The accuracy of MRI in detecting pathological complete response following neoadjuvant chemotherapy in different breast cancer subtypes.

BACKGROUND: Pathological complete response (pCR) following neo-adjuvant chemotherapy (NACT) for breast cancer is associated with improved disease-free and overall survival in certain breast cancer subtypes. Magnetic Resonance Imaging (MRI) is increasingly used as standard to assess treatment response in patients receiving NACT. The aim of this study was to determine the clinical utility of MRI in accurately predicting pCR post-NACT. METHODS: A single-centre, retrospective study was conducted in breast cancer patients, who received NACT between 2013 and 2020. Patients who had an MRI before and after NACT were included. Pathological and MRI radiological response rates to NACT were analyzed and MRI accuracy assessed in detecting pCR according to breast cancer subtype. RESULTS: One hundred and sixty-seven patients were included in the study. Forty-one of the 167 patients achieved pCR (24.6 %), with the highest proportion in HR- HER2+ subgroup (58.3 %), followed by triple negative breast cancer (TNBC) (35 %). Only 22.2 % and 10.5 % of patients with HR + HER2+ and HR + HER2-respectively achieved pCR. The overall accuracy of MRI in predicting pCR after NACT was 77.3 %. The greatest accuracy was in TNBC (87.5 %) with a specificity and positive predictive value (PPV) of 100 % and the highest number of correctly diagnosed complete responses (14 of 40). MRI was less accurate in predicting response rates in HR + HER2- (PPV 91.2 %) and HR + HER2+ groups (PPV 90.5 %). MRI performed significantly better in predicting complete response in TNBC compared to HR + HER2-subtype (p = 0.0057). CONCLUSION: MRI is a clinically useful adjunct in assessing pCR following NACT and appears to predict pathological response more accurately in TNBC compared to HR + HER2-breast cancer subtypes. This has significant clinical implications in terms of surgical planning, adjuvant treatment options and prognosis.

Effect of obesity on perioperative outcomes following gastrointestinal surgery: meta-analysis.

BACKGROUND: Obesity can pose perioperative challenges related to obesity-associated co-morbidities and technical factors. However, the true impact of obesity on postoperative outcomes is not well established and reports are conflicting. The aim was to perform a systematic review and meta-analysis to explore the effect of obesity on perioperative outcomes for general surgery procedures in distinct obesity subtypes. METHODS: A systematic review was performed for studies reporting postoperative outcomes in relation to BMI in upper gastrointestinal, hepatobiliary and colorectal based on an electronic search using the Cochrane Library, Science Direct, PubMed and Embase up to January 2022. The primary outcome was the incidence of 30-day postoperative mortality among patients with obesity undergoing general surgical procedures in comparison to patients with normal range BMI. RESULTS: Sixty-two studies, including 1 886 326 patients, were eligible for inclusion. Overall, patients with obesity (including class I/II/II) had lower 30-day mortality rates in comparison to patients with a normal BMI (odds ratio (OR) 0.75, 95 per cent c.i. 0.66 to 0.86, P < 0.0001, I2 = 71 per cent); this was also observed specifically in emergency general surgery (OR 0.83, 95 per cent c.i. 0.79 to 0.87, P < 0.0000001, I2 = 7 per cent). Compared with normal BMI, obesity was positively associated with an increased risk of 30-day postoperative morbidity (OR 1.11, 95 per cent c.i. 1.04 to 1.19, P = 0.002, I2 = 85 per cent). However, there was no significant difference in postoperative morbidity rates between the cohorts of patients with a normal BMI and class I/II obesity (OR 0.98, 95 per cent c.i. 0.92 to 1.04, P = 0.542, I2 = 92 per cent). Overall, the cohort with obesity had a higher rate of postoperative wound infections compared with the non-obese group (OR 1.40, 95 per cent c.i. 1.24 to 1.59, P < 0.0001, I2 = 82 per cent). CONCLUSION: These data suggest a possible 'obesity paradox' and challenge the assumption that patients with obesity have higher postoperative mortality compared with patients with normal range BMI. Increased BMI alone is not associated with increased perioperative mortality in general surgery, highlighting the importance of more accurate body composition assessment, such as computed tomography anthropometrics, to support perioperative risk stratification and decision-making. REGISTRATION NUMBER: CRD42022337442 (PROSPERO https://www.crd.york.ac.uk/prospero/).

Readability and Quality of Online Health Information Regarding Parathyroidectomy.

Objective: Assessment of the readability and quality of online health information regarding parathyroidectomy. Study Design: Cross-sectional analysis. Setting: Websites providing patient-oriented health information regarding parathyroidectomy obtained via the Google search engine. Methods: The top 75 Google search results for "parathyroidectomy,""parathyroid surgery," and "parathyroid gland removal" were reviewed. Websites were categorized by website type and country of origin. Readability was assessed by Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook. Website quality was assessed per JAMA benchmark criteria and the DISCERN instrument. Results: A total of 74 unique websites were evaluated. The mean readability of the assessed websites exceeded the recommended sixth-grade reading level on the Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook (P < .001). Readability did not vary significantly by website type. Websites originating from the United Kingdom were significantly more readable than those from the United States. The majority of assessed websites were of poor quality (n = 42, 56.8%) on assessment based on the DISCERN instrument. Quality varied significantly by website category on the JAMA benchmark criteria (P < .001) and DISCERN score (P = .049) with commercial websites receiving the highest scores. DISCERN score also varied significantly by country of origin (P = .036) with UK sites receiving highest mean DISCERN scores. Conclusion: Online health information regarding parathyroidectomy is largely of poor quality and is poorly readable for many patients. Institutions utilizing well-defined guidelines for development of patient educational resources may provide online health information of greater quality and readability.

Assessment of cell-free DNA (cfDNA) concentrations in the perioperative period can predict risk of recurrence in patients with non-metastatic breast cancer.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a potential non-invasive biomarker of disease status in patients with cancer, and provides important diagnostic and prognostic information in breast cancer. The goal of this study was to quantify cfDNA concentrations during the perioperative period and investigate its potential utility to detect recurrence outcomes in patients with breast cancer. METHODS: Sixty-two (n = 62) patients with non-metastatic breast cancer, undergoing curative-intent surgery were screened for inclusion. Blood samples were collected from these patients: pre-operatively (Preop) and post-operatively (PO) at either of the following PO time points; PO week 1-2, PO week 3-4 and PO weeks 5-12 following surgery. cfDNA was extracted and quantified using nanodrop spectrophotometer. RESULTS: In a cohort of 62 patients (age, median (IQR), 51.5(45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months), significant association was observed between cfDNA concentrations and risk of recurrence in patients with breast cancer. The group of patients who had disease recurrence during follow-up had significantly higher cfDNA concentrations (cutoff:400 ng/ml) compared to the group of patients who remain disease-free (Preop and PO period: p < 0.0001). The median Recurrence Free Survival (RFS) between the Disease Recurrence (DR) and the Disease Free (DF) groups of patients with breast cancer were 12(20-28.5) months and 72.00 (96-120) months; p < 0.0001). Univariate and multivariate cox regression analysis indicated that postoperative cfDNA concentration (Hazard ratio:5.0, 95% Confidence Interval:1.19-21.28, p = 0.028) was an independent negative prognostic factor for RFS in patients with non-metastatic breast cancer. CONCLUSION: Our study demonstrated that high postoperative cfDNA is associated with increased risk of future recurrence in patients with non-metastatic breast cancer. Further, prospective studies are warranted to validate its clinical utility in breast cancer.

The positive predictive value of vacuum assisted biopsy (VAB) in predicting final histological diagnosis for breast lesions of uncertain malignancy (B3 lesions): A systematic review & meta-analysis.

INTRODUCTION: High-risk or B3 breast lesions are considered lesions of uncertain malignant potential and comprise between 5 and 12% of initial biopsy results. We sought to perform a systematic review and meta-analysis of studies published within the last twenty years to determine the pooled Positive Predictive Value (PPV) of VAB in selected B3 lesions. METHODS: The study report is based on the guidelines of PRISMA and Meta-Analysis of Observational Studies in Epidemiology. OUTCOMES: The primary outcome of this study was to determine the PPV of VAB in determining final histological diagnosis in B3 breast lesions using pooled estimates. The secondary outcomes were to determine if needle gauge or the re-classification of Lobular Carcinoma in Situ(LCIS) introduced in 2012 influenced pooled estimates. RESULTS: 78 studies incorporating 6,377 B3 lesions were included in this review, 1214 of which were upgraded to DCIS or invasive malignancy following surgical excision(19%). The pooled PPV of VAB in Atypical Ductal Hyperplasia(ADH) and Lobular Neoplasia(LN) were 0.79(CI 0.76-0.83) and 0.84(CI 0.8-0.88). VAB of Flat Epithelial Atypia(FEA), radial scar and papillary lesions with/without atypia all had a pooled PPV >90% (underestimation rates 7%, 1%, 5% and 3% respectively). Needle gauge size and the change in LCIS classification did not appear to influence underestimation rates on subgroup analysis. CONCLUSION: Results from this meta-analysis suggests it is reasonable to perform VAB as definitive treatment for certain B3 lesions, specifically LN, FEA, radial scar, and papillary lesions when specific criteria are fulfilled. Surgical excision should continue as the mainstay of treatment for ADH.

Fertility treatment and breast-cancer incidence: meta-analysis.

BACKGROUND: The significance of exogenous hormone manipulation as part of fertility treatment and its relationship to the development of breast cancer remains uncertain. Several historical reviews have been performed with conflicting results. This study is an updated meta-analysis to determine whether there is a causal relationship between different fertility treatments and breast cancer. METHODS: The study report is based on the guidelines of PRISMA and Meta-Analysis of Observational Studies in Epidemiology. Studies published within the last 20 years were included to reflect up to date in vitro fertilization (IVF) practice. This study was prospectively registered on PROSPERO on 07/04/2021, registration identification CRD42021247706. The primary outcome of the study was to determine whether there is an increased incidence of breast cancer in women treated with hormonal fertility treatment. The secondary outcomes were to determine whether fertility treatments were individually associated with excess breast-cancer risk. RESULTS: Overall, 25 studies, including 617 479 participants, were eligible for inclusion. There was no significant breast-cancer risk association with fertility treatment (compared with general and subfertility reference groups). Summary odds ratio of all included studies was 0.97 (95 per cent c.i. 0.90 to 1.04). Women who received six or more IVF cycles did not have an increased risk of breast cancer. Similarly, there was no excess breast-cancer risk associated with clomiphene, human chorionic gonadotropin, gonadotropin analogues and progesterone when examined individually. Comparably, there was no significant association between fertility treatment and excess breast-cancer risk in patients with more than 10 years' follow-up. Summary odds ratio was 0.97 (95 per cent c.i. 0.85 to 1.12). CONCLUSION: This meta-analysis did not find a significant association between fertility treatments and excess breast-cancer risk. Women considering IVF should be informed that it does not appear to increase breast-cancer risk.

Clinical Treatment Score post-5 years as a predictor of late distant recurrence in hormone receptor-positive breast cancer: systematic review and meta-analysis.

BACKGROUND: The Clinical Treatment Score post-5 years (CTS5) integrates four clinicopathological variables to estimate the residual disease recurrence risk in hormone receptor-positive breast cancer patients who have been treated with five years of adjuvant endocrine therapy. This study aimed to determine the accuracy of the CTS5. METHODS: A systematic review was performed in accordance with the PRISMA statement. Studies relevant for inclusion in the current review were identified from The Cochrane Library, EBSCO, Ovid, PubMed, and Embase. RESULTS: Six papers reported on 30 354 postmenopausal patients (age range 42 to 91 years). The pooled hazard ratio (HR) of distant recurrence relative to the low-risk CTS5 category was 5.41 (95% c.i. 4.50 to 6.51; P < 0.05) for the high-risk CTS5 category and 2.32 (95% c.i. 1.90-2.84; P < 0.05) for the intermediate CTS5 category. Three papers reported on 10 425 premenopausal patients (age range 18 to 54 years). The pooled HR of distant recurrence relative to the low-risk CTS5 category was 5.42 (95% c.i. 2.26 to 13.01; P < 0.05) for the high-risk CTS5 category and 2.82 (95% c.i. 1.35 to 5.88; P < 0.05) for the intermediate CTS5 category. Relative to high-risk postmenopausal patients, the mean observed 10-year distant recurrence risk for the high CTS5 category was 13.83 per cent, which differs significantly from the CTS5 estimation of 10-year distant recurrence risk (20.3 per cent, 95% c.i. 17.2 to 24; P = 0.000). CONCLUSION: The CTS5 can predict late distant recurrence risk in pre- and postmenopausal hormone receptor-positive breast cancer patients. CTS5 overestimates the risk for high-risk patients and thus, its use in these patients warrants caution.

Optimal timing of surgery following breast cancer neoadjuvant chemotherapy: A systematic review and meta-analysis.

BACKGROUND: Administration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT). METHODS: The primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between <4 weeks and 4-8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Five studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34-0.65) and DFS(OR 0.71 (95% c. i 0.52-0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46-1.33, P = 0.37). There was no difference in pCR rate between those that had surgery <4 weeks and 4-8 weeks (OR 1.01, 95% c. i 0.80-1.28, P = 0.93). CONCLUSION: This meta-analysis shows that the optimum timing of surgery post completion of NACT is 4-8 weeks as it is associated with increased OS and DFS.

The LOCalizer Radiofrequency Identification System: An Effective New Technology for Localizing Non-Palpable Breast Lesions for Surgery.

Background. Breast screening has decreased morbidity and mortality due to detection of early, non-palpable breast cancers. One of the challenges of performing breast-conserving surgery on non-palpable breast tumours is accurate localization of the cancer. We aimed to perform a feasibility study to examine the outcomes associated with the introduction of a novel radiofrequency identification system (RFID) called LOCalizer as an alternative to traditional wire-guided localization. Methods. Data were prospectively collected on all patients undergoing breast-conserving surgery using the LOCalizer RFID system in a regional cancer centre between July 2019 and March 2020. Patients had a RFID tag placed preoperatively and underwent surgical removal of the tag with the index lesion guided by a handheld LOCalizer probe. The primary aim was successful placement and retrieval of the RFID tag. Re-excision rates, specimen size, specimen weight, cancer subtype and complication rate were all recorded. Results. Sixty-nine patients aged between 50 and 69 years had a LOCalizer tag inserted between July 2019 and March 2020. Of these, 6 (8.7%) were diagnostic and 63 (91.3%) were therapeutic. There was no migration of RFID tags, and all tags were retrieved with the index lesion. The overall re-excision of margin rate was 17.4% (12/69). All re-excision of margins was due to positive radial margins. The overall complication rate was 1.4% with one grade 1 Clavien-Dindo morbidity. Conclusion. The LOCalizer RFID is an effective and safe wire-free localization method for non-palpable breast lesions.

Association of Circulating Tumor DNA With Disease-Free Survival in Breast Cancer: A Systematic Review and Meta-analysis.

Importance: Fragmented DNA is continuously released into the circulation following apoptosis and necrosis of both cancerous and noncancerous cells; when it is released by cancer cells, it is specifically known as circulating tumor DNA (ctDNA). Previous studies have suggested that ctDNA can reflect tumor burden and guide potential therapeutic targets. Objective: To determine the association of ctDNA with breast cancer disease-free survival (DFS) and progression-free survival in early, locally advanced, and metastatic breast cancer. Data Sources: An electronic search was conducted using the Cochrane Library, ScienceDirect, PubMed, and Embase from July 30, 2019, to October 31, 2019; all languages were included. The following search terms were used: ctDNA OR circulating tumor DNA OR liquid biopsy AND breast cancer OR breast carcinoma OR breast tumor AND prognosis OR survival. All titles were screened, and the appropriate abstracts were reviewed. If any data were missing, the authors contacted the study authors for permission to access data and extrapolate hazard ratios (HRs). Study Selection: To be included in the analysis, the studies had to meet the following prespecified inclusion criteria: (1) a ctDNA blood sample was measured; (2) DFS, progression-free survival, or relapse-free survival was reported as an HR; and (3) the patient population only had breast cancer. Retrospective and prospective observational cohort studies were included. Data Extraction and Synthesis: Two authors (C.C. and C.F.) independently reviewed the literature. All data were recorded independently by both authors and were compared at the end of the reviewing process to limit selection bias. Duplicates were removed and any disparities were clarified. Data were pooled using a fixed-effects or random-effects model according to the study heterogeneity. This study adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE). Main Outcomes and Measures: The primary outcome was the association of ctDNA with DFS or relapse-free survival in breast cancer. Secondary outcomes focused on subgroup analysis in the setting of early breast cancer and metastatic breast cancer. Results: From a total of 263 publications found using the predefined search terms, data from 8 studies (3.0%) reporting on 739 patients in total were suitable for inclusion. Circulating tumor DNA gene variation detection (both before and after treatment) was statistically significantly associated with shorter DFS (HR, 4.44; 95% CI, 2.29-8.61; P < .001). Detection of ctDNA was statistically significantly associated with a reduction in DFS in both the early breast cancer subgroup (HR, 8.32; 95% CI, 3.01-22.99; P < .001) and the metastatic or locally advanced subgroup (HR, 1.91; 95% CI, 1.35-2.71; P < .001). Pretreatment and posttreatment plasma sample collection was analyzed in both early and metastatic groups. The posttreatment group encompassed both surgical and oncologic therapy. Pretreatment plasma detection of ctDNA was statistically significantly associated with reduced DFS (HR, 3.30; 95% CI, 1.98-5.52; P < .001). Posttreatment sampling of ctDNA failed to achieve statistical significance (HR, 8.17; 95% CI, 1.01-65.89; P = .05). Conclusions and Relevance: In this systematic review and meta-analysis, elevated plasma ctDNA was associated with a high risk of relapse. This finding suggests that plasma ctDNA may provide an excellent method to stratify risk and personalize patient follow-up.

Can the Neutrophil to Lymphocyte Ratio Predict Complete Pathologic Response to Neoadjuvant Breast Cancer Treatment? A Systematic Review and Meta-analysis.

The systemic inflammatory response plays a role in tumor progression and development. The neutrophil to lymphocyte ratio (NLR) is a biochemical marker of systemic inflammation and is increasingly gaining appreciation for its prognostic role in predicting breast cancer outcomes. Previous research has demonstrated that patients who achieve a complete pathologic response (pCR) to neoadjuvant breast cancer treatment have a more favorable disease-free survival. This study aimed to assess whether the NLR can predict pCR to neoadjuvant therapy in breast cancer. A meta-analysis of 8 relevant studies was performed. The primary endpoint included pCR. Secondary endpoint included 5-year disease-free survival. Eight studies were included, reporting on 1586 patients. A total of 363 (22.88%) patients achieved pCR post neoadjuvant therapy. A lower NLR was associated with a greater rate of pCR (odds ratio, 1.83; 95% confidence interval, 1.15-2.91; P = .0003). Only 4 studies produced data on disease-free survival. A lower NLR was associated with a higher 5-year disease-free survival; however, this did not achieve statistical significance (hazard ratio, 1.38; 95% confidence interval, 0.82-2.31; P = .02). Sub-group analysis of sample size, NLR value, and geographic location proved statistically significant in determining an association between NLR and pCR. This meta-analysis found NLR to be a predictor for pCR in patients with breast cancer. All of the studies reviewed were retrospective cohort studies. Adequately sized, prospective clinical trials are needed to understand if NLR could become an important prognostic indicator of pCR.

Deadly combination: Clostridium septicum and colorectal malignancy.

Gas gangrene is a life-threatening, necrotising soft tissue infection. Colorectal malignancy-associated Clostridiumsepticum is a rare cause of gas gangrene. This case outlines an initial presentation of colonic malignancy as gas gangrene from C.septicum infection.A 69-year-old man presented with abdominal pain, vomiting and constipation. Abdominal X-ray revealed dilated small bowel loops. Lactate was elevated. A diagnosis of small bowel obstruction was made. Subsequent CT revealed caecal thickening and subcutaneous emphysema overlying the left flank. Clinically, he became haemodynamically unstable. Examination revealed crepitus overlying the left flank in keeping with gas gangrene. The patient required immediate surgical debridement. Tissue specimens cultured C.septicum Following a complicated postoperative period, he was transferred to the plastic surgery team for further tissue debridement and reconstruction. A colonoscopy was later performed which was suspicious for malignancy. Colorectal multidisciplinary team discussion is awaited.

Emergency splenectomy postelective colonoscopy.

Colonoscopy is the gold standard for investigation of colorectal carcinoma and inflammatory bowel disease. Splenic injury is a rare but potentially fatal complication of colonoscopy. The present case study outlines the early clinical presentation and rapid deterioration of a patient with a splenic injury after an elective colonoscopy. A 70-year-old female underwent a colonoscopy for investigation of altered bowel habit. The procedure was documented as difficult due to the presence of 'stiff loopy colon'. In recovery, patient's condition deteriorated and she was moved to the ward for further assessment. She gradually became haemodynamically unstable and displayed signs of peritoneal irritation. Initial attempts of fluid resuscitation failed to improve patient's clinical condition. Further testing revealed a significant drop in haemoglobin and CT confirmed the diagnosis of a splenic rupture. She underwent an emergency splenectomy that evening. Postoperatively she was managed in the high dependency unit.