Faculty Bibliography
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692
Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less
BACKGROUND:Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS:Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS:In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS:External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.
PMID: 31441048
ISSN: 1365-2168
CID: 5786552
NON-SELECTIVE beta-ADRENERGIC BLOCKADE IMPACTS PANCREATIC CANCER TUMOR BIOLOGY, DECREASES PERINEURAL INVASION AND IMPROVES PATIENT SURVIVAL [Meeting Abstract]
ISI:000467106005414
ISSN: 0016-5085
CID: 5373032
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
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
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
A MULTI-MODALITY TEST TO GUIDE THE MANAGEMENT OF PATIENTS WITH PANCREATIC CYSTS [Meeting Abstract]
ISI:000470094900190
ISSN: 0016-5107
CID: 4744962
