Successful liver transplantation in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: Case report.

BACKGROUND: HHH syndrome is a rare autosomal recessive disorder of the urea cycle, caused by a deficient mitochondrial ornithine transporter. We report the first successful liver transplantation in HHH syndrome performed in a seven-year-old boy. The patient presented at 4 weeks of age with hyperammonemic coma. The plasma amino acid profile was suggestive of HHH syndrome, and the diagnosis was confirmed when sequencing of the SLC25A15 gene identified two mutations p.R275Q and p.A76D. Although immediate intervention resulted in normalization of plasma ammonia levels within 24 hours, he developed cerebral edema, coma, convulsions, and subsequent neurological sequelae. Metabolic control was difficult requiring severe protein restriction and continued treatment with sodium benzoate and L-arginine. Despite substantial developmental delay, he was referred to our center for liver transplantation because of poor metabolic control. Following cadaveric split liver transplantation, there was complete normalization of his plasma ammonia and plasma amino acid levels under a normal protein-containing diet. This excellent metabolic control was associated with a markedly improved general condition, mood and behavior, and small developmental achievements. Twelve years after liver transplantation, the patient has a stable cognitive impairment without progression of spastic diplegia. CONCLUSION: This first case of liver transplantation in HHH syndrome demonstrates that this procedure is a therapeutic option for HHH patients with difficult metabolic control.

Left-liver Adult-to-Adult Living Donor Liver Transplantation: Can It Be Improved? A Retrospective Multicenter European Study.

OBJECTIVE: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT). SUMMARY BACKGROUND DATA: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe. METHODS: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT. RESULTS: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ±â€Š3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) <0.6% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual GBWR >0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044). CONCLUSIONS: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

Liver transplantation for hepatocellular carcinoma comparing the Milan, UCSF, and Asan criteria: long-term follow-up of a Western single institutional experience.

BACKGROUND: In patients with hepatocellular carcinoma (HCC), the outcome after liver transplantation (LT) is excellent if tumor characteristics are within the Milan criteria (MC). Expanded Asan criteria (AC) have not yet been validated in Western countries. METHODS: A total of 76 patients with HCC underwent LT. Patients were divided and compared according to Milan, UCSF, and Asan criteria. Differences between pre- and post-operative assessment were evaluated. Overall survival (OS) and disease-free survival (DFS) were compared between groups. Predictors of recurrence were investigated. RESULTS: Asan criteria provided 26% and 15% more criteria-fitting patients than MC and UCSF pre-operatively while 49% and 35% at pathological evaluation. Discrepancy between pre- and post-operative evaluation was 32% for MC, 33% for UCSF, and 18% for AC (p = 0.06). After a median follow-up of 70.5 months, patients exceeding MC but fulfilling Asan had comparable 5-yr OS and DFS to patients fulfilling MC (p = 0.17; p = 0.29). Patients exceeding UCSF but fulfilling AC had comparable 5-yr OS and DFS to patients fulfilling UCSF (p = 0.26; p = 0.32). Number of nodules, macro-vascular invasion, capsular invasion, and exceeding AC predicted recurrence at multivariate analysis (p = 0.01, 0.03, 0.01, 0.02, respectively). CONCLUSIONS: The extension to AC allows increasing the number of patients eligible for LT without affecting OS and DFS.

Risk factors and management of conversions to an open approach in laparoscopic liver resection: analysis of 265 consecutive cases.

BACKGROUND: As a consequence of continuous technical developments in liver surgery, laparoscopic liver resection (LLR) is increasingly performed worldwide. METHODS: Between January 2004 and December 2011, 265 LLR were performed in 242 patients for various diseases. The experience of LLR is reported focusing on risk factors of conversion and their management. RESULTS: The overall conversion rate was 17/265 (6.4%), equally distributed over the period of the study. Statistically significant factors for conversion were found to be LLR of the postero-superior (P-S) segments (SI, SIVa; SVII; SVIII) (12.7% converted versus 2.5% non-converted groups, P = 0.01) and a major compared with a minor hepatectomy (15.2% vs. 4.6%, P = 0.02 respectively). A R0 resection was achieved in 93.2% of cases. According to Dindo's classification, complications were recorded as grade I (n = 20); grade II (6); grade III (11) and grade IV(1) events (total morbidity rate of 14%). Univariate analysis identified a major hepatectomy and resection involving P-S segments as prognostic factors for conversion whereas multivariate analysis identified the latter as an independent risk factor [P = 0.003, odds ratio (OR) = 5.9, 95% confidence interval (CI) = 1.8-18.8]. CONCLUSIONS: LLR can be safely performed with low overall morbidity. According to this experience and irrespective of the learning curve, resections of P-S segments were identified as an independent risk factor for conversion in LLR.

Liver transplantation for alcoholic liver disease: a retrospective analysis of recidivism, survival and risk factors predisposing to alcohol relapse.

BACKGROUND AND STUDY AIMS: Alcoholic liver disease (ALD) is the second most common indication for liver transplantation. The aim of this study was to evaluate the alcohol relapse rate and long-term survival after liver transplantation for ALD and to identify risk factors predisposing to alcohol relapse. PATIENTS AND METHODS: Between 2000 and 2007, 108 patients transplanted for ALD in the Ghent University Hospital were included in this retrospective analysis. Relapse was defined as any drinking after transplantation, problem drinking as more than 2 units/day for women and 3 units/day for men. A wide range of variables was obtained from a questionnaire and medical records. RESULTS: The mean follow-up was 55 months. Relapse was observed in 29%, 16% in problem drinking. The one- and five-year survival was 87% and 74% respectively. No significant difference in survival was found between non-relapsers, occasional drinkers and problem drinkers. The following risk factors were found to be significantly associated with relapse into problem drinking in an univariate analysis: a shorter pre-transplant abstinence period, the presence of a first degree relative with alcohol abuse and a higher number of prior attempts to quit. In multivariable analysis, the presence of a first degree relative with alcohol abuse was found associated with relapse into problem drinking. CONCLUSIONS: The presence of a first degree relative with alcohol abuse is a valuable pre-transplant variable evaluating an ALD patient's eligibility for liver transplantation. Other variables are also helpful to outline the broader context of the drinking behavior of the patient.

Expansion of memory-type CD8+ T cells correlates with the failure of early immunosuppression withdrawal after cadaver liver transplantation using high-dose ATG induction and rapamycin.

BACKGROUND: We report on a pilot study investigating the feasibility of early immunosuppression withdrawal after liver transplantation (LT) using antithymocyte globulin (ATG) induction and rapamycin. METHODS: LT recipients received 3.75 mg/kg per day ATG from days 0 to 5 followed by rapamycin-based immunosuppression. In the absence of acute rejection (AR), rapamycin was withdrawn after month 4. Immunomonitoring included analysis of peripheral T-cell phenotypes and clonality, cytokine production in mixed lymphocyte reaction, and characterization of intragraft infiltrating cells. RESULTS: Ten patients were enrolled between October 2009 and July 2010. In the first three patients, complete withdrawal of immunosuppression after month 4 led to AR. No further withdrawals of immunosuppressive were attempted. Two AR occurred in the remaining seven patients. ATG induced profound T-cell depletion followed by CD8(+) T-cell reexpansion exhibiting memory/effector-like phenotype associated with progressive oligoclonal T-cell expansion (Vß/HPRT ratio) and gradually enhanced anti-cytomegalovirus and anti-Epstein-Barr virus T-cell frequencies. Patients developing AR were characterized by decreased TCAIM expression. AR were associated with increased donor-specific production of interferon (IFN)-γ and interleukin (IL)-17, increased intragraft expression of IFN-γ mRNA, and significant CD8(+) T-cell infiltrates colocalizing with IL-17(+) cells. CONCLUSION: High-dose ATG followed by short-term rapamycin treatment failed to promote early operational tolerance to LT. AR correlates with expansion of memory-type CD8(+) T cells and increased levels of IFN-γ and IL-17 in mixed lymphocyte reaction and in the graft. This suggests that resistance and preferential expansion of effector memory T-cell in lymphopenic environment could represent the major barrier for establishment of tolerance to LT in approaches using T-cell-depleting induction.

Lack of a correlation between portal vein flow and pressure: toward a shared interpretation of hemodynamic stress governing inflow modulation in liver transplantation.

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty-one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range = 25%-91%, P = 0.001). Severe PHT (HVPG ≥ 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value ≥ 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT.

Donor haptoglobin phenotype determines outcome following liver transplantation.

Haptoglobin (Hp) is a polymorphic plasma protein with multiple functions defined by three major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). In this article, the effects of the donor Hp phenotype (determined by starch gel electrophoresis) on the outcome and the iron status after liver transplantation were investigated. A total of 450 liver transplant patients were enrolled in this study with a median follow-up of 37 months. Kaplan-Meier and Cox regression survival analyses showed a significantly worse graft survival for liver transplantation cases with an Hp 2-2 donor phenotype, which was associated with an increased mortality rate in this group. In male patients, the Hp 2-2 phenotype was associated with higher serum ferritin concentrations, which may be linked to the significantly increased likelihood of infectious complications in this phenotype. Liver transplant patients with Hp 1-1 and Hp 2-1 grafts had a better outcome probability than recipients of an Hp 2-2 graft, which may be explained by differences in iron metabolism induced by the Hp genotype of the graft.

Expression of placental growth factor in regenerating livers after partial hepatectomy in the rat.

BACKGROUND/AIMS: Placental growth factor (PlGF) is known for its role in pathological conditions to protect parenchymal cells of different organs from injury, whereas its presence in the liver and its potential importance in stimulating liver regeneration has never been described. This was investigated in this study using a rat model of partial hepatectomy (PH). METHODS: The rat model of 70, 80, and 90% PH was used. Liver samples were taken peroperatively, 1 h, 1, 2, 3, and 7 days after surgery. Liver regeneration was evaluated by liver weight/body weight ratio, liver regeneration rate (%), and proliferating cell marker Ki67. The expression of PlGF, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), VEGF receptor 2 (Flk-1), and hypoxia inducible factor-1α mRNA was measured by quantitative real-time PCR and localized by immunohistochemistry. RESULTS: The mRNA expression of PlGF was upregulated immediately after PH. Compared with 70 and 80% PH groups, the 90% PH group had a significantly lower PlGF and hypoxia inducible factor-1α mRNA expression, in parallel to a delayed liver weight/body weight ratio recovery. Only little differences were observed in VEGF, Flt-1, and Flk-1 mRNA expression among the PH groups. CONCLUSION: This study shows for the first time the PlGF upregulation in regenerating livers, which is related to hypoxia stimulation and liver growth. The swift PlGF upregulation immediately after PH may indicate an important role for the PlGF/Flt-1 pathway in the early stage of liver regeneration.

Evolution of laparoscopic left lateral sectionectomy without the Pringle maneuver: through resection of benign and malignant tumors to living liver donation.

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) has gained popularity in its use for benign and malignant tumors. This report describes the evolution of the authors' experience using laparoscopic LLS for different indications including living liver donation. METHODS: Between January 2004 and January 2009, 37 consecutive patients underwent laparoscopic LLS for benign, primary, and metastatic liver diseases, and for one case of living liver donation. Resection of malignant tumors was indicated for 19 (51%) of the 37 patients. RESULTS: All but three patients (deceased due to metastatic cancer disease) are alive and well after a median follow-up period of 20 months (range, 8-46 months). Liver cell adenomas (72%) were the main indication among benign tumors, and colorectal liver metastases (84%) were the first indication of malignancy. One case of live liver donation was performed. Whereas 16 patients (43%) had undergone a previous abdominal surgery, 3 patients (8%) had LLS combined with bowel resection. The median operation time was of 195 min (range, 115-300 min), and the median blood loss was of 50 ml (range, 0-500 ml). Mild to severe steatosis was noted in 7 patients (19%) and aspecific portal inflammation in 11 patients (30%). A median free margin of 5 mm (range, 5-27 mm) was achieved for all cancer patients. The overall recurrence rate for colorectal liver metastases was of 44% (7 patients), but none recurred at the surgical margin. No conversion to laparotomy was recorded, and the overall morbidity rate was 8.1% (1 grade 1 and 2 grade 2 complications). The median hospital stay was 6 days (range, 2-10 days). CONCLUSIONS: Laparoscopic LLS without portal clamping can be performed safely for cases of benign and malignant liver disease with minimal blood loss and overall morbidity, free resection margins, and a favorable outcome. As the ultimate step of the learning curve, laparoscopic LLS could be routinely proposed, potentially increasing the donor pool for living-related liver transplantation.

Open intraperitoneal versus retromuscular mesh repair for umbilical hernias less than 3 cm diameter.

BACKGROUND: mesh techniques are the preferable methods for repair of small ventral hernias, as a primary suture repair shows high recurrence rates. The aim of this prospective study was to compare the retromuscular sublay technique with the intraperitoneal underlay technique for primary umbilical hernias. METHODS: from February 2004 to April 2007, all patients treated for umbilical hernias with maximum diameters of 3 cm were prospectively followed. During the first period of 15 months, all patients were treated with retromuscular repair using a large pore mesh (Vypro). After that period, for all patients, mesh repair using an intraperitoneal Ventralex patch was performed. All patients underwent general anesthesia. This analysis included 116 patients, of whom 56 had retromuscular repair (group I; mean age, 54.8 years; mean body mass index, 28.2 kg/m(2)) and 60 had open intraperitoneal repair (group II; mean age, 48.1 years; mean body mass index, 29.4 kg/m(2)). Operating time was evaluated as skin-to-skin time, and drain management was noted for both techniques. Follow-up was ≥ 2 years for all patients, and both early and late complications were registered, including seroma and hematoma formation, wound infection, fistula formation, and recurrence rates. Preoperative and postoperative pain was evaluated using a visual analogue scale (range, 0-10) on the day of the first outpatient visit; on postoperative days 1, 7, and 21; and after 1 year. Quality of life was estimated using the EQ-5D questionnaire 1 year after surgery. All data were analyzed using SPSS version 15 software. Wilcoxon's rank-sum test was used to analyze continuous variables, and repeated-measures analysis of variance was used for visual analogue scale scores. The χ(2) test and Fisher's exact test were used to assess the differences between categorical data. P values < .05 were considered statistically significant. RESULTS: the mean operative times were 79.9 minutes in group I and 33.9 minutes in group II (P < .001). The mean hospital stay was significantly longer in group I (3.8 vs 2.1 days, P < .001). Seromas and superficial wound infections in the early postoperative period were not different between both groups, although seromas occurred more frequent in the retromuscular group. Postoperative visual analogue scale scores were significantly lower with the intraperitoneal technique at all time points (P < .003, repeated-measures analysis of variance). However, 3 patients with the Ventralex patch had to be readmitted for severe pain. The recurrence rate was higher with the intraperitoneal repair (n = 5 [8.3%] vs n = 2 [3.6%]) than for the retromuscular mesh repair, but not statistically significant. Quality of life was comparable in the two groups after 1 year. CONCLUSIONS: the open intraperitoneal technique using a Ventralex mesh for umbilical hernias seems a very elegant and quick technique. However, possibly because of the less controllable mesh deployment, recurrence rates seem higher. In case open mesh repair is the preferred treatment, a retromuscular repair should be the first choice.

Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: an open, randomized, prospective, multicenter, parallel-group trial.

BACKGROUND: The aim of this trial was to confirm previous results demonstrating the efficacy and safety of a fixed combination tissue sealant versus argon beam coagulation (ABC) treatment in liver resection. METHODS: This trial was designed as an international, multicenter, randomized, controlled surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥ 1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondary hemostasis. Secondary end points were drainage duration, volume, and content. Adverse events were collected to evaluate the safety of treatments. The trial was registered internationally (Eudract number 2008-006407-23). RESULTS: Among 119 patients (60 TachoSil and 59 ABC) randomized in 10 tertiary care centers in Europe, the mean time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC was 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did not differ between the 2 groups. Mortality (2 vs 4 patients) and adverse reactions (24 vs 28 patients) for TachoSil versus ABC did not differ. CONCLUSION: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity and mortality remained unchanged between both groups.

Hypomagnesemia and the risk of new-onset diabetes after liver transplantation.

New-onset diabetes after transplantation (NODAT) is a frequent complication after liver transplantation and has a negative impact on both patient and graft survival. In analogy with the previous finding of an association between posttransplant hypomagnesemia and NODAT in renal transplant recipients, the relation between both pretransplant and posttransplant hypomagnesemia and NODAT was studied in liver transplant recipients (LTRs). One hundred sixty-nine adult LTRs (>18 years old) without diabetes who underwent transplantation between 2004 and 2009 were studied (mean age = 52.11 ± 12.6 years, proportion of LTRs who were male = 67.5%, body mass index = 25.5 ± 4.4 kg/m², proportion receiving tacrolimus = 90.0%). NODAT was defined according to the American Diabetes Association criteria. The association of NODAT with both pretransplant and posttransplant serum magnesium (Mg) was examined. Overall, 52 of 169 patients (30.8%) developed NODAT, and 57.7% of these (30 patients) were treated with antidiabetic drugs. Both pretransplant Mg levels and Mg levels in the first month after transplantation were lower in patients developing NODAT (P = 0.008 and P = 0.001, respectively). A multivariate regression model (adjusted for weight, pretransplant glucose levels, hyperglycemia in the first week after transplantation, gender, hepatitis C, and corticosteroid dosing) demonstrated both pretransplant Mg levels (hazard ratio = 0.844 per 0.1 mg/dL increase, 95% confidence interval = 0.764-0.932, P = 0.001) and posttransplant Mg levels (hazard ratio = 0.659, 95% confidence interval = 0.518-0.838, P = 0.001) to be independent predictors of NODAT together with age, biopsy-proven acute rejection, and cytomegalovirus (CMV) infection in the first year after transplantation. In conclusion, pretransplant hypomagnesemia and early posttransplant hypomagnesemia are independent predictors of new-onset diabetes after liver transplantation. Other risk factors are age, biopsy-proven acute rejection, and CMV infection.

Comparable results with 3-year follow-up for large-pore versus small-pore meshes in open incisional hernia repair.

BACKGROUND: Decreasing the amount of polypropylene by increasing pore size produces a lighter weight mesh that may improve tissue ingrowth and, functional properties of the abdominal wall and diminish mesh-related complications. It was the aim of this prospective observational cohort study to analyze the outcome of incisional hernia repair using small-pore versus large-pore meshes and using a standardized, open, retromuscular surgical technique. METHODS: Across a 6-year period we analyzed 205 patients treated with a heavyweight mesh (group I) and 235 patients treated with a large-pore mesh (group II) for incisional hernias. Patients with a body mass index greater than 40 kg/m(2) and patients with hernias with a transverse diameter of more than 10 cm were not treated by a retromuscular mesh repair and are not included in this analysis. Recurrent incisional hernias also were not included. Both groups had 3 years of follow-up. Patients were evaluated for pain, discomfort, feeling of foreign material, and recurrences. RESULTS: Pre-operative characteristics were comparable between the groups, including body mass index, diabetes, and smoking. The mean total hernia surface was 56 cm(2) for group I versus 48 cm(2) in group II. The mesh surface area was 448 cm(2) for group I and 425 cm(2) for group II. Considering pain scores, there was only a minor difference between the 2 groups at 1-month follow-up, at which time, the Visual Analogue Scale was 5.8 in group I and 4.9 in group II (P = .16). All other scores were comparable between the groups. In group I, 7 recurrences (3.4%) were recorded after 3 years, of which 6 were already apparent 1 year after initial repair. In group II, 9 recurrences (3.8%) were diagnosed, again 6 within the first year after repair. CONCLUSION: Large-pore meshes can be used safely for open primary incisional hernia repair with an equal outcome compared with small-pore meshes in nonobese patients with defects smaller than 10 cm in width, in regard to both recurrence rates and chronic discomfort.

Laparoscopic evaluation shows deficiencies in memory ring deployment during small ventral hernia repair.

BACKGROUND: With the introduction of a self-expanding, memory-containing, circular hernia patch, surgeons have been enthusiastic about its use to repair ventral hernias smaller than 3 cm in diameter. The aim of this study was to evaluate the efficiency, reliability, and safety of the device laparoscopically with respect to adequate deployment of the patch. METHODS: During 1 year all patients with small ventral hernias were treated with this memory-containing patch and were inspected by laparoscopy. Just prior to insertion of the patch, remaining adhesions on top of the peritoneum were analyzed, as was the interference of the umbilical ligament. The final position of the patch was monitored, identifying the cupping phenomenon, exposure of the polypropylene to the viscera, and the amount of tension on the straps. All patients were followed for 2 years and postoperative complications and recurrence rate were monitored. RESULTS: Twenty-eight patients were operated on for repair of a small ventral hernia with laparoscopic control. Adhesions, not digitally palpable, that interfered with adequate patch deployment were observed in more than 80% of the cases. After a median follow-up of 25 months a 14.8% recurrence rate was observed. CONCLUSIONS: The patch, consisting of both polypropylene and ePTFE, leads to unacceptable morbidity and a high rate of recurrences. By laparoscopic evaluation, these recurrences are probably based on a combination of material characteristics and unavoidable technical errors.

Transinguinal preperitoneal memory ring patch versus Lichtenstein repair for unilateral inguinal hernias.

PURPOSE: The aim of this study was to compare the transinguinal preperitoneal technique (TIPP) using a memory ring patch versus the Lichtenstein technique in relation to acute and chronic pain, post-operative complications and recurrence rates. METHODS: During an 18-month period, all adult patients that needed treatment for a unilateral inguinal or femoral hernia were treated by the TIPP repair using the Polysoft mesh. This group was retrospectively compared with a historical cohort of patients treated by the Lichtenstein technique. Our policy concerning type of anaesthesia, post-operative pain management and visual analogue scale measurements did not change over the study period. For post-operative pain evaluation, the visual analogue scale was used (0-10) and scores were measured after 6 h, 24 h, 1 week, 1 month, 1 year and yearly thereafter. Recurrence rates were evaluated at time of clinical examinations. RESULTS: In total, 142 patients have been analysed with the TIPP technique (group I) versus 136 patients operated in the previous 2 years with a Lichtenstein repair (group II). In group I, 112 patients (78.9%) received a medium size patch of 14 x 7.5 cm and 30 patients (21.1%) had a large patch (16 x 9 cm). The mean operative time for a TIPP procedure was statistically shorter than for a Lichtenstein repair, 33 versus 44 min, respectively (p = 0.04). After 24 h, 1 week and 1 month post-surgery, there was significantly less post-operative pain observed in the TIPP group than in the Lichtenstein group. In total, four recurrences were observed in the TIPP group (2.8%), of which one laterally and three medially. In group II, seven recurrences were observed in total (5.1%), of which five were detected within 2 years of follow-up (3.7%). CONCLUSION: For surgeons performing the Lichtenstein repair but looking for modifications concerning pain relief and a quicker procedure, the TIPP approach is a feasible alternative that seems to be associated with less post-operative pain.

Liver transplantation from donation after cardiac death donors: initial Belgian experience 2003-2007.

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From 2003 to 2007, 58 DCD-LT were performed in Belgium. Mean procurement total warm ischemia time was 25 +/- 2 min (mean +/- SEM). Mean cold ischemia time was 451 +/- 18 min. Mean follow-up was 23 +/- 2.2 months. Post-transplant peak aspartate aminotransminases was 2241 +/- 338 UI/l. Patient survivals at 1 month, 1 and 3 years, were 91.3%, 83.3% and 66.9% respectively. Graft survivals at 1 month, 1 and 3 years, were 84.4%, 72.4% and 48.8% respectively. Two patients (3.4%) developed primary nonfunction. Regarding the biliary complications, seven grafts (12%) were lost because of intrahepatic cholangiopathy, and 12 other patients (20.6%) developed bile duct stenoses requiring endoscopic and/or surgical management. The rate of symptomatic ischemic biliary lesions for grafts surviving more than 3 months was 38% (19/50). Although DCD organ donors may be a source of viable liver grafts, results were inferior to those obtained with donation after brain death LT in this series. Prognostic criteria have to be developed to improve results of DCD-LT.

Acute liver transplant rejection upon immunosuppression withdrawal in a tolerance induction trial: potential role of IFN-gamma-secreting CD8+ T cells.

We designed a pilot trial in cadaveric liver transplantation to determine whether induction with antithymocyte globulins (ATG) and sirolimus would allow immunosuppression withdrawal. Patients received ATG 3.75 mg/kg per day from day 1 to 5 after transplantation followed by sirolimus for 4 to 6 months. We monitored interleukin (IL)-7 serum levels, interferon (IFN)-gamma, and IL-2 mRNA accumulation in mixed leukocyte reaction and intragraft IFN-gamma mRNA expression. In the first three patients, immunosuppression discontinuation was followed by reversible acute rejection occurring on days 280, 246, and 163 posttransplantation, corresponding to days 140, 40, and 39 after drug withdrawal, respectively. At the time of rejection, blood CD8+ T-cells counts had returned to or above pretransplant levels in two of three patients, whereas CD4+ T-cell count remained low. IL-7 serum levels rose in all three patients in the first months after transplantation and IFN-gamma mRNA accumulated in mixed leukocyte reaction between recipient T cells and donor spleen cells at the time of rejection. High levels of IFN-gamma mRNA were consistently detected in liver biopsy performed at the time of rejection. In conclusion, lymphopenia-induced IL-7 production after induction with ATG and sirolimus might lead to emergence of IFN-gamma-secreting CD8+ T-cells responsible for acute rejection after immunosuppression withdrawal.

Expression of SGLT1, Bcl-2 and p53 in primary pancreatic cancer related to survival.

Increased expression of glucose transporters has been reported in many cancers. It is not known whether Sodium dependent GLucose Transporter 1 (SGLT1) is up-regulated in pancreatic cancer. We studied the expression of SGLT1, Bcl-2 and p53 in primary pancreatic adenocarcinomas related to survival. In primary tumors, mean SGLT1-Hscore (n = 83) was 4.24 (median 3.0, range 0.5-15.0). Patients with positive staining for Bcl-2 had higher mean SGLT1-Hscores than those without Bcl-2 expression: 5.87 vs. 3.07 (P = 0.025). No correlation was found between expression of p53 and SGLT1 (P = 0.881). On multivariate analysis TNM stage (P = 0.015) and SGLT1 (P = 0.030) showed prognostic value for disease free survival (DFS). For overall survival (OS), TNM stage (P<0.001) and chemotherapy (P = 0.048) were prognostic and SGLT1 showed a trend (P = 0.071). In a subgroup of younger patients (age < or = median, 63.9 y) who did not receive chemotherapy, SGLT1 was a very strong predictor of DFS (P = 0.005). We conclude that high SGLT1 expression (H score > median, 3.0) in pancreatic adenocarcinomas was significantly correlated with DFS and a trend was found for OS, especially in younger patients. High SGLT1 expression in primary tumors was correlated with high Bcl-2 expression, not with p53 expression. This supports our hypothesis that SGLT1 and Bcl-2 expression could serve as prognostic markers in pancreatic cancer.

Split liver transplantation with extended right grafts under patient-oriented allocation policy. Single center matched-pair outcome analysis.

BACKGROUND: Split liver transplantation (SLT) is an established technique developed to optimize the number of available grafts. Few data are available on SLT with extended right liver grafts (eRLG) in the context of patient-oriented allocation policy. METHODS: Between July 1, 2001 and December 31, 2005, 12 whole liver graft (WLG) recipients were matched with 12 eRLG recipients according to their clinical status, indication and year of liver transplantation. RESULTS: There were no differences according to recipient Model for End-stage Liver Disease score, total serum bilirubin, creatinine levels and international normalized ratio in both groups. Fifty percent of donors in eRLG group presented 2 or more extended criteria. Liver transplantation was performed in UNOS status 1/2A in 58% of cases in both groups. Vascular and biliary complications were observed in three patients in the eRLG group. The median follow-up was 25.3 months (range 0.4-63). Early mortality (