Defining Breast Cryoablation Treatment Success: A Guide for the Curative and Palliative Treatment of Breast Cancer.

RATIONALE AND OBJECTIVES: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives. MATERIALS AND METHODS: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, tumor characteristics, procedure details, and imaging follow-up findings were analyzed. Cryoablation was categorized as curative or palliative. Treatment success was defined as achievement of both procedure and patient-specific treatment objectives. RESULTS: Breast cryoablation was performed for 34 lesions in 29 patients with N0M0 (n = 25), N1M0 (n = 2), N2M0 (n = 1), and N0M1 (n = 1) disease. Most tumors were invasive ductal carcinoma (IDC), low to intermediate grade, estrogen receptor (ER) and progesterone receptor (PR) positive and HER2 negative (23 tumors, 68%). Tumor size ranged from 0.4-1.9 (median 0.8) cm for curative cryoablation and 0.6-6.0 (median 1.3) cm for palliative cryoablation. For 27 patients with follow-up imaging, ablation was curative in 14 patients, 14 tumors and palliative in 13 patients, 18 lesions. Imaging follow-up time ranged from 3 to 26 (median 16) months, > 12 months in 22 of 27 patients and 25 of 32 tumors. Complications were limited to 2 cases of skin frost injury, 1 mild and 1 moderate. Treatment success was achieved in 13 of 14 patients with curative and all 13 patients with palliative cryoablation. CONCLUSION: Our study defines treatment success for curative and palliative breast cryoablation, demonstrates breast cryoablation achieves not only procedure (technical) but also patient-specific treatment objectives without significant complications, and may serve as guide for integrating breast cryoablation in the treatment of breast cancer patients.

Laparoscopic Versus Open Ladd Procedure for Midgut Malrotation.

INTRODUCTION: Intestinal malrotation is an uncommon developmental anomaly that can lead to duodenal obstruction and midgut volvulus. The standard correctional operation, Ladd's operation, is traditionally performed using an open approach, but providers are increasingly performing the procedure laparoscopically. However, there remains concern that the reduced adhesive burden associated with laparoscopy could predispose to recurrent volvulus. METHODS: We queried our institutional database from 2012 to 2022 for patients <18 years who underwent Ladd's operation for malrotation. We analyzed baseline characteristics and outcomes including post-operative volvulus, adhesive small bowel obstruction (SBO), duodenal obstruction, and overall abdominal re-operation. RESULTS: We identified 226 patients, of whom 90 (40%) underwent a laparoscopic operation. Those undergoing open surgery were younger and had a higher rate of volvulus compared to laparoscopic patients. There were no differences in surgical history or underlying comorbidities. Laparoscopic patients were less likely to develop a post-operative adhesive SBO [1/90 (1%) vs 14/136 (10.0%); OR 9.4 (1.7-176.4), p = 0.036] with no increased rate of volvulus [1/90 (1%) vs 1/136 (0.7%), p = 0.778]. However, there were four laparoscopic patients that required re-operation for a duodenal stricture or kink, which led the overall rate of abdominal re-operation to not be different [7/90 (8%) vs 16/136 (12%); OR 1.6 (0.6-4.8), p = 0.371]. Median follow up was 2.3 years [IQR 1.0-5.0]. CONCLUSION: Laparoscopic correction of midgut malrotation demonstrates no increased risk of post-operative volvulus and may reduce the rate of adhesive SBO. These benefits must be weighed against the potential increased risk of duodenal stricture or obstruction secondary to an incomplete Ladd's procedure. LEVEL OF EVIDENCE: III.

Postoperative Hydration in Children Using Intermittent Boluses of Balanced Salt Solution: Results of a Randomized Control Trial.

BACKGROUND: Postoperative maintenance fluids are traditionally provided via hypotonic dextrose containing fluids administered intravenously by continuous infusion. We hypothesized that scheduled weight-based boluses of balanced salt solution would be more physiologic, reduce fluid volumes, and improve patient comfort. METHODS: As part of an IRB-approved randomized controlled trial (Boluses of Ringer's in Surgical Kids, BRiSK), we randomized patients aged 1-21 years undergoing elective abdominal or thoracic surgery to post-operatively receive weight-based D50.45NS+20mEq/L KCl at a continuous rate or intermittent boluses of Lactated Ringer's solution until oral liquid toleration. Patients with nephropathy, diabetes, or receiving parenteral nutrition were excluded. We analyzed electrolytes, urine output, fluid volume, and adverse events. RESULTS: We enrolled and randomized 60 patients: 29 to continuous fluids and 31 to bolus fluids. One patient from the bolus group dropped out. No patients crossed over due to difficulties with application of the bolus protocol. There were no baseline differences between groups with a mean age of 12.6 ± 1.4yr and weight of 50.9 ± 7.2 kg. There were no serious adverse events or electrolyte disturbances in either group. Patients in the bolus group received significantly less total fluid than those in the continuous group (0.43 mL/kg/h vs 1.1 mL/kg/h, p < 0.001) with no difference in urine output [1.4 ± 0.2 mL/kg/h vs 1.6 ± 0.3 mL/kg/h, p = 0.211]. There were two episodes of mild hypoglycemia in the bolus group compared to seven episodes of mild hyperglycemia in the continuous group. CONCLUSIONS: Administration of post-operative intravenous fluids as boluses of balanced salt solution is feasible, safe, and results in significantly less fluid administered compared to a traditional continuous protocol. LEVEL OF EVIDENCE: II.

Ileocolic Intussusception: Iterative Quality Improvement to Address a Recurring Problem.

INTRODUCTION: Recent quality improvement (QI) initiatives indicate that pediatric patients with uncomplicated ileocolic intussusception can be safely discharged from the emergency department (ED) after fluoroscopic reduction. These programs improve patient experience and reduce cost. We sought to build on these efforts by developing a QI initiative at our own institution that included patients transferred from a satellite campus and focused on iterative improvement of our treatment pathway based on continual reassessment of our processes and data. MATERIALS AND METHODS: We formed a multidisciplinary team, established a collaborative open-access clinical pathway, and implemented educational plans for each participating division. Data were tracked prospectively, and process adjustments were made as clinically indicated. In this report, we compare patients treated before and after the QI initiative. RESULTS: There were 155 patients treated before the QI initiative (January 1, 2018-June 30, 2022) and 87 after the initiative began (July 1, 2022-October 31, 2023). There were significant improvements in the rate of ED discharge (4/155 (2.6%) versus 51/87 (59%), P < 0.001) and mean time to discharge (40.7 versus 23.1 h, P = 0.002), while the average cost of a visit fell by 30% (P = 0.012). The mean time to discharge from the ED increased (6.9 versus 11.0 h, P < 0.001), and the rate of readmission was unchanged. For patients transferred from the satellite campus, time to fluoroscopic reduction significantly improved during the initiative (9.4 versus 6.5 h, P = 0.048). CONCLUSIONS: We implemented a QI program for patients with fluoroscopically reduced ileocolic intussusception that was serially adjusted based on continual reassessment of data. The protocol was associated with a decreased admission rate, total cost, and time to hospital discharge.

Outpatient Factors Implicated in Timing of Delayed Elective Inguinal Hernia Repair in Premature Neonates: Single Center Analysis Brings Up a Touchy Issue and Balancing Metric.

INTRODUCTION: Among premature infants, the incidence of inguinal hernias (IH) has been reported to be as high as 10-30%. We performed this study to characterize the association between individual and systemic variables that may affect diagnosis to definitive operative repair of the premature neonatal IH in the outpatient setting. METHODS: A single center cohort retrospective review analyzing IH repair in the premature neonatal (<37 GA) population was performed. Data was collected between 2013 and 2022. The cohort was defined as patients who underwent repair before the age of 1 and excluded patients with major medical comorbidities or underwent simultaneous major abdominal surgeries. RESULTS: Of the 836 premature neonates who underwent IH repair, the majority (73%) were repaired electively. Patients were characterized into risk cohorts a-priori. High-risk patients (HR, n = 43) were more likely to have Government insurance (67%). There was a significant difference in HR patient time to surgery between Government versus Commercial insurance, 10.6 versus 4.7 days, respectively (95% CI -11.09 to -0.4396, p = 0.0345). HR patients were also seen more frequently (clinic or emergency department) prior to operative repair (2.51 vs 1.72 95% CI -1.296% to -0.289%, p = 0.0021). A multivariate linear regression model demonstrated that risk class (p = 0.0244), touches (p < 0.0001), GA (p < 0.001), and prior authorization (p < 0.0001) were significantly associated with time to hernia repair. CONCLUSIONS: Systemic variables such as insurance type may increase average wait time for elective outpatient IH repair. This increase in wait time is associated with an increased number of healthcare visits. Therefore, timely access to surgical care prevents potential harm and may decrease health system burden. TYPE OF STUDY: Retrospective comparative study/cohort study. LEVEL OF EVIDENCE: III.

The Prevalence of Sentinel Lymph Node Positivity and Implications for the Utility of Frozen Section Diagnosis Following Neoadjuvant Systemic Therapy in Patients with Clinically Node-Negative HER2-Positive or Triple-Negative Breast Cancer.

BACKGROUND: Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clinically node-negative (cN0) HER2-positive or triple-negative breast cancer. METHODS: We conducted a single-institution observational cohort study including patients with non-inflammatory, cN0, HER2-positive or triple-negative breast cancer treated with neoadjuvant systemic therapy between 2015 and 2019. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section. RESULTS: Overall, 662 patients were eligible for inclusion, and 44 patients had one or more positive SLNs (prevalence: 6.6%, 95% confidence interval [CI] 4.9-8.8). There were 490 (74.0%) patients who had intraoperative frozen section, and 19 (3.9%) tested positive among 33 (6.7%) with positive final pathology. Frozen section sensitivity was 57.6% (95% CI 39.2-74.5), specificity was 100% (95% CI 99.2-100), positive predictive value was 100% (95% CI 82.4-100), and negative predictive value was 97.0% (95% CI 95.1-98.4). The sensitivity of frozen section for detection of micrometastases or isolated tumor cells was 35.3% (95% CI 14.2-61.7). CONCLUSION: In patients with cN0 HER2-positive or triple-negative breast cancer who have been treated with neoadjuvant therapy, positive SLNs are uncommon and frozen section sensitivity is modest. Decisions to defer SLN evaluation to final pathology, which may be reasonable in many settings, can be informed, in part, by these findings.

Impact of microscopic deposits of yolk sac tumor on recurrence of mature sacrococcygeal teratoma.

INTRODUCTION: Sacrococcygeal teratomas (SCT) with malignant histology frequently recur and are treated aggressively, but risk factors and surveillance protocols are less established for mature tumors. In particular, prior studies have not investigated whether microscopic deposits of yolk sac tumor (YST) in otherwise mature teratomas lead to higher recurrence rates. METHODS: We reviewed patients with mature SCTs resected at our institution from 2011 to 2021 and analyzed tumor characteristics, treatment, and outcomes. RESULTS: We identified 56 patients with mature SCT, of which 9 (16%) demonstrated microscopic YST. Following surgery, 7/56 (13%) patients developed local recurrence at a mean of 1.2 ± 0.7 years, while no patients developed metastases. Recurrence was more likely in patients with microscopic YST [5/9 (56%) vs. 2/47 (4%), p = 0.021] and positive margins [6/24 (35%) vs. 1/32 (3.1%), p = 0.030]. A solid tumor component tended to increase recurrence risk as well [6/29 (21%) vs. 1/27 (4%), p = 0.053]. Five patients demonstrated malignant recurrence and were all detected by a rising alpha-fetoprotein (AFP), while two patients demonstrated recurrence of mature teratoma and were detected on surveillance magnetic resonance imaging (MRI). CONCLUSIONS: Microscopic foci of YST may increase recurrence risk for patients with mature SCT. Such patients might benefit from closer postoperative surveillance with serial AFP measurements and MRI.

Muscle-sparing Vertical Thoracotomy in Children and Adolescents.

BACKGROUND: Traditional posterolateral thoracotomy (PLT) is a painful and potentially morbid operation associated with an extensive recovery and a long, unsightly scar. In contrast, vertical thoracotomy (VT) is designed to spare muscles, avoid skin flaps, and minimize incision length, thereby limiting postoperative pain, hastening recovery, and improving scar cosmesis. METHODS: We reviewed children aged 1-21 that underwent PLT and VT at our institution from 1/1/2013-12/1/2023. We analyzed demographic data, operative details, and clinical outcomes with special attention paid to total oral morphine equivalents (OME), time to ambulation, and wound complications. RESULTS: We identified 105 patients who underwent PLT and 74 who underwent VT. Both groups were heterogeneous with a greater proportion of oncology patients that received wedge resection in the VT group and congenital lung lesions that received lobectomy in the PLT group. VT patients tended to be older and heavier than PLT patients. Patients who underwent VT demonstrated improved time to ambulation (1.4 ± 0.3 vs 3.0 ± 1.4 days, p = 0.037) and oral morphine equivalent requirements (1.4 ± 0.4mgOME/kg vs 3.5 ± 1.8mgOME/kg, p = 0.035) compared to those who underwent PLT. Additionally, no patients in the VT group required division of the serratus or latissimus, compared to 8 (8%) in the PLT group (p = 0.004). CONCLUSION: Muscle-sparing vertical thoracotomy provides excellent exposure for most intrathoracic pediatric operations, results in a cosmetically acceptable scar that is easily hidden by the upper arm, may reduce the frequency of division of the latissimus and serratus, and does not worsen time to ambulation or post-operative opioid requirements. LEVEL OF EVIDENCE: III.

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.

Pediatric thoracic cage fractures-Mind the sternum: A retrospective analysis of the ACS-TQIP database.

BACKGROUND: The thoracic cage is an anatomical entity formed by the thoracic spine, ribs, and sternum. As part of this osteoligamentous complex, the sternum contributes substantially to the stability of the thoracic spine. This study investigates the influence of a concomitant sternal fracture (SF) on the treatment and hospital course of pediatric patients with a thoracic vertebral fracture (TVF). METHODS: The Trauma Quality Improvement Program data sets from 2016 to 2020 were reviewed. Patients aged 0 year to 19 years with TVF with or without SF following blunt trauma were identified using the Abbreviated Injury Scale codes and selected for further data collection. Patients with transverse or spinous process fractures or incomplete data were excluded. Data collected included demographics, mechanisms of injury, clinical variables, procedures, intensive care unit admission and length of stay, total length of stay and in-hospital mortality. Continuous variables were analyzed with Wilcoxon rank sum test, categorical variables with χ 2 test. RESULTS: A total of 13,434 patients were identified, of which 10,292 had isolated TVF (TVF), 788 TVF and concomitant SF (TVF + SF), 2,225 isolated SF (excluded), and 126 incomplete data (excluded). Motor vehicle collisions were the most common mechanism of injury in both groups (TVF, 75%; TVF + SF, 88%), followed by falls (TVF: 23%, TVF + SF: 12%). Spinal cord injuries were more common among TVF + SF patients (6.4% vs. 4%). Median injury severity score (17 vs. 12), age (17 vs. 15 years), LOS (5 vs. 3 days), and mortality (5.6% vs. 2.3%) were significantly higher and the need for operative treatment (69% vs. 56%) and ICU admission (53% vs. 36%) significantly more frequent in patients with TVF + SF. CONCLUSION: Concomitant SF occur in 7% of all pediatric patients with TVF and are associated with increased morbidity and mortality. This combination of injuries is likely the result of greater energy transmission and injury potential. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Ostomy Management for Pediatric Perianal Crohn's Disease.

INTRODUCTION: Pediatric patients with perianal Crohn's Disease (CD) suffer recalcitrant fistulas, abscesses, and strictures. Fecal diversion is a palliative last resort, but the expected clinical course and long-term management of the ostomy for this population is unclear. We sought to identify factors predictive of ostomy takedown and establish management recommendations for fistulizing and stenosing disease. METHODS: We reviewed our institutional registry for patients aged 1-18 years with CD who received perianal surgery from 2011 to 2021. We analyzed medical therapy, examinations under anesthesia (EUA), fistula and stenosis response, and rates of fecal diversion and reversal. RESULTS: There were 109 patients with fistulizing CD and 21 with stenosing CD. There were 8 diverted for fistula and 4 due to stricture [8/109 (7 %) vs 4/21 (19 %), p = 0.213]. Three patients with fistulizing disease had their ostomy reversed at an average of 1.46 years. Each demonstrated consistent CD control and with no additional perianal flares. The remainder have been diverted 3.15 ± 4.57 years with 2.1 ± 2.8 EUAs. Only one patient with stricture was durably reversed, but they still require serial anal dilation. Two were reversed but required re-diversion due to stricture progression. CONCLUSION: Reversal rates after fecal diversion for pediatric perianal CD remain disappointingly low and diversion does not obviate the possibility of future EUAs. While reversal was successful for medically responsive patients with fistulizing disease, those with stenosing disease remained dependent on anal dilations and were more likely to fail reversal. Fecal diversion does nothing to reverse an established stricture and such patients will likely need to decide between indefinite dilations or permanent ostomy. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective review.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

A WNT4- and DKK3-driven canonical to noncanonical Wnt signaling switch controls multiciliogenesis.

Multiciliated cells contain hundreds of cilia whose directional movement powers the mucociliary clearance of the airways, a vital host defense mechanism. Multiciliated cell specification requires canonical Wnt signaling, which then must be turned off. Next, ciliogenesis and polarized ciliary orientation are regulated by noncanonical Wnt/planar cell polarity (Wnt/PCP) signaling. The mechanistic relationship between the Wnt pathways is unknown. We show that DKK3, a secreted canonical Wnt regulator and WNT4, a noncanonical Wnt ligand act together to facilitate a canonical to noncanonical Wnt signaling switch during multiciliated cell formation. In primary human airway epithelial cells, DKK3 and WNT4 CRISPR knockout blocks, whereas ectopic expression promotes, multiciliated cell formation by inhibiting canonical Wnt signaling. Wnt4 and Dkk3 single-knockout mice also display defective ciliated cells. DKK3 and WNT4 are co-secreted from basal stem cells and act directly on multiciliated cells via KREMEN1 and FZD6, respectively. We provide a novel mechanism that links specification to cilium biogenesis and polarization for proper multiciliated cell formation.

Extremely Low Incidence of Local-Regional Recurrences Observed Among T1-2 N1 (1 or 2 Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy Without Completion Axillary Node Dissection.

BACKGROUND: Completion axillary node dissection (CLND) is routinely omitted in cT1-2 N0 breast cancer treated with upfront, breast-conserving therapy and sentinel node biopsy (SLNB) showing one to two positive sentinel nodes (SLNs). The purpose of this study was to determine the incidence and impact of axillary treatment among patients treated with mastectomy in a contemporary cohort. METHODS: A prospective, institutional database was reviewed from 2006 to 2015 to identify patients with T1-2 breast cancer treated with upfront mastectomy and SLNB found to have one to two positive SLNs. Patients were stratified by axillary therapy [including CLND and/or post-mastectomy radiation therapy (PMRT)], and clinicopathologic factors and incidence rates of local-regional and distant recurrence were analyzed. RESULTS: A total of 548 patients were identified, including 126 (23%) without CLND. Rates of PMRT were similar between those with and without CLND (35.3% vs. 28.6%, p = 0.16). On multivariate analysis, two rather than one positive SLN, larger SLN metastasis size, frozen-section analysis of the SLNB, and adjuvant chemotherapy were significantly associated with receipt of CLND. At a median follow-up of 7 years, there were only two local-regional recurrences in the no-CLND group, of which only one was an axillary recurrence. The 5-years incidence rate of LRR was not significantly different for those with and without CLND (1.3% vs. 1.8%, p = 0.93). CONCLUSIONS: We found extremely low rates of local-regional recurrence among those with T1-2 breast cancer undergoing upfront mastectomy with 1-2 positive SLNs. Further axillary surgery may not be indicated in selected patients treated with a multidisciplinary approach, including adjuvant therapies.

Trends in Histrelin Implantation at a Pediatric Tertiary Care Center.

INTRODUCTION: Determine procedural outcomes and identify changing trends of utilization among patients undergoing histrelin implantation at a large pediatric tertiary care center over 15 y. METHODS: Retrospective review of all patients undergoing histrelin implantation between January 2008 and April 2022. RESULTS: A total of 746 patients underwent 1794 unique procedures (1364 placements/replacements, 430 removals). Procedures were performed in the clinic (1071, 60%), sedation unit (630, 35%), and operating room (93, 5%). A total of 14 (0.8%) complications were identified, including two patients that required early implant removal and one patient requiring antibiotics. Implants were placed for central precocious puberty (CPP, 579) or gender dysphoria (GD, 167). Cohort included 25.9% males and 74.1% females with mean age of implantation of 9.48 y (SD: 2.34, range: 1.05-17.34). The GD group is comprised of 52.4% males and 47.6% females, compared to 18.3% males and 81.7% females in the CPP. Significant difference was identified for mean age at placement by indication (CPP 8.65 y versus GD 12.34, P < 0.001). New patient referrals and implant procedures increased significantly over 14 y. Yearly frequency of patients receiving implants for CPP and GD increased significantly (P < 0.001), with proportion of GD patients increasing from 7% to 32%. CONCLUSIONS: Histrelin procedures have increased in frequency overall with the greater increase noted in the GD cohort. The development of a streamlined process and a dedicated team have enabled histrelin procedures to be safely performed in the clinic setting for most, with a very low complication rate.