Aberrant hepatic trafficking of gut-derived T cells is not specific to primary sclerosing cholangitis.

BACKGROUND AND AIMS: The "gut homing" hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut-derived T cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here, we examine "the gut homing theory" in patients with PSC with associated inflammatory bowel disease (PSC-IBD) and across multiple inflammatory liver diseases. APPROACH AND RESULTS: Expression of MAdCAM-1, CCL25, and E-Cadherin were assessed histologically and using RT-PCR on explanted liver tissue from patients with CLD undergoing OLT and in normal liver. Liver mononuclear cells were isolated from explanted tissue samples and the expression of gut homing integrins and cytokines on hepatic infiltrating gut-derived T cells was assessed using flow cytometry. Hepatic expression of MAdCAM-1, CCL25 and E-Cadherin was up-regulated in all CLDs compared with normal liver. There were no differences between disease groups. Frequencies of α4ß7, αEß7, CCR9, and GPR15 expressing hepatic T cells was increased in PSC-IBD, but also in CLD controls, compared with normal liver. ß7 expressing hepatic T cells displayed an increased inflammatory phenotype compared with ß7 negative cells, although this inflammatory cytokine profile was present in both the inflamed and normal liver. CONCLUSIONS: These findings refute the widely accepted "gut homing" hypothesis as the primary driver of PSC and indicate that aberrant hepatic recruitment of gut-derived T cells is not unique to PSC, but is a panetiological feature of CLD.

Multivisceral Resection for Locally Invasive Colorectal Liver Metastases: Outcomes of a Matched Cohort Analysis.

Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections. METHODS: From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period. RESULTS: Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted. CONCLUSION: In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to -surgery with comparable morbidity and mortality rates to -isolated hepatectomy.

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence?

The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Total hepatectomy and liver transplantation as a two-stage procedure for fulminant hepatic failure: A safe procedure in exceptional circumstances.

AIM: To evaluate the outcomes of two-stage liver transplant at a single institution, between 1993 and March 2015. METHODS: We reviewed our institutional experience with emergency hepatectomy followed by transplantation for fulminant liver failure over a twenty-year period. A retrospective review of a prospectively maintained liver transplant database was undertaken at a national liver transplant centre. Demographic data, clinical presentation, preoperative investigations, cardiocirculatory parameters, operative and postoperative data were recorded. RESULTS: In the study period, six two-stage liver transplants were undertaken. Indications for transplantation included acute paracetamol poisoning (n = 3), fulminant hepatitis A (n = 1), trauma (n = 1) and exertional heat stroke (n = 1). Anhepatic time ranged from 330 to 2640 min. All patients demonstrated systemic inflammatory response syndrome in the first post-operative week and the incidence of sepsis was high at 50%. There was one mortality, secondary to cardiac arrest 12 h following re-perfusion. Two patients required re-transplantation secondary to arterial thrombosis. At a median follow-up of 112 mo, 5 of 6 patients are alive and without evidence of graft dysfunciton. CONCLUSION: Two-stage liver transplantation represents a safe and potentially life-saving treatment for carefully selected exceptional cases of fulminant hepatic failure.

Candidiasis intraabdominal masiva secundaria a cirugías digestivas en pacientes inmunocompetentes. A propósito de 2 casos / Massive intra-abdominal candida infection secondary to digestive surgery in inmunocompetent patients: A report on 2 cases

La perforación asociada a infección intraabdominal difusa por Candida spp. es excepcional. Suele asociarse a pacientes inmunodeprimidos o con enfermedad tumoral avanzada. Presentamos 2 casos de perforación digestiva secundaria a candidiasis invasiva. En el primer caso, una mujer de 68 años con una perforación duodenal secundaria a Candida spp., se realiza laparotomía exploradora y reparación de la perforación duodenal. Sin embargo, la paciente requiere más de 2 intervenciones, observándose Candida spp. macroscópica diseminada por toda la cavidad abdominal. El segundo caso es el de un varón de 60 años que presenta un postoperatorio complicado de una hemicolectomía derecha, que se asocia con pancretitis, y con posterior diseminación fúngica abdominal secundaria a Candida parapsilopsis, con múltiples complicaciones infecciosas. En ambos casos se intentó un tratamiento basado en resección quirúrgica y cambio de anti-fúngicos, sin éxito. El tratamiento antifúngico precoz evita la diseminación hematógena y el shock séptico, disminuyendo la morbimortalidad de estos pacientes.

Candida spp. as cause of diffuse intraabdominal infection is very rare. Often associated with immunocompromised or patients with advanced tumor disease. We are reporting 2 cases of gastrointestinal perforation secondary to invasive candidiasis. The first case, a 68 years old female with a Candida spp. duodenal perforation. An emergency exploratory laparotomy was performed and a duodenal perforation repair was done. However, the patient required 2 more reoperation due to Candida spp. macroscopic intra-abdominal disemination. The second case, is presented in the context of a postoperative period of a right hemicolectomy, pancreatitis associating abdominal spread and subsequent secondary fungal Candida parapsilopsis with multiple infectious complications. In both cases there were unsuccessful surgical resection and antifungal change. The early antifungal treatment prevents hematogenous dissemination and septic shock, reducing the morbidity and mortality of these patients.