Associations of Race, Ethnicity, and Social Determinants of Health With Colorectal Cancer Screening.

BACKGROUND: Racial and ethnic disparities in receipt of recommended colorectal cancer screening exist; however, the impact of social determinants of health on such disparities has not been recently studied in a national cohort. OBJECTIVE: This study aimed to determine whether social determinants of health attenuate racial disparities in receipt of colorectal cancer screening. DESIGN: This was a cross-sectional telephone survey of self-reported race and ethnicity and up-to-date colorectal cancer screening. Associations between race/ethnicity and colorectal cancer screening were tested before and after adjustment for demographics, behavioral factors, and social determinants of health. SETTING: This was a nationally representative telephone survey of US residents in 2018. PATIENTS: The patients included were US residents aged 50 to 75 years. MAIN OUTCOME MEASURES: The primary outcome was up-to-date colorectal cancer screening status, according to 2008 US Preventive Services Task Force recommendations. RESULTS: This study included 226,106 respondents aged 50 to 75 years. Before adjustment, all minority racial and ethnic groups demonstrated a significantly lower odds of screening than those of non-Hispanic white respondents. After adjustment for demographics, behavioral factors, and social determinants of health, compared to non-Hispanic white respondents, odds of screening were found to be increased among non-Hispanic black respondents (OR, 1.10; p = 0.02); lower but attenuated among Hispanic respondents (OR, 0.73; p < 0.001), non-Hispanic American Indian/Alaskan Native respondents (OR, 0.85; p = 0.048), and non-Hispanic respondents of other races (OR, 0.82; p = 0.01); and lower but not attenuated among non-Hispanic Asian respondents (OR, 0.68; p < 0.001). LIMITATIONS: Recall bias, participant bias, and residual confounding. CONCLUSIONS: Adjustment for social determinants of health reduced racial and ethnic disparities in colorectal cancer screening among all minority racial and ethnic groups except non-Hispanic Asian individuals; however, other unmeasured confounders likely exist. See Video Abstract at http://links.lww.com/DCR/B977 . ASOCIACIN DE RAZA, ETNICIDAD Y DETERMINANTES SOCIALES DE LA SALUD CON LA DETECCIN DEL CNCER COLORRECTAL: ANTECEDENTES: Existen disparidades raciales y étnicas en la recepción de las pruebas recomendadas de detección de cáncer colorrectal; sin embargo, el impacto de los determinantes sociales de la salud en dichas disparidades no se ha estudiado recientemente en una cohorte nacional.OBJETIVO: El objetivo de este estudio fue determinar si los determinantes sociales de la salud atenúan las disparidades raciales en la recepción de pruebas de detección del cáncer colorrectal.DISEÑO: Encuesta telefónica transversal de raza y etnia autoinformada y detección actualizada de cáncer colorrectal. Las asociaciones entre la raza/etnicidad y la detección del cáncer colorrectal se probaron antes y después del ajuste por demografía, factores conductuales y determinantes sociales de la salud.ESCENARIO: Esta fue una encuesta telefónica representativa a nivel nacional de los residentes de EE. UU. en 2018.PACIENTES: Los pacientes eran residentes de EE. UU. de 50 a 75 años.PRINCIPALES MEDIDAS DE RESULTADO: Estado actualizado de detección de cáncer colorrectal, según las recomendaciones del Grupo de Trabajo de Servicios Preventivos de EE. UU. de 2008.RESULTADOS: Este estudio incluyó a 226.106 encuestados de 50 a 75 años. Antes del ajuste, todos los grupos étnicos y raciales minoritarios demostraron probabilidades significativamente más bajas de detección en comparación con los encuestados blancos no hispanos. Después del ajuste por demografía, factores conductuales y determinantes sociales de la salud, en comparación con los encuestados blancos no hispanos, las probabilidades de detección aumentaron entre los encuestados negros no hispanos (OR 1,10, p = 0,02); más bajo pero atenuado entre los encuestados hispanos (OR 0,73, p < 0,001), los encuestados indios americanos/nativos de Alaska no hispanos (OR 0,85, p = 0,048) y los encuestados no hispanos de otras razas (OR 0,82, p = 0,01); y menor pero no atenuado entre los encuestados asiáticos no hispanos (OR 0,68, p < 0,001).LIMITACIONES: Sesgo de recuerdo y sesgo de participante, así como confusión residual.CONCLUSIONES: El ajuste para los determinantes sociales de la salud redujo las disparidades raciales y étnicas en la detección del cáncer colorrectal entre todos los grupos étnicos y raciales minoritarios, excepto las personas asiáticas no hispanas; sin embargo, es probable que existan otros factores de confusión no medidos. Consulte Video Resumen en http://links.lww.com/DCR/B977 . (Traducción-Dr. Felipe Bellolio ).

Long-term surveillance of branch-duct intraductal papillary mucinous neoplasms without worrisome or high-risk features.

INTRODUCTION: Long-term data evaluating clinical outcomes in patients with branch-duct Intraductal papillary mucinous neoplasms (BD-IPMN) without high-risk stigmata (HRS) or worrisome features (WF) remain limited. METHODS: This observational cohort study included all patients diagnosed with BD-IPMN without HRS or WF between 2003 and 2019 who were enrolled in a prospective surveillance program. Time-to-progression analysis was performed using a cumulative incidence function plot and survival analysis was conducted using Kaplan-Meier. RESULTS: The median follow-up time for the 267 patient cohort was 44.5 months (interquartile range [IQR]: 24.1-72.2). Radiographic cyst growth was observed in 123 (46.1%) patients; 65 (24.3%) patients progressed to WF/HRS. Twenty-six (9.7%) patients were selected for resection during surveillance: 21 (80.8%) WF, 4 (15.4%) HRS; 1 (3.9%) transformed to mixed-duct. Of all the patients who underwent resection, 5 (19.2%) had adenocarcinoma, and 1 (3.8%) had carcinoma-in-situ. The probability of any radiographic progression was 21.3% (5-year) and 51.3% (10-year). For the entire cohort, there was 1.1% mortality secondary to pancreatic adenocarcinoma and 8.2% all-cause mortality. The 5-year overall survival rate was 91.5%, and at 10 years, 81.5%. CONCLUSION: Approximately one in four patients with nonworrisome BD-IPMN have progression to WF/HRS stigmata during surveillance. However, the risk of malignant transformation remains low. Surveillance strategy remains prudent in this patient population.

Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancers to treat. Due to the asymptomatic nature of the disease and lack of curative treatment modalities, the 5-y survival rate of PDAC patients is one of the lowest of any cancer type. The recurrent genetic alterations in PDAC are yet to be targeted. Therefore, identification of effective drug combinations is desperately needed. Here, we performed an in vivo CRISPR screen in an orthotopic patient-derived xenograft (PDX) model to identify gene targets whose inhibition creates synergistic tumor growth inhibition with gemcitabine (Gem), a first- or second-line chemotherapeutic agent for PDAC treatment. The approach revealed protein arginine methyltransferase gene 5 (PRMT5) as an effective druggable candidate whose inhibition creates synergistic vulnerability of PDAC cells to Gem. Genetic depletion and pharmacological inhibition indicate that loss of PRMT5 activity synergistically enhances Gem cytotoxicity due to the accumulation of excessive DNA damage. At the molecular level, we show that inhibition of PRMT5 results in RPA depletion and impaired homology-directed DNA repair (HDR) activity. The combination (Gem + PRMT5 inhibition) creates conditional lethality and synergistic reduction of PDAC tumors in vivo. The findings demonstrate that unbiased genetic screenings combined with a clinically relevant model system is a practical approach in identifying synthetic lethal drug combinations for cancer treatment.

Clinical Results of Mentor MemoryGel Xtra Breast Implants From the GLOW Clinical Trial.

BACKGROUND: Mentor MemoryGel Xtra breast implants (Mentor Worldwide LLC, Irvine, CA) were designed to maintain the soft, natural feel of MemoryGel implants while increasing fullness and projection and minimizing wrinkling, rippling, and related complications through optimization of shell gel-fill. OBJECTIVES: To measure 3-year safety and effectiveness of MemoryGel Xtra breast implants in the Mentor MemoryGel and MemoryShape Combined Cohort Clinical Study. METHODS: Participants were implanted with MemoryGel Xtra breast implants in a prospective, multicenter clinical trial. Rates of complications and reoperations were analyzed to assess device safety and BREAST-Q was employed to assess device effectiveness. RESULTS: Two hundred eighty-seven females receiving MemoryGel Xtra breast implants were enrolled. Complication rates in the primary augmentation cohort included rates of 1.5% for implant-related reoperation, 2.3% for explantation, and 1.5% for Baker grade III or IV capsular contracture. For the revisional augmentation cohort, these rates were 2.8% for implant-related reoperation, 4.3% for explantation, and 3.0% for capsular contracture. For the primary reconstruction cohort, these rates were 12.0% for implant-related reoperation, 12.3% for explantation, and 7.3% for capsular contracture. For the revisional reconstruction cohort, these rates were 7.1% for capsular contracture, with zero implant-related reoperations or explantations. There were no reports of infection or implant malposition or displacement in any of these cohorts. Each cohort showed significantly improved satisfaction with breasts and psychosocial and sexual well-being at 1 year following the primary procedure. CONCLUSIONS: These data are consistent with legacy clinical data for MemoryGel and provide the first published safety and effectiveness data regarding the use of MemoryGel Xtra breast implants for breast augmentation and reconstruction.

Perioperative Assessment and Optimization in Major Colorectal Surgery: Medication Management.

The colorectal surgeon is often faced with medications that can be challenging to manage in the perioperative period. In the era of novel agents for anticoagulation and immunotherapies for inflammatory bowel disease and malignancy, understanding how to advise patients about these medications has become increasingly complex. Here, we aim to provide clarity regarding the use of these agents and their perioperative management, with a particular focus on when to stop and restart them perioperatively. This review will begin with the management of both nonbiologic and biologic therapies used in the treatment of inflammatory bowel disease and malignancy. Then, discussion will shift to anticoagulant and antiplatelet medications, including their associated reversal agents. Upon finishing this review, the reader will have gained an increased familiarity with the management of common medications requiring modification by colorectal surgeons in the perioperative period.

A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer.

Checkpoint-blockade therapy (CBT) is approved for select colorectal cancer (CRC) patents, but additional immunotherapeutic options are needed. We hypothesized that vaccination with carcinoembryonic antigen (CEA) and Her2/neu (Her2) peptides would be immunogenic and well tolerated by participants with advanced CRC. A pilot clinical trial (NCT00091286) was conducted in HLA-A2+ or -A3+ Stage IIIC-IV CRC patients. Participants were vaccinated weekly with CEA and Her2 peptides plus tetanus peptide and GM-CSF emulsified in Montanide ISA-51 adjuvant for 3 weeks. Adverse events (AEs) were recorded per NIH Common Terminology Criteria for Adverse Events version 3. Immunogenicity was evaluated by interferon-gamma ELISpot assay of in vitro sensitized peripheral blood mononuclear cells and lymphocytes from the sentinel immunized node. Eleven participants were enrolled and treated; one was retrospectively found to be ineligible due to HLA type. All 11 participants were included in AEs and survival analyses, and the 10 eligible participants were evaluated for immunogenicity. All participants reported AEs: 82% were Grade 1-2, most commonly fatigue or injection site reactions. Two participants (18%) experienced treatment-related dose-limiting Grade 3 AEs; both were self-limiting. Immune responses to Her2 or CEA peptides were detected in 70% of participants. Median overall survival (OS) was 16 months; among those enrolled with no evidence of disease (n = 3), median OS was not reached after 10 years of follow-up. These data demonstrate that vaccination with CEA or Her2 peptides is well tolerated and immunogenic. Further study is warranted to assess potential clinical benefits of vaccination in advanced CRC either alone or in combination with CBT.

Incidence and Characterization of Rectal Complications From Fecal Management Systems.

BACKGROUND: Fecal management systems have become ubiquitous in hospitalized patients with fecal incontinence or severe diarrhea, especially in the setting of perianal wounds. Although fecal management system use has been shown to be safe and effective in initial series, case reports of rectal ulceration and severe bleeding have been reported, with a relative paucity of clinical safety data in the literature. OBJECTIVE: The purpose of this study was to determine the rate of rectal complications attributable to fecal management systems, as well as to characterize possible risk factors and appropriate management strategies for such complications. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a large academic medical center. PATIENTS: All medical and surgical patients who underwent fecal management system placement from December 2014 to March 2017 were included. MAIN OUTCOME MEASURES: We measured any rectal complication associated with fecal management system use, defined as any rectal injury identified after fecal management system use confirmed by lower endoscopy. RESULTS: A total of 629 patients were captured, with a median duration of fecal management system use of 4 days. Overall, 8 patients (1.3%) experienced a rectal injury associated with fecal management system use. All of the patients who experienced a rectal complication had severe underlying comorbidities, including 2 patients on dialysis, 1 patient with cirrhosis, and 3 patients with a recent history of emergent cardiac surgery. In 3 patients the bleeding resolved spontaneously, whereas the remaining 5 patients required intervention: transanal suture ligation (n = 2), endoscopic clip placement (n = 1), rectal packing (n = 1), and proctectomy in 1 patient with a history of pelvic radiotherapy. LIMITATIONS: The study was limited by its retrospective design and single institution. CONCLUSIONS: This is the largest study to date evaluating rectal complications from fecal management system use. Although rectal injury rates are low, they can lead to serious morbidity. Advanced age, severe comorbidities, pelvic radiotherapy, and anticoagulation status or coagulopathy are important factors to consider before fecal management system placement. See Video Abstract at http://links.lww.com/DCR/B698. INCIDENCIA Y CARACTERIZACIN DE LAS COMPLICACIONES RECTALES DE LOS SISTEMAS DE MANEJO FECAL: ANTECEDENTES:Los sistemas de manejo fecal se han vuelto omnipresentes en pacientes hospitalizados con incontinencia fecal o diarrea severa, especialmente en el contexto de heridas perianales. Aunque se ha demostrado que el uso del sistema de tratamiento fecal es seguro y eficaz en la serie inicial, se han notificado casos de ulceración rectal y hemorragia grave, con una relativa escasez de datos de seguridad clínica en la literatura.OBJETIVO:Determinar la tasa de complicaciones rectales atribuibles a los sistemas de manejo fecal. Caracterizar los posibles factores de riesgo y las estrategias de manejo adecuadas para tales complicaciones.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Centro médico académico de mayor volumen.PACIENTES:Todos los pacientes médicos y quirúrgicos que se sometieron a la colocación del sistema de manejo fecal desde diciembre de 2014 hasta marzo de 2017.PRINCIPALES MEDIDAS DE VALORACION:Cualquier complicación rectal asociada con el uso del sistema de manejo fecal, definida como cualquier lesión rectal identificada después del uso del sistema de manejo fecal confirmada por endoscopia baja.RESULTADOS:Se identificaron un total de 629 pacientes, con una duración media del uso del sistema de manejo fecal de 4,0 días. En general, 8 (1,3%) pacientes desarrollaron una lesión rectal asociada con el uso del sistema de manejo fecal. Todos los pacientes que mostraron una complicación rectal tenían comorbilidades subyacentes graves, incluidos dos pacientes en diálisis, un paciente con cirrosis y tres pacientes con antecedentes recientes de cirugía cardíaca emergente. En tres pacientes el sangrado se resolvió espontáneamente, mientras que los cinco pacientes restantes requirieron intervención: ligadura de sutura transanal (2), colocación de clip endoscópico (1), taponamiento rectal (1) y proctectomía en un paciente con antecedentes de radioterapia pélvica.LIMITACIONES:Diseño retrospectivo, institución única.CONCLUSIONES:Este es el estudio más grande hasta la fecha que evalúa las complicaciones rectales del uso del sistema de manejo fecal. Si bien las tasas de lesión rectal son bajas, pueden provocar una morbilidad grave. La edad avanzada, las comorbilidades graves, la radioterapia pélvica y el estado de anticoagulación o coagulopatía son factores importantes a considerar antes de la colocación del sistema de manejo fecal. Consulte Video Resumen en http://links.lww.com/DCR/B698.

Preoperative REM sleep is associated with complication development after colorectal surgery.

BACKGROUND: While total sleep duration and rapid eye movement (REM) sleep duration have been associated with long-term mortality in non-surgical cohorts, the impact of preoperative sleep on postoperative outcomes has not been well studied. METHODS: In this secondary analysis of a prospective observational cohort study, patients who recorded at least 1 sleep episode using a consumer wearable device in the 7 days before elective colorectal surgery were included. 30-day postoperative outcomes among those who did and did not receive at least 6 h of total sleep, as well as those who did and did not receive at least 1 h of rapid eye movement (REM) sleep, were compared. RESULTS: 34 out of 95 (35.8%) patients averaged at least 6 h of sleep per night, while 44 out of 82 (53.7%) averaged 1 h or more of REM sleep. Patients who slept less than 6 h had similar postoperative outcomes compared to those who slept 6 h or more. Patients who averaged less than 1 h of REM sleep, compared to those who achieved 1 h or more of REM sleep, had significantly higher rates of complication development (29.0% vs. 9.1%, P = 0.02), and return to the OR (10.5% vs. 0%, P = 0.04). After adjustment for confounding factors, increased REM sleep duration remained significantly associated with decreased complication development (increase in REM sleep from 50 to 60 min: OR 0.72, P = 0.009; REM sleep ≥ 1 h: OR 0.22, P = 0.03). CONCLUSION: In this cohort of patients undergoing elective colorectal surgery, those who developed a complication within 30 days were less likely to average at least 1 h of REM sleep in the week before surgery than those who did not develop a complication. Preoperative REM sleep duration may represent a risk factor for surgical complications; however additional research is necessary to confirm this relationship.

Wearable technology and the association of perioperative activity level with 30-day readmission among patients undergoing major colorectal surgery.

BACKGROUND: The proliferation of wearable technology presents a novel opportunity for perioperative activity monitoring; however, the association between perioperative activity level and readmission remains underexplored. This study sought to determine whether physical activity data captured by wearable technology before and after colorectal surgery can be used to predict 30-day readmission. METHODS: In this prospective observational cohort study of adults undergoing elective major colorectal surgery (January 2018 to February 2019) at a single institution, participants wore an activity monitor 30 days before and after surgery. The primary outcome was return to baseline percentage, defined as step count on the day before discharge as a percentage of mean preoperative daily step count, among readmitted and non-readmitted patients. RESULTS: 94 patients had sufficient data available for analysis, of which 16 patients (17.0%) were readmitted within 30 days following discharge. Readmitted patients achieved a lower return to baseline percentage compared to patients who were not readmitted (median 15.1% vs. 31.8%; P = 0.004). On multivariable analysis adjusting for readmission risk and hospital length of stay, an absolute increase of 10% in return to baseline percentage was associated with a 40% decreased risk of 30-day readmission (odds ratio 0.60; P = 0.02). Analysis of the receiver operating characteristic curve identified 28.9% as an optimal return to baseline percent threshold for predicting readmission. CONCLUSIONS: Achieving a higher percentage of an individual's preoperative baseline activity level on the day prior to discharge after major colorectal surgery is associated with decreased risk of 30-day hospital readmission.

Evaluating the Impact of Preoperative Geriatric-Specific Variables and Modified Frailty Index on Postoperative Outcomes After Elective Pancreatic Surgery.

BACKGROUND: Pursuing pancreatic resection in elderly patients is often complex and limited by concern for functional status and postoperative risk. This study examines the associations between two different preoperative functional status metrics with postoperative outcomes in the geriatric population. METHODS: Patients who participated in the ACS NSQIP Geriatric Surgery Research File pilot program (2014-2018) undergoing elective pancreatic operations were included. Two clinically meaningful functional status scores were calculated: the presence of one or more geriatric-specific variable (GSV) and a 5-factor modified frailty index (mFI-5). Multivariable logistic regression adjusting for ACS NSQIP-estimated risk was performed to evaluate associations between preoperative GSV, mFI-5 and 30-day outcome measures. RESULTS: A total of 1266 patients were included: 808 (64%) age 65-74, 302 (24%) age 75-80, and 156 (12%) age ≥ 81; 843 (67%) patients underwent pancreatoduodenectomy. Operations were performed for pancreatic adenocarcinoma in 712 (56%) patients. Older patients had greater likelihood of postoperative morbidity (35% vs 31% vs 47%, by age group, p = 0.004) and discharge to a facility (12% vs 23% vs 48%, by age group, p < 0.001). Adjusting for ACS NSQIP predicted risk, patients with a preoperative GSV were more likely to require reoperation and discharge to a facility (OR 1.81 [95% CI 1.03-3.16] and 3.95 [95% CI 2.91-5.38], respectively). The mFI-5 was not associated with postoperative outcomes (all p ≥ 0.18). CONCLUSION: The presence of a preoperative GSV is associated with reoperation and discharge to a skilled facility following elective pancreatic resection. Geriatric-specific variables should be considered in joint preoperative decision making to optimize care.

Efficacy of opioid spinal analgesia for postoperative pain management after pancreatoduodenectomy.

BACKGROUND: Efficacy of single-shot opioid spinal analgesia after pancreatoduodenectomy remains understudied and lacks comparison to standard continuous thoracic epidural analgesia (TEA). METHODS: Pancreatoduodenectomy patients who underwent TEA or opioid spinal for postoperative pain management from 2015 to 2020 were included in this observational cohort study. Primary outcome was patient-reported mean daily pain scores. Secondary outcomes included postoperative morphine milligram equivalents (MMEs) and length of stay (LOS). Multivariable linear regression models were constructed to compare risk-adjusted outcomes. RESULTS: 180 patients were included: 56 TEA and 124 opioid spinal. Compared to epidural patients, opioid spinal patients were more likely to be older (67.0 vs. 64.6, p=0.045), have greater BMI (26.5 vs. 24.4, p=0.02), and less likely to be smokers (19.4% vs. 41.1%, p=0.002). Opioid spinal, compared to TEA, was associated with lower intraoperative MMEs (0.25 vs. 22.7, p<0.001) and postoperative daily MMEs (7.9 vs. 10.3, p=0.03) on univariate analysis. However, after multivariable adjustment, there was no difference in average pain scores across the postoperative period (spinal vs. epidural: 4.18 vs. 4.14, p=0.93), daily MMEs (p=0.50), or LOS (p=0.23). DISCUSSION: There was no significant difference in postoperative pain scores, opioid use, or LOS between patients managed with TEA or opioid spinal after pancreatoduodenectomy.

A Surgeon Badge or Text Message Sign-in Intervention Improves Operating Room Start Efficiency.

BACKGROUND: Operating room (OR) efficiency, often measured by first case on-time start (FCOTS) percentage, is an important driver of perioperative team morale and the financial success of a hospital. MATERIALS AND METHODS: In this quasi-experimental study of elective surgical procedures at a single tertiary academic hospital, an intervention requiring attending surgeon attestation of availability via SMS text message or identification badge swipe was implemented. Key measures of OR efficiency were compared before and after the change. RESULTS: FCOTS percentage increased from 61.6% to 66.9% after the intervention (P = 0.01). After adjusting for patient and procedural characteristics, postintervention period remained associated with an increased odds of an on-time start (odds ratio 1.29, P = 0.01). Additionally, procedural start times from the pre- to postintervention period were significantly improved (-0.08 min/day, P = 0.009). CONCLUSIONS: Implementation of an attending surgeon text or badge sign-in process was associated with improved FCOTS percentage and earlier procedure start times.

Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer.

BACKGROUND: Childhood cancer survivors (CCS) are at elevated risk of secondary malignancies (SM). Enhanced screening for SM is recommended, but compliance is poor. We hypothesized that CCS with adult-onset SM (colorectal cancer [CRC], melanoma, or breast cancer [BC]) would present with more advanced disease and have decreased overall survival (OS). METHODS: The Surveillance, Epidemiology, and End Results Program was queried for patients diagnosed with cancer at age less than or equal to 18 also diagnosed with adult-onset CRC, melanoma, or BC. A cohort without a history of prior malignancy was likewise identified. Tumor features and clinical outcomes were compared. RESULTS: CCS with a SM (n = 224) were compared with patients without a childhood cancer history (n = 1,392,670). CCS were diagnosed younger (BC = 37.6 vs. 61.3, p < 0.01, CRC = 35.0 vs. 67.1, p < 0.01, melanoma = 29.6 vs. 61.3 years old, p < 0.01). CCS with BC were more likely to have Stage III or IV disease (25.2% vs. 16.5%, p = 0.01). Hormone-receptor expression also differed; CCS were less likely to develop Luminal A-type tumors (48.6% vs. 66.9%, p = 0.01). After age-adjustment, CCS had worse OS (Hazard ratio: CRC = 2.449, p < 0.01, melanoma = 6.503, p < 0.01, BC = 3.383, p < 0.01). CONCLUSION: CCS were younger when diagnosed with a SM. After age-adjustment, OS was diminished. Heightened surveillance may be necessary for CCS diagnosed with SM.

Management of Acute Anastomotic Leaks.

Management of the acute anastomotic leak is complex and patient-specific. Clinically stable patients often benefit from a nonoperative approach utilizing antibiotics with or without percutaneous drainage. Clinically unstable patients or nonresponders to conservative management require operative intervention. Surgical management is dictated by the degree of contamination and inflammation but includes drainage with proximal diversion, anastomotic resection with end-stoma creation, or reanastomosis with proximal diversion. Newer therapies, including colorectal stenting, vacuum-assisted rectal drainage, and endoscopic clipping, have also been described.

Diagnosis and Treatment of Rectal Gastrointestinal Stromal Tumors.

CASE SUMMARY: A 69-year-old man presented with a rectal mass that was noted on physical examination. Flexible sigmoidoscopy confirmed the presence of a well-defined mass 3 cm from the anal verge (). Magnetic resonance imaging of the pelvis identified a 5.8-cm heterogeneous mass with intersphincteric extension. Positron emission tomography-computed tomography revealed no evidence of distant metastatic disease. Endoscopic ultrasound (EUS) with fine-needle aspiration revealed a noncircumferential submucosal hypoechoic mass () with pathology significant for spindle cells staining positive for CD117, consistent with a GI stromal tumor (GIST). The patient received 5 months of neoadjuvant imatinib with great response () and subsequently underwent transanal endoscopic microsurgical resection. He continues on adjuvant imatinib and is currently without signs of recurrence at 18 months postprocedure; he is undergoing restaging CT chest/abdomen/pelvis and surveillance flexible sigmoidoscopy every 6 months.

Prognostic impact of postoperative low platelet count after liver transplantation.

BACKGROUND: The positive impact of platelets has been recently implicated in liver transplantation (LT). The aim of this study was to determine the risk factors for graft loss and mortality after LT, focusing on perioperative platelet counts. METHODS: We reviewed all deceased donor LT from 2000 to 2012 and enrolled 975 consecutive recipients. The risk factors for graft loss and mortality were analyzed by multivariate analysis, using Cox's regression model. RESULTS: Using cutoff values acquired by receiver operating characteristics curve analysis, multivariate analyses determined that viral hepatitis C (hazard ratio [HR]=1.32), donor age >40 (HR=1.33), higher peak serum alanine aminotransferase (HR=1.01), reoperation within 30 days (HR=1.51), and platelet count <72 500/µL on postoperative day (POD) 5 (HR=1.30) were independent risk factors for graft loss. Viral hepatitis C (HR=1.33), reoperation within 30 days (HR=1.35), and platelet count <72 500/µL on POD 5 (HR=1.38) were independent risk factors for mortality. CONCLUSION: A low platelet count on POD 5 was associated with graft loss and mortality after LT. Platelet count <72 500/µL on POD 5 can be a predictor of poor graft and overall survival. Maintaining higher postoperative platelet counts could potentially improve graft and overall survival rates.

Prediction of biliary anastomotic stricture after deceased donor liver transplantation: the impact of platelet counts - a retrospective study.

Biliary stricture is a common cause of morbidity after liver transplantation (LT). This study aimed to determine the risk factors for post-transplant biliary anastomotic strictures (BAS), focusing on perioperative platelet counts. We enrolled 771 consecutive recipients who underwent ABO-identical/compatible deceased donor LT with duct-to-duct biliary reconstruction from January 2000 to June 2012. BAS was identified in 142 cases. The median time for stricture development was 176 days. Preoperative and postoperative platelet counts within 5 days after LT were significantly lower in patients with BAS than those without BAS. Using cutoff values acquired by the receiver operating characteristic curve analysis, persistent postoperative thrombocytopenia was defined as platelet counts <41 × 1000/µl and <53 × 1000/µl on postoperative day (POD) 3 and POD 5, respectively. Multivariate analysis indicated persistent postoperative thrombocytopenia (OR = 2.38) was the only independent risk factor for BAS. No significant associations were observed in terms of donor and surgical factors. Multivariate analysis demonstrated estimated blood loss (OR = 1.01, per 100 ml) was an independent contributing factor for persistent postoperative thrombocytopenia. We demonstrated low platelet count was associated with progression of post-transplant BAS. Minimizing intraoperative blood loss potentially contributes to maintain post-transplant platelet count, which may reduce incidence of BAS.

Phosphatidylserine and FVa regulate FXa structure.

Human coagulation FXa (Factor Xa) plays a key role in blood coagulation by activating prothrombin to thrombin on 'stimulated' platelet membranes in the presence of its cofactor FVa (Factor Va). PS (phosphatidylserine) exposure on activated platelet membranes promotes prothrombin activation by FXa by allosterically regulating FXa. To identify the structural basis of this allosteric regulation, we used FRET to monitor changes in FXa length in response to (i) soluble short-chain PS [C6PS (dicaproylphosphatidylserine)], (ii) PS membranes, and (iii) FVa in the presence of C6PS and membranes. We incorporated a FRET pair with donor (fluorescein) at the active site and acceptor (Alexa Fluor® 555) at the FXa N-terminus near the membrane. The results demonstrated that FXa structure changes upon binding of C6PS to two sites: a regulatory site at the N-terminus [identified previously as involving the Gla (γ-carboxyglutamic acid) and EGFN (N-terminus of epidermal growth factor) domains] and a presumptive protein-recognition site in the catalytic domain. Binding of C6PS to the regulatory site increased the interprobe distance by ~3 Å (1 Å=0.1 nm), whereas saturation of both sites increased the distance by a further ~6.4 Å. FXa binding to a membrane produced a smaller increase in length (~1.4 Å), indicating that FXa has a somewhat different structure on a membrane from when bound to C6PS in solution. However, when both FVa2 (a FVa glycoform) and either C6PS- or PS-containing membranes were bound to FXa, the overall change in length was comparable (~5.6-5.8 Å), indicating that C6PS- and PS-containing membranes in conjunction with FVa2 have comparable regulatory effects on FXa. We conclude that the similar functional regulation of FXa by C6PS or membranes in conjunction with FVa2 correlates with similar structural regulation. The results demonstrate the usefulness of FRET in analysing structure-function relationships in FXa and in the FXa·FVa2 complex.