Novel Characterization of Socioecological Determinants of Health in Rural Alabama.

INTRODUCTION: Socioecological determinants of health (SEDOHs) influence disparities in surgical outcomes. However, SEDOHs are challenging to measure, limiting our ability to address disparities. Using a validated survey (SEDOH-88), we assessed SEDOHs in three rural communities in Alabama. We hypothesized that SEDOHs would vary significantly across sites but measuring them would be acceptable and feasible. MATERIALS AND METHODS: This was a retrospective review of a prospectively maintained database involving surgical patients who completed the SEDOH-88 and a secondary survey assessing it's acceptability or feasibility from August 2021 to July 2023. Included patients underwent endoscopic, minimally invasive, or open surgery at three rural hospitals: Demopolis (DM), Alexander City (AC), and Greenville (GV). RESULTS: The 107 participants comprised 48 (44.9%) from DM, 27 (25.2%) from AC, and 32 (29.9%) from GV, respectively. The median age was 64 y, and 65.6% were female. When comparing DM to AC and GV by individual factors, DM had the largest Black population (78.7 versus 22.2 versus 48.3%, P < 0.001) and more often required help reading hospital materials (20.5 versus 3.7 versus 10.3%, P = 0.007). When comparing DM to AC and GV by structural and environmental factors, DM had more Medicaid enrollees (27.3 versus 3.7 versus 6.9%, P = 0.033) and lacked fresh produce (18.2 versus 25.9 versus 39.3%, P = 0.033) and internet access (63.6 versus 100.0 versus 86.2%, P < 0.001). The SEDOH-88 had an overall 90.9% positive acceptability and feasibility score. CONCLUSIONS: SEDOHs varied significantly across rural communities regarding individual (race or health literacy), structural (insurance), and environmental-level factors (nutritious food or internet access). The high acceptability and feasibility of the SEDOH-88 shows it's potential utility in identifying targets for future disparity-reducing interventions.

Disparities in Perioperative Use of Patient Engagement Technologies - Not All Use is Equal.

OBJECTIVE: To determine the association of patient-level characteristics on the use of a patient engagement technology during the perioperative period. SUMMARY OF BACKGROUND DATA: As implementation of patient engagement technologies continues to grow, it remains unclear who uses, and not uses, these technologies. Existing literature suggests significant disparities in usage of other technologies by patient age, race, sex, and geographic location, however, have yet to characterize patient usage of patient engagement technologies. METHODS: This is a retrospective cohort study of patients undergoing elective surgery by a colorectal surgeon between January 2018 and March 2020 who enrolled in a patient engagement technology at a single institution. Patients enrolled received educational content, healthcare reminders, patient reported outcome (PRO) surveys, and health checks preoperatively, in-hospital, and for 30-days postdischarge. The primary outcome was patient activation of the patient engagement technology. Secondary outcomes were completion of at least 1 PRO survey, 1 in-hospital health check, and 1 postdischarge health check. RESULTS: Of 549 patients who enrolled in the patient engagement technology, 473 (86.2%) activated. On multivariable stepwise regression, female patients [odds ratio (OR) 2.4, confidence interval (CI) 1.4-4.0, P = 0.001] and privately insured patients (OR 2.0, CI 1.1-3.8, P = 0.03) were more likely to activate. Black patients were less likely to activate (OR 0.5, CI 0.3-0.9, P = 0.02). Once activated, privately insured patients were more likely to complete PRO surveys (OR 2.3, CI 1.2-4.3, P = 0.01), in-hospital health checks (OR 2.4, CI 1.4-4.1, P = 0.002), and postdischarge health checks (OR 1.9, CI 1.1 -3.3, P < 0.001) than uninsured patients. Black patients were less likely to complete PRO surveys (OR 0.4, CI 0.3-0.7, P = 0.001) and in-hospital health checks (OR 0.6, CI 0.4-0.9, P = 0.03) than White patients. CONCLUSIONS: Use of a patient engagement technology in the perioperative period differs significantly by sex, race/ethnicity, and insurance status. These technologies may not be used equally by all patients, which should be considered during implementation of interventions to improve surgical outcomes.

AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch.

Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in ILC22 cells that resulted in less secretion of IL-22 and inadequate protection against intestinal bacterial infection. Ahr(-/-) mice also lacked postnatally 'imprinted' cryptopatches and isolated lymphoid follicles (ILFs), but not embryonically 'imprinted' Peyer's patches. AHR induced the transcription factor Notch, which was required for NKp46(+) ILCs, whereas LTi-like ILCs, cryptopatches and ILFs were partially dependent on Notch signaling. Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues.

Prospective validation of tumor folate receptor expression density with the association of pafolacianine fluorescence during intraoperative molecular imaging-guided lung cancer resections.

PURPOSE: Pafolacianine, a folate receptor alpha-targeted NIR tracer, has demonstrated clear efficacy in intraoperative molecular imaging-guided (IMI) lung cancer surgery. However, the selection of patients who would benefit from IMI remains challenging given the variability of fluorescence with patient-associated and histopathologic factors. Our goal in this study was to prospectively evaluate whether preoperative FRα/FRß staining can predict pafolacianine-based fluorescence during real-time lung cancer resections. METHODS: This was a prospective study conducted between 2018 and 2022 that reviewed core biopsy and intraoperative data from patients with suspected lung cancer. A total of 196 patients were deemed eligible, of whom core biopsies were taken from 38 patients and assessed for FRα and FRß expression by immunohistochemistry (IHC). All patients underwent infusion of pafolacianine 24 h prior to surgery. Intraoperative fluorescence images were captured with the VisionSense bandpass filter-enabled camera. All histopathologic assessments were performed by a board-certified thoracic pathologist. RESULTS: Of the 38 patients, 5 (13.1%) were found to have benign lesions (necrotizing granulomatous inflammation, lymphoid aggregates) and 1 had metastatic non-lung nodule. Thirty (81.5%) had malignant lesions, with the vast majority (23, 77.4%) being lung adenocarcinoma (7 (22.5%) SCC). None of the benign tumors (0/5, 0%) exhibited in vivo fluorescence (mean TBR of 1.72), while 95% of the malignant tumors fluoresced (mean TBR of 3.11 ± 0.31) compared to squamous cell carcinoma (1.89 ± 0.29) of the lung and sarcomatous lung metastasis (2.32 ± 0.09) (p < 0.01). The TBR was significantly higher in the malignant tumors (p = 0.009). The median FRα and FRß staining intensities were both 1.5 for benign tumors, while the FRα and FRß staining intensities were 3 and 2 for malignant tumors, respectively. Increased FRα expression was significantly associated with the presence of fluorescence (p = 0.01), CONCLUSION: This prospective study sought to determine whether preoperative FRα and FRß expression on core biopsy IHC correlates with intraoperative fluorescence during pafolacianine-guided surgery. These results, although of small sample size, including limited non-adenocarcinoma cohort, suggest that performing FRα IHC on preoperative core biopsies of adenocarcinomas as compared to squamous cell carcinomas could provide low-cost, clinically useful information for optimal patient selection which should be further explored in advanced clinical trials.

Preclinical Evaluation of an Activity-Based Probe for Intraoperative Imaging of Esophageal Cancer.

Background: Early detection and complete resection are important prognostic factors for esophageal cancer (EC). Intraoperative molecular imaging (IMI) using tumor-targeted tracers is effective in many cancer types. However, there are no EC-specific IMI tracers. We sought to test a cathepsin activity-based tracer (VGT-309) for EC resection. Methods: Murine (AKR, HNM007) and human (OE19) EC cell lines were screened for cathepsin expression by western blotting. In vitro binding affinity of VGT-309 was evaluated by fluorescence microscopy. Flank tumor models were developed by injecting EC cells into the flanks of BALB/c or athymic nude mice. Mice pretreated with a cathepsin inhibitor (JPM-OEt) were used to confirm on target binding. Animals were injected with 2 mg/kg VGT-309, underwent IMI, and were sacrificed 24 hours after injection. Results: Cathepsins B, L, S, and X were expressed by EC cell lines, and all cell lines were labeled in vitro with VGT-309. Fluorescent signal was eliminated when cells were pretreated with JPM-OEt. On biodistribution analysis, VGT-309 accumulated in the liver, kidneys, and spleen without other organ involvement. VGT-309 selectively accumulated in flank allografts and xenografts, with mean signal-to-background ratio of 5.21 (IQR: 4.18-6.73) for flank allografts and 4.34 (IQR: 3.75-5.02) for flank xenografts. Fluorescence microscopy and histopathological analysis confirmed the selective accumulation of the tracer in tumors compared to background normal tissues. Conclusions: VGT-309 is an effective tracer for IMI of esophageal cancer. There is potential for clinical translation both as an adjunct to endoscopic detection and for complete removal of disease during esophagectomy.

Comparative Experience of Short-wavelength Versus Long-wavelength Fluorophores for Intraoperative Molecular Imaging of Lung Cancer.

BACKGROUND: Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve cancer resections. The optimal wavelength of the IMI tracer fluorophore has never been studied in humans and has major implications for the field. To address this question, we investigated 2 spectroscopically distinct fluorophores conjugated to the same targeting ligand. METHODS: Between December 2011 and November 2021, patients with primary lung cancer were preoperatively infused with 1 of 2 folate receptor-targeted contrast tracers: a short-wavelength folate-fluorescein (EC17; λ em =520 nm) or a long-wavelength folate-S0456 (pafolacianine; λ em =793 nm). During resection, IMI was utilized to identify pulmonary nodules and confirm margins. Demographic data, lesion diagnoses, and fluorescence data were collected prospectively. RESULTS: Two hundred eighty-two patients underwent resection of primary lung cancers with either folate-fluorescein (n=71, 25.2%) or pafolacianine (n=211, 74.8%). Most tumors (n=208, 73.8%) were invasive adenocarcinomas. We identified 2 clinical applications of IMI: localization of nonpalpable lesions (n=39 lesions, 13.8%) and detection of positive margins (n=11, 3.9%). In each application, the long-wavelength tracer was superior to the short-wavelength tracer regarding depth of penetration, signal-to-background ratio, and frequency of event. Pafolacianine was more effective for detecting subpleural lesions (mean signal-to-background ratio=2.71 vs 1.73 for folate-fluorescein, P <0.0001). Limit of signal detection was 1.8 cm from the pleural surface for pafolacianine and 0.3 cm for folate-fluorescein. CONCLUSIONS: Long-wavelength near-infrared fluorophores are superior to short-wavelength IMI fluorophores in human tissues. Therefore, future efforts in all human cancers should likely focus on long-wavelength agents.

Disparities in Surgical Timing and Guideline-Adherent Staging Work-Up for Colon Cancer.

BACKGROUND: Expedited or delayed surgery for colon cancer without appropriate work-up increases mortality risk. We sought to identify what patient, social, and hospital factors were associated with timely, guideline-adherent work-up for colon cancer. METHODS: Retrospective analysis of 19,046 patients in the Surveillance, Epidemiology, and End Results (SEER) database linked with Medicare administrative claims who underwent elective surgery for colon cancer between 2010 and 2015 was performed. Primary outcome was receipt of complete preoperative work-up (colonoscopy, imaging, tumor marker evaluation) and timely surgery within 60 days of diagnosis. Patients were stratified into four groups: (1) adherent; (2) early surgery (< 30 days) with incomplete work-up; (3) surgery between 30 and 60 days with incomplete work-up; and (4) late surgery (> 60 days) with/without work-up. Characteristics were compared and multinomial logistic regression was performed. RESULTS: Overall, 46.2% of patients received adherent care, 33.1% had early surgery and inadequate work-up, 10.3% had appropriately timed surgery but incomplete work-up, and 10.4% underwent late surgery. Multivariable analysis demonstrated that older, female, Black, and unmarried patients as well as patients living in areas with higher rates of poverty were more likely to receive non-adherent care. A greater proportion of patients at teaching hospitals received complete work-up (57.6% vs. 49.5%) but also underwent late surgery (12.4% vs. 8.6%) compared with non-teaching hospitals. CONCLUSIONS: Patient, societal, and hospital factors impact whether patients receive guideline-adherent colon cancer care. Interventions are needed to improve access to timely and guideline-adherent cancer care as a possible mechanism to combat surgical disparities.

Presence of non-Newtonian fluid in invasive pulmonary mucinous adenocarcinomas impacts fluorescence during intraoperative molecular imaging of lung cancer.

BACKGROUND: Intraoperative molecular imaging (IMI) with folate-targeted NIR tracers has been shown to improve lesion localization in more than 80% of lung adenocarcinomas. However, mucinous adenocarcinomas (MAs) and invasive mucinous adenocarcinomas (IMAs) of the lung, which are variants of adenocarcinoma, appear to have decreased fluorescence despite appropriate folate receptor expression on the tumor surface. We hypothesized that the etiology may be related to light excitation and emission through non-Newtonian fluid (mucin) produced by goblet and columnar cancer cells. METHODS: Intraoperative data for 311 subjects were retrospectively reviewed from a prospectively collected 6-year database. For standardization, all patients underwent infusion of the same targeted molecular optical contrast agent (pafolacianine, folate receptor-targeted NIR fluorochrome) for lung cancer resections. Then, the ratio of the mean fluorescence intensity of the tumors and background tissues (TBR) was calculated. Tumors were examined for mucin, FRa, FRb, and immunofluorescent tracer uptake by a board-certified pathologist. The optical properties of mucin analyzed by imaging software were used to create in vitro gel models to explore the effects on NIR tracer fluorescence intensity. RESULTS: A large proportion (192, 62%) of the patients were female, with an average of 62.8 years and a 34-year mean pack smoking history. There were no severe (Clavien-Dindo > III) complications related to pafolacianine infusion. A total of 195 lesions in the study were adenocarcinomas, of which 19 (6.1%) were of the mucinous subtype. A total of 14/19 of the patients had a smoking history, and more than 74% of the IMA lesions were in the lower lobes. IMA lesions had a lower in situ TBR than nonmucinous adenocarcinomas (2.64 SD 0.23) vs (3.45 SD 0.11), respectively (p < 0.05). Only 9/19 (47%) were localized in situ. Tumor bisection and removal of mucin from IMAs significantly increased pafolacianine fluorescence, with resultant TBR not being significantly different from the control group (4.67 vs 4.89) (p = 0.19). Of the 16 lesions that underwent FR expression analysis, 15/16 had FR presence on cancer cells or tumor-associated macrophages in the tumor microenvironment. There was no statistically significant difference in fluorescence intensity during immunofluorescence analysis (4.99 vs 5.08) (p = 0.16). Physical removal of mucin from IMAs improved the TBR from 3.11 to 4.67 (p < 0.05). In vitro analysis of the impact of synthetic non-Newtonian fluid (agarose 0.5%) on NIR tracer fluorescence showed a decrease in MFI by a factor of 0.25 regardless of the concentration for each 5 mm thickness of mucin. CONCLUSION: The mucinous subtype of lung adenocarcinomas presents a unique challenge in pafolacianine-targeted IMI-guided resections. The presence of non-Newtonian fluids presents a physical barrier that dampens the excitation of the tracer and fluorescence emission detected by the camera. Knowledge of this phenomenon can allow the surgeon to critically analyze lesion fluorescence parameters during IMI-guided lung cancer resections.

Targeted detection of cancer cells during biopsy allows real-time diagnosis of pulmonary nodules.

BACKGROUND: The diagnostic yield of biopsies of solitary pulmonary nodules (SPNs) is low, particularly in sub-solid lesions. We developed a method (NIR-nCLE) to achieve cellular level cancer detection during biopsy by integrating (i) near-infrared (NIR) imaging using a cancer-targeted tracer (pafolacianine), and (ii) a flexible NIR confocal laser endomicroscopy (CLE) system that can fit within a biopsy needle. Our goal was to assess the diagnostic accuracy of NIR-nCLE ex vivo in SPNs. METHODS: Twenty patients with SPNs were preoperatively infused with pafolacianine. Following resection, specimens were inspected to identify the lesion of interest. NIR-nCLE imaging followed by tissue biopsy was performed within the lesion and in normal lung tissue. All imaging sequences (n = 115) were scored by 5 blinded raters on the presence of fluorescent cancer cells and compared to diagnoses by a thoracic pathologist. RESULTS: Most lesions (n = 15, 71%) were adenocarcinoma-spectrum malignancies, including 7 ground glass opacities (33%). Mean fluorescence intensity (MFI) by NIR-nCLE for tumor biopsy was 20.6 arbitrary units (A.U.) and mean MFI for normal lung was 6.4 A.U. (p < 0.001). Receiver operating characteristic analysis yielded a high area under the curve for MFI (AUC = 0.951). Blinded raters scored the NIR-nCLE sequences on the presence of fluorescent cancer cells with sensitivity and specificity of 98% and 97%, respectively. Overall diagnostic accuracy was 97%. The inter-observer agreement of the five raters was excellent (κ = 0.95). CONCLUSIONS: NIR-nCLE allows sensitive and specific detection of cancer cells in SPNs. This technology has far-reaching implications for diagnostic needle biopsies and intraprocedural decision-making.

Early Elective Surgery After Colon Cancer Diagnosis has Higher Risk of Readmission and Death.

OBJECTIVE: We hypothesized colon resection within 30 days of diagnosis of cancer would have higher rates of readmission and cancer specific mortality, unless there was demonstrated evidence of preoperative workup. SUMMARY BACKGROUND DATA: Few studies have examined if negative consequences exist with expedited elective surgery after diagnosis of colon cancer. Surgery in a shorter time frame may result in a lack of appropriate preoperative care. METHODS: Retrospective analysis of 25,407 patients in the Surveillance Epidemiology and End Results registry who underwent elective surgical resection for colon cancer from 2010 to 2015. Cohort stratified by age (66-75 vs >75 years). Primary outcomes of interest were 30-day readmission and 5-year colon cancer specific mortality. Relationships between timing of surgery and outcomes were assessed. RESULTS: On unadjusted analysis, surgery before 20 days of diagnosis was associated with higher risk of 30-day readmission and colon cancer specific mortality in both age groups. Among those age 66 to 75 years old, adjusting for patient factors and preoperative workup eliminated the risk of 30-day readmission (risk ratio 1.5-0.9 for 0-10 days, risk ratio 1.3-0.9 for 11-20 days). However, the risk for colon cancer specific mortality, although reduced, persisted (hazard ratio 2.2-1.3 for 0-10 days, hazard ratio 2.0-1.2 for 11-20 days). In the cohort older than 75 years, adjusting for patient level factors and preoperative workup eliminated risk of surgery 20 days postop or sooner. CONCLUSIONS: The risk associated with short time to surgery (within 30 days) may be mitigated if full oncologic workups are provided.

Preoperative Tamsulosin to Prevent Postoperative Urinary Retention: A Randomized Controlled Trial.

BACKGROUND: The purpose of this study was to evaluate the efficacy of tamsulosin, administered preoperatively, for the prevention of postoperative urinary retention (POUR). POUR is a common complication of abdominal surgery, leading to the use of urinary catheters, which are a risk factor for urinary tract infection. Tamsulosin is a uroselective alpha-1a blocker used for the treatment of lower urinary tract symptoms. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was undertaken from August 2015 to May 2018. Adults undergoing elective inpatient abdominal surgery were randomized to receive either tamsulosin 0.4 mg or placebo daily for 7 d before surgery and continuing for up to 7 d postoperatively. The primary outcome was need for at least a single intermittent catheterization postoperatively. Secondary outcomes included first postvoid residual volume, number of catheterizations, need for replacement of an indwelling catheter, hospital length of stay, and urinary tract infection within 30 d of surgery. RESULTS: A total of 158 participants were enrolled, with a final analytic cohort of 141 participants. The two groups had similar baseline characteristics, operative characteristics, and timing of catheter removal. There was no difference in the incidence of POUR between the two groups (26% in tamsulosin versus 31% in placebo, P = 0.49). There was also no difference in any of the secondary outcomes between the two groups. Epidural usage, open surgery, and age <50 were identified as risk factors for POUR. CONCLUSIONS: Perioperative prophylaxis with tamsulosin is not effective in reducing the incidence of POUR in patients undergoing elective abdominal surgery.

Optimization of xylitol production from xylose by a novel arabitol limited co-producing Barnettozyma populi NRRL Y-12728.

Xylitol is a widely marketed sweetener with good functionality and health-promoting properties. It can be synthetized by many yeast species in a one-step reduction of xylose. Arabinose is a common contaminant found in xylose and there is ongoing interest in finding biocatalysts that selectively produce xyltiol. From a screen of 99 yeasts, Barnettozyma populi Y-12728 was found to selectively produce xylitol from both mixed sugars and corn stover hemicellulosic hydrolysate. Here, fermentation conditions for xylitol production from xylose by B. populi were optimized. The medium for xylitol production was optimized through response surface methodology. The yeast produced 31.2 ± 0.4 g xylitol from xylose (50 g L-1) in 62 h using the optimized medium. The optimal pH for xylitol production was 6.0. Glucose (10 g L-1), acetic acid (6.0 g L-1), HMF (4 mM) and ethanol (2.0 g L-1) inhibited the xylitol production. The glucose inhibition was entirely mitigated by using a 2-stage aeration strategy, indicating that the yeast was inhibited by ethanol produced from glucose under low aeration. This culture strategy will greatly benefit xylitol production from hemicellulosic hydrolysates, which often contain glucose. This is the first report on optimization of xylitol production by a Barnettozyma species.

The Association of Enhanced Recovery Pathway and Acute Kidney Injury in Patients Undergoing Colorectal Surgery.

BACKGROUND: Acute kidney injury is associated with increased postoperative length of hospital stay and increases the risk of postoperative mortality. The association between the development of postoperative acute kidney injury and the implementation of an enhanced recovery after surgery protocol remains unclear. OBJECTIVE: This study aimed to examine the relationship between the implementation of an enhanced recovery pathway and the development of postoperative acute kidney injury. DESIGN: In this retrospective cohort study, a prospectively maintained database of patients who underwent elective colorectal surgery in an enhanced recovery pathway were compared to a hospital historical National Surgical Quality Improvement Program colorectal registry of patients. SETTINGS: This study was conducted at the University of Alabama at Birmingham, a tertiary referral center. PATIENTS: A total of 1052 patients undergoing elective colorectal surgery from 2012 through 2016 were included. MAIN OUTCOME MEASURES: The development of postoperative acute kidney injury was the primary outcome measured. RESULTS: Patients undergoing an enhanced recovery pathway had significantly greater rates of postoperative acute kidney injury than patients not undergoing an enhanced recovery pathway (13.64% vs 7.08%; p < 0.01). Our adjusted model indicated that patients who underwent an enhanced recovery pathway (OR, 2.31; 95% CI, 1.48-3.59; p < 0.01) had an increased risk of acute kidney injury. Patients who developed acute kidney injury in the enhanced recovery cohort had a significantly longer median length of stay than those who did not (median 4 (interquartile range, 4-9) vs 3 (interquartile range, 2-5) days; p=0.04). LIMITATIONS: This study did not utilize urine output as a modality for detecting acute kidney injury. Data are limited to a sample of patients from a large academic medical center participating in the National Surgical Quality Improvement Program. Interventions or programs in place at our institution that aimed at infection reduction or other initiatives with the goal of improving quality were not accounted for in this study. CONCLUSION: The implementation of an enhanced recovery after surgery protocol is independently associated with the development of postoperative acute kidney injury.See Video Abstract at http://links.lww.com/DCR/B69. LA ASOCIACIÓN DE VÍA DE RECUPERACIÓN MEJORADA Y LESIÓN RENAL AGUDA EN PACIENTES DE CIRUGÍA COLORRECTAL: La lesión renal aguda se asocia con una mayor duración en la estancia hospitalaria y aumenta el riesgo de la mortalidad postoperatoria. La asociación entre el desarrollo de la lesión renal aguda postoperatoria y la implementación de un protocolo de Recuperación Mejorada después de la cirugía, sigue sin ser clara.Examinar la relación entre la implementación de una vía de Recuperación Mejorada y el desarrollo de lesión renal aguda postoperatoria.Estudio de cohorte retrospectivo, de una base de datos mantenida prospectivamente, de pacientes que se sometieron a cirugía colorrectal electiva, en una vía de Recuperación Mejorada, se comparó con el registro histórico de los pacientes colorrectales del Programa Nacional de Mejora de la Calidad Quirúrgica.Universidad de Alabama en Birmingham, un centro de referencia terciario.Un total de 1052 pacientes sometidos a cirugía colorrectal electiva desde 2012 hasta 2016.Desarrollo de lesión renal aguda postoperatoria.Los pacientes sometidos a una vía de Recuperación Mejorada, tuvieron tasas significativamente mayores de lesiones renales agudas postoperatorias, en comparación con los pacientes de Recuperación no Mejorada (13.64% vs 7.08%; p < 0.01). Nuestro modelo ajustado indicó que los pacientes que se sometieron a una vía de Recuperación Mejorada (OR, 2.31; IC, 1.48-3.59; p < 0.01) tuvieron un mayor riesgo de lesión renal aguda. Los pacientes que desarrollaron daño renal agudo en la cohorte de Recuperación Mejorada, tuvieron una estadía mediana significativamente más larga en comparación con aquellos que no [mediana 4 (rango intercuartil (RIC) 4-9) versus 3 (RIC 2-5) días; p = 0.04].Este estudio no utilizó la producción de orina como una modalidad para detectar daño renal agudo. Los datos se limitan a una muestra de pacientes de un gran centro médico académico, que participa en el Programa Nacional de Mejora de la Calidad Quirúrgica. Las intervenciones o programas implementados en nuestra institución, destinados a la reducción de infecciones u otras iniciativas, con el objetivo de mejorar la calidad, no se tomaron en cuenta para este estudio.La implementación de una Recuperación Mejorada después del protocolo de cirugía, se asocia independientemente con el desarrollo de lesión renal aguda postoperatoria.Consulte Video Resumen en http://links.lww.com/DCR/B69. (Traducción-Dr. Fidel Ruiz-Healy).

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

BACKGROUND: A major roadblock to reducing the mortality of colorectal cancer (CRC) is prompt detection and treatment, and a simple blood test is likely to have higher compliance than all of the current methods. The purpose of this report is to examine the utility of a mass spectrometry-based blood serum protein biomarker test for detection of CRC. MATERIALS AND METHODS: Blood was drawn from individuals (n = 213) before colonoscopy or from patients with nonmetastatic CRC (n = 50) before surgery. Proteins were isolated from the serum of patients using targeted liquid chromatography-tandem mass spectrometry. We designed a machine-learning statistical model to assess these proteins. RESULTS: When considered individually, over 70% of the selected biomarkers showed significance by Mann-Whitney testing for distinguishing cancer-bearing cases from cancer-free cases. Using machine-learning methods, peptides derived from epidermal growth factor receptor and leucine-rich alpha-2-glycoprotein 1 were consistently identified as highly predictive for detecting CRC from cancer-free cases. A five-marker panel consisting of leucine-rich alpha-2-glycoprotein 1, epidermal growth factor receptor, inter-alpha-trypsin inhibitor heavy-chain family member 4, hemopexin, and superoxide dismutase 3 performed the best with 70% specificity at over 89% sensitivity (area under the curve = 0.86) in the validation set. For distinguishing regional from localized cancers, cross-validation within the training set showed that a panel of four proteins consisting of CD44 molecule, GC-vitamin D-binding protein, C-reactive protein, and inter-alpha-trypsin inhibitor heavy-chain family member 3 yielded the highest performance (area under the curve = 0.75). CONCLUSIONS: The minimally invasive blood biomarker panels identified here could serve as screening/detection alternatives for CRC in a human population and potentially useful for staging of existing cancer.

Postoperative Complications After Colorectal Surgery: Where Are We in the Era of Enhanced Recovery?

PURPOSE OF REVIEW: Individual elements in enhanced recovery pathways may be associated with specific complication risks. In this review, we highlight three areas of controversy surrounding complications in enhanced recovery: (1) whether enhanced recovery is associated with increased rates of acute kidney injury, (2) whether NSAID use is associated with anastomotic leaks, and (3) whether early urinary catheter removal is justified following colorectal surgery. RECENT FINDINGS: Acute kidney injury has been reported at several institutions following implementation of enhanced recovery pathways highlighting the importance of institutional data tracking. NSAID use has been implicated in anastomotic leak rates for non-elective colorectal procedures, and criteria for its use should be implemented. Early urinary catheter removal has been supported despite increased urinary retention rates in order to decrease urinary tract infections. Enhanced recovery protocols will continue to evolve, and risk profiles associated with individual elements should continue to be evaluated.

Panitumumab-IRDye800CW for Fluorescence-Guided Surgical Resection of Colorectal Cancer.

BACKGROUND: Fluorescence-guided surgery (FGS) is a rapidly advancing field that may improve outcomes in several cancer types. Although screening has decreased colorectal cancer (CRC) mortality, it remains a common and often fatal malignancy. In this study, we sought to identify an optical imaging agent for the application of FGS technology to CRC. METHODS: We compared a panitumumab-IRDye800CW conjugate to an IgG-IRDye800CW isotype control. Mice were implanted with one of three CRC cell lines (LS174T, Colo205, and SW948) and imaged with open- and closed-filed fluorescence imaging systems. Fluorescent contrast was quantified by calculating the ratio between tumor and background fluorescence. After 10 d, the mice were sacrificed, and their tumors stained for microscopic imaging. RESULTS: Panitumumab-IRDye800CW produced significantly greater (P < 0.05) fluorescent contrast in all three cell lines. Average tumor to background ratio was 6.00 versus 2.60 for LS174T, 5.78 versus 2.52 for Colo205, and 4.31 versus 1.70 for SW948. A 1-mg tumor fragment produced significantly greater fluorescent contrast in the Colo205 and SW948 cell lines in the panitumumab-IRDye800CW group. Western blotting for epidermal growth factor receptor (EGFR) and a semiquantitative analysis of EGFR expression noted strong expression in all three cell lines; however, EGFR expression did not directly correlate to tumor to background ratio. CONCLUSIONS: Panitumumab-IRDye800CW produces significantly greater fluorescent contrast than IgG-IRDye800CW in a murine model of CRC and is a suitable agent for the application of FGS technology to CRC.

Enhanced Recovery After Surgery (ERAS) Eliminates Racial Disparities in Postoperative Length of Stay After Colorectal Surgery.

OBJECTIVE: To investigate the effects of enhanced recovery after surgery (ERAS) on racial disparities in postoperative length of stay (pLOS) after colorectal surgery. BACKGROUND: Racial disparities in surgical outcomes exist. We hypothesized that ERAS would reduce disparities in pLOS between black and white patients. METHODS: Patients undergoing ERAS in 2015 were 1:1 matched by race/ethnicity, age, sex, and procedure to a pre-ERAS group from 2010 to 2014. After stratification by race/ethnicity, expected pLOS was calculated using the American College of Surgeons National Surgical Quality Improvement Project Risk Calculator. Primary outcome was the observed pLOS and observed-to-expected difference in pLOS. Secondary outcomes were National Surgical Quality Improvement Project postoperative complications including 30-day readmissions and mortality. Adjusted sensitivity analyses on pLOS were also performed. RESULTS: Of 420 patients (210 ERAS and 210 pre-ERAS) examined, 28.3% were black. Black and white patients were similar in age, body mass index, sex, American Anesthesia Association class, and minimally invasive approaches. Within the pre-ERAS group, black patients stayed a mean of 2.7 days longer than expected compared with white patients (P < 0.05). Overall, ERAS patients had a significantly shorter pLOS (5.7 vs 8 days) and observed-to-expected difference (-0.7 vs 1.4 days) compared with pre-ERAS patients (P < 0.01). In the ERAS group, disparities in pLOS were reduced with no differences in readmissions or mortality between black and white patients. On sensitivity analyses, race/ethnicity remained a significant predictor of pLOS among pre-ERAS patients, but not for ERAS patients. CONCLUSIONS: ERAS eliminated racial differences in pLOS between black and white patients undergoing colorectal surgery. Reduced pLOS occurred without increases in mortality, readmissions, and most postoperative complications. ERAS may provide a practical approach to reducing disparities in surgical outcomes.

The role of mechanical bowel preparation and oral antibiotics for left-sided laparoscopic and open elective restorative colorectal surgery with and without faecal diversion.

BACKGROUND: There is significant variation in the use of mechanical bowel preparation and oral antibiotics prior to left-sided elective colorectal surgery. There has been no consensus internationally. METHODS: This was a retrospective analysis of the 2015 American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into four groups: those who had mechanical bowel preparation with oral antibiotics, mechanical bowel preparation alone, oral antibiotics alone and no preparation. The main outcome measures included overall, superficial, deep and organ/space surgical site infections. Secondary outcomes included anastomotic leak, ileus and rate of Clostridium difficile. RESULTS: A total of 5729 patients were included for analysis. The overall surgical site infection rate (any superficial, deep or organ/space infection) was significantly lower in the mechanical bowel preparation and oral antibiotics approach when compared to no preparation (OR = 0.46, 95% CI 0.36-0.59, P < 0.0001). On multivariable logistic regression analysis, mechanical bowel preparation with oral antibiotics maintained a lower risk of overall surgical site infections. MBP and OAB also had a protective effect on anastomotic leak in both the laparoscopic and open cohorts (laparoscopic multivariable adjusted OR = 0.42 (0.19-0.94), P = 0.035; open multivariable adjusted OR = 0.3 (0.12-0.77), P = 0.012). Mechanical bowel preparation alone and oral antibiotics alone was not associated with a significant decrease in surgical site infections. There was no increase in C. difficile occurrences with the use of oral antibiotics. CONCLUSION: Mechanical bowel preparation with oral antibiotics significantly minimised surgical site infections and anastomotic leak following both laparoscopic and open left-sided restorative colorectal surgery. Mechanical bowel preparation alone did not reduce surgical site infections. There was a trend to reduction in surgical site infections with oral antibiotics alone.

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer.

BACKGROUND: Curcumin has proven to be a potent antitumor agent in both preclinical and clinical models of colorectal cancer (CRC). It has also been identified as a ligand of the transcription factor known as the aryl hydrocarbon receptor (AHR). Our laboratory has identified the AHR as a mechanism which contributes to both tumorigenesis in a mouse model of inflammatory CRC as well an apoptotic target in vitro. Curcumin's role as an AHR ligand may modulate its effects to induce colon cancer cell death, and this role may be enhanced via structural modification of the curcumin backbone. We sought to determine if the two piperidone analogs of curcumin, RL66 and RL118, exhibit more robust antitumor actions than their parent compound in the context of colorectal cancer in vitro. Moreover, to ascertain the ability of curcumin, RL66 and RL118 to activate the AHR and evaluate if this activation has any effect on CRC cell death. MATERIALS AND METHODS: DLD1, HCT116, LS513, and RKO colon cell lines were propagated in vitro. Natural curcumin was obtained commercially, whereas RL66 and RL118 were synthesized and characterized de novo. Multiwell fluorescent/luminescent signal detection was used to simultaneously ascertain cell viability, cell cytonecrosis, and relative amounts of apoptotic activity. AHR activity was measured with a dual luciferase reporter gene system. Stable expression of small interfering RNA interference was established in the HCT116 cell lines to create AHR "knock down" cell lines. RESULTS: Both RL66 and RL118 proved to be more potent antitumor agents than their parent compound curcumin in all cell lines tested. The majority of this cell death was due to induction of apoptosis, which occurred earlier and to a greater degree following RL66 and RL118 treatment as opposed to curcumin. Also, RL66 and RL118 were found to be activators of AHR, and a portion of their ability to cause cell death was dependent on this induction. Curcumin was found unable to activate the AHR, and levels of AHR messenger RNA did not change their effects on cell death. CONCLUSIONS: Piperidone analogs of curcumin exhibited enhanced antitumor effects in vitro as opposed to their parent compound. Even more, this enhanced cell death profile may be partially attributed to the ability of these compounds to activate the AHR. Further study of synthetic curcumin analogs as chemopreventives and chemoadjuncts in CRC is warranted. Also, more generally, the AHR may represent a potential putative target for novel anticancer agents for CRC.

Value of MDCT and Clinical and Laboratory Data for Predicting the Need for Surgical Intervention in Suspected Small-Bowel Obstruction.

OBJECTIVE: The purpose of this article is to assess the value of a large panel of clinical and MDCT variables in patients with suspected small-bowel obstruction (SBO) for predicting urgent surgical intervention (< 72 hours), bowel ischemia, and bowel resection. MATERIALS AND METHODS: MDCT studies performed at admission for 179 nonconsecutive adults (mean age, 55.8 years; 86 men and 93 women) with suspected SBO were retrospectively reviewed by three board-certified radiologists. In addition to assessing individual CT features, each radiologist scored the overall likelihood of each main outcome measure using a 5-point scale. All relevant clinical and laboratory data were abstracted from electronic medical record review. Univariate and multivariate analyses were performed. RESULTS: Among all 179 patients with suspected SBO, 56 (31.3%) underwent surgical intervention within 72 hours, 10 (5.6%) had ischemia at surgery, and nine (5.0%) required small-bowel resection. On univariate analysis, multiple CT findings were highly significant (p < 0.01) for predicting the main surgical outcomes, including degree of obstruction, 5-point radiology likelihood scores, and the presence of a transition point, closed loop, and mesenteric congestion. None of the objective clinical or laboratory variables (including serum lactate level) reached this level of significance. At multivariate analysis, forward stepwise logistic regression with 0.05 significance level cutoff included both degree of obstruction (p < 0.001) and closed loop (p < 0.01), with the presence of a transition point showing a trend toward significance (p = 0.081). CONCLUSION: A number of findings at abdominal MDCT are associated with the need for surgery and other important surgical outcomes in patients with suspected SBO. Overall radiologist impression of need for surgical intervention was a better predictor than any clinical or laboratory parameter.