Proctitis in patients with monkeypox infection: a single-center analysis of 42 consecutive cases from a multidisciplinary observational study on monkeypox proctitis.

BACKGROUND: The current monkeypox (MP) virus outbreak was declared an international emergency in July 2022. The aim of this report is to describe our initial experience with patients with MP, focusing on proctitis. METHODS: We conducted an observational study between 20 May and 31 July 2022, on patients with MP at a reference tertiary center in Madrid, Spain. A descriptive analysis on MP was performed, focusing on its characteristics, symptoms, diagnosis, and outcomes. RESULTS: A total of 143 positive MP cases were diagnosed in our center; 42 of them [all male, median age 39 years (range: 22-57 years)] had proctitis (29.37%), and 3 patients (2.09%/MP total cases and 7.14%/MP proctitis) required surgical drainage of a perianal abscess. CONCLUSIONS: General and digestive surgeons must be aware of the presence of proctological impairment and complications due to MP virus.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma. / Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable.

BACKGROUND: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AIM: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. METHODS: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. RESULTS: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. CONCLUSION: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

90Y-Radioembolization After Failed Portal Vein Embolization for Colorectal Liver Metastases: A Case Report.

The main limiting factor for liver resection is insufficient future liver remnant (FLR). Portal vein embolization (PVE) is a standard of care treatment to induce FLR hypertrophy, but it is not always efficient. Radioembolization (RE) has a potential to induce liver hypertrophy for PVE-refractory patients. However, this was reported only for the patients with hepatocellular carcinoma. We described two cases of lobar RE after PVE failure for the patients with colorectal liver metastases. This enabled to reach sufficient FLR, provide good local disease control and bridge the patients to extended hepatectomy.

Factors Associated with Prolonged Recipient Hepatectomy Time During Liver Transplantation: A Single-Centre Experience.

BACKGROUND: Recipient hepatectomy during liver transplantation can be a challenging operation and can increase cold ischaemic time. The aim of this study is to assess factors associated with prolonged recipient hepatectomy. METHODS: From 2005 to 2015, 930 patients were submitted to liver transplantation in our hospital. Prolonged hepatectomy time was defined as operative time >180 min (from knife on skin to total hepatectomy). Patients undergoing early liver retransplantation and living donation were excluded. RESULTS: A total of 715 patients were included in our study. Median age at transplantation was 53 (18-70) years, and median BMI was 26.2 (16-40). Median hepatectomy time was 131 min. Prolonged hepatectomy time occurred in 89 (12.4%) patients. At univariate analysis, previous decompensated cirrhosis with variceal bleeding and/or ascites, higher BMI and previous abdominal surgery were associated with prolonged operating time. Higher surgeon experience and acute liver failure were associated with shorter hepatectomy time. At multivariate analysis, previous episodes of variceal bleeding (p = 0.027, OR 1.78), BMI > 27 (p = 0.01, OR 1.75), previous abdominal surgery (p = 0.04, OR 1.68) and surgeon experience (p = 0.007, OR 2.04) were independently associated with operating time. Prolonged hepatectomy time was significantly associated with cold and total ischaemic time and intraoperative bleeding (p < 0.001, p = 0.002 and p = 0.002, respectively). CONCLUSIONS: Recipient BMI, previous episodes of variceal bleeding, previous abdominal surgery and surgeon experience are independently associated with hepatectomy duration. These factors can be helpful to identify those patients with potentially prolonged hepatectomy time, and therefore, strategies can be put in place to optimize outcomes in this group of patients.

Role of Adult Living Donor Liver Transplantation in the Treatment of Hepatocellular Carcinoma Within and Beyond Milan Criteria: A Comparative Study.

BACKGROUND AND AIMS: In the context of the shortage of donors, adult living donor liver transplantation (aLDLT) represents a feasible alternative for patients within as well as beyond the Milan criteria. METHODS: From 2001, we performed 42 aLDLTs for hepatocellular carcinoma (HCC). Sixteen of the recipients were within the Milan criteria, whereas 26 fulfilled the Barcelona-Clinic Liver Cancer Group (BCLC) expanded criteria (1 tumor ≤7 cm, 5 tumors ≤3 cm, or tumors 3 ≤5 cm without macrovascular invasion or down-staging to Milan after loco-regional therapies). The objective of the current study was to compare the post-transplantation results of these two groups. RESULTS: Six Milan-in and 16 beyond Milan patients received neo-adjuvant loco-regional therapies. One Milan-in and nine patients from the beyond Milan group presented an explant histological stage beyond Milan. After a median follow-up of 64 months, 5- and 10-year overall survival rates were 60.2% and 51.6% in the Milan-in group and 78% and 65% in the beyond Milan group. Five- and 10-year disease-free survival rates were 64.5% and 55.3% in the Milan-in patients and 67.9% and 56.6% in the beyond Milan patients. Being beyond up-to-seven criteria in the histology of the explant was a significant factor for HCC recurrence. CONCLUSION: The use of aLDLT in patients with HCC within and beyond Milan but within the BCLC expanded criteria offers acceptable survival and recurrence rates. Therefore, we believe that its use in this scenario is justified.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Platelet-mediated angiogenesis is independent of VEGF and fully inhibited by aspirin.

BACKGROUND AND PURPOSE: Platelets are major players in every step of vessel development through the local delivery of angiogenesis-modulating factors, including the pro-angiogenic protein VEGF and the anti-angiogenic endostatin. Although thrombin is a potent agonist and is highly elevated in angiogenesis-related diseases, studies regarding its action on the release of platelet angiogenic factors are scarce and controversial. Herein, we have investigated the role of thrombin not only in VEGF and endostatin release but also in net platelet angiogenic activity. EXPERIMENTAL APPROACH: Human platelets were stimulated with thrombin in the presence of the various inhibitors of the signalling pathways involved in platelet activation. Supernatants/releasates were used to determine the levels of angiogenic molecules and to induce angiogenic responses. KEY RESULTS: We found that thrombin induced the secretion of both VEGF and endostatin; however, the overall effect of the releasates was pro-angiogenic as they promoted tubule-like formation and increased the proliferation of endothelial cells. Both responses were only slightly suppressed in the presence of a VEGF receptor-neutralizing antibody. Pharmacological studies revealed that while inhibitors of PKC, p38, ERK1/2, Src kinases or PI3K/Akt exerted only partial inhibitory effects, aspirin fully blocked the pro-angiogenic activity of the releasate. CONCLUSIONS AND IMPLICATIONS: In contrast to current belief, platelet pro-angiogenic responses are independent of VEGF and appear to be the result of the combined action of several molecules. Moreover, our data reinforce the notion that aspirin is a good candidate for a therapeutic agent to treat angiogenesis-related diseases.

Clinical and prognostic usefulness of serum proteomic profile in hepatic colorectal metastases: a pilot prospective study.

PURPOSE: To analyze the use of proteomic profiles to discriminate healthy from patients with colorectal liver metastases (CLM) and to predict neoplastic recurrence after CLM resection. METHODS: From April 2005 to October 2008, 70 patients operated for first curative resection of CLM and 60 healthy controls underwent determination of preoperative serum proteomic profile. We performed a preliminary training with patients and controls and obtained a classification system based on these patients' proteomic profiles training. The system was then tested about the ability to predict the colon versus rectum origin, metachronous or synchronous appearance, risk of recurrence after CLM resection and whether a sample was from a control or a CLM patient. RESULTS: Sensitivity, specificity, positive and negative predictive values for detecting CLM patients were 75, 100, 100 and 54.6 %, respectively. Best CLM appearance time identification was 50 % and primary tumor origin identification was 62.5 %. Best classifications of neoplastic recurrence within the first year after CLM resection and during the follow-up period were 47.5 and 45 %, respectively. Larger training sets and prevalence-based training sets led to better classification of patients and characteristics. CONCLUSION: Proteomic profiles are a promising tool for discriminating CLM patients from healthy patients and for predicting neoplastic recurrence.

Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial.

To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.

Clinical trial on the cost-effectiveness of T-tube use in an established deceased donor liver transplantation program.

The aim of our study was to assess the advantages and disadvantages of T-tube use in liver transplantation, with also paying attention to the economic costs derived from its use. Patients were prospectively randomized to T tube or no T tube. One hundred and seven patients, 53 with T tube and 54 without T tube, were analyzed. Minimum follow-up was three months. Nine patients (8.4%) had bile leak: six in the T-tube group (11.3%) and three in the group without T tube (5.5%), p = ns. Four patients (3.5%) had anastomotic biliary stenosis: one in the T-tube group (1.8%) and three in the group without T tube, p = ns. Twenty of the 53 patients (37.7%) with T tube had T-tube-related complication. The number of diagnostic and therapeutic resources were higher in the T-tube group compared with non-T tube (81 and 17 vs. 18 and 10, respectively, p <0.05). The costs of therapeutic procedures required for the treatment of complications were 28 232 euro in the T-tube group vs. 16 088 euro in the no T-tube group, p <0.05. In conclusion, the systematic use of the T tube in biliary reconstruction in liver transplantation cannot be justified.

Gene transduction of an active mutant of akt exerts cytoprotection and reduces graft injury after liver transplantation.

Akt is expected to be an effective target for the treatment of ischemia-reperfusion injury (I/R) due to its anti-apoptotic properties and its ability to activate the endothelial nitric oxide synthase (eNOS) enzyme. Therefore, this study was aimed to determine the efficacy of an active mutant of Akt (myr-Akt) to decrease I/R injury in a model of orthotopic liver transplantation in pigs. In addition, we analyzed the contribution of nitric oxide in the Akt-mediated effects by using an eNOS mutant (S1179DeNOS) that mimics the phosphorylation promoted by Akt in the eNOS sequence. Donors were treated with adenoviruses codifying for myr-Akt, S1179DeNOS or beta-galactosidase 24 h before liver harvesting. Then, liver grafts were orthotopically transplanted into their corresponding recipients. Levels of transaminases and lactate dehydrogenase (LDH) increased in all recipients after 24 h of transplant. However, transaminases and LDH levels were significantly lower in the myr-Akt group compared with vehicle. The percentage of apoptotic cells and the amount of activated-caspase 3 protein were also markedly reduced in myr-Akt-treated grafts after 4 days of liver transplant compared with vehicle and S1179DeNOS groups. In conclusion, myr-Akt gene therapy effectively exerts cytoprotection against hepatic I/R injury regardless of the Akt-dependent eNOS activation.

Cyclic RGD peptides with high affinity for alpha5beta1 integrin protect genetically fat Zucker rat livers from cold ischemia/reperfusion injury.

We tested a hypothesis that interactions between fibronectin (FN), a key extracellular matrix component, and its integrin alpha5beta1 receptor are important in the development of ischemia/reperfusion (I/R) injury of steatotic liver transplants. We examined the effect of a cyclic RGD peptide (cRGD), with high affinity for alpha5beta1 integrin, in a well-established steatotic rat liver model of ex vivo cold ischemia followed by isotransplantation. In this model, cRGD peptides were administered through the portal vein of steatotic Zucker rat livers prior to and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplants (OLTs) received an additional course of cRGD peptides 1 hour posttransplantation. cRGD peptide therapy significantly inhibited the recruitment of monocyte/macrophages, and repressed the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Moreover, it resulted in selective inhibition of inducible nitric oxide synthase (iNOS), and MMP-9 expression. Importantly, cRGD peptide therapy improved the function and histologic preservation of steatotic liver grafts, extending their 14-day survival in lean recipients from 50% in untreated to 100% in cRGD-treated OLTs. Thus, cRGD peptide-mediated blockade of FN-alpha5beta1 interaction protects against severe I/R injury otherwise experienced by steatotic OLTs.

Blockade of fibronectin-alpha4beta1 adhesive interactions down-regulates cyclooxygenase-2 inducible nitric oxide synthase and prolongs recipient survival in a 24-hour model of cold hepatic ischemia-reperfusion injury.

We investigated the effects of the connecting segment-1 (CS1) peptide, which blocks fibronectin (FN)-alpha4beta1 integrin interactions, upon recipient survival and extent of tissue injury in a well-established rat liver model of ex vivo 24-hour cold ischemia followed by isotransplantation. In this model, CS1 peptides were administered through the portal vein of rat livers prior to and after cold ischemic storage. In addition, recipients of orthotopic liver transplants (OLT) received a dose of CS1 peptides 1 hour post-OLT. CS1 peptide therapy significantly inhibited the intragraft recruitment of T lymphocytes and neutrophil activation/infiltration, and repressed important mediators of inflammation, such as cyclooxygenase-2, and inducible nitric oxide synthase expression. Importantly, CS1 peptide therapy improved function/histological preservation of liver grafts and extended their 14-day survival from 50% in control to 100% in CS1-treated OLTs. Thus, CS1 peptide-mediated blockade of FN-alpha4beta1 interaction protects against severe ischemia-reperfusion injury experienced otherwise by OLTs. These novel findings document the potential of targeting FN-alpha4beta1 in vivo interaction for improving OLT outcomes.

Fibronectin-alpha4beta1 integrin interactions modulate p42/44 MAPK phosphorylation in steatotic liver cold ischemia-reperfusion injury.

We investigated the effects of the connecting segment-1 (CS1) peptide, which blocks fibronectin (FN)-alpha4beta1 integrin interactions upon cell signaling, leukocyte migration, and secretion of proinflammatory cytokines, in a well-established steatotic rat liver model using ex vivo cold ischemia followed by isotransplantation. In this model, CS1 peptides were administered through the portal vein of steatotic Zucker rat livers prior and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplantation (OLT) received an additional 3-day course of CS1 peptides post-OLT. CS1 peptide-treated steatotic OLTs harvested at 1, 3, and 7 days showed moderated levels of p42/44 mitogen-activated protein kinase (MAPK) phosphorylation, comparable to those observed in steatotic naive livers. In contrast, p42/44 MAPK phosphorylation was found up-regulated in 1- to 3-day damaged control OLTs. However, 7-day control OLTs were characterized by virtually lack of p42/44 MAPK phosphorylation. Lack of p42/44 MAPK phosphorylation in 7-day control OLTs was correlated with massive presence of leukocytes in the grafts and elevated levels of proinflammatory cytokines. CS1 peptide-treated OLTs at 7 days showed a profound decrease in T-cell (10 +/- 3 vs 56 +/- 20, P < .03) and monocyte/macrophage (+/++ vs +++) infiltration and significantly reduced levels of cytokine expression, such as IL-2 (approximately sixfold), and IFN-gamma (approximately three- to fourfold), as compared with controls.

Cost/efficacy clinical trial about the use of T-tube in cadaveric donor liver transplant: preliminary results.

UNLABELLED: Biliary reconstruction is the most common cause of morbidity associated with orthotopic liver transplantation. Our objective was to assess the complications and hospital resources related to the use of a T-tube. MATERIAL AND METHODS: Among 95 liver transplants performed from October 2002 to November 2003, 84 patients were randomized to receive a T-tube or no T-tube. We analyzed all patients with a follow-up of at least of 3 months. RESULTS: Fifty-five transplants were analyzed with 8 months mean follow-up, including twenty eight with T-tube and twenty seven without a T-tube. No patient died during the follow-up. The overall rate of biliary complications was 45.4% (25/55) including 21/28 (75%) in the T-tube group and 4/27(14.8%) in the non-T-tube group (P < .0001). Complications related to T-tube extraction occurred in 48.2% (13/27), including 3 cholangitis and 10 leaks. The costs of hospital resources due to radiological studies were 5329 capital JE, Ukrainian for the T-tube group vs 5785 capital JE, Ukrainian for the non-T-tube group. The costs of hospital resources due to treatment were 28,280 capital JE, Ukrainian for the T-tube group vs 10,088 capital JE, Ukrainian for the non-T-tube group. CONCLUSIONS: Use of a T-tube during orthotopic liver transplantation does not seem justified. Biliary anastomosis stenting is followed by an increased incidence of complications, most of which are related to its use. Hospital stay, radiological studies, and cost of hospital resources are higher among the T-tube patients. Therefore its systematic use is not advisable.

One thousand liver transplants: the hospital clinic experience.

OBJECTIVES: Our goal was to study a consecutive series of 1000 liver transplants performed in our institution to evaluate the changes over time in donors, recipients, and results. PATIENTS AND METHODS: With the aim to evaluate differences between transplantation in the first period and the present period, the first consecutive 100 liver transplants performed from June 1988 to June 1990 (first period) were compared with the last consecutive 200 liver transplants performed from January 2001 to June 2003 (second period). RESULTS: Increased donor age, change in donor cerebral death etiology, and increasing numbers of grafts from alternative methods using cadaveric donors were observed in the second period. Piggy-back technique and the biliary anastomosis without a t-tube was also started in the second period. One-year actuarial patient survival was higher in the second period (84% vs 91.3%). The need for retransplantation in the overall series was 95%. One-, 5-, and 10-year actuarial retransplant survival was 67.7%, 51.3%, and 39.4%, respectively. CONCLUSIONS: Technical innovations, better understanding of donor and recipient aspects, and global improvements were the reasons for time-related improved results of liver transplantation.

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

AIM: To review the incidence, timing, and outcome of infectious enteritis after intestinal transplantation (IT). METHOD: A retrospective review of all patients undergoing IT at a single institution between 1991 and 2003 was analyze with standard statistical tools. RESULTS: Among 33 IT recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of infectious enteritis. The recipient demographics were 77% men and median age 2.6 years. Infections were diagnosed at a median of 76 days (32 to 1800) after IT. There were 14 viral (CMV one, rotavirus eight, adenovirus four, EBV one, three bacterial (Clostridium difficile), and three other infections (Giardia lamblia one, cryptosporidium two). Complete resolution was achieved in 17 (94%) infectious after appropriate antimicrobial or conservative therapy. Interestingly, there were six rejection episodes following infectious enteritis. Grafts were lost to rejection after rotaviral enteritis (n = 1) and adenoviral enteritis misdiagnosed as rejection (n = 1). Patient and graft survival were not adversely affected by infections. CONCLUSIONS: Infectious enteritis occurs frequently after IT. Viral agents are the cause in two-thirds of cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection by histopathology can be difficult.

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer.

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.