Citations

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

Total abdominal proctocolectomy with ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC) is associated with substantial complications despite the benefits of managing refractory and/or neoplasia-associated disease. For the purpose of this review, we focused on the diagnosis of some of the most common inflammatory and structural pouch disorders and their respective management. Pouchitis is the most common complication, and it is typically responsive to antibiotics. However, chronic antibiotic refractory pouchitis (CARP) has been increasingly recognized, and biologic therapies have emerged as the mainstay of therapy. Crohn's-like disease of the pouch (CLDP) can affect up to 10% of patients with UC after IPAA. Medical options are similar to CARP therapies, including biologics with immunomodulators. Studies have shown higher efficacy rates of biologics for CLDP when compared with those for CARP. In addition, managing stricturing and fistulizing CLDP is challenging and often requires interventional endoscopy (balloon dilation and/or stricturotomy) and/or surgery. The implementation of standardized diagnostic criteria for inflammatory pouch disorders will help in advancing future therapeutic options. Structural pouch disorders are commonly related to surgical complications after IPAA. We focused on the diagnosis and management of anastomotic leaks, strictures, and floppy pouch complex. Anastomotic leaks and anastomotic strictures occur in approximately 15% and 11% of patients with UC after IPAA, respectively. Further complications from pouch leaks include the development of sinuses, fistulas, and pouch sepsis requiring excision. Novel endoscopic interventions and less invasive surgical procedures have emerged as options for the management of these disorders.

Background: Hypertension prevalence increases in females following menopause. Poor endothelial microvascular function increases risk of hypertension. Endothelial-mediated vasodilation is dependent on nitric oxide (NO). Estrogen enhances NO production; therefore, reduced estrogen levels in postmenopausal females may result in a reduced contribution of NO to endothelial-mediated vasodilation, although studies are limited. Herein, we aimed to investigate the contribution of NO to endothelial-mediated vasodilation in premenopausal and postmenopausal females. We hypothesized that postmenopausal females would have attenuated endothelium-mediated vasodilation and reduced contribution of NO compared to premenopausal females. Methods: Ten premenopausal (27±3 yrs) and eleven postmenopausal (59±4 yrs) normotensive females were studied. Resting brachial blood pressures were measured using a standard arm cuff. Brachial arterial catheters were placed for continuous blood pressure measurement and pharmacologic infusions. Forearm blood flow (FBF) was measured using venous occlusion plethysmography at baseline (saline) and during infusion of an endothelium-dependent vasodilator (acetylcholine; 1.0, 2.0, 4.0, and 8.0 μg/100mL tissue/min) with and without a NO synthase inhibitor (L-NG-monomethylarginine [L-NMMA]; 1.0 mg/min) co-infusion. Forearm vascular conductance (FVC) was calculated as FBF/mean arterial pressure✕100. Data were analyzed using a two-way repeated-measures ANOVA. Results: Resting systolic blood pressure (SBP) but not diastolic blood pressure (DBP) was greater in postmenopausal compared to premenopausal females (SBP: 121±15 vs. 103±9 mmHg, respectively; P<0.01; DBP: 72±11 vs. 65±5 mmHg, respectively; P=0.07). FBF responses to acetylcholine did not differ between premenopausal and postmenopausal females (Group Main Effect: P=0.11). When correcting for blood pressure, premenopausal females exhibited greater FVC responses to acetylcholine compared to postmenopausal females (Group Main Effect: P=0.04). In premenopausal females, FBF and FVC responses to acetylcholine were reduced with co-infusion of L-NMMA compared to acetylcholine infusion only (L-NMMA Main Effect: P=0.02 and P=0.01, respectively). In postmenopausal females, the FBF and FVC responses to acetylcholine were unaffected by L-NMMA (L-NMMA Main Effect: P=0.79 and P=0.76, respectively). Conclusion: Compared to premenopausal females, postmenopausal females have impaired endothelial microvascular function. Attenuated NO contribution during endothelium-mediated vasodilation in postmenopausal women may partially contribute to the increased hypertension risk in this population. AHA 14PRE18040000, AHA 898649, NIH HL083947, NIH HL148144, NCATS UL1 TR000135 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. All patients experience some level of distress associated with a cancer diagnosis and the effects of the disease and its treatment regardless of the stage of disease. Clinically significant levels of distress occur in a subset of patients, and identification and treatment of distress are of utmost importance. The NCCN Distress Management Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights describe updates to the NCCN Distress Thermometer (DT) and Problem List, and to the treatment algorithms for patients with trauma- and stressor-related disorders.

Abstract Obesity is a chronic, relapsing, progressive disease of excess adiposity that increases the risk of developing at least 13 types of cancer. This report provides a concise review of the current state of the science regarding metabolic and bariatric surgery and obesity pharmacotherapy related to cancer risk. Meta-analyses of cohort studies report that metabolic and bariatric surgery is independently associated with a lower risk of incident cancer than nonsurgical obesity care. Less is known regarding the cancer-preventive effects of obesity pharmacotherapy. The recent approval and promising pipeline of obesity drugs will provide the opportunity to understand the potential for obesity therapy to emerge as an evidence-based cancer prevention strategy. There are myriad research opportunities to advance our understanding of how metabolic and bariatric surgery and obesity pharmacotherapy may be used for cancer prevention.

AbstractBackgroundQuestion prompt lists (QPLs) are structured sets of disease‐specific questions, intended to encourage question‐asking by patients and enhance patient‐physician communication. To date, a dysphagia‐specific QPL has not been developed for patients with esophageal dysphagia symptoms. We aim to develop a dysphagia‐specific QPL incorporating both esophageal expert and patient perspectives, applying rigorous methodology.MethodsThe QPL content was generated applying a two‐round modified Delphi (RAND/UCLA) method among 11 experts. In round one, experts provided five answers to the prompts: “What general questions should patients ask when being seen for dysphagia?” and “What questions do I not hear patients asking but, given my experience, I believe they should be asking?” In round two, experts rated proposed questions on a 5‐point Likert scale. Responses rated as “essential” or “important”, determined by an a priori median threshold of ≥4.0, were accepted for inclusion. Subsequently, 20 patients from Stanford Health Care were enrolled to modify the preliminary QPL, to incorporate their perspectives and opinions. Patients independently rated questions applying the same 5‐point Likert scale. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open‐endedly asking “Are there questions we didn't ask, that you think we should?”Key ResultsEleven experts participated in both voting rounds. Of 85 questions generated from round one, 60 (70.6%) were accepted for inclusion, meeting a median value of ≥4.0. Questions were combined to reduce redundancy, narrowing down to 44 questions. Questions were categorized into the following six themes: 1. “What is causing my dysphagia?”; 2. “Associated symptoms”; 3. “Testing for dysphagia”; 4. “Lifestyle modifications”; 5. “Treatment for dysphagia”; and 6. “Prognosis”. The largest number of questions covered “What is causing my dysphagia” (27.3%). Twenty patients participated and modified the QPL. Of the 44 questions experts agreed were important, only 30 questions (68.2%) were accepted for inclusion. Six patients proposed 10 additional questions and after incorporating the suggested questions, the final dysphagia‐specific QPL created by esophageal experts and modified by patients consisted of 40 questions.Conclusions & InferencesIncorporating expert and patient perspectives, we developed a dysphagia‐specific QPL to enhance patient‐physician communication. Our study highlights importance of incorporating patient perspective when developing such a communication tool. Further studies will measure the impact of this communication tool on patient engagement.

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.