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2.
Ann Surg ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39176476

RESUMO

OBJECTIVE: To evaluate the feasibility of developing a computer vision algorithm that uses preoperative computed tomography (CT) scans to predict superior mesenteric artery (SMA) margin status in patients undergoing Whipple for pancreatic ductal adenocarcinoma (PDAC), and to compare algorithm performance to that of expert abdominal radiologists and surgical oncologists. SUMMARY BACKGROUND DATA: Complete surgical resection is the only chance to achieve a cure for PDAC; however, current modalities to predict vascular invasion have limited accuracy. METHODS: Adult patients with PDAC who underwent Whipple and had preoperative contrast-enhanced CT scans were included (2010-2022). The SMA was manually annotated on the CT scans, and we trained a U-Net algorithm for SMA segmentation and a ResNet50 algorithm for predicting SMA margin status. Radiologists and surgeons reviewed the scans in a blinded fashion. SMA margin status per pathology reports was the reference. RESULTS: Two hundred patients were included. Forty patients (20%) had a positive SMA margin. For the segmentation task, the U-Net model achieved a Dice Similarity Coefficient of 0.90. For the classification task, all readers demonstrated limited sensitivity, although the algorithm had the highest sensitivity at 0.43 (versus 0.23 and 0.36 for the radiologists and surgeons, respectively). Specificity was universally excellent, with the radiologist and algorithm demonstrating the highest specificity at 0.94. Finally, the accuracy of the algorithm was 0.85 versus 0.80 and 0.76 for the radiologists and surgeons, respectively. CONCLUSIONS: We demonstrated the feasibility of developing a computer vision algorithm to predict SMA margin status using preoperative CT scans, highlighting its potential to augment the prediction of vascular involvement.

3.
J Surg Oncol ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155697

RESUMO

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS). METHODS: Whole-exome sequencing of resected well-differentiated, low and intermediate-grade (G1 and G2) pNETs and normal adjacent tissue from patients who underwent resection from 2005 to 2015 was performed. Genetic alterations were classified using pan-genomic and oncogenic pathway classifications. Additional samples with genetic and clinicopathologic data available were obtained from the publicly available International Cancer Genome Consortium (ICGC) database and included in the analysis. The prognostic relevance of these genomic signatures on PFS and RFS was analyzed. RESULTS: Thirty-one patients who underwent resection for pNET were identified. Genomic analysis of mutational, copy number, cytogenetic, and complex phenomena revealed similar patterns to prior studies of pNETs with relatively few somatic gene mutations but numerous instances of copy number changes. Analysis of genomic and clinicopathologic outcomes using the combined data from our study as well as the ICGC pNET cohort (n = 124 patients) revealed that the recurrent pattern of whole chromosome loss (RPCL) and metastatic disease were independently associated with disease progression. When evaluating patients with local disease at the time of resection, RPCL and alterations in the TGFß oncogenic pathway were independently associated with the risk of recurrence. CONCLUSIONS: Well-differentiated pNETs are genomically diverse tumors. Pathway signatures may be prognostic for predicting disease progression and recurrence.

4.
Gastro Hep Adv ; 3(3): 370-384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39131137

RESUMO

The continuous evolution of endoscopic tools over the years has paved the way for minimally invasive alternatives to surgical procedures for multiple gastrointestinal conditions. While few endoscopic techniques have supplanted their surgical counterparts like percutaneous gastrostomy tubes, many have emerged as noninferior, less morbid alternatives for such diverse conditions as achalasia (peroral endoscopic myotomy), obesity (endoscopic sleeve gastroplasty), drainage of pancreatic walled off necrosis (EUS-guided cystogastrostomy), and gastric outlet obstruction (EUS-guided gastrojejunostomy). These techniques were based on surgical concepts and would not have been feasible without collaboration between surgeons and endoscopists. Such collaboration is exemplified by the antireflux fundoplication, which features combined hiatal hernia repair with transoral and incisionless fundoplication. The burgeoning armamentarium of endoscopic alternatives to traditional surgical procedures requires a multidisciplinary discussion and individually tailored treatment plans that consider patient preferences as well as the relative risks and benefits of surgical and endoscopic approaches. As technological advances give rise to ever more innovative endoscopic techniques, studies to evaluate clinical outcomes and define their role in treatment algorithms will be required.

5.
J Urol ; 212(3): 401-408, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39115122

RESUMO

PURPOSE: Incisional hernias are a frequent complication following robotic radical prostatectomy. Observational data in men undergoing robotic prostatectomy suggest that transverse closure resulted in lower hernia rates than vertical closure. We sought to compare the incidence of incisional hernia after robotic radical prostatectomy after vertical and transverse extraction site closure. MATERIALS AND METHODS: We conducted a clinically integrated, crossover, cluster randomized trial at a single tertiary referral center (January 2016-September 2021) comparing the rate of hernia after transverse vs vertical extraction site excision in 1356 patients treated with minimally invasive radical prostatectomy. The primary outcome was between-group incidence of incisional hernia within 15 months of prostatectomy defined by physical examination and self-reported patient surveys. RESULTS: Overall, 197 (20%) patients developed an incisional hernia within 15 months, 797 did not have an incisional hernia within this period, and 362 had missing outcome data regarding incisional hernia. We found no significant difference in hernia rates between the 2 incision types (absolute between-group difference 1.8%; 95% CI -3.4%, 6.6%; P = .5) in the primary analysis or in the 3 sensitivity analyses. Notably, because of the inclusive definition of hernia used, these data cannot be used as an estimate of the true prevalence of incisional hernia. CONCLUSIONS: Surgeons should choose the incision and closure approach they are most comfortable with when extracting specimens. Studies of modifications to the surgical technique are best conducted as randomized comparisons, and the clinically integrated, crossover, cluster randomized trial allows large trials to be completed at a single center and at low cost. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407263.


Assuntos
Estudos Cross-Over , Hérnia Incisional , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Pessoa de Meia-Idade , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Idoso , Incidência , Neoplasias da Próstata/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
6.
Surgery ; 176(3): 757-762, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38965006
7.
Surgery ; 176(3): 866-872, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38971697

RESUMO

BACKGROUND: Pancreaticoduodenectomy is a highly morbid operation with significant resource utilization. Using a national cohort, we examined the interhospital variation in pancreaticoduodenectomy hospitalization cost in the United States. METHODS: Adults undergoing elective pancreaticoduodenectomy in the setting of pancreatic cancer were tabulated from the 2016-2020 Nationwide Readmissions Database. A 2-level mixed-effects model was developed to evaluate the interhospital variation in pancreaticoduodenectomy hospitalization costs. Institutions within the top decile of risk-adjusted expenditures were defined as high-cost hospitals. Multivariable regression models were fitted to examine the association between high-cost hospital status and outcomes of interest. To account for the effects of complications on expenditures, a subgroup analysis comprising of patients with no adverse events was conducted. RESULTS: The study included an estimated 24,779 patients with a median hospitalization cost of $38,800. After mixed-effects modeling, 40.9% of the cost variation was attributable to hospital, rather than patient, factors. Multivariable regression models revealed an association between high-cost hospital status and greater odds of complications and longer length of stay. Among patients without an adverse event, interhospital cost variation remained significant at 61.0%, and treatment at high-cost hospitals was similarly linked to longer length of stay. CONCLUSION: Our study identified significant interhospital variation in pancreaticoduodenectomy hospitalization costs in the United States. Although high-cost hospital status was associated with increased odds of complications, variation remained significant even among patients without an adverse event. These results suggest the important role of hospital practices as contributors to expenditures. Further efforts to identify drivers of costs and standardize pancreatic surgical care are warranted.


Assuntos
Custos Hospitalares , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/economia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/estatística & dados numéricos , Masculino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/economia , Feminino , Custos Hospitalares/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Estados Unidos , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos , Adulto
9.
Surg Open Sci ; 20: 101-105, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39021616

RESUMO

Background: Multiagent neoadjuvant chemotherapy (NAT) has been linked with improved survival for locally advanced (LA) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). However, the existence of disparities in its utilization remains to be elucidated. Methods: All adults with PDAC were tabulated from the 2011-2017 Nationwide Cancer Database. Tumor vascular involvement was determined using the clinical T stage and CS_EXTENSION variables. The significance of temporal trends was calculated using Cuzick's non-parametric test. A Cox proportional hazard model was used to assess the impact of NAT utilization on hazard of two-year mortality. A logistic regression model was developed to determine factors associated with receipt of NAT. Results: Of 3811 patients meeting inclusion criteria, 50.8 % received NAT. NAT utilization significantly increased over the study period, from 31.7 % in 2011 to 81.1 % in 2017 (p < 0.001). NAT was associated with significantly reduced two-year mortality (Hazards Ratio 0.34, 95 % Confidence Interval [CI] 0.18-0.67).After adjustment, younger (Adjusted Odds Ratio [AOR] 0.97/year, CI 0.96-0.98) and Black (AOR 0.65, CI 0.48-0.89; ref: White) patients demonstrated reduced odds of NAT. Furthermore, patients with Medicare (AOR 0.73, CI 0.59-0.90; ref: Private) or Medicaid insurance (AOR 0.67, CI 0.46-0.97; ref: Private) had lower odds of NAT, as did those treated at non-academic institutions (Community: AOR 0.42, CI 0.35-0.52, Integrated: 0.68, CI 0.54-0.85) or in the lowest education quartile (AOR 0.52, CI 0.29-0.95; ref: Highest). Conclusions: We identified increasing utilization of NAT for BR/LA pancreatic adenocarcinoma. Despite being linked with significantly reduced two-year mortality, socioeconomic disparities affect odds of NAT.

10.
Ann Surg Oncol ; 31(10): 6875-6882, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38909116

RESUMO

PURPOSE: DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE. METHODS: This was a retrospective analysis of 815 patients who underwent DOTATATE at UCLA from 2014 to 2022. After applying inclusion and exclusion criteria, the study cohort consisted of 163 patients with pathologically diagnosed GEP-NETs, who either underwent primary tumor resection within 1-year prior, or had not undergone resection at the time of DOTATATE imaging. The presence of metastasis was determined using DOTATATE. Fisher's exact test, chi-squared test, and Mann-Whitney test were conducted to compare intergroup difference. Multivariate analysis was performed to identify clinical characteristics associated with metastasis on DOTATATE. RESULTS: Of patients with GEP-NETs, 40.5% (n = 66) were diagnosed with metastases by using DOTATATE. Those with metastatic disease were more likely to exhibit a larger primary tumor size (median 3.4 vs. 1.2, cm, P < 0.001), elevated serum chromogranin A level (CgA, median 208 vs. 97, mg/ml, P = 0.005), and higher tumor grade (P < 0.001). Primary tumor size ≥2 cm and serum CgA level ≥150 ng/mL for metastatic disease had a sensitivity and specificity of 64% and 89%, and 72% and 59%, respectively. Multivariate analysis demonstrated that primary tumor size (≥2/<2, cm, odds ratio [OR] 47.90, P < 0.001), tumor functionality (functional/nonfunctional, adjusted OR 10.17 P = 0.008), serum CgA level (≥150/<150, ng/ml, OR 6.25, P = 0.005), and tumor grade G2 (G2/G1, OR 9.6, P < 0.001) were independently associated with metastases on DOTATATE. CONCLUSIONS: Among patients with GEP-NETs, primary tumor size ≥2 cm, serum CgA level ≥150 ng/mL, and tumor grade G2 are associated with an increased risk of metastases on DOTATATE, and these predictors may be helpful to identify patients where DOTATATE is indicated for complete staging.


Assuntos
Cromogranina A , Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Feminino , Masculino , Cromogranina A/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Intestinais/sangue , Neoplasias Intestinais/patologia , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Idoso , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Seguimentos , Biomarcadores Tumorais/sangue , Adulto , Carga Tumoral , Compostos Organometálicos , Compostos Radiofarmacêuticos
11.
J Surg Oncol ; 130(2): 276-283, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38894577

RESUMO

BACKGROUND AND OBJECTIVES: The SARS-COVID-19 pandemic significantly limited healthcare access. We sought to evaluate whether California's lockdown in March 2020 affected staging and time to treatment of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that patients diagnosed after the lockdown would have longer time to treatment and higher stage at presentation. METHODS: We retrospectively identified and categorized 1294 patients presenting to five University of California healthcare systems with a new diagnosis of PDAC into "pre-lockdown" and "post-lockdown" groups based on timing of pathologic diagnosis. RESULTS: In the 12 months pre-lockdown, 835 patients were diagnosed with PDAC, and 459 patients in the 6 months post-lockdown. Demographics, staging, and treatment type were similar between eras. There was a decreased male:female ratio post- versus pre-lockdown (0.97 vs. 1.25; p = 0.03). Time from symptom onset to first treatment was significantly increased among females post-lockdown (p = 0.001). However, overall time from diagnosis to first treatment was shorter in the post-lockdown era (median 23 vs. 26 days, p < 0.001). CONCLUSIONS: The COVID-19 lockdown did not significantly delay initial presentation, diagnosis, or treatment of newly diagnosed PDAC patients. Time from diagnosis to first treatment was shorter post-lockdown. Reduced healthcare utilization for minor complaints and increased telehealth utilization may have contributed.


Assuntos
COVID-19 , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Masculino , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/epidemiologia , California/epidemiologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Tempo para o Tratamento/estatística & dados numéricos , Quarentena , SARS-CoV-2 , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Adulto
12.
JCO Precis Oncol ; 8: e2300274, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38691813

RESUMO

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Masculino , Feminino , Idoso , Resistencia a Medicamentos Antineoplásicos/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Gencitabina , Terapia Neoadjuvante , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Cisplatino/uso terapêutico , Genômica , Cistectomia
13.
J Surg Oncol ; 130(1): 72-82, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38726668

RESUMO

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Feminino , Masculino , Estudos Retrospectivos , Terapia Neoadjuvante/mortalidade , Idoso , Pessoa de Meia-Idade , Taxa de Sobrevida , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Seguimentos , Procedimentos Cirúrgicos Vasculares/mortalidade , Procedimentos Cirúrgicos Vasculares/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico
15.
Eur Urol Open Sci ; 62: 81-90, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38468865

RESUMO

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design setting and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.

16.
Urol Pract ; 11(2): 356-366, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38315829

RESUMO

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias Urológicas/tratamento farmacológico , Excisão de Linfonodo
17.
Behav Pharmacol ; 35(1): 47-54, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38375659

RESUMO

Amisulpride is an atypical benzamide antipsychotic/antidepressant, whose mechanism of action is thought to depend mainly on dopamine D2/3 receptor activity, but also with some serotonin 5-HT2B/7 effects. The present study examined the role of D2/3 receptors and 5-HT2B/7 receptors in amisulpride's discriminative stimulus. Selective agonists and antagonists of the above receptors were tested in adult, male C57BL/6 mice trained to discriminate 10 mg/kg amisulpride from vehicle in a two-lever drug discrimination assay. After acquisition of the two-lever discrimination, the amisulpride generalization curve yielded an ED50 = 0.56 mg/kg (95% CI = 0.42-0.76 mg/kg). Substitution tests found that the D2/3 antagonist raclopride (62.7% Drug Lever Responding), D2/3 agonist quinpirole (56.6% DLR), 5-HT7 agonist LP-44 (50.1% DLR) and 5-HT7 antagonist SB-269970 (36.7% DLR) produced various degrees of partial substitution for the amisulpride stimulus, whereas the 5-HT2B agonist BW 723C86 (17.9% DLR) and 5-HT2B antagonist SB-204741 (21.1% DLR) yielded negligible amisulpride-like effects. In combination tests with amisulpride, quinpirole decreased percent responding from 98.3% to 57.0% DLR, LP-44 decreased percent responding from 97.6% to 76.7% DLR, and BW 723C86 reduced percent responding from 95.66% to 74.11% DLR. Taken together, the results from stimulus generalization and antagonism studies suggest that amisulpride has a complex discriminative cue that involves mainly mixed D2/3 receptor antagonist/agonist effects and, to a lesser degree, mixed 5-HT7 receptor agonist/antagonist and perhaps 5-HT2B receptor antagonist effects.


Assuntos
Antipsicóticos , Indóis , Piperazinas , Tetra-Hidronaftalenos , Tiofenos , Camundongos , Animais , Masculino , Antipsicóticos/farmacologia , Amissulprida/farmacologia , Quimpirol/farmacologia , Camundongos Endogâmicos C57BL , Relação Dose-Resposta a Droga , Aprendizagem por Discriminação
18.
Surgery ; 175(5): 1377-1385, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38365548

RESUMO

BACKGROUND: Neoadjuvant therapy is being increasingly used for patients with pancreatic cancer. The role of adjuvant therapy in these patients is unclear. The purpose of this study was to identify clinical and pathologic characteristics that are associated with longer overall survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy. METHODS: This study was conducted using multi-institutional data. All patients underwent surgery after at least 1 cycle of neoadjuvant therapy for pancreatic cancer. Patients who died within 3 months after surgery and were known to have distant metastasis or macroscopic residual disease were excluded. Mann-Whitney U test, χ2 analysis, Kaplan-Meier plot, and univariate and multivariate Cox regression analysis were performed as statistical analyses. RESULTS: In the present study, 529 patients with resected pancreatic cancer after neoadjuvant therapy were reviewed. For neoadjuvant therapy, 177 (33.5%) patients received neoadjuvant chemotherapy, and 352 (66.5%) patients received neoadjuvant chemoradiotherapy. The median duration of neoadjuvant therapy was 7.0 months (interquartile range, 5.0-8.7). Patients were followed for a median of 23.0 months after surgery. Adjuvant therapy was administered to 297 (56.1%) patients and was not associated with longer overall survival for the entire cohort (24 vs 22 months, P = .31). Interaction analysis showed that adjuvant therapy was associated with longer overall survival in patients who received less than 4 months neoadjuvant therapy (hazard ratio 0.40; 95% confidence interval 0.17-0.95; P = .03) or who had microscopic margin positive surgical resections (hazard ratio 0.56; 95% confidence interval 0.33-0.93; P = .03). CONCLUSION: In this retrospective study, there was a survival benefit associated with adjuvant therapy for patients who received less than 4 months of neoadjuvant therapy or had microscopic positive margins.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Terapia Combinada , Neoplasias Pancreáticas/patologia , Quimioterapia Adjuvante
19.
Ann Surg Oncol ; 31(2): 1328-1335, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37957512

RESUMO

BACKGROUND: Palliative care consultation (PCC) has been shown to improve quality of life and reduce costs for various chronic life-threatening diseases. Despite PCC incorporation into modern pancreatic cancer care guidelines, limited data regarding its specific utilization and impact on resource use is available. METHODS: The 2016-2020 Nationwide Readmissions Database was used to identify all adult hospitalizations entailing pancreatic cancer. Only patients with at least one readmission within 90 days were included to account for uncaptured out-of-hospital mortality. Multivariable regression models were used to ascertain the relationship between inpatient PCC during initial hospitalization and index as well as cumulative costs, overall length of stay (LOS), readmission rate, and number of repeat hospitalizations. RESULTS: Of an estimated 175,805 patients with pancreatic cancer, 11.1% had inpatient PCC during the index admission. PCC utilization significantly increased from 10.5% in 2016 to 11.6% in 2020 (nptrend < 0.001). After adjustment, PCC was associated with reduced index hospitalization costs [ß: - $1100; 95% confidence interval (CI) - 1500, - 800; P < 0.001] and cumulative 90-day costs (ß: - $11,700; 95% CI - 12,700, - 10,000; P < 0.001). PCC was associated with longer index LOS (ß: + 1.12 days, 95% CI 0.92-1.31, P < 0.001) but significantly reduced cumulative LOS (ß: - 3.16 days; 95% CI - 3.67, - 2.65; P < 0.001). Finally, PCC was linked with decreased odds of 30-day nonelective readmission (AOR: 0.48, 95% CI 0.45-0.50, P < 0.001). DISCUSSION: PCC was associated with decreased costs, readmission rates, and number of hospitalizations among patients with pancreatic cancer. Directed strategies to increase utilization and reduce barriers to consultation should be implemented to encourage practitioners to maximize inpatient PCC referral rates.


Assuntos
Cuidados Paliativos , Neoplasias Pancreáticas , Adulto , Humanos , Pacientes Internados , Qualidade de Vida , Hospitalização , Tempo de Internação , Readmissão do Paciente , Encaminhamento e Consulta , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos
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