semithin sections of material embedded in epoxy resin for observing tissues prior to transmission electron microscopy. The method is suitable for tissue fixed with a glutaraldehyde-formaldehyde mixture and postfixed in osmium tetroxide. No etching or oxidizing procedures are necessary. Sections 0.5-0.8 microm thick are dried onto a slide and stained with either 0.75% methylene blue and 0.25% azure B or 0.5% methylene blue and 0.5% azure II in 0.5% aqueous borax and heated over a flame for 8-10 sec. The slides are rinsed with water, then stained the same way with 0.1% basic fuchsine in 5% aqueous ethanol. Cytoplasm stains blue; nuclei darker blue; collagen, mucus and elastin pink to red; fat and intracellular lipid droplets gray-green.

To establish the incidence of prostate cancer (PCa) in Sicily in patients who entered an early detection protocol.From February 2002 to February 2004, 16,298 subjects aged 40-75 entered the protocol. Patients with suspicious DRE, PSA10 ng/ml, PSAor=2.5 ng/ml, from 2.6 to 4 ng/ml or from 4.1 to 10 ng/ml with F/T PSA ofor=15%,or=20% andor=25% respectively underwent needle biopsy according to an extensive protocol.3266 patients were eligible for biopsy; PSA wasor=4 in 12.7% andor=10 ng/ml in 63.9% of patients. A PCa was found in 1171 cases (36.9%) with a relationship between PCa incidence and PSA and age respectively (chi2-test, p0.0001); 51.8% of patients with PCa had a PSA10 and 8.8% a PSA4 ng/ml; 49% were clinically staged as T1c. The estimated odds ratios for each age group showed increased risk for PCa in the fourth decade with PSA between 2.6 and 4 ng/ml (12.5 times higher) and in the fifth decade with PSA between 4.1 and 10 ng/ml (6.2 times higher).Age and serum PSA levels are the major risk factors for PCa. On their basis it is possible to modulate the most suitable timing for early diagnosis in individual patients.

The aim of this paper is to review and assess the selective principles for a radical treatment of gastric carcinoma with respect to resection type as well as the role of lymphadenectomy.From 1994 to 1999, we operated 222 patients affected by gastric adenocarcinoma at the 1st Surgical Clinic Institute in Padua. Out of the whole group, 138 patients (62.1%) underwent radical surgical treatment (75 patients with total gastrectomy, extended in 30 cases, and 63 patients by means of gastric resection).The overall survival rate at a median follow-up of 4 years was 58% for the patients treated with total gastrectomy, and 77% in case of distal gastric resection; 97% of patients with early gastric cancer are alive at a median follow-up of 3 years.Whenever it is feasible, subtotal gastrectomy could ensure a radical treatment of gastric carcinoma with low morbidity and mortality rate. The survival rate of such patients was 77%. Prognosis of early gastric cancer is excellent. Patients with IV stage tumors surgically treated had a poor outcome, and they should be susceptible of a multidisciplinary palliative approach.

In this study we evaluated the possibility of performing a cross small bowel transplantation (CrSBTx) in which, at the same time, 2 pigs were both donors and later recipients of intestinal grafts. The hemodynamic and metabolic impact of this original transplantation model on the animals was determined.Ten large White adult female pigs underwent a 2 stage procedure. The principal intraoperative hemodynamic and metabolic parameters were measured at different times during the operation. In the 3 days that followed the operation, renal function, liver and pancreatic damage were investigated.Our surgical model permits us to keep excellent hemodynamic and metabolic stability with low mortality.The need of half of animals with respect to conventional models represents an ethical and economic advantage of CrSBTx and we propose it for intestinal transplant studies in large animals.

Ureteral involvement due to Crohn's disease occurs in 3% to 6% of cases. Herein, we present a case of a 22-year-old woman with ileocolic Crohn's disease with right hydronephrosis due to compression of the ureter that was resolved with a 3-stage, minimally invasive procedure (preoperative percutaneous nephrostomy, ureteral stent placement, and sequential laparoscopically assisted ileocolectomy). Percutaneous right nephrostomy drainage permitted us to prevent renal damage before surgery, and successive ureteral double-J catheter placement minimized the risk of ureteral damage during the laparoscopic procedure. The safety and feasibility of sequential minimally invasive management of ileocolonic Crohn's disease involving the right ureter was assessed, and a good cosmetic result was achieved.

Background/Aims : Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). Methods : A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan–Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. Results : In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. Conclusions : BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.

Restorative proctocolectomy (RPC) is the favorite operation for ulcerative colitis, but it may influence health-related quality of life (HRQL). Our aims were to determine the long-term HRQL of patients and its modifications after a 5-year follow-up and to identify any risk factor for a worse outcome. We enrolled 36 patients submitted to RPC (mean follow-up 8.4 +/- 4.7 years), 36 ulcerative colitis (UC) patients, and 36 healthy subjects. We used a previously validated questionnaire that explored bowel symptoms, systemic symptoms, emotional function, and social function. A series of 17 patients had completed the same questionnaire 5 years earlier. Clinical and surgical factors were investigated. Statistical analysis was performed with Student's t-test, Wilcoxon matched-pairs test, and Fisher's exact test. The scores of the RPC patients were significantly better than those of moderate or severe UC patients, similar to those with remission/mild UC, and higher than those of the controls. The scores of patients interviewed 5 years earlier did not change in the present study, except for patients during the first postoperative year, in whom the scores were now significantly better. The analysis of RPC patients in subgroups showed that the use of drugs, high stool frequency, pouchitis, pelvic complications, and younger age at UC diagnosis worsened the HRQL outcome. We concluded that RPC patients, after a long-term follow-up, had an HRQL similar to that of the remission/mild UC patients. Recently operated patients improved their quality of life mainly because of improved emotional function, and patients who had been operated on for a longer time maintained their HRQL. HRQL is influenced by drugs, stool frequency, pouchitis, postoperative pelvic complications, and age at diagnosis.

Objective: To determine the long-term results of liver transplantation for well- or moderately differentiated hepatocellular carcinoma (HCC). Summary Background Data: HCC patient selection for liver transplantation remains controversial, and deciding exclusively on the strength of criteria such as number and size of nodules appears prognostically inaccurate. Methods: Since 1991, preoperative tumor grading has been used at our center to establish whether a patient with HCC is fit for transplantation. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. Thirty-three patients with moderately or well-differentiated HCC were prospectively studied after liver transplantation. A group of 15 patients with incidental HCC transplanted during the same period were also evaluated and compared with the 33 patients with preoperatively diagnosed HCC. Results: On histologic examination, 38% of the entire group of 48 patients did not meet the "Milan criteria" and 42% were pTNM stages III and IV. The median follow-up was 44 months. The 5-year actuarial survival rate was 75% and recurrence-free survival was 92%. HCC recurred in only 3 patients (6%). The only histomorphologic variable differing significantly between incidental and nonincidental HCC was nodule size. The timing of diagnosis (incidental vs. nonincidental HCC), the Milan criteria, and the TNM stage revealed no statistically significant impact on overall and recurrence-free survival rates. Conclusions: The routine pre-orthotopic liver transplantation tumor grading may represent a valid tool in the selection of unresectable HCC patients for transplantation.

Background: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical–pathological parameters remains controversial, however. Methods: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time. Results: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p