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Rosai-Dorfman disease (RDD) is a non-Langerhans cell histiocytosis which usually presents as painless lymphadenopathy. Extranodal involvement is known to occur in various organs, and less than ten cases with primary pancreatic involvement have been reported previously. This case report details the clinical course of an elderly female, presenting with upper abdominal discomfort and imaging suggestive of malignancy. Multiple non-diagnostic fine-needle aspirations were followed by surgical intervention. Histopathological evaluation revealed a pancreatic mass with characteristic features of RDD. The large hallmark RDD histiocytes showed pale, watery-clear cytoplasm, central round nucleus, and prominent nucleolus, with and without lymphocyte emperipolesis. The RDD histiocytes showed positive immunostaining for CD68, CD163, S100 (nuclear and cytoplasmic), OCT-2, Cyclin D1 and are negative for CD1a, Factor XIIIa, fascin and langerin. This case underscores the importance of considering RDD in the differential diagnosis of pancreatic masses alongwith comprehensive evaluation, multidisciplinary approach and pancreatic core needle biopsy evaluation.

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Cecal volvulus is a rare and life-threatening cause of intestinal obstruction with multiple risk factors including prior abdominal surgery and cecal hypermobility. Although its incidence has been reported after common procedures such as cholecystectomy and appendectomy, it has not been well studied after laparoscopy, especially in gynecological surgeries. If untreated, a cecal volvulus can result in serious complications such as intestinal strangulation, necrosis, or perforation. Therefore, early identification of risk factors and intervention is important in prevention of these sequelae. Here, we report a case of cecal volvulus in a patient with endometrial carcinoma after a staging robotic-assisted laparoscopic hysterectomy and the risk factors that may have led to her complication.

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Tumor cell intravasation is essential for metastatic dissemination, but its exact mechanism is incompletely understood. We have previously shown that in breast cancer, the direct and stable association of a tumor cell expressing Mena, a Tie2hi/VEGFhi macrophage, and a vascular endothelial cell, creates an intravasation portal, called a "tumor microenvironment of metastasis" (TMEM) doorway, for tumor cell intravasation, leading to dissemination to distant sites. The density of TMEM doorways, also called TMEM doorway score, is a clinically validated prognostic marker of distant metastasis in breast cancer patients. Although we know that tumor cells utilize TMEM doorway-associated transient vascular openings to intravasate, the precise signaling mechanisms involved in TMEM doorway function are only partially understood. Using two mouse models of breast cancer and an in vitro assay of intravasation, we report that CSF-1 secreted by the TMEM doorway tumor cell stimulates local secretion of VEGF-A from the Tie2hi TMEM doorway macrophage, leading to the dissociation of endothelial junctions between TMEM doorway associated endothelial cells, supporting tumor cell intravasation. Acute blockade of CSF-1R signaling decreases macrophage VEGF-A secretion as well as TMEM doorway-associated vascular opening, tumor cell trans-endothelial migration, and dissemination. These new insights into signaling events regulating TMEM doorway function should be explored further as treatment strategies for metastatic disease.

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BACKGROUND: Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied. METHODS: This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions. RESULTS: Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted. CONCLUSION: Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.

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The physiology and pathophysiology of the pancreas are complex. Diseases of the pancreas, such as pancreatitis and pancreatic adenocarcinoma (PDAC) have high morbidity and mortality. Intravital imaging (IVI) is a powerful technique enabling the high-resolution imaging of tissues in both healthy and diseased states, allowing for real-time observation of cell dynamics. IVI of the murine pancreas presents significant challenges due to the deep visceral and compliant nature of the organ, which make it highly prone to damage and motion artifacts. Described here is the process of implantation of the Stabilized Window for Intravital imaging of the murine Pancreas (SWIP). The SWIP allows IVI of the murine pancreas in normal healthy states, during the transformation from the healthy pancreas to acute pancreatitis induced by cerulein, and in malignant states such as pancreatic tumors. In conjunction with genetically labeled cells or the administration of fluorescent dyes, the SWIP enables the measurement of single-cell and subcellular dynamics (including single-cell and collective migration) as well as serial imaging of the same region of interest over multiple days. The ability to capture tumor cell migration is of particular importance as the primary cause of cancer-related mortality in PDAC is the overwhelming metastatic burden. Understanding the physiological dynamics of metastasis in PDAC is a critical unmet need and crucial for improving patient prognosis. Overall, the SWIP provides improved imaging stability and expands the application of IVI in the healthy pancreas and malignant pancreas diseases.

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Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

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Pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are grave illnesses with high levels of morbidity and mortality. Intravital imaging (IVI) is a powerful technique for visualizing physiological processes in both health and disease. However, the application of IVI to the murine pancreas presents significant challenges, as it is a deep, compliant, visceral organ that is difficult to access, easily damaged and susceptible to motion artefacts. Existing imaging windows for stabilizing the pancreas during IVI have unfortunately shown poor stability for time-lapsed imaging on the minutes to hours scale, or are unable to accommodate both the healthy and tumour-bearing pancreata. To address these issues, we developed an improved stabilized window for intravital imaging of the pancreas (SWIP), which can be applied to not only the healthy pancreas but also to solid tumours like PDAC. Here, we validate the SWIP and use it to visualize a variety of processes for the first time, including (1) single-cell dynamics within the healthy pancreas, (2) transformation from healthy pancreas to acute pancreatitis induced by cerulein, and (3) the physiology of PDAC in both autochthonous and orthotopically injected models. SWIP can not only improve the imaging stability but also expand the application of IVI in both benign and malignant pancreas diseases.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT856-1313) into PDAC tumor cells by attenuated Listeria monocytogenes. This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria-TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria-TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria-TT + GEM-treated mice demonstrated a CD4 T cell-mediated reduction in tumor burden. CD4 T cells from TT-vaccinated mice were able to kill TT-expressing Panc-02 tumor cells in vitro. In addition, peritumoral lymph node-like structures were observed in close contact with pancreatic tumors in KPC mice treated with Listeria-TT or Listeria-TT + GEM. These structures displayed CD4 and CD8 T cells producing perforin and granzyme B. Whereas CD4 T cells efficiently infiltrated the KPC tumors, CD8 T cells did not. Listeria-TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. These results suggest that Listeria-delivered recall antigens could be an alternative to neoantigen-mediated cancer immunotherapy.

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BACKGROUND: Auditory brainstem response (ABR) testing is considered to be relatively resistant to effects of volatile anesthetics. The impact of newer anesthetics on interpretability of ABR testing is unknown. This study compared sevoflurane versus propofol anesthesia on qualitative interpretability of ABR click-testing in children. METHODS: This prospective double-blind crossover study enrolled children (≤18 years old) receiving general anesthesia for elective ABR testing. All subjects received both sevoflurane and propofol anesthesias in the same ABR testing session. Deidentified ABR data were reviewed by 5 audiologists (blinded to anesthetic and patient) to determine threshold levels for hearing loss. The primary outcome was qualitative interpretability (false positive) of ABR click-testing. RESULTS: Each patient was tested at 4 different intensities in each ear: generating 624 records under each anesthetic, for a total of 1248 records. A few patients were tested at 5 different intensities in a single ear accounting for the additional 11 records, yielding 1259 records. Under sevoflurane anesthesia, 21 of the same patients (37 ears) were identified with abnormal ABR levels consistent with hearing loss (one or both ears). The probability of a patient being diagnosed with hearing "loss" in one or both ears was significantly less with propofol versus sevoflurane anesthesia (mid P =.0312). If patients with bilateral loss are compared, the mid P value is 0.0098. The effect size based on patients was medium to large, with a minimum value of Cohen w = 0.320. CONCLUSIONS: Sevoflurane produced more false positives for hearing loss and suggested more severe hearing loss than propofol. False-positive ABR tests, produced by certain anesthetic agents, can have significant life-long impact and negative psychosocial and developmental implications. Use of the intravenous anesthetic propofol is superior to sevoflurane for ABR testing in children.

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The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological and functional differences that drive the extent of metastasis are poorly understood. We analyzed primary tumors and paired metastases using a multifluorescent lineage-labeled mouse model of pancreatic ductal adenocarcinoma (PDAC)-a tumor type in which most patients present with metastases. Genomic and transcriptomic analysis revealed an association between metastatic burden and gene amplification or transcriptional upregulation of MYC and its downstream targets. Functional experiments showed that MYC promotes metastasis by recruiting tumor-associated macrophages, leading to greater bloodstream intravasation. Consistent with these findings, metastatic progression in human PDAC was associated with activation of MYC signaling pathways and enrichment for MYC amplifications specifically in metastatic patients. Collectively, these results implicate MYC activity as a major determinant of metastatic burden in advanced PDAC. SIGNIFICANCE: Here, we investigate metastatic variation seen clinically in patients with PDAC and murine PDAC tumors and identify MYC as a major driver of this heterogeneity.This article is highlighted in the In This Issue feature, p. 275.

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BACKGROUND: Hepatobiliary Scintigraphy (HIDA) aids the diagnosis of acute cholecystitis (AC) but has limitations. We sought to design a model based on the Tokyo Guidelines 2018 (TG18) to predict HIDA results. METHODS: A retrospective review of patients who underwent a HIDA scan during the evaluation of AC was performed. Using logistic regression techniques incorporating the TG18 criterion and additional readily available patient characteristics, a prediction model was created to identify patients likely to test negative for acute cholecystitis by HIDA scan. RESULTS: In 235 patients with suspected AC, a HIDA scan was performed. Variables associated with positive HIDA results were male gender (RR 2.0 (CI 1.33-2.99), age (OR 1.02 (CI 1.01-1.04), right upper quadrant tenderness (RR 1.7 (CI 1.1-2.8)), clinical Murphy's sign (RR 2.2 (CI 1.5-3.4)), ultrasound findings suggestive of AC by any of its components (RR 3.2 (CI 1.6-6.5)), gallbladder wall thickening (RR 2.0 (CI 1.3-3.1)), and gallbladder distention (RR 1.9 (CI 1.3-2.9)). These variables allowed for creation of a model to predict HIDA results. The model predicted HIDA results in 36.9% of patients with an area under the curve of 0.81. CONCLUSIONS: In the era of TG18, HIDA is probably over utilized. We developed an accurate, simple model based on TG18 that identifies a group of patients for whom a HIDA scan is unnecessary to establish the diagnosis of AC.

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BACKGROUND: The safety of surgery in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients remains unclear. On the basis of data from other viral diseases, it has been assumed that coronavirus disease 2019 (COVID-19) has the potential risk of transmission during surgery. The presence of the virus within the peritoneal fluid and the peritoneal tissues is not known. MATERIALS AND METHODS: This is a prospective cross-sectional study including adult patients with confirmed COVID-19 who underwent surgery at a single institution. Using specific real-time reverse transcriptase-polymerase chain reaction, the presence of SARS-CoV-2 was determined in abdominal fluid samples. RESULTS: Six patients with COVID-19 underwent abdominal surgery. Five patients were asymptomatic, and 1 had severe disease. SARS-CoV-2 was tested in 20 different samples, all of which resulted negative. CONCLUSIONS: SARS-CoV-2 was not found in the peritoneal cavity of 6 patients undergoing abdominal surgery. The risk of transmissibility of COVID-19 during surgery is still unclear.

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Many algorithms, checklists, and escalation pathways have been created to encourage perioperative teams to share a mental model and approach patient care as a team. Respecting and empowering the many voices involved in patient care is crucial to avoid errors and improve patient safety. None of the concepts described herein are novel; however, sustained improvements in operating room culture remain elusive in many organizations. The implementation of practices directed toward driving change in operating room culture has led to improvements in Occupational Safety and Health Administration (OSHA) recordables, perioperative communication, and patient care practices. In this paper, we will review the importance of culture, mutual accountability, and communication in improving patient care, and share several of the processes that have been created at our pediatric tertiary care center.

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We report a case of a common bile duct neuroendocrine tumor discovered in a patient with von Hippel-Lindau disease to emphasize the importance of recognizing this unusual diagnosis. This case illustrates the importance of endoscopic evaluation and the potential diagnostic pitfalls which may impact its appropriate management: the anatomic proximity of more common von Hippel-Lindau disease-related tumors, pathologic evaluation, and staging. Therefore, awareness of this rare diagnosis is important for appropriate treatment.

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BACKGROUND: Outcomes after adrenalectomy in patients with primary aldosteronism (PA) are variable. The aldosteronoma resolution score (ARS) uses preoperative variables to calculate a score that identifies those patients that are more likely to have resolution of hypertension after adrenalectomy. We aim to determine the efficacy of adrenalectomy and whether the ARS accurately predicts clinical success in a Black and Hispanic population. METHODS: We reviewed patients who underwent adrenalectomy for PA from 2004 to 2018 at two academic centers treating primarily Hispanic and Black patients. Postoperative outcomes were evaluated based on the primary aldosteronism surgical outcome consensus criterion. Retrospectively, the accuracy of ARS was determined by a receiver operating characteristic curve and the area under the curve (AUC). RESULTS: Forty-three Hispanic and 10 Black patients underwent adrenalectomy for PA. Twenty-two patients (41.5%) had complete clinical success. Variables associated with complete clinical success in the univariate analysis were female gender (p = 0.026), younger age (p = 0.001), lower preoperative aldosterone (p = 0.035), lower preoperative systolic blood pressure (p = 0.001), fewer number of preoperative antihypertensive medications (p = 0.007) and a higher ARS (p = 0.003). On multivariate analysis, only fewer number of preoperative antihypertensive medications was independently associated with complete clinical success (p = 0.026). The AUC of the ARS was 0.746. CONCLUSION: The rate of clinical success from adrenalectomy is good for Hispanic and Black patients with PA. Our analysis shows that the ARS is an accurate test of clinical success in Hispanic and Black patients. The ARS may be utilized preoperatively to frame expectations after adrenalectomy in these populations.

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BACKGROUND: Currently, there are no methods to identify patients with an increased risk of liver metastases to guide patient selection for liver-directed therapies. We tried to determine whether quantitative image features (radiomics) of the liver obtained from preoperative staging CT scans at the time of initial colon resection differ in patients that subsequently develop liver metastases, extrahepatic metastases, or demonstrate prolonged disease-free survival. METHODS: Patients who underwent resection of stage II/III colon cancer from 2004 to 2012 with available preoperative CT scans were included in this single-institution, retrospective case-control study. Patients were grouped by initial recurrence patterns: liver recurrence, extrahepatic recurrence, or no evidence of disease at 5 years. Radiomic features of the liver parenchyma extracted from CT images were compared across groups. RESULTS: The cohort consisted of 120 patients divided evenly between three recurrence groups, with an equal number of stage II and III patients in each group. After adjusting for multiple comparisons, 44 of 254 (17%) imaging features displayed different distributions across the three patient groups (p < 0.05), with the clearest distinction between those with liver recurrence and no evidence of disease. Increased heterogeneity in the liver parenchyma by radiomic analysis was protective of liver metastases. CONCLUSIONS: CT radiomics is a promising tool to identify patients at high risk of developing liver metastases and is worthy of further investigation and validation.

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BACKGROUND: The impact of emergency department admission prior to pancreatic resection on perioperative outcomes is not well described. We compared patients who underwent pancreatic cancer surgery following admission through the emergency department (ED-surgery) with patients receiving elective pancreatic cancer surgery (elective) and outcomes. STUDY DESIGN: The Nationwide Inpatient Sample database was used to identify patients undergoing pancreatectomy for cancer over 5 years (2008-2012). Demographics and hospital characteristics were assessed, along with perioperative outcomes and disposition status. RESULTS: A total of 8158 patients were identified, of which 516 (6.3%) underwent surgery after admission through the ED. ED-surgery patients were more often socioeconomically disadvantaged (non-White 39% vs. 18%, Medicaid or uninsured 24% vs. 7%, from lowest income area 33% vs. 21%; all p < .0001), had higher comorbidity (Elixhauser score > 6: 44% vs. 26%, p < .0001), and often had pancreatectomy performed at sites with lower annual case volume (< 7 resections/year: 53% vs. 24%, p < .0001). ED-surgery patients were less likely to be discharged home after surgery (70% vs. 82%, p < .0001) and had higher mortality (7.4% vs. 3.5%, p < .0001). On multivariate analysis, ED-surgery was independently associated with a lower likelihood of being discharged home (aOR 0.55 (95%CI 0.43-0.70)). CONCLUSION: Patients undergoing pancreatectomy following ED admission experience worse outcomes compared with those who undergo surgery after elective admission. The excess of socioeconomically disadvantaged patients in this group suggests factors other than clinical considerations alone drive this decision. This study demonstrates the need to consider presenting patient circumstances and preoperative oncologic coordination to reduce disparities and improve outcomes for pancreatic cancer surgery.

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BACKGROUND: The impact of the stage of cancer on perioperative mortality remains obscure. The purpose of this study was to investigate whether cancer stage influences 30-d mortality for gastric, pancreatic, and colorectal cancers. METHODS: Data were collected from the National Cancer Database for patients undergoing resections for cancers of the stomach, pancreas, colon, or rectum between 2004 and 2015. The main analysis was conducted among patients with cancer stages 1-3. A sensitivity analysis also included cancer stage 4. Descriptive statistics were used to compare the patients' baseline characteristics. Generalized linear mixed models were used to evaluate the relationship between stage and 30-d mortality, controlling for other disease-, patient- and hospital-level factors. Pseudo R2 statistics (%Δ pseudo R2) were used to quantify the relative explanatory capacity of the variables to the model for 30-d mortality. All analyses were performed using SAS 9.4. RESULTS: The cohort included 24,468, 28,078, 176,285, and 64,947 patients with stomach, pancreas, colon, and rectal cancers, respectively. After adjusting for other variables, 30-d mortality was different by stage for all cancer types examined. The factor most strongly associated with 30-d mortality was age (%Δ pseudo R2 range 14%-39%). The prognostic impact of cancer stage (Stages 1, 2, or 3) on 30-d mortality was comparable to that of the Charlson comorbidity index. CONCLUSIONS: Cancer stage contributes to explaining differences observed in short-term mortality for gastrointestinal cancers. Short-term mortality models would benefit by including more granular cancer stage, beyond disseminated status alone.

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