Faculty Bibliography

The association between cigarette smoking and mortality from hepatocellular carcinoma (HCC) is ambiguous. We analyzed the association between smoking and mortality in HCC patients seen at our center. We collected data retrospectively on patients diagnosed with HCC between 2002 and 2009. We estimated the association of smoking history with demographic, clinical and treatment factors. We then modeled these factors as predictors of mortality. Among smokers, we analyzed the effects of pack-year history and cessation times on survival. Two hundred and twenty-three out of 444 patients with HCC had a history of smoking. Smokers were more likely to be younger at diagnosis, to have alpha fetoprotein (AFP) values less than the median, and to have had surgery (p=0.04) compared to non-smokers. In a Cox model, younger age, lower AFP and Child's Class were all independently predictive of survival, but smoking was not. Smokers with over 20 pack-years did not have worse survival than lighter smokers, and cessation times also did not affect survival after controlling for age. We found a significant interaction between smoking and drinking. In our data, smoking was not independently associated with HCC survival in a multivariable model. Smoking was associated with favorable prognostic features which likely outweighed any independent effect of smoking.

BACKGROUND:The prognosis for patients with esophageal cancer is poor, even among those who undergo potentially curative esophagectomy. The neutrophil:lymphocyte ratio (NLR) is hypothesized to reflect the systemic inflammatory response created by a tumor and is possibly predictive of tumor aggressiveness and propensity for metastasis. METHODS:We performed a single-center retrospective analysis of esophageal cancer patients who underwent attempted curative esophagectomy at Weill Cornell Medical Center between 1996 and 2009. We collected data on patient demographics, clinical characteristics, and receipt of neoadjuvant treatment. Preoperative blood tests were used to calculate NLR. Elevated NLR was defined a priori as ≥5.0. Logistic regression modeling was performed to analyze characteristics associated with elevated NLR. We conducted Kaplan-Meier analyses and Cox regression modeling to determine estimates and predictors of disease-free and overall survival. RESULTS:We identified a total of 295 patients who underwent esophagectomy. The median duration of follow-up was 31 months (interquartile range [IQR] 13-61). There were 56 patients (18.9%) who had elevated NLR preoperatively. Receipt of neoadjuvant therapy was independently associated with high NLR (odds ratio [OR] 2.14, 95% confidence interval [95% CI] 1.02-4.51). In multivariable analyses, elevated NLR was associated with significantly worse disease-free (hazard ratio [HR] 2.26, 95% CI 1.43-3.55) and overall survival (HR 2.31, 95% CI 1.53-3.50). CONCLUSIONS:Preoperative NLR is a potential prognostic marker for recurrence and death after esophagectomy. It is unclear whether NLR reflects the degree of inflammatory response to the primary tumor or other patient-specific or tumor characteristics that predispose to recurrence. Further investigation is warranted to clarify the mechanisms explaining the observed associations between elevated NLR and poor outcomes in esophageal cancer.

BACKGROUND:We hypothesized that hepatocellular carcinoma (HCC) patients with higher Body Mass Index (BMI) might have more microvascular invasion (MVI) in their tumors. METHODS:Records from 138 consecutive patients who underwent surgery at Columbia University Medical Center from January 1, 2002 to January 9, 2008 were evaluated. RESULTS:40 patients (29%) had MVI, including 14% with BMI <25, 31% with BMI = 25-30, and 40% with BMI >30 (p = .05). However, only maximum alpha-fetoprotein was significantly associated with overall mortality in a Cox model. CONCLUSIONS:MVI was associated with obesity. A better understanding of the mechanism of this association may lead to interventions for the treatment and prevention of HCC.

BACKGROUND:The Milan criteria have been adopted by United Network for Organ Sharing (UNOS) to preoperatively assess outcome in patients with hepatocellular carcinoma (HCC) who receive orthotopic liver transplantation (OLT). These criteria rely solely on radiographic appearances of the tumor, providing no measure of tumor biology. Recurrence rates, therefore, remain around 20% for patients within the criteria. The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status previously established as a prognostic indicator in colorectal liver metastases. We aimed to determine whether NLR predicts outcome in patients undergoing OLT for HCC. DESIGN/METHODS:Analysis of patients undergoing OLT for HCC between 2001 and 2007 at our institution. A NLR > or =5 was considered to be elevated. RESULTS:: A total of 150 patients were identified, with 13 patients having an elevated NLR. Of these, 62% developed recurrence compared with 14% with normal NLR (P < 0.0001). The disease-free survival for patients with high NLR was significantly worse than that for patients with normal NLR (1-, 3-, and 5-year survivals of 38%, 25%, and 25% vs. 92%, 85%, and 75%, P < 0.0001). Patients with high NLR also had poorer overall survival (5-year survival, 28% vs. 64%, P = 0.001). Patients within Milan with an elevated NLR had significantly poorer disease-free survival than those with normal NLR within Milan (5-year survival, 30% vs. 81%, P < 0.0001). On univariate analysis, 9 factors including an NLR > or =5 were significant predictors of poor disease-free survival. However, only a raised NLR remained significant on multivariate analysis (P = 0.005, HR: 19.98). CONCLUSION/CONCLUSIONS:Elevated NLR significantly increases the risk for tumor recurrence and recipient death. Preoperative NLR measurement may provide a simple method of identifying patients with poorer prognosis and act as an adjunct to Milan in determining, which patients benefit most from OLT.

OBJECTIVES/OBJECTIVE:To further our understanding of the potential protective effects of one organ allograft for another in combined organ transplants by comparing rejection-free survival and the 1-year rejection rate of each type of combined organ transplant. SUMMARY BACKGROUND DATA/BACKGROUND:Liver allografts have been thought to be immunoprotective of other donor-specific allografts. Recent observations have extended this property to other organs. METHODS:Analysis of data from the United Network of Organ Sharing included recipients 18 years or older (except those receiving intestinal transplants) transplanted between January 1, 1994, and October 6, 2005, and excluded those with a previous transplant (n = 45,306), live-donor transplant (n = 80,850), or insufficient follow-up (n = 4304). Patients were followed from transplant until death (n = 41,524), retransplantation (n = 4649), or last follow-up (n = 87,243). RESULTS:A total of 133,416 patients were analyzed. Rejection rates for allografts co-transplanted with donor-specific primary liver, kidney, and heart allografts are significantly lower than rejection rates for allografts transplanted alone. Allografts accompanying primary intestinal or pancreatic allografts did not have reduced rejection rates. A decreased rate of rejection was seen in interval kidney-heart transplants when allografts shared partial antigenic identity. Decreased rates of rejection were also seen in transplants of 2 donor-specific organs of the same type. CONCLUSIONS:In combined simultaneous transplants, heart, liver, and kidney allografts are themselves protected and protect the other organ from rejection. Analysis of interval heart-kidney allografts suggests the need for partial antigenic identity between organs for the immunoprotection to take effect. This was not demonstrated in interval liver-kidney transplants. Increased antigen load of identical antigens, as seen in double-lung and double-kidney transplants, also offers immunologic protection against rejection.