Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.

Factors affecting Naseptin treatment success - A prospective cohort study.

OBJECTIVE: To assess patient factors to predict treatment success of Naseptin for recurrent paediatric epistaxis. METHODS: This prospective cohort study of paediatric patients referred to a tertiary paediatric otolaryngology clinic with recurrent epistaxis treated with Naseptin cream and education. Patients with red flag symptoms and bleeding diathesis were omitted, along with patients with concurrent otolaryngology complaints. Statistical analysis included logistic regression analysis to assess for predictive factors contributing to treatment success. RESULTS: 125 of 210 patients on the waiting list met the inclusion criteria and were given a complete trial of Naseptin. 80.8% (n = 101) of patients found that the frequency and severity of epistaxis had reduced, with the remaining 19.2% (n = 24) reporting that the episodes of epistaxis remained the same and required further management (i.e., silver nitrate cautery). Five patients (4%) reported minor side effects (skin irritation etc.) with no significant adverse events reported. CONCLUSION: We found that Naseptin is a safe, well-tolerated treatment that should be trialled in most cases of recurrent paediatric epistaxis. Most children will benefit from it with complete epistaxis cessation or at least reduced frequency and severity.

Reef islands have continually adjusted to environmental change over the past two millennia.

Global environmental change is identified as a driver of physical transformation of coral reef islands over the past half-century, and next 100 years, posing major adaptation challenges to island nations. Here we resolve whether these recent documented changes in islands are unprecedented compared with the pre-industrial era. We utilise radiometric dating, geological, and remote sensing techniques to document the dynamics of a Maldivian reef island at millennial to decadal timescales. Results show the magnitude of island change over the past half-century (±40 m movement) is not unprecedented compared with paleo-dynamic evidence that reveals large-scale changes in island dimension, shape, beach levels, as well as positional changes of ±200 m since island formation ~1,500 years ago. Results highlight the value of a multi-temporal methodological approach to gain a deeper understanding of the dynamic trajectories of reef islands, to support development of adaptation strategies at timeframes relevant to human security.

Is radiomic MRI a feasible alternative to OncotypeDX® recurrence score testing? A systematic review and meta-analysis.

BACKGROUND: OncotypeDX® recurrence score (RS) aids therapeutic decision-making in oestrogen-receptor-positive (ER+) breast cancer. Radiomics is an evolving field that aims to examine the relationship between radiological features and the underlying genomic landscape of disease processes. The aim of this study was to perform a systematic review of current evidence evaluating the comparability of radiomics and RS. METHODS: A systematic review was performed as per PRISMA guidelines. Studies comparing radiomic MRI tumour analyses and RS were identified. Sensitivity, specificity and area under curve (AUC) delineating low risk (RS less than 18) versus intermediate-high risk (equal to or greater than 18) and low-intermediate risk (RS less than 30) and high risk (RS greater than 30) were recorded. Log rate ratios (lnRR) and standard error were determined from AUC and 95 per cent confidence intervals. RESULTS: Nine studies including 1216 patients met inclusion criteria; the mean age at diagnosis was 52.9 years. Mean RS was 16 (range 0-75); 401 patients with RS less than 18, 287 patients with RS 18-30 and 100 patients with RS greater than 30. Radiomic analysis and RS were comparable for differentiating RS less than 18 versus RS 18 or greater (RR 0.93 (95 per cent c.i. 0.85 to 1.01); P = 0.010, heterogeneity (I2)=0%) as well as RS less than 30 versus RS 30 or greater (RR 0.76 (95 per cent c.i. 0.70 to 0.83); P < 0.001, I2=0%). MRI sensitivity and specificity for RS less than 18 versus 18 or greater was 0.89 (95 per cent c.i. 0.85 to 0.93) and 0.72 (95 per cent c.i. 0.66 to 0.78) respectively, and 0.79 (95 per cent c.i. 0.72 to 0.86) and 0.74 (95 per cent c.i. 0.68 to 0.80) for RS less than 30 versus 30 or greater. CONCLUSION: Radiomic tumour analysis is comparable to RS in differentiating patients into clinically relevant subgroups. For patients requiring MRI, radiomics may complement and enhance RS for prognostication and therapeutic decision making in ER+ breast cancer.

Optimal reconstructive strategies in the setting of post-mastectomy radiotherapy - A systematic review and network meta-analysis.

BACKGROUND: A third of breast cancer patients require mastectomy. In some high-risk cases postmastectomy radiotherapy (PMRT) is indicated, threatening reconstructive complications. Several PMRT and reconstruction combinations are used. Autologous flap (AF) reconstruction may be immediate (AF→PMRT), delayed-immediate with tissue expander (TE [TE→PMRT→AF]) or delayed (PMRT→AF). Implant-based breast reconstruction (IBBR) includes immediate TE followed by PMRT and conversion to permanent implant (PI [TE→PMRT→PI]), delayed TE insertion (PMRT→TE→PI), and prosthetic implant conversion prior to PMRT (TE→PI→PMRT). AIM: Perform a network metanalysis (NMA) assessing optimal sequencing of PMRT and reconstructive type. METHODS: A systematic review and NMA was performed according to PRISMA-NMA guidelines. NMA was conducted using R packages netmeta and Shiny. RESULTS: 16 studies from 4182 identified, involving 2322 reconstructions over three decades, met predefined inclusion criteria. Studies demonstrated moderate heterogeneity. Multiple comparisons combining direct and indirect evidence established AF-PMRT as the optimal approach to avoid reconstructive failure, compared with IBBR strategies (versus PMRT→TE→PI; OR [odds ratio] 0.10, CrI [95% credible interval] 0.02 to 0.55; versus TE→PMRT→PI; OR 0.13, CrI 0.02 to 0.75; versus TE→PI→PMRT OR 0.24, CrI 0.05 to 1.05). PMRT→AF best avoided infection, demonstrating significant improvement versus PMRT→TE→PI alone (OR 0.12, CrI 0.02 to 0.88). Subgroup analysis of IBBR found TE→PI→PMRT reduced failure rates (OR 0.35, CrI 0.15-0.81) compared to other IBBR strategies but increased capsular contracture. CONCLUSION: Immediate AF reconstruction is associated with reduced failure in the setting of PMRT. However, optimal reconstructive strategy depends on patient, surgeon and institutional factors. If IBBR is chosen, complication rates decrease if performed prior to PMRT. PROSPERO REGISTRATION: CRD 42020157077.

Clinicopathological and prognostic significance of programmed cell death ligand 1 expression in patients diagnosed with breast cancer: meta-analysis.

BACKGROUND: Uncertainty exists regarding the clinical relevance of programmed cell death ligand 1 (PD-L1) expression in breast cancer. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Observational studies that compared high versus low expression of PD-L1 on breast cancer cells were identified. Log hazard ratios (HRs) for disease-free and overall survival and their standard errors were calculated from Kaplan-Meier curves or Cox regression analyses, and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (ORs) using the Mantel-Haenszel method. RESULTS: Sixty-five studies with 19 870 patients were included; 14 404 patients were classified as having low and 4975 high PD-L1 expression. High PD-L1 was associated with achieving a pathological complete response following neoadjuvant chemotherapy (OR 3.30, 95 per cent confidence interval 1.19 to 9.16; P < 0.01; I2 = 85 per cent). Low PD-L1 expression was associated with human epidermal growth factor receptor 2 (OR 3.98, 1.81 to 8.75; P < 0.001; I2 = 96 per cent) and luminal (OR 14.93, 6.46 to 34.51; P < 0.001; I2 = 99 per cent) breast cancer subtypes. Those with low PD-L1 had favourable overall survival rates (HR 1.30, 1.05 to 1.61; P = 0.02; I2 = 85 per cent). CONCLUSION: Breast cancers with high PD-L1 expression are associated with aggressive clinicopathological and immunohistochemical characteristics and are more likely to achieve a pathological complete response following neoadjuvant chemotherapy. These breast cancers are, however, associated with worse overall survival outcomes.

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer.

BACKGROUND: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. METHODS: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P < 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P < 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P < 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P < 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Clinical utility of the 21-gene assay in predicting response to neoadjuvant endocrine therapy in breast cancer: A systematic review and meta-analysis.

INTRODUCTION: OncotypeDX© Recurrence Score (RS) is a multigene panel used to aid therapeutic decision making in early-stage, estrogen receptor positive (ER+)/human epidermal growth factor receptor-2 negative (HER2-) breast cancer. AIM: To compare responses to neoadjuvant endocrine therapy (NET) in patients with ER+/HER2-breast cancer following substratification by RS testing. METHODS: This systematic review was performed in accordance to the PRISMA guidelines. Studies evaluating pathological complete response (pCR), partial response (PR), and successful conversion to breast conservation surgery (BCS) rates following NET guided by RS were retrieved. Dichotomous outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs) following estimation by Mantel-Haenszel method. RESULTS: Eight prospective studies involving 691 patients were included. The mean age was 62.6 years (range 25-85) and the mean RS was 14.5 (range 0-68). Patients with RS < 25 (OR: 4.60, 95% CI: 2.53-8.37, P < 0.001) and RS < 30 (OR: 3.40, 95% CI: 1.96-5.91, P < 0.001) were more likely to achieve PR than their counterparts. NET prescription failed to increase BCS conversion rates for patients with RS < 18 (OR: 0.23, 95% CI: 0.04-1.47, P = 0.120) and RS > 30 (OR: 1.27, 95% CI: 0.64-2.49, P = 0.490) respectively. Only 22 patients achieved pCR (2.8%) and RS group failed to predict pCR following NET (P = 0.850). CONCLUSION: Estimations from this analysis indicate that those with low-intermediate RS on core biopsy are four times more likely to respond to NET than those with high-risk RS. Performing RS testing on diagnostic biopsy may be useful in guiding NET prescription.

Oncological outcomes of laparoscopic versus open rectal cancer resections: meta-analysis of randomized clinical trials.

BACKGROUND: The role of laparoscopic rectal cancer surgery has been questioned owing to conflicting reports on pathological outcomes from recent RCTs. However, it is unclear whether these pathological markers and the surgical approach have an impact on oncological outcomes. This study assessed oncological outcomes of laparoscopic and open rectal cancer resections. METHODS: A meta-analysis of RCTs was performed. Primary endpoints included oncological outcomes (disease-free survival (DFS), overall survival (OS), local recurrence). Secondary endpoints included surrogate markers for the quality of surgical resection. RESULTS: Twelve RCTs including 3744 patients (2133 laparoscopic, 1611 open) were included. There was no significant difference in OS (hazard ratio (HR) 0.87, 95 per cent c.i. 0.73 to 1.04; P = 0.12; I2 = 0 per cent) and DFS (HR 0.95, 0.81 to 1.11; P = 0.52; I2 = 0 per cent) between laparoscopic and open rectal resections. There was no significant difference in locoregional (odds ratio (OR) 1.03, 95 per cent c.i. 0.72 to 1.48; P = 0.86; I2 = 0 per cent) or distant (OR 0.87, 0.70 to 1.08; P = 0.20; I2 = 7 per cent) recurrence between the groups. Achieving a successful composite score (intact mesorectal excision, clear circumferential resection margin and distal margin) was significantly associated with improved DFS (OR 0.55, 0.33 to 0.74; P < 0.001; I2 = 0 per cent). An intact or acceptable mesorectal excision (intact mesorectal excision with or without superficial defects) had no impact on DFS. Finally, a positive CRM was associated with worse DFS. CONCLUSION: Well performed surgery (laparoscopic or open) achieves excellent oncological outcomes with very little difference between the two modalities. The advantage and benefit of minimally invasive surgery should be assessed on an individual basis.

Value of a 21-gene expression assay on core biopsy to predict neoadjuvant chemotherapy response in breast cancer: systematic review and meta-analysis.

BACKGROUND: A recurrence score based on a 21-gene expression assay predicts the benefit of adjuvant chemotherapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This systematic review aimed to determine whether the 21-gene expression assay performed on core biopsy at diagnosis predicted pathological complete response (pCR) to neoadjuvant chemotherapy. METHODS: The study was performed according to PRISMA guidelines. Relevant databases were searched to identify studies assessing the value of the 21-gene expression assay recurrence score in predicting response to neoadjuvant chemotherapy in patients with breast cancer. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Results are reported as risk ratio (RR) with 95 per cent confidence interval using the Cochrane-Mantel-Haenszel method for meta-analysis. Sensitivity analyses were carried out where appropriate. RESULTS: Seven studies involving 1744 patients reported the correlation between pretreatment recurrence score and pCR. Of these, 777 patients (44.6 per cent) had a high recurrence score and 967 (55.4 per cent) a low-intermediate score. A pCR was achieved in 94 patients (5.4 per cent). The pCR rate was significantly higher in the group with a high recurrence score than in the group with a low-intermediate score (10.9 versus 1.1 per cent; RR 4.47, 95 per cent c.i. 2.76 to 7.21; P < 0.001). A significant risk difference was observed between the two groups (risk difference 0.10, 0.04 to 0.15; P = 0.001). CONCLUSION: A high recurrence score is associated with higher pCR rates and a low-intermediate recurrence score may indicate chemoresistance. Routine assessment of recurrence score by the 21-gene expression assay on core biopsy might be of value when considering neoadjuvant chemotherapy in patients with ER-positive, HER2-negative breast cancer.

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers - A systematic review and meta-analysis.

BACKGROUND: The non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers. AIMS: To evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis. METHODS: A systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel-Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method. RESULTS: Twenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77-7.42, P < 0.001, heterogeneity (I2) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44-5.11, P = 0.510, I2 = 80%), disease recurrence (HR:1.16, 95%CI: 0.78-1.72, P = 0.470, I2 = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79-3.15, P = 0.200, I2 = 38%) and death (HR:1.10, 95%CI: 0.72-1.69, P = 0.660, I2 = 38%) were equivalent for combined BCT and mastectomy. CONCLUSIONS: Survival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.

Disease recurrence and oncological outcome of patients treated surgically with curative intent for estrogen receptor positive, lymph node negative breast cancer.

BACKGROUND: The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses. AIMS: To describe clinicopathologic features, oncological outcome and relapse patterns in LABC. METHODS: Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses. RESULTS: Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07-2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21-4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25-2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49-4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19-8.22, P = 0.020) predicted OS. CONCLUSION: Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.

Five-year follow-up of patients treated with intra-dermal botulinum toxin for axillary hyperhidrosis.

BACKGROUND: Axillary hyperhidrosis is a common complaint affecting 5% of the general population. It can significantly impact quality of life (QOL) and may be extremely debilitating. Administration of intra-dermal botulinum toxin type-A (Botox) has been proven to be effective in managing axillary hyperhidrosis; however, to date, no long-term data has assessed its efficacy. AIM: We aim to assess long-term (> 5 years) QOL outcomes in this patient cohort. METHODS: In this single-centre series, all patients attending for axillary botox, with five or more years of follow-up, were prospectively included. QOL was assessed in all patients using the validated assessment tool, the modified Dermatology Life Quality Index (DLQI). Standard statistical methods were utilised with data reported as mean (± standard deviation). Subgroup analysis utilising previously published departmental data allowed for further assessment of change in QOL over time. RESULTS: A total of 75 patients (83% female) met the inclusion criteria with 67% completing the DLQI assessment. Follow-up ranged from 5 to 10 years with a mean age of 37.6 years (± 8.82). The mean number of treatments over the study period was 12 (± 3.1). Mean overall post-treatment DLQI score was 1.6 (± 2.01). This represented a significant improvement in patient QOL (p = < 0.0001) associated with long-term botox application. This statistical significance was identified consistently across all components of the DLQI tool. CONCLUSION: These data suggest that the established early QOL benefits associated with intra-dermal botox administration for AH are sustained in the long term. This benefit was seen across all subsets of the DLQI tool.

Meta-analysis of the impact of progesterone receptor status on oncological outcomes in oestrogen receptor-positive breast cancer.

BACKGROUND: Assessment of the oestrogen receptor (ER) provides important prognostic information in breast cancer. The impact of progesterone receptor (PgR) status is less clear. Standardization of immunohistochemical analysis of these receptors has reduced interstudy heterogeneity. The aim of this meta-analysis was to evaluate the impact of PgR negativity on outcomes in ER-positive (ER+) breast cancer. METHODS: This study was performed according to PRISMA and MOOSE guidelines. PubMed, Embase and the Cochrane Library were searched systematically to identify studies comparing disease-free survival as the primary outcome and overall survival as secondary outcome between PgR-positive (PgR+) and PgR-negative (PgR-) status in ER+ breast cancer. A meta-analysis of time-to-effect measures from included studies was undertaken. RESULTS: Eight studies including 13 667 patients, 11 838 in the ER+PgR+ group and 1829 in the ER+PgR- group, met the inclusion criteria. Treatment characteristics did not differ significantly between the two groups. Patients in the ER+PgR- group had a higher risk of disease recurrence than those who had ER+PgR+ disease (hazard ratio (HR) 1·57, 95 per cent c.i. 1·38 to 1·79; P < 0·001). This hazard was increased in patients with human epidermal growth factor receptor 2-negative tumours (HR 1·62, 1·37 to 1·93; P < 0·001). A similar result was observed for overall survival (HR 1·69, 1·33 to 2·14; P < 0·001). CONCLUSION: PgR negativity is associated with significant reductions in disease-free and overall survival in ER+ breast cancer. Treatment and surveillance strategies in these patients should be tailored accordingly.

ANTECEDENTES: La evaluación del receptor de estrógenos (oestrogen receptor, ER) proporciona una importante información pronóstica en el cáncer de mama. El impacto de del estado del receptor de la progesterona (progesterone receptor, PgR) está menos claro. La estandarización del análisis inmunohistoquímico de estos receptores ha reducido la heterogeneidad entre los estudios. El objetivo de este metaanálisis fue evaluar el impacto de la negatividad de PgR (PgR-) en los resultados del cáncer de mama ER positivo (ER+). MÉTODOS: Este estudio se realizó de acuerdo con las directrices PRISMA/MOOSE. Se llevó a cabo una búsqueda sistemática en MEDLINE, PubMed y biblioteca Cochrane para identificar estudios que comparasen la supervivencia libre de enfermedad (disease free survival, DFS) como resultado primario y la supervivencia global (overall survival, OS) como resultado secundario entre los estados PgR+ y PgR- en el cáncer de mama ER+. Se realizó un metaanálisis de los estudios incluidos de las medidas de tiempo hasta el efecto. RESULTADOS: Ocho estudios que incluían 13.533 pacientes, 11.724 en el grupo ER+PgR+ y 1.809 en el grupo ER+PgR- cumplieron con los criterios de inclusión. Las características del tratamiento no diferían significativamente entre los dos grupos. Los pacientes en el grupo ER+PgR- presentaron un riesgo más elevado de recidiva de la enfermedad que aquellas que tenían enfermedad ER+PgR+ (DFS, cociente de riesgos instantáneos, hazard ratio, HR 1,57; i.c. del 95% 1,38-1,79; P < 0,001). Este riesgo se incrementó en pacientes que eran HER2 negativo (DFS HR 1,62; i.c. del 95% 1,37-1,93; P < 0,001). Un resultado similar se observó para la OS (HR 1,69; i.c. del 95% 1,33-2,14, P < 0,001). CONCLUSIÓN: La negatividad de PgR se asocia con disminuciones significativas de DFS y OS en el cáncer de mama ER+. En estas pacientes, las estrategias de tratamiento y seguimiento en deberán adecuarse a cada caso particular.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer.

BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.