Impact of Postoperative Antibiotic Prophylaxis on Surgical Site Infections Rates After Mastectomy with Drains but Without Immediate Reconstruction: A Multicenter, Double-Blinded, Randomized Control Superiority Trial.

BACKGROUND: There is no consensus on the use of postoperative antibiotic prophylaxis (PAP) after mastectomy with indwelling drains. We explored the utility of continued PAP in reducing surgical site infection (SSI) rates after mastectomy without immediate reconstruction and with indwelling drains. PATIENTS AND METHODS: A multicenter, two-armed, randomized control superiority trial was conducted in Pakistan. We enrolled all consenting adult patients undergoing mastectomy without immediate reconstruction. All patients received a single preoperative dose of cephalexin within 60 min of incision, and postoperatively were randomized to receive either continued PAP using cephalexin (intervention) or a placebo (control) for the duration of indwelling, closed-suction drains. The primary outcome was the development of SSI within 30 days and 90 days postoperatively. Secondary outcomes included study-drug-associated adverse events. Intention-to-treat analysis was performed using multivariable Cox regression. RESULTS: A total of 369 patients, 180 (48.8%) in the intervention group and 189 (51.2%) in the control group, were included in the final analysis. Overall cumulative SSI rates were 3.5% at 30 days and 4.6% at 90 days postoperatively. PAP was not associated with SSI reduction at 30 (hazard ratio, HR 1.666 [95% confidence interval CI 0.515-5.385]) or 90 (1.575 [0.558-4.448]) days postoperatively, or with study-drug-associated adverse effects (0.529 [0.196-1.428]). CONCLUSIONS: Continuing antibiotic prophylaxis for the duration of indwelling drains after mastectomy without immediate reconstruction offers no additional benefit in terms of SSI reduction. There is a need to update existing guidelines to provide clearer recommendations regarding use of postoperative antibiotic prophylaxis after mastectomy in the setting of indwelling drains.

Breast Cancer Management Consensus By The Society of Surgeons and Surgical Oncology Society of Pakistan.

The Society of Surgeons of Pakistan and The Society of Surgical Oncology of Pakistan with factions from various major centres comprising of surgical oncology, medical and radiation oncology collaborated to reach consensus on breast cancer management guidelines and a framework of "good practice" minimum standards of care. The aim of the task force was to enhance treatment standards, which have a direct correlation with improving patient mortality and morbidity and long-term survival whilst taking into consideration economic limitations of access to leading centers of excellence as well as minimum expertise required in health care. These multidisciplinary guidelines, whilst not exhaustive, aim to provide an algorithm of care for breast cancer patients at tertiary care centres and district level hospitals to provide most appropriate treatment.

Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

Trauma Evaluation and Management TEAM® course for medical students in Pakistan.

OBJECTIVES: To assess the immediate effect of TEAM® on trauma related knowledge of undergraduate medical students and to highlight the stakeholders' acceptability of TEAM® for trauma training of undergraduate medical students. METHODS: Effectiveness of TEAM® course in terms of knowledge gain was assessed using 20-item-MCQs at three different timings to three cohorts of medical students from year 2017 (Group A), 2018 (Group B) and 2019 (Group C). Group A attempted the test after traditional teaching in wards, Group B attempted it after reading books and videos of TEAM®, along with traditional trauma teaching. Finally Group C attempted the test after TEAM® course along with videos and books. Students and faculty also filled evaluation questionnaire for their acceptability assessment. Kruskal-Wallis Test was applied for comparison between scores of the three groups. The evaluation questionnaire of students as well as for faculty was evaluated by determining frequencies and percentages. RESULTS: A statistically significant difference is found after comparing the scores of the three groups (p< 0.00). More than 85% of the students were of a view that this course would help in their future practice and application. Similarly, 80% of the faculty would prefer to be involved in TEAM® teaching in future. CONCLUSION: There is an improvement in trauma cognitive knowledge, after the TEAM® program. Students and faculty strongly supported its introduction in the undergraduate curriculum and hence acceptable to both.

Age and stage of breast cancer in Pakistan: An experience at a tertiary care center.

OBJECTIVE: To determine the age and stage of breast cancer in a tertiary care center in Karachi, Pakistan. METHODS: This retrospective, descriptive study was conducted at Breast Unit, Department of Surgery, Liaquat National Hospital Karachi, Pakistan. From 1994 to 2016 all biopsy-proven breast cancer patients were reviewed and their age and stage at presentation were noted . RESULTS: In the given time period 10, 018 patients with Breast cancer were registered. The most frequent age at diagnosis was in the fourth decade of life (28.51%). The majority of patients were diagnosed in stage 2 (47.26%) and only less than 4% were detected in stage 1. The stage of presentation did not differ between young and older age group of women. CONCLUSIONS: Breast cancer is diagnosed at a younger age group in Pakistan, at least a decade earlier than the west and at an advanced stage, commonest being stage 2.

Is breast cancer awareness campaign effective in Pakistan?

OBJECTIVE: To assess the effectiveness of existing breast cancer awareness strategies in terms of early breast cancer detection.. METHODS: This descriptive, retrospective study was conducted at the Breast Surgery department of the Liaquat National Hospital, Karachi, and comprised records of all biopsy-proven stage 1 breast cancer patients from 1994 to 2014.All relevant records were retrieved year-wise from computerised database and age and stage of each case at presentation were noted. Data of stage 1 breast cancer patients was calculated in all age groups in absolute numbers and in percentage. The total number of women aged below 40 years and stage 1 patients in each year were counted and percentages were calculated and year-wise plotted and compared with whole group. RESULTS: A total of 8,291 patients were registered during the study period. Their number increased from 53(0.64%) in 1994 to 847(10.21%) in 2014. Over the study period, there was a slow trend towards improvement in early diagnosis of breast cancer. CONCLUSIONS: With existing breast cancer awareness strategies, the rate of change for early diagnosis of this deadly disease was very slow.

Discordance of biomarker status in recurrent breast cancer.

OBJECTIVE: To study the pattern of percentage change of biomarker status in recurrent breast cancer and to compare it with its primary biomarker. METHODS: Patients with recurrent breast disease presenting to the Breast Unit of Liaquat National Hospital and Medical College, Karachi, between January 2004 and January 2011 were included in this study. Outcome of interest was any change in the biomarker status of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2/neu) with respect to their respective primary status. SPSS 18 was used for statistical analysis. RESULTS: The study had a total of 58 female patients with biopsy-proven recurrent breast carcinoma with a mean age of 46 +/- 11.3 years. Time to recurrence varied between 2 to 3 years with a mean of 2.3 +/- 1.9 years. Invasive ductal carcinoma was the most prevalent recurrent tumour (50/58 patients: 86%). There was a change of 25.9% in oestrogen receptor status (p < 0.01); change of 36.2% in progesterone receptor status (p = 0.036); and 22.4% change in Her2/neu status (p = < 0.01). Of the 42 (72.27%) patients who were triple negative at presentation, 30 (71.4%) remained triple negative (p = 0.02). Six of the 16 (37.5%) patients became triple negative upon recurrence (p < 0.01). CONCLUSIONS: The study demonstrated that there was indeed a change in biomarker status in patients presenting with recurrent breast carcinoma. There is need for clinicians to check biomarker status in recurrent breast cancer patients as it may assist a shift in the management plan.

Clinicopathological Features and Survival Outcomes of Metaplastic Breast Carcinoma - An Observational Multi-Centric Study.

Purpose: To describe the clinicopathological features, and subtypes of metaplastic breast cancer (MpBC) in Pakistan and further to understand its response to treatment, including region-specific survival outcomes. Patients and Methods: This retrospective cohort study was conducted at two private tertiary care hospitals in Karachi, Pakistan. Our selection criteria included a total of 215 patients who were diagnosed with MpBC at an age older than 18 years from 1994 to 2021. Data regarding clinicopathological features, staging, receptor status, treatment modalities, recurrence, and survival was obtained. Death was scored as an event, and patients who were alive were censored at the time of the last follow-up. Results: The incidence of MpBC at our study centers is 3.21%. The median age of diagnosis was 50 years (range 22 to 80 years) and most patients presented at Stages II (45.1%) and III (44.2%). Among patients who received neoadjuvant chemotherapy, 31.7% achieved complete pathological response. The 3-year survival of those who received neoadjuvant chemotherapy was 96%. During our study, 19.1% of patients died and the median survival duration was 9 years 7 months 9 days. Survival of patients was significantly lower in patients who had metastasis (p-value = 0.042) and those who had tumor recurrence (p-value = 0.001). Conclusion: Metaplastic breast cancer is an extremely rare variant of breast cancer with features that exist as a spectrum. Our study demonstrated considerable success with the use of neoadjuvant chemotherapy. The pathological complete response achieved in our study is one of the highest ever reported. Our success, though limited, warrants further research in the use of neoadjuvant chemotherapy in MpBC.

Association of neutrophil-to-lymphocyte ratio with clinical, pathological, radiological, laboratory features and disease outcomes of invasive breast cancer patients: A retrospective observational cohort study.

Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy.

Using the 'Twelve tips for applying change models' for undergraduate medical curriculum reform in Pakistan: Incorporating a new Trauma Evaluation and Management TEAM® course.

Background: Trauma evaluation and management skills are not taught enough in medical school undergraduate curriculums worldwide. It has been recommended by trauma educators to incorporate trauma training in medical schools' curriculum as first-line management of trauma cases is usually required by junior doctors in ERs. The introduction of formal trauma training in the form of the Trauma Evaluation and Management TEAM® course is a change introduced into the curriculum. Even when introducing such a simple change, certain factors need to be considered including the stakeholders' apprehensions and involvement, the complexity of the internal and external environment, cultural context and political influences, and finally the psychological impact of change. Methods: Based primarily on the " Twelve tips for applying change models to curriculum design, development and delivery" by McKimm and Jones (2018), these 12 tips provide educators, involved in curriculum or program development, a practical example of the systematic and organized outlines to improve medical curricula. Results & Conclusions: While addressing these factors, this framework can guide educators for the successful development and implementation of a suggested change in the existing curriculum.

Utility of post mastectomy radiotherapy among patients with T1/ T2 N1 disease: A retrospective cohort study.

BACKGROUND: Pakistan has the highest incidence of breast cancer among Asian Countries but there is insufficient representation of local data addressing breast cancer treatment and outcome. We sought to determine the role of post-mastectomy radiotherapy (PMRT) in T1- T2 breast cancer with 1-3 positive axillary lymph nodes. METHODS: Data was reviewed retrospectively of total 755 patients out of which 291 received PMRT and 464 did not from two large breast cancer centres. RESULTS: With a median follow up of 78 months, 4 (4.5%) patients developed loco regional recurrence (LRR) in the PMRT group while a substantial number 74 (24.4%) recurred in the non PMRT group (p = 0.000). Loco regional free survival rate (LRFS) and overall survival rate (OS) was significantly better for PMRT patients than non-PMRT patients (P = <0.000). Multivariate analysis identified young age, lymphovascular invasion, extra capsular extension, triple negative and ER/PR negative were independent prognostic factors affecting loco regional free survival (LRFS). CONCLUSION: Disease recurrence is a substantial issue in 1-3 node group despite early stage, PMRT has an instrumental effect in improving LRFS and OS.

Impact of duration of antibiotic prophylaxis on rates of surgical site infection (SSI) in patients undergoing mastectomy without immediate reconstruction, comparing a single prophylactic dose versus continued antibiotic prophylaxis postoperatively: a multicentre, double-blinded randomised control trial protocol.

INTRODUCTION: In breast surgeries, prophylactic antibiotics given before the surgical incision as per Joint Commission Surgical Care Improvement Project guidelines have been shown to decrease the rate of postoperative infections. There is, however, no clear consensus on postoperative antibiotic prophylaxis in patients undergoing mastectomy with indwelling drains. This trial protocol proposes to study the difference in rates of surgical site infection (SSI) with or without continuation of postoperative antibiotics in patients undergoing mastectomy without immediate reconstruction and with indwelling drains. METHODS AND ANALYSIS: In this multicentre, double-blinded clinical trial, all patients undergoing mastectomy (without immediate reconstruction) will receive a single prophylactic dose of preoperative antibiotics at induction of anaesthesia and will then get randomised to either continue antibiotic prophylaxis or a placebo postoperatively, for the duration of indwelling drains. The primary and secondary outcomes will be development of an SSI and antibiotic-associated adverse effects, respectively. Data will be collected through a standard questionnaire by wound assessors. Intention-to-treat analysis will be carried out using STATA V.12. For categorical variables, frequencies and percentages will be assessed by χ2 test/Fisher's exact test as appropriate. The quantitative variables will be computed by their mean±SD or median (IQR) and will be assessed by independent t-test/Mann-Whitney test as appropriate. Unadjusted and adjusted relative risk with their 95% CI will be reported using Cox proportional regression. A p value of <0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: Ethical approval has been obtained from each site's Ethical Review Board. The study background and procedure will be explained to the study participants and informed consent will be obtained. Participation in the study is voluntary. All data will be deidentified and kept confidential. The study findings will be published in scientific media and authorship guidelines of International Committee of Medical Journal Editors will be followed. TRIAL REGISTRATION NUMBER: NCT04577846. (patient recruitment).

Coeliac artery aneurysm.

Aneurysms of coeliac artery are extremely rare and account for less than 4% of all splanchnic aneurysms. The detection of such aneurysms, which are often asymptomatic, is mostly occasional. Approximately 15% to 20% of the cases may get complicated by rupture with a mortality rate of around 80%. A reported case of a 55 year old male, who presented with pain and palpable mass in left upper abdomen was diagnosed to have coeliac artery aneurysm. Diagnosis was made on CT scan with selective visceral angiography. Simple ligation with partial excision of the coeliac artery aneurysm was performed.

Do Neural Information Extraction Algorithms Generalize Across Institutions?

PURPOSE: Natural language processing (NLP) techniques have been adopted to reduce the curation costs of electronic health records. However, studies have questioned whether such techniques can be applied to data from previously unseen institutions. We investigated the performance of a common neural NLP algorithm on data from both known and heldout (ie, institutions whose data were withheld from the training set and only used for testing) hospitals. We also explored how diversity in the training data affects the system's generalization ability. METHODS: We collected 24,881 breast pathology reports from seven hospitals and manually annotated them with nine key attributes that describe types of atypia and cancer. We trained a convolutional neural network (CNN) on annotations from either only one (CNN1), only two (CNN2), or only four (CNN4) hospitals. The trained systems were tested on data from five organizations, including both known and heldout ones. For every setting, we provide the accuracy scores as well as the learning curves that show how much data are necessary to achieve good performance and generalizability. RESULTS: The system achieved a cross-institutional accuracy of 93.87% when trained on reports from only one hospital (CNN1). Performance improved to 95.7% and 96%, respectively, when the system was trained on reports from two (CNN2) and four (CNN4) hospitals. The introduction of diversity during training did not lead to improvements on the known institutions, but it boosted performance on the heldout institutions. When tested on reports from heldout hospitals, CNN4 outperformed CNN1 and CNN2 by 2.13% and 0.3%, respectively. CONCLUSION: Real-world scenarios require that neural NLP approaches scale to data from previously unseen institutions. We show that a common neural NLP algorithm for information extraction can achieve this goal, especially when diverse data are used during training.

Location of appendix in pregnancy: does it change?

OBJECTIVES: This study aimed to determine the change in anatomical location of appendix in full-term pregnancy. STUDY DESIGN: This was a descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Liaquat National University Hospital, Karachi, Pakistan, Department of General Surgery, January 01 to July 31, 2010. PATIENTS AND METHODS: Full-term pregnant women undergoing caesarean section were enrolled. The anatomical position of the appendix was noted by visual inspection with reference to the transtubercular plane (TTP). SPSS-10 was used for analysis. RESULTS: Seventy-seven full-term pregnant female patients who underwent caesarean section were included in the study. Their mean age was 29 years, the mean height was 5.3 feet, and mean gestational age was 38 weeks. Appendix was found at the normal anatomical location in 63 out of 77 patients (81.8%), while it was located above the TTP in 14 patients (18.2%). CONCLUSION: Appendix does not migrate up with increasing gestational age in the majority of pregnant women. In most full-term pregnant female patients, appendix is located at the normal anatomical position.

"Is our choice of empirical antibiotics appropriate for patients with methicillin resistant Staphylococcus aureus in breast abscess?"

BACKGROUND AND OBJECTIVES: Breast abscesses remain as one of the most common reasons for females to come for a surgical consult. This retrospective cohort study includes both lactating and non-lactating females with breast abscesses. Due to changing trends in bacteriology of organisms, we need to reconsider our empirical choices of antibiotics. In our study, the main causative organism in breast abscess was Staphylococcus aureus with predominant species being MRSA. MATERIALS AND METHODS: This is an analytical review of all breast abscesses treated in a single center from 2012 to 2015. This study included bacterial cultures, antibiotic sensitivities and resistance pattern in breast abscesses. RESULTS: 268 patients were included in the study. 143 (53.4%) were Lactational abscesses and 125 (46.6%) were non-Lactational abscesses. 169 (63.0%) harbored S. aureus in which 86 (50.8%) were MRSA. MRSA was the predominant organism in the Lactational group while non-Lactational group had no growth or other organisms in culture in this study. Other growing organisms were Klebsiella pneumoniae, Bacteroides, Pseudomonas, Streptococcus species and Mycobacterium tuberculosis. On comparative analysis, MRSA showed statistically a significant difference with p<0.0001, when it comes to predominant growth in lactating mothers. First line prescribed empirical antibiotics received by the patient, which is amoxicillin clavulanate, is mostly resistant. It is recommended that the institutional antibiogram targeted treatment be offered to patients with breast abscess. We also recommend ciprofloxacin with clindamycin as initial empirical therapy. CONCLUSION: MRSA was the most common organism seen in breast abscesses. Our first line treatment of antibiotics was resistant. Clindamycin and ciprofloxacin should be the preferred 1st choice for treatment.