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Here we present the case of a cystic fibrosis (CF) patient with preserved pulmonary function who developed acute liver failure requiring liver transplant following an episode of binge drinking and ingestion of a modest amount of acetaminophen. Cystic Fibrosis Liver Disease (CFLD) is the third most common cause of death among CF patients. The pathogenesis of CFLD is complex and still not fully understood. It is important that patients suffering from CF know about the possible dangers associated with acetaminophen and ethanol ingestion. Our case report highlights the need for more research that needs to be done to truly understand the underlying pathogenesis of CFLD and the significant risk factors that play a part in the development of acute liver failure in patients with CF.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score &gt, 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0&ndash, 10%, 11&ndash, 20%, &gt, 20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0&ndash, 10% GS (58.0%), 11&ndash, 20% GS (13.5%), &gt, 20% GS (19.7%), 8.8% were not biopsied. The rate of kidney discard was 48.5%, 33.6% in 0&ndash, 10% GS, 68.9% in 11&ndash, 20% GS, and 77.4% in &gt, 20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0&ndash, 10% GS, 70.9% for &gt, 10% GS, and 74.8% for the no biopsy group. Among kidneys with &gt, 10% GS, there was no significant difference in death-censored graft survival between 11&ndash, 20% GS and &gt, 20% GS. Recipients with &gt, 10% GS had an increased risk of graft failure (HR = 1.27, p &lt, 0.001), compared with 0&ndash, 10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and &gt, 10% GS. Conclusion: In &gt, 85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS &gt, 10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

From 1991 to 2013, Mississippi was without liver transplant services. In 2013, a new liver transplant program was established at the University of Mississippi Medical Center. Here, we describe our experience with the first 150 transplants over a 4.5-year period. This study is a review of 147 patients who underwent the first 150 liver transplants at the University of Mississippi Medical Center between March 5, 2013, and January 4, 2018. There were no exclusion criteria for this study. Donor, recipient, and outcome variables were analyzed. Recipients were 46% female and 74% white. Age at the time of transplant was 57 [IQR 49–63]. BMI at transplant was 30 [IQR 25–35]. Thirty per cent of transplants were for alcoholic cirrhosis, 25% non-alcoholic steatohepatitis, 24% hepatitis C, and 12% cholestatic. Mean model for end-stage liver disease (MELD) at the time of transplant was 20 [95% confidence interval 19–21] and MELD-Na was 22 [95% confidence interval 20–23]. One-year patient- and graft survival were 89% and 87%, respectively, which were as expected based on Scientific Registry of Transplant Recipient reports after risk adjustment. The data published here verifies it is possible to establish a new liver transplant center in an underserved area previously lacking comprehensive liver care and to achieve results similar to other high-volume centers across the country.

Background Chronic, obliterative portal vein (PV) thrombosis (PVT) represents a relative contraindication to liver transplantation (LT) in some centers. When PV thromboembolectomy is not feasible, alternative techniques (portacaval hemitransposition, portal arterialization, multivisceral transplantation) are associated with suboptimal outcomes. In cases where a chronically thrombosed PV has become obliterated, we developed PV recanalization (PVR)-transjugular intrahepatic portosystemic shunt (TIPS) to potentiate LT. We evaluated the impact of PVR-TIPS on liver function, transplant eligibility, and long-term outcomes after LT. Methods Forty-four patients with chronic obliterative main PVT were identified during our institutional LT selection committee. After joint imaging review by transplant surgery/radiology, these patients underwent PVR-TIPS to potentiate transplant eligibility. Patients were followed by hepatology/transplant until LT, and ultimately in posttransplant clinic. The TIPS venography and serial ultrasound/MRI were used subsequently to document PV patency. Results The main PV (MPV) was completely thrombosed in 17 of 44 (39%) patients; near complete (>95%) occlusion was noted in 27 of 44 (61%) patients. Direct transhepatic and transsplenic punctures were required in 11 of 43 (26%) and 3 of 43 (7%) cases, respectively. Technical success was 43 of 44 (98%) cases. At PVR-TIPS completion, persistence of MPV thrombus was noted in 33 of 43 (77%) cases. One-month TIPS venography demonstrated complete resolution of MPV thrombosis in 22 of 29 (76%) without anticoagulation. Thirty-six patients were listed for transplantation; 18 (50%) have been transplanted. Eighty-nine percent MPV patency rate and 82% survival were achieved at 5 years. Conclusions The PVR-TIPS may be considered for patients with obliterative PVT who are otherwise appropriate candidates for LT. The high rate of MPV patency post-TIPS placement suggests flow reestablishment as the dominant mechanism of thrombus resolution.

Background The goal of this study was to assess systems and processes involved in the operating room (OR) to intensive care unit (ICU) handoff in an attempt to understand the criticality of specific steps of the handoff. Methods We performed a failure modes, effects, and criticality analysis (FMECA) of the OR to ICU handoff of deceased donor liver transplant recipients using in-person observations and descriptions of the handoff process from a multidisciplinary group of clinicians. For each step in the process, failures were identified along with frequency of occurrence, causes, potential effects and safeguards. A Risk Priority Number (RPN) was calculated for each failure (frequency × potential effect × safeguard; range 1-least risk to 1,000-most risk). Results Using FMECA, we identified 37 individual steps in the OR to ICU handoff process. In total, 81 process failures were identified, 22 of which were determined to be critical and 36 of which relied on weak safeguards such as informal human verification. Process failures with the greatest risk of harm were lack of preliminary OR to ICU communication (RPN 504), team member absence during handoff communication (RPN 480), and transport equipment malfunction (Risk Priority Number 448). Conclusion Based on the analysis, recommendations were made to reduce potential for patient harm during OR to ICU handoffs. These included automated transfer of OR data to ICU clinicians, enhanced ICU team member notification processes and revision of the postoperative order sets. The FMECA revealed steps in the OR to ICU handoff that are high risk for patient harm and are currently being targeted for process improvement.

Vascular access is the lifeline of the hemodialysis patient. However, many patients lack early nephrology care that results in late referral for vascular access placement and dialysis initiation with a central venous catheter in 80% of the United States incident dialysis population. Despite these hurdles, arteriovenous fistulae (AVF) have doubled, to 65%, in the United States prevalent hemodialysis population over the last decade. The endovascular revolution has resulted in better rescue and maintenance of established AVF and arteriovenous grafts (AVG). Newer conduits are available for those needing an AVG, and a number of devices have been approved or are in trials to address specific issues, such as high-grade central stenosis, deep AVF, slow maturation, need for immediate cannulation, and persistent backwall injury. Finally, new techniques to deal with distal hypoperfusion ischemic syndrome, or “steal syndrome,” have been developed.

Laparoscopic approaches to complex hepatobiliary cases are becoming more commonplace. As the practice of living donor liver transplants (LDLT) has evolved into an accepted alternative for certain patients as a source of donor organs, the application of laparoscopic techniques to these operations has also been introduced with an interest in improving donor outcomes and potential appeal of the donor procedure. The scope of laparoscopy ranges from the laparoscopically assisted left or right hepatic lobectomy (“hybrid”) approach, to pure laparoscopic left lateral segments. Recently, robotic and purely laparoscopic approaches to right and left lobes have been reported by advanced minimally invasive surgeons with extensive experience in robotic and laparoscopic liver resection. Safety remains paramount to the performance of LDLT, and laparoscopic techniques must always be considered in light of optimal donor safety.

Inflammatory bowel diseases such as ulcerative colitis represent serious health burdens, both because of the tissue-damaging disease itself, and because of an elevated risk of colon cancer. The increased expression of many members of the matrix metalloproteinase (MMP) family of enzymes that occurs in colitis, has long been associated with the destructive nature of the disease. Recent findings in cancer and other MMP-associated diseases, however, led us to question whether MMPs are indeed detrimental in the setting of colitis. Here, we focus on a single MMP family member, MMP10, and assess its role in a murine model of colonic tissue damage induced by dextran sulphate sodium (DSS) treatment. Using mice genetically deficient for MMP10, we find that absence of this enzyme leads to significantly worse disease scores and failure to resolve inflammation even after extended recovery periods. We show that MMP10 is produced predominantly by infiltrating myeloid cells in both murine and human colitis. Through bone marrow transplant experiments, we confirm that bone marrow-derived MMP10 contributes to colitis severity. Mice lacking MMP10 have a significantly higher propensity for development of dysplastic lesions in the colon after two rounds of DSS exposure. Thus, we conclude that MMP10 is required for resolution of DSS-induced colonic damage, and in its absence, chronic inflammation and ultimately dysplasia occurs.

This meta-analysis was conducted with the aims to summarize all available evidence on (1) prevalence of pre-existing atrial fibrillation (AF) and/or incidence of AF following kidney transplantation; (2) the outcomes of kidney transplant recipients with AF; and (3) the trends of estimated incidence of AF following kidney transplantation over time. A literature search was conducted utilizing MEDLINE, EMBASE, and the Cochrane Database from inception through March 2018. We included studies that reported (1) prevalence of pre-existing AF or incidence of AF following kidney transplantation or (2) outcomes of kidney transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018086192). Eight cohort studies with 137,709 kidney transplant recipients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing kidney transplantation was 7.0% (95% CI: 5.6–8.8%) and pooled estimated incidence of AF following kidney transplantation was 4.9% (95% CI: 1.7–13.0%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF (p = 0.93) or post-operative AF after kidney transplantation (p = 0.16). The pooled odds ratios (OR) of mortality among kidney transplant recipients with AF was 1.86 (3 studies; 95% CI: 1.03–3.35). In addition, AF is also associated with death-censored allograft loss (2 studies; OR: 1.55, 95% CI: 1.02–2.35) and stroke (3 studies; OR: 2.54, 95% CI: 1.11–5.78) among kidney transplant recipients. Despite advances in medicine, incidence of AF following kidney transplant does not seem to decrease over time. In addition, there is a significant association of AF with increased mortality, allograft loss, and stroke after kidney transplantation.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It represents the fifth most common cancer worldwide, and one whose incidence is on the rise. Liver cancer is the third most common cause of cancer mortality globally and thus a major health concern worldwide. Therapeutic options for this tumor include surgical resection, local ablative therapies, and systemic treatment. Liver transplantation has emerged as a highly effective treatment for patients with HCC, particularly in the setting of significant underlying liver disease. Current protocols in transplantation for this tumor utilize strict size criteria and staging (TNM classification) to select patients for this therapy. Selection criteria for liver transplantation for HCC that are accepted in the U.S. include: 1 tumor < 5cm, no greater than three tumor nodules, each less than 3cm in diameter 3) no macroscopic invasion of blood vessels or lymph nodes, and no extra-hepatic spread of tumor. Eligibility criteria and immunosuppression strategies are continuing to evolve in this field. Nonetheless, in appropriately selected patients, liver transplantation may provide a cure for HCC with survival rates equal to that of liver transplantation for end-stage liver disease (ESLD) from other causes. Liver transplantation has been established as one of the principal treatment modalities for this difficult disease.

Background/aim: The anterior and posterior vagal trunks supply the each side of the gastric mucosa separately, and the denervation of either side does not impair the functional capacity of the other, leaving gastric acid output and circulating gastrin levels unchanged. In this study, we investigated the importance of the neural innervation and the brain-gut axis in cancer initiation by performing vagotomy in hypergastrinemic transgenic (INS-GAS) mice with a phenotype of spontaneous gastric cancer. Methods: Age/sex matched wild-type (WT) and INS-GAS mice were killed at 1, 2, 4, 6, 8, 10 and 12 months of age (at least 10 mice/ group) for histological examination of gastric cancer. INS-GAS mice at 6 months of age were randomized into 4 groups of surgery: unilateral anterior truncal vagotomy (29 mice), bilateral truncal vagotomy with pyloroplasty (24), pyloroplasty (27), and sham operation (25). Both the anterior and posterior sides of the stomachs were removed at 6 months postoperatively (i.e., 12 months of age) for pathological and immunohistochemical analyses. Results: Gastric cancer was found neither in WT mice regardless of age nor in INS-GAS mice that were

Ulcerative colitis is the most common inflammatory bowel disease, and is associated with increased risk of colon cancer. Understanding the mechanisms by which carcinogenesis occurs in the setting of colitis could lead to both prevention strategies and improved therapies. Matrix metalloproteinase-10 (MMP10), a member of the matrix metalloproteinase family of proteolytic enzymes, is expressed at healing edges of colonic ulcers. Although MMPs are usually considered as destructive players in inflammatory disease, we considered the possibility that MMP10 had a beneficial role in ulcerative colitis. We used dextran sulfate sodium (DSS) treatment in MMP10-null and corresponding control wild-type mice to investigate the consequences of MMP10 deletion on colitis development and recovery. Groups of mice were exposed to DSS for 7-day periods and sacrificed at different timepoints following the cessation of the DSS. Strikingly, MMP10-null mice were more severely affected by the treatment as determined by gross observations such as weight loss and colon length. Histological analysis at the various timepoints indicated that wild-type mice showed almost complete recovery from DSS within 14 days after DSS treatment. In contrast, MMP10-null mice still showed clear signs of damage with persistent inflammatory foci and non-healing ulcers. In situ hybridization indicated MMP10 expression predominantly in inflammatory cells, although some fibroblasts were also positive. Colonic epithelium was negative for MMP10. Bone marrow transplant experiments indicated that wild-type bone marrow partially rescued the MMP10-null phenotype. Measurement of cytokines by ELISA in colonic lavage fluid from MMP10-null and wild-type mice showed that IL-1α was significantly increased in the absence of MMP10. Levels of other cytokines such as TNFα, IL6, IL17 and G-CSF were not different. Multiple exposures to DSS results in conversion of an acute colitis to a chronic inflammatory disease. With only 2 DSS exposures, MMP10-null mice manifested a chronic condition which failed to resolve even after 3 months. Similarly-treated wild-type mice, however, appeared normal at this timepoint. Examination of the colonic tissue from the DSS double exposure showed a significant increase in the number of dysplastic foci present in the MMP10-null mice. Thus, expression of MMP10 appears necessary for resolution of colitis, and in its absence, the development of chronic colitis results in tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1351.