Who should get a right colectomy in low-grade appendiceal adenocarcinomas? Association of lymphovascular invasion and nodal metastases.

BACKGROUND: There is variation in the probability of nodal metastases from low-grade appendiceal adenocarcinomas, and the role of right colectomy is unclear. We aimed to define the prevalence and utility of lymphovascular invasion in predicting the risk of nodal metastases to help stratify patients who may benefit from right hemicolectomy. METHODS: Patients with nonmetastatic low-grade appendiceal adenocarcinomas were identified from the National Cancer Database (2010-2017). The primary outcome was probability of nodal metastases. Logistic regression was used to identify independent predictors of nodal metastases. A 4-tier risk model-the COH Composite Score-was calculated by assigning 1 point each for a high-risk feature (lymphovascular invasion, T3/T4 T stage, or nonmucinous histology). Survival analysis was performed using the Kaplan-Meier method. Multivariate Cox regression analysis was used to identify independent predictors of survival. RESULTS: A total of 1,303 patients with nonmetastatic low-grade appendiceal adenocarcinomas (64.2% mucinous) were identified. Of the 1,133 patients with known lymphovascular invasion status, 78 (6.9%) were lymphovascular invasion positive. In multivariate analysis, lymphovascular invasion was independently associated with nodal metastases (odds ratio, 8.68; P < .001). Overall accuracy of lymphovascular invasion in predicting nodal metastases was 86%. The COH Composite Score stratified patients in 4 categories with increasing risk of nodal metastases and incrementally worse survival. For patients with the COH Composite Score of 0 (12%), the nodal metastasis rate was 3.1%, and a right hemicolectomy in this group did not improve survival. CONCLUSION: The presence of lymphovascular invasion is strongly predictive of nodal metastases. Lymphovascular invasion as part of the COH Composite Score may help guide the extent of surgery in low-grade appendiceal adenocarcinomas.

Barriers to Surgical Outcomes Research in Low- and Middle-Income Countries: A Scoping Review.

INTRODUCTION: Systematic collection and analysis of surgical outcomes data is a cornerstone of surgical quality improvement. Unfortunately, there remains a dearth of surgical outcomes data from low- and middle-income countries (LMICs). To improve surgical outcomes in LMICs, it is essential to have the ability to collect, analyze, and report risk-adjusted postoperative morbidity and mortality data. This study aimed to review the barriers and challenges to developing perioperative registries in LMIC settings. METHODS: We conducted a scoping review of all published literature on barriers to conducting surgical outcomes research in LMICs using PubMed, Embase, Scopus, and GoogleScholar. Keywords included 'surgery', 'outcomes research', 'registries', 'barriers', and synonymous Medical Subject Headings derivatives. Articles found were subsequently reference-mined. All relevant original research and reviews published between 2000 and 2021 were included. The performance of routine information system management framework was used to organize identified barriers into technical, organizational, or behavioral factors. RESULTS: Twelve articles were identified in our search. Ten articles focused specifically on the creation, success, and obstacles faced during the implementation of trauma registries. Technical factors reported by 50% of the articles included limited access to a digital platform for data entry, lack of standardization of forms, and complexity of said forms. 91.7% articles mentioned organizational factors, including the availability of resources, financial constraints, human resources, and lack of consistent electricity. Behavioral factors highlighted by 66.6% of the studies included lack of team commitment, job constraints, and clinical burden, which contributed to poor compliance and dwindling data collection over time. CONCLUSIONS: There is a paucity of published literature on barriers to developing and maintaining perioperative registries in LMICs. There is an immediate need to study and understand barriers and facilitators to the continuous collection of surgical outcomes in LMICs.

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.

Challenges and opportunities in the establishment of a hereditary breast cancer clinic at an academic medical center in a low-middle income country.

It is now standard of care to offer genetic testing to patients at risk of hereditary breast cancer and make management decisions based on these results. Although great strides have been made in ensuring access to genetic testing and genetic counseling by establishing hereditary breast cancer clinics in well-resourced countries, these are essentially non-existent in low-middle income countries like Pakistan. We established a hereditary breast cancer clinic involving a multidisciplinary team, including a medical geneticist and a genetic counselor. Our efforts were based on consensus guidelines and included educating medical providers about the importance of genetic testing in breast cancer care and the mandatory presence of a genetics team member at the weekly Breast Tumor Board meeting. This resulted in an increase in the number of referrals of breast cancer patients for genetic testing. In this report, we describe the challenges we faced in setting up such a system in Pakistan and the measures to overcome them. There is a need to establish such hereditary breast cancer clinics, which can also be replicated at other centers in low-resource settings, to improve standardized assessment and management of the patients with hereditary breast cancer according to consensus guidelines.