Which Localizing Strategy is the Most Cost-Effective in Reoperative Primary Hyperparathyroidism?

INTRODUCTION: 2%-10% of patients with primary hyperparathyroidism (PHPT) who undergo parathyroidectomy develop persistent/recurrent disease. The aim of this study was to determine which preoperative localization method is most cost-effective in reoperative PHPT. METHODS: Clinical decision analytic models comparing cost-effectiveness of localizing studies in reoperative PHPT were constructed using TreeAge Pro. Cost and probability assumptions were varied via Probabilistic Sensitivity Analysis (PSA) to test the robustness of the base case models. RESULTS: Base case analysis of model 1 revealed ultrasound (US)-guided fine-needle aspiration with PTH assay as most cost-effective after localizing US. This was confirmed on PSA of model 1. Model 2 showed four-dimensional computed tomography (4D-CT) as most cost-effective after negative US. If not localized by US, on PSA, 4D-CT was the next most cost-effective test. CONCLUSIONS: US-guided FNA with PTH is the most cost-effective confirmatory test after US localization. 4D-CT should be considered as the next best test after negative US.

Factors Associated With Upstaging of Melanoma Thickness on Final Excision.

INTRODUCTION: The incidence and risk factors associated with upstaging from initial biopsy to definitive excision in cutaneous melanoma have not been established. The aim of this study was to determine the incidence of tumor stage upstaging and associated risk factors using the National Cancer Database. METHODS: A retrospective study of the National Cancer Database between 2012 and 2016 was performed. The cohort of patients undergoing excision of melanoma with available data comprised 133,592 patients. Differences in characteristics for upstaging were determined using Wilcox rank-sum, chi-square, or Fisher's exact tests. Multivariable analysis was performed using logistic regression to determine factors associated with upstaging. RESULTS: Incidence of upstaging was 5.2%. Upstaged patients were older, male, of non-White race, and of lower education level (P < 0.001). Lesions of the head/neck and lower extremity had increased incidence of upstaging compared to the trunk (P < 0.001). Nodular and acral lentiginous melanoma was associated with higher incidence of upstaging compared to superficial spreading melanoma (P < 0.001). Patients with lymphovascular invasion had increased risk of upstaging (P < 0.001). CONCLUSIONS: Upstaging of melanoma is infrequent but is significantly more prevalent in non-White patients and those with lower educational status. Provider and patient education should include the higher risk of upstaging in these groups and the possible need for further surgical intervention, such as re-excision of margins and sentinel lymph node biopsy.

Robotic pancreatoduodenectomy: trends in technique and training challenges.

BACKGROUND: More complex cases are being performed robotically. This study aims to characterize trends in robotic pancreatoduodenectomy (RPD) over time and assess opportunities for advanced trainees. METHODS: Using the ACS-NSQIP database from 2014 to 2019, PD cases were characterized by operative approach (open-OPN, laparoscopic-LAP, robotic-ROB). Proficiency and postoperative outcomes were described by approach over time. RESULTS: 24,268 PDs were identified, with the ROB approach increasing from 2.8% to 7.5%. Unplanned conversion increased over time for LAP (27.7-39.0%, p = 0.003) but was unchanged for ROB cases (14.8-14.7%, p = 0.257). Morbidity increased for OPN PD (35.5-36.8%, p = 0.041) and decreased for ROB PD (38.7-30.3%, p = 0.010). Mean LOS was lower in ROB than LAP/OPN (9.5 vs. 10.9 vs. 10.9 days, p < 0.00001). Approximately, 100 AHPBA, SSO, and ASTS fellows are being trained each year in North America; however, only about 5 RPDs are available per trainee per year which is far below that recommended to achieve proficiency. CONCLUSION: Over a 6-year period, a significant increase was observed in the use of RPD without a concomitant increase in conversion rates. RPD was associated with decreased morbidity and length of stay. Despite this shift, the number of cases being performed is not adequate for all fellows to achieve proficiency before graduation.

Rare cases of colonic schwannomas.

Schwannomas of the gastrointestinal tract are rare spindle cell tumors that account for 2-6% of mesenchymal tumors. An elderly male was found to have a left colon mass on CT scan and colonoscopy with pathology of fibrotic tissue. A laparoscopic-assisted left hemi-colectomy with primary anastomosis was performed. Pathology demonstrated spindle cell neoplasm arranged in short fascicles that were strongly and diffusely positive for S100. An elderly female was found to have a submucosal lesion on surveillance colonoscopy in the proximal transverse colon. Biopsy with jumbo forceps revealed spindle cell neoplasm positive for S100. Patient underwent an uncomplicated limited non-oncologic segmental transverse colectomy. We report only the ninth case of left and sixth in the transverse colon described in the literature. As is true for other mesenchymal tumors, mucosal biopsy is usually inconclusive and deep biopsy or submucosal resection is required, making pre-operative surgical decision difficult.

Pancreatoduodenectomy: the Metabolic Syndrome is Associated with Preventable Morbidity and Mortality.

BACKGROUND: Patients with metabolic syndrome (MS) may have increased perioperative morbidity and mortality. The aim of this analysis was to investigate the association of MS with mortality, serious morbidity, and pancreatectomy-specific outcomes in patients undergoing pancreatoduodenectomy (PD). METHODS: Patients with MS who underwent PD were selected from the 2014-2018 ACS-NSQIP pancreatectomy-specific database. MS was defined as obesity (BMI ≥ 30 kg/m2), diabetes, and hypertension. Demographics and outcomes were compared by χ2 and Mann-Whitney tests, and adjusted odds ratios from multivariable logistic regression assessed the association between MS and primary outcomes. RESULTS: Of 19,054 patients who underwent PD, 7.3% (n = 1388) had MS. On univariable analysis, patients with MS had significantly worse outcomes (p < 0.05): 30-day mortality (3% vs 1.8%), serious morbidity (26% vs 23%), re-intubation (4.9% vs 3.5%), pulmonary embolism (2.0% vs 1.1%), acute renal failure (1.5% vs 0.9%), cardiac arrest (1.9% vs 1.0%), and delayed gastric emptying (18% vs 16.5%). On multivariable analysis, 30-day mortality was significantly increased in patients with MS (aOR: 1.53, p < 0.01). CONCLUSION: Metabolic syndrome is associated with increased morbidity and mortality in patients undergoing pancreatoduodenectomy. The association with mortality is a novel observation. Perioperative strategies aimed at reduction and/or mitigation of cardiac, pulmonary, thrombotic, and renal complications should be employed in this population given their increased risk.

Expression of PD-L1 in Patients With Malignant Peritoneal Mesothelioma: A Pilot Study.

INTRODUCTION: Frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM) have not been well characterized. The purpose of this study was to determine PD-L1 expression in patients with MPM and perform an exploratory analysis for associations between PD-L1 and its biological behavior in MPM. METHODS: Tumor samples were collected from patients undergoing surgical interventions between January 2018 and June 2020. Specimens were stained with anti-PD-L1 antibodies (Dako 22c3) and positivity was determined by tumor proportion score (TPS) or combined positive score (CPS) being ≥1%. RESULTS: Twenty one samples were obtained from 21 patients. Sixteen of 21 (76%) samples were CPS positive and 9 of 21 (43%) were TPS positive. Three samples had more aggressive biphasic/sarcomatoid histology and a high CPS and TPS (CPS: 3, 75, 95%; TPS: 2, 60, 90%). On an exploratory analysis, as the CPS or TPS threshold increased, there was a trend towards worse survival. CONCLUSIONS: MPM has a high frequency of PD-L1 expression, which may be associated with more aggressive tumor biology. These data provide the foundation for continued evaluation of checkpoint inhibition in patients with MPM.

Neoadjuvant Therapy for Pancreatic Cancer: Increased Use and Improved Optimal Outcomes.

BACKGROUND: The introduction of more effective chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to assess the evolving use of NAT in individuals with PDAC undergoing pancreatoduodenectomy (PD) and to compare their outcomes with patients undergoing upfront operation. STUDY DESIGN: The American College of Surgeons NSQIP Procedure Targeted Pancreatectomy database was queried from 2014 to 2019. Patients undergoing pancreatoduodenectomy were evaluated based on the use of NAT versus upfront operation. Multivariable analysis was performed to determine the effect of NAT on postoperative outcomes, including the composite measure optimal pancreatic surgery (OPS). Mann-Kendall trend tests were performed to assess the use of NAT and associated outcomes over time. RESULTS: A total of 13,257 patients were identified who underwent PD for PDAC between 2014 and 2019. Overall, 33.6% of patients received NAT. The use of NAT increased steadily from 24.2% in 2014 to 42.7% in 2019 (p < 0.0001). On multivariable analysis, NAT was associated with reduced serious morbidity (odds ratio [OR] 0.83, p < 0.001), clinically relevant pancreatic fistulas (OR 0.52, p < 0.001), organ space infections (OR 0.74, p < 0.001), percutaneous drainage (OR 0.73, p < 0.001), reoperation (OR 0.76, p = 0.005), and prolonged length of stay (OR 0.63, p < 0.001). OPS was achieved more frequently in patients undergoing NAT (OR 1.433, p < 0.001) and improved over time in patients receiving NAT (50.7% to 56.6%, p < 0.001). CONCLUSION: NAT before pancreatoduodenectomy increased more than 3-fold over the past decade and was associated with improved optimal operative outcomes.

CovidStats: Development and Implementation of a Daily COVID-19 Clinical Dashboard in an Urban Teaching Hospital.

BACKGROUND AND OBJECTIVES: Dashboards have been utilized in health care to improve quality and patient care. The purpose of our project was to create a concise, timely, and accurate dashboard for administrative and clinical leadership during the COVID-19 pandemic. METHODS: Two authors collaborated to identify 14 metrics and design a comprehensive dashboard (CovidStats, CS) using Microsoft Excel. The dashboard was updated daily and distributed to leadership between December 2020 and April 2021. The utility of this quality measure was assessed by survey of hospital leadership. RESULTS: The 14 metrics included were as follows: (1) elective surgery census threshold; (2) daily COVID admissions; (3) daily COVID discharges; (4) net COVID admissions; (5) ED (emergency department) bed holds; (6) COVID ED bed holds; (7) hospital census; (8) percent COVID census; (9) active COVID census; (10) COVID ICU (intensive care unit); (11) MICU (medical ICU) census; (12) ventilators in use; (13) high-flow oxygen devices in use; and (14) weekly hospital census. The leadership response survey revealed unanimous approval for CS, with a mean rating of 4.9 ± 0.3 (rated 1-5). CONCLUSIONS: Effective clinical dashboards can be created using affordable basic computer software. Implementation of the CS dashboard conveyed relevant and timely information, which influenced the decision making of hospital leadership during the COVID-19 pandemic.

Outcomes of Barotrauma in Critically Ill COVID-19 Patients With Severe Pneumonia.

BACKGROUND: Pneumomediastinum and pneumothorax are complications which may be associated with barotrauma in mechanically ventilated patients. The current literature demonstrates unclear outcomes regarding barotrauma in critically ill patients with severe COVID-19. The purpose of this study was to examine the incidence of barotrauma in patients with severe COVID-19 pneumonia and its influence on survival. STUDY DESIGN AND METHODS: A retrospective cohort study was performed from March 18, 2020 to May 5, 2020, with follow-up through June 18, 2020, encompassing critically ill intubated patients admitted for COVID-19 pneumonia at an academic tertiary care hospital in Brooklyn, New York. Critically ill patients with pneumomediastinum, pneumothorax, or both (n = 75) were compared to those without evidence of barotrauma (n = 206). Clinical characteristics and short-term patient outcomes were analyzed. RESULTS: Barotrauma occurred in 75/281 (26.7%) of included patients. On multivariable analysis, factors associated with increased 30-day mortality were elevated age (HR 1.015 [95% CI 1.004-1.027], P = 0.006), barotrauma (1.417 [1.040-1.931], P = 0.027), and renal dysfunction (1.602 [1.055-2.432], P = 0.027). Protective factors were administration of remdesivir (0.479 [0.321-0.714], P < 0.001) and receipt of steroids (0.488 [0.370-0.643], P < 0.001). CONCLUSION: Barotrauma occurred at high rates in intubated critically ill patients with COVID-19 pneumonia and was found to be an independent risk factor for 30-day mortality.

Assessing the immediate impact of COVID-19 on surgical oncology practice: Experience from an NCI-designated Comprehensive Cancer Center in the Northeastern United States.

BACKGROUND: The effects of the coronavirus disease 2019 (COVID-19) pandemic on surgical oncology practice are not yet quantified. The aim of this study was to measure the immediate impact of COVID-19 on surgical oncology practice volume. METHODS: A retrospective study of patients treated at an NCI-Comprehensive Cancer Center was performed. "Pre-COVID" era was defined as January-February 2020 and "COVID" as March-April 2020. Primary outcomes were clinic visits and operative volume by surgical oncology subspecialty. RESULTS: Abouyt 907 new patient visits, 3897 follow-up visits, and 644 operations occurred during the study period. All subspecialties experienced significant decreases in new patient visits during COVID, though soft tissue oncology (Mel/Sarc), gynecologic oncology (Gyn/Onc), and endocrine were disproportionately affected. Telehealth visits increased to 11.4% of all visits by April. Mel/Sarc, Gyn/Onc, and Breast experienced significant operative volume decreases during COVID (25.8%, p = 0.012, 43.6% p < 0.001, and 41.9%, p < 0.001, respectively), while endocrine had no change and gastrointestinal oncology had a slight increase (p = 0.823) in the number of cases performed. CONCLUSIONS: The effects of the COVID-19 pandemic are wide-ranging within surgical oncology subspecialties. The addition of telehealth is a viable avenue for cancer patient care and should be considered in surgical oncology practice.

Clinical Characteristics and Outcome of Pneumomediastinum in Patients with COVID-19 Pneumonia.

Introduction: Pneumomediastinum (PM) is characterized by the presence of air within the mediastinum. The association between PM and coronavirus 2019 (COVID-19) has not been well established in the current literature. We sought to summarize the limited body of literature regarding PM in patients with COVID-19 and characterize the presentation and clinical outcomes of PM in patients with severe acute respiratory syndrome (SARS)-COV-2 pneumonia at our institution to better define the incidence, prognosis, and available treatment for this condition. Materials and Methods: All patients with a proven diagnosis of COVID-19 and PM between March 18, 2020 and May 5, 2020 were identified through hospital records. Retrospective analysis of radiology records and chart review were conducted. Clinical characteristics and outcomes were collected and descriptive statistics was analyzed. Results: Thirty-six patients met inclusion criteria. Out of the 346 intubated COVID-19 patients, 34 (10%) had PM. The incidence of PM increased for the first 4 weeks of the pandemic, and then began to decrease by week 5. At the endpoint of the study, 12 (33.33%) patients were alive and 24 patients (66.67%) had died. Conclusion: PM, although a rare phenomenon, was more prevalent in COVID-19 patients compared with historical patients with adult respiratory distress syndrome. The etiology of this condition may be attributed to higher susceptibility of patients infected with SARS-CoV-2 to a combination of barotrauma and airway injury.

A rare case of perianal apocrine adenocarcinoma.

Apocrine adenocarcinoma is a rare primary cutaneous malignancy that arises from areas with high apocrine gland density, most frequently described in the axilla. There have only been three previously reported cases of apocrine adenocarcinoma in the anal/perianal region. A 72-year-old female presented for evaluation of a perianal lesion with persistent drainage that she had noticed for over a year. The patient proceeded with surgical excision of the perianal nodule. Diagnosis was made based on pathology demonstrating areas of mixed solid and trabecular areas with large nuclei and many prominent mitotic figures, which stained positive for periodic acid-Schiff-diastase, cytokeratin 7 and gross cystic disease fluid protein 15. We are reporting just the fourth such case of apocrine adenocarcinoma in the anal/perianal region. It is important to consider apocrine adenocarcinoma in our differential, because though apocrine adenocarcinoma has a benign clinical presentation, it can have a high incidence of lymph invasion on presentation.

Role of Immune Checkpoint Inhibitors in Gastrointestinal Malignancies.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid and hematological malignancies. ICIs are not only able to produce long and durable responses, but also very well tolerated by patients. There are several approved indications of use of ICIs in treatment of metastatic gastrointestinal malignancies including gastric, esophageal, colorectal and hepatocellular carcinoma. In addition, ICIs can be used in microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB) tumors in chemotherapy-resistant setting. Despite having good efficacy and superior safety profile, ICIs are clinically active in small subset of patients, therefore, there is a huge unmet need to enhance their efficacy and discover new predictive biomarkers. There are several ongoing clinical trials that are exploring the role of ICIs in various gastrointestinal cancers either as single agent or in combination with chemotherapy, radiation therapy, targeted agents or other immunotherapeutic agents. In this review, we discuss the published and ongoing trials for ICIs in gastrointestinal malignancies, including esophageal, gastric cancer, pancreatic, hepatocellular, biliary tract, colorectal and anal cancers. Specifically, we focus on the use of ICIs in each line of therapy and discuss the future directions of these agents in each type of gastrointestinal cancer.

Pneumococcal Polysaccharide Vaccine Ameliorates Murine Lupus.

Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (TFH) and T follicular regulatory cells (TFR), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with fewer TFH and increased TFR. Together, the data support use of Prevnar vaccination in individuals with SLE.

Nonreceptor tyrosine kinases ITK and BTK negatively regulate mast cell proinflammatory responses to lipopolysaccharide.

BACKGROUND: Mast cells are indispensable for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate septic responses. ITK and BTK regulate mast cell responses to allergens, but their roles in mast cell responses in LPS-induced sepsis are unclear. OBJECTIVE: We sought to investigate the roles of ITK and BTK in mast cell responses during LPS-induced septic inflammation. METHODS: Mice (genetically modified or bone marrow-derived mast cell-reconstituted Sash) were given LPS to induce septic hypothermia in the presence or absence of indicated inhibitors. Flow cytometry was used to determine LPS-induced cell influx and TNF-α production in peritoneal cells. Microarray was used for genomewide gene expression analysis on bone marrow-derived mast cells. Quantitative PCR and multiplex were used to determine transcribed and secreted proinflammatory cytokines. Microscopy and Western blotting were used to determine activation of signal transduction pathways. RESULTS: The absence of ITK and BTK leads to exacerbation of LPS-induced septic hypothermia and neutrophil influx. Itk(-/-)Btk(-/-) mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, and lead to more severe LPS-induced septic hypothermia when reconstituted into mast cell-deficient Sash mice. LPS-induced nuclear factor kappa B, Akt, and p38 activation is enhanced in Itk(-/-)Btk(-/-) mast cells, and blockage of phosphatidylinositol-4,5-bisphosphate 3-kinase, Akt, or p38 downstream mitogen-activated protein kinase interacting serine/threonine kinase 1 activation significantly suppresses TNF-α hyperproduction and attenuates septic hypothermia. CONCLUSIONS: ITK and BTK regulate thermal homeostasis during septic response through mast cell function in mice. They share regulatory function downstream of Toll-like receptor 4/LPS in mast cells, through regulating the activation of canonical nuclear factor kappa B, phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt, and p38 signaling pathways.

The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor.

Tec family kinases play critical roles in the activation of immune cells. In particular, Itk is important for the activation of T cells via the T cell Receptor (TcR), however, molecules that cooperate with Itk to activate downstream targets remain little explored. Here we show that Itk interacts with the heterotrimeric G-protein α subunit Gα13 during TcR triggering. This interaction requires membrane localization of both partners, and is partially dependent on GDP- and GTP-bound states of Gα13. Furthermore, we find that Itk interacts with Gα13 via the zinc binding regions within its Tec homology domain. The interaction between Itk and Gα13 also results in tyrosine phosphorylation of Gα13, however this is not required for the interaction. Itk enhances Gα13 mediated activation of serum response factor (SRF) transcriptional activity dependent on its ability to interact with Gα13, but its kinase activity is not required to enhance SRF activity. These data reveal a new pathway regulated by Itk in cells, and suggest cross talk between Itk and G-protein signaling downstream of the TcR.