A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Impact of Postoperative Antibiotic Prophylaxis on Surgical Site Infections Rates After Mastectomy with Drains but Without Immediate Reconstruction: A Multicenter, Double-Blinded, Randomized Control Superiority Trial.

BACKGROUND: There is no consensus on the use of postoperative antibiotic prophylaxis (PAP) after mastectomy with indwelling drains. We explored the utility of continued PAP in reducing surgical site infection (SSI) rates after mastectomy without immediate reconstruction and with indwelling drains. PATIENTS AND METHODS: A multicenter, two-armed, randomized control superiority trial was conducted in Pakistan. We enrolled all consenting adult patients undergoing mastectomy without immediate reconstruction. All patients received a single preoperative dose of cephalexin within 60 min of incision, and postoperatively were randomized to receive either continued PAP using cephalexin (intervention) or a placebo (control) for the duration of indwelling, closed-suction drains. The primary outcome was the development of SSI within 30 days and 90 days postoperatively. Secondary outcomes included study-drug-associated adverse events. Intention-to-treat analysis was performed using multivariable Cox regression. RESULTS: A total of 369 patients, 180 (48.8%) in the intervention group and 189 (51.2%) in the control group, were included in the final analysis. Overall cumulative SSI rates were 3.5% at 30 days and 4.6% at 90 days postoperatively. PAP was not associated with SSI reduction at 30 (hazard ratio, HR 1.666 [95% confidence interval CI 0.515-5.385]) or 90 (1.575 [0.558-4.448]) days postoperatively, or with study-drug-associated adverse effects (0.529 [0.196-1.428]). CONCLUSIONS: Continuing antibiotic prophylaxis for the duration of indwelling drains after mastectomy without immediate reconstruction offers no additional benefit in terms of SSI reduction. There is a need to update existing guidelines to provide clearer recommendations regarding use of postoperative antibiotic prophylaxis after mastectomy in the setting of indwelling drains.

Practice Patterns of Antibiotic Prophylaxis in Patients Undergoing Mastectomy: A Survey of Members of the American Society of Breast Surgeons.

BACKGROUND: Surgical site infections after breast surgery range from 1 to 16%. Both the American Society of Breast Surgeons (ASBrS) and the American Association of Plastic Surgeons guidelines lack clarity on postoperative antibiotic prophylaxis (AP) after mastectomy. We surveyed the ASBrS membership to understand their practice patterns of AP after mastectomy and familiarity with ASBrS guidelines. METHODS: A self-designed, 19-question survey was emailed to all 2934 ASBrS members. Information was obtained on the participants' training, familiarity with ASBrS guidelines, and practices of prescribing perioperative AP after mastectomy with/without reconstruction and with indwelling drains. RESULTS: In total, 556 (19%) responses were analyzed. Half were fellowship-trained breast surgeons/surgical oncologists (50.2%), with 55.6% having practiced for > 15 years and 66.9% in community/private practice. Only 53.6% reported familiarity with ASBrS guidelines for perioperative AP. Most (> 90%) surgeons reported "always" placing drains after mastectomy and "always" prescribing preoperative AP. Postoperatively, preference for continuing AP in cases with drains in place varied by procedure: 7.7% when no reconstruction, 29.1% when autologous-only, and 52.5% when implant reconstruction. Academic surgeons were less likely than surgeons in community/private practice to continue postoperative AP, whether for the duration of indwelling drains (5.1% versus 9.4%) or even till 7 days postoperatively (0.6% versus 3.2%) (p < 0.05). CONCLUSIONS: Surgeons uniformly adhere to ASBrS guidelines for preoperative AP. However, there is wide variation in AP postoperatively in patients with/without reconstruction and with indwelling drains. Our results highlight the need for high-quality evidence based on which guidelines must be updated, and the need to familiarize surgeons with current guidelines.

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy.

INTRODUCTION: Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of biomarker [hormone receptor (HR) and HER2] change and its effect on disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: A total of 303 patients treated with NAT from 2008 to 2016 were identified from a prospective database. Biomarker status at diagnosis was determined and retested after NAT in patients with RD. DFS and OS were compared among three groups: no biomarker change, clinically insignificant change in either ER or PR without alteration in HR status, and clinically significant change in at least one biomarker with resultant change in HR or HER2 status. Subgroups with no change and HR change were examined [HR+HER2- no change, triple negative (TN) no change, HR+HER2- to TN, TN to HR+HER2]. RESULTS: Overall, 61.4% of patients had RD. Of these, 32.8% had changes in at least one biomarker. At median follow up of 5.48 years, no biomarker change was associated with improved DFS compared with changes in HR or HER2 status (p = 0.043). In addition, no biomarker change (p = 0.005) and clinically insignificant changes in biomarker status (p = 0.019) were associated with improved OS compared with clinically significant changes in HR or HER2 status. Among subgroups, HR+HER2- to TN was associated with worse DFS (p = 0.029) and OS (p = 0.008) compared with HR+HER2- no change. CONCLUSIONS: Among those with RD, biomarker status change was common and impacted survival in subgroups of HR+ or TN disease. Retesting biomarkers after NAT has prognostic implications.

Changes in utilization of axillary dissection in women with invasive breast cancer and sentinel node metastasis after the ACOSOG Z0011 trial.

The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial demonstrated no survival advantage for women with clinical T1-T2 invasive breast cancer with 1-2 positive sentinel lymph nodes (SLN) who received whole-breast radiation, and no further axillary surgery when compared to women who did undergo axillary lymph node dissection (ALND). We used the National Cancer Database (NCDB) to study changes in utilization of ALND after the publication of this trial. NCDB was queried for female patients from 2012 to 2015 who met Z0011 criteria. Patients were divided into four groups based on Commission on Cancer facility accreditation. Outcome measures include the rate of ALND (nonadherence to Z0011) and the average number of nodes retrieved with ALND. 27,635 patients were identified, with no significant differences in T stage and receptor profiles between groups. Overall rate of ALND decreased from 34.0% in 2012 to 22.7% in 2015. Nonadherence was lowest in Academic Programs (decreasing from 30.1% in 2012 to 20.5% in 2015) and was highest in Community Cancer Programs (41.2% in 2012 to 29.1% in 2015). Median number of positive SLN did not differ between groups (p = .563). Median number of nodes retrieved on ALND decreased from 9 (IQR 5-14) in 2012 to 7 (IQR 4-12) in 2015 (p < .001). In patients who met the ACOSOG Z11 trial guidelines, rates of ALND have decreased over time. However, rates of nonadherence to Z0011 are significantly higher in Community Cancer Programs compared to Academic Programs.

Use of the End to End Anastomotic Stapler From Above for Difficult Pelvic Surgery for Distal Rectal Disease.

INTRODUCTION: Transabdominal utilization (TAU) of the end to end anastomotic (EEA) stapler in low anterior resection (LAR) for rectal cancer is an excellent alternative to the most widely performed techhnique. METHODS: We performed a retrospective analysis of a prospectively maintained database which obtained data on 104 patients with rectal disease who underwent EEA-assisted LAR with TAU. Records of all patients were used to evaluate demographics, complications, tumor location, margin status, postoperative complications, clinical sphincter function, adjuvant or neoadjuvant treatment, disease stage, and survival. RESULTS: Of the 104 patients, 48% were women with a mean age of 64 years (range 34-85 years). The average tumor location was 8 cm above the dentate line, and the mean tumor distance from the distal margin was 1.9 cm. All distal margins in cases for patients with rectal cancer were negative. Hospital length of stay averaged 8.7 days (6-15 days). There were no anastomotic complications (leaks, bleeding, or obstruction), and there were no leaks at the separate colotomy site. All patients have had normal postoperative sphincter function. CONCLUSION: Transabdominal utilization of the EEA stapler in LAR for colorectal carcinoma is an alternative to the conventional approach and may be advantageous in avoidance of the lithotomy position with potential nerve injury, risk of deep venous thrombosis, and stapler-induced sphincter trauma.

Factors associated with general surgery residents' decisions regarding fellowship and subspecialty stratified by burnout and quality of life.

BACKGROUND: Although most surgery residents pursue fellowships, data regarding those decisions are limited. This study describes associations with interest in fellowship and specific subspecialties. METHODS: Anonymous surveys were distributed to 607 surgery residents at 19 US programs. Subspecialties were stratified by levels of burnout and quality of life using data from recent studies. RESULTS: 407 (67%) residents responded. 372 (91.4%) planned to pursue fellowship. Fellowship interest was lower among residents who attended independent or small programs, were married, or had children. Residents who received AOA honors or were married were less likely to choose high burnout subspecialties (trauma/vascular). Residents with children were less likely to choose low quality of life subspecialties (trauma/transplant/cardiothoracic). CONCLUSIONS: Surgery residents' interest in fellowship and specific subspecialties are associated with program type and size, AOA status, marital status, and having children. Variability in burnout and quality of life between subspecialties may affect residents' decisions.

The Clinicopathological Aspects of Primary Presacral Neuroendocrine Neoplasms: One Center Experience.

OBJECTIVES: Presacral neuroendocrine neoplasms (NENs) are rare entities that are found at the presacral space. We report our experience in the diagnosis, management, and outcomes of primary presacral NENs. METHODS: This was an institutional review board-approved retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of NENs at Cedars-Sinai Medical Center between January 2000 and April 2016. RESULTS: Ten patients were identified. The median age at presentation was 38 years (range, 20-77 years), and 8 were women. One patient presented with carcinoid-like symptoms, 2 were diagnosed incidentally, and 7 presented with symptoms related to mass effect. The median size of the tumor was 7.0 cm (range, 3-12 cm). On pathologic review, 3 of 10 were low-grade and well-differentiated, 5 of 10 were intermediate-grade and well-differentiated, 2 of 10 were grade 3 and classified as high-grade and poorly differentiated neuroendocrine tumors. Seven cases were metastatic on presentation with lymph node, liver, lung, or skeletal metastasis. Seven of 8 cases were detectable using Octreoscan. Eight patients were treated with a somatostatin analog and 5 patients were treated surgically. CONCLUSIONS: Presacral NENs are clinically similar to gastroenteropancreatic tumors. Octreoscan imaging and somatostatin analog therapies were frequently applied. Further biologic characterization of this rare subtype is needed.

Breast cancer following ovarian cancer in BRCA mutation carriers.

IMPORTANCE: BRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized. OBJECTIVES: To determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers. MAIN OUTCOMES AND MEASURES: Incidence of breast cancer and methods of surveillance. RESULTS: Of 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%. CONCLUSIONS AND RELEVANCE: The risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.

Intraductal papillary lesions of the breast: clinical and pathological correlation.

Papillary lesions of the breast range from a spectrum of benign intraductal papillomas with and without atypia to papillary carcinoma. Distinction between benign and malignant lesions on core needle biopsy (CNB) is difficult without surgical excision. We examined if clinical findings in patients with benign intraductal papillomas (IP) on CNB correlate with pathology at surgical excision. Between 1998 and 2011, 103 patients were identified with a papillary lesion on CNB. Clinical variables were studied to determine if there was clinical correlation with pathological outcomes at final surgical excision. Of the 103 patients, 59 (57%) patients had IP on initial CNB and were included in our analysis. On final pathology, 17 (29%) of these were upstaged to intraductal papilloma with atypia and six (10%) were found to have carcinoma. A clinically palpable mass was the only significant predictor of upstaging to malignancy (P<0.05). No radiographic findings were found to be significant predictors of pathological upstaging. In conclusion, surgical excision is still recommended for benign papillary lesions diagnosed on CNB because the correlation with clinical and radiological findings does not assure benign pathology.

Activation of CCR9/CCL25 in cutaneous melanoma mediates preferential metastasis to the small intestine.

PURPOSE: Specific chemokines and their respective receptors have been implicated in distant tumor cell metastasis. Cutaneous melanoma has a distinct pattern of metastasis, preferentially targeting the submucosa of the small intestine. However, the underlying pathogenic mechanism remains unknown. Migration of CCR9(+) lymphocytes to the small intestine is known to occur in response to the chemoattractant effects of CCL25 (thymus-expressed chemokine). The integrin heterodimers alphabeta are also known to be important mediators of cellular adhesion. We hypothesize that the mechanism of small intestinal metastasis by melanoma is via the CCR9-CCL25 axis and specific integrins. EXPERIMENTAL DESIGN: Quantitative reverse transcription-PCR, flow cytometry, and immunohistochemistry were used to assess melanoma tumors for CCR9 and CCL25. Integrin expression was assessed using flow cytometry. CCR9 expression by quantitative reverse transcription-PCR was assessed in primary (n = 23) and metastatic (n = 198) melanomas, and melanoma lines derived from small intestinal metastases (n = 23). RESULTS: We showed CCR9 expression in 88 of 102 paraffin-embedded metastatic melanomas from the small intestine, 8 of 8 melanoma lines derived from metastases in the small intestine, and 0 of 96 metastatic melanomas from other sites. In vitro migration and invasion studies done on CCR9(+) melanoma lines showed migration in response to CCL25 that was inhibited by anti-CCR9 antibody or by short interfering RNA CCR9. Flow cytometric analysis confirmed CCR9 expression by melanomas to the small intestine and showed concomitant alpha(4)beta(1) integrin expression. CONCLUSIONS: Our findings show that functionally active CCR9 on melanoma cells facilitates metastasis to the small intestine. The CCR9-CCL25 axis may explain the high incidence of melanoma metastasis to this specific location.

Chemokine receptor CXCR4 expression in patients with melanoma and colorectal cancer liver metastases and the association with disease outcome.

OBJECTIVE: To determine the role of chemokine receptor (CR) expression in patients with melanoma and colorectal cancer (CRC) liver metastases. SUMMARY BACKGROUND DATA: Murine and in vitro models have identified CR as potential factors in organ-specific metastasis of multiple cancers. Chemokines via their respective receptors have been shown to promote cell migration to distant organs. METHODS: Patients who underwent hepatic surgery for melanoma or CRC liver metastases were assessed. Screening cDNA microarrays of melanoma/CRC cell lines and tumor specimens were analyzed to identify CR. Microarray data were validated by quantitative real-time RT-PCR (qRT) in paraffin-embedded liver metastases. Migration assays and immunohistochemistry were performed to verify CR function and confirm CR expression, respectively. RESULTS: Microarray analysis identified CXCR4 as the most common CR expressed by both cancers. qRT demonstrated CXCR4 expression in 24 of 27 (89%) melanoma and 28 of 29 (97%) CRC liver metastases. In vitro treatment of melanoma or CRC cells with CXCL12, the ligand for CXCR4, significantly increased cell migration (P < 0.001). Low versus high CXCR4 expression in CRC liver metastases correlated with a significant difference in overall survival (median 27 months vs. 10 months, respectively; P = 0.036). In melanoma, low versus high CXCR4 expression in liver metastases demonstrated no difference in overall survival (median 11 months vs. 8 months, respectively; P = not significant). CONCLUSIONS: CXCR4 is expressed and functional on melanoma and CRC cells. The ligand for CXCR4 is highly expressed in liver and may specifically attract melanoma and CRC CXCR4 (+) cells. Quantitative analysis of CXCR4 gene expression in patients with liver metastases has prognostic significance for disease outcome.

Long-term survival after radiofrequency ablation of complex unresectable liver tumors.

HYPOTHESIS: Radiofrequency ablation (RFA) may improve survival of high-risk patients with unresectable and refractory tumors. DESIGN: Retrospective analysis of a prospective database. SETTING: A tertiary referral cancer center. PATIENTS AND METHODS: Between November 1, 1997, and January 31, 2005, we performed 219 RFA procedures to ablate 521 hepatic tumors in 181 patients. RESULTS: Of the 181 patients, 52% were male and 48% were female, and the mean age was 61.3 years (age range, 27-91 years). Radiofrequency ablation was performed via celiotomy (n = 135), via laparoscopy (n = 48), or percutaneously (n = 36). In 106 patients (79%), RFA was used in combination with surgical resection. The most common tumors included colorectal cancer (40.9%), hepatocellular carcinoma (14.9%), carcinoid tumor (13.8%), melanoma (9.4%), and breast cancer (5.0%). The average number of tumors per patient was 3.3 tumors. The average number of RFA-treated lesions per procedure was 2.38 lesions; the mean lesion size was 3.56 cm (lesion size range, 0.8-9.0 cm). At a mean follow-up of 33.2 months (follow-up range, 12-91 months), overall survival was 48.3 months for carcinoid tumors, 25.2 months for hepatocellular carcinoma, 18.5 months for melanoma, 29.7 months for colorectal cancer, and 30.1 months for breast cancer. Seventy-eight patients (43%) developed recurrences. Of 521 tumors that were treated, 125 (24%) recurred; the incidence of local recurrence was 28% for tumors larger than 3 cm vs 18% for tumors 3 cm or smaller (P = .04). Twenty-nine patients underwent serial ablations. Seventy-one patients (39%) were disease free at last follow-up. CONCLUSION: A significant number of patients whose hepatic malignancies are unresectable or refractory to chemotherapy may be considered for RFA as part of a multimodality therapeutic regimen. In these patients, RFA is safe and may prolong survival.

The clinical significance of MAGEA3 expression in pancreatic cancer.

The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.

FTY720 pretreatment reduces warm hepatic ischemia reperfusion injury through inhibition of T-lymphocyte infiltration.

Ischemia and reperfusion (IR) injury remains a significant problem in clinical liver transplantation. We investigated the effects of lymphocyte depletion with FTY720 in models of warm hepatic IR. Using 60-min partial warm hepatic IR, three groups of rats were studied: Sham--laparotomy alone; Control--water p.o. x 3 d before ischemia; Treatment--FTY720 p.o. x 3 d before ischemia. Animals were sacrificed for analysis at 6 h and 24 h post reperfusion. The effect of FTY720 pretreatment on survival was also studied using 150 min total hepatic IR with portojugular shunt. FTY720 treatment significantly reduced serum glutamic pyruvic transaminase and peripheral blood lymphocytes compared to controls at 6h and 24h (p < 0.0005). Histological grade was significantly improved in treated livers vs. controls (p < 0.05). CD3 immunocytochemical analysis revealed a significant reduction in T-cell infiltration in FTY720-treated livers (p < 0.0002). No difference in tissue myeloperoxidase levels was observed. Seven-day survival was significantly improved in treated rats vs. controls following total hepatic ischemia (p < 0.05). In conclusion, FTY720 ameliorates the biochemical and histological manifestations of hepatic IR by preventing T-lymphocyte infiltration and prolongs survival following a more severe ischemic insult. Myeloperoxidase data suggest this mechanism is independent of neutrophil activation. These results indicate that T lymphocytes are pivotal mediators in hepatic IR and may have important implications in liver transplantation.