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1.
bioRxiv ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37745359

RESUMO

The mismatch repair (MMR) pathway is known as a tumor suppressive pathway and genes involved in MMR are commonly mutated in hereditary colorectal or other cancer types. However, the function of MMR genes/proteins in breast cancer progression and metastasis are largely unknown. We found that MSH2, but not MLH1, is highly enriched in basal-like breast cancer (BLBC) and that its protein expression is inversely correlated with overall survival time (OS). MSH2 expression is frequently elevated due to genomic amplification or gain-of-expression in BLBC, which results in increased MSH2 protein to pair with MSH6 (collectively referred to as MutSα). Genetic deletion of MSH2 or MLH1 results in a contrasting phenotype in metastasis, with MSH2-deletion leading to reduced metastasis and MLH1-deletion to enhanced liver or lung metastasis. Mechanistically, MSH2-deletion induces the expression of a panel of chemokines in BLBC via epigenetic and/or transcriptional regulation, which leads to an immune reactive tumor microenvironment (TME) and elevated immune cell infiltrations. MLH1 is not correlated with chemokine expression and/or immune cell infiltration in BLBC, but its deletion results in strong accumulation of neutrophils that are known for metastasis promotion. Our study supports the differential functions of MSH2 and MLH1 in BLBC progression and metastasis, which challenges the paradigm of the MMR pathway as a universal tumor suppressive mechanism.

2.
J Affect Disord ; 331: 57-63, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36948464

RESUMO

INTRODUCTION: While suicidal thoughts are relatively common in the general population, roughly affecting one in ten people during their lifetime, the transition from suicidal thoughts to a suicide attempt is rarer. There is limited consensus on the transition rate from suicidal ideation to suicide attempts. OBJECTIVE: To review and summarize evidence on the rate of transition from suicidal ideation to a suicide attempt, and the factors associated with this transition, in the general population. METHODS: A comprehensive search was conducted using MEDLINE, PsycINFO, and Embase for relevant articles published between January 1, 2000, and March 3, 2021. We identified 18 eligible studies that examined the transition from suicidal ideation to a suicide attempt in non-clinical populations. We assessed the quality of the included studies using the MASTER scale. The review has been registered with PROSPERO (CRD42021248325). RESULTS: Rates of transitioning to a suicide attempt among people with suicidal ideation varied substantially across studies, from 2.6 % to 37 %. Follow-up periods also varied substantially, from 12 to 300 months, impeding reliable comparisons across studies or pooling data for further analyses. The most examined risk factors were mental health disorders such as major depressive and anxiety disorders, which were typically associated with higher odds of transition to a suicide attempt. LIMITATIONS: High level of heterogeneity and limited quality of the studies. CONCLUSION: The risk of transition from suicidal thoughts to a suicide attempt is moderate to high. Further longitudinal research is required to refine the rate and explore social determinants of transition from suicidal ideation to suicide attempts.


Assuntos
Transtorno Depressivo Maior , Tentativa de Suicídio , Humanos , Tentativa de Suicídio/psicologia , Ideação Suicida , Transtornos de Ansiedade , Fatores de Risco
3.
Surg Laparosc Endosc Percutan Tech ; 33(1): 18-21, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730232

RESUMO

BACKGROUND: Pancreatic-enteric drainage procedures have become standard therapy for symptomatic pancreatic pseudocysts and walled-off pancreatic necrosis. The need for pancreatic resection after cyst-enteric drainage procedure in the event of recurrence is not well studied. This study aimed to quantify the percentage of patients requiring resection due to recurrence after surgical cystogastrostomy and identify predictors of drainage failure. METHODS: A single-institution retrospective review was conducted to identify all patients undergoing surgical cystogastrostomy between 2012 and 2020. Demographic, disease, and treatment characteristics were identified. Failure of surgical drainage was defined as the need for subsequent pancreatic resection due to recurrence. Characteristics between failure and nonfailure groups were compared with identifying predictors of treatment failure. RESULTS: Twenty-four cystogastrostomies were performed during the study period. Three patients (12.5%) required a subsequent distal pancreatectomy after surgical drainage. There was no difference in comorbidities between drainage alone and failure of drainage groups. Mean cyst size seemed to be larger in patients that underwent drainage alone versus those that needed subsequent resection (15.2 vs 10.3 cm, P =0.05). Estimated blood loss at initial operation was similar between groups (126 vs 166 mL, P =0.36). CONCLUSION: Surgical pancreatic drainage was successful in the initial management of pancreatic fluid collections. We did not identify any predictors of failure of initial drainage. There was a trend suggesting smaller cyst size may be associated with cystgastrostomy failure. Resection with distal pancreatectomy for walled-off pancreatic necrosis and pancreatic pseudocysts can be reserved for cases of failure of drainage.


Assuntos
Cistos , Pseudocisto Pancreático , Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/cirurgia , Pseudocisto Pancreático/cirurgia , Pseudocisto Pancreático/complicações , Pâncreas , Drenagem/métodos , Estudos Retrospectivos
4.
Am Surg ; 89(6): 2820-2823, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34797195

RESUMO

Development of a post-esophagectomy hiatal hernia (PEHH) is a rare, but problematic, sequela with the current reported prevalence ranging up to 20%. To determine the incidence rate of PEHH at our institution, a retrospective review of all transhiatal esophagectomies performed from 2012 to 2020 was conducted. Demographic, operative, and oncologic data were collected, rates of PEHH were calculated, and characteristics of subsequent repair were reviewed and analyzed. A total of 160 transhiatal esophagectomies were included, of which four patients (2.5%) developed a PEHH at a mean of 12 months postoperatively (range: 3-28 months) with symptomatology driving the diagnosis for three patients. The limited size of our study does not allow for statistically significant determinations regarding risk factors or method of repair. The true prevalence of a hiatal defect is likely higher than reported, as clinically asymptomatic patients are not captured in our current literature.


Assuntos
Hérnia Hiatal , Laparoscopia , Humanos , Hérnia Hiatal/diagnóstico , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Estudos Retrospectivos , Fatores de Risco , Incidência , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Herniorrafia/métodos
5.
Surg Endosc ; 37(6): 4926-4933, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36167870

RESUMO

BACKGROUND: Burnout has become a prominent topic, yet there are limited data on the manifestation of this phenomenon among surgical fellows. The goal of this study is to elucidate the prevalence of burnout and determine if there are protective or predisposing factors in surgical fellowship training. METHODS: A confidential electronic survey was distributed to Fellowship Council accredited fellows during the 2020-2021 academic year. Demographic information and training characteristics were queried. The fellows were then asked to complete the Maslach Burnout Inventory (MBI), Perceived Stress Scale (PSS), Short Grit Scale (SGS), Satisfaction with Life Scale (SLS), and General Self-Efficacy Scale (SE). Data were analyzed using p values of ≤ 0.05 as statistically significant. RESULTS: At the end of the survey period, 92 out of 196 (46.9%) fellowship trainees responded. 69.6% of respondents identified as men, 29.7% as international medical school graduates (IMGs), and 15.3% non-US IMGs. Based on criteria defined by the MBI, there was an 8.4% rate of burnout. Most respondents noted low stress levels (62.3%), good satisfaction with life (58.9%), a moderate amount of grit, and a high level of self-esteem. On comparative analysis, fellows with burnout had significantly higher stress levels, lower levels of satisfaction with life, and less self-esteem. CONCLUSIONS: Overall, there was a low rate of burnout among fellows. We suggest this may be reflective of a self-selecting effect, as trainees who choose to undergo additional training may be less likely to experience this syndrome. In addition, there may be a protective factor during fellowship that results from inherent mentoring, increased specialization, and autonomy. Further investigation of the predisposing factors to burnout in fellowship trainees is warranted based on the results of this study.


Assuntos
Esgotamento Profissional , Masculino , Humanos , Prevalência , Esgotamento Profissional/epidemiologia , Inquéritos e Questionários , Bolsas de Estudo
6.
Heliyon ; 8(12): e11945, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36478793

RESUMO

Background: Surgical intervention in the geriatric population has a higher risk of perioperative morbidity and mortality due to frailty, comorbidities, and lack of compensatory physiologic reserve. The literature on esophagectomy in octogenarians is limited and there is concern about elderly patients being with-held surgery. The purpose of this study is to analyze the outcomes of esophagectomies for esophageal cancer in octogenarians to assess the safety of esophagectomy in this population. Methods: 145 transhiatal esophagectomies performed for esophageal cancer between 2012 and 2020 were retrospectively reviewed in this IRB approved study. Two aborted esophagectomies were excluded. Patient demographics, surgical outcomes, and oncologic outcomes were reviewed. The octogenarian group was analyzed compared to patients younger than 80 years of age. Results: Among 143 esophagectomies, 136 patients were <80 years old while 7 were ≥80 years old. Octogenarians received significantly less neoadjuvant therapy compared to younger patients (42.9% vs 80.2%, p = 0.02). No statistically significant difference was noted in complication rate, length of stay (LOS), estimated blood loss (EBL), or mortality. However, octogenarians were found to have an increase in severity of complications compared to younger patients. Conclusion: This study demonstrates that esophagectomy can be performed in carefully selected octogenarians. This comes at a cost with increased severity of complications without an increase in complication rates or mortality. This data suggests that esophagectomy can be offered selectively to older patients with clear expectations and planning for the high risk of more severe post-operative complications.

7.
J Pancreat Cancer ; 8(1): 9-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36583028

RESUMO

Purpose: Resectability in localized pancreatic ductal adenocarcinoma (PDAC) is deemed through radiological criteria. Despite initial evaluation classifying tumors as "resectable," they often have ill-defined borders that can result in more extensive cancer than predicted on final pathology analysis. We attempt to categorize these tumors radiologically and define them as "infiltrative" and contrast them to more well-defined or "mass-forming" tumors and assess their correlation with surgical oncological outcomes. We hypothesize that mass-forming lesions will result in fewer positive resection margins. Methods: Patients diagnosed with PDAC of the head of the pancreas and who underwent subsequent curative intent resection between 2016 and 2018 were included. A retrospective chart review of patients was conducted and computed tomography images at the time of diagnosis were reviewed by two radiologists and scored as "mass forming" or "infiltrative" using a newly developed classification system. These classifications were then correlated with margin status. Results: Sixty-eight consecutive pancreatoduodenectomies performed for PDAC from 2016 to 2018 were identified. After screening, 54 patients were eligible for inclusion. Radiologically defined mass-forming lesions had a trend toward a lower rate of positive resection margins (35.7% vs. 50.0%; p = 0.18), specifically the bile duct margin and pancreas margin as well as an overall larger size (4.03 cm vs. 3.25 cm, p = 0.02) compared with infiltrative lesions. Conclusion: We propose a new radiological definition of PDAC into "mass forming" and "infiltrative," a nomenclature that resonates with other tumor sites. Infiltrative lesions trended toward a higher rate of positive resection margins. This classification may help tailor therapy for infiltrative tumors toward a neoadjuvant approach even if they appear resectable.

8.
Surg Open Sci ; 10: 156-157, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36248182

RESUMO

We describe a straightforward model to implement a high volume specialty surgery program at a community hospital. Using pancreatic surgery as an example, we employed published processes in three arenas. First, mandatory multidisciplinary tumor board presentations captured all the patients considered for surgery. Then, perioperative protocols using tools such as enhanced recovery and teamwork in the perioperative arena created a reproducible and safe environment for complex surgery. We critically reviewed all complications using the Clavien-Dindo methodology, and confirmed our favorable outcomes via the targeted NSQIP program. These standard steps can be used for implementation of a new complex surgical procedure.

9.
Heliyon ; 8(4): e09187, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434393

RESUMO

Background: Duodenal adenomas are pre-malignant lesions. Transduodenal resection and pancreaticoduodenectomy remain the only two surgical options. The optimal surgical management remains controversial between these two strategies. Methods: A retrospective review was conducted to identify patients who underwent intervention for duodenal adenomas. Patient were stratified by type of procedure, pancreaticoduodenectomy or transduodenal resection, and their demographic data as well as perioperative outcomes were compared. Results: 26 patients underwent surgery for duodenal adenomas. 11 underwent a pancreaticoduodenectomy (PD) (42.3%) and 15 underwent a transduodenal resection (TDR) (57.7%). Median operative time, median estimated blood loss, and mean length of stay were longer in the PD vs TDR group. Two patients (13.3%) in the TDR group developed recurrent adenomas. Conclusion: Transduodenal resection should be considered in patients who are suspected to harbor benign duodenal tumors. Duodenal tumors with high grade dysplasia or invasive cancer should undergo an oncologic procedure. Endoscopic surveillance appears to be indicated after transduodenal resection.

11.
Open Forum Infect Dis ; 9(1): ofab620, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35036466

RESUMO

BACKGROUND: We sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs). METHODS: We conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis. RESULTS: We identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum ß-lactamase-producing E. coli and Klebsiella pneumoniae, 80%-90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68-2.16), 0.84 (95% CI, 0.46-1.52), and 0.94 (95% CI, 0.52-1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day). CONCLUSIONS: These results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI.

12.
Surg Open Sci ; 7: 62-67, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35036890

RESUMO

BACKGROUND: The Whipple procedure in its current form owes its evolution to the groundbreaking and innovative work of giants in the field of surgery. From being a multistep procedure with high morbidity and mortality, it is now ubiquitously performed in a single setting, often offered via minimally invasive approaches. Training to perform this procedure is an arduous task, and different training paradigms vary significantly. OBJECTIVES/METHODS: The purpose of this paper is to share a standard method by which the surgeon can perform the Whipple procedure in a systematic manner. Using illustrations to make the steps clearer, the authors will postulate that an improvement in mean operative time can be realistically achieved by most pancreatic surgeons. The focus is also on presenting this complex procedure as reproducible and teachable techniques for trainees. CONCLUSION: This illustrated review of the Whipple procedure as performed at our institution is intended to help facilitate a streamlined and stepwise progression through what is undoubtedly a challenging surgical procedure. Although the procedure described will not apply to all Whipple operations given the heterogeneity in anatomy and circumstances, our hope is that this will lead to a more efficient procedure and decreased operating room time and costs as well as provide a framework to teach and measure technical progress for surgical trainees.

14.
Am Surg ; 88(6): 1250-1255, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33565895

RESUMO

BACKGROUND: The Americas Hepato-Pancreato-Biliary Association (AHPBA) Education and Training Committee standardized a Hepatopancreatobiliary (HPB) Surgery Fellowship certification process in 2010. Several classes of fellows have since graduated from HPB, combined Society of Surgical Oncology/AHPBA, and combined American Society of Transplant Surgeons/AHPBA fellowships, but there is little information on their career outcomes. We seek to offer long-term data on the careers of HPB fellowship graduates. METHODS: A 26-question anonymous survey was distributed among graduates of accredited programs for the last 10 years. We generated descriptive statistics from the responses. RESULTS: The respondents were evenly distributed in terms of graduation years between 2010 and 2019. Fifty-eight percent of fellows had completed a prior fellowship, 82% received 1 to 3 job offers during the fellowship, and 75% of respondents were still at their first job. The majority of graduates (>60%) were able to secure a job with a >50% HPB practice and >40 HPB cases per year within 3 years of graduation. Overall, >90% candidates rated their satisfaction with fellowship training greater than 8 out of 10. DISCUSSION: This survey helps shed light on the early formative years in the practices of HPB fellowship graduates. These data show that HPB fellowship training is essential and effective in providing job security and helps fellowship graduates develop a gratifying practice.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Cirurgiões , Competência Clínica , Procedimentos Cirúrgicos do Sistema Digestório/educação , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Humanos , Cirurgiões/educação , Inquéritos e Questionários , Estados Unidos
15.
JSLS ; 25(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803368

RESUMO

BACKGROUND AND OBJECTIVES: The primary aim of this study is to assess the necessity of fundoplication for reflux in patients undergoing Heller myotomy for achalasia. The secondary aim is to assess the safety of the robotic approach to Heller myotomy. METHODS: This is a single institution, retrospective analysis of 61 patients who underwent robotic Heller myotomy with or without fundoplication over a 4-year period (January 1, 2015 - December 31, 2019). Symptoms were evaluated using pre-operative and postoperative Eckardt scores at < 2 weeks (short-term) and 4 - 55 months (long-term) postoperatively. Incidence of gastroesophageal reflux and use of antacids postoperatively were assessed. Long-term patient satisfaction and quality of life (QOL) were assessed with a phone survey. Finally, the perioperative safety profile of robotic Heller myotomy was evaluated. RESULTS: The long-term average Eckardt score in patients undergoing Heller myotomy without fundoplication was notably lower than in patients with a fundoplication (0.72 vs 2.44). Gastroesophageal reflux rates were lower in patient without a fundoplication (16.0% vs 33.3%). Additionally, dysphagia rates were lower in patients without a fundoplication (32.0% vs 44.4%). Only 34.8% (8/25) of patients without fundoplication continued use of antacids in the long-term. There were no mortalities and a 4.2% complication rate with two delayed leaks. CONCLUSION: Robotic Heller myotomy without fundoplication is safe and effective for achalasia. The rate of reflux symptoms and overall Eckardt scores were low postoperatively. Great patient satisfaction and QOL were observed in the long term. Our results suggest that fundoplication is unnecessary when performing Heller myotomy.


Assuntos
Acalasia Esofágica , Miotomia de Heller , Laparoscopia , Acalasia Esofágica/cirurgia , Fundoplicatura , Humanos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
16.
Surg Neurol Int ; 12: 206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084633

RESUMO

BACKGROUND: The spine surgery complexity score (SSCS), previously reported by us, is a simple grading system to predict postoperative complications and hospital length of stay (LOS). This scale is based on the technical difficulty of the spinal procedures being performed. METHODS: We performed a retrospective chart review to validate SSCS in 671 consecutive patients undergoing spine procedures at a quaternary academic hospital. RESULTS: The SSCS was predictive of the hospital LOS and postoperative complications (defined by the ClavienDindo score), based on linear regression analysis (P < 0.001 for both). CONCLUSION: Categorizing procedures according to the SSCS may enable neurosurgeons to assess surgical risk and predict longer LOS courses after spine surgery. Thus, it may prove useful in preoperative patient evaluation/ education and determining a prognosis based on surgical complexity.

17.
World J Surg ; 45(8): 2556-2566, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33876267

RESUMO

BACKGROUND: Selection biases affecting candidate matches to fellowship programs directly influence diversity within the surgical community. The review of selection bias has never been distinctively investigated in the Hepatopancreatobiliary (HPB) surgery community. This study seeks to (i) evaluate factors affecting selection of candidates to HPB fellowships, (ii) examine explicit biases among program directors and faculty of HPB programs in North America, and (iii) compare the demography of the HPB faculty and recently graduated fellows to general surgery residents. STUDY DESIGN: An anonymous, self-reported survey consisting of 10 sets of fictional applications was distributed to 52 faculty members, including program directors, of AHPBA-affiliated HPB fellowships in North America. The respondents had to pick a preferred candidate between two abridged, fictional HPB fellow applications and give an open-ended response as to why they picked that candidate. The applications were nearly identical with one notable characteristic of interest. Demographic information of both faculty and their recent fellows was also collected. This survey was administered and collected between February and April, 2020. RESULTS: A total of 29 fully completed responses were received, comprising a 55.7% response rate. Respondents were 72.4% male, 69.0% Caucasian, and 79.3% held US medical degrees (MD). 50.0% of respondents preferred an MD candidate to a DO candidate, and 37% preferred US graduates to foreign-trained candidates. The respondents were unanimous in stating that gender, race, and family status were not a factor in their selection process. 5.0% said they would support an LGBTQ candidate when faced with otherwise similar applicants. Seventy-six HPB fellows from the past 5 years were 76.3% male, 56.6% Caucasian, and 51.3% US graduated Doctor of Medicine (US MD). CONCLUSION: This is the first study explicitly exploring the impact of demographic factors in the HPB fellowship selection process. The respondents unanimously and explicitly stated that race and gender do not play any role in their selection process. Yet, there is stark discordance between general surgery resident demographics and HPB fellow demographics. A greater effort to promote a more diverse HPB surgery community may be needed.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Internato e Residência , Competência Clínica , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Feminino , Humanos , Masculino , Inquéritos e Questionários
18.
Mol Cancer Res ; 19(7): 1156-1167, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33753551

RESUMO

Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2-M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors. IMPLICATIONS: AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.


Assuntos
Aminopiridinas/farmacologia , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Morfolinas/farmacologia , Fase S/genética , Fator de Transcrição AP-2/genética , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Perfilação da Expressão Gênica/métodos , Técnicas de Inativação de Genes , Células HCT116 , Humanos , Camundongos , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Interferência de RNA , RNA-Seq/métodos , Fator de Transcrição AP-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
19.
Abdom Radiol (NY) ; 46(7): 3179-3183, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33665733

RESUMO

PURPOSE: 68Ga-DOTATATE PET is becoming a popular imaging technique for detecting neuroendocrine tumors (NETs). The sensitivity and specificity of 68Ga-DOTATATE PET compared to standard cross-sectional imaging with triple phase CT or MRI with Eovist has not been studied extensively. METHODS: 68Ga-DOTATATE PET scans ordered at our institution between 11/2017 and 7/2018 were reviewed. Patients with evidence of liver metastases were sorted and cross-sectional imaging results were reviewed. Specifically, the number of lesions detected by standard cross-sectional imaging versus 68Ga-DOTATATE PET was compared. RESULTS: 32 patients with 68Ga-DOTATATE PET scans and a corresponding MRI or CT were identified. Primary tumors were pancreatic (43.8%), small bowel (25%), hepatic (9.4%), gastric (6.3%), appendiceal (3.1%), and not localized (12.5%). 26/32 (81%) patients had CT scans and 17/32 (53%) had MRI scans. 25/32 (78%) patients had at least equal or increased number of lesions identified on 68Ga-DOTATATE PET when compared with CT or MRI. 7/32 (21.9%) had fewer lesions on 68Ga-DOTATATE PET compared to CT or MRI. However, 3 of these cases had numerous liver lesions. The overall sensitivity and specificity of 68Ga-DOTATATE PET are 92.9% and 75% respectively. CONCLUSION: 68Ga-DOTATATE PET appears to have superior sensitivity in detecting metastatic NET to the liver. Further studies are needed to determine if it should be considered the test of choice for evaluating patients with metastatic NET to the liver. While standard cross-sectional imaging will be needed for surgical planning, 68Ga-DOTATATE PET will identify lesions that may not be seen on other imaging modalities.


Assuntos
Neoplasias Hepáticas , Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons
20.
J Surg Educ ; 78(5): 1593-1598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33516749

RESUMO

OBJECTIVE: The goal of the 1-year Advanced Gastrointestinal (AGI) surgery fellowship is to train the general surgeon to perform advanced and complex operations that they had insufficient experience with in residency training. This study examines the case logs of AGI fellows that have completed Society for Surgery of the Alimentary Tract (SSAT)-sponsored Fellowship Council (FC)-accredited AGI fellowships to determine the role of these fellowships in providing complex gastrointestinal operative experience. DESIGN/PARTICIPANTS: Institutional Review Board-approved retrospective surgical case log analysis. Case logs of 60 AGI fellows in 12 different AGI fellowships from 2014 to 2019 were requested by the SSAT and provided in a de-identified format from the FC. Cases were categorized as colorectal surgery, anus, hernia-abdomen, hernia inguinal, esophagus-hiatal hernia, esophagus-Heller, pancreas, liver, bile duct, diagnostic/therapeutic esophagogastroduodenoscopy (EGD), diagnostic/therapeutic colonoscopy, thoracic esophagus, thoracic lung, spleen, thyroid, diaphragm, gastric, abdomen, adrenal/kidney, bariatric, diagnostic/therapeutic bronchoscopy, kidney/liver/pancreas transplant, and trauma. RESULTS: AGI fellows performed a mean of 345 cases per year (range: 184-558). Our results showed that 5 programs provided >30 colorectal cases, 6 provided >50 hernia (hernia-abdomen and hernia-inguinal) cases, 8 provided >25 hiatal hernia cases, 2 provided >100 endoscopy cases (diagnostic/therapeutic EGD and diagnostic/therapeutic colonoscopy), 6 provided >30 gastric cases, 3 provided >100 bariatric cases, 6 provided >10 pancreas cases, 3 provided >10 liver cases, and 4 provided >6 biliary cases. CONCLUSION: SSAT-sponsored FC-accredited AGI fellowship programs provide a wide array of training in complex gastrointestinal surgeries. Most programs provide broad training in hiatal work, colorectal surgery, hepato-pancreato-biliary surgery, and abdominal wall reconstruction. This FC-accredited AGI training paradigm prepares trainees for broad-based complex abdominal surgery, an area that is sorely needed to augment insufficient experience in many general surgical training programs.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Cirurgia Geral , Internato e Residência , Competência Clínica , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Cirurgia Geral/educação , Estudos Retrospectivos
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