Citations

Background/Aims: Barrett’s esophagus (BE), defined by the presence of intestinal metaplasia (IM) on histology, is thought to be the only identifiable precursor lesion for esophageal adenocarcinoma (EAC). Recent studies have suggested the possibility of an alternate, non-IM associated EAC that is a more aggressive form of EAC with worse survival. Among EAC patients, we aimed to compare survival of patients with and without IM at the time of diagnosis. Methods: This was a retrospective cohort study of all patients with histologic confirmed EAC evaluated at a tertiary care center from 2013 to 2019. Cases were categorized according to the presence or absence of IM on histologic specimens (Group I—IM-EAC and Group II—non-IM-EAC). We compared demographic characteristics, clinical stage, therapy, and survival between the 2 groups using the Chi-square and ANOVA tests (for categorical and continuous variables, respectively). We used Cox proportional hazards regression to determine the association of IM with overall survival, adjusting for sex, age at diagnosis, tumor location, histologic grade, and clinical stage. Results: A total of 475 patients were included in this analysis (mean age 64.8 years [SD 10.8], 89% white) and 109 (23.0%) had no evidence of IM. Compared with IM-EAC (Group I), individuals in the non-IM-EAC group were younger ( P = .01) and had a greater proportion of patients diagnosed with advanced disease (49.5 vs 20.2% for stage 4, P < .001). These patients were less likely to undergo endoscopic therapy alone (0.92% vs 29.78%, P < .001) or surgery alone (0 vs 9.84%, P = .001). On multivariable analysis, the presence of IM-EAC was associated with improved overall survival compared to non-IM-EAC (HR 0.69, 95% CI 0.49-0.96). Additional factors associated with poor survival was increasing stage of diagnosis (HR 6.49: 95% CI 3.77-11.15 for stage 4, HR 2.19: 95% CI 1.25-3.84 for stage 3, HR 2.04: 95% CI 0.98-4.25 for stage 2 compared to stage 1) and more advanced histologic stage (HR 2.00, 95% CI 1.26-3.19) for poorly/undifferentiated compared to well differentiated). Conclusions: EAC without the presence of IM on histology was associated with worse survival compared to those with IM. Future prospective studies with detailed molecular sequencing are required to clarify if 2 separate phenotypes of EAC exist (IM-EAC and non-IM-EAC). If confirmed, this may have significant implications for screening and management strategies.

Purpose Medical schools must have clear policies and procedures for promotion and tenure (P&T) of faculty. Social media and digital scholarship (SMDS) is an emerging form of scholarship capable of reaching audiences quickly, conveniently, and in a wide variety of formats. It is unclear how frequently SMDS is considered during P&T reviews. The authors sought to determine whether current P&T guidelines at medical schools consider SMDS. Method The authors acquired P&T guidelines from any U.S. Liaison Committee on Medical Education–accredited medical school (or their governing university) that were available online between October and December 2020. Using an iterative process, they developed a bank of keywords that were specific to SMDS or that could include SMDS between October and December 2020. The authors searched each school’s guidelines for each keyword and determined whether the word was being used in relation to crediting faculty for SMDS in the context of P&T procedures. The primary outcome measure was the dichotomous presence or absence of SMDS-specific keywords in each school’s P&T guidelines. Results The authors acquired P&T guidelines from 145/154 (94%) medical schools. After removing duplicate documents, the authors considered 139 guidelines. The keyword bank included 59 terms, of which 49 were specific to SMDS and 10 were umbrella terms that could be inclusive of SMDS. Of the 139 guidelines, 121 (87%) contained at least 1 SMDS-specific keyword. Schools had a median of 3 SMDS-specific keywords in their P&T guidelines. Conclusions As the presence and impact of SMDS increase, schools should provide guidance on its role in the P&T process. Faculty should receive clear guidance on how to document quality SMDS for their promotion file.

With the incidence of breast cancer steadily rising, it is important to explore novel technologies that can allow for earlier detection of disease as well more a personalized and effective treatment approach. The concept of “liquid biopsies” and the data they provide have been increasingly studied in the recent decades. More specifically, circulating tumor DNA (ctDNA) has emerged as a potential biomarker for various cancers, including breast cancer. While methods such as mammography and tissue biopsies are the current standards for the detection and surveillance of breast cancer, ctDNA analysis has shown some promise. This review discusses the versatility of ctDNA by exploring its multiple emerging uses for the management of breast cancer. Its efficacy is also compared to current biomarkers and technologies.

Objectives To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation. Design Nationwide population-based cohort study 1990–2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum. Results We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002–2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males). Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa. Conclusions In Sweden, the incidence of CD increased until 2002–2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.

Abstract Background Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. Methods PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided. Results Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P &lt; .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P &lt; .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction &lt; .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P &lt; .001) but not for right-sidedness. Conclusions The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.

Background. The study aims is to use the fragility index (FI) to examine the strength of evidence of randomized controlled trials (RCTs) published in the last decade on kidney transplantation. Methods. We searched MEDLINE for studies on kidney transplantation. We included the RCTs that compared 2 groups with 1:1 randomization and reported significant P values (<0.05) for a dichotomous outcome and were published in the top 10 transplant journals. We calculated the FI; a calculation used to determine the minimum number of subjects needed to change from a nonevent to an event to make the study results nonsignificant (P ≥ 0.05). Results. Fifty-seven RCTs met our inclusion criteria. The median sample size was 100 participants in each arm, the median number of events was 16 (interquartile range, 8–30) in the intervention group. Among the included trials, 79% were industry-funded, 93% involved medications, and the majority were open label. The median FI was 3 (interquartile range, 1–11). In 43% of the trials, the number of patients reported lost to follow-up was higher than or equal to the FI. Only 4% of the RCTs imputed a value for the missing dichotomous outcome. Furthermore, the median number of subjects who discontinued the trial because of adverse effects was 21, which was greater than the FI in 60% of the RCTs. Conclusions. The arbitrary classification of results into “significant” and “nonsignificant” based on P value <0.05 should perhaps be interpreted with the help of other statistical parameters and FI is one of them.