Circulating microRNAs can predict chemotherapy-induced toxicities in patients being treated for primary breast cancer.

PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

The impact of psychiatric comorbidities on emergency general surgical patients' outcomes.

BACKGROUND: Psychiatric disorders are increasingly prevalent. Studies have demonstrated that the presence of comorbid psychiatric conditions (CPC) is associated with a number of worsening outcomes in hospitalised patients in general. The relationship between a wide range of psychiatric comorbidities and acute surgical presentations has not been studied to date. STUDY DESIGN: The Hospital In-Patient Enquiry (HIPE) system and prospectively maintained eHandover were used to identify all surgical emergency admissions to Mayo University Hospital, Ireland. Patient demographics, comorbidities, primary diagnoses, length of stay (LoS), and procedures undergone were recorded over a 12-months period. Subgroup analyses examining LoS variation in surgical presentation types were performed. RESULTS: 1028 admissions occurred over this one year period, amongst 995 patients, the presence of psychiatric comorbidities increased the mean LoS by 1.9 days (p = 0.002). Comorbid depression, dementia, and intellectual disability conferred a significant increase in LoS by 2.4 days, 2.8 days and 6.7 days respectively. Subgroup analysis revealed greater LoS in patients with CPC diagnosed with non-specific abdominal pain (1.4 days, p = 0.019), skin and soft tissue infections (2.5 days, p = 0.040), bowel obstruction (4.3 days, p = 0.047), and medical disorders (18.6 days, p = 0.010). No significant difference was observed in mortality and readmission rates. CONCLUSION: Psychiatric comorbidities significantly impact length of hospital stay and discharge planning in surgical inpatients. Greater awareness of this can facilitate better care delivery for this population to reduce the LoS and subsequent economic burden on the healthcare system.

Evaluating the Role of Circulating MicroRNAs to Aid Therapeutic Decision Making for Neoadjuvant Chemotherapy in Breast Cancer: A Prospective, Multicenter Clinical Trial.

OBJECTIVE: To evaluate whether circulating micro ribonucleic acids (miRNAs) predict response to neoadjuvant chemotherapy (NAC) and inform decision-making in breast cancer patients. INTRODUCTION: Deciphering response to NAC remains a challenge. Those unlikely to respond may benefit from NAC de-escalation before completion, while "responders" should complete treatment. Establishing biomarkers which identify response to NAC is imperative to personalize treatment strategies. miRNAs are small noncoding RNA molecules which modulate genetic expression. miRNAs are believed to inform response to NAC. METHODS: This prospective, multicenter trial (NCT01722851) recruited 120 patients treated with NAC across 8 Irish treatment sites. Predetermined miRNAs were quantified from patient whole bloods using relative quantification polymerase chain reactiond. Venous sampling was performed at diagnosis and midway during NAC. Trends in miRNA expression between timepoints were correlated with treatment response. Data analysis was performed using R 3.2.3. RESULTS: A total of 120 patients were included (median age: 55 years). Overall, 49.2% had luminal breast cancers (59/120), 17.5% luminal B (L/HER2) (21/120), 12.5% human epidermal growth factor receptor-2 positive (HER2+) (15/120), and 20.8% triple negative disease (25/120). In total, 46.7% of patients responded to NAC (56/125) and 26.7% achieved a pathological complete response (pCR) (32/120). For patients with L/HER2, increased Let-7a predicted response to NAC ( P =0.049), while decreased miR-145 predicted response to NAC in HER2+ ( P =0.033). For patients with luminal breast cancers, reduced Let-7a predicted achieving a pCR ( P =0.037) and reduced miR-145 predicted achieving a pCR to NAC in HER2+ ( P =0.027). CONCLUSIONS: This study illustrates the potential value of circulatory miRNA measurement in predicting response to NAC. Further interrogation of these findings may see miRNAs personalize therapeutic decision-making for patients undergoing NAC for early breast cancer.

The Use of Clinical Parameters as Adjuncts to Endoscopic Evaluation of Mural Thickening on Conventional Computed Tomography in Diagnosing Malignancy.

BACKGROUND: Mural thickening (MT) on computed tomography (CT) poses a diagnostic dilemma in the absence of clear reporting guidelines. The aim of this study was to analyse CT reports, identifying patients in whom gastrointestinal wall MT was observed, and to correlate these reports with subsequent endoscopic evaluation. METHODS: Patients with MT who had follow-up endoscopy were included in the study (n = 308). The cohort was subdivided into upper gastrointestinal mural thickening (UGIMT) & lower gastrointestinal mural thickening (LGIMT). RESULTS: In total, 55.71% (n = 122) of colonoscopies and 61.8% (n = 55) of gastroscopies were found to be normal. Haemoglobin (HB) level in combination with MT was a predictor of neoplasia in both arms (p = 0.04 UGIMT cohort, p < 0.001 LGIMT cohort). In addition to this, age was a significant correlative parameter in both UGIMT and LGIMT cohorts (p = 0.003, p < 0.001 respectively). Dysphagia and weight loss were associated with UGI malignancies (38 and 63% respectively) and rectal bleeding was correlative in 20% of patients with LGI malignancies. CONCLUSION: HB, advancing age, and red flag symptoms are potentially useful adjuncts to MT in predicting upper and lower gastrointestinal malignancies. We propose the adoption of a streamlined pathway to delineate patients who should undergo endoscopic investigation following CT identification of MT.

Impact of targeted trainer feedback via video review on trainee performance of laparoscopic cholecystectomy.

INTRODUCTION: Tools for improving operative performance for surgical trainees are increasingly desirable, particularly in the context of EWTD and 'run-through' training programmes. In addition, positive direct trainer feedback to trainees can improve skill acquisition and motivation, whilst negative feedback may have the opposite effect.1 We aimed to examine the impact of targeted trainer feedback based on video analysis on trainee confidence and objective operative performance in laparoscopic cholecystectomy. METHODS: Selected procedures designated as training cases were recorded. These were assessed by the trainers using the Independence-Scaled Procedural Assessment Score for laparoscopic cholecystectomy. Targeted feedback based on video review of selected procedures was then delivered by the trainers to the trainees. Trainees completed a self-reported questionnaire based on their response to this feedback. Subsequent to the feedback intervention, further training procedures were recorded and assessed. RESULTS: A total of 6 trainees and 4 trainers participated in the study. For the pre-intervention assessment 15 cases were recorded, with a further 13 for the post-intervention assessment (total n = 28). The overall scores for the procedures performed post video feedback were improved, with a trend towards statistical significance (p = 0.08). However, there was a statistically significant improvement in the scores for performance of the triangle of Calot dissection after the feedback intervention (p = 0.009). The response rate to the questionnaire was 100%, with all trainees agreeing that they felt more confident and competent after the feedback intervention. CONCLUSION: Targeted feedback to trainees based on post-procedure video review improves trainee confidence and may also improve performance. ACGME Core Competencies; Patient Care and Procedural Skills; Practice Based Learning and Improvement.

The prognostic value of neutrophil-to-lymphocyte ratio in colorectal cancer: A systematic review.

BACKGROUND AND OBJECTIVES: The detection of a simple and reliable prognostic biomarker for colorectal cancer (CRC) outcomes remains a significant challenge. The use of neutrophil-to-lymphocyte ratio (NLR), has been reported to predict surgical and survival outcomes. The aim of our review was to assess the predictive value of pre-operative NLR in predicting post-operative outcomes in CRC. METHODS: A systematic review of the available studies on NLR in CRC was performed. Primarily, we assessed its ability to predict survival outcomes, and highlight values that would help adjuvant therapy choices. RESULTS: 19 studies comprising 10 259 patients were included. Eleven and eight studies reported on patients with localized CRC and colorectal liver metastasis, respectively. Five-year survival for those with localized CRC was 77.2% in patients with a "low" pre-operative NLR versus 50.8% in those with a "high" pre-operative NLR value. Alternatively, for patients with colorectal liver metastasis, patients with a "high" pre-operative NLR value had a 5-year survival of 27%. CONCLUSION: Elevated pre-operative NLR>5 is associated with poorer long-term survival in both patients with localized CRC and those with liver metastasis. NLR is a useful biomarker in delineating those patients with poorer prognosis and whom may benefit from adjuvant therapies.

The Utility of Neutrophil to Lymphocyte Ratio as a Predictor of Intervention in Acute Diverticulitis.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) is a novel biomarker that has been recently studied in diverticulitis. The primary aim of this study was to assess the accuracy of NLR in predicting which patients had complicated diverticulitis and which patients required a radiological or surgical intervention. The accuracy of NLR was compared to C-reactive protein (CRP), white blood cell (WBC) count, neutrophil count and white cell to lymphocyte ratio (WLR). METHODS: Details of all patients admitted with acute diverticulitis over an 18-month period were collected prospectively. Median CRP, WBC, neutrophil count, WLR and NLR values at initial presentation were compared using the Mann-Whitney U test. The diagnostic accuracy of each test was assessed using receiver operating characteristic curve analysis. Optimal cut-off points were determined for each biomarker using Youden's Index (J). RESULTS: CRP, WBC, neutrophil count, WLR and NLR had variable accuracy in predicting complicated diverticulitis. NLR had the greatest accuracy of the 5 biomarkers in predicting the need for intervention with an area under the curve of 0.79 (p < 0.0001). The optimal cut-off point for NLR was 5.34 (J = 0.45). CONCLUSION: NLR was more accurate than CRP, WBC, neutrophil count and WLR in predicting the need for intervention. This cost-neutral, readily available biomarker can easily be calculated from the complete blood count and is a useful adjunct to CT.

A National Evaluation of the Conservative Management of Uncomplicated Acute Appendicitis: How Common Is This and What Are the Issues.

INTRODUCTION: The management approach for acute appendicitis has been challenged in recent years, with numerous randomized controlled trials demonstrating that antibiotics/conservative management is an efficacious treatment, with lower complication rates. METHODS: A national survey of all consultant general surgeons evaluating their practices was performed. Reasons for changed practices, choice of antibiotics and follow-up investigations were evaluated. In addition, the role of interval appendicectomy and conservative management in the pediatric population was also assessed. RESULTS: The response rate for this survey was 74.7% (n = 74/99). Over one-fifth (n = 17, 22.9%) routinely treat acute appendicitis conservatively, while another 14.8% (n = 11) consider this approach in selected cases. Main reasons for modified practices included the presence of inflammatory phlegmon (75%), delayed presentation (64%), and recent evidence-based medicine developments (46%). Co-amoxiclav/clavulanic acid was the most popular antibiotic for conservative management (53%). Alternatively, combinations of antibiotics were also utilized. One-third felt interval appendicectomy was warranted, while one-fifth supported conservative management in the paediatric setting. The overwhelming majority (>95%) advocate follow-up colonoscopy ± computed tomography in any patient aged >40 years managed conservatively. CONCLUSION: Considerable variation in management of uncomplicated appendicitis remains in Ireland despite growing evidence suggesting that the non-operative approach is safe. Reasons for adopting a conservative management practice have been identified and reflect the expanding literature on this subject.

The Utility of Neutrophil-to-Lymphocyte Ratio as a Severity Predictor of Acute Appendicitis, Length of Hospital Stay and Postoperative Complication Rates.

BACKGROUND: Numerous screening tools have been reported to aid in diagnosing appendicitis, but have poor severity prediction and lack accurate estimation of postoperative complications or total length of hospital stay (LOS). AIM: This study aims at evaluating the utility of neutrophil-to-lymphocyte (NLR) ratio in predicting the severity of appendicitis, LOS and 30-day complication rates. METHODS: Patients who underwent appendicectomy over a 4-year period were evaluated. Demographics, blood results, severity of appendicitis, LOS and 30-day complications were recorded. Recommended cut-off values of NLR and C-reactive protein (CRP) for severity of appendicitis were determined using receiver operating characteristic analysis. The Mann-Whitney test was performed to assess the correlations between LOS and 30-day complications with NLR. RESULTS: A total of 663 patients were included in the study of which 57.3% (n = 380) were male with mean patient age of 23.6 years, and 461 appendix specimens (69.6%) had simple inflammation on histological evaluation. A NLR of >6.35 or CRP of >55.6 were statistically associated with severe acute appendicitis, with a median of one extra hospital day admission (p < 0.0001). Mean NLR was statistically higher in patients with postoperative co(13.69 for severe vs. 7.29 for simple appendicitis group, p = 0.016). CONCLUSION: We advocate that NLR is a useful adjunct in predicting severity of appendicitis. It aids in delineating severe inflammation requiring surgery without substantial delay.

Association of clinical biomarkers and response to neoadjuvant therapy in breast cancer.

INTRODUCTION: Neoadjuvant therapy is an essential component of multimodality therapy for locally advanced breast adenocarcinoma (BC). Complete pathologic response (pCR) is a useful surrogate for long-term oncologic outcome. AIM: To assess the association between clinicopathologic, molecular and immunological markers and treatment response to neoadjuvant therapy in BC. METHODS: BC patients undergoing neoadjuvant therapy were identified from a prospectively maintained institutional database. Serum haematological/biochemical values, histopathologic, immunohistochemical data and TNM stage were obtained from electronic records. Patients were categorised into complete responders vs non-complete responders and responders vs non-responders. Statistical analysis was performed via SPSS. RESULTS: Overall, 299 BC patients were included. The average age was 49.8 ± 11.5 years. A pCR was evident in 22.6% (n = 69). pCR was associated with early T stage and non-luminal subtypes (HER2 enriched [HER2 +] and triple negative [TNBC]). The neutrophil-lymphocyte ratio (NLR) pre-operatively was lower in patients with a pCR (p = 0.02). The lymphocyte-CRP ratio (LCR) was also slightly reduced in responders (p = 0.049) at diagnosis. A pre-op NLR greater than 2 was not found to be a significant predictive factor (p = 0.071) on multivariable logistic regression analysis. T stage at diagnosis (p = 0.024), N stage (p = 0.001) and breast cancer subtype (p = 0.0001) were also determined to be significant predictive factors of complete response. CONCLUSION: pCR was more likely in patients with less advanced disease in BC. The presence of HER2 + or TNBC in BC also increases the likelihood of pCR. Neoadjuvant therapy stimulates the systemic inflammatory response; however, a reduced baseline NLR may be associated with increased pCR. Confirmation with larger datasets is required.

Assessing awareness of colorectal cancer symptoms and screening in a peripheral colorectal surgical unit: a survey based study.

BACKGROUND: The National Screening Program for colorectal cancer is scheduled to commence in the near future. Previous studies on the topic of colorectal cancer and screening have highlighted paucity in public awareness of epidemiology, symptoms and signs of colorectal cancer. The aim of this study was to assess understanding of colorectal cancer and screening in a representative sample of the local catchment population of Mayo General Hospital. METHODS: A prospective cohort study was instituted utilising an anonymous survey, which was distributed at consecutive general surgical out-patient clinics over a one month period prior to initiation of the screening program. Data collected included demographics, presenting complaint type and duration, and general knowledge of colorectal cancer facts. Attitudes towards screening were also evaluated. RESULTS: Eighty-eight of the one hundred and thirty six patients sampled were female (65%). Thirty-six per cent of the sample was within the screening target age-group (55-74), with mean age 53 years (+/-18). Most respondents recognised bleeding per rectum as a possible symptom of colorectal cancer. A significant proportion, however, incorrectly selected less sinister symptoms as concerning, while only fifty per cent correctly cited weight loss. Family history was acknowledged as a risk factor by fifty-seven per cent with age and gender cited less often (29%, 4%), while forty-seven per cent incorrectly cited stress as a risk. Screening was defined as testing of symptomatic patients or those with a positive family history by eighty-one per cent of respondents, with only nineteen per cent associating screening with an asymptomatic cohort. Strikingly, twenty-five per cent of patients would decline screening. CONCLUSIONS: There remains poverty of awareness regarding colorectal cancer. More public health initiatives are required to help improve understanding of the disease process, and to improve public compliance with the screening initiative.

Evaluating the Role of Circulating MicroRNAs in Predicting Long-Term Survival Outcomes in Breast Cancer: A Prospective, Multicenter Clinical Trial.

BACKGROUND: While long-term outcomes have improved for patients with breast cancer, 20% to 30% will still develop recurrence, and identifying these patients remains a challenge. MicroRNAs (miRNAs) are small, noncoding molecules that modulate genetic expression and affect oncogenesis. STUDY DESIGN: This prospective, multicenter trial (ICORG10/11-NCT01722851) recruited patients undergoing neoadjuvant chemotherapy across 8 Irish centers. Predetermined miRNAs were quantified from patient whole blood using quantitative reverse transcriptase polymerase chain reaction. Venous sampling was performed at diagnosis (timepoint 1) and midway during neoadjuvant chemotherapy (timepoint 2 [T2]). miRNA expression profiles were correlated with recurrence-free survival (RFS), disease-free survival (DFS), and overall survival. Data analysis was performed using R v3.2.3. RESULTS: A total of 124 patients were recruited with a median age of 55.0 years. The median follow-up was 103.1 months. Increased miR-145 expression at T2 was associated with improved RFS (hazard ratio 0.00; 95% confidence interval [CI] 0.00 to 0.99; p = 0.050). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved RFS (p = 0.041). Increased miR-145 expression at T2 trended towards significance in predicting improved DFS (hazard ratio 0.00; 95% CI 0.00 to 1.42; p = 0.067). Using survival regression tree analysis, a relative cutoff of increased miR-145 expression greater than 0.222 was associated with improved DFS (p = 0.012). No miRNAs correlated with overall survival. CONCLUSIONS: ICORG10/11 is the first Irish multicenter, translational research trial evaluating circulatory miRNAs as biomarkers predictive of long-term survival and correlated increased miR-145 expression with enhanced outcomes in early-stage breast cancer. Validation of these findings is required in the next generation of translational research trials.

Negative appendicectomy rates as a quality measure in a regional surgical unit: a retrospective review.

INTRODUCTION: Historically, high negative appendicectomy rates (NAR) were acceptable to offset the risks of perforation, previously exceeding 20%. With improved imaging and clinical scoring algorithms, there is growing demand for lower negative appendicectomy rates. The objectives were to (1) establish the NAR in our institution and (2) correlate clinical parameters and imaging modalities with histological findings. METHODS: Patients undergoing an appendicectomy between January 2012 and June 2018 were identified using a prospectively maintained pathology database. Histology findings were cross referenced against our radiology system, and anonymised data was collected for gender, age, WCC, Neutrophil and CRP level. RESULTS: One thousand one hundred fifty-three patients met the inclusion criteria. Fifty-three percent were males (n = 610), with 81% (n = 933) of histology reports classified as appendicitis. Sixty patients had a histologically normal appendix equating to a 5.2% NAR. If lymphoid hyperplasia, fibrosis and atrophy are included, it equates to a NAR of 14.57%. (p < 0.0001). Sixty-six percent of patients had no pre-operative imaging. CT imaging demonstrated a higher sensitivity (93.33%) and positive predictive value (99.60%) compared to ultrasonography. WCC and CRP are statistically significant in predicting appendicitis (p < 0.0001). CONCLUSION: There is no consensus on defining a negative appendicectomy or for imaging modality utilisation. CT imaging is the most sensitive and should be used in cases of diagnostic uncertainty. A standardised algorithm regarding the workup of patients with RIF pain along with a consensus on the use of imaging will further reduce negative appendicectomy rates.

The DATA protocol: developing an educational tool to optimise note-writing in hospitals.

BACKGROUND: Good clinical record-keeping is central in ensuring patient safety and effective communication between healthcare professionals. Poor communication is the root cause of many adverse events in medicine. AIMS: To assess the standard of notation for surgical inpatients, to create and pilot an educational tool to improve the quality of documentation, and to assess the adequacy of intern training in this area. METHODS: Healthcare records were retrospectively assessed during the first audit cycle for inclusion of basic criteria as per the current guidelines from the Health Service Executive. The intervention comprised a teaching session and an educational tool which was designed utilising the mnemonic DATA (date and time, addressograph, team, author details). A second audit cycle was carried out prospectively. Irish interns were also surveyed to assess the level of training they had received with regard to clinical record-keeping. Comparative analyses of quantitative data were performed using chi-squared test for categorical variables. RESULTS: A total of 200 notes were analysed. Those written after the intervention were significantly more likely to contain patient details, time seen, author name, job title, bleep number, and medical council registration number. Of the 59 interns who responded to the survey, 78% had not received training on how to properly write a clinical note and many had simply copied the format of notes written by the previous team. Very few had been made aware of the national guidelines available for record-keeping. CONCLUSION: The use of the educational tool and a formal training session significantly improved the quality of notes written for surgical inpatients. Junior doctors do not feel adequately trained in this area. The authors recommend that formal training in record-keeping be included in all hospital induction programmes.

The adequacy of lymph node clearance in colon cancer surgery performed in a non-specialist centre; implications for practice.

BACKGROUND: Despite recent medical advances, surgery remains the mainstay treatment in colon cancer. It is well established that better patient outcomes are achieved when complex surgery including pancreatic, oesophageal and rectal surgeries are carried out in high-volume centres. However, it is unclear as to whether or not colon cancer patients receive the same benefit. Lymph node adequacy is a key performance indicator of successful oncological colonic resection which impacts on patient outcome. AIM: To assess the adequacy of lymph node clearance during colonic resection performed with curative intent in a non-specialist centre post introduction of the National Cancer Strategy. METHODS: Retrospective analysis was performed of a prospectively maintained database examining the lymph node clearance of all oncological resections for colon cancer over a 7-year period (Nov 2010-Dec 2017) at a satellite unit with links to a regional specialist centre. Primary outcome measured was the number of lymph nodes retrieved. Secondary outcomes included resection margins, 30-day complication rate and survival at 1 year. Statistical analysis was performed using SPSS Statistics for Windows, version 24.0 (IBM Corp, Armonk, N.Y., USA). RESULTS: One hundred sixty-seven patients were included. Mean age was 71.0 ± 11.6 years. Majority were male (n = 90, 53.6%). The majority of resections was right sided (n = 112.66.7%) with 78.6% of all resections being undertaken electively. All margins were free of tumour. The average lymph node count was 19.93 ± 8.63 (4.62) with only 17 (10.2%) of specimens containing < 12 nodes. The anastomotic leak rate was 3.3%. There was no association between surgeon or pathologist volume, nor emergent status and achieving oncological lymph node count (p = 0.14, 0.29, 0.97). 90.5% of patients were alive at 1 year. CONCLUSIONS: This study demonstrates that colonic cancer surgery can be safely performed in a non- specialist centre with technical outcomes comparable to nationally reported figures.

The Impact of Preoperative Breast Magnetic Resonance Imaging on Surgical Management in Symptomatic Patients With Invasive Lobular Carcinoma.

OBJECTIVE: Due to an insidious proliferative pattern, invasive lobular breast cancer (ILC) often fails to form a defined radiological or palpable lesion and accurate diagnosis remains challenging. This study aimed to determine the value of preoperative magnetic resonance imaging (MRI) for ILC and its impact on surgical outcomes. METHODS: Consecutive symptomatic patients diagnosed with ILC in a tertiary centre over a 9-year period were reviewed. The time from diagnosis until surgery, initial type of surgery/index operation (breast-conserving surgery [BCS]/mastectomy) and the rates of reoperation (re-excision/completion mastectomy) were recorded. Patients were grouped into those who received conventional imaging and preoperative MRI (MR+) and those who received conventional imaging alone (MR-). RESULTS: There were 218 cases of ILC, and 32.1% (n = 70) had preoperative MRI. Time from diagnosis to surgery was longer in the MR+ than the MR- group (32.5 vs 21.1 days, P < .001) even when adjusting for age and breast density. Initial BCS was performed on 71.4% (n = 50) of MR+ patients and 72.3% (n = 107) of the MR- group. While the rate of completion mastectomy following initial BCS was higher in the MR+ group (30.0%, n = 15 vs 14.0%, n = 15; χ2 = 5.63; P = .018), this association was not maintained in multivariable analysis. No difference was recorded in overall (initial and completion) mastectomy rate between the MR+ and MR- group (50.0%, n = 35 vs 37.8%, n = 56; χ2 = 2.89; P = .089). Margin re-excision following BCS was comparable between groups (8.0%, n =4, vs 9.3%, n = 10; χ2 = 0.076, P = .783) despite the selection bias for borderline conservable cases in the MR+ group. The rate of usage of MRI for ILC cases declined over the study period. CONCLUSION: While MRI was associated with minor delays in treatment and did not reduce overall rates of margin re-excision or completion mastectomy, it altered the choice of surgical procedure in almost a quarter of MR+ cases. The benefit of preoperative breast MRI appears to be confined to select (younger, dense breast, borderline conservable) cases in symptomatic ILC.

Prospective Assessment of Systemic MicroRNAs as Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer.

Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce tumour burden prior to surgical resection. However, only a subset of NACT treated patients will respond to treatment or achieve a pathologic complete response (pCR). This multicenter, prospective study (CTRIAL-IE (ICORG) 10-11 study) evaluated circulating microRNA as novel non-invasive prognostic biomarkers of NACT response in breast cancer. Selected circulating microRNAs (Let-7a, miR-21, miR-145, miR-155, miR-195) were quantified from patients undergoing standard of care NACT treatment (n = 114) from whole blood at collected at diagnosis, and the association with NACT response and clinicopathological features evaluated. NACT responders had significantly lower levels of miR-21 (p = 0.036) and miR-195 (p = 0.017), compared to non-responders. Evaluating all breast cancer cases miR-21 was found to be an independent predictor of response (OR 0.538, 95% CI 0.308-0.943, p < 0.05). Luminal cancer NACT responders were found to have significantly decreased levels of miR-145 (p = 0.033) and miR-21 (p = 0.048), compared to non-responders. This study demonstrates the prognostic ability of miR-21, miR-195 and miR-145 as circulating biomarkers stratifying breast cancer patients by NACT response, identifying patients that will derive the maximum benefit from chemotherapy.

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer.

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer.

Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

BACKGROUND: The development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer. METHODS: Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5. RESULTS: 114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators. CONCLUSION: HER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy.

Management of the acute scrotum in a district general hospital: 10-year experience.

The acutely painful scrotum is a common urologic emergency. The primary objective of management is to avoid testicular loss. This requires a high index of clinical suspicion and prompt surgical intervention. In our series conducted between January 1996 and December 2005, 119 patients (age range: 4-62 years) underwent emergency operative exploration for acute scrotal pain. The most common finding was torted cyst of Morgagni (63/119, 52.9%), followed by testicular torsion (41/119, 34.4%). The majority of testicular torsions occurred in the pubertal group (22/41, 53.6%). Only one patient in this group had an unsalvageable testis necessitating orchidectomy, a testicular loss rate in torsion of 2.4%. There were no postoperative wound infections or scrotal haematomas. Testicular salvage depends critically on early surgical intervention, so the delay incurred in diagnostic imaging may extend the period of ischaemia. Furthermore, all radiological investigations have a certain false-negative rate. We advocate immediate surgical exploration of the acute scrotum. We report a low orchidectomy rate (2.4%) in testicular torsion.