A 22-year single institution review of 119 cases of salivary duct carcinoma.

Objective: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. Methods: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. Results: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Conclusion: Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level of Evidence: Level 3.

Ghost Cell Odontogenic Carcinoma: A Case Report and Literature Review.

Ghost cell odontogenic carcinoma (GCOC) is an exceptionally rare malignant odontogenic neoplasm with a significant potential for aggressive growth. Although the literature on this tumor is limited, its high recurrence rates suggest that early and multimodal intervention may be beneficial. This study reports a case of GCOC of the mandible that was successfully treated with surgical resection, reconstruction, and radiation. A comprehensive literature review was performed, and the relevant genomic and histopathological characteristics of this malignancy were determined. Laryngoscope, 133:830-833, 2023.

Audit of Postoperative Readmissions and Patient Messages following Endoscopic Transnasal Transsphenoidal Surgery.

Objectives The aim of this study was to identify the reasons for patient messages, phone calls, and emergency department (ED) visits prior to the first postoperative visit following discharge after endoscopic transnasal transsphenoidal (eTNTS) surgery. Design This is a retrospective review of patients at a tertiary care academic center who underwent eTNTS for resection of a sellar region tumor between May 2020 and August 2021. Patient, tumor, and surgical characteristics were collected, along with postoperative, postdischarge, and readmission information. Regression analyses were performed to investigate risk factors associated with postdischarge phone calls, messages, ED visits, and readmissions. Main Outcome Measures The main outcomes were the number of and reasons for phone calls, patient messages, and ED visits between hospital discharge and the first postoperative visit. We additionally determined whether these reasons were addressed in each patient's discharge instructions. Results A total of 98 patients underwent eTNTS during the study period. The median length of hospital stay was 2 days (interquartile range [IQR]: 1-4 days), at which point most patients (82%) were provided with eTNTS-specific discharge instructions. First postoperative visit took place 9 days after discharge (IQR: 7-10 days). Within that time, 54% of patients made at least one phone call or sent at least electronic message and 17% presented to the ED. Most common reasons for call/message were nasal care, appointment scheduling, and symptom and medication questions. Conclusion Through this work, we highlight the most common reasons for resource utilization via patient phone calls, messages, and ED visits among our cohort to better understand any shortfall or gap in the discharge process that may reduce these events.

Perioperative Antibiotic Use in Endoscopic Endonasal Skull Base Surgery.

Introduction Improved evidence-based guidelines on the optimal type and duration of antibiotics for patients undergoing endoscopic endonasal transsphenoidal surgery (EETS) are needed. We analyze the infectious complications among a large cohort of EETS patients undergoing a standardized regimen of cefazolin for 24 hours, followed by cephalexin for 7 days after surgery (clindamycin if penicillin/cephalosporin allergic). Methods A retrospective review of 132 EETS patients from 2018 to 2020 was conducted. Patient, tumor, and surgical characteristics were collected, along with infection rates. Multivariate logistic regression determined the variable(s) independently associated with infectious outcomes. Results Nearly all patients (99%) received postoperative antibiotics with 78% receiving cefazolin, 17% receiving cephalexin, 3% receiving clindamycin, and 2% receiving other antibiotics. Fifty-three patients (40%) had an intraoperative cerebrospinal fluid (CSF) leak, and three patients (2%) developed a postoperative CSF leak requiring surgical repair. Within 30 days, no patients developed meningitis. Five patients (4%) developed sinusitis, two patients (3%) developed pneumonia, and one patient (1%) developed cellulitis at a peripheral intravenous line. Two patients (2%) developed an allergy to cephalexin, requiring conservative management. After adjustment for comorbidities and operative factors, presence of postoperative infectious complications was independently associated with increased LOS ( ß = 3.7 days; p = 0.001). Conclusion Compared with reported findings in the literature, we report low rates of infectious complications and antibiotic intolerance, despite presence of a heavy burden of comorbidities and high intraoperative CSF leak rates among our cohort. These findings support our standardized 7-day perioperative antibiotic regimen.

Frailty is independently associated with worse outcomes and increased resource utilization following endometrial cancer surgery.

OBJECTIVE: Frailty has been associated with poorer surgical outcomes and is a critical factor in procedural risk assessment. The objective of this study is to assess the impact of frailty on surgical outcomes in patients with endometrial cancer. METHODS: Patients undergoing inpatient gynecologic surgery for endometrial cancer were identified using the 2005-2017 Nationwide Inpatient Sample database. The Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator was used to designate frailty. Multivariate regression models were used to assess the association of frailty with postoperative outcomes and resource use. RESULTS: Of 339 846 patients, 2.9% (9868) were considered frail. After adjusting for patient and hospital characteristics, frailty was associated with a four-fold increase in inpatient mortality (adjusted OR (aOR) 4.1; p<0.001), non-home discharge (aOR 5.2; p<0.001), as well as increased respiratory (aOR 2.6; p<0.001), neurologic (aOR 3.3; p<0.001), renal (aOR 2.0; p<0.001), and infectious (aOR 3.2; p<0.001) complications. While frail patients exhibited increased mortality with age, the rate of mortality in this cohort decreased significantly over time. Compared with non-frail counterparts, frail patients had longer lengths of stay (7.6 vs 3.4 days; p<0.001) and increased hospitalization costs with surgical admission ($25 093 vs $13 405; p<0.001). CONCLUSIONS: Frailty is independently associated with worse surgical outcomes, including increased mortality and resource use, in women undergoing surgery for endometrial cancer. Though in recent years there have been improvements in mortality in the frail population, further efforts to mitigate the impact of frailty should be explored.

Quantifying Cell-Derived Changes in Collagen Synthesis, Alignment, and Mechanics in a 3D Connective Tissue Model.

Dysregulation of extracellular matrix (ECM) synthesis, organization, and mechanics are hallmark features of diseases like fibrosis and cancer. However, most in vitro models fail to recapitulate the three-dimensional (3D) multi-scale hierarchical architecture of collagen-rich tissues and as a result, are unable to mirror native or disease phenotypes. Herein, using primary human fibroblasts seeded into custom fabricated 3D non-adhesive agarose molds, a novel strategy is proposed to direct the morphogenesis of engineered 3D ring-shaped tissue constructs with tensile and histological properties that recapitulate key features of fibrous connective tissue. To characterize the shift from monodispersed cells to a highly-aligned, collagen-rich matrix, a multi-modal approach integrating histology, multiphoton second-harmonic generation, and electron microscopy is employed. Structural changes in collagen synthesis and alignment are then mapped to functional differences in tissue mechanics and total collagen content. Due to the absence of an exogenously added scaffolding material, this model enables the direct quantification of cell-derived changes in 3D matrix synthesis, alignment, and mechanics in response to the addition or removal of relevant biomolecular perturbations. To illustrate this, the effects of nutrient composition, fetal bovine serum, rho-kinase inhibitor, and pro- and anti-fibrotic compounds on ECM synthesis, 3D collagen architecture, and mechanophenotype are quantified.

Opiate Use After Endoscopic Endonasal Transsphenoidal Surgery.

BACKGROUND: The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited. OBJECTIVE: To determine the risk factors for higher opiate use following EETS and the quantity of opiates used after discharge. METHODS: A retrospective review of 144 patients undergoing EETS from July 2018 to July 2020 was conducted. Patient, tumor, and surgical factors were documented. Pain scores and medications used on postoperative days (POD) 0 and 1, and discharge prescriptions, were recorded. Opiate use was quantified using morphine milligram equivalents (MME) dose. Multiple linear regression determined risk factors independently associated with POD0 to 1 opiate use. RESULTS: On POD 0 to 1, mean pain score was 4.9/10 (standard deviation [SD] ± 2.0). Mean acetaminophen use was 3.4 tablets (SD ± 1.6; 650 mg per tablet). Mean opiate use was 35.6 MME (SD ± 36.3), equivalent to 4.7 tablets (SD ± 4.8) of oxycodone 5 mg. Multiple linear regression showed that current smokers required an additional 37.1 MME (P = .011), and patients with grade 3 intraoperative cerebrospinal fluid leaks required an additional 36.7 MME (P = .046) on POD0 to 1. On discharge, mean opiate prescription was 117.7 MME (SD ± 102.1), equivalent to 15.7 tablets (SD ± 13.6) of oxycodone 5 mg. Thirty-nine patients (27.1%) did not require prescriptions. Only 10 patients (6.9%) required opiate refill(s) within 30 days after surgery. CONCLUSION: Patients undergoing EETS have higher opiate needs compared to those undergoing endoscopic sinus surgery, although the overall requirements are still considered low. Independent risk factors associated with higher opiate use in the immediate postoperative period included current smokers and grade 3 intraoperative cerebrospinal fluid leaks.

National trends and predictors of mastectomy with immediate breast reconstruction.

PURPOSE: This study aimed to evaluate national trends in utilization, resource use, and predictors of immediate breast reconstruction (IR) after mastectomy. METHODS: The 2005-2014 National Inpatient Sample database was used to identify adult women undergoing mastectomy. IR was defined as any reconstruction during the same inpatient stay. Multivariable regression models were utilized to identify factors associated with IR. RESULTS: Of 729,340 patients undergoing mastectomy, 41.3% received IR. Rates of IR increased from 28.2% in 2005 to 58.2% in 2014 (NP-trend<0.001). Compared to mastectomy alone, IR was associated with increased length of stay (2.5 vs. 2.1 days, P < 0.001) and hospitalization costs ($17,628 vs. $8,643, P < 0.001), which increased over time (P < 0.001). Predictors of IR included younger age, fewer comorbidities, White race, private insurance, top income quartile, teaching hospital designation, high mastectomy volume, and performance of bilateral mastectomy. CONCLUSION: Mastectomy with IR is increasingly performed with resource utilization rising at a steady pace. Our study points to persistent sociodemographic and hospital level disparities associated with the under-utilization of IR. Efforts are needed to alleviate disparities in IR.

Outcomes and resource use for liver transplantation in the United States: Insights from the 2009-2017 National Inpatient Sample.

INTRODUCTION: Liver transplantation (LT) is a life-saving treatment for end-stage liver disease patients that requires significant resources. We used national data to evaluate LT outcomes and factors associated with hospital resource use. METHODS: Using the National Inpatient Sample, we identified all patients undergoing LT from 2009 to 2017 and defined high-resource use (HRU) as having costs ≥ 90th percentile. Hierarchical regression models were used to assess factors associated with length of stay (LOS) and HRU. RESULTS: Over the study period, approximately 53,000 patients underwent LT, increasing from 5,582 in 2009 to 7,095 in 2017 (nptrend < 0.001). Morbidity and mortality were 42.2% and 3.9%, respectively, with a median post-LT LOS of 10 days. Hospitalization costs increased from $106,866 to $145,868 (nptrend < 0.001). Acute kidney injury (ß:4.7 days, P < .001) and end-stage renal disease (ESRD) with dialysis (ß:4.3 days, P < .001) were associated with greater LOS while the Northeast region (AOR:5.2, P < .001), ESRD with dialysis (AOR:3.4, P < .001), heart failure (AOR:2.5, P < .001), and fulminant liver disease (AOR:1.8, P = .01) were associated with HRU. CONCLUSION: The cost of LT has increased over time. Renal dysfunction, regional practice patterns, and patient acuity were associated with greater resource use. Transplanting patients before health deterioration may help contain costs, mitigate resource use, and improve LT outcomes.

National trends and outcomes of inpatient robotic-assisted versus laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy has reached nearly universal adoption in the management of gallstone-related disease. With advances in operative technology, robotic-assisted cholecystectomy has been used increasingly in many practices, but few studies have examined the adoption of robotic assistance for inpatient cholecystectomy and the temporal outcomes on a national scale. The present study aimed to identify trends in utilization, as well as outcomes and factors associated with the use of robotic-assisted cholecystectomy. METHODS: The 2008 to 2017 database of the National Inpatient Sample was used to identify patients undergoing inpatient cholecystectomy. Independent predictors of the use of robotic assistance for cholecystectomy were identified using multivariable logistic regression adjusting for patient and hospital characteristics. RESULTS: Of an estimated 3,193,697 patients undergoing cholecystectomy, 98.7% underwent laparoscopic cholecystectomy and 1.3% robotic-assisted cholecystectomy. Rates of robotic-assisted cholecystectomy increased from 0.02% in 2008 to 3.2% in 2017 (nptrend < .001). Compared with laparoscopic cholecystectomy, patients undergoing robotic-assisted cholecystectomy had a greater burden of comorbidities as measured by the Elixhauser index (2.2 vs 1.9, P < .001). Although mortality rates were similar, robotic-assisted cholecystectomy was associated with greater complication rates (15.5% vs 11.7%, P < .001), most notably gastrointestinal-related complications (3.7% vs 1.5%, P < .001). On multivariable regression, robotic-assisted cholecystectomy was associated with increased costs of hospitalization (ß: $2,398, P < .001). CONCLUSION: Using the largest national database available, we found a dramatic increase in the use of robotic-assisted cholecystectomy with no difference in mortality or duration of hospital stay, but there was a statistically significant increase in complications and costs. These findings warrant further investigation.

The impact of obesity on outcomes in patients receiving extracorporeal life support.

Extracorporeal life support (ECLS) has been increasingly utilized to manage cardiac and pulmonary dysfunction. The impact of obesity on outcomes of ECLS is poorly defined. The purpose of the study was to compare in-hospital mortality, resource use, complications, and readmissions in obese versus non-obese patients receiving ECLS. We performed a retrospective cohort study of all adult ECLS patients with and without an obesity diagnosis using the 2010-2016 Nationwide Readmissions Database (NRD). Mortality, length of stay (LOS), hospital charges, complications, and readmissions were evaluated using multivariable logistic and linear regression. Of 23 876, patients who received ECLS, 1924 (8.1%) were obese. Obese patients received ECLS more frequently for respiratory failure (29.5% vs. 23.7%, P = .001). After adjustment for patient and hospital factors, obesity was not associated with increased odds of mortality (AOR = 1.06, P = .44) and was associated with decreased LOS (13.7 vs. 21.2 days, P < .001), hospital charges ($171 866 vs. $211 445, P < .001), and 30-day readmission (AOR = 0.71, P = .03). Obesity was also associated with reduced odds of hemorrhage (AOR = 0.43, P < .001), neurologic complications (AOR = 0.55, P = .004), and acute kidney injury (AOR=0.83, P = .04). After stratification by ECLS indication, obesity remained predictive of shorter LOS (AOR range: 0.53-0.78, all P < .05 ) and did not impact mortality (all P > .05). Respiratory support remains the most common indication for ECLS among obese patients. Among all patients, as well as by individual ECLS indication, obesity was not associated with increased odds of mortality. These findings suggest that obesity should not be considered a high-risk contraindication to ECLS.

Directing fibroblast self-assembly to fabricate highly-aligned, collagen-rich matrices.

Extracellular matrix composition and organization play a crucial role in numerous biological processes ranging from cell migration, differentiation, survival and metastasis. Consequently, there have been significant efforts towards the development of biomaterials and in vitro models that recapitulate the complexity of native tissue architecture. Here, we demonstrate an approach to fabricating highly aligned cell-derived tissue constructs via the self-assembly of human dermal fibroblasts. By optimizing mold geometry, cell seeding density, and media composition we can direct human dermal fibroblasts to adhere to one another around a non-adhesive agarose peg to facilitate the development of cell-mediated circumferential tension. By removing serum and adding ascorbic acid and l-proline, we tempered fibroblast contractility to enable the formation of stable tissue constructs. Similarly, we show that the alignment of cells and the ECM they synthesize can be modulated by changes to seeding density and that constructs seeded with the lowest number of cells have the highest degree of fibrillar collagen alignment. Finally, we show that this highly aligned, tissue engineered construct can be decellularized and that when re-seeded with fibroblasts, it provides instructive cues which enable cells to adhere to and align in the direction of the remaining collagen fiber network. STATEMENT OF SIGNIFICANCE: Cell and extracellular matrix organization is directly related to biological function including cell signaling and tissue mechanics. Changes to this organization are often associated with injury or disease. The majority of in vitro tissue engineering models investigating cell and matrix organization rely on the addition of stress-shielding exogenous proteins and polymers and, or the application of external forces to promote alignment. Here we present a completely cell-based approach that relies on the development of cell-mediated tension to direct anisotropic cellular alignment and matrix synthesis using human dermal fibroblasts. A major challenge with this approach is excessive cellular contractility that results in necking and failure of the tissue construct. While other groups have tried to overcome this challenge by simply adding more cells, here we show that matrix alignment is inversely related to cell seeding density. To engineer tissue constructs with the highest degree of alignment, we optimized media components to reduce cellular contractility and promote collagen synthesis such that fibroblast toroids remained stable for at least 28 days in culture. We subsequently showed that these collagen-rich tissue constructs could be decellularized while maintaining their collagen microstructure and that cells adhered to and responded to the decellularized cell-derived matrix by aligning and elongating along the collagen fibers. The complexity of cell-derived matrices has been shown to better recapitulate in vivo tissue architecture and composition. This study provides a straight-forward approach to fabricating instructive cell-derived matrices with a high degree of uniaxial alignment generated purely by cell-mediated tension.