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PURPOSE: Infantile hypertrophic pyloric stenosis (IHPS) is suspected to have worse outcomes when length of illness prior to presentation is prolonged. Our objective was to evaluate how social determinants of health influence medical care and outcomes for babies with IHPS. METHODS: A retrospective review was performed over 10 years. Census data were used as proxy for socioeconomic status via Geo-Identification codes and correlated with food access and social vulnerability variables. The cohort was subdivided to understand the impact of Medicaid Managed Care (MMC). RESULTS: The cohort (279 cases) was divided into two groups; early group from 2011 to 2015 and late from 2016 to 2021. Cases in the late group were older at the time of presentation (41.5 vs. 36.5 days; p = 0.022) and presented later in the disease course (12.8 vs. 8.9 days; p = 0.021). There was no difference in race (p = 0.282), gender (p = 0.874), or length of stay. CONCLUSIONS: Patients who presented with IHPS after implementation of phased MMC were older, had a longer symptomatic course, and shorter pylorus measurements. Patients with public insurance after the implementation of MMC were more likely to follow-up with an outpatient pediatrician within a month of hospitalization. These results suggest that MMC may have improved access to care for infants with IHPS.
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Cobertura del Seguro , Estenosis Hipertrófica del Piloro , Humanos , Estenosis Hipertrófica del Piloro/cirugía , Estudios Retrospectivos , Femenino , Masculino , Lactante , Estados Unidos , Cobertura del Seguro/estadística & datos numéricos , Recién Nacido , Medicaid/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Determinantes Sociales de la Salud/estadística & datos numéricosRESUMEN
INTRODUCTION: The perceptions of teaching faculty toward pregnant general surgery residents have been overlooked despite the daily interactions amongst these groups. METHODS: A 32-question survey designed to measure general surgery teaching faculty perceptions toward pregnant residents was distributed electronically from March 2022 to April 2022 to general surgery teaching faculty in the United States. Descriptive statistics were used to characterize responses and differences in perceptions, and qualitative analysis identified recurring themes from free-text responses. RESULTS: Among 163 respondents included in the final analysis, 58.5% were male and 41.5% were female. Despite 99.4% of surgeons feeling comfortable if a resident told them they were pregnant, 22.4% of surgeons disagreed that their institutions have supportive cultures toward pregnancy. Almost half (45.4%) have witnessed negative comments about pregnant residents and half (50.3%) believe that pregnant surgical residents are discriminated against by their coresidents. Nearly two-thirds of surgeons (64.8%) believe that someone should have a child whenever they wish during training. Given recent reports, 80.2% of surgeons recognized that female surgeons have increased risks of infertility and pregnancy complications. Recurring themes of normalizing pregnancy, improving policies, and creating a culture change were expressed. CONCLUSIONS: In this national survey, although there appears to be positive perceptions of pregnancy in surgical training amongst those surveyed, there is acknowledged necessity of further normalizing pregnancy and improving policies to better support pregnant residents. These data provide further evidence that though perceptions may be improving, changes are still needed to better support pregnancy during training.
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Docentes Médicos , Cirugía General , Internado y Residencia , Humanos , Femenino , Internado y Residencia/estadística & datos numéricos , Internado y Residencia/organización & administración , Embarazo , Cirugía General/educación , Docentes Médicos/psicología , Docentes Médicos/estadística & datos numéricos , Masculino , Encuestas y Cuestionarios , Estados Unidos , Actitud del Personal de Salud , Adulto , Cirujanos/psicología , Cirujanos/educación , Cirujanos/estadística & datos numéricos , Médicos Mujeres/psicología , Médicos Mujeres/estadística & datos numéricosRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. METHODS: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. RESULTS: Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. CONCLUSION: In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Linfocitos Infiltrantes de Tumor , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Linfocitos T CD8-positivos , Inflamación/patología , Pronóstico , Microambiente TumoralRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS: Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS: Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS: Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.
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Carcinoma Ductal Pancreático , Neoplasias de Cabeza y Cuello , Neoplasias Pancreáticas , Humanos , Caquexia/genética , Caquexia/complicaciones , Estudios Retrospectivos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/complicacionesRESUMEN
Chest masculinization is the most common surgery performed in transgender men, and although incidence of occult cancer is lower than in cis-gender women receiving mastectomy or reduction mammoplasties, the incidence of high-risk lesions is comparable. In patients with concerns for occult malignancy, Magtrace is a nonradioactive tracer available to assist management for its delayed sentinel lymph node mapping capabilities. We present the first case report using Magtrace before masculinizing mastectomies in a transgender man.
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Over the last two decades, there have been many reported advances in the clinical management of pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate changes in survival for patients diagnosed with PDAC between 2004 and 2017. The National Cancer Database was queried for patients diagnosed with PDAC between 2004 and 2017. There were 55,401 patients who underwent surgery and 109,477 patients who underwent non-surgical treatment for PDAC between 2004 and 2017. Patients were categorized into four groups by year of diagnosis. Median survival improved from 15.5 months to 25.3 months for patients treated with surgery between the years 2016 and 2017 compared with between 2004 and 2007 (p < 0.001). Median survival improved from 7.2 months to 10.1 months for patients treated without surgery during the same years (p < 0.001). On multivariable analysis, the hazard ratio for death was estimated to multiply by 0.975 per year for patients treated with surgery and 0.959 per year for patients treated without surgery (p < 0.001). This increase in survival in the setting of evolving care validates continued efforts aimed at improving survival for patients with this devastating disease.
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BACKGROUND: Biopsy of suspected pancreatic cancer (PDAC) in surgical candidates is informative however not always necessary. Biopsies impact treatment options as histological diagnosis are presently required for neo-adjuvant therapy, but not surgical resection. We explored the impact of pursuing tissue diagnosis by endoscopic ultrasound (EUS) biopsy on time to treatment in patients with resectable and borderline resectable PDAC. METHODS: A retrospective review of surgical patients with ultimately proven PDAC was performed (2011-2021). Milestone dates (cancer suspected, biopsy(ies), surgical or neo-adjuvant treatment) were collected. Mann-Whitney-Wilcoxon tests, Pearson's chi-squared tests, Fisher's exact tests, linear regressions, and Cox proportional hazard models were used for data analysis. RESULTS: Among 131 resectable and 58 borderline resectable patients, the borderline resectable group underwent more biopsies (1.2 vs 0.7, p < 0.0001), were more likely to undergo biopsy at tertiary care centers (67.2% vs 30.5%, p < 0.0001), and trended toward longer time to treatment (49 vs 44 days, p = 0.070). Significant increases in days to treatment were seen in patients with Black race (29 days, p = 0.0002) and Medicare insurance (22 days, p = 0.038) and no biopsies at a tertiary care center (10 days, p = 0.039). After adjusting for covariates, additional biopsies significantly delayed treatment (1 biopsy: 21 days, p = 0.0001; 2 biopsies: 44 days, p < 0.0001; 3 biopsies: 68 days, p < 0.0001). CONCLUSIONS: EUS biopsy significantly impacts time between suspicion and treatment of PDAC. This may be exacerbated by clinical practices increasingly favoring neo-adjuvant therapy that necessitates biopsy-proven disease. Time to treatment may also be impacted by access to tertiary centers and racial disparities.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anciano , Humanos , Estados Unidos , Carcinoma Ductal Pancreático/cirugía , Medicare , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/diagnóstico , Biopsia , Estudios RetrospectivosRESUMEN
BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.
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Neoplasias Duodenales , Laparoscopía , Neoplasias Pancreáticas , Humanos , Pancreaticoduodenectomía/métodos , Neoplasias Duodenales/cirugía , Estudios Prospectivos , Páncreas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
Appendiceal cancer treatment may include cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We investigated whether patient race/ethnicity influences outcomes and overall survival for patients with appendiceal cancer who undergo CRS/HIPEC. We queried the National Cancer Database for adult patients with appendiceal cancer treated with CRS/HIPEC from 2006 to 2018. Patients were stratified by race/ethnicity: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and Other. Sociodemographics and outcomes were compared using descriptive statistics. Kaplan-Meier survival analysis and Log-rank tests assessed differences in overall survival (OS). Cox Multivariate Regression evaluated factors associated with OS. In total, 2532 patients were identified: 2098 (82.9%) NHW, 186 (7.3%) NHB, 127 (5.0%) Hispanic, and 121 (4.8%) Other patients. The sociodemographics were statistically different across groups. The perioperative and postoperative outcomes were similar. OS was significantly different by race/ethnicity (p = 0.0029). NHB patients compared to Hispanic patients had the shortest median OS (106.7 vs. 145.9 months, p = 0.0093). Race/ethnicity was independently associated with OS: NHB (HR: 2.117 [1.306, 3.431], p = 0.0023) and NHW (HR: 1.549 [1.007, 2.383], p = 0.0463) patients compared to Hispanic patients had worse survival rates. Racial/ethnic disparities exist for patients with appendiceal cancer undergoing CRS/HIPEC. Despite having similar tumor and treatment characteristics, OS is associated with patient race/ethnicity.
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PURPOSE: The standard of care in resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC) has evolved to include neoadjuvant treatment before surgical resection. Current guidelines call for obtaining histologic tissue diagnosis via endoscopic ultrasound fine-needle aspiration before administration of neoadjuvant therapy, which differ from guidelines discouraging delay in surgical resection for a biopsy. MATERIALS AND METHODS: Whether to proceed with treatment before a biopsy confirms that malignancy is a nuanced decision and includes considerations of physical and psychological risks entailed in both pursuing and forgoing a biopsy. RESULTS: Accuracy of imaging and biopsy results, the presence of contributing clinical signs/symptoms, and the existing precedents of considering biopsies as waivable such as in scenarios with high clinical suspicion and primary surgical resection. CONCLUSION: When considering the aspects of ethical medical practice including beneficence (doing good), nonmaleficence (avoiding harm), autonomy (allowing patients to make decisions about their care), and utilitarianism (doing the most good for the most people), analysis of whether guidelines guiding biopsies should continue to differ between resection and neoadjuvant treatments in PDAC is prudent.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patología , Terapia Neoadyuvante , BiopsiaRESUMEN
BACKGROUND: Minimally invasive (laparoscopic and robotic) surgery (MIS) for colorectal cancer is associated with improved outcomes. We sought to characterize possible disparities in surgical approach and outcomes. PATIENTS AND METHODS: In this cross-sectional study, colorectal adenocarcinoma cases among non-Hispanic white (NHW), non-Hispanic Black (NHB), and Hispanic patients were identified using the National Cancer Database (2010-2017). Logistic and Poisson regressions, generalized logit models, and Cox proportional hazards were used to assess outcomes, with reclassification of surgery type if converted to open. RESULTS: NHB patients were less likely to undergo robotic surgery. After multivariable analysis, NHB patients were 6% less likely, while Hispanic patients were 12% more likely to undergo a MIS approach. Lymph node retrieval was higher (> 1.3% more, p < 0.0001) and length of stay was shorter (> 17% shorter, p < 0.0001) for MIS approaches. Unplanned readmission was lower for MIS colon cancer operations compared with open operations, but not for rectal cancer. Race/ethnicity-adjusted risk of death was lower with MIS approaches for colon as well as rectal cancer. After adjusting for surgery type, risk of death was 12% lower for NHB and 35% lower for Hispanic patients compared with NHW patients. Hispanic patients had 21% lower risk of death, while NHB patients had 12% higher risk of death than NHW patients with rectal cancer, after adjusting for surgery type. CONCLUSIONS: Racial/ethnic disparities exist in utilization of MIS for colorectal cancer treatment, disproportionately affecting NHB patients. Since MIS has the potential to improve outcomes, suboptimal access may contribute to harmful and thus unacceptable disparities in survivorship.
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Neoplasias Colorrectales , Laparoscopía , Neoplasias del Recto , Humanos , Estudios Transversales , Etnicidad , Neoplasias Colorrectales/cirugía , Neoplasias del Recto/cirugíaRESUMEN
BACKGROUND: Fundoplication is known to improve allograft outcomes in lung transplant recipients by reducing retrograde aspiration secondary to gastroesophageal reflux disease, a modifiable risk factor for chronic allograft dysfunction. Laparoscopic Nissen fundoplication has historically been the anti-reflux procedure of choice, but the procedure is associated with discernable rates of postoperative dysphagia and gas-bloat syndrome. Laparoscopic Toupet fundoplication, an alternate anti-reflux surgery with lower rates of foregut complications in the general population, is the procedure of choice on our institution's lung transplant protocol. In this work, we evaluated the efficacy and safety of laparoscopic Toupet fundoplication in our lung transplant recipients. METHODS: A prospective case series of 44 lung transplant recipients who underwent laparoscopic Toupet fundoplication by a single surgeon between September 2018 and November 2020 was performed. Preoperative and postoperative results from 24-h pH, esophageal manometry, gastric emptying, and pulmonary function studies were collected alongside severity of gastroesophageal reflux disease and other gastrointestinal symptoms. RESULTS: Median DeMeester score decreased from 25.9 to 5.4 after fundoplication (p < 0.0001), while percentage of time pH < 4 decreased from 7 to 1.1% (p < 0.0001). The severity of heartburn and regurgitation were also reduced (p < 0.0001 and p = 0.0029 respectively). Overall, pulmonary function, esophageal motility, gastric emptying, severity of bloating, and dysphagia were not significantly different post-fundoplication than pre-fundoplication. Patients with decreasing rates of FEV1 pre-fundoplication saw improvement in their rate of change of FEV1 post-fundoplication (p = 0.011). Median follow-up was 32.2 months post-fundoplication. CONCLUSIONS: Laparoscopic Toupet fundoplication provides objective pathologic acid reflux control and symptomatic gastroesophageal reflux improvement in lung transplant recipients while preserving lung function and foregut motility. Thus, laparoscopic Toupet fundoplication is a safe and effective antireflux surgery alternative in lung transplant recipients.
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Trastornos de Deglución , Reflujo Gastroesofágico , Laparoscopía , Humanos , Fundoplicación/métodos , Trastornos de Deglución/cirugía , Receptores de Trasplantes , Laparoscopía/métodos , Reflujo Gastroesofágico/cirugía , Reflujo Gastroesofágico/complicaciones , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/diagnóstico , Pulmón , Resultado del TratamientoRESUMEN
BACKGROUND/OBJECTIVES: The inherently immunosuppressive tumor microenvironment along with the heterogeneity of pancreatic ductal adenocarcinoma (PDAC) limits the effectiveness of available treatment options and contributes to the disease lethality. Using a machine learning algorithm, we hypothesized that PDAC may be categorized based on its microenvironment inflammatory milieu. METHODS: Fifty-nine tumor samples from patients naïve to treatment were homogenized and probed for 41 unique inflammatory proteins using a multiplex assay. Subtype clustering was determined using t-distributed stochastic neighbor embedding (t-SNE) machine learning analysis of cytokine/chemokine levels. Statistics were performed using Wilcoxon rank sum test and Kaplan-Meier survival analysis. RESULTS: t-SNE analysis of tumor cytokines/chemokines revealed two distinct clusters, immunomodulating and immunostimulating. In pancreatic head tumors, patients in the immunostimulating group (N = 26) were more likely to be diabetic (p = 0.027), but experienced less intraoperative blood loss (p = 0.0008). Though there were no significant differences in survival (p = 0.161), the immunostimulating group trended toward longer median survival by 9.205 months (11.28 vs. 20.48 months). CONCLUSION: A machine learning algorithm identified two distinct subtypes within the PDAC inflammatory milieu, which may influence diabetes status as well as intraoperative blood loss. Opportunity exists to further explore how these inflammatory subtypes may influence treatment response, potentially elucidating targetable mechanisms of PDAC's immunosuppressive tumor microenvironment.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pérdida de Sangre Quirúrgica , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Aprendizaje Automático , Citocinas , Microambiente TumoralRESUMEN
Oral dysbiosis has long been associated with pancreatic ductal adenocarcinoma (PDAC). In this work, we explore the relationship between the oral and tumor microbiomes of patients diagnosed with PDAC. Salivary and tumor microbiomes were analyzed using a variety of sequencing methods, resulting in a high prevalence and relative abundance of oral bacteria, particularly Veillonella and Streptococcus, within tumor tissue. The most prevalent and abundant taxon found within both saliva and tumor tissue samples, Veillonella atypica, was cultured from patient saliva, sequenced and annotated, identifying genes that potentially contribute to tumorigenesis. High sequence similarity was observed between sequences recovered from patient matched saliva and tumor tissue, indicating that the taxa found in PDAC tumors may derive from the mouth. These findings may have clinical implications in the care and treatment of patients diagnosed with PDAC.
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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality rate. Within the next decade, PDAC is projected to become the second leading cause of cancer-associated death in the United States. Understanding the pathophysiology of PDAC tumorigenesis and metastases is crucial toward developing new therapeutics. One of the challenges in cancer research is generating in vivo models that closely recapitulate the genomic, histological, and clinical characteristics of human tumors. An ideal model for PDAC not only captures the tumor and stromal environment of human disease, but also allows for mutational control and is easy to reproduce in terms of time and cost. In this review, we highlight evolution of in vivo models for PDAC including spontaneous tumors models (i.e., chemical induction, genetic modification, viral delivery), implantation models including patient derived xenografts (PDX), and humanized PDX. We discuss the implementation of each system and evaluate the benefits and shortcomings of these models. Overall, this review provides a broad overview of prior and current techniques of in vivo PDAC modeling and their associated challenges.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animales , Humanos , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Modelos Animales de Enfermedad , Genómica , Neoplasias PancreáticasRESUMEN
BACKGROUND: There is a lack of data regarding the knowledge and perceptions teaching faculty possess about breast pumping among general surgery residents despite breast pumping becoming more common during training. This study aimed to examine faculty knowledge and perceptions of breast pumping amongst general surgery residents. METHODS: A 29-question survey measuring knowledge and perceptions about breast pumping was administered online to United States teaching faculty from March-April 2022. Descriptive statistics were used to characterize responses, Fisher's exact test was used to report differences in responses by surgeon sex and age, and qualitative analysis identified recurrent themes. RESULTS: 156 responses were analyzed; 58.6% were male and 41.4% were female, and the majority (63.5%) were less than 50 years old. Nearly all (97.7%) women with children breast pumped, while 75.3% of men with children had partners who pumped. Men more often than women indicated "I don't know" when asked about frequency (24.7 vs. 7.9%, p = 0.041) and duration (25.0 vs. 9.5%, p = 0.007) of pumping. Nearly all surgeons are comfortable (97.4%) discussing lactation needs and support (98.1%) breast pumping, yet only two-thirds feel their institutions are supportive. Almost half (41.0%) of surgeons agreed that breast pumping does not impact operating room workflow. Recurring themes included normalizing breast pumping, creating change to better support residents, and communicating needs between all parties. CONCLUSIONS: Teaching faculty may have supportive perceptions about breast pumping, but knowledge gaps may hinder greater levels of support. Opportunities exist for increased faculty education, communication, and policies to better support breast pumping residents.
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Extracción de Leche Materna , Cirugía General , Internado y Residencia , Niño , Femenino , Masculino , Humanos , Estados Unidos , Persona de Mediana Edad , Docentes , Educación de Postgrado en Medicina , Periodo Posparto , Cirugía General/educaciónRESUMEN
In pancreatic cancer clinical trials, Black patients are under-represented while having higher morbidity and mortality rates as compared to other racial groups. Multiple factors, including socioeconomic and lifestyle factors may contribute to this disparity, but genomic contributions remain unclear. In an exploratory project to identify genes that may contribute to differences in survival between Black (n = 8) and White (n = 20) patients with pancreatic cancer, transcriptomic sequencing of over 24,900 genes was performed in human pancreatic tumor and non-tumor tissue obtained from Black and White patients. Over 4,400 genes were differentially expressed in tumor and non-tumor tissue, irrespective of race. To validate these results, the expression of four genes (AGR2, POSTN, TFF1, and CP) reported to be up-regulated in pancreatic tumor tissue as compared to non-tumor tissue were confirmed using quantitative PCR. Transcriptomic analysis that compared pancreatic tumor tissue from Black and White patients revealed differential expression in 1,200 genes, while a comparison of the non-tumor and tumor gene expression differences within each race revealed over 1,500 tumor-specific differentially expressed genes in pancreatic tumor and non-tumor tissue from Black patients. We identified TSPAN8 as a potential tumor-specific gene significantly overexpressed in pancreatic tumor tissue in Black patients as compared to White patients. Using Ingenuity Pathway Analysis software to compare the race-associated gene expression profiles, over 40 canonical pathways were identified to be potentially impacted by the gene expression differences between the races. Heightened expression of TSPAN8 was associated with poor overall survival, suggesting TSPAN8 as one potential genetic factor contributing to the differential outcomes in Black patients with pancreatic cancer, supporting the potential utility of larger genomic studies to further explore the role of TSPAN8 in pancreatic cancer.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Mucoproteínas/genética , Proteínas Oncogénicas/genética , Neoplasias Pancreáticas/patología , Tetraspaninas/genética , Transcriptoma , Población Blanca , Población Negra , Neoplasias PancreáticasRESUMEN
Traditional clinical trial eligibility criteria restrict study populations, perpetuating enrollment disparities. We aimed to assess implementation of modernized eligibility criteria guidelines among pancreatic cancer (PC) clinical trials. Interventional PC trials in the United States since January 1, 2014, were identified via clinicaltrials.gov with December 31, 2017, as the transition for pre- and postguidance eras. Trials were assessed for guideline compliance and compared using Fisher exact test. In total, 198 trials were identified: 86 (43.4%) were pre- and 112 (56.6%) postguidance era. Improvements were seen in allowing patients with history of HIV (8.6% vs 43.8%; P < .0001), prior cancer (57.0% vs 72.3%; P = .034), or concurrent and/or stable cancer (2.1% vs 31.1%; P < .0001) to participate. Most (>95%) trials were compliant with laboratory reference ranges, QT interval corrected for heart rate (QTc) cutoffs, and rationalizing excluding prior therapies both pre- and postguidance eras. However, overall compliance with modernized criteria remains poor. We advocate for stakeholders to update protocols and scrutinize traditionally restrictive eligibility criteria.