Research Spotlight

Posted October 15th 2016

Liver transplantation for “very early” intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

Göran Klintmalm M.D.

Göran Klintmalm M.D.

Sapisochin, G., M. Facciuto, L. Rubbia-Brandt, J. Marti, N. Mehta, F. Y. Yao, E. Vibert, D. Cherqui, D. R. Grant, R. Hernandez-Alejandro, C. H. Dale, A. Cucchetti, A. Pinna, S. Hwang, S. G. Lee, V. G. Agopian, R. W. Busuttil, S. Rizvi, J. K. Heimbach, M. Montenovo, J. Reyes, M. Cesaretti, O. Soubrane, T. Reichman, J. Seal, P. T. Kim, G. Klintmalm, C. Sposito, V. Mazzaferro, P. Dutkowski, P. A. Clavien, C. Toso, P. Majno, N. Kneteman, C. Saunders and J. Bruix (2016). “Liver transplantation for “very early” intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.” Hepatology 64(4): 1178-1188.

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The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that “very early” iCCA (single tumors 2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the “very early” iCCA group and 33/48 (69%) the “advanced” group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the “advanced” group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results.


Posted October 15th 2016

Data sharing: lessons from Copernicus and Kepler.

Milton Packer M.D.

Milton Packer M.D.

Packer, M. (2016). “Data sharing: Lessons from copernicus and kepler.” Bmj 354: i4911.

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To understand the workings of science, pick up a copy of De Revolutionibus Orbium Coelestium. Published with great reluctance by the astronomer Nicolaus Copernicus in 1543, the book puts forth a compelling argument for a heliocentric universe. Turn the pages and you will see the book is filled with data. Whose data? Copernicus relied on the data collected by others in addition to his own to formulate his revolutionary theory. Publication of these data subsequently allowed Johannes Kepler to identify discrepancies, which led to his innovative proposal in 1605 that the planets moved in an ellipse (rather than in a circle), an idea that he had previously assumed to be too simple for earlier astronomers to have overlooked. Of course, Kepler presented his data at the same time that he published his conclusions. In contrast, Tycho Brahe (who opposed Copernicus) famously withheld his astronomical data from Kepler because he knew they could be used to confirm Copernicus’s heliocentric model.


Posted October 15th 2016

Contrast-Induced Acute Kidney Injury.

Peter McCullough M.D.

Peter McCullough M.D.

McCullough, P. A., J. P. Choi, G. A. Feghali, J. M. Schussler, R. M. Stoler, R. C. Vallabahn and A. Mehta (2016). “Contrast-induced acute kidney injury.” J Am Coll Cardiol 68(13): 1465-1473.

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Coronary angiography and percutaneous intervention rely on the use of iodinated intravascular contrast for vessel and chamber imaging. Despite advancements in imaging and interventional techniques, iodinated contrast continues to pose a risk of contrast-induced acute kidney injury (CI-AKI) for a subgroup of patients at risk for this complication. There has been a consistent and graded signal of risk for associated outcomes including need for renal replacement therapy, rehospitalization, and death, according to the incidence and severity of CI-AKI. This paper reviews the epidemiology, pathophysiology, prognosis, and management of CI-AKI as it applies to the cardiac catheterization laboratory.


Posted October 15th 2016

Simple Method for Microscopic Confirmation of Previous Biopsy Site.

John R. Griffin M.D.

John R. Griffin M.D.

Tran, C. and J. R. Griffin (2016). “Simple method for microscopic confirmation of previous biopsy site.” Am J Dermatopathol 38(10): 791-792.

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Aluminum chloride is commonly used by dermatologists as a hemostatic agent after minor surgical procedures such as shave skin biopsies. Two studies have reported that aluminum chloride induces proliferation of histiocytes with aluminum-containing basophilic cytoplasmic granules in biopsy sites.1,2 These aluminum granulomas can be used to identify specimens obtained from previous biopsy sites, such as a reexcision specimen.1 However, the granules may be difficult to visualize with routine hematoxylin and eosin staining.2 The ability to identify that a specimen is from a previous biopsy site is important because rebiopsied tissue may not be labeled as such when submitted for histologic analysis.


Posted October 15th 2016

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria.

Göran Klintmalm M.D.

Göran Klintmalm M.D.

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 264(4): 650-658.

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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. 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.