Faculty Bibliography
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692
A MULTI-MODALITY TEST TO GUIDE THE MANAGEMENT OF PATIENTS WITH PANCREATIC CYSTS [Meeting Abstract]
ISI:000470094900190
ISSN: 0016-5107
CID: 4744962
CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan
ISI:000480385800007
ISSN: 2041-1723
CID: 4744992
Variation in the surgical management of locally advanced pancreatic cancer. [Meeting Abstract]
ISI:000487345805309
ISSN: 0732-183x
CID: 4745032
Response to the Comment on "Anatomical Resections Improve Disease-free Survival in Patients With KRAS-mutated Colorectal Liver Metastases." [Comment]
PMID: 30845013
ISSN: 1528-1140
CID: 4741062
HPB : the official journal of the International Hepato Pancreato Biliary Association. 2019:21(10):1327-1335.DOI: 10.1016/j.hpb.2019.02.005
A national assessment of the utilization, quality and cost of laparoscopic liver resection
BACKGROUND:Despite recent enthusiasm for the use of laparoscopic liver resection, data evaluating costs associated with laparoscopic liver resections are lacking. We sought to examine the use of laparoscopic liver surgery, and investigate variations in cost among hospitals performing these procedures. METHODS:A nationally representative sample of 12,560 patients who underwent a liver resection in 2012 was identified. Multivariable analyses were performed to compare outcomes associated with liver resection. RESULTS:Among the 12,560 patients who underwent liver resection, 685 (5.4%) underwent a laparoscopic liver resection. The proportion of liver resections performed laparoscopically varied among hospitals ranging from 4.6% to 20.0%; the median volume of laparoscopic liver resections was 10 operations/year. Although laparoscopic surgery was associated with lower postoperative morbidity (aOR = 0.60, 95%CI: 0.36-0.99) and shorter lengths of stay [(LOS) aIRR = 0.83, 95%CI: 0.70-0.97], it was not associated with inpatient mortality (p = 0.971) or hospital costs (p = 0.863). Costs associated with laparoscopic liver resection varied ranging from $5,907 (95%CI: $5,140-$6,674) to $67,178 (95%CI: $66,271-$68,083). The observed variations between hospitals were due to differences in morbidity (coefficient: $20,415, 95%CI: $16,000-$24,830) and LOS (coefficient: $24,690, 95%CI: $21,688-$27,692). CONCLUSIONS:Although laparoscopic liver resection was associated with improved short-term perioperative clinical outcomes, utilization of laparoscopic liver resection remains low.
PMID: 30850188
ISSN: 1477-2574
CID: 4741072
A Phase II clinical trial of GVAX pancreas vaccine (with Cyclophosphamide) in combination with Nivolumab and Stereotactic Body Radiation Therapy (SBRT) followed by definitive resection for patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC) [Meeting Abstract]
ISI:000488129900146
ISSN: 0008-5472
CID: 4745042
Analysis of spatial relationships between infiltrating immune cells within the tumor microenvironment following combinatorial immunotherapy [Meeting Abstract]
ISI:000488279402050
ISSN: 0008-5472
CID: 4745052
Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood
BACKGROUND:Despite improvements in cancer management, most pancreatic cancers are still diagnosed at an advanced stage. We have recently identified promoter DNA methylation of the genes ADAMTS1 and BNC1 as potential blood biomarkers of pancreas cancer. In this study, we validate this biomarker panel in peripheral cell-free tumor DNA of patients with pancreatic cancer. RESULTS:Sensitivity and specificity for each gene are as follows: ADAMTS1 87.2% and 95.8% (AUC = 0.91; 95% CI 0.71-0.86) and BNC1 64.1% and 93.7% (AUC = 0.79; 95% CI 0.63-0.78). When using methylation of either gene as a combination panel, sensitivity increases to 97.3% and specificity to 91.6% (AUC = 0.95; 95% CI 0.77-0.90). Adding pre-operative CA 19-9 values to the combined two-gene methylation panel did not improve sensitivity. Methylation of ADAMTS1 was found to be positive in 87.5% (7/8) of stage I, 77.8% (7/9) of stage IIA, and 90% (18/20) of stage IIB disease. Similarly, BNC1 was positive in 62.5% (5/8) of stage I patients, 55.6% (5/9) of stage IIA, and 65% (13/20) of patients with stage IIB disease. The two-gene panel (ADAMTS1 and/or BNC1) was positive in 100% (8/8) of stage I, 88.9% (8/9) of stage IIA, and 100% (20/20) of stage IIB disease. The sensitivity and specificity of the two-gene panel for localized pancreatic cancer (stages I and II), where the cancer is eligible for surgical resection with curative potential, was 94.8% and 91.6% respectively. Additionally, the two-gene panel exhibited an AUC of 0.95 (95% CI 0.90-0.98) compared to 57.1% for CA 19-9 alone. CONCLUSION:The methylation status of ADAMTS1 and BNC1 in cfDNA shows promise for detecting pancreatic cancer during the early stages when curative resection of the tumor is still possible. This minimally invasive blood-based biomarker panel could be used as a promising tool for diagnosis and screening in a select subset of high-risk populations.
PMCID:6451253
PMID: 30953539
ISSN: 1868-7083
CID: 4741092
HPB : the official journal of the International Hepato Pancreato Biliary Association. 2019:21(11):1527-1534.DOI: 10.1016/j.hpb.2019.03.368
KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases
BACKGROUND:A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined. METHODS:Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response. RESULTS:319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, PÂ =Â 0.01) and wtKRAS status remained independently associated with a major response (PÂ =Â 0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (PÂ =Â 0.023). CONCLUSIONS:Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.
PMID: 30979646
ISSN: 1477-2574
CID: 4741102
Intraductal Papillary Mucinous Neoplasms Arise From Multiple Independent Clones, Each With Distinct Mutations
BACKGROUND & AIMS:Intraductal papillary mucinous neoplasms (IPMNs) are lesions that can progress to invasive pancreatic cancer and constitute an important system for studies of pancreatic tumorigenesis. We performed comprehensive genomic analyses of entire IPMNs to determine the diversity of somatic mutations in genes that promote tumorigenesis. METHODS:We microdissected neoplastic tissues from 6-24 regions each of 20 resected IPMNs, resulting in 227 neoplastic samples that were analyzed by capture-based targeted sequencing. Somatic mutations in genes associated with pancreatic tumorigenesis were assessed across entire IPMN lesions, and the resulting data were supported by evolutionary modeling, whole-exome sequencing, and in situ detection of mutations. RESULTS:We found a high prevalence of heterogeneity among mutations in IPMNs. Heterogeneity in mutations in KRAS and GNAS was significantly more prevalent in IPMNs with low-grade dysplasia than in IPMNs with high-grade dysplasia (P < .02). Whole-exome sequencing confirmed that IPMNs contained multiple independent clones, each with distinct mutations, as originally indicated by targeted sequencing and evolutionary modeling. We also found evidence for convergent evolution of mutations in RNF43 and TP53, which are acquired during later stages of tumorigenesis. CONCLUSIONS:In an analysis of the heterogeneity of mutations throughout IPMNs, we found that early-stage IPMNs contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. These findings challenge the model in which pancreatic neoplasms arise from a single clone. Increasing our understanding of the mechanisms of IPMN polyclonality could lead to strategies to identify patients at increased risk for pancreatic cancer.
PMID: 31175866
ISSN: 1528-0012
CID: 4741202
