Can Colorectal Surgery Be Performed as an Outpatient Surgery?

The potential to discharge patients safely within the same day after colorectal surgery has developed over time with concurrent advances in concepts of enhanced recovery pathways, along with minimally invasive techniques available to surgeons. The advent of planned same-day discharges after elective colectomy is made possible by research establishing improved length of stay with minimal morbidity in patients undergoing minimally invasive surgery and especially minimally invasive surgery in the setting of an enhanced recovery after surgery (ERAS) protocol. In tracing the timeline of research and development of knowledge in this setting, the safety of outpatient colorectal surgery can be established.

Potentially Avoidable Admissions and Prolonged Hospitalization in Patients with Suspected Colon Cancer.

BACKGROUND: Suspicion of cancer in the Emergency Department (ED) may lead to potentially avoidable and prolonged admissions. We aimed to examine the reasons for potentially avoidable and prolonged hospitalizations after admissions from the ED for new colon cancer diagnoses (ED-dx). METHODS: A retrospective, single-institution analysis was conducted of patients with ED-dx between 2017 and 2018. Defined criteria were used to identify potentially avoidable admissions. Patients without avoidable admissions were examined for ideal length of stay (iLOS), using separate defined criteria. Prolonged length of stay (pLOS) was defined as actual length of stay (aLOS) being greater than 1 day longer than iLOS. RESULTS: Of 97 patients with ED-dx, 12% had potentially avoidable admissions, most often (58%) for cancer workup. Very little difference in demographic, tumor characteristics, or symptoms were found, except patients with potentially avoidable admissions were more functional (Eastern Cooperative Oncology Group [ECOG] score 0-1: 83% vs. 46%; p = 0.049) and had longer symptom duration prior to ED presentation {24 days (interquartile range [IQR] 7-75) vs. 7 days (IQR 2-21)}. Among the 60 patients who had necessary admissions but did not require urgent intervention, 78% had pLOS, most often for non-urgent surgery (60%) and further oncologic workup. The median difference between iLOS and aLOS was 12 days (IQR 8-16) for pLOS. CONCLUSIONS: Potentially avoidable admissions following Ed-dx were uncommon but were mostly for oncologic workup. Once admitted, the majority of patients had pLOS, most often for definitive surgery and further oncologic workup. This suggests a lack of systems to safely transition to outpatient cancer management.

Feasibility and Outcome of Routine Use of Concurrent Chemoradiation in HIV-positive Patients With Squamous Cell Anal Cancer.

OBJECTIVES: Clinical concerns about hematologic toxicities in human immunodeficiency virus (HIV)+ patients with squamous cell anal cancer (SCAC) may lead to de-escalation of treatment intensity. The objective of this study is to evaluate clinical outcomes including toxicity following standard concurrent curative-intent chemoradiation for HIV+ and HIV- patients with SCAC. MATERIALS AND METHODS: Among 97 evaluable patients treated between 2009 and 2016 (median age 52.2 y), 43 (44.3%) were HIV+ and 54 (55.7%) HIV-. The majority of the radiation was delivered using intensity-modulated radiation therapy and chemotherapy consisting primarily (93%) of 5-fluorouracil and mitomycin C. Clinical outcomes assessed included toxicity, locoregional control (LRC), distant metastasis (DM), progression-free survival (PFS), colostomy-free survival (CFS), overall survival (OS), and cause-specific survival (CSS). RESULTS: With a median follow-up of 45 months, HIV+ patients exhibited a trend toward reduced OS compared with HIV- patients (4 y OS 61.2% vs. 78.3%; HR 2.09; 95% CI, 0.97-4.52; P=0.055) on univariable analysis, but HIV status was not significant after adjusting for additional parameters on multivariable analysis. Toxicity rates, LRC, CFS, PFS, freedom from DM, and CSS were similar between the 2 cohorts. On multivariable analysis, tumor size >5 cm impacted all clinical outcomes (trend for LRC) except CFS. Radiation treatment extension beyond 7 days was found to negatively impact LRC and CSS. Male sex was associated with worse CFS. CONCLUSIONS: Radiation therapy with concurrent 5-fluorouracil and mitomycin C chemotherapy is reasonably well-tolerated as curative treatment for HIV+ patients with SCAC, and no significant difference in outcomes was noted relative to HIV- patients.

Are you better off than you were 4 years ago? Measuring the impact of the ABS flexible endoscopy curriculum.

INTRODUCTION: In 2014, the ABS introduced the Flexible Endoscopy Curriculum (FEC). The FEC did not alter the minimum defined category case volumes for endoscopy; however, it did introduce specific cognitive and technical milestones for endoscopy training. It also mandated that residents pass the Fundamentals of Endoscopic Skills (FES) exam to qualify for board certification. Although significant research has been published regarding residents' success on the FES exam, very little is known regarding how the FEC has changed the way general surgery programs train their residents in surgical endoscopy. The aim of this study was to quantify changes in flexible endoscopy education at a large academic program in the 4 years since the FEC was published. METHODS: We classified the impact of FEC into four categories: (a) case volume or distribution, (b) clinical rotations, (c) required didactics or simulation exercises, and (d) FES pass rates. For category (a), we reviewed current and historical case logs for all categorical residents from 2013 to 2018. Mann-Whitney U tests were used to compare endoscopy volumes for each PGY level in 2013-2014 to the respective PGY level in 2017-2018 with p < 0.05 considered significant. For categories (b)-(d), we gathered historical records from the residency coordinator and endoscopy rotation director. RESULTS: Complete data were available for 57 residents in the 2013-2014 academic year and 56 residents in the 2017-2018 academic year. Median total endoscopies performed by PGY2, PGY3, and PGY5 residents all significantly increased during the FEC rollout. Our program's focus on endoscopy also expanded with absolute increases in endoscopy rotations, didactics, and simulation exercises. These changes translated into significantly increased pass rates on the FES exam from 40 to 100%. CONCLUSIONS: Implementation of the FEC at a large academic program led to measurable improvements in clinical experience, program structure, educational programing, and performance on high-stakes assessments.

The Fuel Gauge: A Simple Tool for Assessing General Surgery Resident Well-Being.

OBJECTIVE: Resident well-being is an increasingly relevant issue in medical education; however, there is no consensus on how to best measure well-being. The "fuel gauge," is a simple, easy-to-use tool developed to measure resident well-being and previously applied in an Internal Medicine Residency Program at our institution. The current study sought to evaluate its acceptability and usefulness in a surgery program. DESIGN: Weekly fuel gauge data was retrospectively collected from August 2017 through December 2018 along with resident Postgraduate Year designations. SETTING: This study was conducted at a single, large general surgery residency program that rotates through a variety of hospitals, including a University hospital, a large county hospital, a Veterans Affairs hospital, and a freestanding Children's hospital. PARTICIPANTS: Categorical general surgery residents at every level of training as well as preliminary interns and off service intern rotators from urology, oral and maxillofacial surgery, and otolaryngology were eligible for the study. Fuel gauge submissions which did not denote a score were excluded from analysis. RESULTS: Out of 130 residents, 103 (79.2%) completed at least 1 fuel gauge assessment with a weekly mean response rate of 41.5%. Low scores were submitted by 39.8% of resident participants. Narrative feedback was provided in 6.2% of submissions with increased length associated with decreased fuel gauge score. CONCLUSIONS: The fuel gauge was well accepted by a large general surgery program with no decline in participation rates over the study period. The tool provided residents with a direct line of communication with their program's administration, and a feasible way for the program director's office to monitor and identify residents who were struggling with regard to their well-being.

Neurologic injuries following road traffic accidents in the Dominican Republic: Examining causes and potential solutions.

Objective: Road traffic accidents (RTAs) are the number one cause of traumatic brain injuries (TBIs) worldwide. This study examines RTA-related TBIs in the Dominican Republic, a country in the Caribbean with the highest RTA fatality rate in the Western Hemisphere. Methods: We interviewed 117 adult patients or medical guardians of patients admitted to Hospital Traumatológico Dr. Ney Arias Lora in Santo Domingo following an RTA. Information regarding the type of accident, patient demographics, and injuries sustained was collected for each patient. Results: Most study participants were males (79.5%), and the most common method of transportation was motorized 2-wheeled vehicle (MTW; 74.4%). Of the 69 patients who suffered a TBI, 66.7% were classified as moderate-severe TBIs and 30.3% were classified as mild TBIs. The most common types of intracranial hemorrhage were subdural hemorrhage (12%) and subarachnoid hemorrhage (9.4%). Helmet use among admitted MTW riders was reported at 22.4%, and none of the 9 MTW riders who died in the hospital were wearing a helmet. Only 58.1% of patients lived in an area that offered 911 emergency response services at the time of the study. At 66.2%, the majority of people living within the 911 service area utilized emergency response services following an RTA. Multiple logistic regression determined that the utilization of 911 emergency response services was associated with a decrease in the likelihood of presenting with a moderate/severe TBI by a factor of 0.78 (adjusted odds ratio [OR]; P < .008; 95% confidence interval [CI], 0.65, 0.93). Nonuse of a helmet was associated with a 1.22 times increased risk of presenting with a moderate/severe TBI (adjusted OR; P < .04; 95% CI, 1.01, 1.61). Age and gender were not statistically significant in this model. Conclusions: The results of this study support 2 important avenues for reducing the burden of RTA-associated neurologic disease in the Dominican Republic. As with many other middle-income countries, MTWs represent an economical and efficient mode of transportation. Therefore, increasing helmet use may be the most effective way to reduce RTA-associated TBIs. In addition, continuing the expansion of postcrash emergency response services may mitigate the severity of RTA-associated neurologic disease.

A Phase I Clinical Trial of the Phosphatidylserine-targeting Antibody Bavituximab in Combination With Radiation Therapy and Capecitabine in the Preoperative Treatment of Rectal Adenocarcinoma.

OBJECTIVES: There is interest in improving the tumoricidal effects of preoperative radiotherapy for rectal carcinoma by studying new radiosensitizers. The safety and toxicity profile of these combination regimens needs rigorous clinical evaluation. The primary objective of this study was to evaluate the toxicity of combining bavituximab, an antibody that targets exposed phosphatidylserine, with capecitabine and radiation therapy. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma were enrolled on a phase I study combining radiation therapy, capecitabine, and bavituximab. A standard 3+3 trial designed was used. RESULTS: In general, bavituximab was safe and well tolerated in combination with radiation therapy and capecitabine in the treatment of rectal adenocarcinoma. One patient at the highest dose level experienced a grade III infusion reaction related to the bavituximab. One tumor demonstrated a complete pathologic response to the combination treatment. CONCLUSIONS: Bavituximab is safe in combination with capecitabine and radiation therapy at the doses selected for the study. Further clinical investigation would be necessary to better define the efficacy of this combination.

Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis.

Down-regulation of miR-26 family members has been implicated in the pathogenesis of multiple malignancies. In some settings, including glioma, however, miR-26-mediated repression of PTEN promotes tumorigenesis. To investigate the contexts in which the tumor suppressor versus oncogenic activity of miR-26 predominates in vivo, we generated miR-26a transgenic mice. Despite measureable repression of Pten, elevated miR-26a levels were not associated with malignancy in transgenic animals. We documented reduced miR-26 expression in human colorectal cancer and, accordingly, showed that miR-26a expression potently suppressed intestinal adenoma formation in Apc(min/+) mice, a model known to be sensitive to Pten dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal cancer that overrides putative oncogenic activity, highlighting the therapeutic potential of miR-26 delivery to this tumor type.

An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration.

Downregulation of the miR-143/145 microRNA (miRNA) cluster has been repeatedly reported in colon cancer and other epithelial tumors. In addition, overexpression of these miRNAs inhibits tumorigenesis, leading to broad consensus that they function as cell-autonomous epithelial tumor suppressors. We generated mice with deletion of miR-143/145 to investigate the functions of these miRNAs in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in the absence of these miRNAs, epithelial regeneration after injury was dramatically impaired. Surprisingly, we found that miR-143/145 are expressed and function exclusively within the mesenchymal compartment of intestine. Defective epithelial regeneration in miR-143/145-deficient mice resulted from the dysfunction of smooth muscle and myofibroblasts and was associated with derepression of the miR-143 target Igfbp5, which impaired IGF signaling after epithelial injury. These results provide important insights into the regulation of epithelial wound healing and argue against a cell-autonomous tumor suppressor role for miR-143/145 in colon cancer.

Inhibition of prostate cancer cell growth by activated eosinophils.

BACKGROUND: Host Immune response to prostate cancer primarily involves the CTL and NK effector cells. Recent immunotherapeutic strategies incorporating cytokine genes into the tumor cell and/or dendritic cells have had encouraging results. In this study, we describe the inhibitory activity of a third potential effector cell, the eosinophil, against DU 145 and PC-3 prostate tumor cells growth in vitro. METHODS: Subconfluent monolayer cultures of DU 145 and PC-3 cells were incubated with peripheral blood eosinophils from allergic or asthmatic individuals and also with eosinophil cultured supernatants. Newly established eosinophil cell lines were also studied. After harvesting, the plates were washed and stained with Hematoxylin/eosin (H/E) then photographed. The combination of monolayer cell growth inhibition and colony formation inhibition assays were used to evaluate eosinophil inhibitory activity. In the colony formation inhibition assay one hundred cells per well in 6-well plates were incubated overnight, after which peripheral blood eosinophils, conditioned media and cytokines, IL-4 and TNF-alpha were added. The plates were harvested after 10 days incubation period. Colonies were stained and counted. RESULTS: Hypo- and hyperdense peripheral blood eosinophils from allergic and asthmatic individuals as well as eosinophil cell lines established from these subpopulations inhibited both DU 145 and PC-3 cell growth at 58-78% and 10-38%, respectively. IL-5 up-regulated eosinophil cell line activity by 21-24%. The conditioned media which contained the released mediators of activated eosinophils were potent in their actions on both DU 145 and PC-3, inhibiting colony formation by as much as 90-100%. CONCLUSION: These results clearly demonstrate the inhibitory potential of activated eosinophils and their released "soup" of mediators and therefore support the hypothesis that eosinophils may participate in host response to prostate cancer together with CTLs and NK cells. Furthermore, this study offers insights into possible strategies for enhancing eosinophilic activity in prostate cancer.

Activated eosinophils infiltrate MCF-7 breast multicellular tumor spheroids.

BACKGROUND: Previous studies in our laboratory have shown that activated eosinophils and eosinophilic cell lines inhibit the in vitro growth of MCF-7 breast tumor cells. We have also shown that IL-4 and IL-5 partially inhibit MCF-7 growth in vitro. In this study MCF-7 multicellular tumor spheroids (MTS) were developed to study the effect of eosinophils and IL-4 on tumor growth. MATERIALS AND METHODS: Hypo- and hyperdense metrizamide density gradient fractions of eosinophils from peripheral blood of individuals with mild to moderate esoinophilia were co-cultured with 2-day-old MCF-7 MTS in medium containing bacto agar overlay at 37 degrees C. RESULTS: Light microscopic analyses revealed the attachment of eosinophil effector cells to the spheroid borders. Moreover, the culture media was greater than 90% devoid of effector cells. At six days post co-culture, very large spheroids were observed in both test and control dishes; however the necrotic cores in the co-cultures were more intense and larger than in the control. When MCF-7 tumor cells (1 x 10(6)) were pretreated with IL-4 at 0.5 ng/ml, there was a dramatic decrease in the number of spheroids formed. CONCLUSION: These data strongly indicate that cytokines like IL-4 and perhaps other eosinophil mediators are capable of killing and inhibiting tumor growth; they suggest that tumor infiltrating eosinophils can degranulate and release toxic inhibitory factors into the tumor milieu which destroy the surrounding tumor. These observations, along with the use of the eosinophil: MTS tumor model provide a unique model system for in depth studies of the role of eosinophils and the cytokines they produce in breast cancer and may offer potential therapeutic implications.