Research Spotlight

Zhang, J. and P. A. McCullough (2016). “Lipoic acid in the prevention of acute kidney injury.” Nephron 134(3): 133-140.

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Hypoxia, reactive oxygen species (ROS) and oxidative stress contribute to contrast-induced acute kidney injury (CI-AKI) and ischemic reperfusion injury (IRI) in the kidney and heart. Imbalance between the increased formation of ROS by hypoxia in the cardiac and renal tissue and the low availability of endogenous antioxidants is a common cause of cellular and tissue damage. Therefore, a strategy to inhibit ROS generation or to scavenger free radicals becomes an important intervention to prevent CI-AKI and myocardial IRI. Evidence has shown that a naturally occurring cellular antioxidant lipoic acid (LA) (1,2-dithilane-3-pentanoic acid) acts as a free radical scavenger of ROS and reactive nitrogen oxide species for cardioprotection and renoprotection. The mechanisms whereby LA exerts its protective effects are not entirely understood, but may be related to the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway and the PI3-kinase/Akt pathways. This review will provide the current information of LA as an exogenous antioxidant for cardioprotection and renoprotection, with emphasis on antioxidant functions of LA and multiple signaling pathways underlying protective effects of LA on CI-AKI as well as cardiac and renal IRI.

Zaydfudim, V. M., N. Vachharajani, G. B. Klintmalm, W. R. Jarnagin, A. W. Hemming, M. B. Doyle, K. M. Cavaness, W. C. Chapman and D. M. Nagorney (2016). “Liver resection and transplantation for patients with hepatocellular carcinoma beyond milan criteria.” Ann Surg: 2016 Jul [Epub ahead of print].

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OBJECTIVES: To assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria. BACKGROUND: The role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center. METHODS: Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival. RESULTS: Of 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P >/= 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P /= 0.017). CONCLUSIONS: Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

Yoshimatsu, G., M. Takita, M. A. Kanak, W. Z. Haque, C. Chang, S. P. Balaji, M. C. Lawrence, M. F. Levy and B. Naziruddin (2016). “Mir-375 and mir-200c as predictive biomarkers of islet isolation and transplantation in total pancreatectomy with islet autotransplantation.” J Hepatobiliary Pancreat Sci: 2016 Jul [Epub ahead of print].

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BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a promising treatment for refractory chronic pancreatitis. Predictable biomarkers for the endocrine function after transplantation would be helpful in selecting patients for TPIAT. This study aims to identify novel biomarkers for predicting the outcome of islet isolation and transplantation in TPIAT patients. METHODS: This paper studied microRNA of 31 TPIAT patients and 11 deceased donors from plasma samples before TPIAT. MiR-7, miR-200a, miR-200c, miR-320, and miR-375 were analyzed along with patient characteristics and the outcomes of islet isolation and transplantation via univariate and multivariate regression analysis. RESULTS: MiR-375 before TPIAT showed a significant correlation with C-peptide (r = -0.396, P = 0.03) and post-digestion islet count (r = -0.372, P = 0.04). And also miR-200c was significantly correlated with insulin requirement, C-peptide, and SUITO index at 1 year after transplantation. Moreover it was confirmed that miR-200c was a predictable factor of endocrine outcome in multi regression analysis (coefficient = -7.081, P = 0.001). CONCLUSIONS: We concluded that miR-375 and miR-200c could potentially serve as novel biomarkers in predicting the islet yield in islet isolation and the metabolic function after transplantation for chronic pancreatitis patients.

Trotter, J. F. and A. Cardenas (2016). “Liver transplantation around the world.” Liver Transpl 22(8): 1059-1061.

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In the recent issues of Liver Transplantation, we have asked transplant doctors and colleagues from around the world to share insights about the state of liver transplantation in their countries. The purpose of these articles is to provide a perspective for each of us to learn how our colleagues organize and provide transplant services based on the challenges and opportunities in their different settings. By learning from the experience of these different countries, we hope that individual physicians might improve their own programs or appreciate the benefits that they might enjoy. To a great extent, the practice of liver transplantation within each country is a reflection of its own unique culture. Western countries are more organized, regulated, and have reached a plateau of transplant volume, whereas emerging countries are less systematic and growing rapidly in both their capabilities and volumes. We hope that these reviews will help provide a better appreciation for the practice of liver transplant within each of our countries by reviewing the experiences reported by Australia, New Zealand, Brazil, Germany, India, Ireland, Japan, Spain, and the United Kingdom. In future issues, authors from more countries around the globe will be invited to also share their experiences.

Thorud, J. C., D. C. Jupiter, J. Lorenzana, T. T. Nguyen and N. Shibuya (2016). “Reoperation and reamputation after transmetatarsal amputation: A systematic review and meta-analysis.” J Foot Ankle Surg: 2016 Jul [Epub ahead of print].

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Transmetatarsal amputations have generally been accepted as a relatively more definitive amputation compared with other lesser ray resections. However, many investigators have reported a high occurrence of more proximal amputation after transmetatarsal amputation. A systematic review was performed to evaluate the occurrence of reamputation and reoperation after transmetatarsal amputations. A search of the Medline, CINAHL, and Cochrane Central databases yielded 159 abstracts. After review, 24 reports were included in the study. A total of 391 (26.9%) reoperations were identified after 1453 transmetatarsal amputations. Any level reamputation occurred in 152 (29.7%) of 365 transmetatarsal amputations and major amputation occurred in 380 (33.2%) of 1146 transmetatarsal amputations. Using a random effects model, the reoperation rate was estimated at 24.43% (95% confidence interval 11.64% to 37.21%), the reamputation rate was estimated at 28.37% (95% confidence interval 19.56% to 37.19%), and the major amputation rate was estimated at 30.16% (95% confidence interval 23.86% to 36.47%). These findings raise questions about the conventional wisdom of performing primary transmetatarsal amputation in lieu of other minor amputations, such as partial first ray amputation, and suggest that the choice between transmetatarsal amputation and other minor amputations might be a decision that depends on very patient-specific factors.