Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database.

BACKGROUND: Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. METHODS: Patients with non-metastatic IBC treated in 2010-2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), ER-/HER2- and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan-Meier curves and Cox proportional hazards regression to analyse overall survival. RESULTS: Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2- in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER-/HER2- in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2- (6·2 per cent), HER2+ (38·8 per cent), ER-/HER2- (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2- 64·9 per cent, HER2+ 74·0 per cent, ER-/HER2- 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER-/HER2- subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival. CONCLUSION: Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.

ANTECEDENTES: En tanto que el cáncer inflamatorio de mama (inflammatory breast cancer, IBC) se ha postulado como una entidad biológica distinta, las guías de práctica clínica y datos previos sugieren que el tratamiento y los resultados están influenciados por aproximación al subtipo biológico estándar. El objetivo de este estudio fue la validación en una cohorte reciente de pacientes incluidas en una extensa Base de Datos Nacional de Cáncer (National Cancer Database, NCDB). MÉTODOS: A partir de la NCDB, se identificaron las pacientes con IBC no metastásico tratadas en con neoadyuvancia sistémica y cirugía durante el periodo 2010-2015. El subtipo biológico aproximado se categorizó como ER+/HER2-, ER-/HER2- y HER2+. La respuesta patológica completa total (pathologic complete response, pCR) se definió como ypT0/ypTis, ypN0. Se utilizaron pruebas de ji al cuadrado para comparar las tasas de pCR y las curvas de Kaplan-Meier y la regresión de riesgos proporcionales de Cox para analizar la supervivencia global (overall survival, OS). RESULTADOS: En las 4.068 pacientes con IBC (mediana de edad 56 años), el subtipo biológico aproximado fue ER+/HER2- en 1.575 (39%), HER2+ en 1.323 (33%) y ER-/HER2- en 1.170 (29%). Un total de 3.351 pacientes (84%) eran cN+ en el momento de la presentación, sin diferencias entre los subtipos. Las tasas totales de pCR variaron significativamente en función del subtipo: ER+/HER2- (6%), HER2+ (39%), ER-/HER2- (19%), P < 0,001, así como las tasas de pCR de la mama (10%, 45%, 25%) y las tasas de pCR de los ganglios linfáticos (17%, 57%, 33%). La OS a los 5 años varió significativamente según los subtipos (ER+/HER2- 65%, HER2+ 74%, ER-/HER2- 44%, P < 0,001) y según la pCR en cada uno de los subtipo (en cada uno P < 0,01). En el análisis multivariable, el subtipo ER-/HER2- (cociente de riesgos instantáneos, hazard ratio, HR 2,9, P < 0,001 versus HER2+) y la ausencia de pCR total (HR 3,2, P < 0,001) predijeron una peor supervivencia. CONCLUSIÓN: Tanto la respuesta al tratamiento del IBC y como la supervivencia variaron en función del subtipo biológico aproximado, tal como sucede en otros cánceres de mama invasivos. Estos datos apoyan la importancia de continuar ajustando el tratamiento sistémico al subtipo biológico aproximado y resaltan la mejoría reciente de los resultados en las pacientes HER2+.

Evidence-based wound classification for vulvar surgery: Implications for risk adjustment.

OBJECTIVES: The correct wound classification for vulvar procedures (VP) is ambiguous according to current definitions, and infection rates are poorly described. We aimed to analyze rates of surgical site infection (SSI) in women who underwent VP to correctly categorize wound classification. METHODS: Patients who underwent VP for dysplasia or carcinoma were collected from the National Surgical Quality Improvement Program database (NSQIP). SSI rates of vulvar cases were compared to patients who underwent abdominal hysterectomy via laparotomy, stratified by the National Academy of Sciences wound classification. Descriptive analyses and trend tests of categorical variables were performed. RESULTS: Between 2008 and 2016, 2116 and 31,506 patients underwent a VP or TAH, respectively. Among VP, 1345 (63.6%), 364 (17.2%), and 407 (19.2%) women underwent simple vulvectomy, radical vulvectomy, or radical vulvectomy with lymphadenectomy, respectively. The overall rate of SSI for VP was higher than that observed for TAH (5.6% vs. 3.8%; p < 0.0001). While patients undergoing TAH displayed a corresponding increase in the rate of SSI with wound type (type I: 3.4%; type II: 3.8%, type III: 6.8%; type IV 10.6%; p < 0.001), no such correlation was observed for simple VP (type I: 3.3%, type II: 3.0%; type III: 3.2%; type IV: 0%; p = 0.40). On the other hand, a non-significant correlation was observed for radical VP (type I: 4.0%, type II: 10.1%; type III: 14.3%; type IV: 20.0%; p = 0.08). The overall rate of SSI in patients undergoing any radical VP was similar to patients undergoing hysterectomy with a type IV wound (10.1% vs 10.6%, p = 0.87). CONCLUSION: Patients undergoing VP are at high risk of infection. Simple vulvectomy should be classified as a type II and radical vulvectomy as a type III wound. These recommendations are important for proper risk adjustment.

Outcomes with multimodal therapy for elderly patients with rectal cancer.

BACKGROUND: Treatment guidelines for stage II and III rectal cancer include neoadjuvant chemoradiotherapy, surgery and postoperative adjuvant chemotherapy. Although data support this recommendation in younger patients, it is unclear whether this benefit can be extrapolated to elderly patients (aged 75 years or older). METHODS: This was a retrospective review of patients aged at least 75 years with stage II or III rectal cancer who underwent surgery with curative intent from 1996 to 2013 at the Mayo Clinic. Kaplan-Meier analysis and log rank test were used to compare overall survival between therapy groups. Cox proportional hazards model was used to estimate the independent effect of treatment group on survival. RESULTS: A total of 160 elderly patients (median age 80 years) with stage II (66) and stage III (94) rectal cancer underwent surgical resection. Only 30·0 and 33·8 per cent received neoadjuvant or adjuvant therapy respectively. Among patients with stage II disease, there was no significant difference in 60-month survival between patients who received any additional therapy and those who had surgery alone (55 versus 38 per cent respectively; P = 0·184), whereas additional therapy improved survival in patients with stage III tumours (58 versus 30 per cent respectively; P = 0·007). Multivariable analysis found a survival benefit for additional therapy in elderly patients with stage III disease (hazard ratio 0·58, 95 per cent c.i. 0·34 to 0·98). CONCLUSION: A multimodal approach in elderly patients with stage III rectal cancer improved oncological outcomes.

Is Chemotherapy or Radiation Therapy in Addition to Surgery Beneficial for Locally Advanced Rectal Cancer in the Elderly? A National Cancer Data Base (NCDB) Study.

INTRODUCTION: Current National Comprehensive Cancer Network guidelines for Stages II and III rectal cancer recommend neoadjuvant chemoradiation followed by curative intent surgery and adjuvant chemotherapy. It is unclear whether therapies in addition to surgery are truly beneficial in elderly patients. Our aim was to compare the survival of patients over 80 with Stages II and III rectal cancer undergoing curative intent surgery with or without additional therapy. MATERIALS AND METHODS: The National Cancer Data Base (NCDB 2006-2011) was queried for patients over 80 with Stages II and III rectal cancer. The primary outcome was overall survival. Patients were stratified based upon therapy group. Univariate group comparisons were made. Unadjusted Kaplan-Meier and multivariable Cox proportional hazards modeling survival analyses were performed. RESULTS: The query yielded 3098 patients over 80 with Stage II (N = 1566) or Stage III (N = 1532) disease. Approximately, half of the patients received surgery only. Kaplan-Meier analysis showed improved survival for patients receiving neoadjuvant and/or adjuvant therapy in addition to surgery, but there was no significant difference between those that received guideline concordant care (GCC), neoadjuvant chemoradiation only, or post-operative chemotherapy only. Cox proportional hazard modeling identified age >90 and margin positivity as independent risk factors for decreased overall survival. CONCLUSION: Analysis of NCDB data for Stages II and III rectal cancer in patients over 80 shows a survival benefit of adjuvant and/or neoadjuvant therapy over surgery alone. There does not appear to be a difference in survival between patients who received neoadjuvant chemoradiation, post-resection adjuvant chemotherapy, or GCC.

Combined APRI/ALBI score to predict mortality after hepatic resection.

BACKGROUND: Aspartate aminotransferase/platelet ratio index (APRI) and albumin-bilirubin grade (ALBI) are validated prognostic indices implicated as predictors of postoperative liver dysfunction after hepatic resection. The aim of this study was to evaluate the relevance of the combined APRI/ALBI score for postoperative clinically meaningful outcomes. METHODS: Patients undergoing hepatectomy were included from the American College of Surgeons National Surgical Quality Improvement Program database. The association between APRI/ALBI score and postoperative grade C liver dysfunction, liver dysfunction-associated and overall 30-day mortality was assessed. RESULTS: A total of 12 055 patients undergoing hepatic resection from 2014 to 2017 with preoperative blood values and detailed 30-day postoperative outcomes were included (exploration cohort: January 2014 to December 2016; validation cohort: 2017). In the exploration cohort (8538 patients), the combination of both scores (APRI/ALBI) was significantly associated with postoperative grade C liver dysfunction, 30-day mortality, and liver dysfunction-associated 30-day mortality, and was superior to either score alone. The association with postoperative 30-day mortality was confirmed in multivariable analysis. A predictive model was generated using the exploration cohort. The predicted incidence of events closely followed the observed incidence in the validation cohort (3517 patients). Subgroup analyses of tumour types were used to generate disease-specific risk models to assess risk in different clinical scenarios. These findings informed development of a smartphone application (https://tellaprialbi.37binary.com). CONCLUSION: The predictive potential of the combined APRI/ALBI score for clinically relevant outcomes such as mortality was demonstrated. An evidence-based smartphone application will allow clinical translation and facilitation of risk assessment before hepatic resection using routine laboratory parameters.

Surgery alone is adequate treatment for early stage soft tissue sarcoma of the extremity.

BACKGROUND: Evolving evidence suggests that, in selected patients with tumour category 1 (T1) extremity soft tissue sarcoma (ESTS), surgery alone offers satisfactory results without decreasing survival. This study assessed the effect of sarcoma treatments on survival outcomes of T1 ESTS in a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results database, 1618 patients with primary ESTS underwent limb-sparing surgery. Multivariable analysis was used to assess the impact of radiotherapy on overall survival (OS) and sarcoma-specific survival (SSS), adjusting for co-variables. RESULTS: Some 803 patients (49.6 per cent) underwent surgery alone for T1 ESTS. Radiotherapy in patients with low- and high-grade tumours did not result in any significant difference in OS or SSS. When stratified by grade, multivariable analysis showed that adjuvant radiotherapy was not an independent predictor of SSS (hazard ratio (HR) 1.05; P = 0.906) or OS (HR 0.89; P = 0.695) in low-grade tumours. Neither was radiotherapy a significant predictor of SSS (HR 0.87; P = 0.608) or OS (HR 0.67; P = 0.071) in high-grade tumours. CONCLUSION: This population-based appraisal validated previous evidence supporting a role for surgery alone in the treatment of T1 ESTS. Future policies should be tailored to offer patients minimal yet effective therapy, rather than maximum tolerated therapy.

A 25 year experience of perineal hernia repair.

PURPOSE: Though perineal hernias remain rare, the incidence is reportedly rising. Secondary to the historical rarity, optimal method of repair and outcomes after repair remain poorly understood. Therefore, we reviewed the past 25 years of our institutional experience with perineal hernia repair. METHODS: A retrospective review of an institution-maintained database was conducted from January 1, 1994 to January 31, 2018 for patients undergoing perineal hernia repair. Data were collected on patient characteristics, operative technique, and post-operative outcomes. RESULTS: Twenty-one patients (n = 12 male) underwent perineal hernia repair in the study period with two-thirds of the operations occurring in the most recent 7 years (since January 1, 2011). The median time to repair was 13 months (range 2-127) after index operation. The approach was transabdominal in nine, perineal in nine, and combined in three. Mesh, a tissue flap, or a combination of these was used in 19 of the cases and 6 additional abdominal wall hernias were repaired concurrently. Post-operative complications consisted of superficial surgical-site infection (n = 2), infected seroma (n = 1), and a missed enterotomy (n = 1). Follow-up ranged from 0 to 112 months (median 2 months) and only one recurrence was noted. CONCLUSION: Presentation for repair of perineal hernia has increased at our instituion over the past 2 decades. Outcomes did not differ between the three repair approaches and the choice of mesh or tissue-based repair. Surgeons should base these decisions on hernia complexity and local tissue conditions.

Surgical trends of groin hernia repairs performed for recurrence in medicare patients.

BACKGROUND: The recurrence rate after groin hernia repair (GHR) has been estimated to be between 1-10% in adult patients. Neither national rates nor trends in recurrence over time have been reliably established for Medicare patients in the USA. MATERIALS: We evaluated patients undergoing GHR (inguinal = IHR; femoral = FHR) from 2011 to 2014 from the Medicare Provider Analysis and Review database. Patients were identified using ICD-9 diagnosis and ICD-9 and CPT procedure codes, stratified both by primary vs. recurrent hernia repair and by sex. One-tailed Cochran-Armitage tests evaluated trends over time and a generalized estimating equation model estimated factors associated with recurrent IHR or FHR. RESULTS: We identified 407,717 patients (87.0%, ≥ 65 years) who underwent an IHR and 11,578 (91.0%, ≥ 65 years) who underwent a FHR. The proportion of IHRs for recurrence decreased statistically from 14.3% in 2011 to 13.9% in 2014 (p < 0.01) in males and was increased, but not statistically so (7.0-7.4%) in females (p = 0.08). The proportion of FHRs for recurrence was decreased, but not statistically so (16.3-14.8%, p = 0.29) in males and increased in females (5.3-6.3%, p = 0.02). On multivariable analysis, males were more than twice as likely as females to undergo recurrent repair (IHR or FHR, both p < 0.01). CONCLUSIONS: Within the Medicare population, recurrence rates after groin hernia repairs were found to be higher than previously reported but have remained clinically stable over time. Establishing and reducing this rate is important for patient outcomes and expectations.

2019 John Charnley Award: Increased risk of prosthetic joint infection following primary total knee and hip arthroplasty with the use of alternative antibiotics to cefazolin: the value of allergy testing for antibiotic prophylaxis.

AIMS: The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. PATIENTS AND METHODS: We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. RESULTS: Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. CONCLUSION: PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9-15.

Proportion of femoral hernia repairs performed for recurrence in the United States.

PURPOSE: Recurrence rates after femoral hernia repair (FHR) have not been reliably established in the USA. We sought to determine this trend over time. METHODS: The proportion of primary and recurrent FHRs was determined for patients age ≥ 18 from: ACS-NSQIP (1/2005-12/2014), Premier (1/2010-09/2015), and institutional (1/2005-12/2014) data. Trends were analyzed using a one-tailed Cochran-Armitage test. RESULTS: In the NSQIP database, 6649 patients underwent a FHR. In females, the proportion of FHRs performed for recurrence decreased from 14.0% in 2005 to 6.2% in 2014, p = 0.02. In males, there was no change: 16.7-16.1% 2005-2014 (p = 0.18). The Premier database included 4495 FHRs and our institution 315 FHRs. There was no difference for either gender over time in either data source, all p > 0.05. CONCLUSIONS: The proportion of femoral hernia repairs performed for recurrence in the USA remained relatively constant in males in two large national databases between 2005 and 2015. In females, a decrease was seen in one of the large national databases.