Publications by authors named "Nicholas Petrelli"

151 Publications

Characteristics of Gastrointestinal Stromal Tumors incidentally discovered during abdominal surgery.

Am J Surg 2021 Apr 22. Epub 2021 Apr 22.

Helen F Graham Cancer Center and Research Institute at Christiana Care Department of General and Surgical Oncology, Newark, DE, USA.

Background: Gastrointestinal Stromal Tumors (GISTs) are rare sarcomas with 5000 new cases arising in the United States each year. Despite their low incidence, general surgeons should be familiar with GISTs since a quarter of these neoplasms are encountered incidentally.

Methods: A retrospective medical records review was conducted to create a database of all GISTs resected from January 2005 to May 2019. We isolated patients who had incidental discovery of GISTs intraoperatively or within final pathology. Characteristics of patient (Age, gender), index procedure (malignant vs. benign, elective vs. emergent) and tumor (location, size and mitotic rate) were analyzed.

Results: A total 48 patients were incidentally discovered to have a GIST excised during index operation. The mean age of these patients was 62 years, with 27 females and 21 males. The primary location of tumors in descending frequency was stomach (30), small bowel (15), colon/rectum (2) and esophagus (1). The average size of all tumors was 1.2 cm, with the average size of the stomach, small bowel, colon/rectum and esophagus at 0.9 cm, 1.7 cm, 0.9 cm and 0.3 cm respectively. Mitotic rate was less than 5 mitosis per 50 HPF in 96% of patients. Incidental tumors were identified during both bariatric (13) and non-bariatric stomach surgery (8), colorectal surgery (14), hernia repair (4), ampullary/pancreatic surgery (5), esophageal surgery (2) liver surgery (1) and uterine surgery (1). Most incidental-GISTs were identified during elective surgery (81%, 39). Finally, 15 of the tumors were identified during surgery for other malignancies.

Conclusions: One quarter (25%) of the GISTs encountered at our academic community cancer center over a 15-year period were discovered incidentally. These tumors had less malignant characteristics overall and were likely cured with surgical resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjsurg.2021.04.010DOI Listing
April 2021

The disclosure slide-Informative or obligatory, 5 years of SSO Cancer Symposium oral presentations.

J Surg Oncol 2021 Apr 18. Epub 2021 Apr 18.

Division of Surgical Oncology, Helen F Graham Cancer Center and Research Institute, Christiana Care Health System, Newark, Delaware, USA.

Background: Financial disclosure (FD) highlights potential conflicts of interest but is often overlooked at academic conferences.

Methods: Retrospective review of 2015-2019 Society of Surgical Oncology Cancer Symposium oral presentation slide and/or verbal FD frequency, duration, and content.

Results: Of 963 presentations, 331 (34%) omitted disclosure slide/verbalization. 575 (60%) included a slide, 551 (57%) gave verbal disclosure and 133 (14%) stated relevance. 164 presentations (17%) cited 1 + FD. 2019 had greater median FDs/talk than 2015-2018 (3.50 vs. 2.00; p = .010). Compared to 2015-2018, 2019 yielded shorter median slide display of all disclosures (2.00 s vs. 2.47 s; p = .006), median 1 + FD display (3.37 s vs. 4.81 s; p = .04) and median 1 + FD verbalization (2.81 s vs. 3.66 s; p = .54). 2019 all disclosure verbalization increased (1.97 s vs. 1.14 s; p < .001). Multivariable modeling showed longer display with 2015-2018 (+1.3 s, 95% confidence interval [CI] -0.06 to 2.5 s, p = .04), <4 authors (+3.2 s, 95% CI: 2.1-4.3 s; p < .001) and longer verbalization with 2019 (+0.8 s, 95% CI: 0.2-1.4 s; p = .01), relevance (+1.0 s, 95% CI: 0.4-1.6 s; p = .002), ≤ 4 authors (+0.8 s, 95% CI: 0.3-1.3 s, p < .001) and noncommercial FD (+3.8 s, 95% CI: 2.0-5.0 s; p < .001). The five most cited commercial entities were in 39% of talks.

Conclusion: Presenters' FDs were brief or omitted. Despite FD increase, disclosure time decreased. Improved FD attention will highlight potential COIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26456DOI Listing
April 2021

Microbiome and colorectal cancer: A review of the past, present, and future.

Surg Oncol 2021 Apr 3;37:101560. Epub 2021 Apr 3.

Department of Surgical Oncology, Helen F. Graham Cancer Center, ChristianaCare, Newark, DE, USA.

The gastrointestinal tract is home to diverse and abundant microorganisms, collectively referred to as the microbiome. This ecosystem typically contains trillions of microbial cells that play an important role in regulation of human health. The microbiome has been implicated in host immunity, nutrient absorption, digestion, and metabolism. In recent years, researchers have shown that alteration of the microbiome is associated with disease development, such as obesity, inflammatory bowel disease, and cancer. This review discusses the five decades of research into the human microbiome and the development of colorectal cancer - the historical context including experiments that sparked interest, the explosion of research that has occurred in the last decade, and finally the future of testing and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2021.101560DOI Listing
April 2021

A Comparison of Colectomy Outcomes Utilizing Open, Laparoscopic, and Robotic Techniques.

Am Surg 2020 Dec 19:3134820973384. Epub 2020 Dec 19.

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE, USA.

Introduction: Robotic colectomy could reduce morbidity and postoperative recovery over laparoscopic and open procedures. This comparative review evaluates colectomy outcomes based on surgical approach at a single community institution.

Methods: A retrospective review of all patients who underwent colectomy by a fellowship-trained colon and rectal surgeon at a single institution from 2015 through 2019 was performed, and a cohort developed for each approach (open, laparoscopic, and robotic). 30-day outcomes were evaluated. For dichotomous outcomes, univariate logistic regression models were used to quantify the individual effect of each predictor of interest on the odds of each outcome. Continuous outcomes received a similar approach; however, linear and Poisson regression modeling were used, as appropriate.

Results: 115 patients were evaluated: 14% (n = 16) open, 44% (n = 51) laparoscopic, and 42% (n = 48) robotic. Among the cohorts, there was no statistically significant difference in operative time, rate of reoperation, readmission, or major complications. Robotic colectomies resulted in the shortest length of stay (LOS) (Kruskal-Wallis < .0001) and decreased estimated blood loss (EBL) (Kruskal-Wallis = .0012). Median age was 63 years (interquartile range [IQR] 53-72). 54% (n = 62) were female. Median American Society of Anesthesiologists physical status classification was 3 (IQR 2-3). Median body mass index was 28.67 (IQR 25.03-33.47). A malignant diagnosis was noted on final pathology in 44% (n = 51).

Conclusion: Among the 3 approaches, there was no statistically significant difference in 30-day morbidity or mortality. There was a statistically significant decreased LOS and EBL for robotic colectomies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003134820973384DOI Listing
December 2020

Meta-Analysis on the Effect of Pasireotide for Prevention of Postoperative Pancreatic Fistula.

Am Surg 2020 Dec 1;86(12):1728-1735. Epub 2020 Sep 1.

Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute Christiana Care Health System, DE, USA.

Background: A randomized controlled trial of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting.

Methods: Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed.

Results: Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts ( < .001) and softer glands ( = .04). For all pancreatectomies, there was no difference in POPF rates (odds ratio [OR] 0.84; 95% CI 0.60-1.16, = .29). Patients undergoing distal pancreatectomy (OR 0.70; 95% CI 0.30-1.63, = .41) had similar rates of POPF versus pancreaticoduodenectomy (PD) patients who experienced a lower incidence of POPF (OR 0.60; 95% CI 0.42-0.86, = .006).Mortality rates and LOS were similar. Readmission rates were decreased with pasireotide (OR 0.61; 95% CI 0.44-0.85).

Conclusions: Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD, and decreased readmission rates. Further prospective, randomized studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003134820947371DOI Listing
December 2020

Meta-analysis on the Effect of Pasireotide for Prevention of Postoperative Pancreatic Fistula.

Am Surg 2020 May;86(5):429-436

Division of Surgical Oncology, Helen F. Graham Cancer Center and Research Institute, Christiana Care Health System, Newark, DE, USA.

Background: A randomized controlled trial (RCT) of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting.

Methods: Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed.

Results: Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts ( ≤.001) and softer glands ( = .04). For all pancreatectomies, there was no difference in POPF rates (OR 0.84; 95% CI 0.60-1.16, = .29). Patients undergoing distal pancreatectomy (OR 0.70; 95% CI 0.30-1.63, = .41) had similar rates of POPF versus pancreaticoduodenectomy (PD) patients that experienced a lower incidence of POPF (OR 0.60; 95% CI 0.42-0.86, = .006). Mortality rates and LOS were similar. Readmission rates were decreased with pasireotide (OR 0.61; 95% CI 0.44-0.85).

Conclusions: Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD and decreased readmission rates. Further prospective, randomized studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003134820918260DOI Listing
May 2020

Editorial.

Surg Oncol 2020 06 4;33:192. Epub 2020 May 4.

Helen F. Graham Cancer Center & Research Institute Christiana Care, 4701 Ogletown Stanton Road Newark , Delaware , 19713 USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2020.04.030DOI Listing
June 2020

Health-Care Workers' Perception of Reimbursement for Complex Surgical Oncology Procedures.

Am Surg 2020 Feb;86(2):140-145

Perception of physician reimbursement for surgical procedures is not well studied. The few existing studies illustrate that patients believe compensation to be higher than in reality. These studies focus on patient perceptions and have not assessed health-care workers' views. Our study examined health-care workers' perception of reimbursement for complex surgical oncology procedures. An anonymous online survey was distributed to employees at our cancer center with descriptions and illustrations of three oncology procedures-hepatectomy, gastrectomy, and pancreaticoduodenectomy. Participants estimated the Medicare fee and gave their perceived value of each procedure. Participants recorded their perception of surgeon compensation overall, both before and after revealing the Medicare fee schedule. Most of the 113 participants were physicians (33.6%) and nurses (28.3%). When blinded to the Medicare fee schedules, most felt that reimbursements were too low for all procedures (60-64%) and that surgeons were overall undercompensated (57%). Value predictions for each procedure were discordant from actual Medicare fee schedules, with overestimates up to 374 per cent. After revealing the Medicare fee schedules, 55 per cent of respondents felt that surgeons were undercompensated. Even among health-care workers, a large discrepancy exists between perceived and actual reimbursement. Revealing actual reimbursements did not alter perception on overall surgeon compensation.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2020

Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204).

Oncologist 2020 05 18;25(5):e798-e807. Epub 2019 Dec 18.

Northwestern University, Chicago, Illinois, USA.

Background: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum.

Subjects, Materials, And Methods: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles.

Results: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue.

Conclusion: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer.

Implications For Practice: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216434PMC
May 2020

Precision Medicine.

Surg Oncol Clin N Am 2020 Jan;29(1):xv-xvi

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2019.10.001DOI Listing
January 2020

Precision Medicine in Colorectal Surgery.

Surg Oncol Clin N Am 2020 01;29(1):23-34

Department of Surgery, California Northstate University College of Medicine, Elk Grove, CA 95757, USA. Electronic address:

This article reviews advances in precision medicine for colorectal carcinoma that have influenced screening and treatment, and potentially prevention. Advances in molecular techniques have made it possible for better patient selection for therapies; therefore, mutational analysis should be performed at diagnosis to guide treatment. Future efforts should focus on validating these treatments in specific subgroups and on understanding the mechanisms of resistance to therapies to enable treatment optimization, promote efficacy, and reduce treatment costs and toxicities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2019.09.001DOI Listing
January 2020

High volume pancreaticoduodenectomy performed at an academic community cancer center.

Am J Surg 2019 08 28;218(2):349-354. Epub 2018 Oct 28.

Helen F. Graham Cancer Center & Research Institute at Christiana Care Health System, Department of Surgery, 4701 Ogletown-Stanton Road Suite 4000, Newark, DE, USA, 19713. Electronic address:

Background: We sought to evaluate the post-operative outcomes of patients undergoing pancreaticoduodenectomy at a high volume academic community cancer center.

Methods: A retrospective review was performed of patients undergoing pancreaticoduodenectomy over a 10-year period.

Results: Over 10 years, 213 patients underwent pancreaticoduodenectomy. Median age was 66y. Most patients had significant comorbidities (median ASA = 3) and were overweight (median BMI = 27). Median operative time and blood loss were 253 min and 500 ml, respectively. 160 (75%) out of 213 patients had a malignant lesion on final pathology. 121 (76%) out of 160 had R0 resection. Median lymph nodes harvested was 13. Overall incidence of DGE was 31% (67/213), with clinically significant DGE in 15% (32/213). Pancreatic leak rate was 18% (37/213), with clinically significant leaks in 10% (21/213). Median length of stay was 8 days. Grade 3/4 morbidity rate was 21% (44/206), and 30-day mortality was 2% (5/213).

Conclusions: At a high volume academic community cancer center, pancreaticoduodenectomy can be performed with excellent outcomes on par with any academic center or university hospital.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjsurg.2018.10.041DOI Listing
August 2019

Operative Approach to Rectal Cancer: An Anatomical and Technical Description.

Surg Oncol 2018 06;27(2):A5-A15

Helen F Graham Cancer Center at Christiana Care, Newark Delaware.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2018.05.033DOI Listing
June 2018

Rectal Cancer Management- no longer a solo sport for surgeons.

Surg Oncol 2018 06;27(2):A1

Bank of America Endowed Medical Director, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, Delaware.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2018.05.034DOI Listing
June 2018

Editorial -March issue surgical oncology.

Surg Oncol 2018 03 6;27(1):A1. Epub 2018 Feb 6.

Professor of Oncology, Department of Surgery, California Northstate University College of Medicine, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2018.02.001DOI Listing
March 2018

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma.

Cell Rep 2017 Nov;21(7):1953-1967

Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2017.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726788PMC
November 2017

Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines.

Cell Rep 2017 Nov;21(7):1936-1952

The Wistar Institute, Molecular and Cellular Oncogenesis Program, Tumor Microenvironment and Metastasis Program, and Melanoma Research Center, Philadelphia, PA, USA.

Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified. Multiple minor melanoma subtypes were also recapitulated, including melanomas with multiple activating mutations in the MAPK-signaling pathway and chromatin-remodeling gene mutations. These well-characterized melanoma PDXs and cell lines can be used not only as reagents for a large array of biological studies but also as pre-clinical models to facilitate drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2017.10.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709812PMC
November 2017

Foreword.

Surg Oncol Clin N Am 2017 10 18;26(4):xiii-xiv. Epub 2017 Aug 18.

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, 4701 Ogletown-Stanton Road, Suite 1233, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2017.07.001DOI Listing
October 2017

Foreword.

Surg Oncol Clin N Am 2017 07 5;26(3):xiii-xiv. Epub 2017 May 5.

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health Systems, 4701 Ogletown-Stanton Road, Suite 1233, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2017.02.001DOI Listing
July 2017

Knockdown of sodium-calcium exchanger 1 induces epithelial-to-mesenchymal transition in kidney epithelial cells.

J Biol Chem 2017 07 26;292(27):11388-11399. Epub 2017 May 26.

From the Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803,

Mesenchymal-to-epithelial transition (MET) and epithelial-to-mesenchymal transition (EMT) are important processes in kidney development. Failure to undergo MET during development leads to the initiation of Wilms tumor, whereas EMT contributes to the development of renal cell carcinomas (RCC). The role of calcium regulators in governing these processes is becoming evident. We demonstrated earlier that Na/Ca exchanger 1 (NCX1), a major calcium exporter in renal epithelial cells, regulates epithelial cell motility. Here, we show for the first time that NCX1 mRNA and protein expression was down-regulated in Wilms tumor and RCC. Knockdown of NCX1 in Madin-Darby canine kidney cells induced fibroblastic morphology, increased intercellular junctional distance, and induced paracellular permeability, loss of apico-basal polarity in 3D cultures, and anchorage-independent growth, accompanied by expression of mesenchymal markers. We also provide evidence that NCX1 interacts with and anchors E-cadherin to the cell surface independent of NCX1 ion transport activity. Consistent with destabilization of E-cadherin, NCX1 knockdown cells showed an increase in β-catenin nuclear localization, enhanced transcriptional activity, and up-regulation of downstream targets of the β-catenin signaling pathway. Taken together, knockdown of NCX1 in Madin-Darby canine kidney cells alters epithelial morphology and characteristics by destabilization of E-cadherin and induction of β-catenin signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M116.752352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500804PMC
July 2017

Gastric and Esophageal Cancer 2017.

Surg Oncol Clin N Am 2017 04 6;26(2):xiii-xiv. Epub 2017 Jan 6.

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health Systems, 4701 Ogletown-Stanton Road, Suite 1233, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2016.11.001DOI Listing
April 2017

Anal Cancer 2016.

Surg Oncol Clin N Am 2017 01 27;26(1):xiii-xiv. Epub 2016 Aug 27.

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health Systems, 4701 Ogletown-Stanton Road, Suite 1233, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2016.08.001DOI Listing
January 2017

Folates as adjuvants to anticancer agents: Chemical rationale and mechanism of action.

Crit Rev Oncol Hematol 2016 Oct 9;106:118-31. Epub 2016 Aug 9.

Helen F Graham Cancer Center and Research Institute at Christiana Care Health System, Newark, DE, USA.

Folates have been used with cytotoxic agents for decades and today they are used in hundreds of thousands of patients annually. Folate metabolism is complex. In the treatment of cancer with 5-fluorouracil, the administration of folates mechanistically leads to the formation of [6R]-5,10-methylene-tetrahydrofolate, and the increased concentration of this molecule leads to stabilization of the ternary complex comprising thymidylate synthase, 2'-deoxy-uridine-5'-monophosphate, and [6R]-5,10-methylene-tetrahydrofolate. The latter is the only natural folate that can bind directly in the ternary complex, with other folates requiring metabolic activation. Modulation of thymidylate synthase activity became central in the study of folate/cytotoxic combinations and, despite wide use, research into the folate component was neglected, leaving important questions unanswered. This article revisits the mechanisms of action of folates and evaluates commercially available folate derivatives in the light of current research. Better genomic insight and availability of new analytical techniques and stable folate compounds may open new avenues of research and therapy, ultimately bringing increased clinical benefit to patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.critrevonc.2016.08.001DOI Listing
October 2016

Sarcomas 2016.

Surg Oncol Clin N Am 2016 10 14;25(4):xiii-xiv. Epub 2016 Jun 14.

Helen F. Graham Cancer Center & Research Institute, Christiana Care Health Systems, 4701 Ogletown-Stanton Road, Suite 1233, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2016.05.015DOI Listing
October 2016

Report on demographics of gall bladder cancer in Delaware and retrospective review of treatment strategies for gallbladder cancer in a large community cancer center.

Surg Oncol 2016 Jun 17;25(2):86-91. Epub 2016 Mar 17.

Christiana Care Health System, Department of Internal Medicine, Newark, DE, USA; Christiana Care Health System, Helen F. Graham Cancer Center, Cancer Genetics Program, Newark, DE, USA; Thomas Jefferson University, Department of Surgery, Philadelphia, PA, USA; University of Delaware, Department of Biological Sciences, Newark, DE, USA. Electronic address:

Background: GBC is frequently found incidentally on pathologic review of the removed gallbladder. NCCN guidelines have treatment recommendations based on specific stage of gallbladder cancer (GBC). However, there is limited information on the experience of community cancer centers in treating GBC based on these guidelines.

Objective: To utilize the Delaware cancer registry to describe patients with GBC in Delaware, and to conduct a review of the treatment strategies and outcomes of GBC at a large community cancer center.

Methods: A retrospective cohort study of GBC cases in the state of Delaware utilizing the statewide cancer registry to gather useful demographic and treatment information, such as patient age, gender, date of diagnosis, type of surgeries, systemic or radiation therapy, and survival time. Analysis of surgical management of GBC at Delaware's largest community cancer center comparing their management of patients with different AJCC stages of GBC to the NCCN guidelines.

Results: Our analysis revealed that there were 109 patients diagnosed with GBC in Delaware from 1995 to 2012. The male to female ratio was 2.7:1 and average age at time of diagnosis was 68. Most of GBC diagnosed were stage T2. During this time period, there were 23 extended radical cholecystectomies done for stage T2 and above GBC. Most of the ERC surgeries were performed by fellowship trained surgical oncologists. Our results show that there was mortality benefit in all operable stages of GBC, and the average survival time was higher for all T2 and above stages of GBC.

Conclusion: A statewide cancer registry is instrumental in retrospective review of demographics and treatment outcomes for rare and aggressive tumors such as GBC. We demonstrated that a large community cancer center, such as Christiana Care Health System, with on staff surgical oncologists is capable of providing GBC treatment that is according to NCCN guidelines and comparable to major academic centers based on mortality outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suronc.2016.03.003DOI Listing
June 2016

Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes: Secondary Analysis of NSABP C-07/NRG Oncology Randomized Clinical Trial.

JAMA Oncol 2016 Sep;2(9):1162-9

National Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology, Pittsburgh, Pennsylvania7Division of Medical Oncology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.

Importance: Oxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit.

Objective: To test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy.

Design, Setting, And Participants: Participants in the NSABP C-07 trial were divided into discovery (n = 848) and validation (n = 881) cohorts based on the order of tissue block submission. A reestimated centroid using 72 genes was used to determine Colorectal Cancer Assigner subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was examined with a locked-down algorithm for subtype classification and statistical analysis plan. Post hoc analysis included examination of the entire cohort with Colorectal Cancer Assigner, Colorectal Cancer Subtype (CCS), and Consensus Molecular Subtype (CMS) methods.

Interventions: Fluorouracil plus leucovorin with or without oxaliplatin.

Main Outcomes And Measures: Percent recurrence-free survival.

Results: Among 1729 patients, 744 (43%) were female and mean (SD) age was 58 (11) years. Although C-07 participants with stage III disease with an enterocyte subtype showed a statistically significant benefit from oxaliplatin in the discovery cohort (hazard ratio, 0.22 [95% CI, 0.09-0.56]; P = .001 [N = 65]), no statistically significant benefit was observed in the validation cohort (hazard ratio, 0.53 [95% CI, 0.22-1.24]; P = .14 [N = 70]). The stemlike subtype was associated with poor prognosis and lack of benefit from oxaliplatin treatment (HR, 0.99 [95% CI, 0.73-1.34]; P = .96 [N = 367]). Examination of the different subtyping methods shows that all 3 methods robustly identified patients with poor prognosis (stemlike, CCS-3, and CMS-4) in both stage II and III.

Conclusions And Relevance: Patients with stemlike tumors may be appropriate for clinical trials testing experimental therapies because stemlike tumors were robustly identified and associated with a poor prognosis regardless of stage or chemotherapy regimen. The clinical utility of using subtyping for the identification of patients for treatment with oxaliplatin requires validation in independent clinical trial cohorts.

Trial Registration: clinicaltrials.gov Identifier: NCT00004931.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065181PMC
http://dx.doi.org/10.1001/jamaoncol.2016.2314DOI Listing
September 2016

Lung Cancer.

Surg Oncol Clin N Am 2016 07 31;25(3):xiii-xiv. Epub 2016 Mar 31.

Helen F. Graham Cancer Center and Research Institute, Christiana Care Health System, 4701 Ogletown-Stanton Road, Suite 1233, Newark, DE 19713, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2016.03.001DOI Listing
July 2016

Pancreatic Neoplasms.

Surg Oncol Clin N Am 2016 Apr;25(2):xiii-xiv

Bank of America Endowed Medical Director, Helen F Graham Cancer Center & Research Institute, Christiana Care Health Systems, 4701 Ogletown Stanton Road, Suite 1233, Newark, DE 19713, USA; Professor of Surgery, Thomas Jefferson University, Philadelphia, PA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soc.2015.12.004DOI Listing
April 2016

Treatment outcomes in stage IIIA non-small-cell lung cancer in a community cancer center.

J Community Support Oncol 2015 Aug;13(8):292-5

Helen F Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, Delaware, USA.

Background: Treatment outcomes for non-small-cell lung cancer (NSCLC) patients diagnosed at stage IIIA have been analyzed in many studies, which generally involve patients younger and healthier than the average patient with this disease.

Objective: To analyze demographics and treatment outcomes in patients with stage IIIA NSCLC at a community cancer center.

Methods: We reviewed charts of 226 patients diagnosed with stage IIIA NSCLC from January 2003 to December 2008 treated at our community cancer center. Results Median overall survival for all patients and sequentially and concurrently treated chemoradiation patients were 18 months, and 18 months, and 20 months, respectively. Median overall survival for women and men was 24 months and 16 months, respectively.

Results: Median overall survival for all patients and sequentially and concurrently treated chemoradiation patients were 18 months, and 18 months, and 20 months, respectively. Median overall survival for women and men was 24 months and 16 months, respectively.

Limitations: Study design was retrospective and some medical records were not available. However, this population is likely representative of patients treated in similar settings.

Conclusions: In our population, advanced age and male gender were associated with lower median survival. Responses to concurrent and sequential chemoradiation seemed to differ based on age group, which may be useful as a prognostic guideline for similar populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12788/jcso.0159DOI Listing
August 2015