Patient- and system-level factors associated with racial/ethnic disparities in the delivery of guideline-concordant therapy among US patients with gastric cancer.

BACKGROUND: Disparities in gastric cancer (GC) outcomes show a higher disease burden among minorities. We aimed to evaluate the associations between sociodemographic and system-level factors and guideline-concordant treatment among GC patients. METHODS: Cohort study with GC patients in the National Cancer Data Base (2006-2018) treated with upfront resection or neoadjuvant therapy (NAT). We used logistic regression to identify associations between deviations from guideline-concordant therapy and patient- and system-level factors, and Cox regression models to assess risk of death. RESULTS: The cohort included 43 597 GC patients treated with endoscopic resection (8.9%), surgery only (47.1%), surgery and adjuvant therapy (20.6%), or NAT followed by surgery (23.5%). A total of 31 470 patients (72.2%) received guideline-concordant therapy. Relative to Non-Hispanic Whites (NHWs), Non-Hispanic Blacks (NHBs) (odds ratio [OR] 1.19, [95% confidence intervals 1.10-1.28]) and Asian/Pacific Islanders (APIs) (OR 1.12 [1.03-1.23]) had an increased risk of deviations from treatment guidelines. Medicare/Medicaid increased the risk of deviations while treatment at high-volume facilities decreased its risk for all races/ethnicities. Deviations from guidelines were associated with an increased risk of death (hazard ratio 1.56 [1.50-1.63]. CONCLUSIONS: Racial disparities in the delivery of guideline-concordant therapy among GC patients are affected by several sociodemographic factors at the patient- and system-level.

Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US.

BACKGROUND: The objective of this study was to describe real-world adjuvant therapy (AT) use by disease substage and assess determinants of treatment choice among patients with stage III melanoma. METHODS: This non-interventional retrospective study included survey responses and data from patient records provided by US medical oncologists. Survey responses, patient demographic/clinical characteristics, treatment utilization, and reasons for treatment were reported descriptively. The association between patient and disease characteristics and AT selection was assessed using logistic and multinomial regression models, overall and stratified by AJCC8 substage (IIIA vs. IIIB/C/D) and type of AT received (anti-PD1 monotherapy, BRAF/MEK, no AT), respectively. RESULTS: In total 152 medical oncologists completed the survey and reviewed the charts of 507 patients (168 stage IIIA; 339 stages IIIB/IIIC/IIID); 405 (79.9%) patients received AT (360/405 (88.9%) received anti-PD1 therapy; 45/405 (11.1%) received BRAF/MEK therapy). Physicians reported clinical guidelines (61.2%), treatment efficacy (37.5%), and ECOG performance status (31.6%) as drivers of AT prescription. Patient-level data confirmed that improving patient outcomes (79%) was the main reason for anti-PD1 prescription; expected limited treatment benefit (37%), patient refusal (36%), and toxicity concerns (30%) were reasons for not prescribing AT. In multivariable analyses stage IIIB/IIIC/IIID disease significantly increased the probability of receiving AT (odds ratio [OR] 1.74) and anti-PD1 therapy (OR 1.82); ECOG 2/3 and Medicaid/no insurance decreased the probability of AT receipt (OR 0.37 and 0.42, respectively) and anti-PD1 therapy (OR 0.41 and 0.42, respectively) among all patients and patients with stage IIIA disease. CONCLUSION: Most patients were given AT with a vast majority treated with an anti-PD1 therapy. Physician- and patient-level evidence confirmed the impact of disease substage on AT use, with stage IIIA patients, patients without adequate insurance coverage, and worse ECOG status having a lower probability of receiving AT.

New Model to Predict Recurrence After Endoscopic Mucosal Resection of Non-pedunculated Colonic Polyps ≥ 20 mm.

BACKGROUND: Polyp recurrence is common after endoscopic mucosal resection (EMR) of non-pedunculated colonic polyps ≥ 20 mm. Two models haven been published for polyp recurrence prediction: Sydney EMR recurrence tool (SERT) and the size, morphology, colonic site, and access to target (SMSA) score. None of these models have been evaluated in a real-world United States (U.S.) cohort. We aimed to evaluate the external validity of these two models and develop a new model. METHODS: Retrospective cohort study of patients with non-pedunculated polyps ≥ 20 mm that underwent EMR between 1/1/2012 and 6/30/2020. Univariate and multivariate analysis were performed to identify predictors of polyp recurrence to build a new model. Receiver Operating Characteristic (ROC) curves for the new model, SERT and a modified version of SMSA were derived and compared. RESULTS: A total of 461 polyps from 461 unique patients were included for analysis. The average polyp size was 29.1 ± 12.4 mm. Recurrence rate at first or second surveillance colonoscopy was 29.0% at a 15.6 months median follow up (IQR 12.3-17.4). A model was created with 4 variables from index colonoscopy: size > 40 mm, tubulovillous adenoma histology, right colon location and piecemeal resection. ROC curves showed that the Area Under the ROC (AUC) for the new model was 0.618, for SERT 0.538 and for mSMSA 0.550. CONCLUSION: SERT score and mSMSA have poor external validity to predict polyp recurrence after EMR of non-pedunculated polyps > 20 mm. Our new model is simpler and performs better in this multiethnic, non-referral cohort from the U.S.

Chromatic polymorphism in Trichomycterus jacupiranga from eastern Brazilian Coastal basins (Siluriformes: Trichomycteridae).

Trichomycterinae catfishes often have high intraspecific variability in colour patterns that may be associated with ontogenetic changes or habitat preferences. In species of the eastern South American genus Trichomycterus s.s., some cases of chromatic polymorphism have been reported but colour pattern is still considered an important tool for species identification. Herein, we first describe chromatic polymorphism in the geographically widespread T. jacupiranga, comparing populations from Tijuca National Park and Ribeira do Iguape basin, identifying four syntopic colour morphs. In addition, we performed a phylogenetic analysis using partial sequences of the mitochondrial gene 12Ss gene for 16 individuals of T. jacupiranga, with a maximum of 0.2% of genetic distance, corroborating T. jacupiranga as a single widespread species. Finally, based on our results and field observations, we concluded that it is not possible at the present to associate chromatic polymorphism in T. jacupiranga with habitat preferences, since specimens with different colouration in variable ontogenetic stages were found at the same microhabitats.

Two new miniature translucent catfish species of the rare genus Tridens (Siluriformes: Trichomycteridae) from the Madeira River basin, northern Brazil.

Two new miniature species of the trichomycterid genus Tridens are described from the Madeira River drainage, Acre and Rondônia States, Brazil. Until this work, Tridens was a monotypic genus composed solely of Tridens melanops, from the Putumayo/Içá River drainage, upper Amazonas River basin. Tridens vitreus sp.n. is known from upper and middle Madeira River drainage and differs from all other congeners by the lack of pelvic fins and girdle and by vertebra and dorsal-fin ray counts. Tridens chicomendesi sp.n. is known from Abunã River, middle Madeira River drainage and is distinguished from all other congeners by the number of vertebrae, dorsal-fin ray count and anal-fin base colouration pattern. Tr. chicomendesi sp.n. is further distinguished from T. vitreus by a combination of character states regarding the position of urogenital opening, dorsal-fin position, anal-fin position, maxillary barbel length, number of premaxillary teeth, number of dorsal-fin rays, number of anal-fin rays, number of lateral-line system pores, frontal bone anatomy, degree of ossification of maxilla, anatomy of quadrate-hyomandibular joint, size of posterodorsal process of hyomandibula, length of opercular patch of odontodes, number of interopercular odontodes, proportion of upper hypural plate cartilage relative to its area ; by the absence of a proximal, distal and ventral cartilages on ventral hypohyal; by the absence of a lateral process on basibranchial 4; by the presence of a cartilage block on the lateral process of autopalatine, the presence of a well-developed ossification on proximal margin of ventral hypohyal, the presence of hypobranchial foramen; and by the presence of an anterior cartilaginous joint between quadrate and base of posterodorsal process of hyomandibula. This work represents the first species description for the subfamily Tridentinae in more than 30 years and for the genus Tridens since its original description in 1889.

Survival outcomes in veterans with hepatocellular carcinoma, with and without HIV infection.

BACKGROUND: HIV infection has been associated with survival disparities among persons with hepatocellular carcinoma (HCC). However, most studies examining survival do not control for provider (e.g. type of HCC treatment given) or individual-level factors (e.g. homelessness, substance use) that could impact survival. In this study, we evaluate the effect of HIV status on survival among persons with HCC, in a comprehensive model that accounts for key individual, provider, and systems-level factors. METHODS: We conducted a retrospective cohort study of persons with HIV (PWH) matched 1 : 1 to HIV-negative controls based on age and year of HCC diagnosis in the national Veterans Administration (VA) health system. The primary outcome was survival. We used Cox regression models to evaluate the effect of HIV status on risk of death. RESULTS: This cohort included 200 matched pairs diagnosed with HCC between 2009 and 2016. A total of 114 PWH (57.0%) and 115 HIV-negative patients (57.5%) received guideline-concordant therapy ( P  = 0.92). Median survival was 13.4 months [95% confidence interval (CI) 8.7-18.1] among PWH and 19.1 months (95% CI 14.6-24.9) for HIV-negative patients. In adjusted models, older age, homelessness, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and not receiving any HCC treatment predicted risk of death. HIV status was not associated with risk of death [adjusted hazard ratio (aHR) 0.95; 95% CI 0.75-1.20; P  = 0.65]. CONCLUSION: HIV status was not associated with worse survival among HCC patients, in a single-payer, equal access healthcare system. These results suggest that HIV infection alone should not exclude PWH from receiving standard therapy.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Evolution of endoscopic mucosal resection (EMR) technique and the reduced recurrence of large colonic polyps from 2012 to 2020.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective method for removing non-pedunculated polyps ≥ 20 mm. We aimed to examine changes in EMR techniques over a 9-year period and evaluate frequency of histologic-confirmed recurrence. METHODS: We identified patients who underwent EMR of non-pedunculated polyps ≥ 20 mm at a safety net and the Veteran's Affairs (VA) hospital in Houston, Texas between 2012 and 2020. Odds ratios (ORs) and 95% confidence intervals (CI) for associations with recurrence risk were estimated using multivariable logistic regression. RESULTS: 461 unique patients were included. The histologic-confirmed recurrence was 29.0% at 15.6 months median follow up (IQR 12.3 - 17.4). Polyps removed between 2018 and 2020 had a 0.43 decreased odds of recurrence vs. polyps removed between 2012 and 2014. The use of viscous lifting agents increased over time (from 0 to 54%), and the use of saline was associated with increased risk of recurrence (OR 2.28 [CI 1.33 - 3.31]). CONCLUSIONS: Histologic-confirmed recurrence after EMR for non-pedunculated polyps ≥ 20 mm decreased over the seven year-period. Saline was associated with a higher risk of recurrence and the use of more viscous agents increased over time.

Integrative Taxonomy, Distribution and Ontogenetic Colouration Change in Neotropical Mountain Catfishes of the Trichomycterus nigroauratus Group (Siluriformes: Trichomycteridae).

Catfishes of the genus Trichomycterus comprise the most diverse fish group in mountain river basins crossing the Atlantic Forest of south-eastern Brazil, with a great concentration of species in the Rio Paraíba do Sul basin. The present study is directed to the T. nigroauratus group, endemic to the Rio Paraíba do Sul basin, comprising species commonly found associated with bottom leaf litter. Field studies revealed two sympatric, distinct colour morphs, one comprising small specimens with a black longitudinal stripe over a pale brown ground colour on the flank and another comprising a single larger specimen with small dark browns spots scattered over a pale-yellow ground colour. These specimens were found in the upper Rio Paraitinga drainage, an area disjunct from the area inhabited by the other species of the group. We performed coalescent single-locus analyses for species delimitation using a cytochrome b fragment (1088 bp) for specimens from eight localities, including sequences taken from specimens exhibiting different colouration morphs and topotypes of all the three nominal species of the T. nigroauratus group. The analyses supported the two colouration morphs as belonging to a single species that is herein described. It is distinguished from other congeners by its unique colour pattern, dorsal and anal fins fin more posteriorly placed, and by the morphology of the opercle, metapterygoid and pelvic bone. The Maximum Likelihood analysis indicated the new species as sister to a clade containing all other congeners of the group, which is corroborated by osteological data. The occurrence of different lineages in neighbouring areas of the upper Rio Paraíba do Sul basin is interpreted as a possible vestige of a past complex paleogeographical scenario during the Cenozoic. The present record of striking ontogenetic colouration change, revealed only after checking DNA sequences of individuals exhibiting different colouration phenotypes, again highlights the importance of combining morphological and molecular data in taxonomical studies.

Clinical Understaging, Treatment Response, and Survival Among Esophageal Adenocarcinoma Patients.

INTRODUCTION: Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS: This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS: Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS: Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.

Understanding the association between clinical staging accuracy, treatment response, and survival among gastric cancer patients through Bayesian analysis.

BACKGROUND: Neoadjuvant therapy (NAT) improves survival among patients with locally advanced gastric cancer (GC), but it remains unclear whether its benefit is contingent on treatment response. METHODS: This is a national cohort study of stage Ib-III GC patients in the National Cancer Data Base (2006-2015) treated with upfront resection or NAT followed by surgery. Bayesian analysis was used for NAT patients to ascertain staging concordance and to account for down-staging. We used multivariable Cox regression to evaluate the association between staging concordance, treatment, response to NAT, and survival. RESULTS: The cohort included 13 340 patients treated at 1124 hospitals. Staging concordance ranged from 86.1% for cT3-4N+ to 34.7% for cT2N0 patients. Relative to accurately staged patients treated with upfront surgery, NAT was associated with a decreased risk of death if there was disease down-staging among those with cT1-2N+ (hazard ratio [HR]: 0.43 [0.30-0.61]), cT3-4N0 (HR: 0.69 [0.54-0.88]), and cT3-4N+ (HR: 0.51 [0.48-0.58]) tumors, and in the absence of down-staging among cT3-4N+ patients (HR: 0.83 [0.74-0.92]). Conversely, NAT without down-staging increased the risk of death among those with intermediate-stage disease. CONCLUSIONS: NAT is associated with improved survival for GC, but it seems to be contingent on treatment response among patients with intermediate-stage disease.

Developing and optimizing a computable phenotype for incident venous thromboembolism in a longitudinal cohort of patients with cancer.

Background: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer. Methods: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated on the entire sample using inverse probability weighting, followed by bootstrapped receiver operating curve analysis to calculate the concordance statistic (c statistic). Results: Among 800 patients sampled, 280 had a confirmed acute VTE during the first year after cancer diagnosis. The ICD/medication algorithm had a weighted PPV of 95% and a weighted sensitivity of 81%, with a c statistic of 0.90 (95% confidence interval [CI], 0.89-0.91). Adding Current Procedural Terminology codes for inferior vena cava filter removal or early death did not improve the performance. The NLP algorithm had a weighted PPV of 80% and a weighted sensitivity of 90%, with a c statistic of 0.93 (95% CI, 0.92-0.94). The combined algorithm had a weighted PPV of 98% at the higher cutoff and a weighted sensitivity of 96% at the lower cutoff, with a c statistic of 0.98 (95% CI, 0.97-0.98). Conclusions: Our ICD/medication-based algorithm can accurately identify VTE phenotype among patients with cancer with a high PPV of 95%. The combined algorithm should be considered in EHR databases that have access to such capabilities.

Surgery or active surveillance for pNETs < 2 cm: Preliminary results from a single center Brazilian cohort.

BACKGROUND AND OBJECTIVES: Incidence of pancreatic neuroendocrine tumors (pNETS) seems to be rising over the years, with many cases incidentally diagnosed. Surgery and active surveillance are current treatment modalities for small pNETS. We review our institutional series and compare outcomes for small asymptomatic and nonfunctioning tumors. METHODS: This retrospective cohort study included patients with 2 cm or less and well differentiated pNETS at a single Brazilian Cancer Center. From 2002 to 2020, patients received active surveillance or surgery as a treatment strategy. Short and long-term results were compared. RESULTS: Sixty-four patients were included, 41 in surgical strategy and 23 in the active surveillance approach. Baseline group characteristics were comparable. More patients on active surveillance underwent abdominal magnetic resonance imaging (MRI) and had tumors located in the pancreatic head (41% vs. 17%, p = 0.038). Minimally invasive procedure was chosen in 80.1% of the surgical patients. No patient died after surgery. Median follow-up period was 38.6 and 46.4 months for active surveillance and surgery cohorts, respectively. No difference in disease progression rate was observed. CONCLUSION: Both approaches seem to be safe for small pNETs. Long-term outcome and quality of life should be considered when discussing such options with patients.

PD-L1 expression in gastric and gastroesophageal junction cancer patients treated with perioperative chemotherapy.

BACKGROUND AND OBJECTIVES: The incidence, predictive, and prognostic impact of programmed cell death (PD-L1) expression in gastric (GC) and gastroesophageal junction tumors (GEJC) treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes. METHODS: Retrospective cohort of patients with GC and GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS). RESULTS: We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survival was 60.5% with a median OS not reached. PD-L1 expression was neither associated with pathological response or survival outcomes. CONCLUSIONS: PD-L1 expression in the setting of locally advanced GC tumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological response in this population.

Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations.

The epidemiology of cancer-associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well-characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/- lower extremity deep vein thrombosis (PE/LE-DVT) within 1 year of diagnosis. We used multivariable Fine-Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non-Hispanic White (NHW), 28% Non-Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1-year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76-0.99]) and API versus NHW (SHR 0.58 [0.44-0.77]). PE/LE-DVT was higher for NHB versus NHW (SHR 1.18 [1.01-1.39]). CAT was also associated with chemotherapy-based regimens (+/- immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials.

A new catfish species of the genus Cambeva (Siluriformes: Trichomycteridae) from the Rio Iguaçu drainage, southern Brazil, with a remarkable unique colour pattern.

Cambeva melanoptera sp. nov. is described from stream tributaries of the Rio Iratim, Rio Iguaçu drainage, southern Brazil. This new species is remarkable with a colour pattern not found elsewhere among trichomycterid catfishes, consisting of a broad distal black zone in all unpaired and pectoral fins, strongly contrasting with a pale-yellow proximal zone. C. melanoptera also differs from all other trichomycterids from eastern South America by the presence of the nasal barbel about thrice longer than the maxillary and rictal barbels. Due to the presence of a similar bicolour caudal fin, the new species is tentatively considered closely related to Cambeva castroi and Cambeva diabola, as well as more closely related to C. castroi than to C. diabola, with the first two species sharing the presence of a curved lateral process of the parurohyal and a trapezoidal projection on the lateral margin of the lateral ethmoid. The great morphological diversity found in Cambeva species endemic to the Rio Iguaçu drainage, including numerous exclusive characteristics not occurring in congeners and in any other species of closely related trichomycterine genera, indicates the need for more studies focusing on possible causal factors responsible for such unique diversification pattern.

Increasing Incidence of Gallbladder Cancer among Non-Hispanic Blacks in the United States: A Birth Cohort Phenomenon.

BACKGROUND: Gallbladder cancer incidence varies among racial/ethnic subgroups in the United States (US). We investigated trends in gallbladder cancer incidence rates in 50 states from 2001 to 2018. METHODS: Age-adjusted incidence rates and trends in adults were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percentage of changes (APC). We analyzed incidence trends by time periods, age groups, and birth cohorts through age-period-cohort modeling. RESULTS: Overall, age standardized incidence rates for gallbladder cancer decreased by 0.3% annually between 2001 and 2018 [95% confidence interval (CI) -0.5% to -0.1%]. However, secular trends varied by race/ethnicity. Although gallbladder cancer rates declined in other racial/ethnic groups, rates increased by 1.4% annually among non-Hispanic Blacks (NHB) between 2001 and 2018 (APC = 1.4%; 95% CI, 0.9%-2.0%). We found evidence for period and birth cohort effects with increasing rates among successive birth cohorts of NHBs. Relative to NHB cohorts born circa 1946, gallbladder cancer rates were 85% higher in NHB cohorts born circa 1971 [incidence rate ratio (IRR), 1.85; 95% CI, 1.26-2.72). The rates among NHBs in South region were higher in cohorts born circa 1971 (IRR, 2.17; 95% CI, 1.27-3.73) relative to those born circa 1946. CONCLUSIONS: The incidence of gallbladder cancer has consistently increased in the US among NHBs. A notable increase in incidence was observed among NHBs with evidence of birth cohort effects in South, Northeast, and Midwest regions. IMPACT: The cohort effect observed among NHBs with increasing rates in different US regions suggests that gallbladder cancer rates will continue to rise in the US in the near future.

Sociodemographic and Facility-Related Disparities in the Delivery of Guideline-Concordant Therapy Among Patients With Esophageal Adenocarcinoma.

PURPOSE: Evidence on health disparities among patients treated with multimodality therapy protocols is still limited. We aimed to evaluate the associations between patient-level and system-level factors and the receipt of guideline-concordant therapy among patients with esophageal adenocarcinoma (EA). METHODS: This is a national cohort study of patients with stage I-III EA in the National Cancer Database (2006-2018) treated with either upfront resection or neoadjuvant therapy followed by surgery. Clinical and pathologic staging data were used for defining guideline-concordant therapy. Logistic regression models were built to identify independent associations between deviations from treatment guidelines and clinical, sociodemographic, and hospital-related factors. RESULTS: Among 18,803 patients with EA treated at 1,049 hospitals, 4,511 had an endoscopic resection, 4,866 had upfront resection, and 9,426 had neoadjuvant therapy followed by surgery. A total of 16,002 patients (85.1%) received guideline-concordant therapy. Patients who were age 70 years or older (odds ratio [OR] 1.35; 95% CI, 1.14 to 1.60), had a Charlson-Deyo modified score of ≥ 1, and were treated at hospitals with a safety-net burden of ≥ 10% (OR 1.13; 95% CI, 1.02 to 1.25) had higher risk of deviations from guidelines, whereas treatment at high-volume facilities (OR 0.84; 95% CI, 0.74 to 0.95) and diagnosis after 2011 decreased this risk. Relative to cT0-1N0 patients, those with cT2N0 disease had the highest risk of deviations from guideline-concordant therapy (OR 3.76; 95% CI, 3.30 to 4.29). Among patients treated at high-volume facilities, safety-net burden over 10% increased the risk of deviations (OR 1.26; 95% CI, 1.01 to 1.57). CONCLUSION: The delivery of guideline-concordant therapy among patients with EA varies significantly across clinical stage groups and is associated with several sociodemographic disparities. This knowledge should be a resource for future quality improvement strategies intended to address inequitable care within vulnerable populations.

Bayesian Approach to Understand the Association Between Treatment Down-staging and Survival for Patients With Pancreatic Adenocarcinoma.

OBJECTIVE: To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: NAT is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging. METHODS: This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging. RESULTS: Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p< 0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death [HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease], even among those without tumor down-staging [HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4]. CONCLUSIONS: NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients.