Faculty Bibliography
Searched for:
in-biosketch:true
person:wolfgc01
Total Results:
686
Gastric cancer following pancreaticoduodenectomy: Experience from a high-volume center and review of existing literature
Background/UNASSIGNED:Prolonged survival of patients after pancreaticoduodenectomy can be associated with late complications due to altered gastrointestinal anatomy. The incidence of gastric cancer is increasingly reported. We set out to examine our experience with gastric cancer as a late complication after pancreaticoduodenectomy with a focus on incidence, risk factors, and outcomes. Methods/UNASSIGNED:We queried our prospectively collected institutional database for patients that developed gastric cancer after pancreaticoduodenectomy and conducted a systematic review of the literature. Results/UNASSIGNED:Our database revealed 6 patients who developed gastric cancer following pancreaticoduodenectomy, presenting with a mean age of 62.2 years and an even sex distribution. All of those patients underwent pancreaticoduodenectomy for malignant indications with an average time to development of metachronous gastric cancer of 8.3 years. Four patients complained of gastrointestinal discomfort prior to diagnosis of secondary malignancy. All of these cancers were poorly differentiated and were discovered at an advanced T stage (≥ 3). Only half developed at the gastrointestinal anastomosis. Four underwent surgery with a curative intent, and 2 patients are currently alive (mean postgastrectomy survival = 25.5 months). In accordance with previous literature, biliopancreatic reflux from pancreaticoduodenectomy reconstruction, underlying genetic susceptibility, and adjuvant therapy may play a causative role in later development of gastric cancer. Conclusion/UNASSIGNED:Long-term survivors after pancreaticoduodenectomy who develop nonspecific gastrointestinal complaints should be evaluated carefully for complications including gastric malignancy. This may serve as an opportunity to intervene on tumors that typically present at an advanced stage and with aggressive histology.
PMCID:7486455
PMID: 32954246
ISSN: 2589-8450
CID: 4741672
Impact and clinical usefulness of genetic data in the surgical management of colorectal cancer liver metastasis: a narrative review
Importance/UNASSIGNED:In patients who undergo surgery for colorectal cancer liver metastases (CRLM), a number of somatic mutations have been associated with worse overall (OS) and recurrence-free survival (RFS). Although useful, an association with prognosis does not necessarily equate to an impact on surgical management. Objective/UNASSIGNED:The aim of this review was to investigate whether the best-studied somatic mutations impact surgical management of CRLM by informing: (I) post-hepatectomy surveillance; (II) selection of surgical technique; (III) selection of optimal margin width; and (IV) selection of patients for surgery. Lastly, we discuss the refinement of genetic data from overall mutation status to specific variants, as well as lesser studied somatic mutations. Evidence Review/UNASSIGNED:We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to genetic data and CRLM. Findings/UNASSIGNED:Genetic data may impact surgical management of CRLM in three ways. Firstly, KRAS mutations can predict lung recurrences. Secondly, KRAS mutations may help tailor margin width. Thirdly, KRAS mutations may help tailor surgical technique. Conclusions/UNASSIGNED:Although genetic data may impact post-hepatectomy surveillance, selection of surgical technique and optimal margin width, their use to guide surgical selection remains elusive, as the data cannot support denying surgery to patients according to their somatic mutation profile.
PMCID:7720057
PMID: 33299826
ISSN: 2304-3881
CID: 4741792
Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer
BACKGROUND:Screening high-risk individuals (HRI) can detect potentially curable pancreatic ductal adenocarcinoma (PDAC) and its precursors. We describe the outcomes of high-risk individuals (HRI) after pancreatic resection of screen-detected neoplasms. METHODS:Asymptomatic HRI enrolled in the prospective Cancer of the Pancreas Screening (CAPS) studies from 1998 to 2014 based on family history or germline mutations undergoing surveillance for at least 6Â months were included. Pathologic diagnoses, hospital length of stay, incidence of diabetes mellitus, operative morbidity, need for repeat operation, and disease-specific mortality were determined. RESULTS:Among 354 HRI, 48 (13.6%) had 57 operations (distal pancreatectomy (31), Whipple (20), and total pancreatectomy (6)) for suspected pancreatic neoplasms presenting as a solid mass (22), cystic lesion(s) (25), or duct stricture (1). The median length of stay was 7Â days (IQR 5-11). Nine of the 42 HRI underwent completion pancreatectomy for a new lesion after a median of 3.8Â years (IQR 2.5-7.6). Postoperative complications developed in 17 HRI (35%); there were no perioperative deaths. New-onset diabetes mellitus after partial resection developed in 20% of HRI. Fourteen PDACs were diagnosed, 11 were screen-detected, 10 were resectable, and 9 had an R0 resection. Metachronous PDAC developed in remnant pancreata of 2 HRI. PDAC-related mortality was 4/10 (40%), with 90% 1-year survival and 60% 5-year survival, respectively. CONCLUSIONS:Screening HRI can detect PDAC with a high resectability rate. Surgical treatment is associated with a relatively short length of stay and low readmission rate, acceptable morbidity, zero 90-day mortality, and significant long-term survival. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:NCT2000089.
PMCID:6908777
PMID: 31197699
ISSN: 1873-4626
CID: 4741232
Surgical Resection of 78 Pancreatic Solid Pseudopapillary Tumors: a 30-Year Single Institutional Experience
BACKGROUND:Solid pseudopapillary tumors (SPTs) are rare, benign tumors of the pancreas that present as heterogeneous masses. We sought to evaluate the short- and long-term outcomes of surgical resected SPTs. Patients managed via initial surveillance were compared to those who underwent upfront resection. METHODS:A prospectively maintained institutional database was used to identify patients who underwent surgical resection for a SPT between 1988 and 2018. Data on clinicopathological features and outcomes were collected and analyzed. RESULTS:Seventy-eight patients underwent surgical resection for SPT during the study period. The mean age was 34.0 ± 14.6 years and a majority were female (N = 67, 85.9%) and white (N = 46, 58.9%). Thirty patients (37.9%) were diagnosed incidentally. Imaging-based presumed diagnosis was SPT in 49 patients (62.8%). A majority were located in the body or tail of the pancreas (N = 47, 60.3%), and 48 patients (61.5%) underwent a distal pancreatectomy. The median tumor size was 4.0 cm (IQR, 3.0-6.0), nodal disease was present in three patients (3.9%), and R0 resection was performed in all patients. No difference was observed in clinicopathological features and outcomes between patients who were initially managed via surveillance and those who underwent upfront resection. None of the patients under surveillance had nodal disease or metastasis at the time of resection; however, one of them developed recurrence of disease 95.1 months after resection. At a median follow-up of 36.1 months (IQR, 8.1-62.1), 77 (%) patients were alive and one patient (1.3%) had a recurrence of disease at 95.1 months after resection and subsequently died due to disease. CONCLUSIONS:SPTs are rare pancreatic tumors that are diagnosed most frequently in young females. While a majority are benign and have an indolent course, malignant behavior has been observed. Surgical resection can result in exceptional outcomes.
PMID: 31073801
ISSN: 1873-4626
CID: 4741132
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
HPB : the official journal of the International Hepato Pancreato Biliary Association. 2019:21(8):998-1008.DOI: 10.1016/j.hpb.2018.12.002
Isolated pulmonary recurrence after resection of pancreatic cancer: the effect of patient factors and treatment modalities on survival
BACKGROUND:The literature suggests favorable survival for patients with isolated pulmonary recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) as compared to other recurrence patterns. Within this cohort, it remains unclear what factors are associated with improved survival. METHODS:Patients who developed pulmonary recurrence after pancreatectomy were selected from a prospective database. Predictors for post-recurrence survival (PRS) were analyzed using a multivariable Cox regression model. RESULTS:Ninety-six patients were included. Median recurrence-free survival (RFS), PRS and overall survival (OS) were 16.3, 18.8 and 39.6 months, respectively. Further systemic treatment and/or metastasectomy (n = 64, 67%) was associated with significantly improved PRS and OS when compared to best supportive care (n = 35, 22%) (26.3 vs. 5.3 and 48.1 vs. 18.4, respectively; both P < 0.001). Patients who were able to undergo metastasectomy (n = 19) achieved a PRS and OS of 35.0 and 68.9 months, respectively. More than 5 pulmonary lesions, symptoms and CA 19-9 ≥100 U/mL at time of recurrence were predictive of decreased PRS. A recurrence-free interval of >16 months and treatment for recurrence were independently associated with improved PRS. CONCLUSIONS:Isolated pulmonary recurrence occurs in 13% of patients with recurrent PDAC and is associated with a median OS of 40 months. Aggressive treatment in highly selected patients was correlated with improved survival.
PMID: 30777697
ISSN: 1477-2574
CID: 4741022
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
Direct Interactions With Cancer-Associated Fibroblasts Lead to Enhanced Pancreatic Cancer Stem Cell Function
OBJECTIVE:Cancer-associated fibroblasts (CAFs) play an important role in the progression of pancreatic ductal adenocarcinoma (PDAC) by promoting tumor cell migration and drug resistance. We determined the impact of CAFs on PDAC cancer stem cells (CSCs). METHODS:Fibroblast cell lines from patients' tumors were cocultured with PDAC cells and examined for clonogenic growth and self-renewal using colony-forming assays and migration in vitro. Changes in the frequency of CSCs was determined by flow cytometry. The effect of integrin-focal adhesion kinase (FAK) signaling on CAF-mediated clonogenic growth was evaluated using short hairpin RNAs against β1 integrin and FAK as well as a small-molecule FAK inhibitor. RESULTS:Cancer-associated fibroblasts enhanced PDAC clonogenic growth, self-renewal, and migration that was associated with an increase in the frequency of CSCs. These fibroblast cells were activated by PDAC cells and increased collagen synthesis resulting in FAK activation in PDAC cells. Knockdown of β1-integrin and FAK or the inhibition of FAK kinase activity in PDAC cells abrogated the impact of CAFs on clonogenic growth. CONCLUSION/CONCLUSIONS:Therefore, CAFs enhance PDAC clonogenic growth, self-renewal, and the frequency of CSCs through type I collagen production that enhances integrin-FAK signaling in PDAC cells.
PMCID:6411432
PMID: 30747824
ISSN: 1536-4828
CID: 4741012
Variation in the surgical management of locally advanced pancreatic cancer. [Meeting Abstract]
ISI:000487345805309
ISSN: 0732-183x
CID: 4745032
