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Penn Evidence-Based Literature Review (PEBLR)
Summarized highlights from contemporary literature in surgical and allied disciplines for general surgery residents.
July 2016
  1. Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors.
    Orandi et al., New England Journal of Medicine 2016 (PDF)
    Contributor: David Aufhauser
    Discipline: Transplant Surgery
Brief Summary
Synopsis: Many patients on the renal transplant waiting list are sensitized to HLA antigens either to pregnancy, blood transfusions, and increasingly, prior transplant; finding compatible organs for these patients can be challenging even if they have willing living donors and they often spend a long time on the waitlist. This was a 22-center retrospective case controlled study over 10 years comparing survival benefit of a strategy of desensitization followed by HLA-incompatible living donor transplant (n=1025) with waiting for a deceased donor transplant. The authors conclude that desensitization and HLA-incompatible living donor transplant was associated with reduced risk of death (reduced by factor of 1.83, P<0.001). Flaws in this study: 1. Deceased donor control groups were poorly matched to the desensitization groups with differences in patient socioeconomic support, immune function, and fitness for transplant; 2. Criteria for a patient being "HLA-incompatible" is highly variable center to center; many patients included would not have been consider incompatible at other centers; 3. Deceased donor waitlist survival data is obsolete with changes in allocation system to increase priority for sensitized patients; 4. Idea of desensitization and HLA-incompatible living donor is also nearly obsolete with non-controversial evidence that compatible living donor is superior and with advances in computer algorithms to facilitate paired or chain exchanges at regional and national level.
  1. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients with Acute Kidney Injury: The ELAIN randomized trial.
    Zarbock et al., JAMA 2016 (PDF)
    Contributor: Grace Lee
    Discipline: Surgical Critical Care/Trauma/Acute Care Surgery
Brief Summary
Synopsis: Acute kidney injury is common and previously demonstrated to affect morbidity and mortality; however, the optimal timing and the benefits/harms of CRRT decisions are not well known. The ELAIN trial is a randomized parallel group trial at a single center in Germany comparing early (<8hr from diagnosis of AKI) vs. late (>8hr from diagnosis of AKI) use of CRRT, primarily in critically ill surgical patients meeting extensive inclusion criteria. Results demonstrated a significant mortality benefit (HR 0.66), increased renal recovery (OR 0.55), shorter time on RRT (HR 0.69), and shorter hospital stays (HR 0.34) in the early CRRT cohort. The major limitation of this study is that it is a small single center trial but findings are compelling to initiate a multicenter trial to evaluate these benefits.
  1. Can Laparoscopic Cholecystectomy Prevent Recurrent Idiopathic Acute Pancreatitis? A Prospective Randomized Multicenter Trial.
    Raty et al. Annals of Surgery Nov 2015 (PDF)
    Summary by: Brett Ecker
    Discipline: General Surgery/MIS/Colorectal
Brief Summary
Synopsis: The authors hypothesize that idiopathic acute pancreatitis may often be due to microlithiaisis; despite negative conventional US imaging, laparoscopic cholecystectomy can prevent pancreatitis recurrence. A multicenter RCT of 85 (39 cholecystectomy, 46 control) patients in Finland performed. At median follow-up of 36 (5–58) months, recurrence rate was higher in the control group (14/46 vs. 4/39, P=0.016).  During surgery, nearly 60% of gallbladders were found to contain biliary stones or sludge undetected by US. A total of 5 patients needed to be treated (NNT-value) to prevent 1 episode of recurrent pancreatitis. Limitations of this study: 1. MRCP was not available at all participating institutions (utilized in 32% of cases); 2. genetic testing for CF (CFTR) or autoimmune pancreatitis (PRSS1 and SPINK-1) was guided only by family history without exclusion for index cases.
  1.  RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases.
    Brudwik et al. Annals of Surgical Oncology 2016 (PDF)
    Summary by: Jash Datta
    Discipline: Surgical Oncology/HPB/Cancer Biology, Immunology
Brief Summary
Synopsis: In an era of increasing molecular and immune-based prognostication in cancer treatment, surgical decision-making guided by such factors has lagged similar paradigms in other oncologic disciplines. Mutant RAS (mRAS) in colorectal liver metastasis (CRLM) are associated with unfavorable tumor biology and worse surgical/cancer outcomes. This was a single-institution study of 663 patients between 2005-2013 stratifying surgical outcomes in CRLM by RAS mutational status. mRAS was associated with nearly twice the risk of margin-positive resections (11.4 vs. 5.4%). Among patients with liver-first recurrence, mRAS had narrower margins at initial resection. Positive margin (HR 3.36) and mRAS (HR 1.63) were independently associated with worse overall survival. Importantly, association between mRAS and +ve margins was independent of the association between mRAS and response to preoperative chemotherapy. The take-home message is that tumor biology should guide operative decision-making in CRLM. Limitations: 1. Single-institution retrospective study; 2. mutational analysis algorithms varied during length of study; 3. Expanding list of RAS mutations signify functionally redundant alterations in the same signaling pathway, so unclear which ones are most important for prognosis-- this study throws all mutations into a single bucket.

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