Primary Clear Cell Carcinoma of the Pancreas: A Systematic Review.

Over the years, the world has witnessed many advances in diagnosing and treating multiple types of cancers. These breakthroughs have revolutionized the understanding of the molecular drive behind these neoplasms, leading to tangible therapeutic evolution and promising prognostic implications. However, pancreatic cancer remains a highly lethal disease. With recent discoveries, modern medicine has been able to delineate histopathologic subtypes of pancreatic cancer in hopes of improved diagnosis and treatment to improve survival. A once vague entity, clear cell adenocarcinoma of the pancreas, in particular, has been better characterized on a histopathological and molecular level over the past two decades. With novel technological support, this disease has become less inconspicuous, and more researchers have reported its occurrence. Its diagnosis relies heavily on a mix of histological and immunohistochemical clues such as a clear cell cytoplasm and positivity for cytokeratins and other markers. However, new molecular markers, such as hepatocyte nuclear factor 1 beta, have been associated with this entity and may aid in further diagnostic and therapeutic strategies. This review article aims to portray how the identification and description of clear cell adenocarcinoma of the pancreas have evolved over the past few decades and how this may impact future treatment strategies.

Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting.

Clopidogrel is an oral antiplatelet pro-drug prescribed to 40 million patients worldwide who are at risk for thrombotic events or receiving percutaneous coronary intervention (PCI). However about a fifth of patients treated with clopidogrel do not respond adequately to the drug. From a cohort of 105 patients on whom we had functional data on clopidogrel response, we used ultra-high throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to respond. Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predicted if a patient would respond to clopidogrel 52.4% of the time. Similarly, testing of the ABCB1 gene only correctly foretold response in 51 (48.6%) patients. These results are clinically relevant and suggest that until additional genetic factors are discovered that predict response more completely, functional assays are more appropriate for clinical use.

Impact of New York Heart Association classification, advanced age and patient-prosthesis mismatch on outcomes in aortic valve replacement surgery.

OBJECTIVES More elderly patients (>80 years of age) are being referred for aortic valve replacement (AVR) with or without CABG. Current risk stratification models may not accurately predict the preoperative risk in these patients. We sought to determine which perioperative variables were relevant in determining short-term (30-day to in-hospital) outcomes in our intuition's series of consecutive AVR and AVR+CABG surgeries. We constructed a novel variable, patient-prosthesis mismatch (PPM) in the presence of diminished functional status (NYHA) classification, and studied its role as a predictor of mortality risk. METHODS From 2006 to 2010, 509 patients undergoing AVR or AVR+CABG were evaluated. We created four groups based on the age and procedure (AVR >80, AVR+CABG >80, AVR <80 and AVR+CABG <80). PPM was defined as a calculated effective orifice area index value of ≤ 0.85, and it was calculated from manufacturer-generated charts. In-hospital and 30-day outcomes were assessed using the Chi-square and logistic regression analyses. RESULTS Overall observed 30-day mortality for all groups was lower (n = 8, 1.6%) than the STS-predicted mortality. Reoperation and PPM+NYHA class III-IV were associated with short-term mortality, but age >80 years was not. Octogenarians referred for surgery often had advanced heart failure. CONCLUSIONS Overall, short-term outcomes after AVR with or without CABG were excellent and lower than predicted by the STS model. The low risk of AVR with CABG supports the consideration for earlier surgical referral and intervention for patients with a high likelihood of aortic stenosis progression before the onset of advanced heart failure ensues, regardless of the age. This should help further decrease the already very low mortality observed in these series. Efforts to avoid PPM in the setting of advanced heart failure may improve short-term results in this subset of patients.

Use of an objective tool to assess platelet inhibition prior to off-pump coronary surgery to reduce blood usage.

BACKGROUND: The current standard of care is to delay coronary surgery 5-7 days after clopidogrel exposure to prevent bleeding complications. We sought to determine the utility of an objective tool (ie, the VerifyNow assay) to measure platelet inhibition (PI) in patients receiving preoperative clopidogrel prior to off-pump coronary artery bypass grafting surgery (OPCABG). PATIENTS AND METHODS: Between June 2007 and July 2009, a total of 482 isolated OPCABG procedures were performed at our institution. In 160 patients, the VerifyNow assay results were used to determine timing of the OPCABG. These patients were compared to the remaining 322 patients. We divided the cohort into 4 subgroups: Group 1 patients (n = 205) were not taking clopidogrel; Group 2 patients (n = 117) were taking clopidogrel, but the test was not performed; Group 3 patients (n = 122) were taking clopidogrel and had a preoperative PI result of ≤20%; and Group 4 patients (n = 38) had ≥21% preoperative PI. RESULTS: Demographic and clinical factors were compared in all groups. The median waiting time for surgery from the last dose of clopidogrel was 6 days for the control groups and 3 days for the groups where the test was performed (P<.001). Reoperation for bleeding occurred most often in Group 4 (7.9%; P=.003). Blood utilization was lower in Group 1 (24.4%) than in Groups 2 (34.2%), 3 (40.2%), or 4 (55.3%) (P<.001). Major complications and postoperative length of stay were similar in all groups. CONCLUSIONS: Utilization of a PI tool in the preoperative assessment of OPCABG patients exposed to clopidogrel can provide valuable information to guide the timing of coronary surgery and may lead to a decrease in reoperation for bleeding and blood usage.

Propensity matched analysis of bilateral internal mammary artery versus single left internal mammary artery grafting at 17-year follow-up: validation of a contemporary surgical experience.

OBJECTIVES: Bilateral internal mammary arteries (BIMA) remains widely underutilized in coronary artery bypass grafting (CABG). Although prior research has demonstrated a long-term benefit of the use of BIMA over left internal mammary artery (LIMA)-only, validation of these results is lacking in a contemporary surgical experience. We compared complications and survival at 17-year follow-up in a large series of consecutive CABG patients from a single institution that underwent BIMA grafting with a propensity-matched group where LIMA only was used. METHODS: Propensity scores representing the estimated probabilities of patients receiving either BIMA or LIMA alone were developed based on 22 observed baseline covariates in a logistic regression model with procedure group as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 928 patients each balanced for baseline factors. We compared 30-day morbidity and mortality, as well as long-term survival at 5-year intervals up to 17-year follow-up. RESULTS: In-hospital and 30-day mortality was 0.8% for the BIMA group and 1.1% for the LIMA-saphenous vein grafting (SVG). No significant difference was found in complications, mortality and/or length-of-stay between these two groups. Off-pump was done in 48.9% of BIMA cases and 51.3% of LIMA cases. Regardless of the types of grafts used, on-pump patients were more likely to have postoperative permanent strokes and longer postoperative lengths of stay. Use of the BIMA over LIMA-only had a statistically significant impact conferring a 10% survival advantage at 10-year and 18% at 15-year follow-up. The Kaplan-Meier survival curves comparing off-/on-pump BIMA and off-/on-pump LIMA-SVG patients demonstrated a 22% survival advantage for off-pump BIMA patients when compared with on-pump LIMA-SVG patients at 15-year follow-up. CONCLUSIONS: Perioperative complications do not increase with the use of BIMAs. Long-term survival is optimized with off-pump CABG and BIMA grafting. The low morbidity and mortality rates in this series are likely due to the continuous evolution of technology and the adoption of less invasive options for CABG patients. A more widespread use of BIMAs in CABG patients would continue to improve the overall excellent short- and long-term results of this operation.