Should breast surgery be considered for patients with de novo metastatic inflammatory breast cancer?

INTRODUCTION: We aimed to identify factors predicting surgery for de novo stage IV inflammatory breast cancer (IBC) and determine the association of surgery with overall survival (OS). METHODS: Female patients with unilateral AJCC clinical stage IV IBC treated 2010-2018 in the NCDB were identified. Logistic regression and multivariable proportional Cox hazards regressions determined factors associated with treatment and OS. RESULTS: Of 1049 patients, 29.1% underwent breast surgery (BS) and 70.9% had no surgery (NS). Increasing age and more recent treatment year were significantly associated with NS. 2-Year OS was superior in BS patients (71% vs 38% NS). Single-site and bone-only metastasis had no association with treatment type or OS. CONCLUSION: Contrary to guidelines, 1/3 of de novo stage IV IBC patients underwent BS, and had an independent OS benefit irrespective of extent or site of metastasis. Further research is needed to determine which patients with stage IV IBC should undergo BS.

Using MammaPrint on core needle biopsy to guide the need for axillary staging during breast surgery.

BACKGROUND: At present, the only opportunity to omit axillary staging is with Choosing Wisely criteria for women ages >70 y with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. However, many women are diagnosed when pathologic node status-negative, raising the question of additional opportunities to omit sentinel lymph node biopsy. We sought to investigate the association between MammaPrint, a genomic test that estimates estrogen receptor-positive breast cancer recurrence risk, and pathologic node status, with the aim that low-risk MammaPrint could be considered for omission of sentinel lymph node biopsy if associated with pathologic node status-negative. METHODS: A single-institution database was queried for all women with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer with breast surgery as their first treatment and MammaPrint performed from 2020 to 2021. Patient and tumor factors, including MammaPrint score, were compared with axillary node status for correlation. RESULTS: A total of 668 women met inclusion criteria, with a median age of 66 y. MammaPrint was low-risk luminal A in 481 (72%) and high-risk luminal B in 187 (28%). At the time of breast surgery, 588 (88%) had sentinel lymph node biopsy, 27 (4%) had axillary lymph node dissection, and 53 (7.9%) had no axillary staging. Most women in both the pathologic node status-negative and pathologic node status-positive cohorts had low-risk MammaPrint (355 [73.3%] pathologic node status-negative vs 91 [69.5%] pathologic node status-positive), and women with low-risk MammaPrint did not have a significantly lower risk of pathologic node status-positive (P = .377). CONCLUSION: Low-risk MammaPrint does not predict lower risk of pathologic node status-positive breast cancer. Based on our results, genomic testing does not appear to provide additional personalization for the ability to omit sentinel lymph node biopsy for patients outside of the Choosing Wisely guidelines.

Artificial intelligence in orthopaedics: can Chat Generative Pre-trained Transformer (ChatGPT) pass Section 1 of the Fellowship of the Royal College of Surgeons (Trauma & Orthopaedics) examination?

PURPOSE: Chat Generative Pre-trained Transformer (ChatGPT) is a large language artificial intelligence (AI) model which generates contextually relevant text in response to questioning. After ChatGPT successfully passed the United States Medical Licensing Examinations, proponents have argued it should play an increasing role in medical service provision and education. AI in healthcare remains in its infancy, and the reliability of AI systems must be scrutinized. This study assessed whether ChatGPT could pass Section 1 of the Fellowship of the Royal College of Surgeons (FRCS) examination in Trauma and Orthopaedic Surgery. METHODS: The UK and Ireland In-Training Examination (UKITE) was used as a surrogate for the FRCS. Papers 1 and 2 of UKITE 2022 were directly inputted into ChatGPT. All questions were in a single-best-answer format without wording alterations. Imaging was trialled to ensure ChatGPT utilized this information. RESULTS: ChatGPT scored 35.8%: 30% lower than the FRCS pass rate and 8.2% lower than the mean score achieved by human candidates of all training levels. Subspecialty analysis demonstrated ChatGPT scored highest in basic science (53.3%) and lowest in trauma (0%). In 87 questions answered incorrectly, ChatGPT only stated it did not know the answer once and gave incorrect explanatory answers for the remaining questions. CONCLUSION: ChatGPT is currently unable to exert the higher-order judgement and multilogical thinking required to pass the FRCS examination. Further, the current model fails to recognize its own limitations. ChatGPT's deficiencies should be publicized equally as much as its successes to ensure clinicians remain aware of its fallibility.

Combined quadriceps medial patellofemoral ligament reconstruction and osteochondral fixation offers good patient-reported outcomes and low rates of recurrent instability for osteochondral defects secondary to acute patella dislocation.

PURPOSE: Chondral injuries secondary to traumatic patella dislocation are common, and a subgroup of these are significant defects with fragments amenable to fixation. There is a paucity of published evidence assessing patients managed with combined acute patellofemoral stabilisation and osteochondral fixation. The purpose of this study is to report the outcomes of patients with osteochondral injuries secondary to acute traumatic patella dislocation treated with combined early fragment fixation and MPFL reconstruction using a quadriceps tendon turndown technique which has distinct advantages for this cohort, including preventing chondral overloading and non-violation of the patella bone. METHODS: Patients who underwent combined quadriceps tendon MPFL reconstruction and osteochondral fixation were included. Patient demographics, defect characteristics, complications and reoperations were evaluated. Patients were assessed with Lysholm, Kujala, KOOS-PF scores and satisfaction scale at follow up. Pre-operative MRI was assessed for presence of radiological risk factors for patella dislocation and post-operative MRI was used to assess cartilage quality with MOCART 2.0 score. RESULTS: A total of 19 patients (63.2% female) were included. The mean age was 17.4 ± 4.8 years and patients were followed up at a mean 15.8 ± 5.1 months post-surgery. The mean defect size was 2.4 cm2 ± 1.3 cm2, with the most common defect location being the patella (13/19; 68.4%) followed by the lateral femoral condyle (5/19; 26.3%). At final follow up, the overall mean Lysholm, Kujala, and KOOS-PF scores were 84.9 ± 11.1, 89.7 ± 5.8 and 80.6 ± 13.6, respectively. Seventeen patients (89.5%) were satisfied with their outcome. The mean MOCART 2.0 score at final follow-up was 72.5. One patient required medial capsular plication with removal of a loose chondral body and microfracture and 3 knees required minor reoperations. CONCLUSION: Combined acute osteochondral fragment fixation and MPFL reconstruction using a quadriceps tendon graft offers good radiological and patient-reported outcomes with high satisfaction and low rates of recurrent patella dislocation. To our knowledge, this is currently the largest series of its kind in the literature and the results of this study provide a rationale for a combined approach using a quadriceps tendon graft for this cohort. LEVEL OF EVIDENCE: Level IV.

Guideline-Consistent Treatment for Inflammatory Breast Cancer Provides Associated Survival Benefit Independent of Age.

BACKGROUND: Guideline-consistent treatment (GCT) for inflammatory breast cancer (IBC) includes neoadjuvant chemotherapy (NAC), modified radical mastectomy (MRM), and radiation. We hypothesized that younger patients more frequently receive GCT, resulting in survival differences. METHODS: Using the National Cancer Database (2004-2018), female patients with unilateral IBC (by histology code and clinical stage T4d) were stratified by age (< 50, 50-65, > 65 years). Factors associated with NAC, MRM, radiation, and "GCT" (defined as all three treatments) were identified using multivariable logistic regression. Multivariable Cox proportional hazards regression identified predictors of overall survival. RESULTS: Of 3278 IBC patients, 30% were younger than 50 years, 44% were 50-65 years of age, and 26% were older than 65 years. The youngest group comprised the greatest proportion of non-White patients ([35%] vs. [29%] age 50-65 years and [23%] age > 65 years, p < 0.001) and was most often treated at academic facilities ([33%] vs. [28%] age 50-65 years; and [23%] age > 65, p < 0.001). Patients older than 65 years received NAC, MRM, and radiation less frequently, and only 35% underwent GCT (vs. [57%] age 50-65 years and [52%] age < 50 years; p < 0.001). On multivariable logistic regression, age older than 65 years independently predicted omission of NAC (odds ratio [OR], 0.36), MRM (OR, 0.56), and radiation (OR, 0.56) (all p < 0.001), and patients older than 65 years also were less likely to undergo GCT than patients 50-65 years of age (OR, 0.65; p = 0.001). GCT was associated with superior overall survival in all three age groups ([hazard ratio {HR}, 0.61] age < 50 years, [HR, 0.62] age 50-65 years, [HR, 0.53] age > 65 years; all p < 0.001). CONCLUSION: Advanced age alone should not limit receipt of GCT for IBC. Multimodal care should be performed for IBC patients of all ages to improve oncologic outcomes for this aggressive breast cancer subtype.

Neoadjuvant Endocrine Therapy as an Alternative to Neoadjuvant Chemotherapy Among Hormone Receptor-Positive Breast Cancer Patients: Pathologic and Surgical Outcomes.

BACKGROUND: Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. METHODS: Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). RESULTS: Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. CONCLUSIONS: Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.

A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.

BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic ß cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions.RESULTSDantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, ß cell functions were not significantly improved, but there was a significant correlation between baseline ß cell functions and change in ß cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1ß, TNF-α, and isoprostane, were elevated in subjects.CONCLUSIONThis study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02829268FUNDINGNIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs.

Despite Equivalent Outcomes, Men Receive Neoadjuvant Chemotherapy Less Often Than Women for Lymph Node-Positive Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) downstages breast cancer and provides prognostic information. Males with breast cancer are known to receive less treatment overall and have poorer outcomes relative to females. We hypothesized that males would be less likely to receive NAC. PATIENTS AND METHODS: Patients with a primary diagnosis of cN1-3 breast cancer were identified in the National Cancer Database (2004-2016). Multivariable logistic regression determined the association between NAC utilization and sex, and the relationship between sex and NAC response, controlling for demographic and tumor factors. Overall survival was analyzed using a multivariable Cox model. RESULTS: In total, 196,027 patients (194,010 females, 2017 males) met inclusion criteria. A significantly greater proportion of males underwent mastectomy (80% vs. 60%, P < 0.001), and axillary lymph node dissection (76% vs. 74%, P = 0.022). Overall fewer men received chemotherapy than women (73% vs. 84%, P < 0.001); men also received NAC at a significantly lower rate (26% men vs. 45% women, P < 0.001). After accounting for demographic and oncologic factors including hormone receptor (HR) subtype, females remained more likely to undergo NAC (OR 1.84, P < 0.001). On multivariable analysis, sex was not associated with pathologic response or overall survival after NAC. CONCLUSIONS: Although oncologic outcomes after NAC were similar, males with node-positive breast cancer received less NAC and more aggressive surgery than females. These data suggest men achieve outcomes comparable to women with cN1-3 disease, and NAC should be used in appropriate male patients to downstage the breast and axilla.

Hospital System Adoption of Magnetic Seeds for Wireless Breast and Lymph Node Localization.

BACKGROUND: As an alternative to traditional wire localization, an inducible magnetic seed system can be used to identify and remove nonpalpable breast lesions and axillary lymph nodes intraoperatively. We report the largest single-institution experience of magnetic seed placement for operative localization to date, including feasibility and short-term outcomes. METHODS: Patients who underwent placement of a magnetic seed in the breast or lymph node were identified from July 2017 to March 2019. Imaging findings, core needle biopsy, surgical pathology results, and type of surgery were collected. Outcomes included procedural complications, magnetic seed and biopsy clip retrieval rates, and need for additional surgery. RESULTS: A total of 842 magnetic seeds were placed by nine radiologists in 673 patients and retrieved by six surgeons at six operative locations. The majority of breast lesions were malignant (395/659, 59.9%); 136 seeds were placed for lymph node localization. The overall magnetic seed retrieval rate was 98.6%, whereas the biopsy clip retrieval rate was 90.9%. Only six patients (0.7%) experienced a complication from magnetic seed placement. Reexcision was performed in 15.2% of patients with breast cancer; 9.6% of benign/high risk lesions were upgraded to malignancy at surgical excision. CONCLUSIONS: The magnetic seed technique is safe, effective, and accurate for localization of breast lesions and lymph nodes, and importantly uncouples surgery from the localization procedure. The high magnetic seed retrieval rate and low reexcision rate may reflect the accuracy of magnetic marker placement as a "second chance" localization procedure, especially in cases with biopsy clip migration.

Reducing the Risk and Impact of Brachial Plexus Injury Sustained From Prone Positioning-A Clinical Commentary.

INTRODUCTION: Prone positioning is deployed as a critical treatment for improving oxygenation in patients with Acute Respiratory Distress Syndrome. This regimen is currently highly prevalent in the COVID-19 pandemic. The pandemic has brought about increased concern about how best to safely avoid brachial plexus injuries when caring for unconscious proned patients. METHODS: A review of the published literature on brachial plexus injuries secondary to proning ventilated patients was performed. This was combined with a review of available international critical care guidelines in order to produce a succinct set of guidelines to aid critical care departments in reducing brachial plexus injuries during these challenging times. DISCUSSION: There is no one manner in which prone positioning an unconscious patient can be made universally safe. This paper provides 6 key steps to reducing the incidence of brachial plexus injuries while proning and suggests a safe and sensible management and referral pathway for the conscious patient in which a brachial plexus injury is identified. CONCLUSION: There is in truth no completely safe position for every patient and certainly there will be anomalies in anatomy that will predispose certain individuals to nerve injury. Thus the injury rate cannot be reduced to zero but an understanding of the principles of protection will inform those undertaking positioning.

Anatomic, diagnostic and management challenges in paediatric pelvic injuries: a review.

Pelvic injuries have an incidence of 1: 100 000 children per year in the UK, of which 10% are unstable. A literature review was conducted. Clinical examination alone in a stable patient precludes the need for imaging. Imaging options in the acute pelvic injury are critically reviewed. Where appropriate Judet views or limited exposure computed tomography scan remain of diagnostic benefit. Displacement greater than 1 cm should be reduced and held with an appropriate method. Closed reduction and external fixation for rotationally unstable fractures, and closed or open reduction with internal fixation of two columns should be considered for rotationally and vertically unstable fractures.

Calciphylaxis of the Postmenopausal Female Breast: An Uncommonly Encountered Mimic of Carcinoma.

Calciphylaxis is a serious medical condition that is typically associated with end-stage renal disease and presents as the sequelae of calcifications in arterioles with subsequent ischemia of affected tissues. Classically, calciphylaxis produces ulcerated and necrotic skin lesions. These may be biopsied to aid in confirmation of the diagnosis. Herein we report a case of a large necrotic breast lesion in the clinical setting of calciphylaxis, and we emphasize that a multidisciplinary approach to diagnosis and management is important to avoid unnecessary oncological resection.

Immediate Reconstruction in Inflammatory Breast Cancer: Challenging Current Care.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive disease that is treated with trimodality therapy consisting of neoadjuvant chemotherapy, surgery, and post-mastectomy radiation therapy (PMRT). Traditionally, modified radical mastectomy without reconstruction has been the operation of choice for patients with IBC due to fears of high rates of margin positivity, risk of local recurrence, and the need for PMRT. METHODS: A retrospective review was performed to evaluate women with IBC at our institution from 2006 to 2014 who completed trimodality therapy. Patients were identified as undergoing reconstruction or no reconstruction (NR), with reconstruction being further classified as immediate (IR) if reconstruction occurred at the initial surgery, or delayed (DR) if initial reconstruction occurred after PMRT. RESULTS: Sixty women with IBC were identified using inclusion criteria. The median follow-up was 2.3 years (range 1.4-4.6). Patients with IR had a statistically significant increased risk (p = 0.006) in postoperative complication rates compared with DR (0 %) and NR (2.6 %). Two patients had positive skin margins on final pathology (one IR, one NR), with both eventually having recurrence. Time to PMRT was delayed 10 days in patients with IR compared with those without IR. No statistically significant difference in recurrence rates was observed (p = 0.86) when comparing patients with IR and those with NR, and no difference in survival was observed between patients who had reconstruction and those without (p = 0.91). CONCLUSION: Performing IR with mastectomy for IBC is associated with increased complications, but is not associated with decreased survival or increased recurrence in selected patients. IR in selected IBC patients can facilitate successful breast reconstruction.