Pathologic Outcomes of Short-Course and Long-Course Radiotherapy for Locally Advanced Rectal Cancers Treated With Total Neoadjuvant Therapy.

INTRODUCTION: Total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is now the standard of care. Randomized trials suggest the use of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are oncologically equivalent. OBJECTIVE: To describe pathologic outcomes after surgical resections of patients receiving SCRT versus LCRT as part of TNT for LARC. PARTICIPANTS: All patients with LARC treated at a single tertiary hospital who underwent proctectomy after completing TNT were included. Patients were excluded if adequate details of TNT were not available in the electronic medical record. RESULTS: A total of 53 patients with LARC were included. Thirty-nine patients (73.5%) received LCRT and 14 (26.4%) received SCRT. Forty-nine patients (92.5%) were clinical stage III (cN1-2) prior to treatment. The average lymph node yield after proctectomy was 20.9 for SCRT and 17.0 for LCRT (P = .075). Of the 49 patients with clinically positive nodes before treatment, 76.9% of those who received SCRT and 72.2% of those who received LCRT achieved pN0 disease after TNT. Additionally, there were no significant differences in rates of pathologic complete response between patients who received SCRT and LCRT, 7.1% and 12.8%, respectively (P = .565). CONCLUSION: Pathologic outcomes of patients with LARC treated with SCRT or LCRT, as part of TNT, may be similar. Further prospective trials are needed to assess long-term clinical outcomes and to determine best treatment protocols.

Rectal Cancer Survival for Residual Carcinoma In Situ Vs. Pathologic Complete Response After Neoadjuvant Therapy.

BACKGROUND: Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. OBJECTIVE: To compare survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. DESIGN: Retrospective cohort study. SETTING: National public database. PATIENTS: A total of 4,594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative, ypTis or ypT0 on final pathology were included. 4,321 (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. MAIN OUTCOME MEASURES: Overall survival. RESULTS: Median age was 60 years. 1,822 patients (39.7%) were female. 54.5% (n = 2,503) had stage II disease and 45.5% (n = 2,091) had stage III disease on initial staging. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42, 95% CI 1.04-1.95, p = 0.028). Other factors associated with decreased overall survival were an older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage 2 versus stage 3. LIMITATIONS: Standard therapy versus total neoadjuvant therapy were unable to be abstracted. Overall survival was defined as time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. CONCLUSIONS: ypTis is associated with worse overall survival than ypT0 for locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract.

Low translational and rotational movements with 2-point stainless-steel retainers over a period of 1 and 3 years.

OBJECTIVES: Long-term stabilization of orthodontic treatment outcomes is an everyday challenge in orthodontics. The use of permanently attached lingual retainers has become gold standard. However, in some cases, patients with fixed lingual retainers show retainer-associated side effects. Aiming to reduce these side effects, clinical knowledge about how tooth and arch form stability adaption takes place over time is important to improve long-term retention protocols. Therefore, the present study aimed to investigate occlusion stability and risks for a newly developing malocclusion in a time-dependent manner in patients being treated with permanent 2­point steel retainers. MATERIALS AND METHODS: In this retrospective cohort study, a total of 66 consecutive patients with round stainless-steel retainers were analyzed for postorthodontic occlusion changes after 1 year (group 1, n = 33) and 3 years (group 2, n = 33). Digital Standard Tessellation Language (STL) datasets of the lower jaw were obtained before retainer insertion (T0), and after a 1- (T1) or 3­year (T2) retention period. Using superimposition software, T1 and T2 situations were compared to T0 regarding rotational and translational changes in tooth positions in all three dimensions. RESULTS: Occlusion changes were low in both groups. The investigated lower canines were nearly stable in the 1­ and 3­year group, although a retention-time-dependent increase in tooth position change of the central and lateral incisors could be observed. CONCLUSION: The present data provide evidence for time-dependent development of posttherapeutic occlusal adaption limited to central and lateral incisors in patients treated with a 2-point retainer. The observed occlusal changes should be interpreted as an occlusal adaption process rather than severe posttreatment changes associated with the orthodontic retainer.

Prevalence of and Risk Factors for Incidental Colonic Diverticulosis.

INTRODUCTION: The true prevalence and pathogenesis of diverticulosis is poorly understood. Risk factors for diverticulosis are presently unclear, with most clinicians attributing its development to years of chronic constipation. Previous studies have been limited by their failure to include young, ethnically diverse patient populations. METHODS: Patients who presented to the emergency department of our hospital from January-September 2019 and underwent abdominal computerized tomography (CT) scan for the evaluation of appendicitis were included. CT's were reviewed for the presence of diverticulosis. Risk factors for diverticulosis were determined for two age groups: >40 and ≤ 40. RESULTS: A total of 359 patients were included in the study. The median age was 38.57.1% were male. 81.6% were Hispanic. 43.5% had colonic diverticulosis on CT. 198 patients (55.1%) were ≤ age 40. The rate of diverticulosis in this group was 35.3% (n = 70). Those with diverticulosis were not significantly older (median age 29 versus 27, P = 0.061) but had a higher median body mass index (BMI) (28.4 versus 25.3, P = 0.003) compared to those without diverticulosis. On multivariate analysis, no characteristics were associated with the presence of diverticulosis for this group. Over age 40, 53.4% of patients (n = 86) had diverticulosis. Patients with diverticulosis were more likely to be Hispanic (95.3% versus 73.3%, P ≤ 0.001), less likely to be Asian (2.4% versus 16.0%, P = 0.004), had a higher median BMI (28.7 versus 25.5, P ≤ 0.001), and were more likely to use alcohol (30.2% versus 14.7%, P = 0.024) than those without diverticulosis. On multivariate analysis, characteristics associated with the presence of diverticulosis were BMI >30 (odds ratio OR 2.22, 95% confidence interval CI 1.03-4.80), Hispanic ethnicity (OR 10.05, 95% CI 1.74-58.26), and alcohol use (OR 3.44, 95% CI 1.26-9.39). CONCLUSIONS: There was a higher rate of asymptomatic diverticulosis in the <40 cohort than previously reported in the literature. Obesity, alcohol use, and Hispanic ethnicity were associated with the presence of diverticulosis in patients > age 40, but no risk factors for diverticulosis were identified for patients ≤ age 40, suggesting that diverticular pathogenesis may differ by age. Constipation was not a risk factor for diverticulosis in either age group. The data regarding the prevalence of diverticulosis in Hispanic patients is lacking and should be the focus of future inquiry.

LigaSure™ haemorrhoidectomy and the risk of postoperative bleeding.

AIM: LigaSure™ is an electro-surgical device that has increasingly been utilized in haemorrhoid surgery. However, recent literature has highlighted a possible increased risk of delayed postoperative bleeding following LigaSure haemorrhoidectomy (LH). We aim to evaluate the rates of postoperative bleeding following LigaSure compared to Ferguson (closed) haemorrhoidectomy (FH). METHODS: A retrospective cohort study was undertaken at our single academic safety-net county hospital from August 2016 through July 2019 evaluating patients who received FH or LH. Patient demographics, surgical data, postoperative emergency department visit for pain or bleeding within 30 days and resulting transfusion requirement, and rates of readmission and interventions within 30 days were collected. RESULTS: Sixty-one FH and 66 LH patients were identified. The groups had no difference in demographics. The LH group and FH group had similar rates of postoperative emergency department visits (29% vs. 23%, P = 0.454), as well as visits for bleeding (20% vs. 11%, P = 0.204). The average operating time was also significantly shorter with LH (14.5 min vs. 24.9 min, P ≤ 0.001). On multivariate analysis, male sex (OR 7.28, 95% CI 1.88-28.25) and haemorrhoid grade ≤2 (OR 4.64, 95% CI 1.31-16.49) were significantly associated with postoperative bleeding on multivariate analysis. Use of LH was not independently associated with postoperative bleeding risk (OR 1.89, 95% CI 0.70-5.11). CONCLUSIONS: LH and FH have similar risks for postoperative bleeding and other complications. Male sex and haemorrhoid Grades 1 or 2 may be associated with increased postoperative bleeding risk. Excisional haemorrhoidectomy should be undertaken with caution for male patients with lower internal haemorrhoid grades.

COVID-19 Impact on Colorectal Daily Practice-How Long Will It Take to Catch Up?

BACKGROUND: All elective surgeries have been postponed at our institution starting 3/16/20 due to the COVID-19 pandemic. We assessed changes in hospital resource utilization and estimated the future backlog of cases in the colorectal surgery division of a large safety-net hospital. METHODS: Patients undergoing colorectal procedures from 3/16/20 to 4/23/20 (COVID) were compared with those from January through June 2018 (historical). Resource utilization rates were calculated by weekly case volumes and hospital stay in each group. A future catch up timeframe and new wait times from scheduling to surgery dates were calculated. RESULTS: The COVID and historical groups included 13 and 239 patients, respectively. The COVID group showed a 74% relative decrease in weekly surgical case rates (9.2 to 2.4 patients per week). Both groups had similar lengths of stay. The COVID group had a longer average ICU stay (1.4 ± 2.5 days vs. 0.4 ± 1.2 days, P = 0.016) and a 132% increase in ICU resource utilization. Overall, the COVID group had a 48% relative decrease in hospital resource utilization, owing to reduced volume but higher acuity. If the surgery numbers returns to pre-COVID volumes, the calculated "catch up" times range from 4.6 weeks to 9.2 weeks. Wait times for new cases may increase by 70% compared with pre-COVID levels. CONCLUSION: Cancelling elective colorectal surgeries results in a decrease in overall but increase in ICU-specific resource utilization. Though necessary, cancellations result in an increasing backlog of cases that poses significant future logistical and clinical challenges in an already overburdened safety-net hospital. Effective triage systems will be critical to prioritize this backlog.

Comparative Effectiveness and Risks of Bowel Preparation Before Elective Colorectal Surgery.

OBJECTIVE: The objective of this study was to determine the relationship between bowel preparation and surgical site infections (SSIs), and also other postoperative complications, after elective colorectal surgery. BACKGROUND: SSI is a major source of postoperative morbidity/costs after colorectal surgery. The value of preoperative bowel preparation to prevent SSI remains controversial. METHODS: We analyzed 32,359 patients who underwent elective colorectal resections in the American College of Surgeons National Surgery Quality Improvement Program database from 2012 to 2014. Univariable and multivariable analyses were performed; propensity adjustment using patient/procedure characteristics was used to account for nonrandom receipt of bowel preparation. RESULTS: 26.7%, 36.6%, 3.8%, and 32.9% of patients received no bowel preparation, mechanical bowel preparation (MBP), oral antibiotics (OA), and MBP + OA, respectively. After propensity adjustment, MBP was not associated with decreased risk of SSI compared with no bowel preparation. In contrast, both OA and OA + MBP were associated with decreased risk of any SSI (adjusted odds ratio 0.49, 95% confidence interval 0.38-0.64; and adjusted odds ratio 0.45, 95% confidence interval 0.40-0.50, respectively) compared with no bowel preparation. OA and MBP + OA were associated with decreased risks of anastomotic leak, postoperative ileus, readmission, and also shorter length of stay (all P < 0.05). Bowel preparation was not associated with increased risk of cardiac/renal complications compared with no preparation. CONCLUSIONS: The use of MBP alone before elective colorectal resection to prevent SSI is ineffective and should be abandoned. In contrast, OA and MBP + OA are associated with decreased risks of SSI and are not associated with increased risks of other adverse outcomes compared with no preparation. Prospective studies to determine the efficacy of OA are warranted; in the interim, MBP + OA should be used routinely before elective colorectal resection to prevent SSI.

An Informed Consent Program Enhances Surgery Resident Education.

OBJECTIVE: First-year residents often obtain informed consent from patients. However, they typically receive no formal training in this area before residency. We wished to determine whether an educational program would improve residents' comfort with this process. DESIGN: Our institution created an informed consent educational program, which included a didactic component, a role-play about informed consent, and a simulation exercise using standardized patients. Residents completed surveys before and after the intervention, and responses to survey questions were compared using the signed-rank test. SETTING: This study took place at Temple University Hospital, a tertiary care institution in Philadelphia, PA. PARTICIPANTS: First-year surgery and emergency medicine residents at Temple University Hospital in 2014 participated in this study. Thirty-two residents completed the preintervention survey and 27 residents completed the educational program and postintervention survey. RESULTS: Only 37.5% had ever received formal training in informed consent before residency. After participating in the educational program, residents were significantly more confident that they could correctly describe the process of informed consent, properly fill out a procedure consent form, and properly obtain informed consent from a patient. Their comfort level in obtaining informed consent significantly increased. They found the educational program to be very effective in improving their knowledge and comfort level in obtaining informed consent. In all, 100% (N = 27) of residents said they would recommend the use of the program with other first-year residents. CONCLUSIONS: Residents became more confident in their ability to obtain informed consent after participating in an educational program that included didactic, role-play, and patient simulation elements.

Adherence to chronic opioid therapy prescribing guidelines in a primary care clinic.

OBJECTIVE: Characterize primary care patients prescribed opioids for chronic noncancer pain (CNCP), explore guideline-recommended opioid-monitoring practices, and investigate predictors of pain agreements. DESIGN: Retrospective chart review. SETTING: Primary care clinic at a tertiary academic medical center. PATIENTS: Adults prescribed chronic opioids (three or more monthly prescriptions within a year) for CNCP between April 1, 2014 and April 1, 2015. Patients without CNCP served as controls. MAIN OUTCOME MEASURE: Patient demographics, medical diagnoses, tobacco status, provider status, documentation of guideline-recommended opioid-monitoring practices, pain agreement status, and opioid prescription. Univariate statistics were used to explore differences in patient demographics, comorbidities, and guideline-recommended opioid-monitoring practices by chronic pain and pain agreement status. Logistic regression was used to investigate predictors of agreement status. RESULTS: The clinic had 834 (9 percent) patients on chronic opioids, with 335 on a pain agreement. Documentation of opioid-monitoring practices was lacking. Logistic regression indicated that patients were significantly more likely to be on an agreement if they were Caucasian (adjusted odds ratio [OR] 2.17 [95% CI 1.41, 3.39]), had a baseline urine drug screen (adjusted OR 10.72 [95% CI 6.16, 19.41]), were prescribed a schedule II controlled medication (adjusted OR 11.92 [95% CI 6.93, 21.62]), and had risk assessed to some degree (adjusted OR 3.06 [95% CI 1.90, 4.96]). CONCLUSIONS: Aside from race, most patient characteristics were not predictive of pain agreement implementation. However, controlled medication of higher schedules and the use of certain guideline-recommended practices were associated with an agreement. Studies are needed to examine whether pain agreement or guideline-adherence influence clinical outcomes.

Nuquantus: Machine learning software for the characterization and quantification of cell nuclei in complex immunofluorescent tissue images.

Determination of fundamental mechanisms of disease often hinges on histopathology visualization and quantitative image analysis. Currently, the analysis of multi-channel fluorescence tissue images is primarily achieved by manual measurements of tissue cellular content and sub-cellular compartments. Since the current manual methodology for image analysis is a tedious and subjective approach, there is clearly a need for an automated analytical technique to process large-scale image datasets. Here, we introduce Nuquantus (Nuclei quantification utility software) - a novel machine learning-based analytical method, which identifies, quantifies and classifies nuclei based on cells of interest in composite fluorescent tissue images, in which cell borders are not visible. Nuquantus is an adaptive framework that learns the morphological attributes of intact tissue in the presence of anatomical variability and pathological processes. Nuquantus allowed us to robustly perform quantitative image analysis on remodeling cardiac tissue after myocardial infarction. Nuquantus reliably classifies cardiomyocyte versus non-cardiomyocyte nuclei and detects cell proliferation, as well as cell death in different cell classes. Broadly, Nuquantus provides innovative computerized methodology to analyze complex tissue images that significantly facilitates image analysis and minimizes human bias.

Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men.

Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known as the metabolic or insulin resistance syndrome. How obesity promotes insulin resistance remains incompletely understood. Plasma concentrations of free fatty acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and oxidative stress are all elevated in obesity and have been shown to induce insulin resistance. However, they may be late events that only develop after chronic excessive nutrient intake. The nature of the initial event that produces insulin resistance at the beginning of excess caloric intake and weight gain remains unknown. We show that feeding healthy men with ~6000 kcal/day of the common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 week produced a rapid weight gain of 3.5 kg and the rapid onset (after 2 to 3 days) of systemic and adipose tissue insulin resistance and oxidative stress but no inflammatory or ER stress. In adipose tissue, the oxidative stress resulted in extensive oxidation and carbonylation of numerous proteins, including carbonylation of GLUT4 near the glucose transport channel, which likely resulted in loss of GLUT4 activity. These results suggest that the initial event caused by overnutrition may be oxidative stress, which produces insulin resistance, at least in part, via carbonylation and oxidation-induced inactivation of GLUT4.