Oncologic safety of breast conserving surgery after neoadjuvant chemotherapy in patients with multiple ipsilateral breast cancer: A retrospective multi-institutional cohort study.

INTRODUCTION: The recent ACOSOG Z11102 trial demonstrated low recurrence rates with breast conserving surgery (BCS) in women with multiple ipsilateral breast cancers (MIBC). Questions remain regarding the oncologic safety of BCS in women with MIBC receiving neoadjuvant chemotherapy (NAC). METHODS: We conducted a retrospective cohort study of adult patients who underwent BCS following NAC for stage I-III breast cancer from 2012 to 2021 at two academic centers. Descriptive statistics were used to summarize the data and the Kaplan-Meier method was used to provide estimates for recurrence and survival outcomes. MIBC was defined as ≥2 foci of malignancy. RESULTS: A total of 544 patients were included; 29.4% (n = 160) ER+/HER2-, 17.7% (n = 96) ER+/HER2+, 18.2% (n = 99) ER-/HER2+, and 34.7% (n = 189) with ER-/HER2-disease. Overall, 80.5% (n = 438) had unifocal breast cancer while 19.5% (n = 106) had MIBC. Of patients with MIBC, 90.6% (n = 96) had multifocal and 9.4% (n = 10) had multicentric disease. Pathologic complete response was achieved in 41.1% of patients with MIBC versus 41.5% of patients with unifocal disease (p = 0.94). At a median follow-up of 55 months (IQR 32-83); 4.8% of patients in the unifocal group and 4.7% of patients in the MIBC group had had a local recurrence (p = 0.97). There was no difference in 5-year local recurrence-free survival (p = 0.92), recurrence-free survival (p = 0.06), or overall survival (p = 0.07) between the groups. CONCLUSION: In this large cohort of women undergoing BCS post-NAC, there was no significant difference in in breast tumor recurrence or survival outcomes between patients with unifocal disease and those with MIBC.

Opioid prescribing practices in breast oncologic surgery-A retrospective cohort study.

BACKGROUND: In breast oncologic surgery, 75% of patients receive a postoperative opioid prescription at discharge, and 10%-20% will develop persistent opioid use. To inform future institutional guidelines, the objective of this study was to determine baseline opioid prescribing patterns in a single high-volume, referral-based breast center. We hypothesized that opioid prescribing practices varied between procedures and operating surgeons. METHODS: A retrospective analysis of all women undergoing breast cancer surgery between January and December 2019. Opioid prescriptions at discharge were converted to morphine milligram equivalents (MME). The primary outcome of interest was MME prescribed at discharge. Multiple linear regression was used to identify factors independently associated with MME prescribed. RESULTS: 392 patients met inclusion criteria; 68.3% underwent partial mastectomy. Median age was 61 (interquartile range [IQR] 51-70). Median MME prescribed at discharge was 112.5 (IQR 75-150); 83.9% of patients were prescribed co-analgesia. The prescriber was a trainee in 37.7% of cases. 15 patients (3.8%) required opioid renewal. On multivariate analysis, axillary procedure was associated with increased MME (ß = 17, 95% CI 5.5-28 and ß = 32, 95% CI 17-47, for sentinel node and axillary dissection, respectively). However, the factor with the greatest impact on MME was operating surgeon (ß = 72, 95% CI 58-87). Residents prescribed less MME compared to attending surgeons (ß = 11, 95% CI -22; -0.06). CONCLUSION: In a tertiary care center, the operating surgeon had the greatest influence on opioid prescribing practices, and trainees tended to prescribe less MME. These findings support the need for a standardized approach to optimize prescribing and reduce opioid-related harms after oncologic breast surgery.

Watchful waiting for large primary nonparasitic splenic cysts.

BACKGROUND: Primary nonparasitic splenic cysts (NPSC) are typically diagnosed incidentally. The management of large (≥ 5 cm) asymptomatic cysts remains controversial; there is a lack of evidence guiding management. The purpose of this study was to describe the outcomes of nonoperative management of large NPSC. METHODS: Patients diagnosed with NPSC between January 2004 and December 2019 were identified at our academic institution. Adult patients with an NPSC of at least 5 cm who had at least 1 additional hospital visit were included. Data are presented as medians with interquartile ranges (IQR). RESULTS: We identified 512 medical records that included the term splenic cyst during the study period. Sixty-eight of the patients had no reported cyst size, 410 had cysts smaller than 5 cm, 1 patient underwent an elective splenectomy at another institution and 12 patients were excluded for other reasons; 21 patients with cysts of at least 5 cm were included in the study. Eight symptomatic patients underwent surgery at our institution. Of these, 2 presented acutely: 1 with hemoperitoneum who required admission for transfusions and later underwent elective laparoscopic splenectomy and 1 with increasingly severe abdominal pain who underwent laparoscopic cyst unroofing. The remaining 6 symptomatic patients had elective surgery for pain (4 cyst unroofing, 1 total splenectomy, 1 partial splenectomy). Thirteen patients were asymptomatic (10 female, median age 49.2 [IQR 38.1 to 64.6] yr). Two of these patients chose to undergo elective surgery. The remaining 11 asymptomatic patients, with a median initial cyst size of 8.0 (IQR 5.3 to 10.8) cm, were followed for a median of 31.0 (IQR 23.5 to 71.0) months. There was no change in median cyst size (0 [IQR -1 to 0] cm), and none of these patients underwent intervention for their NPSC. CONCLUSION: Asymptomatic patients managed nonoperatively for large NPSC did not become symptomatic or require intervention during the study period. This supports watchful waiting with serial radiologic and clinical monitoring for asymptomatic large NPSC.

Sentinel lymph node biopsy in women over 70: Evaluation of rates of axillary staging and impact on adjuvant therapy in elderly women.

BACKGROUND: The 2016 Society of Surgical Oncology Choosing Wisely guidelines recommended against routine sentinel lymph node biopsy in women ≥70 years old with favorable, early-stage breast cancer, as sentinel lymph node biopsy does not decrease recurrence or mortality in these patients. This study's objective was to evaluate the use of sentinel lymph node biopsy and its effect on management in elderly patients. METHODS: A retrospective analysis of female patients ≥70 years old with stage I-II, clinically node-negative, hormone-receptor positive, HER2-negative disease undergoing upfront breast cancer surgery between 2017 and 2019. Primary outcome was rate of sentinel lymph node biopsy. Secondary outcome was effect of sentinel lymph node biopsy on adjuvant therapy. RESULTS: In total, 142 patients were included. Median age was 76 (interquartile range 73-81), and 71.8% underwent lumpectomy. On final pathology, 57.7% had invasive ductal carcinoma, and median tumor size was 15 mm (interquartile range 10-24.3). A total of 118 patients (83.1%) underwent sentinel lymph node biopsy; of these, 27 (22.9%) were positive for N1mi (7 patients) or N1a disease (20 patients). On multivariate regression analysis, patients undergoing sentinel lymph node biopsy were more likely to be younger (odds ratio 0.87, 95% confidence interval 0.78-0.95). The major risk factor for sentinel lymph node biopsy positivity was lymphovascular invasion (odds ratio 13.4, 95% confidence interval 4.57-40.1). Patients with sentinel lymph node biopsy positivity were more likely to receive local adjuvant radiation therapy (odds ratio 4.66, 95% confidence interval 1.49-16.8) and tended to receive more adjuvant regional radiation therapy (75.0% if sentinel lymph node biopsy positive compared with 15.3% if sentinel lymph node biopsy negative, P < .001). CONCLUSION: Despite the 2016 Choosing Wisely guidelines, more than 80% of patients ≥70 years old underwent sentinel lymph node biopsy at our institution. If sentinel lymph node biopsy was positive, this is associated with over 4-fold higher rates of adjuvant radiation therapy.

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial.

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain. Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery. Design, Setting, and Participants: This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization. Interventions: Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge. Main Outcomes and Measures: Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle. Results: A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled. Conclusions and Relevance: The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04254679.

A retrospective study evaluating outcomes of surgical excision versus radiologic follow-up of benign breast papillomas without atypia.

BACKGROUND: There is uncertainty whether benign breast papillomas without atypia (BP) can be followed by imaging or require surgical resection. METHODS: A single-center, retrospective cohort study of patients diagnosed with BP (2011-2021) to determine the upgrade rate on surgery, and factors associated with surgical intervention and upgrade. RESULTS: 139 BPs were included. 27(19.4%) had upfront surgery; 112(80.6%) had imaging follow-up. The upfront surgery group had higher rates of pre-excision nipple inversion (n = 2(8.3%)vs.n = 0(0%),p = 0.003). In the imaging group, the median follow-up was 3.8years, and 9 had subsequent resection. Upgrade rate was 5.8%(8/139). Of all BPs undergoing surgery (n = 36), patients ≥60years (75.0%vs.25.0%,p = 0.049) or with family history of breast cancer (87.5%vs.48.1%,p = 0.048) were more likely to have upgrade. CONCLUSIONS: Despite a low number of events, this study supports radiologic follow-up of BP except in patients ≥60 years or with family history of breast cancer, adding to the growing body of evidence supporting watchful waiting of BPs.

Factors predicting recurrence in thymic epithelial neoplasms.

OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a heterogeneous group of rare thoracic malignancies. We analysed the clinicopathological features, survival outcomes, risk factors, and patterns of recurrence in patients undergoing resection. METHODS: Records were reviewed for adult patients with TEN who underwent resection from 2006 to 2019. Survival rates were assessed using the Kaplan-Meier method. Univariable and multivariable analyses were performed using the log-rank test and Cox proportional hazards model. RESULTS: A total of 100 patients were analysed (51 females, median age 58 years). Thymoma was the most common histology (n = 92), followed by thymic carcinoma (n = 5) and thymic neuroendocrine tumour (n = 3). Stage II (Masaoka) tumours were most common (n = 51), followed by stage I (n = 27). World Health Organization B2/B3 was the most prominent histological subtype (n = 34). Complete resection (R0) was achieved in 91 patients: 86/92 thymoma, 4/5 thymic carcinoma and 1/3 neuroendocrine tumour. The most common treatment modality was surgery alone in 72 patients, followed by surgery and radiation therapy in 24, and adjuvant chemoradiotherapy in 3 patients. Only one patient with thymic carcinoma received neoadjuvant chemotherapy. The 10-year overall and disease-free survival rates were 86.6% and 83.9%, respectively. Recurrence was most common in neuroendocrine tumours (3/3). Risk factors for recurrence identified on multivariable analyses were: R1/2 resection (hazard ratio 9.30; 95% confidence interval 1.82-36.1), TEN subtype (hazard ratio 8.08; 95% confidence interval 1.24-34.6), and presence of lymphovascular invasion (hazard ratio 9.56; 95% confidence interval 2.56-25.8). CONCLUSIONS: Complete resection remains critical in patients with TEN. Incomplete resection, high-risk histology, and lymphovascular invasion highlight the need for effective adjuvant modalities. Given the rarity of these diseases, emphasis must be placed on collaborative research conducted on TEN.

Delays in operative management of early-stage, estrogen receptor-positive breast cancer during the COVID-19 pandemic: A multi-institutional matched historical cohort study.

BACKGROUND: During the COVID-19 pandemic, guidelines recommended that breast cancer centers delay estrogen receptor-positive breast cancer surgeries with neoadjuvant endocrine therapy. We aimed to evaluate pathologic upstaging of breast cancer patients affected by these guidelines. METHODS: Female patients with stage I/II breast cancer receiving neoadjuvant endocrine therapy were prospectively identified and were matched to a historical cohort of stage I/II estrogen receptor-positive breast cancer patients treated with upfront surgery ≤35 days. Primary outcomes were pathologic T and N upstaging versus clinical staging. RESULTS: After matching, 28 neoadjuvant endocrine therapy and 48 control patients remained. Median age in each group was 65 (P = .68). Most patients (78.6% and 79.2%) had invasive ductal carcinoma with a clinical tumor size of 0.9 cm vs 1.7 cm (P = .056). Time to surgery was 68 days in the neoadjuvant endocrine therapy group and 26.5 days in the control (P < .001). A total of 23 neoadjuvant endocrine therapy patients (82.1%) had the same or lower pT-stage compared with 31 (64.5%) control patients (P = .115). Only 3 (10.7%) neoadjuvant endocrine therapy patients had increased pN-stage vs 14 (29.2%) control patients (P = .063). CONCLUSION: Despite 2.5-times longer delays, patients with early-stage estrogen receptor-positive breast cancer receiving neoadjuvant endocrine therapy did not experience pathologic upstaging during the COVID-19 pandemic. These findings may support the use of neoadjuvant endocrine therapy in similar patients if delays to surgery are projected.