Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR. Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. Trial Registration: ClinicalTrials.gov Identifier NCT01042379.

HDAC inhibition prevents transgene expression downregulation and loss-of-function in T-cell-receptor-transduced T cells.

T cells that are gene-modified with tumor-specific T cell receptors are a promising treatment for metastatic melanoma patients. In a clinical trial, we treated seven metastatic melanoma patients with autologous T cells transduced to express a tyrosinase-reactive T cell receptor (TCR) (TIL 1383I) and a truncated CD34 molecule as a selection marker. We followed transgene expression in the TCR-transduced T cells after infusion and observed that both lentiviral- and retroviral-transduced T cells lost transgene expression over time, so that by 4 weeks post-transfer, few T cells expressed either lentiviral or retroviral transgenes. Transgene expression was reactivated by stimulation with anti-CD3/anti-CD28 beads and cytokines. TCR-transduced T cell lentiviral and retroviral transgene expression was also downregulated in vitro when T cells were cultured without cytokines. Transduced T cells cultured with interleukin (IL)-15 maintained transgene expression. Culturing gene-modified T cells in the presence of histone deacetylase (HDAC) inhibitors maintained transgene expression and functional TCR-transduced T cell responses to tumor. These results implicate epigenetic processes in the loss of transgene expression in lentiviral- and retroviral-transduced T cells.

Enhanced recovery after surgery: A clinical review of implementation across multiple surgical subspecialties.

Enhanced recovery after surgery (ERAS) is a multimodal protocol applied towards perioperative patient care. ERAS programs are implemented by a multidisciplinary team centered around the patient, incorporating outpatient clinical staff, preoperative nurses, anesthesiologists, operative nurses, postoperative recovery staff, floor inpatient nurses, dieticians, physical therapists, social workers, and surgeons. Initial studies on perioperative care measures focused on cardiac surgery. Subsequently, the development of the ERAS Study Group in 2001 focused on colorectal surgery and postoperative outcome measures. Today, ERAS protocols have been implemented across many surgical subspecialties including: bariatric, breast, plastic, cardiac, colorectal, esophageal, head and neck, hepatic, gynecologic, neurosurgical, orthopedic, pancreatic, thoracic, and urologic surgery. The goal of ERAS programs is to promote rapid recovery as quantified by decreasing the length of hospital stay, complications, and cost of specific surgical interventions. In the setting of the opioid crisis in America, there is also an increasing focus on minimizing perioperative narcotic use. The purpose of this review is to compare ERAS protocols across surgical subspecialties, focusing on quantified metrics of improvement, and to provide a clear and concise summary of the literature in regards to current ERAS practices and success rates.

The laparoscopic approach to distal pancreatectomy is a value-added proposition for patients undergoing care in moderate-volume and high-volume centers.

BACKGROUND: Little is known regarding the impact of the minimally invasive approach to distal pancreatectomy on the aggregate costs of care for patients undergoing distal pancreatectomy. METHODS: We queried the Healthcare Cost and Utilization Project State Inpatient Database to identify patients undergoing elective laparoscopic distal pancreatectomy or open distal pancreatectomy between 2012 and 2014. Multivariable regression was used to evaluate postoperative outcomes including readmissions to 90 days after distal pancreatectomy. RESULTS: A total of 267 (11%) patients underwent laparoscopic distal pancreatectomy, and a total of 2,214 (89%) underwent open distal pancreatectomy. On multivariable regression, patients undergoing laparoscopic distal pancreatectomy had a decreased odds risk of having any severe adverse outcome (odds ratio 0.73, 95% confidence interval [0.54-0.97]), prolonged length of stay (odds ratio 0.49, 95% confidence interval [0.30-0.79]), and of being in the highest quartile for aggregate costs of care (odds ratio 0.46, 95% confidence interval [0.32-0.66]) relative to those undergoing open distal pancreatectomy. Patients undergoing laparoscopic distal pancreatectomy had a lower average 90-day aggregate cost of care than those undergoing open distal pancreatectomy when procedures were performed in high-volume (-$16,153, 95% CI: [-$23,342 to -$8,964]) centers. CONCLUSION: Patients undergoing laparoscopic distal pancreatectomy have a lower risk of severe adverse outcomes, prolonged overall length of stay, and lower associated costs of care relative to those undergoing open distal pancreatectomy. This association is independent of hospital volume.

Considerations for sentinel lymph node biopsy in breast cancer patients with biopsy proven axillary disease prior to neoadjuvant treatment.

BACKGROUND: Axillary disease can be downstaged with neoadjuvant treatment for breast cancer. We attempted to identify factors to consider in determining whether to perform a sentinel lymph node biopsy in patients with biopsy proven axillary metastases (cN+) prior to neoadjuvant treatment. METHODS: A retrospective chart review was conducted on patients at a single tertiary care center who underwent neoadjuvant treatment followed by surgery between 9/2013 and 2/2017. RESULTS: 47% of patients with node positive disease prior to neoadjuvant treatment were downstaged to node negative (ypN0) disease. These patients were more likely to have triple negative or Her2 positive disease than those patients who remained node positive (ypN+) as these were more likely to have hormone receptor positive disease. These patients were also more likely to demonstrate complete clinical imaging response of the primary tumor and axilla on preoperative breast MRI. CONCLUSIONS: Tumor biology and clinical response noted on breast MRI can help guide the decision to perform sentinel lymph node biopsy in patients with axillary node positive disease prior to neoadjuvant treatment.

Epidemiology of breast cancer.

This article outlines the current incidence, prevalence, and mortality of breast cancer and reviews the epidemiology of the disease. Major risk factors for the development of breast cancer are covered, including reproductive, genetic, and environmental variables. Understanding the epidemiology of breast cancer will help clinicians identify high-risk patients for appropriate screening and informed disease management decisions.

Are there gender differences in choosing a surgical career?

BACKGROUND: Interest in general surgery has declined among US medical students, with the increasing number of female medical students being cited as a causative factor. This study evaluates factors related to choosing a general surgery career and determines if they differ between men and women. METHODS: A survey assessing factors that contributed to career choice was distributed to a 2002 graduating medical school class to be returned with their match lists. Students were asked, from a given list, which factors influenced their career choice. Those students who did not pursue a career in general surgery were asked what factors contributed to that decision. The results were stratified by gender. RESULTS: Of 120 surveys, 54 women and 48 men responded (response rate=85%). The reason most commonly cited for a particular career choice by both men and women was the intellectual challenge of the field, chosen by 41 men (85%) and 46 women (85%). The two next most common reasons cited by male students were an elective in the field and practice lifestyle (40 of 48 respondents, or 82%, for each). Practice lifestyle was a contributing factor for 37 of the 54 women, or 69% (P=.132). The other reasons most commonly cited by women were an elective and faculty in the chosen field (46 of 54, or 85%, and 38 of 54, or 70%). Thirty-seven of the 48 men, or 77% (P=.588), felt that faculty in the field contributed to their career choice. The most commonly cited reasons for not choosing general surgery--residency lifestyle, practice lifestyle, and length of training--were the same for both groups. CONCLUSIONS: Fewer women than men considered practice lifestyle in choosing their medical career. However, both men and women considered lifestyle, elective in the field of choice, and faculty important in career choice. In 2002, men and women had the same reasons for pursuing a career in general surgery or seeking another specialty.

Vascular complications associated with pancreaticoduodenectomy adversely affect clinical outcome.

BACKGROUND: Early survival after pancreaticoduodenectomy has improved, but its morbidity remains high. The purpose of this study is to determine how the intra-operative (OR) occurrence of major vascular complications affects the outcome of pancreaticoduodenectomy. METHODS: The medical records of 180 consecutive patients having pancreaticoduodenectomy from 1991 to 2001 were reviewed. Vascular complications were defined as "an unanticipated injury or thrombosis of a major vessel necessitating intervention." Age, sex, type of pancreaticoduodenectomy, tumor size, estimated blood loss, OR time, time in intensive care, post-OR hospitalization, and survival were compared. RESULTS: Eighteen vascular complications were identified. Differences in age, sex, and type of resection between patients with or without vascular complications were not significant. OR time, estimated blood loss, blood transfusions, tumor size, time in intensive care, and post-OR hospitalization were all significantly greater in patients with vascular complications. Median survival for patients with vascular complications was significantly shorter than for patients without vascular complications. Thirty-day mortality was greater in patients with vascular complications. CONCLUSION: Vascular complications significantly affect the outcome of pancreaticoduodenectomy increasing OR time, estimated blood loss, blood transfusion requirements, time in intensive care, post-OR hospitalization, and mortality.

Human heparanase-1 gene expression in pancreatic adenocarcinoma.

Extracellular matrix degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the extracellular matrix. HPR1 is not expressed in normal epithelial cells but can be detected in a variety of malignancies. In the present study, we examined HPR1 expression in pancreatic cancer by using in situ hybridization and tested whether HPR1 expression correlated with any clinicopathlogic parameters. HPR1 was not detected in the ductal cells of normal pancreas samples obtained from 10 patients at autopsy. However, HPR1 was detected in 77 (78%) of 99 pancreatic adenocarcinomas. Among them, 69 (78%) of 89 primary pancreatic adenocarcinomas and 8 (80%) of the 10 metastases were HPR1 positive. Age, sex, tumor stage, and lymph node status were not predictive of HPR1 expression. Log-rank test of the Kaplan-Meier survival curves revealed that HPR1 expression in early-stage tumors was associated with decreased survival. HPR1 expression was frequent in pancreatic adenocarcinomas and was associated with decreased survival in early-stage tumors. This suggests that HPR1 may contribute to the highly invasive and early metastatic behavior of pancreatic cancer.