Adoption of Optimal Small (6-9 mm) Colorectal Polyp Resection Technique Over Time.

BACKGROUND: Cold snare polypectomy (CSP) is the preferred resection technique for small (6-9 mm) polyps due to lower rate of incomplete resection compared to cold forceps polypectomy (CFP) and improved safety profile over hot snare polypectomy (HSP). AIMS: To describe resection techniques for small (6-9 mm) polyps and determine factors associated with sub-optimal technique. METHODS: This was retrospective cohort study of colonoscopies performed by gastroenterological and surgical endoscopists from 2012 to 2019 where at least one 6-9 mm polyp was removed. Patient, provider, and procedure characteristics were collected. Univariate and multivariate regression analyses were performed to determine factors associated with sub-optimal technique. RESULTS: In total, 773 colonoscopies where 1,360 6-9 mm polyps removed by 21 endoscopists were included. CSP was used for 1,122 (82.5%), CFP for 61 (4.5%), and HSP for 177 (13.0%). Surgeon specialty was associated with CFP use (aOR 7.81; 95% CI 3.02-20.16). Polyp location in left colon (aOR 1.65; 95% CI 1.17-2.33) and pedunculated morphology (aOR 12.76; 95% CI 7.24-22.50) were associated with HSP. There was a significant increase in overall CSP use from 30.4% in 2012 to 96.8% in 2019. CONCLUSIONS: 82.5% of all 6-9 mm polyps removed from 2012 to 2019 were removed using a cold snare with significant increase in CSP from 2012 to 2019. Differences in how optimal technique was adopted over time based on specialty highlight the need for standardized practice guidelines and quality monitoring.

Improved survival in rectal cancer patients who are treated with long-course versus short-course neoadjuvant radiotherapy: A propensity-matched analysis of the NCDB.

BACKGROUND: Randomized controlled trials have demonstrated comparable survival outcomes for short-course (SCRT) and long-course neoadjuvant radiotherapy (LCRT) in patients with rectal cancer. METHODS: Using the National Cancer Data Base (2004-2015), a propensity score was used to match 188 patients with rectal cancer receiving SCRT to 376 patients receiving LCRT. Perioperative, oncologic, and survival outcomes were compared. RESULTS: Patient and clinical tumor characteristics were similar between groups. Patients in the LCRT were more likely to undergo surgery (91% vs 85%; P = 0.03). The LCRT group were more likely to have tumor (T) (56% vs 43%) and nodal (N) (25% vs 19%) downstaging, and a complete pathological response (15% vs 6%) compared with the SCRT group (all P < 0.05). Length of stay (6 vs 8 days), 30-day (1% vs 5%) mortality, and 90-day mortality (1% vs 10%) were significantly lower in the LCRT group (all P < 0.05). After adjusting for patient and tumor-related characteristics, LCRT was associated with a 50% reduction in the risk of mortality compared with SCRT (hazard ratios, 0.50; 95% confidence interval, 0.35-0.70). CONCLUSIONS: In this analysis, LCRT was superior to SCRT in terms of tumor response to neoadjuvant therapy, perioperative mortality, and overall survival. These findings provide evidence for the use of LCRT when neoadjuvant therapy is indicated.

Laparoscopic colectomy in obese patients: a comparison of laparoscopic and hand-assisted laparoscopic techniques.

BACKGROUND: Recent American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP)-based evidence indicates that laparoscopic (LAP) colectomy results in improved outcomes compared to hand-assisted laparoscopic (HAL) colectomy in the general population. Previous comparative studies demonstrated that the HAL technique offers distinct advantages for obese patients. The aim of this study was to perform comparative analyses of HAL and LAP colectomy and low anterior resection (LAR) in obese patients. METHODS: The ACS-NSQIP public use file and targeted colectomy dataset, 2012-2014, were utilized for patients undergoing colectomy and LAR. Only obese patients (BMI > 30) and laparoscopic or hand-assisted operations were included. Patient, operation, and outcome variables were compared in two separate cohorts: colectomy and LAR. Bivariate analysis compared the approaches, followed by multivariable regression. RESULTS: Of 9610 obese patients included, HAL and LAP colectomy were performed in 3126 and 3793 patients and LAR in 1431 and 1260 patients, respectively. In comparison to LAP colectomy, HAL colectomy patients had increased comorbidities including class 2 and 3 obesity. HAL colectomy was associated with higher overall morbidity (20 vs. 16%, p < 0.001), infectious complications (10.2 vs. 7.7%, p < 0.001), anastomotic leaks (3.0 vs. 2.2%, p = 0.03), and ileus (11 vs. 8%, p < 0.001). Multivariate analysis indicated that overall morbidity (OR 1.27, 95% CI 1.11-1.44), infectious complications (OR 1.35, 95% CI 1.14-1.59), and ileus (OR 1.33, 95% CI 1.12-1.57) were each increased in the HAL colectomy cohort but not different for HAL and LAP LAR. CONCLUSIONS: In comparison to LAP colectomy, the HAL technique is used more often in obese patients with an increased operative risk profile. While inherent bias and unmeasured variables limit the analysis, the available data indicate that the HAL technique is associated with increased perioperative morbidity. Alternatively, HAL and LAP LAR are performed in obese patients with a similar risk profile and result in similar postoperative outcomes.

Experimental models of B cell tolerance in transplantation.

The use of conventional immunosuppression has successfully improved short-term allograft survival, however, long-term allograft survival has remained static and is complicated by serious side effects secondary to the long-term use of immunosuppressive agents. Immunological tolerance is the ultimate goal of organ transplantation, however it is an infrequent event in humans. Accordingly, over the past several decades, there has been a push to fully understand both the cellular and molecular mechanisms that play a role in the induction and maintenance of tolerance, with recent data implicating B cells and donor specific alloantibody as a barrier to and potential mediator of allograft tolerance. The study of B cells and alloantibody in transplant tolerance has evolved over recent years from using rodent models to non-human primate models. This review will discuss the role of B cells and alloantibody as antagonists and facilitators of transplantation tolerance, and highlight the experimental models developed for elucidating the mechanisms of B cell tolerance to alloantigen.

Management of Rectal Polyps.

Colorectal cancer is one of the most common causes of cancer and cancer morbidity in the United States. In comparison to colon polyps, rectal polyps pose a unique challenge. Advances in endoscopic techniques have allowed for more thorough rectal adenoma detection and removal; however, there remains a concern over piecemeal resection and negative resection margins. Advances in transanal excision techniques, such as transanal endoscopic microsurgery, have been proposed for the removal of benign polyps as well as some early stage rectal cancers, with emphasis on proper patient selection. This review will discuss the current endoscopic and surgical considerations of both benign and malignant rectal polyps.

Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection.

The contribution of T cells and graft-reactive antibodies to acute allograft rejection is widely accepted, but the role of graft-infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T-cell-mediated (N = 21), antibody-mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African-American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3(+) T cells as the dominant cell type, followed by CD20(+) B cells and CD138(+) plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B-cell density trended toward significance. Surprisingly T-cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ≥6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid-resistant acute rejection.

Disparities in colorectal cancer mortality for rural populations in the United States: Does screening matter?

INTRODUCTION: Rural compared to urban populations in the US have increased colorectal cancer (CRC) incidence with known disparity in screening rates and mortality. We hypothesize that rural-urban disparities are different at a regional level. METHODS: We assessed screening rates according to the 2016 Behavioral Risk Factor Surveillance System guidelines using state and city-level data for county level estimates and correlating with county CRC mortality data from the National Cancer Institute. We used multivariable modeling to examine associations between rurality, screening rates, and mortality. RESULTS: Highest screening rate states had the smallest urban-rural disparities; lowest screening rate states had the largest disparities. Percent screened and urban-rural classification correlated significantly with mortality. Rural counties experienced ∼5 more deaths per 100,000 population even controlling for screening rates. CONCLUSIONS: National urban-rural disparities in CRC screening mask greater state/regional disparities, not fully explaining the urban-rural mortality gap. Other factors (i.e. access to care, treatment differences) must be considered.

Impact of immunosuppression on recall immune responses to influenza vaccination in stable renal transplant recipients.

BACKGROUND: The recommendation by the American Society of Transplantation for annual trivalent inactivated influenza vaccination greater than 3 to 6 months post-kidney transplantation provides a unique opportunity to test the in vivo impact of immunosuppression on recall T- and B-cell responses to influenza vaccination. METHODS: This study took advantage of recent breakthroughs in the single-cell quantification of human peripheral blood B-cell responses to prospectively evaluate both B- and T-cell responses to the seasonal (2010 and 2011) influenza vaccine in 23 stable renal transplant recipients and 22 healthy controls. RESULTS AND CONCLUSION: The results demonstrate that the early B-cell response to influenza vaccination, quantified by the frequency of influenza-specific antibody-secreting cells (ASC) in peripheral blood, was significantly reduced in stable transplant recipients compared to healthy controls. The magnitude of the seroresponse and the rate of seroconversion were also blunted. The influenza-specific interferon-gamma (IFNγ) T-cell response was significantly reduced in transplant recipients; however, there was no correlation between the magnitude of the influenza-specific IgG ASC and IFNγ responses. The induction of memory T- and B-cell responses to influenza vaccination supports the recommendation to vaccinate while the blunted responses demonstrate the efficacy of immunosuppression in controlling memory responses individual transplant recipients.

CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2.

Efficient generation of regulatory T cells (T(reg) cells) in the thymus requires CD28 costimulation, but it is not known why. Here, molecular mapping of CD28 costimulation showed that T(reg) cell generation requires a motif that binds the tyrosine kinase Lck, precisely the same motif that is required for CD28 costimulation of interleukin 2 production. Nevertheless, CD28 costimulation provides more than interleukin 2 to developing T(reg) cells, as CD28 costimulation of T cell receptor-signaled double-positive thymocytes induced expression of Foxp3, considered to be the T(reg) 'master gene', as well as GITR and CTLA-4, two proteins expressed on T(reg) cells. Thus, CD28 costimulation directly signals developing thymocytes to express Foxp3 and to initiate the T(reg) cell differentiation program.

CD5-mediated inhibition of TCR signaling during intrathymic selection and development does not require the CD5 extracellular domain.

CD5 functions as a negative regulator of TCR signaling during intrathymic T cell development, but it is not known if this negative regulatory function requires CD5 engagement of an extracellular ligand. The present study has specifically examined the role of the CD5 extracellular domain in T cell development by introducing into CD5-/- mice a chimeric CD5 molecule in which the extracellular domain of CD5 is replaced with the extracellular domain of human IL-2R p55 (Tac) for which no ligand exists in the mouse. We now report that CD5 mediated down-regulation of TCR signaling during thymocyte development does not require the CD5 extracellular domain and, consequently, does not involve CD5 binding of an extracellular ligand in the thymus.