Solitary pancreatic head metastasis from tibial adamantinoma: a rare indication to pancreaticoduodenectomy.

Pancreatic metastases are rare, <2% of all pancreatic neoplasia. This is the first case of pancreatic metastasis from adamantinoma, a rare, low grade and slow growing tumor which is frequently localized in long bones. We describe a case of a 45-year-old woman presenting with increased bilirubin level. Computed tomography and ecoendoscopic ultra sonography revealed a pancreatic head mass. Fine-needle aspiration biopsy was consistent with metastatic adamantinoma. The patient was submitted to a standard pancreaticoduodenectomy. As in the case presented, standard pancreatic resections are safe and feasible options to treat non-pancreatic primary tumor improving patient's survival and quality of life.

Preoperative oral immunonutrition versus standard preoperative oral diet in well nourished patients undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy is still associated to high morbility, especially due to pancreatic surgery related and infectious complications: many risk factors have already been advocated. Aim of this study is to evaluate the role of preoperative oral immunonutrition in well nourished patients scheduled for pancreaticoduodenectomy. METHODS: From February 2014 to June 2015, 54 well nourished patients undergoing pancreaticoduodenectomy were enrolled for 5 days preoperative oral immunonutrition. A series of consecutive patients submitted to the same intervention in the same department, with preoperative standard oral diet, was matched 1:1. For analysis demographic, pathological and surgical variables were considered. Mortality rate, overall postoperative morbility, pancreatic fistula, post pancreatectomy haemorrhage, delayed gastric emptying, infectious complications and length of hospital stay were described for each groups. Chi squared test, Fisher's Exact test and Student's T test were used for comparison. Differences were considered statistically significant at p < 0.05. Statistics was performed using a freeware Microsoft Excel (®) based program and SPSS v 10.00. RESULTS: No statistical differences in term of mortality (2.1% in each groups) and overall morbility rate (41.6% vs 47.9%) occurred between the groups as well as for pancreatic surgery related complications. Conversely, statistical differences were found for infectious complications (22.9% vs 43.7%, p = 0.034) and length of hospital stay (18.3 ± 6.8 days vs 21.7 ± 8.3, p = 0.035) in immunonutrition group. CONCLUSION: Preoperative oral immunonutrition is effective for well nourished patients scheduled for pancreaticoduodenectomy; it helps to reduce the risk of postoperative infectious complications and length of hospital stays.

Role of TachoSil® in distal pancreatectomy: a single center experience.

AIM: Distal pancreatectomies (DP) are associated with high risk of postoperative complications, and in many series higher morbidity rate than duodenopancreatectomies has been reported. To evaluate the role of a collagen sponge with human fibrinogen and thrombin film (TachoSil®) in limiting the incidence of complications after DP. METHODS: From 1996 to 2013, 221 patients have been submitted to distal pancreatectomy (± splenectomy) in our Division. A retrospective analysis has been conducted in a group of 36 consecutive and prospectively collected DP treated with intraoperative placement of TachoSil® on pancreatic stump from 2010 to 2013 (group 1). A control series of 36 consecutive patients (group 2) was matched 1:1 from hystorical database. The variables considered in the analysis were: age, gender, ASA score, pancreatic texture (hard vs. soft), histology, operative time, postoperative mortality, morbility (postoperative pancreatic fistula - POPF, postoperative hemorrage - PPH, delayed gastric emptying - DGE) and hospital stay. Differences between POPF, PPH, DGE and hospital stays between grops were investigated with χ² and t-Student test. Univariate analysis was conducted to determine factors related to POPF development. Statistical analysis was performed using freeware Microsoft Excel based program. RESULTS: Post operative mortality was 0% in both groups. POPF were registered in 36.1% (13/36) and 41.6 % (15/36) in groups 1 and 2, respectively (P=n.s.); in group 1 we didn't observe grade C POPF, while 4 patients in control group developed grade C POPF (P<0,05). No differences were found between two groups in terms of incidence of PPH and DGE. The median duration of postoperative hospital stay in group 1 was 21.8 (7-189) days compared with 31.13 (9-249) days in group 2 (P<0.001). CONCLUSION: The use of TachoSil® seems to be associated with lower incidence of grade C POPF but larger controlled trials are needed to surely assess the usefulness of TachoSil® in pancreatic surgery in order to reduce pancreatic specific complications and their severity.

Inflammatory biomarker profile in children with cystic fibrosis: preliminary study.

The aim of this preliminary study was to determine specific proteins, related to inflammation process and nutritional status as well as to total antioxidant capacity, in children suffering from cystic fibrosis (CF). The study was performed on 17 nonhospitalized children (12 boys and 5 girls) with CF aged 3 months to 10 years, who were assisted at the Nutrition Service from Pedro de Elizalde Hospital. Transferrin, transthyretin, ceruloplasmin (Cp), haptoglobin, C-reactive protein (CRP) and fibrinogen were measured by single radial immunodiffusion techniques. Total antioxidant capacity (TAC) was determined by a decolorization assay. Statistical analyses were performed by the Student's t test. Transferrin and transthyretin values were lower in CF patients in comparison with data obtained from healthy children (reference group, RG). The decreased transferrin concentration and the tendency towards low plasma transthyretin values suggested an abnormal nutritional status. However, higher Cp and haptoglobin levels were shown in patients than in RG. The fact that 23 and 50% of patients exceeded the desirable values for fibrinogen (<285.0 mg/dl) and CRP (<0.2 mg/dl), respectively, should be highlighted. The TAC (mM; Trolox equivalents) was shown to be lower in the CF group than in RG. The diminished TAC concomitant with an increased plasma Cp concentration would exacerbate the inflammatory status and could explain the depression of the immune system. These preliminary results could explain the need to include biochemical and functional parameters in the early nutritional status evaluation in CF patients in order to use appropriate nutritional and pharmacological therapies and consequently to improve their survival and quality of life.

The diagnostic accuracy of the immunocytochemical markers in the pre-operative evaluation of follicular thyroid lesions.

UNLABELLED: Aim of the study was to consider the diagnostic accuracy of galectine-3 (GAL3) in the pre-operative cytological evaluation of follicular lesions. MATERIALS AND METHODS: We retrospectively evaluated 100 patients suffering from thyroid nodular disease submitted to thyroidectomy from 2006 to 2007 in our Institution. Before surgery all patients underwent fine needle aspiration biopsy. The immunocytochemical analysis was performed on fine needle aspiration specimens using species-specific monoclonal antibodies and a biotin-free detection system. Based on preoperative cytological reports, 40 patients had pre-operative malignant results, and 60 patients (46 females and 14 males) showed follicular lesions. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of GAL3 was evaluated. STATISTICAL ANALYSIS: Chi-square test was used to compare frequencies of GAL3 expression between the different hystopathological groups. RESULTS: GAL3 proved to have 55% sensitivity, 100% specificity, 70% negative predictive value, and 78% diagnostic accuracy. The GAL3 expression in neoplastic and benign lesions was significantly different (GAL3+ in 16 out of 29 neoplastic lesions, GAL3+ 0 out of 31 benign lesions, p<0.01). Even comparing the GAL3 positivity between the follicular adenomas (0 GAL3+ out of 20) and the group of follicular carcinomas (5 GAL3+ out of 6), we found a statistically significant difference (p<0.01). CONCLUSIONS: Based on the data from our experience, the patients with a cytological diagnosis of GAL3 positive follicular neoformation should be referred for surgery without any further immunocytological testing.

Ischemic preconditioning (IP) of the liver as a safe and protective technique against ischemia/reperfusion injury (IRI).

The aim of the study was to evaluate safety and efficacy of IP in LT, particularly in marginal grafts. From 2007 to 2008, 75 LT donors were randomized to receive IP (IP+) or not (IP-). Considering the graft quality, we divided the main groups in two subgroups (marg+/marg-). IP was performed by 10-min inflow occlusion (Pringle maneuver utilizing a toruniquet). Donor variables considered were gender, age, AST/ALT, ischemia time and steatosis. Recipient variables were gender, age, indication to LT and MELD/CHILD/UNOS score. AST/ALT levels, INR, bilirubin, lactic acid, bile output on postoperative days 1, 3 and 7 were evaluated. Histological analysis was performed evaluating necrosis/steatosis, hepatocyte swelling, PMN infiltration and councilman bodies. Thirty patients received IP+ liver. No differences were seen between groups considering recipient and donor variables. Liver function and AST/ALT levels showed no significant differences between the main two groups. Marginal IP+ showed lower AST levels on day1 compared with untreated marginal livers (936.35 vs. 1268.23; p = 0.026). IP+ livers showed a significant reduction of moderate-severe hepatocyte swelling (33.3% vs. 65.9%; p = 0.043). IP+ patients had a significant reduction of positive early microbiological investigations (36.7% vs. 57.1%; p = 0.042). In our experience IP was safe also in marginal donors, showing a protective role against IRI.

Antiangiogenic and immunomodulatory effects of rapamycin on islet endothelium: relevance for islet transplantation.

Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angiogenesis-related factors VEGF, alphaVbeta3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation.

Use of hepatitis C virus-positive grafts in liver transplantation: a single-centre experience.

AIM: Our goal was to evaluate the outcome of HCV(+) recipients after liver transplantation (LT) using HCV(+) donors and the interaction between donor and recipient viral strain. METHODS: We performed a retrospective analysis of 21 LT performed between 1998 and 2004 using livers from HCV(+) donors in HCV(+) recipients. Two hundred thirty-seven patients with HCV cirrhosis who underwent LT with livers from HCV(-) donors were the control group. Ishak score (IS) was evaluated for all HCV(+) grafts. The considered variables included donor age, hepatic enzymes, intensive care unit stay, HCV genotype, ischemia time, recipient age, UNOS status, Child score, HCV genotype (before and 6 months after LT) and IS (after LT). We analyzed patient, graft, and disease-free survival. RESULTS: HCV(+) donors were significantly older than HCV(-) donors. The cumulative 5-year patient and graft survivals and disease free intervals were not different between groups. IS grading was more than 2/18 in two cases; the only graft with a staging score over 2/6 was retransplanted for early nonfunction. In two cases, different HCV genotypes were matched and donor strain took over the recipient strain. In one patient, donor genotyping 2a-2c took over recipient genotyping 1b and 9 months after LT recurrent hepatitis was documented, but antiviral therapy cleared HCV. CONCLUSIONS: Livers from HCV(+) donors can safely be used in HCV(+) recipients. Hepatic biopsy must always be performed; livers with bridging fibrosis should not be used. The takeover of one strain by another may change the prognosis of the patient if the predominant strain is more sensitive to antiviral therapy.

Mycophenolate mofetil monotherapy in liver transplantation.

AIM: Calcineurin inhibitors (CI) are associated with significant morbidity in transplant recipients. The aim of this study was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in liver transplantation (LT). METHODS: We analysed 32 patients (24 males, 8 female, of mean age 55.7 years) who underwent LT between 1994 and 2003. In 29 patients immunosuppressive therapy was cyclosporine; in three patients it was tacrolimus. Eleven patients were submitted for LT due to hepatitis B cirrhosis; eight for hepatitis C cirrhosis, six for alcoholic cirrhosis, and seven for other diseases. In these patients, MMF was added gradually, simultaneously reducing the dosage of CI up to complete withdrawal. We considered the efficacy (decrease in serum creatinine) and the incidence of complications (acute and chronic rejection, leukopenia, diarrhea). RESULTS: Patients were converted to MMF after a median of 50 months after LT. MMF monotherapy was started after a median of 9 months in association with CI. Indications for switch to MMF monotherapy were adverse effects of CI (renal disfunction in 30 patients) and de novo tumoral evidence after LT in two patients. Median dosage of MMF was 750 mg twice daily (500-1500 mg). There was a statistically significant decrease in serum creatinine levels (2.02-1.7 mg/dL; P = .0001). Side effects were: leukopenia in five of 32 patients (15.6%), diarrhea in four of 32 patients (12.5%), and one acute rejection. CONCLUSION: MMF monotherapy improved renal function and was not associated with a significant risk of allograft rejection. Side effects were mild with dose regimens up to 750 mg twice daily.

New-onset diabetes after liver transplantation.

AIM: The impact of new-onset diabetes (NOD) posttransplantation has been underestimated in the past. The aim of this study was to evaluate the incidence of diabetes after liver transplantation. METHODS: We retrospectively analyzed the incidence of NOD in 899 patients transplanted in our center. According to International Consensus 2003 Guidelines, criteria for diagnosis of diabetes were: fasting plasma glucose > or =126 mg/dL, symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dL, and 2-hour plasma glucose levels > or =200 mg/dL during an oral glucose tolerance test. We considered only patients with follow-up over 10 months. We evaluated the risk factors correlated with NOD (age, hepatitis C virus [HCV] positivity, tacrolimus vs cyclosporine, steatosic graft), and the outcomes of diabetic patient and their grafts. RESULTS: The incidence of NOD was 10.8% (90/830 patients). Sixty nine patients were diabetic before transplantation. Recipient age >45 years (14.7% vs 6.8%, P = .002, OR = 2.4) and HCV positivity (15.5% vs 7.8%, P = .001, OR = 2.2) significantly correlated with NOD. Multivariate analysis confirmed these variables to be independently associated with diabetic risk. Tacrolimus was associated with an increased risk of NOD (16.2% in HCV-negative patients, 25% in HCV-positive patients), but this difference was not statistically significant. Steatotic grafts (>10%) were associated with an increased risk of NOD (28.6% vs 10%, P = .001, OR = 3.6). The outcome of patients and grafts in the group of diabetic patients was not significantly different from all other patients. CONCLUSIONS: The incidence of NOD was more relevant in patients older than 45 years and/or HCV-positive. A steatotic graft was an important risk factor, and the match with high-risk patients should be avoided.

Use of arterial conduit as an alternative technique in arterial revascularization during orthotopic liver transplantation.

BACKGROUND: The risk of hepatic artery thrombosis after orthotopic liver transplantation is higher in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, unsafe native hepatic arteries. AIMS: To assess the use of arterial conduits as alternative technique for graft revascularization. PATIENTS: At the Liver Transplant Center of the "S. Giovanni Battista" Hospital in Torino, a review has been made of 600 consecutive orthotopic liver transplantations in 545 adult patients from 1990 to 1999. METHODS: In 95 orthotopic liver transplantations (15.8%) in 88 patients, the graft was supplied by infrarenal conduit, while in 505 orthotopic liver transplantations (84.2%) in 457 patients, a direct anastomosis was used. RESULTS AND CONCLUSIONS: The overall incidence of hepatic artery thrombosis in our series was 3.5% (21/600): 5.3% (5/91) for conduits and 3.2% (16/505) for standard technique (p=ns, chi2 test). The actuarial 5-year graft survival was 67.7% for conduits and 68.6% for the standard technique; p (log rank): ns. The iliac prosthesis torsion was the only complication related to the use of infrarenal iliac conduit. The arterial conduit, performed with donor iliac artery, is an effective and safe revascularization technique in patients at high risk of arterial thrombosis.

Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis.

BACKGROUND/AIMS: Treatment with hepatitis B virus immune globulins (HBIG) or lamivudine has reduced the rate of hepatitis B recurrence after liver transplantation to approximately 50%. METHODS: To further decrease hepatitis B recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated with lamivudine before liver transplantation and with lamivudine together with low-dose HBIG (46 500 IU the first month followed by 5,000 lU/monthly) after surgery. RESULTS: While on lamivudine, serum HBV DNA level decreased significantly in all patients and in 11 (33%) the Child-Pugh score improved. Twenty-six patients were transplanted. Among the 25 who survived for longer than 12 months, only one (4%) experienced a hepatitis B recurrence over an average follow-up of 31 months, a rate significantly lower (P = 0.0002) than the 50% recurrence rate among a historical control group of 12 patients. However, low-level HBV replication was detected sporadically throughout the follow-up in 64% of patients. CONCLUSIONS: Over the medium-term, combined prophylaxis with lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence after liver transplantation. Though low-level HBV infection recurred in two thirds of patients, the pathogenic expression of HBV was prevented.

Effect of macrovescicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation.

The influence of steatosis and of other donor and recipient characteristics in affecting liver performance post-orthotopic liver transplantation (OLT) was evaluated in 311 consecutive liver transplantations made in 278 patients. Donor variables considered were age, sex, blood group, cause of death, intensive care unit (ICU) days, need for vasopressors, hepatic enzymes and bilirubin, total and warm ischemia time, and macro- and microvescicular steatosis. Recipient variables considered were age, sex, blood group, biliary output, and post-OLT peak levels of hepatic enzymes. Patient and graft survival were the main outcome indicators. In the multivariate analysis, macrovescicular steatosis involving 25% or more of the hepatocytes was the only variable independently associated with shorter patient survival (p < 0.05). Five (62.5%) of the eight livers with macrovescicular steatosis involving 25% or more of the hepatocytes incurred in a delayed non-function (DNF) and one (12.5%) in a primary non-function (PRNF). The incidence of DNF and PRNF in the group with macrovescicular steatosis involving less than 25% of the liver cells was 1.6% (p < 0.001) and 2.3%, respectively. Microvescicular steatosis of any degree was not associated with a worse prognosis. Macrovescicular steatosis involving 25% or more of the hepatocytes identifies marginal livers, the use of which significantly increases the risk of graft non-function post-OLT.