Travis J. McKenzie

Artificial and bioartificial liver support.

Acute liver failure (ALF) is a widespread problem with an unfavorable prognosis. Currently, liver transplantation is the only direct means of treatment for patients in ALF. Due to the scarcity of donor organs, liver support technologies are being developed and clinically tested with the intent of supporting a patient in ALF until the patient regains native liver function or until a donor organ becomes available. Two major categories of devices are currently being tested. Artificial liver support is purely mechanical, including albumin dialysis. Bioartificial devices contain cellular material. No single system has reproducibly demonstrated improvement in patient mortality. However, with the advent of new technology and cell acquisition techniques, further randomized controlled trials will be necessary to determine the role of artificial and bioartificial liver support devices in the treatment of patients with ALF.

Portal hypertension correlates with splenic stiffness as measured with MR elastography

To investigate the correlation between MR elastography (MRE) assessed spleen stiffness and direct portal vein pressure gradient (D‐HVPG) measurements in a large animal model of portal hypertension.

Role of Kupffer cells and toll-like receptor 4 in acetaminophen-induced acute liver failure.

BACKGROUND Significant morbidity associated with acute liver failure (ALF) is from the systemic inflammatory response syndrome (SIRS). Toll-like receptor 4 (TLR4) has been shown to play an integral role in the modulation of SIRS. However, little is known about the mechanistic role of TLR4 in ALF. Also, no cell type has been identified as the key mediator of the TLR4 pathway in ALF. This study examines the role of TLR4 and Kupffer cells (KCs) in the development of the SIRS following acetaminophen (APAP)-induced ALF. MATERIALS AND METHODS Five groups of mice were established: untreated wild-type, E5564-treated (a TLR4 antagonist), gadolinium chloride -treated (KC-depleted), clodronate-treated (KC-depleted), and TLR4-mutant. Following APAP administration, 72-h survival, biochemical and histologic liver injury, extent of lung injury and edema, and proinflammatory gene expression were studied. Additionally, TLR4 expression was determined in livers of wild-type and KC-depleted mice. RESULTS Following APAP administration, wild-type, TLR4-mutant, E5564-treated, and KC-depleted mice had significant liver injury. However, wild-type mice had markedly worse survival compared with the other four treatment groups. TLR4-mutant, E5564-treated, and KC-depleted mice had less lung inflammation and edema than wild-type mice. Selected proinflammatory gene expression (interleukin 1β, interleukin 6, tumor necrosis factor) in TLR4-mutant, E5564-treated, and KC-depleted mice was significantly lower compared with wild-type mice after acute liver injury. CONCLUSION This study demonstrates that survival in APAP-induced ALF potentially correlates with the level of proinflammatory gene expression. This study points to a link between TLR4 and KCs in the APAP model of ALF and, more importantly, demonstrates benefits of TLR4 antagonism in ALF.

Erratum to: The Effect of Laparoscopic Sleeve Gastrectomy with Concomitant Hiatal Hernia Repair on Gastroesophageal Reflux Disease in the Morbidly Obese

Background The effect of laparoscopic sleeve gastrectomy (LSG) on gastroesophageal reflux disease (GERD) is controversial. Although concomitant hiatal hernia repair (HHR) at the time of LSG is common and advocated by many, there are few data on the outcomes of GERD symptoms in these patients. The aim of this study was to evaluate the effect of concomitant HHR on GERD symptoms in morbidly obese patients undergoing LSG.

Aldosteronomas—State of the Art

Primary aldosteronism (PA) is the most common cause of secondary hypertension in nonsmokers. Widespread screening of unselected hypertensives has identified PA in as many as 15% of patients. With such screening efforts using the PAC/PRA ratio and PAC, the widespread prevalence of the disease has become apparent while the relative percentage of APA has decreased. PA is confirmed by demonstrating lack of aldosterone suppressibility with sodium loading. Subtype evaluation is best achieved with high resolution CT scanning and AVS in the appropriate setting. In patients with PA and a unilateral source of aldosterone excess, laparoscopic adrenalectomy is the treatment of choice with excellent outcomes and low morbidity as compared with older open approaches. Patients with IHA, or those not amenable or agreeable to surgery, are best managed with a MR antagonist.

Robotic vs. Laparoscopic Roux-En-Y Gastric Bypass: a Systematic Review and Meta-Analysis.

We aim to summarize the available literature on patients treated with robotic RYGB and compare the clinical outcomes of patients treated with robotic RYGB with those treated with the standard laparoscopic RYGB. A systematic literature search of PubMed and Scopus databases was conducted in accordance with the PRISMA guidelines. Fourteen comparative and 11 non-comparative studies were included in this study, reporting data on 5145 patients. This study points to comparable clinical outcomes between robotic and laparoscopic RYGB. Robotic-assisted RYGB was associated with significantly less frequent anastomotic stricture events, reoperations, and a decreased length of hospital stay compared with the standard laparoscopic procedures; however, these findings should be interpreted with caution given the low number and poor quality of the studies currently available in the literature.

Hepatic Resection for the Carcinoid Syndrome in Patients with Severe Carcinoid Heart Disease: Does Valve Replacement Permit Safe Hepatic Resection?

BACKGROUND Hepatic resection of metastatic carcinoid cancer can prolong survival and control symptomatic endocrinopathy. Decompensated carcinoid heart disease (CHD) can develop in some patients with metastatic carcinoid cancers, which can preclude operation for resectable hepatic metastases. We hypothesized that outcomes after hepatic resection for patients with the carcinoid syndrome after valve replacement for CHD would be similar to carcinoid patients without CHD. STUDY DESIGN We compared the survival and symptom control after hepatic resection for patients undergoing valve replacement for CHD to carcinoid patients without CHD matched for age, sex, and extent of hepatectomy. RESULTS Fourteen patients with earlier valve replacement for CHD were compared with 28 carcinoid patients without CHD. All patients had hepatic resection for metastatic carcinoid disease and carcinoid syndrome. Mean age, sex distribution, and extent of hepatectomy (major hepatectomy, 78%) was similar between groups. Mean interval from valve replacement to hepatectomy was 101 days. There was no operative mortality. Major operative morbidity, inclusive of operative blood loss and cardiorespiratory events, occurred in 28.5% and 14.2% for CHD and non-CHD groups, respectively (p = 0.16). Symptom-free survival for CHD and non-CHD groups was 69% and 81% at 1 year (p = 0.22) and 61% and 44% (p = 0.17) at 5 years, respectively. Octreotide-free survival after hepatectomy 69% and 84% (p = 0.15) at 1 year and 62% and 52% (p = 0.29) 5 years, respectively. Overall survival CHD and non-CHD groups 100% at 1 year and 100% and 70% (p = 0.002) 5 years. CONCLUSIONS Valve replacement for severe CHD is safe and hepatic resection is associated with similar outcomes as patients without CHD undergoing hepatic resection for carcinoid syndrome. Identifying resectable hepatic metastases from carcinoids in patients with severe CHD should prompt valve replacement and interval hepatic resection.

In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs

In utero cell transplantation (IUCT) can lead to the postnatal engraftment of human cells in the xenogeneic recipient. Most reports of IUCT have involved hematopoietic stem cells. It is unknown whether human hepatocytes used for IUCT in fetal pigs will lead to the engraftment of these same cells in the postnatal environment. In this study, fetal pigs received direct liver injections of 1 × 107 human hepatocytes in utero and were delivered by cesarean section at term. The piglets received a second direct liver injection of 5 × 107 human hepatocytes 1 week after birth. The serum was analyzed for human albumin 2, 4, and 6 weeks after engraftment. Piglet livers were harvested 6 weeks after transplantation and were examined by immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization for human‐specific sequences. Piglets undergoing IUCT with human hepatocytes that were postnatally engrafted with human hepatocytes showed significant levels of human albumin production in their serum at all postengraftment time points. Human albumin gene expression, the presence of human hepatocytes, and the presence of human beta‐2 microglobulin were all confirmed 6 weeks after engraftment. IUCT in fetal pigs with human hepatocytes early in gestation allowed the engraftment of human hepatocytes, which remained viable and functional for weeks after transplantation. IUCT followed by postnatal engraftment may provide a future means for large‐scale expansion of human hepatocytes in genetically engineered pigs. Liver Transpl 19:328–335, 2013.

Optimization of mass transfer for toxin removal and immunoprotection of hepatocytes in a bioartificial liver.

This study was designed to determine optimal operating conditions of a bioartificial liver (BAL) based on mass transfer of representative hepatotoxins and mediators of immune damage. A microprocessor‐controlled BAL was used to study mass transfer between patient and cell compartments separated by a hollow fiber membrane. Membrane permeability (70, 150, or 400 kDa molecular weight cut‐off—MWCO), membrane convection (high: 50 mL/min; medium: 25 mL/min; low: 10 mL/min; diffusion: 0 mL/min), and albumin concentration in the cell compartment (0.5 or 5 g%) were considered for a total of 24 test conditions. Initially, the patient compartment contained pig plasma supplemented with ammonia (0.017 kDa), unconjugated bilirubin (0.585 kDa), conjugated bilirubin (0.760 kDa), TNF‐α (17 kDa), pig albumin (67 kDa), pig IgG (147 kDa), and pig IgM (900 kDa). Mass transfer of each substance was determined by its rate of appearance in the cell compartment. Membrane fouling was assessed by dextran polymer technique. Of the three tested variables (membrane pore size, convection, and albumin concentration), membrane permeability had the greatest impact on mass transfer (P < 0.001). Mass transfer of all toxins was greatest under high convection with a 400 kDa membrane. Transfer of IgG and IgM was insignificant under all conditions. Bilirubin transfer was increased under high albumin conditions (P = 0.055). Fouling of membranes ranged from 7% (400 kDa), 24% (150 kDa) to 62% (70 kDa) during a 2‐h test interval. In conclusion, optimal toxin removal was achieved under high convection with a 400‐kDa membrane, a condition which should provide adequate immunoprotection of hepatocytes in the BAL. Biotechnol. Bioeng. 2009; 104: 995–1003.

Recalcitrant hypocalcemia after thyroidectomy in patients with previous Roux-en-Y gastric bypass

BACKGROUND Hypocalcemia is a potential complication after thyroidectomy. Patients with previous roux-en-Y gastric bypass (RYGBP) may be at increased risk for recalcitrant symptomatic hypocalcemia after thyroidectomy. This complication is poorly described and there is no current consensus on optimal management in this unique population. METHODS All patients from 2000 to 2012 who underwent thyroidectomy with history of preceding RYGBP were identified retrospectively. Each of the 19 patients meeting inclusion criteria were matched 2:1 for age, gender, and body mass index (BMI) to a cohort who underwent thyroidectomy without previous RYGBP. The study cohort and matched controls were compared for incidence of symptomatic postoperative hypocalcemia, requirement of intravenous (IV) calcium supplementation, and duration of hospital stay. RESULTS Age, proportion of female patients, and BMI were equivalent between cases (n = 19) and controls (n = 38). Comparison of primary outcomes demonstrated that the study group had a significantly higher incidence of symptomatic hypocalcemia (42% vs. 0%; P < .01), administration of IV calcium (21% vs. 0%; P < .01), and duration of hospital stay (2.2 vs. 1.2 days, P = .02). CONCLUSION Patients with previous RYGBP have a greater incidence of recalcitrant symptomatic hypocalcemia after thyroidectomy, resulting in prolonged duration of hospital stay. In this patient population, calcium levels should be closely monitored and early calcium and vitamin D supplementation initiated preemptively.