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1.
J Surg Oncol ; 127(1): 34-39, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36181515

ABSTRACT

BACKGROUND AND OBJECTIVES: In 2003, the Society of Surgical Oncology (SSO) initiated a breast surgical oncology fellowship, which has now grown to 60 SSO accredited programs as of 2021. Limited knowledge exists on the traits of successful applicants and the factors influencing the rank list. METHODS: A web-based, anonymous survey was sent to all SSO Breast Surgical Oncology Fellowship program directors. The survey consisted of 26 questions. Descriptive statistics were used to analyze survey responses and evaluate impact on applicant interview and rank list. RESULTS: Thirty-four programs (57% response rate) completed the survey. Programs received an average of 70 applications and granted 24 interviews. Most programs reported a minimum ABSITE cut-off score (n = 28, 82%) and a defined publication requirement (n = 22, 65%), including a first-author requirement (n = 18, 53%) to extend an invitation to interview. For postinterview rank, applicant interpersonal skills were highly valued. The interview was the most important aspect for the rank list. CONCLUSIONS: Many programs have ABSITE and publication thresholds before offering an interview. Upon receiving interview invitation, the applicant's interview performance, interpersonal skills, and letters of recommendation were the most important aspect in rank list decision making.


Subject(s)
Internship and Residency , Surgical Oncology , Humans , Fellowships and Scholarships , Surveys and Questionnaires
2.
Am J Surg ; 224(5): 1256-1261, 2022 11.
Article in English | MEDLINE | ID: mdl-35999087

ABSTRACT

BACKGROUND: Post-operative pancreatic fistula (POPF) is a serious complication following pancreas surgery. We aimed to establish factors associated with POPF specifically in patients with pancreatic neuroendocrine tumors (PNET). METHODS: The 2014-2018 American College of Surgeons National Surgical Quality Improvement Program database was querried for patients undergoing resection for PNET. The impact of patient, tumor, and operative factors on POPF formation was evaluated. RESULTS: 3532 patient underwent resections for PNET. The POPF rate was significantly higher in patients with PNET (24.8%) versus non-PNET (16.4%) (p < 0.0001). Male sex (OR 1.45, 95% CI 1.11-1.89), enucleation (OR 3.14, 95% CI 1.10-8.98), pancreaticoduodenectomy (OR 1.51, 95% CI 1.13-2.03), small duct size <3 mm (OR 3.24, 95% CI 1.62-6.48), and soft gland texture (OR 1.81, 95% CI 1.18-2.77) were independently associated with POPF in PNET patients on multivariable analysis. CONCLUSIONS: POPF is more common in patients undergoing resection for PNET and is dictated primarily by surgical approach and gland characteristics.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Male , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Quality Improvement , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/pathology , Pancreaticoduodenectomy/adverse effects , Pancreas/surgery , Postoperative Complications/etiology , Pancreatic Neoplasms/pathology , Risk Factors , Retrospective Studies
3.
Cancer Immunol Res ; 10(8): 932-946, 2022 08 03.
Article in English | MEDLINE | ID: mdl-35749374

ABSTRACT

Adoptive cellular therapy (ACT) targeting neoantigens can achieve durable clinical responses in patients with cancer. Most neoantigens arise from patient-specific mutations, requiring highly individualized treatments. To broaden the applicability of ACT targeting neoantigens, we focused on TP53 mutations commonly shared across different cancer types. We performed whole-exome sequencing on 163 patients with metastatic solid cancers, identified 78 who had TP53 missense mutations, and through immunologic screening, identified 21 unique T-cell reactivities. Here, we report a library of 39 T-cell receptors (TCR) targeting TP53 mutations shared among 7.3% of patients with solid tumors. These TCRs recognized tumor cells in a TP53 mutation- and human leucocyte antigen (HLA)-specific manner in vitro and in vivo. Twelve patients with chemorefractory epithelial cancers were treated with ex vivo-expanded autologous tumor-infiltrating lymphocytes (TIL) that were naturally reactive against TP53 mutations. However, limited clinical responses (2 partial responses among 12 patients) were seen. These infusions contained low frequencies of mutant p53-reactive TILs that had exhausted phenotypes and showed poor persistence. We also treated one patient who had chemorefractory breast cancer with ACT comprising autologous peripheral blood lymphocytes transduced with an allogeneic HLA-A*02-restricted TCR specific for p53R175H. The infused cells exhibited an improved immunophenotype and prolonged persistence compared with TIL ACT and the patient experienced an objective tumor regression (-55%) that lasted 6 months. Collectively, these proof-of-concept data suggest that the library of TCRs targeting shared p53 neoantigens should be further evaluated for the treatment of patients with advanced human cancers. See related Spotlight by Klebanoff, p. 919.


Subject(s)
Hematopoietic Stem Cell Transplantation , Neoplasms , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Genes, T-Cell Receptor , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Neoplasms/genetics , Neoplasms/therapy , Receptors, Antigen, T-Cell/immunology , T-Lymphocytes/immunology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/immunology
4.
J Surg Res ; 269: 1-10, 2022 01.
Article in English | MEDLINE | ID: mdl-34507081

ABSTRACT

INTRODUCTION: North America is in the midst of an opioid epidemic. The role of pediatric surgeons and other procedural specialists in this public health crisis remains unclear. There is likely considerable variation in the use of opioid and non-opioid analgesics, but the spectrum of practice is still uncertain. METHODS: We performed an online survey in July 2018 of the 2086 pediatric surgeons and proceduralists who were active members in the American Academy of Pediatrics. The survey inquired about practice environment, use of opioid and non-opioid pain medications, and attitudes towards the opioid epidemic. RESULTS: 178 specialists completed the survey for a response rate of 8.5%. Most respondents utilize oral acetaminophen (86%) and ibuprofen (80%) after procedures >75% of the time. Self-reported opioid prescribing increases with age after both outpatient and inpatient procedures (P < 0.001). Pediatric general surgeons prescribe opioids less frequently than other specialists, particularly after inpatient procedures. The majority of respondents (81%) believe that the opioid epidemic is a major problem but only 31% indicated that they have a major role to play. CONCLUSIONS: There is significant variation in opioid prescribing patterns as reported by pediatric surgeons and proceduralists. Guidelines are needed to standardize the use of non-opioid analgesics and decrease reliance on opioids for outpatient and inpatient procedures.


Subject(s)
Analgesics, Opioid , Pediatrics , Analgesics, Opioid/adverse effects , Child , Humans , Pain, Postoperative/drug therapy , Practice Patterns, Physicians' , Surveys and Questionnaires , United States
5.
JAMA Oncol ; 2021 Jun 17.
Article in English | MEDLINE | ID: mdl-34137798
6.
Int J Mol Sci ; 15(9): 15061-72, 2014 Aug 27.
Article in English | MEDLINE | ID: mdl-25167133

ABSTRACT

The α-chemokine, stromal-derived factor-1 (SDF-1), has been linked to the homing of circulating tumor cells to bone. SDF-1 is expressed by bone microvascular cells and osteoblasts and normally functions to attract blood-borne hematopoietic stem and progenitor cells to marrow. It has been shown that treatment of cancer cells with soluble SDF-1 results in a more aggressive phenotype; however, the relevance of the administration of the soluble protein is unclear. As such, a flow device was functionalized with P-selectin and SDF-1 to mimic the bone marrow microvasculature and the initial steps of cell adhesion. The introduction of SDF-1 onto the adhesive surface was found to significantly enhance the adhesion of lymphoma cells, as well as low-density bone marrow cells (LDBMC), both in terms of the number of adherent cells and the strength of cell adhesion. Thus, SDF-1 has a synergistic effect with P-selectin on cancer cell adhesion and may be sufficient to promote preferential metastasis to bone.


Subject(s)
Bone Marrow Cells/physiology , Chemokine CXCL12/metabolism , P-Selectin/metabolism , Bone Marrow Cells/metabolism , Cell Adhesion , Cells, Immobilized/metabolism , Cells, Immobilized/physiology , Chemokine CXCL12/genetics , Humans , Microfluidics , Microvessels/cytology , Microvessels/physiology , P-Selectin/genetics , U937 Cells
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