Device-assisted enteroscopy in the surveillance of intestinal hamartomas in Peutz-Jeghers syndrome.

Background and study aims Peutz-Jeghers syndrome (PJS) is an autosomal-dominant genetic disorder characterized by the formation of hamartomatous polyps in the gastrointestinal tract. These polyps result in significant morbidity due to adverse events (AEs) including intestinal obstruction, bleeding, and malignancy. The aim of this study was to describe the role of device-assisted enteroscopy (DAE) in monitoring and prophylactic polypectomy within the small bowel. Patients and methods Electronic medical records were surveyed to identify all DAE procedures performed in patients with PJS at three US referral centers between January 1, 2007 and January 1, 2020. Individual charts were reviewed to collect and analyze specific data points. Primary end points included AEs associated with DAE-related polypectomy and the rate of laparotomy in PJS patients prior to, and following, index DAE. Secondary data points included patient characteristics, procedural details, and size/location/distribution of small bowel hamartomas. Results Twenty-three patients met our inclusion criteria. Of these, 18 (75%) had previously undergone small bowel surgery prior to index DAE. Between 2007 and 2020, 46 DAEs were performed in these patients with an average of one exam every 2.5 years. A total of 131 polypectomies were performed with an AE rate of 1.5%. None of our cohort required emergent surgery related to AEs of small bowel hamartomas over 336 years of aggregated follow-up. Conclusions Endoscopic management of small bowel polyps in patients with PJS using DAE is an effective strategy for prophylactic removal of hamartomas. DAE surveillance and endoscopic polypectomy is safe and may decrease the need for repeated laparotomy in patients with PJS.

Hispanic Farmers Experience Shorter EMS Response Times but Longer Emergency Department Length of Stay Following Occupational Injuries.

BACKGROUND: Agriculture has the highest rate of fatal injuries by sector. Hispanic workers also experience more fatal work injuries than every other minority group combined. Pre-hospital and initial trauma evaluation represent an important marker to understand the impact of a trauma system. We sought to investigate whether Hispanic agricultural workers in the United States (US) experience disparities following traumatic occupational injuries in terms of pre-hospital and emergency department care. METHODS: We retrospectively analyzed the National Trauma Data Bank from 2012-2016 to understand differences between Hispanic and non-Hispanic farmers in Emergency Medical Services (EMS) response and transport times (minutes), transport mode, transfer rates, presentation to University or Level I trauma hospitals, Injury Severity Scores (ISS), length of stay (LOS) in the emergency department (ED, minutes) or hospital (days), need for the operating room (OR), admittance to the Intensive Care Unit (ICU), and mortality. RESULTS: A total of 6,161 farmers were included in our analyses (median age 47 years, females 7.0%). Multivariable analyses indicate differences regarding EMS response, EMS transport, and LOS in the ED. Rates of admission to the ICU, surgical operations, days on a ventilator, discharge from the hospital with supportive care, and mortality did not differ between groups. CONCLUSIONS: Non-Hispanic patients have longer median EMS response and total transport times. Hispanic patients have longer median LOS in the ED. However, the lack of significant differences in management variables other than EMS times and ED LOS indicate an equitable delivery of trauma care once patients were transferred from the ED.

Influence of Insurance Status on Subdural Hematoma Management: A National Trauma Data Bank Analysis.

BACKGROUND: Traumatic brain injury is a major public health concern with a rising incidence in the United States. Prior studies have looked at associations between insurance status and traumatic brain injury, but none have focused specifically on traumatic subdural hematomas (SDH). It is important to evaluate whether insurance and/or other social determinants of health play a role in treatment and outcomes of traumatic SDH. METHODS: A retrospective analysis of the National Trauma Data Bank was conducted from 2012 to 2016 to look at associations between insurance status and management of SDH with surgery versus intracranial pressure (ICP)/EVD monitoring. Secondary outcomes of interest were emergency department (ED) length of stay (LOS), hospital LOS, ICU admission, ICU LOS, and mortality. RESULTS: We identified 68,687 adult patients with a single diagnosis of subdural hematoma. Overall, self-pay patients with SDH were younger, predominately male, and more likely to be non-white compared to patients with public or private health insurance.  More specifically, Black/African American SDH patients made up a large percentage of the self-pay category (15.5%; P < 0.001) compared to publicly and privately insured (7.5% and 8.0%, respectively). After adjusting for age, sex, injury severity score (ISS), Glasgow Coma Scale, alcohol intoxication, and trauma center level, publicly insured patients were 1.86 (95% CI 1.36-2.55, P < 0.001) times more likely to undergo a craniotomy or craniectomy compared to self-pay patients. However, insurance status did not appear to impact whether a patient received ICP/EVD monitoring (OR 0.52; 95% CI 0.24-1.18, P = 0.118). There was no statistically significant difference in ED LOS, Hospital LOS, and ICU LOS between insurance categories. CONCLUSIONS: Publicly insured patients have higher odds of undergoing surgical management for traumatic SDH compared to self-pay patients. Further studies evaluating this association are warranted.

A Fast-Track Pathway for Emergency General Surgery at an Academic Medical Center.

BACKGROUND: Fast Track Pathways (FTP) directed at reducing length of stay (LOS) and overall costs are being increasingly implemented for emergency surgeries. The purpose of this study is to evaluate implementation of a FTP for Emergency General Surgery (EGS) at an academic medical center (AMC). METHODS: The study included 165 patients at an AMC between 2016 and 2018 who underwent laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), or laparoscopic inguinal hernia repair (LI). The FTP group enrolled 89 patients, and 76 controls prior to FTP implementation were evaluated. Time to surgery (TTS), LOS, and post-operative LOS between groups were compared. Direct costs, reimbursements, and patient reported satisfaction (satisfaction 1 = never, 4 = always) were also studied. RESULTS: The sample was 60.6% female, with a median age of 40 years. Case distribution differed slightly (56.2% versus 42.1% LA, 40.4% versus 57.9% LC, FTP versus control), but TTS was similar between groups (11h39min versus 10h02min, P = 0.633). LOS was significantly shorter in the FTP group (15h17min versus 29h09min, P < 0.001), reflected by shorter post-operative LOS (3h11min versus 20h10min, P< 0.001), fewer patients requiring a hospital bed and overnight stay (P < 0.001). Direct costs were significantly lower in the FTP group, reimbursements were similar (P < 0.001 and P = 0.999 respectively), and average patient reported satisfaction was good (3.3/4). CONCLUSION: In an era focused on decreasing cost, optimizing resources, and ensuring patient satisfaction, a FTP can play a significant role in EGS. At an AMC, an EGS FTP significantly decreased LOS, hospital bed utilization while not impacting reimbursement or patient satisfaction.

Predicting Survival and Response to Treatment in Gastroesophageal Neuroendocrine Tumors: An Analysis of the National Cancer Database.

BACKGROUND: Neuroendocrine tumors (NETs) of the esophagus and stomach are rare neoplasms with variable behavior. We aim to describe their epidemiology and response to treatment. METHODS: NETs of the stomach and the esophagus were selected from the National Cancer Database (2004-2013) and classified by location. Survival analyses were performed with respect to tumor characteristics and treatment variables. RESULTS: NETs of the stomach (n = 2700; 92.8%) and esophagus (n = 210, 7.2%) were identified. Gastric cardia NETs had demographics and behavior similar to esophageal tumors and were associated with worse overall survival than NETs of the noncardia stomach independent of grade (p < 0.001). Poorly differentiated histology [hazard ratio (HR) 4.14, 95% confidence interval (CI) 2.26-7.57; p < 0.001] and distant metastases (HR 3.28, 95% CI 1.94-5.56; p < 0.001) were the greatest independent predictors of survival. For patients with poorly differentiated NETs, surgery was the only treatment to have benefit on overall survival (HR 0.38, 95% CI 0.27-0.54; p < 0.001) regardless of extent of disease. There was no additional benefit to adjuvant chemotherapy or radiation in patients undergoing resection (p = 0.39), even for patients with lymph node metastases (surgery alone versus surgery plus adjuvant therapy, p = 0.46), distant metastases (p = 0.19), or positive margins (p = 0.33). CONCLUSIONS: Esophageal and gastric cardia NETs have worse survival than those of the noncardia stomach. Surgery offers the only survival benefit for poorly differentiated tumors, with no additional survival advantage to adjuvant chemotherapy or radiation.

STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive Phenotype In Vitro.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and few therapeutic options. Stathmin1 (STMN1) is a cytosolic protein involved in microtubule dynamics through inhibition of tubulin polymerization and promotion of microtubule depolymerization, which has been implicated in carcinogenesis and aggressive behavior in multiple epithelial malignancies. We aimed to evaluate expression of STMN1 in ACC and to elucidate how this may contribute to its malignant phenotype. METHODS: STMN1 was identified by RNA sequencing as a highly differentially expressed gene in human ACC samples compared with benign adrenal tumors. Expression was confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical (IHC) staining of a tissue microarray (TMA) from two independent cohorts. The biologic relevance of STMN1 was investigated in NCI-H295R cells by lentivirus-mediated silencing. RESULTS: Differential gene expression demonstrated an eightfold increase in STMN1 messenger RNA (mRNA) in malignant compared with benign adrenal tissue. IHC showed significantly higher expression of STMN1 protein in ACC compared with normal and benign tissues. STMN1 knockdown in an ACC cell line resulted in decreased cell viability, cell-cycle arrest at G0/G1, and increased apoptosis in serum-starved conditions compared with scramble short hairpin RNA (shRNA) controls. STMN1 knockdown also decreased migration, invasion, and anchorage-independent growth compared with controls. CONCLUSIONS: STMN1 is overexpressed in human ACC samples, and knockdown of this target in vitro resulted in a less aggressive phenotype of ACC, particularly under serum-starved conditions. Further study is needed to investigate the feasibility of interfering with STMN1 as a potential therapeutic target.

The impact of the robotic platform on assistant variability in complex gastrointestinal surgery.

BACKGROUND: Nissen fundoplication is considered an advanced minimally invasive procedure whether performed laparoscopically or robotically. In laparoscopic surgery, it is evident that assistant skill level impacts operative times. However, the robotic platform allows improved surgeon autonomy. We aimed to determine the impact of assistant training level on operative times in robotic Nissen fundoplication (RNF) and laparoscopic Nissen fundoplication (LNF). METHODS: A prospectively maintained Nissen database (2011-2016) from a single academic institution was utilized to collect patient characteristics, operative times, length of stay, intraoperative complications, postoperative complications, readmission rate, and assistant training level. Assistants were either postgraduate year-3 surgery residents defined as junior-level assistants or a minimally invasive surgery (MIS) fellow defined as senior-level assistants. RESULTS: There were 105 patients included in our analyses. When comparing postgraduate year-3 residents to MIS fellows performing LNF, the median operative time was significantly decreased when senior-level assistants were present in the LNF group, 85 (75-103) versus 129 (74-269) min, P = 0.02. In comparison, median operative times in the RNF group were independent of the assistant's level of training, 154 (71-300) versus 158 (101-215) min, P = 0.34. There were no significant differences in outcomes between the junior- and senior-level assistant cohorts for estimated blood loss, length of stay, postoperative complications, and 30-d readmission rates in either the LNF or RNF group. CONCLUSIONS: Assistant training level impacted operative time for LNF but not RNF. These differences are most likely attributed to increased autonomy of the operating surgeon afforded by the robotic platform reducing assistant variability.

CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors.

Purpose: Poorly differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors, including papillary thyroid cancer (PTC) and ATC, are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1-targeting agents for the treatment of aggressive cancer. We developed a third-generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive T-cell therapy as a new treatment modality.Experimental Design: ICAM-1 CAR T cells were applied to multiple malignant and nonmalignant target cells to investigate specific target cell death and "off-tumor" toxicity in vitroIn vivo therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases.Results: ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines in vitro Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable. In mice with systemic ATC, a single administration of ICAM-1 CAR T cells mediated profound tumor killing that resulted in long-term remission and significantly improved survival. Patient-derived ATC cells overexpressed ICAM-1 and were largely eliminated by autologous ICAM-1 CAR T cells in vitro and in animal models.Conclusions: Our findings are the first demonstration of CAR T therapy against both a metastatic, thyroid cancer cell line and advanced ATC patient-derived tumors that exhibit dramatic therapeutic efficacy and survival benefit in animal studies. Clin Cancer Res; 23(24); 7569-83. ©2017 AACR.

The Impact of Nodal Dissection on Staging in Adrenocortical Carcinoma.

BACKGROUND: The role of lymphadenectomy in adrenocortical carcinoma (ACC) is controversial, and formal lymph node (LN) dissection is not routine. We sought to determine the minimum number of LNs that must be examined to accurately identify a patient as node negative. METHODS: The National Cancer Database was used to identify patients diagnosed with ACC from 2004 to 2013 who underwent surgical resection. Patients with distant metastases, multivisceral resection, or missing surgical or lymphadenectomy data were excluded. The primary outcome was overall survival (OS). RESULTS: LNs were identified on histopathology in 156 patients. Of these, 35 (22%) had at least one positive LN. Positive LNs were associated with positive surgical margins (odds ratio [OR] 5.80, p = 0.002) and increasing LN yield (OR 1.06, p = 0.02). Overall, on Cox regression analysis, LN positivity (hazard ratio [HR] 3.02, p < 0.001) and positive surgical margins (HR 2.06, p = 0.048) independently predicted poor OS after controlling for other factors that may influence survival. LN(-) disease in patients with one to three LNs examined had poorer overall survival compared with when at least four LNs were examined (p = 0.02). None of the other patient, tumor, and treatment variables had any impact on OS of the LN(-) cohort. The likelihood of identifying nodal involvement was higher on examination of at least four LNs compared with examination of one to three LNs (30 vs. 16%, p = 0.03). CONCLUSIONS: LN positivity in ACC tumors independently predicts worse 5-year OS and a minimum of four LNs may be required to accurately determine LN negativity.

Well-Differentiated Thyroid Cancer Neovasculature Expresses Prostate-Specific Membrane Antigen-a Possible Novel Therapeutic Target.

Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein receptor, is highly expressed in prostate cancer and in the tumor neovasculature of colon, breast, and adrenocortical tumors. Here, we analyzed PSMA expression in the neovasculature of various thyroid cancer subtypes and assessed whether PSMA expression is correlated with aggressive behavior. From a prospectively maintained database, we evaluated 91 samples from 68 patients, including 37 primary differentiated thyroid cancers (DTCs) [11 classic papillary (cPTC), 9 follicular-variant (FvPTC), 11 follicular (FTC), 6 radioactive iodine-refractory (RAIR)], 5 anaplastic (ATC) carcinomas, 9 distant and 12 lymph node metastases, 21 benign thyroid nodules, and 7 normal thyroid specimens. Formalin-fixed paraffin-embedded tissue blocks were immunostained for vascular endothelial marker CD31 and PSMA with proper controls. PSMA expression was not detected in normal thyroid tissue. DTC tumors demonstrated a significantly higher PSMA expression, in regard to both intensity and percentage of vessels stained, than benign tumors (p < 0.001). Among the histologic subtypes, cPTC, FTC, and RAIR carcinomas demonstrated the highest percent of moderate to strong PSMA staining. PSMA expression was seen more frequently in specimens from distant metastases (100%) compared with specimens from only lymph node metastases (67%). PSMA is significantly overexpressed in the neovasculature of DTCs compared with normal and benign thyroid nodules specifically with increased expression in RAIR carcinomas and distant metastases. PSMA should be further explored as a novel therapeutic target for metastatic and RAIR carcinomas.

The role of molecular diagnostic testing in the management of thyroid nodules.

INTRODUCTION: Fine needle aspiration (FNA) with cytologic examination remains the standard of care for investigation of thyroid nodules. However, as many as 30% of FNA samples are cytologically indeterminate for malignancy, which confounds clinical management. To reduce the burden of repeat diagnostic testing and unnecessary surgery, there has been extensive investigation into molecular markers that can be detected on FNA specimens to more accurately stratify a patient's risk of malignancy. Areas covered: In this review, the authors discuss recent evidence and progress in molecular markers used in the diagnosis of thyroid cancer highlighting somatic gene alterations, molecular technologies and microRNA analysis. Expert commentary: The goal of molecular markers is to improve diagnostic accuracy and aid clinicians in the preoperative management of thyroid lesions. Modalities such as direct mutation analysis, mRNA gene expression profiling, next-generation sequencing, and miRNA expression profiling have been explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no perfect test has been discovered, molecular diagnostic testing has revolutionized the management of thyroid nodules.