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1.
Ann Surg Oncol ; 31(1): 614-621, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872456

RESUMO

INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipertermia Induzida/efeitos adversos , Neoplasias Peritoneais/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias do Apêndice/patologia , Adenocarcinoma Mucinoso/patologia , Estudos Retrospectivos , Taxa de Sobrevida
2.
Ann Surg ; 275(6): e743-e751, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33074899

RESUMO

OBJECTIVE: The study objective is to determine the association between travel distance and surgical volume on outcomes after esophageal, pancreatic, and rectal cancer resections. SUMMARY OF BACKGROUND DATA: "Take the Volume Pledge" aims to centralize esophagectomies, pancreatectomies, and proctectomies to hospitals meeting minimum volume standards. The impact of travel, and possible care fragmentation, on potential benefits of centralized surgery is not well understood. METHODS: Using the National Cancer Database (2004-2016), patients who underwent esophageal, pancreatic, or rectal resections at far HVH meeting volume standards versus local intermediate (IVH) and low-volume (LVH) hospitals were identified. Perioperative outcomes and 5-year OS were compared. RESULTS: Of 49,454 patients, 17,544 (34.5%) underwent surgery at far HVH, 11,739 (23.7%) at local IVH, and 20,171 (40.8%) at local LVH. The median (interquartilerange) travel distances were 77.1 (51.1-125.4), 13.2 (5.8-27.3), and 7.8 (3.1-15.5) miles to HVH, IVH, and LVH, respectively. By multivariable analysis, LVH was associated with increased 30-day mortality for all resections compared to HVH, but IVH was associated with mortality only for proctectomies [odds ratio 1.90, 95% confidence interval (CI) 1.31-2.75]. Compared to HVH, both IVH (hazard ratio 1.25, 95% CI 1.19-1.31) and LVH (hazard ratio 1.35, 95% CI 1.29-1.42) were associated with decreased 5-year OS. CONCLUSIONS: Compared to far HVH, 30-day mortality was higher for all resections at LVH, but only for proctectomies at IVH. Five-year OS was consistently worse at local LVH and IVH. Improving long-term outcomes at IVH may provide opportunities for greater access to quality cancer care.


Assuntos
Hospitais com Alto Volume de Atendimentos , Neoplasias Retais , Bases de Dados Factuais , Esofagectomia , Humanos , Viagem
3.
Ann Surg Oncol ; 27(3): 855-863, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31701298

RESUMO

BACKGROUND: Small (< 2 cm) and diminutive (< 1 cm) rectal neuroendocrine tumors (RNETs) are often described as indolent lesions. A large single-center experience was reviewed to determine the incidence of metastasis and the risk factors for its occurrence. METHODS: Cases of RNET between 2010 and 2017 at a single institution were retrospectively reviewed. The rate of metastasis was determined, and outcomes were stratified by tumor size and grade. Uni- and multivariable predictors of metastasis were identified, and a classification and regression tree analysis was used to stratify the risk for distant metastasis. RESULTS: The study identified 98 patients with RNET. The median follow-up period was 28 months. Of the 98 patients, 79 had primary tumors smaller than 1 cm, 8 had tumors 1 to 2 cm in size, and 11 had tumors 2 cm in size or larger. In terms of grade, 86 patients had grade 1 (G1) tumors, 8 patients had grade 2 (G2) tumors, and 4 patients had grade 3 (G3) tumors. Twelve patients developed metastatic disease. Both size and grade were associated with distant metastasis in the uni- and multivariable analyses, but when stratified by grade, size was predictive of metastasis only for G1 tumors (p < 0.001). Among the 12 patients with metastatic disease, 3 (25%) had diminutive primary tumors, and 9 (75%) had primary tumors 2 cm in size or larger. Diminutive tumors that metastasized were all G2. CONCLUSIONS: Patients with diminutive and small RNETs are at risk for metastatic disease. Tumor grade is a dominant predictor of dissemination. More rigorous staging, closer surveillance, or more aggressive initial management may be warranted for patients with G2 tumors, irrespective of size.


Assuntos
Recidiva Local de Neoplasia/patologia , Tumores Neuroendócrinos/secundário , Neoplasias Retais/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/terapia , Tumores Neuroendócrinos/terapia , Neoplasias Retais/terapia , Estudos Retrospectivos , Fatores de Risco
4.
Surg Endosc ; 34(10): 4472-4480, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31637603

RESUMO

BACKGROUND: Utilization of robotic proctectomy (RP) for rectal cancer has steadily increased since the inception of robotic surgery in 2002. Randomized control trials evaluating the safety of RP are in process to better understand the role of robotic assistance in proctectomy. This study aimed to characterize the trends in the use of RP for rectal cancer, and to compare oncologic outcomes with center-level RP volume. MATERIALS AND METHODS: 8107 patients with rectal adenocarcinoma who underwent RP were identified in the National Cancer Database (2010-2015). Logistic regression was used to evaluate associations between center-level volume and conversion to open proctectomy, margin status, lymph node yield, 30- and 90-day post-operative mortality, and overall survival. RESULTS: The utilization of RP increased from 2010 to 2015. On multivariate regression, lower center-level volume of RP was associated with significantly higher rates of conversion to open, positive margins, inadequate lymph node harvest (≥ 12), and lower overall survival. The present study was limited by its retrospective design and lack of information regarding disease-specific survival. CONCLUSIONS: This series suggests a volume-outcome relationship association; patients who have robot-assisted proctectomies performed at low-volume centers are more likely to have poorer overall survival, positive margins, inadequate lymph node harvest, and require conversion to open surgery. While these data demonstrate the increased adoption of robot-assisted proctectomy, an understanding of the appropriateness of this intervention is still lacking. As with any new intervention, further information from ongoing randomized controlled trials is needed to better clarify the role of RP in order to optimize patient outcomes.


Assuntos
Protectomia , Procedimentos Cirúrgicos Robóticos , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Retais/cirurgia , Fatores de Tempo , Resultado do Tratamento
5.
HPB (Oxford) ; 22(1): 83-90, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31239188

RESUMO

BACKGROUND: Studies supporting surgical management of metastatic pancreatic neuroendocrine tumor (PNET) are limited by selection bias. Chromogranin A (CgA) has been used as a biomarker for PNET and may reflect disease burden or biology. This study aimed to correlate CgA level with overall survival and to use it to match patients selected for different treatment approaches in an analysis of the impact of surgical management. METHODS: 1478 patients diagnosed with PNET in the National Cancer Database (2004-2014) were retrospectively identified, and logistic regression analyses were used to evaluate associations between the presence of metastatic disease and CgA level. After matching patients by CgA level and other factors predictive of surgical management, Kaplan-Meier survival analysis was performed. RESULTS: Median CgA level was significantly higher in metastatic versus localized PNET(169 ng/mL versus 66 ng/mL, p < 0.001). On multivariate logistic regression, CgA level was predictive of metastatic disease(OR 1.002, p < 0.001) and survival in metastatic and non-metastatic patients. After matching for CgA level, surgery was associated with improved overall survival. DISCUSSION: CgA level is predictive of the presence of distant metastatic disease and overall survival in PNET. When matched by CgA and other predictors of treatment approach, patients with metastatic PNET undergoing surgery have improved survival.


Assuntos
Cromogranina A/sangue , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/sangue , Neoplasias Pancreáticas/sangue , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
6.
Ann Surg Oncol ; 26(12): 3972-3979, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31201596

RESUMO

BACKGROUND: Simultaneous proctectomy and hepatic resection for stage IV rectal cancer remains controversial due to concerns for increased morbidity and mortality. While small series have described simultaneous rectal and hepatic resection, surgical outcomes in a large national cohort have not been described. METHODS: Overall, 9012 patients with stage IV rectal adenocarcinoma with hepatic metastases were identified in the National Cancer Data Base (2010-2015). Associations between treatment selection, tumor and patient characteristics, 30- and 90-day mortality, and factors predictive of survival after surgery were examined. Logistic regression analyses were used to evaluate associations between tumor/patient characteristics, and selection of combined proctectomy and hepatectomy (C-PH). Kaplan-Meier analysis was used to identify median survival stratified by age and other patient-specific factors. RESULTS: Among patients included for analysis, 1331 (14.8%) underwent C-PH. Factors associated with lower rates of C-PH included increasing age, Black/Hispanic race, increased Charlson comorbidity score, Medicare/Medicaid/uninsured status, and treatment at a community cancer program. Thirty- and 90-day mortality increased with age (Chi square 11.4, p < 0.005; and Chi square 23.9, p < 0.001, respectively). On multivariate analysis, poorer survival after C-PH was associated with age > 70 years (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.0-2.5, p < 0.001), perineural invasion (HR 1.5, 95% CI 1.2-1.9, p < 0.001), kras mutation (HR 1.5, 95% CI 1.1-2.1, p = 0.006), positive circumferential margin (HR 1.3, 95% CI 1.0-1.7, p = 0.03), and omission of postoperative chemotherapy (HR 1.4, 95% CI 1.1-1.7, p = 0.002). CONCLUSIONS: C-PH should be utilized with caution in frail, high-risk patients. Such patients may be better served by staged surgical management or nonsurgical therapy.


Assuntos
Adenocarcinoma/cirurgia , Hepatectomia/mortalidade , Protectomia/mortalidade , Neoplasias Retais/cirurgia , Adenocarcinoma/secundário , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
8.
Dis Colon Rectum ; 61(12): 1372-1379, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30312223

RESUMO

BACKGROUND: Rectal neuroendocrine tumors are often found incidentally. Local excision alone has been advocated for lesions ≤2 cm; however, the evidence base for this approach is limited. OBJECTIVE: Associations among tumor size, degree of differentiation, and presence of distant metastatic disease were examined. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted using a nationwide cohort. PATIENTS: A total of 4893 patients with rectal neuroendocrine tumors were identified in the National Cancer Database (2006-2015). MAIN OUTCOME MEASURES: Logistic regression analyses were used to evaluate associations among tumor size, degree of differentiation, and presence of regional and distant metastatic disease. Cut point analysis was performed to identify an optimal size threshold predictive of distant metastatic disease. RESULTS: Of patients included for analysis, 3880 (79.3%) had well-differentiated tumors, 540 (11.0%) had moderately differentiated tumors, and 473 (9.7%) had poorly differentiated tumors. On logistic regression, increasing size was associated with a higher likelihood of pathologically confirmed lymph node involvement (among patients undergoing proctectomy), and both size and degree of differentiation were independently associated with a higher likelihood of distant metastatic disease. The association between tumor size and distant metastatic disease was stronger for well-differentiated and moderately differentiated tumors (OR = 1.4; p < 0.001 for both) than for poorly differentiated tumors (OR = 1.1; p = 0.010). For well-differentiated tumors, the optimal cut point for the presence of distant metastatic disease was 1.15 cm (area under the curve = 0.88; 88% sensitive and 88% specific). Tumors ≥1.15 cm in diameter were associated with a substantially increased incidence of distant metastatic disease (72/449 (13.8%)). For moderately differentiated tumors, the optimal cut point was also 1.15 cm (area under the curve = 0.87, 100% sensitive and 75% specific). LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Tumor size and degree of differentiation are predictive of regional and distant metastatic disease in rectal neuroendocrine tumors. Patients with tumors >1.15 cm are at substantial risk of distant metastasis and should be staged and managed accordingly. See Video Abstract at http://links.lww.com/DCR/A778.


Assuntos
Tumores Neuroendócrinos/secundário , Neoplasias Retais/patologia , Carga Tumoral , Idoso , Bases de Dados Factuais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/cirurgia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Estados Unidos
9.
Clin Transplant ; 32(6): e13260, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29656398

RESUMO

INTRODUCTION: The new kidney allocation system (KAS) prioritizes patients based on date of dialysis initiation or waitlisting, whichever is earlier. We hypothesized that this change would increase transplant rates for patients with prolonged pretransplant dialysis times (DT) and aimed to assess the impact of prolonged DT on post-transplant outcomes. METHODS: We used United Network for Organ Sharing registry data to assess outcomes for patients added to the renal transplant waitlist from January 1, 1998 to December 31, 2010 and patients transplanted from January 1, 1998 to December 3, 2012. RESULTS: Compared with patients transplanted pre-emptively, patients with <5 years, 5-9 years, and ≥10 years DT had progressively decreased graft and patient survival (P < .001). The rates of short-term complications including delayed graft function, graft loss within 30 days, and patient death within 30 days were significantly higher in cohorts with ≥10 years DT than in cohorts with less DT (P < .001). CONCLUSIONS: Patients with pretransplant DT of ≥10 years had worse outcomes than patients pre-emptively transplanted or transplanted with shorter DT. Durations of dialysis dependence beyond 10 years were associated with further deterioration in short-term but not long-term post-transplant outcomes.


Assuntos
Função Retardada do Enxerto/mortalidade , Transplante de Rim/mortalidade , Diálise Renal/mortalidade , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Doadores de Tecidos , Transplantados , Listas de Espera , Adulto Jovem
10.
HPB (Oxford) ; 20(11): 1062-1066, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29887262

RESUMO

BACKGROUND: Subtotal cholecystectomy (SC) involves removal of a portion of the gallbladder typically due to hazardous inflammation. While this technique reliably prevents common bile duct (CBD) injury, future procedures can be required if the gallbladder remnant becomes symptomatic. The morbidity associated with resection of gallbladder remnants in patients that previously underwent SC is reviewed. METHODS: Records for patients having undergone redo cholecystectomy for symptomatic gallbladder remnants in a tertiary care system from 2013 to 2017 were retrospectively reviewed. RESULTS: Fourteen patients underwent repeat cholecystectomy. Five surgeons dictated the initial procedure as a subtotal cholecystectomy. All patients returned with symptomatic cholelithiasis between zero months and seven years after the index cholecystectomy. Redo cholecystectomy was attempted laparoscopically in two patients but ultimately required an open approach in all. One patient had a recognized CBD injury requiring a hepaticojejunostomy, and a second patient had a minor wound infection. Symptoms resolved in 13/14 patients. CONCLUSIONS: Redocholecystectomy (RC) for gallbladder remnants has been detailed in case reports, but no sizable North American series have been presented. These results illustrate a drawback to the reconstituting technique of SC. RC effectively resolves symptoms but requires adherence to safe principles of cholecystectomy and is one indication for an open approach.


Assuntos
Colecistectomia Laparoscópica , Colecistectomia/métodos , Colelitíase/cirurgia , Vesícula Biliar/cirurgia , Adulto , Idoso , Colecistectomia/efeitos adversos , Colecistectomia Laparoscópica/efeitos adversos , Colelitíase/diagnóstico por imagem , Colelitíase/etiologia , Feminino , Vesícula Biliar/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Transplantation ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38685198

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation. METHODS: Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors. RESULTS: Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage (P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI (P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia (P < 0.01 for AST and P < 0.01 for ALT). CONCLUSIONS: Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.

13.
Surg Oncol Clin N Am ; 32(2): 327-342, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36925189

RESUMO

Minimally invasive pancreatectomy is increasingly used. Although offering potential advantages over open approaches, minimally invasive pancreatectomy has many challenges to maintain high-quality of oncologic resection. Multiple patient and surgical factors should be considered in planning laparoscopic or robotic resection, including the learning curve required to produce proficiency. For pancreaticoduodenectomy, distal pancreatectomy, and other pancreatic resections, a safe, margin-negative resection remains the goal. National and societal guidelines for the adoption of minimally invasive pancreatectomy are ongoing and will continue to be important as these techniques are further adopted.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Pancreatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Pancreáticas/cirurgia , Robótica/métodos , Laparoscopia/métodos , Resultado do Tratamento
14.
Am J Surg ; 225(1): 53-57, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36207173

RESUMO

BACKGROUND: The value of individual variable contributions to post-hepatectomy length of stay (LOS) are difficult to quantify within bundled care pathways. METHODS: Poisson regression and marginal effects models for prolonged post-hepatectomy LOS (>25% median) included Kawaguchi-Gayet (KG) complexity, perioperative variables, and pathways (minimally-invasive = MIS; low-intermediate-risk = KGI/II; high-risk = KGIII; combination). RESULTS: Median LOS was 2, 4, 5, and 5 days for MIS, KGI/II, KGIII and combination pathways (N = 978). Poisson regression identified age, intraoperative fluids, delayed diet tolerance, and combination cases as associated with increased LOS (p < 0.01). Marginal effects analysis demonstrated the following added probability of longer LOS: each year of age 0.03x, 250 mL intraoperative fluids 0.06x, each operative hour 0.2x, additional day before diet tolerance 0.4x, combination cases 0.7x. MIS was associated with 1.2x increased probability of shorter LOS. CONCLUSIONS: Optimizing intraoperative fluids, operative time, and postoperative diet, while favoring MIS approach when feasible, may maximize effects of post-hepatectomy care pathways to reduce LOS.


Assuntos
Procedimentos Clínicos , Hepatectomia , Humanos , Recém-Nascido , Tempo de Internação , Duração da Cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Minimamente Invasivos
15.
J Oral Maxillofac Surg ; 70(10): 2356-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22265168

RESUMO

Metastatic renal cell carcinoma to the head and neck is rare. Most reported cases of metastases to the head and neck involve the thyroid and parotid glands. Metastasis to other salivary glands is exceedingly rare. This report describes a case of a solitary metastasis of renal cell carcinoma to the submandibular gland 9 years after nephrectomy. To the authors' knowledge, this is the first case successfully diagnosed preoperatively using a combination of fine-needle aspiration and clinical history. The patient subsequently underwent a submandibular gland resection with preservation of the facial nerve branches. For the 3 years since resection of the submandibular gland, the patient has been free of disease.


Assuntos
Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias da Glândula Submandibular/secundário , Diagnóstico Diferencial , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Seguimentos , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Nefrectomia
16.
Abdom Radiol (NY) ; 47(12): 4073-4080, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35476146

RESUMO

Neuroendocrine tumors are a rare subset of tumors that are increasing in incidence over the last 4 decades. These tumors occur along the gastrointestinal tract and bronchopulmonary tree and frequently metastasize. Up to 90% of patients with gastroenteropancreatic neuroendocrine tumors develop liver metastases (NeLM) during their clinical course. The development of NeLM and their appropriate management has a profound impact on patient morbidity and mortality. Workup of NeLM involves biopsy to define tumor grade, cross-sectional imaging to delineate the distribution and number of metastases, and hormonal studies to determine tumor functionality. Depending on these three factors, a combination of cytoreductive surgery, liver-directed therapies, and medical management-with cytostatic and cytotoxic chemotherapies, is utilized. The multidisciplinary management of patients with NeLM should carefully consider all these factors.


Assuntos
Neoplasias Intestinais , Neoplasias Hepáticas , Tumores Neuroendócrinos , Cirurgiões , Humanos , Hepatectomia , Tumores Neuroendócrinos/patologia , Neoplasias Intestinais/patologia , Neoplasias Hepáticas/cirurgia
17.
Transplantation ; 106(11): 2166-2171, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35655356

RESUMO

BACKGROUND: There is increasing evidence that estrogen is responsible for improved outcomes in female kidney transplant recipients. Although the exact mechanism is not yet known, estrogen appears to exert its protective effects by ameliorating ischemia-reperfusion injury (IRI). In this study, we have examined whether the beneficial effects of exogenous estrogen in renal IRI are replicated by therapy with any one of several selective estrogen receptor modulators. METHODS: C57BL/6 adult mice underwent standardized warm renal ischemia for 28 min after being injected with the selective estrogen receptor modulators, raloxifene, lasofoxifene, tamoxifen, bazedoxifene, or control vehicle (dimethyl sulfoxide), at 16 and 1 h before IRI. Plasma concentrations of blood urea nitrogen and creatinine were assessed 24, 48, 72, and 96 h post-IRI. Tissue was collected 30 d postischemia for fibrosis analysis using Sirius Red staining. RESULTS: Raloxifene treatment in female mice resulted in significantly lower blood urea nitrogen and creatinine after IRI and significantly lower fibrosis 30 d following IRI. CONCLUSIONS: Raloxifene is protective against both acute kidney injury and fibrosis resulting from renal IRI in a mouse model.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Feminino , Camundongos , Animais , Cloridrato de Raloxifeno/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Creatinina , Dimetil Sulfóxido/farmacologia , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia , Rim/patologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Estrogênios/farmacologia , Fibrose
18.
Sci Rep ; 11(1): 9018, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907245

RESUMO

Histone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.


Assuntos
Proteínas Correpressoras/metabolismo , Histona Desacetilase 2/metabolismo , Túbulos Renais Proximais/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Proteínas Correpressoras/antagonistas & inibidores , Endotelinas/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Deleção de Genes , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/antagonistas & inibidores , Histona Desacetilase 2/genética , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout
19.
Clin Colorectal Cancer ; 18(4): 292-300, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31447135

RESUMO

BACKGROUND: Few studies have confirmed a benefit for adjuvant chemotherapy (aCTX) in stage II colon cancer. We used the National Cancer Database to explore the use and efficacy of aCTX in patients with both normal-risk (NR) and high-risk (HR) young stage II colon cancer. PATIENTS AND METHODS: We identified patients with stage II colon cancer who underwent colectomy between 2010 and 2015. HR patients included at least: lymphovascular or perineural invasion, < 12 lymph nodes, poor/un-differentiation, T4, or positive margins. Rates of aCTX by age and risk were calculated, and adjusted factors associated with aCTX were identified. Overall survival was estimated using the Kaplan-Meier method and Cox multivariable analyses for patients < 50 years. RESULTS: Among the 81,066 stage II patients who underwent colectomy, 6093 (7.5%) were < 50 years old. Of these, 2669 patients were HR. Thirty percent of NR and almost 60% of HR patients < 50 years received aCTX, compared with 8% and 23% of patients > 50 years (P < .001). In NR patients < 50 years, 35.3% with microsatellite-stable tumors and 18% with microsatellite unstable tumors received aCTX (P < .001), whereas 63.6% and 43.2%, respectively, of HR patients did (P < .001). The most significant multivariable predictors of aCTX were risk status and age. On univariate analysis, there was no survival benefit associated with aCTX in patients < 50 years. Multivariate analysis failed to demonstrate a survival benefit for aCTX for either group (HR, 0.97; P = .84; NR, 0.1.03; P = .90). CONCLUSION: Young patients with HR and NR colon cancer received aCXT more frequently than older patients with no demonstrable survival benefit. This bears further evaluation to avoid the real risks of over-treatment in this increasing population.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Quimioterapia Adjuvante/estatística & dados numéricos , Neoplasias do Colo/mortalidade , Uso Excessivo de Medicamentos Prescritos/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Taxa de Sobrevida
20.
Surg Obes Relat Dis ; 12(1): 11-20, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26410537

RESUMO

BACKGROUND: Short- and mid-term data on Roux-en-Y gastric bypass (RYGB) indicate sustained weight loss and improvement in co-morbidities. Few long-term studies exist, some of which are outdated, based on open procedures or different techniques. OBJECTIVES: To investigate long-term weight loss, co-morbidity remission, nutritional status, and complication rates among patients undergoing RYGB. SETTING: An academic, university hospital in the United States. METHODS: Between October 2000 and January 2004, patients who underwent RYGB≥10 years before study onset were eligible for chart review, office visits, and telephone interviews. Revisional surgery was an endpoint, ceasing eligibility for study follow-up. Outcomes included weight loss measures and rates of co-morbidity remission, complications, and nutritional deficiencies. RESULTS: RYGB was performed in 328 patients with a mean preoperative body mass index of 47.5 kg/m(2). Of 294 eligible patients, 134 (46%) were contacted for follow-up at ≥ 10 years (10+Year follow-up). Mean percentage excess weight loss (%EWL) was 58.9% at 10+Year. Higher %EWL was achieved by non-super-obese versus super-obese (61.3% versus 52.9%, P = .034). Blood pressure, lipid panel, and hemoglobin A1c improved significantly. At 10 years, remission of co-morbidities was 46% for hypertension and hyperlipidemia and 58% for diabetes mellitus. Thirty patients (9%) had revisional surgery for weight regain. Sixty-four patients (19.5%) had long-term complications requiring surgery. All-cause mortality was 2.7%. Nutritional deficiencies were seen in 87% of patients. CONCLUSIONS: Weight loss after RYGB appears to be significant and sustainable, especially in the non-super-obese. Co-morbidities are improved, with a substantial number in remission a decade later. Nutritional deficiencies are almost universal.


Assuntos
Previsões , Derivação Gástrica/métodos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Redução de Peso , Adulto , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Incidência , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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