Annual Structured Communication Skills Training for Surgery Residents.

INTRODUCTION: There is no formalized communication curriculum for surgical training. The aim of this study is to determine the benefit of annual communication skill-building workshops for surgical residents over several years. METHODS: The general surgery and the integrated cardiothoracic surgery residents in a tertiary care, urban academic center participated in a 2-hour communication skill-building workshop each year from July 2017 to June 2021. Each participant was administered an anonymous pre-session and post-session survey with a 5-point Likert scale to assess their self-reported preparedness and their evaluation of the workshop. Survey responses were divided into three groups based on their experience in this workshop; no experience (Experience 0), 1 y of experience (Experience 1), and two or more years of experience (Experience 2+). They were compared among groups. RESULTS: Seventy-one surgical residents participated in the workshop generating 124 survey results (Experience 0, 71 [57.3%], Experience 1, 41 [33.1%], and Experience 2+, 12 [9.7%]). Self-reported preparedness scores improved for the overall group as well as for each experience group. While scores decreased significantly in the following years, they improved after each workshop. Scores were significantly better with more experience (4, interquartile range [IQR] 3-4 in Experience 0, 4, IQR 3-5 in Experience 1, 4, IQR 4-5 in Experience 2+, P < 0.001 between Experience 0 and Experience 1, P = 0.041 between Experience 1 and Experience 2+). All residents reported an overwhelmingly positive review of the curriculum. CONCLUSIONS: Yearly 2-hour communication skills practice increased surgical residents' self-reported preparedness, and the repetition helped the improvement. Annual workshops are important for residents to be more prepared for serious illness communication.

Novel Expression of GABAA Receptors on Resistance Arteries That Modulate Myogenic Tone.

The clinical administration of GABAergic medications leads to hypotension which has classically been attributed to the modulation of neuronal activity in the central and peripheral nervous systems. However, certain types of peripheral smooth muscle cells have been shown to express GABAA receptors, which modulate smooth muscle tone, by the activation of these chloride channels on smooth muscle cell plasma membranes. Limited prior studies demonstrate that non-human large-caliber capacitance blood vessels mounted on a wire myograph are responsive to GABAA ligands. We questioned whether GABAA receptors are expressed in human resistance arteries and whether they modulate myogenic tone. We demonstrate the novel expression of GABAA subunits on vascular smooth muscle from small-caliber human omental and mouse tail resistance arteries. We show that GABAA receptors modulate both plasma membrane potential and calcium responses in primary cultured cells from human resistance arteries. Lastly, we demonstrate functional physiologic modulation of myogenic tone via GABAA receptor activation in human and mouse arteries. Together, these studies demonstrate a previously unrecognized role for GABAA receptors in the modulation of myogenic tone in mouse and human resistance arteries.

Diagnostic Modalities in Gastrointestinal Bleeding.

A variety of diagnostic modalities is available to assist in the evaluation of patients presenting with acute gastrointestinal (GI) bleeding. This article reviews some older technologies like colonoscopy, nuclear scintigraphy, and conventional angiography and will also review the newest additions to the lower GI bleeding diagnostic toolbox, which are video capsule endoscopy and computed tomography (CT) angiography. The management algorithm used at a given institution depends on the available expertise and resources.

Elevation of Serum CEA in Patients with Squamous Cell Carcinoma of the Anus.

The proportion of anal cancer cases that produce elevated carcinoembryonic antigen (CEA) levels is not well described in the medical literature. In this study, we used electronic health record data from a single urban cancer center to identify patients from 2004-2018 with anal cancer who have also had a pre-initial treatment CEA measurement. We identified 40 patients who met our eligibility criteria. Of those, 11 (27.5%) had an elevated pretreatment CEA. Elevated CEA was not associated with any of the clinical or demographic covariates; however, three out of five patients with a recurrence had an elevated CEA.

Correction to: Anal canal squamous cell cancer: are surgical alternatives to chemoradiation just as effective?

One of the author's middle name of this article was incorrectly published as "Emmanouil E. Pappou." This is now presented correctly in this article as "Emmanouil P. Pappou."

Anal canal squamous cell cancer: are surgical alternatives to chemoradiation just as effective?

PURPOSE: The purpose of this paper is to study long-term oncologic outcomes after different treatment strategies for anal canal cancer (SCAC). METHODS: Patients with SCAC (2004-2013) were identified from Surveillance, Epidemiology, and End Results (SEER) database. Patients undergoing radiation (RT) were compared to those undergoing local excision (LE), abdominoperineal resection (APR), and abdominoperineal resection after radiation (RT + APR). Overall survival (OS) and cancer-specific survival (CSS) data were evaluated using Kaplan-Meier and Cox regression. RESULTS: Two thousand seven hundred and seventy-two (83.8%) patients underwent RT, 382 (11.6%) LE, 77 (2.3%) APR, 76 (2.3%) RT + APR. Median age for the four groups was 60, 57, 64, and 56 years and 32, 49.7, 53.2, and 39.5% were male, respectively, while median tumor size was 4.4, 2.6, 5.3, and 5.5 cm, respectively. Five-year OS of RT, LE, APR, and RT + APR groups was 63.7, 79.6, 25.8, and 41.8% while CSS was 79.6, 92.5, 75.6, and 58.8%, respectively, (p < 0.001). Adjusted hazard ratios for OS for LE, APR, and RT + APR with RT as reference were 1.007 (0.702-1.444), 2.311 (1.367-3.906), and 2.072 (1.016-4.228), respectively. CONCLUSION: These data suggest that APR does not provide better outcomes in treatment of SCAC. Chemoradiation remains the gold standard treatment for majority of patients. Local excision is associated with favorable outcomes in some circumstances.

Use of an ACE inhibitor or angiotensin receptor blocker is a major risk factor for dehydration requiring readmission in the setting of a new ileostomy.

PURPOSE: Diverting ileostomies help prevent major complications related to anastomoses after colorectal resection but can cause metabolic derangement and hypovolemia, leading to readmission. This paper aims to determine whether angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use increased the risk of readmission, or readmission specifically for dehydration after new ileostomy creation. METHODS: Retrospective analysis of patients undergoing diverting ileostomy at a tertiary-care hospital, 2009-2015. Primary outcome was 60-day readmission for dehydration; secondary outcomes included 60-day readmission for any cause, or for infection obstruction. RESULTS: Ninety-nine patients underwent diverting ileostomy creation, 59% with a primary diagnosis of colorectal cancer. The 60-day readmission rate was 36% (n = 36). Of readmitted patients, 39% (n = 14) were admitted for dehydration. Other readmission reasons were infection (33%) and obstruction (3%). The majority (64%, n = 9) of patients readmitted for dehydration were taking either an ACEi or an ARB. Compared to patients not readmitted for dehydration, those who were readmitted for dehydration were more likely to be on an ACEi or an ARB (11/85, 13% vs. 9/14, 64%). After controlling for covariates, ACEi or ARB use was significantly associated with risk of readmission (p < 0.0001, odds ratio = 13.56, 95% confidence interval 3.54-51.92,). No other diuretic agent was statistically associated with readmission for dehydration. CONCLUSIONS: ACEi and ARB use is a significant risk factor for readmission for dehydration following diverting ileostomy creation. Consideration should be given to withholding these medications after ileostomy creation to reduce this risk.

Hypoxia-related proteins in patients with rectal cancer undergoing neoadjuvant combined modality therapy.

BACKGROUND: We have previously demonstrated the prognostic significance of rectal cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other cancers have reported that hypoxia influences response to neoadjuvant chemoradiation. OBJECTIVE: This study aimed to 1) characterize hypoxia-related protein expression in locally advanced rectal cancer before neoadjuvant chemoradiation, 2) determine the comodulation of hypoxia-related protein expression, and 3) evaluate the relationship between hypoxia-related protein expression and overall survival, time to recurrence, and tumor regression grade. DESIGN: Immunohistochemical analysis of 4 hypoxia-related proteins (HIF-1α, CA-IX, VEGF, and GLUT-1) was performed on archival pretreatment rectal cancer biopsies. PATIENTS: : Eighty-five patients with locally advanced rectal cancer treated with neoadjuvant radiation and 5-fluorouracil-based chemotherapy were included. MAIN OUTCOME MEASURES: The impact of hypoxia-related protein expression on outcome was evaluated by use of Cox proportional hazards model. Hypoxia-related protein expression was correlated with tumor regression grade by use of Spearman correlation coefficients. RESULTS: Median follow-up was 54 months. CA-IX expression was associated with overall survival (p = 0.01). HIF-1α expression was weakly correlated with VEGF (r = 0.26, p = 0.02) and GLUT-1 (r = 0.35, p = 0.001). Hypoxia-related protein expression was not associated with time to recurrence or Mandard tumor regression grade. CONCLUSIONS: Elevated CA-IX expression may be associated with poorer overall survival in locally advanced rectal cancer treated by neoadjuvant chemoradiation and resection. The expression of the hypoxia-related proteins HIF-1α, VEGF, and GLUT-1 may be comodulated in locally advanced rectal cancer. Further studies are needed to evaluate the mechanisms governing hypoxia regulation and the role of hypoxia in rectal cancer response to neoadjuvant chemoradiation.

Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer.

Clinical outcomes in colorectal cancer (CRC) correlate with T cell infiltrates, but the specific contributions of heterogenous T cell types remain unclear. To investigate the diverse function of T cells in CRC, we profiled 37,931 T cells from tumors and adjacent normal colon of 16 patients with CRC with respect to transcriptome, TCR sequence, and cell surface markers. Our analysis identified phenotypically and functionally distinguishable effector T cell types. We employed single-cell gene signatures from these T cell subsets to query the TCGA database to assess their prognostic significance. We found 2 distinct cytotoxic T cell types. GZMK+KLRG1+ cytotoxic T cells were enriched in CRC patients with good outcomes. GNLY+CD103+ cytotoxic T cells with a dysfunctional phenotype were not associated with good outcomes, despite coexpression of CD39 and CD103, markers that denote tumor reactivity. We found 2 distinct Treg subtypes associated with opposite outcomes. While total Tregs were associated with good outcomes, CD38+ Tregs were associated with bad outcomes independently of stage and possessed a highly suppressive phenotype, suggesting that they inhibit antitumor immunity in CRC. These findings highlight the potential utility of these subpopulations in predicting outcomes and support the potential for novel therapies directed at CD38+ Tregs or CD8+CD103+ T cells.

Obesity, regardless of comorbidity, influences outcomes after colorectal surgery-time to rethink the pay-for-performance metrics?

An elevated body mass index (BMI) is associated with increased morbidity and mortality after colorectal surgery. While coexistent comorbid conditions are captured in some determinations of case-severity, BMI itself is not factored into pay for performance (P4P) initiatives. From the National Surgical Quality Improvement Program database 2006-2011, obese (BMI ≥30 kg/m(2)) and nonobese (BMI <30 kg/m(2)) patients with and without comorbidity undergoing colorectal resection were identified. Pre- and intraoperative factors as well as postoperative outcomes were compared. Of 130,415 patients, 31.3 % were obese. 80.4 % of obese and 72.9 % of nonobese patients had comorbid conditions. Among obese patients, overall rates of surgical site infection (SSI), wound dehiscence, and various medical complications were significantly higher for those with comorbidity compared to those without (p < 0.001 for all). Obese patients with comorbidity overall had greater risk of renal failure and urinary tract infection than nonobese patients. Regardless of comorbidity, obese patients more commonly had pulmonary embolism, failure to wean from the ventilator, overall SSI, and wound dehiscence. Comorbid factors associated with obesity influence outcomes; however, obesity itself in their absence is associated with worse outcomes. This supports inclusion of obesity as an independent determinant of case-severity, quality, and reimbursement after colorectal surgery.

Patients with colorectal and renal cell carcinoma diagnoses appear to be at risk for additional malignancies.

UNLABELLED: Patients with colorectal cancer (CRC) and renal cell carcinoma (RCC) may be at risk for additional primary malignancies. A review of 101 patients with these concurrent diagnoses was performed. Forty-two percent of patients had 1 or more additional malignancies; none appeared to be associated with Lynch syndrome (LS). This suggests the need for careful follow-up in these patients and further study. BACKGROUND: Small studies have demonstrated that patients who have both colorectal and renal cell carcinoma may be at increased risk for the development of additional malignancies. A possible genetic basis has been suggested. Our study describes the clinicopathologic features of these patients and clarifies the relationship of this cohort with Lynch syndrome (LS). METHODS: Patients with primary CRC and RCC treated at our institution were identified. Medical records were reviewed for demographic and clinical information. Immunohistochemical staining for mismatch repair (MMR) proteins was performed on tumor tissue when possible. RESULTS: During the study period, 24,642 patients were treated for CRC and 7,366 were treated for RCC at our institution. One hundred seventy-nine patients had both diagnoses, with 101 patients eligible for inclusion in our cohort. Tumors were typically early stage. The 2 cancers presented as synchronous lesions in 42% of patients. Thirty-two patients had 1 additional primary malignancy, 7 patients had 2 additional primary malignancies, and 3 patients had 3 additional primary malignancies. No patient had a family history that met the Amsterdam II criteria (AC) for LS, but 50% had family members with 1 malignancy. One of 10 colorectal tumors analyzed for the absence of MMR protein expression demonstrated the absence of MSH6, but the corresponding RCC demonstrated intact expression of all 4 MMR proteins. CONCLUSION: It is rare for patients to be diagnosed with both CRC and RCC. The clinicopathologic features of this cohort and the results of immunohistochemical analysis performed on a sample of these patients do not suggest LS. However, the high rate of additional carcinomas suggests a need for careful follow-up. Multicenter longitudinal studies are warranted to further understand the natural history and possible genetic basis for this entity.

Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer.

BACKGROUND: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. METHODS: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. RESULTS: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. CONCLUSIONS: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00588276.

Systematic immunohistochemistry screening for Lynch syndrome in early age-of-onset colorectal cancer patients undergoing surgical resection.

BACKGROUND: Lynch syndrome (LS), defined by a deleterious (pathogenic) germline mutation in a mismatch repair (MMR) gene, is characterized by early age-of-onset colorectal cancer (CRC). Because clinical criteria for LS, such as the Amsterdam II Criteria, may miss cases, reflex tumor tissue testing of all CRC patients for LS has been proposed. Our study describes the impact of routine immunohistochemistry (IHC) analysis of tumor tissue for loss of MMR protein expression in early age-of-onset CRC patients undergoing resection. STUDY DESIGN: A prospective institutional program was established to perform IHC analysis on all early age-of-onset (≤50 years) CRC patients undergoing resection. Patients with abnormal IHC analysis were referred to the Clinical Genetics Service for further evaluation. The study cohort excluded patients with other polyposis syndromes and inflammatory bowel disease. RESULTS: IHC was performed on 198 patients from July 2006 to June 2010. The median age was 42.8 years (range 23.1 to 50.6 years). Abnormal IHC was reported in 38 (19.1%) patients, and 22 (57.8%) with abnormal IHC analysis had germline genetic testing. Seventeen (77.2%) had an alteration detected in an MMR gene: 10 were known to be deleterious mutations and 7 were variants of uncertain significance. Overall, LS was detected in 5.1% of patients. Only 2 of the 10 (20%) with a deleterious mutation actually met the Amsterdam II Criteria. CONCLUSIONS: Reflex IHC testing for LS on early age-of-onset CRC patients undergoing resection is feasible at the institutional level. This strategy identifies a substantial number of LS patients who would have been missed if genetic testing was based on the Amsterdam II Criteria alone.

Prospective immunohistochemical analysis of primary colorectal cancers for loss of mismatch repair protein expression.

BACKGROUND: Evaluation of patients for Lynch syndrome includes assessment of age and family cancer history as well as testing for microsatellite instability and alterations in mismatch repair (MMR) genes. We examined the value of routine immunohistochemistry (IHC) for MMR proteins in patients with colorectal cancer (CRC) undergoing resection at a single institution. PATIENTS AND METHODS: Beginning in July 2006, all patients aged < 50 years who were undergoing resection of primary CRC had their specimens routinely examined by IHC for MMR proteins. Patients aged 50-60 years were examined if histopathology suggestive of Lynch syndrome was reported, and patients of any age were examined if strong clinical suspicion was present. Family cancer history was analyzed and fulfillment of Amsterdam II criteria determined. RESULTS: Over an 18-month period, 96 patients aged < 50 years underwent CRC resection. Out of these, 72 patients (75%) had immunohistochemical testing, with an overall MMR protein loss rate of 19%. In selected patients aged 50-60 years and > 60 years, loss rates were 26% and 65%, respectively. Of all patients with MMR protein loss, 10 (32%) had reported histopathology, and 3 (10%) had family histories suggesting Lynch syndrome. CONCLUSION: We demonstrate the feasibility of routine immunohistochemical testing for MMR proteins in patients with CRC. As only a minority of patients with MMR protein loss met Amsterdam II criteria or had suggestive histopathology reported, routine IHC may identify patients with Lynch syndrome who might otherwise be missed.