Management of Locally Advanced Rectal Cancer: ASCO Guideline.

PURPOSE: To provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer. METHODS: A systematic review of the literature published from 2013 to 2023 was conducted to identify relevant systematic reviews, phase II and III randomized controlled trials (RCTs), and observational studies where applicable. RESULTS: Twelve RCTs, two systematic reviews, and one nonrandomized study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RECOMMENDATIONS: Following assessment with magnetic resonance imaging, for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, total neoadjuvant therapy (TNT; ie chemoradiation [CRT] and chemotherapy) should be offered as initial treatment for patients with tumors located in the lower rectum and/or patients who are at higher risk for local and/or distant metastases. Patients without higher-risk factors may discuss chemotherapy with selective CRT depending on extent of response, TNT, or neoadjuvant long-course CRT or short-course radiation. For patients who are candidates for TNT, the preferred timing for chemotherapy is after radiation, and neoadjuvant long-course CRT is preferred over short-course radiation therapy (RT), however short-course RT may also be a viable treatment option depending on circumstances. Nonoperative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. For patients whose tumors are microsatellite instability-high or mismatch repair deficient, immunotherapy is recommended.Additional information is available at http://www.asco.org/gastrointestinal-cancer-guidelines.

Pelvic exenteration for locally advanced rectal cancer and associated outcomes in England between 1995 and 2016: Analysis of a national database.

AIM: The clinical burden of pelvic exenteration (PE) for locally advanced rectal cancer (LARC) is nationally under-reported. The widespread use of pelvic MRI since 2005 has increased the accuracy of local staging and awareness of the need for 'beyond TME (total mesorectal excision)' surgery. The aim of this study was to assess the volume of patients undergoing PE within England, which factors affected survival outcomes and whether the use of MRI has influenced these outcomes. METHOD: The volume of patients undergoing PE and associated survival outcomes across England between 1995 and 2016 was evaluated from Public Health England Hospital Episode Statistics data. RESULTS: A total of 2996 patients were recorded as undergoing PE. The 5-year overall survival rate improved after 2005 compared with prior to 2005 (61.7% vs. 37%, p < 0.001), with no significant difference between cancer registries throughout England. After 2005, the volume of patients undergoing PE and undergoing preoperative MRI increased, as did the number of non-T4 cancers operated on. After 2005, age, preoperative MRI and preoperative radiotherapy were the significant factors influencing 5-year overall survival on multivariate analysis. CONCLUSION: This review of national data confirms that PE outcomes are under-reported. MRI staging aids with the identification of patients suitable for perioperative treatment, surgery or palliation and facilitates treatment planning. Since 2005, MRI, likely in combination with advances in surgery and perioperative treatment, has improved survival outcomes. It is imperative that detailed information from patients with LARC undergoing PE is captured and reported in order to optimize care and future service provision.

Oncological outcomes of local excision versus radical surgery for early rectal cancer in the context of staging and surveillance: A systematic review and meta-analysis.

BACKGROUND: Local resection (LR) methods for rectal cancer are generally considered in the palliative setting or for patients deemed a high anaesthetic risk. This systematic review and meta-analysis aimed to compare oncological outcomes of LR and radical resection (RR) for early rectal cancer in the context of staging and surveillance assessment. METHODS: A literature search of MEDLINE, Embase and Emcare databases was performed for studies that reported data on clinical outcomes for both LR and RR for early rectal cancer from January 1995 to April 2023. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. The quality of assessment was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2.0 tool for randomised controlled trials. RESULTS: Twenty studies with 12,022 patients were included: 6,476 patients had LR and 5,546 patients underwent RR. RR led to an improvement in 5-year overall survival (OR 1.84; 95 % CI 1.54-2.20; p < 0.0001; I2 20 %) and local recurrence (OR 3.06; 95 % CI 2.02-4.64; p < 0.0001; I2 39 %) when compared to LR. However, when staging and surveillance methods were clearly adopted in LR cases, there was an improvement in R0 rates (96.7 % vs 85.6 %), 5-year disease-free survival (93.0 % vs 77.9 %) and overall survival (81.6 % vs 79.0 %) compared to when staging and surveillance was not reported/performed. CONCLUSIONS: LR may be appropriate for selected patients without poor prognostic factors in early rectal cancer. This study also highlights that there is currently no single standardised staging or surveillance approach being adopted in the management of early rectal cancer. A more specified and standardised preoperative staging for patient selection as well as clinical and image-based surveillance protocols is needed.

Racial and Ethnic Disparities in COVID-19 Treatments in the United States.

INTRODUCTION: Racial and ethnic disparities in patient outcomes following COVID-19 exist, in part, due to factors involving healthcare delivery. The aim of the study was to characterize disparities in the administration of evidence-based COVID-19 treatments among patients hospitalized for COVID-19. METHODS: Using a large, US hospital database, initiation of COVID-19 treatments was compared among patients hospitalized for COVID-19 between May 2020 and April 2022 according to patient race and ethnicity. Multivariate logistic regression models were used to examine the effect of race and ethnicity on the likelihood of receiving COVID-19 treatments, stratified by baseline supplemental oxygen requirement. RESULTS: The identified population comprised 317,918 White, 76,715 Black, 9297 Asian, and 50,821 patients of other or unknown race. There were 329,940 non-Hispanic, 74,199 Hispanic, and 50,622 patients of unknown ethnicity. White patients were more likely to receive COVID-19 treatments, and specifically corticosteroids, compared to Black, Asian, and other patients (COVID-19 treatment: 87% vs. 81% vs. 85% vs. 84%, corticosteroids: 85% vs. 79% vs. 82% vs. 82%). After covariate adjustment, White patients were significantly more likely to receive COVID-19 treatments than Black patients across all levels of supplemental oxygen requirement. No clear trend in COVID-19 treatments according to ethnicity (Hispanic vs. non-Hispanic) was observed. CONCLUSION: There were important racial disparities in inpatient COVID-19 treatment initiation, including the undertreatment of Black patients and overtreatment of White patients. Our new findings reveal the actual magnitude of this issue in routine clinical practice to clinicians, policymakers, and guideline developers. This is crucial to ensuring equitable and appropriate access to evidence-based therapies.

No Health Equity Without Diversity: Strengthening Nursing Programs in Historically Black Colleges and Universities.

In April 2022, Adtalem Global Education sponsored a virtual summit entitled Advancing Equity in Healthcare, in which several of the authors of this article and other prominent health-care professionals examined the need to diversify the health-care profession. Topics included educational justice and its impact on health care, the business case for transforming and advancing health equity, and addressing systemic inequities and improving health outcomes for historically marginalized persons. The summit inspired the authors to write this paper to advocate for authentic, sustainable partnerships led by Historically Black Colleges and Universities, as a means to diversify nursing leadership and to stem systemic and structural inequities in health care.

Radiological Biomarkers in MRI directed Rectal Cancer Radiotherapy Volume Delineation.

Our study evaluated whether an MRI reporting system highlighting areas of contiguous and discontinuous extramural venous invasion (EMVI) can improve the accuracy of gross tumour volume (GTV) delineation. Initially, 27 consecutive patients with locally advanced rectal cancer treated between 2012 and 2014 were evaluated. We used an MRI reporting proforma that documented the position of the primary tumour, lymph nodes and EMVI. The new GTVs delineated were compared with historical radiotherapy treatment volumes to identify the frequency of GTV geographical miss. We observed that the delineation of involved nodes and areas of EMVI was more likely to represent sources of uncertainty wherein nodal GTV geographical miss was evident in 5 out of 27 patients (19%). Complete EMVI GTV geographical miss occurred in two patients (7%). We re-evaluated our radiotherapy practice in a further 27 patients after the implementation of a modified MRI reporting system. An improvement was seen; nodal miss was observed in two patients (7%) and partial EMVI miss in one patient (4%), although these areas were encompassed in the planning target volume (PTV). Our study shows that extramural venous invasion and involved nodes need to be highlighted on MRI to improve the accuracy of rectal cancer GTV delineation.

Implications of the new MRI-based rectum definition according to the sigmoid take-off: multicentre cohort study.

BACKGROUND: The introduction of the sigmoid take-off definition might lead to a shift from rectal cancers to sigmoid cancers. The aim of this retrospective cohort study was to determine the clinical impact of the new definition. METHODS: In this multicentre retrospective cohort study, patients were included if they underwent an elective, curative total mesorectal excision for non-metastasized rectal cancer between January 2015 and December 2017, were registered in the Dutch Colorectal Audit as having a rectal cancer according to the previous definition, and if MRI was available. All selected rectal cancer cases were reassessed using the sigmoid take-off definition. The primary outcome was the number of patients reassessed with a sigmoid cancer. Secondary outcomes included differences between the newly defined rectal and sigmoid cancer patients in treatment, perioperative results, and 3-year oncological outcomes (overall and disease-free survivals, and local and systemic recurrences). RESULTS: Out of 1742 eligible patients, 1302 rectal cancer patients were included. Of these, 170 (13.1 per cent) were reclassified as having sigmoid cancer. Among these, 93 patients (54.7 per cent) would have been offered another adjuvant or neoadjuvant treatment according to the Dutch guideline. Patients with a sigmoid tumour after reassessment had a lower 30-day postoperative complication rate (33.5 versus 48.3 per cent, P < 0.001), lower reintervention rate (8.8 versus 17.4 per cent, P < 0.007), and a shorter length of stay (a median of 5 days (i.q.r. 4-7) versus a median of 6 days (i.q.r. 5-9), P < 0.001). Three-year oncological outcomes were comparable. CONCLUSION: Using the anatomical landmark of the sigmoid take-off, 13.1 per cent of the previously classified patients with rectal cancer had sigmoid cancer, and 54.7 per cent of these patients would have been treated differently with regard to neoadjuvant therapy or adjuvant therapy.

Inter-rater agreement between radiologists using the novel CT-TDV (T3c+; tumour deposits; EMVI) system in patients with potentially curable right colon cancer.

OBJECTIVES: The novel CT-TDV scoring system, identifying T3c + disease; the presence/absence of tumour deposits and EMVI has been shown to be superior in predicting prognosis when compared to the CT-TNM staging system in the evaluation of colon cancer. Reproducibility of this scoring system between specialist GI radiologists has not been assessed previously. The aim of this study was to assess the inter-rater agreement of gastrointestinal radiologists in assessing the novel pre-operative CT-TDV scoring of patients with potentially curable right-sided colon cancer. METHODS: Ninety-three right colon cancer pre-operative CT scans were graded as CT TDV "good" versus TDV "poor" by four radiologists. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC) between all four readers and individual readers against the central radiologist using Cohen's κ statistic. RESULTS: The ICC comparing those graded as TDV "good" versus TDV "poor" for all 93 cases was 0.61 (0.51-0.70) indicating moderate reliability. Individual κ scores across the 93 cases were 0.76, 0.59 and 0.59 (p < 0.001) indicating moderate to substantial agreement. CONCLUSION: The CT TDV scoring system is reproducible amongst trained gastrointestinal radiologists in the assessment of newly diagnosed right colon cancer. ADVANCES IN KNOWLEDGE: This further validates the clinical utility of the CT TDV scoring system as a prognostic tool to guide the management of patients with potentially curable right colon cancer.

Why we need to re-define long-term success for people living with HIV.

Over the past few decades, the life expectancy of people living with HIV has markedly improved due to the advances in HIV diagnosis, linkage to care, and treatment. However, with these advances, a new set of challenges has emerged that must be addressed to ensure the long-term well-being of people living with HIV. In this article, as part of a wider journal supplement, we explore the unmet needs and challenges across the HIV continuum of care and re-define what long-term success looks like to support the healthy ageing of all people affected by HIV.

Long-term success for people living with HIV: A framework to guide practice.

OBJECTIVES: In recent decades, the needs of people living with HIV have evolved as life expectancy has greatly improved. Now, a new definition of long-term success (LTS) is necessary to help address the multifaceted needs of all people living with HIV. METHODS: We conducted a two-phase research programme to delineate the range of experiences of people living with HIV. The insights garnered from these research phases were explored in a series of expert-led workshops, which led to the development and refinement of the LTS framework. RESULTS: The insights generated from the research phases identified a series of themes that form a part of LTS. These themes were subsequently incorporated into the LTS framework, which includes five outcome pillars: sustained undetectable viral load, minimal impact of treatment and clinical monitoring, optimized health-related quality of life, lifelong integration of healthcare, and freedom from stigma and discrimination. A series of supporting statements were also developed by the expert panel to help in the achievement of each of the LTS pillars. CONCLUSIONS: The LTS framework offers a comprehensive and person-centric approach that, if achieved, could help improve the long-term well-being of people living with HIV and support the LTS vision of 'every person living with HIV being able to live their best life'.

Adolescent and young adult research across the HIV prevention and care continua: an international programme analysis and targeted review.

INTRODUCTION: Human immunodeficiency virus (HIV) continues to rise in young people among low- and middle-income countries (LMIC). The US National Institutes of Health (NIH) supports the largest public investment in HIV research globally. Despite advancements in the last decade, adolescents and young adults (AYA) remain underrepresented in research to improve HIV prevention and care. We undertook a programme analysis of NIH grants and conducted a targeted review of linked publications on international AYA research across the HIV prevention and care continuum (HPCC) to inform new initiatives to address the needs of AYA in these settings. METHODS: NIH-funded grants from 2012 to 2017, pertaining to AYA in LMIC, and evaluating areas of HIV prevention, care and/or treatment were identified. A systematic review of publications limited to funded grants was performed in two waves: 2012-2017 and 2018-2021. The review included a landscape assessment and an evaluation of NIH-defined clinical trials, respectively. Data on outcomes across the HPCC were abstracted and analysed. RESULTS: Among grant applications, 14% were funded and linked to 103 publications for the analytic database, 76 and 27 from the first and second waves, respectively. Fifteen (15%) wave 1 and 27 (26%) wave 2 publications included an NIH-defined clinical trial. Among these, 36 (86%) did not target a key population (men who have sex with men, drug users and sex workers) and 37 (88%) were exclusively focused on sub-Saharan Africa. Thirty (71%) publications addressed at least one HPCC milestone. Specific focus was on milestones in HIV prevention, care or both, for 12 (29%), 13 (31%) and five (12%) of publications, respectively. However, few addressed access to and retention in HIV care (4 [14%]) and none included microbicides or treatment as prevention. More focus is needed in crucial early steps of the HIV care continuum and on biomedical HIV prevention interventions. DISCUSSION AND CONCLUSIONS: Research gaps remain in this portfolio across the AYA HPCC. To address these, NIH launched an initiative entitled Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC3 H) to generate needed scientific innovation for effective public health interventions for AYA affected by HIV in LMIC.

Promoting health equity with HBCUs: Breaking away from structural racism.

BACKGROUND: The United States continues to be plagued with pervasive health disparities. Leading health and professional organizations acknowledge structural racism as a contributing factor for the lack of a racially diverse nursing workforce particularly those serving in leadership roles which could help to mitigate health disparities among historically stigmatized populations. PURPOSE: Purpose Lack of funding for Historically Black Colleges and Universities (HBCUs) and lack of meaningful partnerships, stymie efforts that can be made by nursing programs at HBCUs. DISCUSSION: Discussion This position paper examines collaborative actions that can address upstream factors that perpetuate healthcare disparities through deep engagement between the policymakers, professional associations, industry, and educational institutions. METHODS: Faculty representing HBCU's and predominately White institutions, professional organizations, and staff met via videoconference to refine the focus of the paper, determine topic areas for writing teams, and refine details which occurred during weekly meetings. CONCLUSION: To disengage from structural racism, three critical recommendations are amplified with associated examples.

Relationship Between Baseline Rectal Tumor Length and Magnetic Resonance Tumor Regression Grade Response to Chemoradiotherapy: A Subanalysis of the TRIGGER Feasibility Study.

BACKGROUND: It is widely believed that small rectal tumors are more likely to have a good response to neoadjuvant treatment, which may influence the selection of patients for a 'watch and wait' strategy. OBJECTIVE: The aim of this study was to investigate whether there is a relationship between baseline tumor length on magnetic resonance imaging (MRI) and response to chemoradiotherapy. METHOD: The 96 patients with locally advanced rectal cancer randomised (2:1-intervention:control) in the TRIGGER feasibility study where eligible. Baseline tumor length was defined as the maximal cranio-caudal length on baseline MRI (mm) and was recorded prospectively at study registration. Magnetic resonance tumor regression grade (mrTRG) assessment was performed on the post-chemoradiotherapy (CRT) MRI 4-6 weeks (no later than 10 weeks) post completion of CRT. This was routinely reported for patients in the intervention (mrTRG-directed management) arm and reported for the purposes of this study by the central radiologist in the control arm patients. Those with an mrTRG I/II response were defined as 'good responders' and those with an mrTRG III-V response were defined as 'poor responders'. RESULTS: Overall, 94 patients had a post-CRT MRI performed and were included. Forty-three (46%) patients had a good response (mrTRG I/II) and 51 (54%) patients had a poor response (mrTRG III/IV). The median tumor length of good responders was 43 mm versus 50 mm (p < 0.001), with considerable overlap in tumor lengths between groups. CONCLUSION: Baseline tumor length on MRI is not a clinically useful biomarker to predict mrTRG tumor response to CRT and therefore patient suitability for a deferral of surgery trial.

Beyond Total Mesorectal Excision: Compartment-based Anatomy of the Pelvis Revisited for Exenterative Pelvic Surgery.

OBJECTIVE: Magnetic resonance imaging-based subdivision of the pelvis into 7 compartments has been proposed for pelvic exenteration. The aim of the present anatomical study was to describe the topographic anatomy of these compartments and define relevant landmarks and surgical dissection planes. BACKGROUND: Pelvic anatomy as it relates to exenterative surgery is complex. Demonstration of the topographic peculiarities of the pelvis based on the operative situs is hindered by the inaccessibility of the small pelvis and the tumor bulk itself. MATERIALS AND METHODS: Thirteen formalin-fixed pelvic specimens were meticulously dissected according to predefined pelvic compartments. Pelvic exenteration was simulated and illustrated in a stepwise manner. Different access routes were used for optimal demonstration of the regions of interest. RESULTS: All the 7 compartments (peritoneal reflection, anterior above peritoneal reflection, anterior below peritoneal reflection, central, posterior, lateral, inferior) were investigated systematically. The topography of the pelvic fasciae and ligaments; vessels and nerves of the bladder, prostate, uterus, and vagina; the internal iliac artery and vein; the course of the ureter, somatic (obturator nerve, sacral plexus), and autonomic pelvic nerves (inferior hypogastric plexus); pelvic sidewall and floor, ischioanal fossa; and relevant structures for sacrectomy were demonstrated. CONCLUSIONS: A systematic approach to pelvic anatomy according to the 7 magnetic resonance imaging-defined compartments clearly revealed crucial anatomical landmarks and key structures facilitating pelvic exenterative surgery. Compartment-based pelvic anatomy proved to be a sound concept for beyond TME surgery and provides a basis for tailored resection procedures.

PAs in Myanmar: Courage and humanitarianism required.

ABSTRACT: Myanmar might be the most recent country to graduate its first class of physician assistants (PAs). The country has a history of medics serving in underserved areas, but graduated its first six PAs in 2020, after a 5-year training program. These clinicians will care for a largely rural population, who live in areas of unreliable infrastructure and security. The PA profession in Myanmar aims to reduce maternal mortality, graduate 75 PAs by 2029, and improve access to healthcare in remote regions.

Training of radiology specialists in local staging of primary rectal cancer on MRI: a prospective intervention study exploring the impact of various educational elements on the interpretive performance.

BACKGROUND: MRI interpretation and accurate radiological staging are crucial to the important treatment decisions and a consequent successful patient outcome in rectal cancer. AIMS: To investigate the effect of intensive training on rectal cancer MRI staging performance of radiologists and the impact of different course elements on learning outcomes. METHODS: In this prospective intervention study, 17 radiology specialists and 1 radiology registrar participated in a training programme including a 6-hour imaging workshop, a 3-hour session of individual feedback and independent MRI readings of primary rectal cancer cases. Their rectal MRI interpretive performance was evaluated through repeated readings of 30 training cases before and after each course element and a time interval with no educational intervention. A proforma template for MRI staging of primary rectal cancer was used and the results were compared with a reference standard of an expert panel. Participants repeatedly reported on confidence scores and self-assessed learning outcome. Outcomes were analysed using mixed-effects models. RESULTS: At baseline the quality of rectal MRI assessment varied significantly, with a higher interpretive performance among participants with shorter radiological experience (10.2 years vs 19.9 years, p=0.02). The ability to perform correct treatment allocation improved from 72% to 82% (adjusted OR=2.36, 95% CI 1.64 to 3.39). The improvement was largely driven by the participants with lower performance at baseline and by prevention of overstaging. Individual feedback had a significant impact on the improved interpretive performance (adjusted OR=1.82, 95% CI 1.27 to 2.63), whereas no significant change was seen after workshop or case readings only. Confidence scores increased significantly during training. CONCLUSIONS: Targeted and individualised training improves the rectal cancer MRI interpretive performance essential to successful patient treatment, especially among radiology specialists with lower performance at baseline.

The Diagnostic Accuracy of 18 F-FGD-PET/CT for Cancer of the Gallbladder: A Retrospective Study.

Background Gallbladder cancer has a poor prognosis and imaging can have variable diagnostic accuracy. We assessed the ability of preoperative 18 F-fluorodeoxyglucose positron emission tomography computed tomography ( 18 F-FDG-PET/CT) imaging to predict a postoperative histological diagnosis of gallbladder cancer. Method A retrospective analysis was undertaken in a cohort of patients, who had suspected gallbladder cancer on cross-sectional imaging and that underwent preoperative FDG-PET/CT scan. The discriminatory power of FDG-PET/CT was determined in receiver operator characteristic (ROC) analysis and diagnostic accuracy parameters were estimated at different thresholds of maximum standard unit value (SUV max ) . Results Twenty-two patients were included in the study; 7 had malignant and 15 benign diagnoses. There was no statistically significant difference between the measured SUV max between the two groups ( p = 0.71). With an area under the curve of 0.486, the ROC curve did not indicate any discriminatory power of FDG-PET/CT at any potential threshold of SUV max. Conclusion This study indicates that the diagnosis of primary gallbladder cancer cannot be accurately confirmed with FDG PET/CT scanning.