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Introduction Fewer than 10% of colon cancers are found at the splenic flexure. A standard surgical approach to these cancers has not been defined. The goal of this study was to compare lymph node harvest and post-operative morbidity between segmental resection and formal left hemicolectomy for splenic flexure colon cancers. Method Patients diagnosed with a splenic flexure cancer were identified from the 2012–2018 ACS-NSQIP colectomy-targeted database. Patients were categorized based on type of surgical resection – left hemicolectomy with colorectal anastomosis or segmental colectomy with colocolonic anastomosis. Demographic, clinicopathologic, and post-operative outcomes were compared between groups. Factors independently associated with lymph node harvest, operative time, and post-operative morbidity were investigated by linear and binomial logistic regression models. Results A total of 3,049 patients underwent colectomy for a splenic flexure cancer. Of these, 83.6% had a segmental colectomy and 73% were performed by a minimally invasive approach. T- and N-stage did not differ between segmental and left hemicolectomy groups (p = 0.703 and p = 0.429, respectively). Inadequate nodal harvest (p = 0.13). Operative time was significantly shorter for segmental colectomy (213 ± 83.5 min vs. 193 ± 84.1 min, p p = 0.75). After accounting for demographic, clinicopathologic, and operative factors, binomial logistic regression showed that type of procedure was not significantly associated with LN harvest (OR 0.80, 95%CI 0.54–1.17) or major morbidity (OR 1.17, 95%CI 0.36–3.81). However, on linear regression, segmental splenic flexure resection was associated with shorter operative time (estimate 20.29, 95%CI 12.61–27.97, p Conclusion Splenic flexure resection for colon cancer is associated with an adequate lymph node harvest. Compared to a formal left hemicolectomy, a segmental resection also has a shorter operative time with equivalent post-operative morbidity.

Colorectal cancer is increasing in young adults. Our understanding of the adenoma-carcinoma sequence in young patients aged50 years is lacking. The yield obtained by lowering the age of screening colonoscopy remains unclear.The goal of this study was to understand the burden and histology of colorectal polyps in young adults and to explore predictors of adenoma detection in this population.This is a retrospective cohort study.Colonoscopies were performed at a single university-affiliated tertiary care center.This study included adults aged50 years who underwent a colonoscopy between 2014 and 2019. Patients with inflammatory bowel disease and genetic disorders were excluded.Adenoma detection rates were analyzed according to age. Predictors of adenoma detection were investigated by multiple logistic regression.A total of 4475 patients were analyzed. The mean age was 40.2 ± 8.0 years, 56.4% were female, and the mean BMI was 26.3 ± 5.5 kg/m2. A family history of colorectal cancer was reported in 23.8% of patients. The overall polyp and adenoma detection rates were 22% and 14%. The majority of polyps were adenomatous (58.9% of all polypectomies) and located in the left colon or rectum (61.4%). The detection rates of adenomas, advanced neoplasias, and adenocarcinomas were highest in patients aged 45 to 49 (19.3%, 4.8%, and 1.3%). On multivariate analysis, variables independently associated with adenoma detection included age (OR 1.08, 95% CI, 1.06-1.1), female sex (OR 1.80, 95% CI, 1.44-2.27), BMI (OR 1.01, 95% CI, 1.01-1.05), and having undergone a diagnostic colonoscopy (OR 1.81, 95% CI, 1.44-2.29). On subgroup analysis of patients aged 45 to 49, the same variables remained associated with adenoma detection except for age.The study was limited due to the retrospective nature with heterogenous data.Adenoma detection in young adults aged 45 to 49 approaches the current adenoma detection of older adults. Predictors of adenoma detection in these young adults are female gender and BMI, which may help guide colorectal cancer screening guidelines in the future. See Video Abstract at http://links.lww.com/DCR/B843.ANTECEDENTES:El cáncer colorrectal está aumentando en adultos jóvenes. No se conoce la secuencia adenoma-carcinoma en pacientes jóvenes50 años. El rendimiento obtenido al reducir la edad de la colonoscopia de detección sigue sin estar claro.OBJETIVO:Comprender la carga y la histología de los pólipos colorrectales en adultos jóvenes y explorar los predictores de detección de adenomas en esta población.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Las colonoscopias se realizaron en un único centro de atención terciario afiliado a la universidad.PACIENTES:Adultos jóvenes50 años que se sometieron a una colonoscopia entre 2014-2019. Se excluyeron los pacientes con enfermedad inflamatoria intestinal y trastornos genéticos.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron las tasas de detección de adenomas según la edad. Los predictores de la detección de adenomas se investigaron mediante regresión logística múltiple.RESULTADOS:Se analizaron 4475 pacientes. La edad media fue de 40,2 ± 8,0 años, el 56,4% eran mujeres y el IMC medio fue de 26,3 ± 5,5 kg / m2. Se informó de antecedentes familiares de cáncer colorrectal en el 23,8% de los pacientes. Las tasas generales de detección de pólipos y adenomas fueron del 22% y el 14%, respectivamente. La mayoría de los pólipos eran adenomatosos (58,9% de todas las polipectomías) y estaban localizados en colon izquierdo o recto (61,4%). Las tasas de detección de adenomas, neoplasias avanzadas y adenocarcinomas fueron más altas en pacientes de 45 a 49 años (19,3%, 4,8% y 1,3%, respectivamente). En el análisis multivariado, las variables asociadas de forma independiente con la detección de adenomas incluyeron: edad (OR 1.08; IC del 95%: 1,06-1,1), sexo femenino (OR 1,80; IC del 95%: 1,44-2,27), IMC (OR 1,01; IC del 95%: 1,01-1,05)) y haber sido sometido a una colonoscopia diagnóstica (OR 1,81; IC 95% 1,44-2,29). En el análisis de subgrupos de pacientes de 45 a 49 años, las mismas variables permanecieron asociadas con la detección de adenomas, excepto la edad.LIMITACIONES:Carácter retrospectivo con datos heterogéneos.CONCLUSIONES:La detección de adenomas en adultos jóvenes de 45 a 49 años se acerca a la detección actual de adenomas en adultos mayores. Los predictores de la detección de adenomas en estos adultos jóvenes son el sexo femenino y el IMC, que pueden ayudar a guiar las pautas de detección del cáncer colorrectal en el futuro. Consulte Video Resumen en http://links.lww.com/DCR/B843. (Traducción-Dr. Hagerman).

SGLT2 inhibitors are a new class of oral antihyperglycaemic agents that have garnered much attention for their attractive efficacy profile in glycaemic control along with the added benefit of weight loss. There has been increasing concern for the risk of euglycaemic (serum glucose 4–8 mmol/L) ketoacidosis with these agents. In the setting of a postoperative patient, the use of these drugs may exacerbate the normal physiological stresses of the body and increase the risk of developing euglycaemic ketoacidosis (euKDA). This case highlights a postoperative patient who was using an SGLT2 inhibitor and developed severe euKDA after a pancreaticoduodenectomy. The goal of this case report was to bring awareness to the possibility of this rare adverse event. In doing so, it may aid in preoperative planning of the diabetic patient and trigger appropriate management for those who develop euKDA.

AE1 [anion exchanger 1, also known as SLC4A1 (solute carrier family 4, anion exchanger, member 1) and band 3 (erythrocyte membrane protein band 3)] is a major membrane glycoprotein expressed in human erythrocytes where it mediates the exchange of chloride and bicarbonate across the plasma membrane. Glycophorin A (GPA) is a sialoglycoprotein that associates with AE1 in erythrocytes forming the Wrb (Wright b) blood group antigen. These two integral proteins may also form a complex during biosynthesis, with GPA facilitating the cell surface expression of AE1. This study investigates the interaction of GPA with AE1 in K562 cells, a human erythroleukaemic cell line that expresses GPA, and the role of GPA in the cell surface expression of AE1. In K562 cells, GPA was dimeric and N- and O-glycosylated similar to erythroid GPA. GPA was localized at the cell surface, but also localized to the Golgi. AE1 expressed in K562 cells contained both complex and high-mannose oligosaccharides, and co-localized with GPA at the cell surface and in the endoplasmic reticulum (ER). The Wrb antigen was detected at the cell surface of AE1-transfected K562 cells, indicating the existence of an AE1–GPA complex. Immunofluorescence and co-immunoprecipitation studies using AE1 and an ER-localized hereditary spherocytosis mutant (R760Q AE1) showed that GPA and AE1 could interact in the ER. GPA knockdown by shRNAs (small-hairpin RNAs), however, had no effect on the level of cell surface expression of AE1. The results indicate that AE1 and GPA form a complex in the ER of human K562 cells, but that both proteins can also traffic to the cell surface independently of each other.

Kidney anion exchanger 1 (kAE1) is a membrane glycoprotein expressed in alpha-intercalated cells in the collecting ducts of the kidney where it mediates electroneutral chloride/bicarbonate exchange. Human kAE1 is a truncated form of erythroid AE1 missing the first 65 residues of the N-terminal cytosolic domain, which includes a disordered acidic region (residues 1-54) and the first beta-strand (residues 55-65) of the folded region. Unlike erythroid AE1, kAE1 does not bind deoxyhemoglobin, glycolytic enzymes, or cytoskeletal components. To understand the effect of the N-terminal deletion on the structure of the cytosolic domain, we performed an extensive biophysical analysis on His 6 tagged cytosolic domains of erythroid AE1 (cdAE1), kidney AE1 (cdkAE1), and a novel truncation mutant (cdDelta54AE1) missing the first 54 residues, but retaining the beta-strand. Circular dichroism did not detect any major differences in secondary structure, and sedimentation analyses showed that all three proteins were dimeric. Differential scanning calorimetry revealed that cdAE1 and cdDelta54AE1 had similar thermal stabilities with midpoints of transition higher than cdkAE1. cdAE1 and cdDelta54AE1 underwent similar pH-dependent fluorescence changes, while cdkAE1 exhibited a higher intrinsic fluorescence at neutral and acidic pH. Urea denaturation resulted in dequenching of tryptophan fluorescence in cdAE1, while tryptophans in cdkAE1 were already dequenched in the native state. We conclude that the absence of the central beta-strand in cdkAE1 results in a less stable and more open structure than cdAE1. This structural change, in addition to the loss of the acidic amino-terminal region, may account for the altered protein binding properties of kAE1.