The Ethics of Cancer Screening Based on Race and Ethnicity

Racial and ethnic disparities in incidence and mortality are well documented for many types of cancer. As a result, there is understandable policy and clinical interest in race- and ethnicity-based clinical screening guidelines to address cancer health disparities. Despite the theoretical benefits, such proposals do not typically address associated ethical considerations. Using the examples of gastric cancer and esophageal adenocarcinoma, which have demonstrated disparities according to race and ethnicity, this article examines relevant ethical arguments in considering screening based on race and ethnicity. Race- and ethnicity-based clinical preventive care services have the potential to improve the balance of harms and benefits of screening. As a result, programs focused on high-risk racial or ethnic groups could offer a practical alternative to screening the general population, in which the screening yield may be too low to demonstrate sufficient effectiveness. However, designing screening according to socially based categorizations such as race or ethnicity is controversial and has the potential for intersectional stigma related to social identity or other structurally mediated environmental factors. Other ethical considerations include miscategorization, unintended negative effects on health disparities, disregard for underlying risk factors, and the psychological costs of being assigned higher risk. Given the ethical considerations, the practical application of race and ethnicity in cancer screening is most relevant in multicultural countries if and only if alternative proxies are not available. Even in those instances, policymakers and clinicians should carefully address the ethical considerations within the historical and cultural context of the intended population. Further research on alternative proxies, such as social determinants of health and culturally based characteristics, could provide more adequate factors for risk stratification.

The Annual Cost of Cancer Screening in the United States

Background: Cancer has substantial health, quality-of-life, and economic impacts. Screening may decrease cancer mortality and treatment costs, but the cost of screening in the United States is unknown. Objective: To estimate the annual cost of initial cancer screening (that is, screening without follow-up costs) in the United States in 2021. Design: Model using national health care survey and cost resources data. Setting: U.S. health care systems and institutions. Participants: People eligible for breast, cervical, colorectal, lung, and prostate cancer screening with available data. Measurements: The number of people screened and associated health care system costs by insurance status in 2021 dollars. Results: Total health care system costs for initial cancer screenings in the United States in 2021 were estimated at $43 billion. Approximately 88.3% of costs were attributable to private insurance; 8.5% to Medicare; and 3.2% to Medicaid, other government programs, and uninsured persons. Screening for colorectal cancer represented approximately 64% of the total cost; screening colonoscopy represented about 55% of the total. Facility costs (amounts paid to facilities where testing occurred) were major drivers of the total estimated costs of screening. Limitations: All data on receipt of cancer screening are based on self-report from national health care surveys. Estimates do not include costs of follow-up for positive or abnormal screening results. Variations in costs based on geography and provider or health care organization are not fully captured. Conclusion: The $43 billion estimated annual cost for initial cancer screening in the United States in 2021 is less than the reported annual cost of cancer treatment in the United States in the first 12 months after diagnosis. Identification of cancer screening costs and their drivers is critical to help inform policy and develop programmatic priorities, particularly for enhancing access to recommended cancer screening services. Primary Funding Source: None.

Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis: A Sham-Controlled, Randomized Trial: Annals of Internal Medicine: Vol 177, No 6

Background: No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis. Objective: To investigate the pain-relieving effect of pancreatic duct decompression in patients with chronic pancreatitis and intraductal stones. Design: 24-week, parallel-group, randomized controlled trial (ClinicalTrials.gov: NCT03966781) Setting: Asian Institute of Gastroenterology in India from February 2021 to July 2022. Participants: 106 patients with chronic pancreatitis. Intervention: Combined extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde pancreatography (ERP) compared with sham procedures. Measurements: The primary end point was pain relief on a 0- to 10-point visual analog scale (VAS) at 12 weeks. Secondary outcomes were assessed after 12 and 24 weeks and included 30% pain relief, opioid use, pain-free days, questionaries, and complications to interventions. Results: 52 patients in the ESWL/ERP group and 54 in the sham group were included. At 12 weeks, the ESWL/ERP group showed better pain relief compared with the sham group (mean difference in change, −0.7 [95% CI, −1.3 to 0] on the VAS; P = 0.039). The difference between groups was not sustained at the 24-week follow-up, and no differences were seen for 30% pain relief at 12- or 24-week follow-up. The number of pain-free days was increased (median difference, 16.2 days [CI, 3.9 to 28.5 days]), and the number of days using opioids was reduced (median difference, −5.4 days [CI, −9.9 to −0.9 days]) in the ESWL/ERP group compared with the sham group at 12-week follow-up. Safety outcomes were similar between groups. Limitation: Single-center study and limited duration of follow-up. Conclusion: In patients with chronic pancreatitis and intraductal stones, ESWL with ERP provided modest short-term pain relief. Primary Funding Source: Asian Institute of Gastroenterology and Aalborg University Hospital.

Reversal of Intestinal Failure With Teduglutide in PERCC1-Associated Enteropathy: A Case Report

Endoscopic Ultrasound-Guided Rendezvous Technique Versus Precut Sphincterotomy as Salvage Technique in Patients With Benign Biliary Disease and Difficult Biliary Cannulation: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 177, No 10

Background: The standard salvage technique used for difficult bile duct cannulation is precut sphincterotomy, whereas endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a relatively newer method. Prospective comparative data between these 2 techniques as salvage for biliary access in patients with benign biliary disease and difficult bile duct cannulation is lacking. Objective: To compare EUS-RV and precut sphincterotomy as salvage technique for difficult bile duct cannulation in benign biliary obstruction. Design: Participant-masked, parallel-group, superiority, randomized controlled trial. (Clinical Trials Registry of India: CTRI/2020/07/026613) Setting: Tertiary care academic institute from July 2020 to May 2021. Participants: All patients with benign biliary disease and difficult bile duct cannulation requiring salvage strategy. Intervention: Patients were randomly assigned by computer-generated randomized blocks sequence in 1:1 fashion to either EUS-RV or precut sphincterotomy. Patients with failure in EUS-RV were crossed over to precut sphincterotomy and vice versa. Measurements: The primary outcome measure was technical success. The other outcome measures included procedure time, radiation dose, and adverse events. Results: In total, 100 patients were randomly assigned to EUS-RV (n = 50) and precut sphincterotomy (n = 50). The technical success rate (92% vs. 90%; P = 1.00; relative risk, 1.02 [95% CI, 0.90 to 1.16]), median procedure time (10.1 vs. 9.75 minutes), and overall complication rate (12% vs. 10%; relative risk, 1.20 [CI, 0.39 to 3.68]) were similar between the 2 groups. Five patients (10%) in the EUS-RV group and 5 patients (10%) in the precut sphincterotomy group had developed post–endoscopic retrograde cholangiopancreatography pancreatitis. All failed cases in either salvage group could be successfully cannulated when crossed over to the other group. Limitation: Single center study done by experts. Conclusion: Endoscopic ultrasound-guided rendezvous technique and precut sphincterotomy have similar success rates as salvage techniques in the technically challenging cohort of difficult bile duct cannulation for benign biliary disease, with acceptable complications rates. Primary Funding Source: None.

Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists

Background: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. Objective: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. Design: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615) Setting: 6 centers across the United States. Participants: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. Intervention: Real-time use of CADx during routine colonoscopy. Measurements: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. Results: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. Limitation: Decision making based on CADx might differ outside a clinical trial. Conclusion: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. Primary Funding Source: Olympus America Corporation served as the clinical study sponsor.

Comparative Performance of Common Fecal Immunochemical Tests: A Cross-Sectional Study: Annals of Internal Medicine: Vol 177, No 10

Background: Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited. Objective: To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard. Design: Cross-sectional study. (ClinicalTrials.gov: NCT03264898) Setting: Three U.S. academic medical centers and affiliated endoscopy units. Participants: Patients aged 50 to 85 years undergoing screening or surveillance colonoscopy. Intervention: Participants completed 5 different FITs before their colonoscopy, including 4 qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, QuickVue iFOB) and 1 quantitative test (OC-Auto FIT, which was run at the manufacturer's threshold for positivity of >100 ng/mL). Measurements: The primary outcome was test performance (sensitivity and specificity) for each of the 5 FITs for advanced colorectal neoplasia (ACN), defined as advanced polyps or CRC. Positivity rates, positive and negative predictive values, and rates of unevaluable tests were compared. Multivariable models were used to identify factors affecting sensitivity. Results: A total of 3761 participants were enrolled, with a mean age of 62.1 years (SD, 7.8); 63.2% of participants were female, 5.7% were Black, 86.4% were White, and 28.7% were Hispanic. There were 320 participants with ACN (8.5%), including 9 with CRC (0.2%). The test positivity rate varied 4-fold (3.9% to 16.4%) across FITs. Rates of unevaluable FITs ranged from 0.2% to 2.5%. The sensitivity for ACN varied from 10.1% to 36.7%, and specificity varied from 85.5% to 96.6%. Differences in sensitivity between FITs were all statistically significantly different except between Hemosure iFOB and QuickVue iFOB, and specificity differences were all statistically significantly different from one another. In addition to FIT brand, distal location of ACN was also associated with higher FIT sensitivity. Limitation: The study did not assess the programmatic sensitivity of annual FIT. Conclusion: Although considered a single class, FITs have varying test performance for detecting ACN and should not be considered interchangeable. Primary Funding Source: National Institutes of Health.

Shifting Trends in the Indication of Glucagon-like Peptide-1 Receptor Agonist Prescriptions: A Nationwide Analysis

Endoscopic Submucosal Dissection Versus Endoscopic Mucosal Resection of Large Colon Polyps: Use Both for the Best Outcomes

Comparison of Hospital Mortality and Readmission Rates by Physician and Patient Sex

Background: Little is known as to whether the effects of physician sex on patients’ clinical outcomes vary by patient sex. Objective: To examine whether the association between physician sex and hospital outcomes varied between female and male patients hospitalized with medical conditions. Design: Retrospective observational study. Setting: Medicare claims data. Patients: 20% random sample of Medicare fee-for-service beneficiaries hospitalized with medical conditions during 2016 to 2019 and treated by hospitalists. Measurements: The primary outcomes were patients’ 30-day mortality and readmission rates, adjusted for patient and physician characteristics and hospital-level averages of exposures (effectively comparing physicians within the same hospital). Results: Of 458 108 female and 318 819 male patients, 142 465 (31.1%) and 97 500 (30.6%) were treated by female physicians, respectively. Both female and male patients had a lower patient mortality when treated by female physicians; however, the benefit of receiving care from female physicians was larger for female patients than for male patients (difference-in-differences, −0.16 percentage points [pp] [95% CI, −0.42 to 0.10 pp]). For female patients, the difference between female and male physicians was large and clinically meaningful (adjusted mortality rates, 8.15% vs. 8.38%; average marginal effect [AME], −0.24 pp [CI, −0.41 to −0.07 pp]). For male patients, an important difference between female and male physicians could be ruled out (10.15% vs. 10.23%; AME, −0.08 pp [CI, −0.29 to 0.14 pp]). The pattern was similar for patients’ readmission rates. Limitation: The findings may not be generalizable to younger populations. Conclusion: The findings indicate that patients have lower mortality and readmission rates when treated by female physicians, and the benefit of receiving treatments from female physicians is larger for female patients than for male patients. Primary Funding Source: Gregory Annenberg Weingarten, GRoW @ Annenberg.

De Novo Esophageal Small-Cell Neuroendocrine Carcinoma in a Patient With Achalasia: A Case Report | Annals of Internal Medicine: Clinical Cases

Esophageal neuroendocrine carcinoma (NEC) is rare and aggressive, representing 0.4% to 2% of esophageal cancers, with small-cell NEC comprising 95% of cases. Achalasia is known to increase the risk for esophageal malignancy, particularly squamous cell carcinoma. We describe an 81-year-old woman with longstanding achalasia who developed dysphagia. Endoscopy showed a fungating mass, and biopsy confirmed small-cell NEC. She was treated with platinum–etoposide chemotherapy, resulting in complete resolution. This case demonstrates remission with chemotherapy alone, challenging traditional surgical approaches. To our knowledge, this is the first reported case of esophageal small-cell NEC arising in conjunction with achalasia. Further research is warranted to establish optimal management strategies for such rare presentations.

Renal Cell Carcinoma Metastasis to Esophagus 45 Years After Nephrectomy: A Case Report | Annals of Internal Medicine: Clinical Cases

Renal cell carcinoma (RCC) is a common malignancy, often discovered incidentally with abdominal imaging modalities. Metastasis of RCC to the esophagus is extremely rare. In this case, a patient presented with melena and dysphagia and was found to have an isolated metastasis of RCC in the proximal esophagus on endoscopy. He was previously treated for RCC 45 years ago, making this case the longest relapse of RCC documented in the literature to the best of our knowledge.

Isolated Cutaneous Perianal Crohn Disease With Rare Perineal Involvement | Annals of Internal Medicine: Clinical Cases

We present a rare case of isolated perianal Crohn disease (iPCD) with perineal involvement in a 28-year-old woman who remained free of luminal gastrointestinal symptoms for more than 10 years. The diagnosis was significantly delayed due to clinical overlap with hidradenitis suppurativa and pilonidal disease. The patient had multiple unsuccessful treatments, including antibiotics, immunosuppressants, and biological agents. Complete remission was ultimately achieved with combination therapy using infliximab and azathioprine. This case underscores the importance of early recognition, accurate differentiation from mimicking conditions, and a multidisciplinary approach to managing iPCD.

Acute Severe Enteritis by HSV-1 Variant in a Young Patient Who is Immunocompetent | Annals of Internal Medicine: Clinical Cases

We present a unique case of a 26-year-old man who is immunocompetent with severe abdominal pain and diarrhea, diagnosed with acute severe enteritis caused by a herpes simplex virus type 1 (HSV-1) variant, with intestinal inflammatory changes observed through computed tomography imaging, necessitating an empirical antibiotic. Biopsies from the esophagus and terminal ileum confirmed the presence of HSV-1, with immunostaining highlighting viral inclusion bodies. Notably, the genomic characterization of the HSV-1 variant was elucidated through next-generation sequencing analysis of mucosal biopsy samples from the gastrointestinal tract. The findings contribute to understanding atypical presentations of HSV-1 infection in patients who are immunocompetent and the role of advanced molecular techniques in HSV tropism.

Sigmoid Volvulus | Annals of Internal Medicine: Clinical Cases

An 83-year-old woman who resided in a nursing home presented to the emergency department with abdominal pain and vomiting resulting in the diagnosis of sigmoid volvulus. She needed intermittent catheter reduction of the colonic air but no surgical intervention has been performed so far.

EBV Acalculous Cholecystitis Secondary to Cystic Duct Node Lymphadenitis With Positive EBER in Situ Hybridization | Annals of Internal Medicine: Clinical Cases

Primary Epstein-Barr virus (EBV) infections are commonly subclinical and seen in adolescents. Although infectious mononucleosis is the most common manifestation, EBV has diverse manifestations within the gastrointestinal system. We describe a rare case of a 27-year-old woman with acute EBV acalculous cholecystitis and hepatitis secondary to cystic duct node lymphadenitis causing compression. EBV-encoded RNA in situ hybridization stained positive within sinusoids of liver and cystic duct lymphoid tissue but negative in gallbladder tissue. Work-up for a cause of hepatitis was negative except for serology confirming primary EBV infection. She underwent laparoscopic cholecystectomy, with a resolution of symptoms.

α-Gal Syndrome: Busting Paradigms in Food Allergy | Annals of Internal Medicine: Clinical Cases

α-Gal syndrome, also known as red or mammalian meat allergy, results from immunoglobulin E–mediated hypersensitivity responses to the carbohydrate galactose-α-1,3-galactose (α-gal). Patients with α-gal syndrome experience immediate onset of allergic symptoms following the injection of pharmaceutical products containing α-gal. However, it typically takes 2 hours or more after dietary α-gal ingestion before patients with α-gal syndrome experience immunoglobulin E–mediated hypersensitivity responses. The case report by Heffes-Doon and colleagues highlights the lack of official guidelines on when and how to reintroduce mammalian meat products into the diet when there is clear laboratory evidence of declining α-gal immunoglobulin E levels.

Hyperlipasemia Due to Duodenal Obstruction Secondary to Gastrostomy Tube Migration | Annals of Internal Medicine: Clinical Cases

A nonverbal woman with cerebral palsy and a chronic gastrostomy tube presented with nonbilious vomiting of tube feeds and abdominal pain. Initial work-up showed elevated lipase; however, computed tomography imaging revealed duodenal obstruction from gastrostomy tube migration as the cause of her symptoms. This case represents alternative causes to hyperlipasemia, such as bowel obstruction.

Pouchitis After Immune Checkpoint Inhibitors | Annals of Internal Medicine: Clinical Cases

Immune checkpoint inhibitors (ICIs) are becoming increasingly used for various cancers, but their association with immune-related adverse events often leads to significant morbidity and mortality. Here we report 2 unusual cases of pouchitis after ICI therapy—treated with steroids and biologics. To our knowledge, this is the first example to be reported in literature. One patient achieved short-term remission, while the other achieved long-term remission without further flares.

Linagliptin-Induced Pancreatitis | Annals of Internal Medicine: Clinical Cases

Incretin-based medications are well-established agents used for glycemic control in patients with type 2 diabetes mellitus. Of these medications, glucagon-like peptide 1 agonists have a well-known association with pancreatitis. However, controversy still exists about a similar association with dipeptidyl peptidase 4 inhibitors. Linagliptin, in particular, has not been studied thoroughly. Therefore, to the best of our knowledge, we report linagliptin-induced pancreatitis, the fourth case reported in the medical literature, that resolved after stopping the medication and did not recur with the resumption of all of the other patient's medications.

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