[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of this study was to determine the utility of the Model for End-Stage Liver Disease Excluding INR (MELD-XI) in predicting early outcomes (30 days and 1 year) and late outcomes (5 years) in patients after orthotopic heart transplantation (OHT).
The United Network for Organ Sharing database was queried for all adult patients (aged ≥18 years) undergoing OHT from 2000 to 2012. A MELD-XI was calculated and the population stratified into score quartiles. Early and late survivals were compared among the MELD-XI cohorts. Multivariable Cox proportional hazards models were constructed to determine the capacity of MELD-XI (when modeled both as a categoric and a continuous variable) to predict 30-day, 1-year, and 5-year mortality. Conditional models were also designed to determine the effect of early mortality on long-term survival.
A total of 22,597 patients were included for analysis. The MELD-XI cutoff scores were established as follows: low (≤10.5), low-intermediate (10.6 to 12.6), intermediate-high (12.7 to 16.4), and high (>16.4). The high MELD-XI cohort experienced statistically worse 30-day, 1-year, and 5-year unconditional survivals when compared with patients with low scores (p < 0.001). Similarly, a high MELD-XI score was also predictive of early and late mortality (p < 0.001) after risk adjustment. There was, however, no difference in 5-year survival between the high score and low score cohorts after accounting for 1-year deaths. Subanalysis of patients bridged to transplant with a continuous-flow left ventricular assist device demonstrated similar findings.
This is the first known study to examine the relationship between a high MELD-XI score and outcomes in patients after OHT. Patients with hepatic or renal dysfunction before OHT should be closely monitored and aggressively optimized as early mortality appears to drive long-term outcomes.
The Annals of thoracic surgery 09/2015; DOI:10.1016/j.athoracsur.2015.07.026 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: International Study Group of Pancreatic Fistula (ISGPF) grade C postoperative pancreatic fistulas (POPF) are the greatest contributor to major morbidity and mortality following pancreatoduodenectomy (PD); however, their infrequent occurrence has hindered deeper analysis. This study sought to develop a predictive algorithm, which could facilitate effective management of this challenging complication.
Data were accrued from 4301 PDs worldwide. Demographics, postoperative management, and microbiological characteristics of grade C POPFs were evaluated. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) preoperative and intraoperative variables were compared between grade C POPFs and a 639-case sample of non-grade C POPFs. Risk factors for grade C POPF formation were identified using regression analysis.
Grade C POPFs developed in 79 patients (1.8 %). Deaths (90 days) occurred in 2.0 % (N = 88) of the overall series, with 35 % (N = 25) occurring in the presence of a grade C POPF. Reoperations occurred 72.2 % of the time. The rates of single- and multi-system organ failure were 28.2 and 39.7 %, respectively. Mortality rates escalated with pulmonary, renal, and neurologic organ failure, but they were unaffected by reoperation(s). The median number of complications incurred was four (IQR: 2-5), and the median duration of hospital stay was 32 (IQR: 21-54) days. Warning signs for impending grade C POPFs most often presented on postoperative day (POD) 6. Adjuvant chemotherapy might have benefited 55.7 % of grade C POPF patients, yet it was delayed in 25.6 % and never delivered in 67.4 % of these patients. Predictive models for grade C POPF occurrence based on preoperative factors alone and preoperative and intraoperative factors yielded areas under the receiver operating characteristic curve of 0.73 and 0.84 (both P < 0.000001), respectively.
This global study represents the largest analysis of grade C POPFs following PD. It describes the severe burden that grade C POPFs incur on patients, with high rates of reoperation and infection, while also potentially worsening overall survival by causing death and delay/omission of adjuvant therapy. Additionally, aggressive clinical management for these POPFs did not improve or worsen 90-day mortality. Predictive tools developed through these data may provide value in managing this difficult complication.
Journal of Gastrointestinal Surgery 07/2015; DOI:10.1007/s11605-015-2884-2 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study was to investigate the prognostic significance of early (30-day) hospital readmission (EHR) on mortality after pancreatectomy.
Using a prospectively collected institutional database linked with a statewide dataset, we evaluated the association between EHR and overall mortality in all patients undergoing pancreatectomy at our tertiary institution (2005 to 2010).
Of 595 pancreatectomy patients, EHR occurred in 21.5%. Overall mortality was 29.4% (median follow-up 22.7 months). Patients with EHR had decreased survival compared with those who were not readmitted (P = .011). On multivariate analysis adjusting for baseline group differences, EHR for gastrointestinal-related complications was a significant independent predictor of mortality (hazard ratio 2.30, P = .001).
In addition to known risk factors, 30-day readmission for gastrointestinal-related complications following pancreatectomy independently predicts increased mortality. Additional studies are necessary to identify surgical, medical, and social factors contributing to EHR, as well as interventions aimed at decreasing postpancreatectomy morbidity and mortality.
American journal of surgery 06/2015; 210(4). DOI:10.1016/j.amjsurg.2015.05.009 · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs).
FNA is a common method of diagnosis for pancreatic cancer, yet it has traditionally been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and tumor heterogeneity.
In vitro mixing studies were performed to deduce the minimum cellularity needed for genetic analysis. DNA from both simulated FNAs and clinical FNAs was sequenced. Mutational concordance was determined between simulated FNAs and that of the resected specimen.
Limiting dilution studies indicated that mutations present at allele frequencies as low as 0.12% are detectable. Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 patients with unresectable disease, we identified at least 1 driver gene mutation in all patients including actionable somatic mutations in ATM and MTOR. The constellation of mutations identified in these patients was different than that reported for resectable pancreatic cancers, implying a biologic basis for presentation with locally advanced pancreatic cancer.
FNA sequencing is feasible and subsets of patients may harbor actionable mutations that could potentially impact therapy. Moreover, preoperative FNA sequencing has the potential to influence the timing of surgery relative to systemic therapy. FNA sequencing opens the door to clinical trials in which patients undergo neoadjuvant or a surgery-first approach based on their tumor genetics with the goal of utilizing cancer genomics in the clinical management of pancreatic cancer.
Annals of surgery 05/2015; DOI:10.1097/SLA.0000000000001156 · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of prolonged graft ischemia (≥6 hours) on outcomes following lung transplantation is controversial.
To evaluate the effect of prolonged total graft ischemia times on long-term survival rates and the development of primary graft failure (PGF) following lung transplantation.
In this retrospective study, the United Network for Organ Sharing database was queried for adult patients who underwent lung transplantation from May 1, 2005, through December 31, 2011. Primary stratification by the presence of prolonged graft ischemia was performed. Kaplan-Meier estimates at 1 and 5 years were used to compare survival in the 2 cohorts. A multivariable Cox proportional hazards regression model was constructed to identify predictors of 1- and 5-year mortality. A risk-adjusted predictive model for the development of PGF was formulated in a similar fashion.
The primary outcome of interest was 1- and 5-year survival. Secondary outcomes included PGF and other postoperative events, such as renal failure, biopsy-proven rejection, and stroke.
Of the 10 225 patients who underwent lung transplantation, 3127 (30.6%) had allografts exposed to prolonged ischemia. There was no difference in survival at 1 (83.6% [95% CI, 82.3%-84.9%] vs 84.1% [95% CI, 83.3%-85.0%]; P = .41) or 5 (52.5% [95% CI, 51.0%-54.0%] vs 53.5% [95% CI, 51.3%-55.6%]; P = .82) years between patients who received grafts that were or were not exposed to ischemia that lasted 6 hours or more, respectively. Prolonged graft ischemia did not independently predict 1- or 5-year mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P = .37). Furthermore, prolonged ischemia did not independently predict 1-year (hazard ratio, 1.09; 95% CI, 0.97-1.22; P =.15) or 5-year (hazard ratio, 1.05; 95% CI, 0.98-1.14; P =.18) mortality or the development of PGF (odds ratio, 1.11; 95% CI, 0.88-1.39; P =.37).
No association was found between prolonged total graft ischemia times and primary graft failure or survival following lung transplantation. Given the scarcity of organs and the paucity of suitable recipients, prolonged ischemia time should not preclude transplantation. It is, therefore, reasonable to consider extending the accepted period of ischemia to more than 6 hours in certain patient populations to improve organ use.
JAMA SURGERY 04/2015; 150(6). DOI:10.1001/jamasurg.2015.12 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST).
Patients and methods:
Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan-Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed.
Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively).
In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.
British Journal of Cancer 01/2015; 112(4). DOI:10.1038/bjc.2014.647 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Long noncoding RNA (lncRNA) have proven to play key roles in cell physiology from nuclear organization and epigenetic remodeling to post-transcriptional regulation. Last decade, gene expression based-classifications have been developed in clear-cell renal cell carcinoma (ccRCC) to identify distinct subtypes of disease and predict patient’s outcome. However, there are no current lncRNA comprehensive characterizations in ccRCC.
Patients and Methods
RNA-sequencing profiles of 475 primary ccRCC samples from the Cancer Genome Atlas (TCGA) were used to assess expressed lncRNA and identify lncRNA-based classification. In addition, integrative analysis was performed to correlate tumor subtypes with copy-number alterations and somatic mutations.
Using stringent criteria, we identify 1,934 expressed lncRNA and assessed their chromatin marks. Unsupervised clustering unravels four lncRNA subclasses in ccRCC associated with distinct clinicopathological and genomic features of this disease. Cluster C2 (23.4%) defines the most aggressive tumours, with the highest Fuhrman grade and stage and the worst overall survival time. Furthermore, cluster C2 is enriched for 9p deletion and chromatin remodeler BAP1 somatic mutations. Interestingly, cluster C4 (7.8%) is related to a tumour subtype arising from the distal tubules of the nephron. Consistent with its distinct ontogeny, cluster C4 is devoid of classical alterations seen in ccRCC, bears frequent 1p deletion and 17q gain, and is enriched for MiTF/TFE translocations. In addition, reexaminations of copy-number data from one side and tumor histology by pathologists from the other side reveal misclassified tumors within C4 cluster including chromophobe RCC and clear cell papillary RCC.
this study establishes a foundation for categorizing lncRNA subclasses, which may contribute to understand tumour ontogeny and help predicting patients’ outcome in ccRCC.
[Show abstract][Hide abstract] ABSTRACT: Readmission after pancreatectomy is common, but few data compare patterns of readmission to index and nonindex hospitals.
To evaluate the rate of readmission to index and nonindex institutions following pancreatectomy at a tertiary high-volume institution and to identify patient-level factors predictive of those readmissions.
Retrospective analysis of a prospectively collected institutional database linked to statewide data of patients who underwent pancreatectomy at a tertiary care referral center between January 1, 2005, and December 2, 2010.
The primary outcome was unplanned 30-day readmission to index or nonindex hospitals. Risk factors and reasons for readmission were measured and compared by site using univariable and multivariable analyses.
Among all 623 patients who underwent pancreatectomy during the study period, 134 (21.5%) were readmitted to our institution (105 [78.4%]) or to an outside institution (29 [21.6%]). Fifty-six patients (41.8%) were readmitted because of a gastrointestinal or nutritional problem related to surgery and 42 patients (31.3%) because of a postoperative infection. On multivariable analysis, factors independently associated with readmission included age 65 years or older (odds ratio [OR], 1.80; 95% CI, 1.19-2.71), preexisting liver disease (OR, 2.28; 95% CI, 1.23-4.24), distal pancreatectomy (OR, 1.77; 95% CI, 1.11-2.84), and postoperative drain placement (OR, 2.81; 95% CI, 1.00-7.14).
In total, 21.5% of patients required early readmission after pancreatectomy. Even in the setting of a tertiary care referral center, 21.6% of these readmissions were to nonindex institutions. Specific patient-level factors were associated with an increased risk of readmission.
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of this study was to determine which factors predict poor postoperative performance and to evaluate the impact of these variables on 1-year mortality.
The United Network for Organ Sharing database was queried for adult patients undergoing lung transplantation (LTx) from 2007 to 2011. Patients were divided based on their preoperative Karnofsky Performance Status score (KPS) into 3 groups. Regression analysis was conducted to determine which factors predicted poor postoperative performance. Cox modeling was utilized to identify which of these factors was associated with an increased risk of mortality after LTx.
Of the 7,832 patients included in this study, 30.1% required complete assistance, 57.7% required partial assistance, and 12.3% needed no assistance preoperatively. Postoperative KPS was assessed at a mean of 2.6 ± 1.5 years after transplant. A number of factors, including primary graft failure, redo and single LTx, and intensive care unit status prior to LTx independently predicted poor performance; whereas a body mass index 18.5 kg/m(2) or greater and some degree of preoperative functional independence were protective. Age greater than 60 years, donor tobacco use, and intensive care unit status, extracorporeal membrane oxygenation support, and mechanical ventilation prior to LTx were associated with an increased risk 1-year mortality, while preoperative functional independence and a body mass index 18.5 to 30 kg/m(2) were protective.
This is the largest known study to examine the issue of disability in LTx and its relationship to mortality. Preoperative performance status significantly impacts post-LTx mortality. Patient optimization may improve outcomes and should alter decisions regarding graft selection and allocation.
The Annals of Thoracic Surgery 12/2014; 99(2). DOI:10.1016/j.athoracsur.2014.09.038 · 3.85 Impact Factor