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1.
Ann Surg Oncol ; 30(8): 5105-5112, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37233954

RESUMO

BACKGROUND: Solid pseudopapillary neoplasms (SPN) are rare tumors of the pancreas, typically affecting young women. Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. We explore the idea that small, localized SPN could be safely observed. METHODS: This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code 8452. RESULTS: A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. CONCLUSIONS: Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.


Assuntos
Carcinoma Papilar , Neoplasias Pancreáticas , Humanos , Feminino , Adulto , Masculino , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias Pancreáticas
2.
J Surg Res ; 285: 150-157, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36680875

RESUMO

INTRODUCTION: The COVID-19 pandemic immediately interrupted procedural training. The lasting impact of reduced caseloads and service redeployments on procedural-resident training has been underexplored. This longitudinal study investigated the long-term perspectives of skill decay after short breaks in training and implications for ensuring resident competency attainment. METHODS: Web-based cross-sectional surveys distributed immediately after (June 2020) compared to 1 y after (July 2021) COVID-19 redeployments at two tertiary academic medical centers of an integrated health system in New York. Participants included general surgery, surgical subspecialty, and anesthesiology residents and faculty. RESULTS: Fifty-five residents and 33 faculty completed the survey. Ninety-point nine percent of residents and 36.4% of faculty were redeployed to COVID-ICUs. Sixty-three-point seven percent of residents and 75.0% of faculty reported a reduction in resident technical skills in the short-term, with significantly less (45.5% of residents and 21.2% of faculty) reporting persistent reduction in technical skill after 1 y (P = 0.001, P < 0.001). Seventy-five percent of residents and 100% of faculty were confident residents would be able to practice independently at the conclusion of their training. Sixty-five-point five percent of residents and 63.6% of faculty felt that residents experienced a durable improvement in critical care skills. Residents also reported a positive long-term impact on professional core competencies at 1 y. CONCLUSIONS: Longitudinal surveillance of residents after COVID-19 redeployments suggests washout of temporary skill decay and return of resident confidence upon resumption of traditional training. This may provide insight into the impact of other short-term training interruptions on resident skill and promote greater resident support upon training resumption to ensure competency attainment.


Assuntos
COVID-19 , Internato e Residência , Humanos , Estudos Longitudinais , Estudos Transversais , Pandemias , Competência Clínica , Docentes de Medicina
3.
HPB (Oxford) ; 25(9): 1074-1082, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37258312

RESUMO

BACKGROUND: Resection of neuroendocrine tumors (NET) with surgical debulking of liver metastasis (NETLM) is associated with improved survival. In patients with an unknown primary (UP-NETLM), the effects of debulking remains unclear. METHODS: The National Cancer Database (2004-2016) was queried for patients with small intestine (SI) and pancreas (P) NETLMs. If the liver was listed as the primary site, the patient's disease was classified as UP-NETLM. RESULTS: Patients with UP-NETLM, SI-NETLM, and P-NETLM who were managed non-operatively demonstrated a significant difference in 5-year overall survival (OS) (21.5% vs. 39.2% vs. 17.1%; p < 0.0001). OS in patients who underwent debulking was higher (63.7% vs. 73.2% vs. 54.2%). Patients with UP-NETLMs who underwent debulking had similar OS to patient with SI-NETLM (p = 0.051), but significantly higher OS, depending on tumor differentiation, compared to patients with P-NETLMs. If well-differentiated, surgery for UP-NETLMs was associated with a higher rate of OS (p = 0.009), while no difference was observed if moderately (p = 0.209) or poorly/undifferentiated (p = 0.633). P-NETLMs were associated with worse OS (p < 0.001) on multivariate analysis. DISCUSSION: Debulking in patients with UP-NETLMs was associated with similar OS compared to patients with SI-NETLMs and better or similar OS compared to patient with P-NETLMs.


Assuntos
Neoplasias Hepáticas , Neoplasias Primárias Desconhecidas , Tumores Neuroendócrinos , Humanos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Primárias Desconhecidas/cirurgia , Estudos Retrospectivos
4.
Ann Surg ; 276(3): 450-462, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35972511

RESUMO

OBJECTIVE: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. BACKGROUND: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. METHODS: During 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. RESULTS: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. CONCLUSION: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Antineoplásicos/uso terapêutico , Etnicidade , Humanos , Grupos Minoritários , Terapia Neoadjuvante , Organoides , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas
5.
Ann Surg ; 274(6): e564-e573, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31851004

RESUMO

OBJECTIVE: To assess the impact of a granular measure of SED on pancreatic surgical and cancer-related outcomes at a high-volume cancer center that employs a standardized clinic pathway. SUMMARY OF BACKGROUND DATA: Prior research has shown that low socioeconomic status leads to less treatment and worse outcomes for PDAC. However, these studies employed inconsistent definitions and categorizations of socioeconomic status, aggregated individual socioeconomic data using large geographic areas, and lacked detailed clinicopathologic variables. METHODS: We conducted a retrospective cohort study of 1552 PDAC patients between 2008 and 2015. Patients were stratified using the area deprivation index, a validated dataset that ranks census block groups based on SED. Multivariable models were used in the curative surgery cohort to predict the impact of SED on (1) grade 3/4 Clavien-Dindo complications, (2) initiation of adjuvant therapy, (3) completion of adjuvant therapy, and (4) overall survival. RESULTS: Patients from high SED neighborhoods constituted 29.9% of the cohort. Median overall survival was 28 months. The rate of Clavien-Dindo grade 3/4 complications was 14.2% and completion of adjuvant therapy was 65.6%. There was no evidence that SED impacted surgical evaluation, receipt of curative-intent surgery, postoperative complications, receipt of adjuvant therapy or overall survival. CONCLUSIONS: Although nearly one-quarter of curative-intent surgery patients were from high SED neighborhoods, this factor was not associated with measures of treatment quality or survival. These observations suggest that treatment at a high-volume cancer center employing a standardized clinical pathway may in part address socioeconomic disparities in pancreatic cancer.


Assuntos
Adenocarcinoma/cirurgia , Procedimentos Clínicos , Neoplasias Pancreáticas/cirurgia , Fatores Socioeconômicos , Adenocarcinoma/mortalidade , Institutos de Câncer/estatística & dados numéricos , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Utilização de Instalações e Serviços , Feminino , Humanos , Masculino , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Complicações Pós-Operatórias , Características de Residência , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia
6.
Ann Surg Oncol ; 28(13): 8318-8328, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34312800

RESUMO

BACKGROUND: Ampullary neuroendocrine tumors (NETs) make up < 1% of all gastroenteropancreatic NETs, and information is limited to case series. This study compares patients with ampullary, duodenal, and pancreatic head NETs. METHODS: The National Cancer Database (2004-2016) was queried for patients with ampullary, duodenal, and pancreatic head NETs. Survival was evaluated using Kaplan-Meier analysis and Cox regression. RESULTS: Overall, 872, 9692, and 6561 patients were identified with ampullary, duodenal, and pancreatic head NETs, respectively. Patients with ampullary NETs had more grade 3 tumors (n = 149, 17%) than patients with duodenal (n = 197, 2%) or pancreatic head (n = 740, 11%) NETs. Patients with ampullary NETs had more positive lymph nodes (n = 297, 34%) than patients with duodenal (n = 950, 10%) or pancreatic head (n = 1513, 23%) NETs. On multivariable analysis for patients with ampullary NETs, age (hazard ratio [HR] 1.03, p < 0.0001), Charlson-Deyo score of 2 (HR 2.3, p = 0.001) or ≥3 (HR 2.9, p = 0.013), grade 2 (HR 1.9, p = 0.007) or grade 3 tumors (HR 4.0, p < 0.0001), and metastatic disease (HR 2.0, p = 0.001) were associated with decreased survival. At 5 years, the overall survival (OS) for patients with ampullary, duodenal, and pancreatic head NETs was 59%, 71%, and 50%, respectively (p < 0.0001), whereas the 5-year OS for patients with ampullary, duodenal, and pancreatic head NETs who underwent surgery was 62%, 78%, and 76%, respectively (p < 0.0001). CONCLUSIONS: Ampullary NETs were more likely to present with high-grade tumors and lymph node metastases. Based on the clinicopathologic and survival data, ampullary NETs have a unique underlying biology compared with duodenal and pancreatic head NETs.


Assuntos
Neoplasias do Ducto Colédoco , Neoplasias Duodenais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/cirurgia , Humanos , Tumores Neuroendócrinos/cirurgia , Modelos de Riscos Proporcionais
7.
J Surg Oncol ; 122(6): 1074-1083, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32673436

RESUMO

BACKGROUND AND OBJECTIVES: Current guidelines recommend neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) patients with anatomically resectable tumors but elevated CA 19-9. However, this recommendation is based on data from anatomically resectable and borderline resectable PDAC patients. Therefore, we analyzed the association of preoperative CA 19-9 with oncologic outcomes in a cohort of anatomically resectable PDAC patients. METHODS: A single-institution PDAC database from 2007 to 2015 included patients who underwent guideline-based staging and were anatomically resectable. Patients with bilirubin above 1.5 after decompression, nonsecretors of CA 19-9, and borderline resectable patients were excluded. Statistical analysis included frequency testing and regression modeling for recurrence and survival. RESULTS: One hundred forty-four PDAC patients were identified; 16 (11.1%) had elevated preoperative CA 19-9 ≥ 1000. A CA 19-9 level ≥1000 was not associated with demographic, clinical, or pathological factors. After adjustment for potential confounders, CA 19-9 levels (continuous, median, 500 U/mL, or 1000 U/mL cut-offs) were not associated with recurrence or overall survival (OS). CONCLUSIONS: Although guidelines recommend CA 19-9 to determine the management of anatomically resectable PDAC patients, CA 19-9 was not associated with recurrence or OS in this cohort. Our findings do not suggest that CA 19-9 alone should determine the PDAC treatment strategy.


Assuntos
Adenocarcinoma/mortalidade , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/mortalidade , Recidiva Local de Neoplasia/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Cuidados Pré-Operatórios , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Pancreáticas
8.
HPB (Oxford) ; 22(2): 241-248, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31563326

RESUMO

BACKGROUND: Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC). It is estimated that only 40-80% eligible patients initiate intended adjuvant chemotherapy. Completion rates are largely unknown. METHODS: A retrospective analysis of outcomes of patients with resected PDAC over an 8-year period at H. Lee Moffitt Cancer Center (MCC) was performed. RESULTS: From a total of 309 patients, 299 were included for further analysis. 242 (81%) initiated adjuvant therapy (AT) and 195 (65%) completed the intended course. The median time-to-initiation of AT was 53 days (7.6 weeks). The most common reasons for early discontinuation of AT (n = 47) were toxicity (n = 29), disease recurrence (n = 9), patient decision (n = 4), unrelated comorbidities (n = 3), and death (n = 1). Completion of AT was an independent predictor of overall survival (OS) and recurrence-free survival (RFS) on multivariable analysis (OS: HR 0.41, CI 0.27-0.61, p < 0.001; RFS: HR 0.52, CI 0.36-0.76, p < 0.001). Factors associated with early termination of AT were vascular resection (OR 0.29, CI 0.13-0.67, p = 0.004) and administration of AT with local oncologist as opposed to MCC (OR 0.41, CI 0.21-0.82, p = 0.010). CONCLUSION: Completion of AT is associated with improved survival in patients with resected PDAC. Factors associated with an inability to complete AT include vascular resection and administration of AT with local care team in the patient's community.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
10.
Int J Cancer ; 138(6): 1494-505, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26481559

RESUMO

A recent gene expression classification of hepatocellular carcinoma (HCC) includes a poor survival subclass termed S2 representing about one-third of all HCC in clinical series. S2 cells express E-cadherin and c-myc and secrete AFP. As the expression of fibroblast growth factor receptors (FGFRs) differs between S2 and non-S2 HCC, this study investigated whether molecular subclasses of HCC predict sensitivity to FGFR inhibition. S2 cell lines were significantly more sensitive (p < 0.001) to the FGFR inhibitors BGJ398 and AZD4547. BGJ398 decreased MAPK signaling in S2 but not in non-S2 cell lines. All cell lines expressed FGFR1 and FGFR2, but only S2 cell lines expressed FGFR3 and FGFR4. FGFR4 siRNA decreased proliferation by 44% or more in all five S2 cell lines (p < 0.05 for each cell line), a significantly greater decrease than seen with knockdown of FGFR1-3 with siRNA transfection. FGFR4 knockdown decreased MAPK signaling in S2 cell lines, but little effect was seen with knockdown of FGFR1-3. In conclusion, the S2 molecular subclass of HCC is sensitive to FGFR inhibition. FGFR4-MAPK signaling plays an important role in driving proliferation of a molecular subclass of HCC. This classification system may help to identify those patients who are most likely to benefit from inhibition of this pathway.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/genética , Inibidores de Proteínas Quinases/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Animais , Biomarcadores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Receptores Proteína Tirosina Quinases/genética
11.
Cancer ; 122(8): 1216-27, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26914713

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC)-associated mortality is increasing at an alarming rate, and there is a readily identifiable cohort of at-risk patients with cirrhosis, viral hepatitis, nonalcoholic fatty liver disease, and diabetes. These patients are candidates for chemoprevention. Metformin is an attractive agent for chemoprevention because it is inexpensive, has a favorable safety profile, and is well tolerated over long time periods. METHODS: The authors studied the efficacy of metformin as a prevention agent in a clinically relevant rat model of HCC, in which tumors develop in the setting of chronic inflammation and cirrhosis. Repeated injections of diethylnitrosamine were used to induce sequential cirrhosis and HCC, and metformin was administered at the first signs of either fibrosis or cirrhosis. RESULTS: Prolonged metformin exposure was safe and was associated with decreases in fibrotic and inflammatory markers, especially when administered early at the first signs of fibrosis. In addition, early metformin treatment led to a 44% decrease in HCC incidence, whereas tumor burden was unchanged when metformin was administered at the first signs of cirrhosis. It is noteworthy that activation of the hepatic progenitor/stem cell compartment was first observed at the onset of cirrhosis; therefore, only early metformin treatment suppressed receptor for advanced glycation end products and inhibited the activation of hepatic progenitor cells. CONCLUSIONS: The current results are the first to demonstrate an effect on progenitor/stem cells in the setting of chemoprevention and provide further rationale to explore metformin as an early intervention in clinical trials of patients with chronic liver disease at high risk for HCC.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Transformação Celular Neoplásica/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Metformina/farmacologia , Células-Tronco/efeitos dos fármacos , Animais , Biópsia por Agulha , Western Blotting , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Reação em Cadeia da Polimerase/métodos , Distribuição Aleatória , Ratos , Ratos Wistar , Valores de Referência , Células-Tronco/citologia , Resultado do Tratamento
14.
J Hepatol ; 63(3): 689-96, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26022693

RESUMO

BACKGROUND & AIMS: Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy. METHODS: Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (ΔR1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content. RESULTS: ΔR1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of ΔR1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver. CONCLUSIONS: EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis.


Assuntos
Cirrose Hepática Experimental/patologia , Imageamento por Ressonância Magnética/métodos , Sirolimo/uso terapêutico , Animais , Ductos Biliares , Modelos Animais de Doenças , Técnicas de Imagem por Elasticidade , Ligadura , Cirrose Hepática Experimental/tratamento farmacológico , Masculino , Curva ROC , Ratos
15.
Hepatology ; 59(4): 1577-90, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24677197

RESUMO

UNLABELLED: Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer-related mortality in the United States. Because of the lack of viable treatment options for HCC, prevention in high-risk patients has been proposed as an alternative strategy. The main risk factor for HCC is cirrhosis and several lines of evidence implicate epidermal growth factor (EGF) in the progression of cirrhosis and development of HCC. We therefore examined the effects of the EGF receptor (EGFR) inhibitor erlotinib on liver fibrogenesis and hepatocellular transformation in three different animal models of progressive cirrhosis: a rat model induced by repeated, low-dose injections of diethylnitrosamine (DEN), a mouse model induced by carbon tetrachloride (CCl4 ), and a rat model induced by bile duct ligation (BDL). Erlotinib reduced EGFR phosphorylation in hepatic stellate cells (HSC) and reduced the total number of activated HSC. Erlotinib also decreased hepatocyte proliferation and liver injury. Consistent with all these findings, pharmacological inhibition of EGFR signaling effectively prevented the progression of cirrhosis and regressed fibrosis in some animals. Moreover, by alleviating the underlying liver disease, erlotinib blocked the development of HCC and its therapeutic efficacy could be monitored with a previously reported gene expression signature predictive of HCC risk in human cirrhosis patients. CONCLUSION: These data suggest that EGFR inhibition using Food and Drug Administration-approved inhibitors provides a promising therapeutic approach for reduction of fibrogenesis and prevention of HCC in high-risk cirrhosis patients who can be identified and monitored by gene expression signatures.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Quinazolinas/uso terapêutico , Animais , Ductos Biliares/fisiopatologia , Tetracloreto de Carbono/efeitos adversos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dietilnitrosamina/efeitos adversos , Modelos Animais de Doenças , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Ligadura/efeitos adversos , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Fosforilação/efeitos dos fármacos , Prognóstico , Quinazolinas/farmacologia , Ratos , Ratos Wistar , Transcriptoma
16.
Ann Surg Oncol ; 22(11): 3451-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26224403

RESUMO

PURPOSE AND DESIGN: In recent years, there have been dramatic improvements in the diagnosis and treatment of patients with melanoma. The development of molecular markers and associated targeted therapies have given new hope to subsets of patients with advanced disease. Here we discuss the most important advances in molecular targeted therapy and how these developments are likely to affect the practice of the clinical surgeon. RESULTS AND CONCLUSIONS: Germ-line and somatic mutations are common in melanoma and provide prognostic information that can now be harnessed to provide a more personalized approach to cancer treatment. BRAF mutation at the V600 position is the most commonly identified mutation in patients with melanoma. Treatment with targeted inhibitors in patients with BRAF-mutant melanoma has afforded dramatic responses in about half of selected patients. Unfortunately, disease control is not durable and recurrences are common. We predict an increasing role for the surgeon in the multidisciplinary treatment of patients with metastatic disease, as well as a role for molecular profiling in patients with high-risk early stage disease. Further, we are only beginning to understand the prognostic significance of various gene mutations in patients with melanoma.


Assuntos
Sistema de Sinalização das MAP Quinases/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas B-raf/genética , Mutação em Linhagem Germinativa , Humanos , Imunoterapia , Melanoma/cirurgia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores
17.
Am J Surg ; 227: 77-84, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37798150

RESUMO

BACKGROUND: Since 2013, North American Neuroendocrine Tumor Society (NANETS) consensus-guidelines have endorsed consideration of surgical intervention for pancreatic- neuroendocrine tumors (PNET) with liver metastases. METHODS: Patients with non-functional PNET with liver only metastases from 2010 to 2019 were identified from the National Cancer Database. RESULTS: 34.7% underwent surgical intervention (13% PNET resection, 2.1% surgical management of liver metastases (SMLM), 19.5% PNET resection â€‹+ â€‹SMLM). In multivariable analysis, government insurance, year of diagnosis>2013, increasing primary tumor size were associated with lower rate of surgical intervention. Receiving treatment at an academic center (OR 3.59, 95%CI 1.81-7.11; P â€‹< â€‹0.001) or integrated cancer network (OR 3.21, 95%CI 1.57-6.54; P â€‹= â€‹0.001) was associated with a higher rate of surgical intervention. The overall rate of surgical intervention decreased from 45.7% in 2010 to 23.0% in 2019. CONCLUSION: Despite guideline recommendations and the suggested survival benefits, only one-third of patients underwent surgical intervention, potentially influenced by the rising utilization of systemic therapy in the past decade.


Assuntos
Neoplasias Hepáticas , Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Pancreatectomia , Tumores Neuroectodérmicos Primitivos/cirurgia , Estudos Retrospectivos
18.
Gynecol Oncol Rep ; 48: 101245, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576353

RESUMO

Background: Amid the height of the COVID-19 pandemic in the US, the US Surgeon General ordered hospitals and healthcare systems to stop all elective surgical procedures. The aim of our study was to evaluate the additional mental health impact of surgical delay on patients awaiting surgery for benign, pre-malignant and malignant conditions within the context of the COVID-19 pandemic. Study design: All patients over the age of 18 awaiting surgery for benign, pre-malignant or malignant conditions within the gynecologic oncology, surgical oncology and colorectal services across Northwell Health were eligible for participation. Upon successful enrollment, participants completed a baseline questionnaire consisting of the Generalized Anxiety Disorder Questionnaire, the Penn State Worry Questionnaire, and Brief-Illness Patient Questionnaire. Results: The surgical delay was considered moderately to extremely concerning by 72 % of survey respondents, with one third indicating the highest (10/10) level of concern. Fifty-five percent of patients with a pre-operatively suspected/confirmed cancer or pre-malignant condition demonstrated mild to severe anxiety in their completion of the GAD-7 scale. The average time awaiting surgery was 117 days (range 8-292); and 63 % of respondents indicated that the delay had a moderate to severe impact on their daily life. Conclusions: Patients awaiting surgery for confirmed, suspected or pre-malignant conditions expressed decreased sense of control and increased levels of distress compared to patients awaiting procedures for benign conditions (p < 0.05, 95 % CI [-2.65, -0.08]). Future research will focus on the effects of COVID-19 related delays in operative care on clinical outcomes, including cancer morbidity and mortality.

19.
Surgery ; 171(2): 459-466, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34563351

RESUMO

BACKGROUND: The timing and the dose of Advanced Care Planning in patients with pancreatic ductal adenocarcinoma undergoing curative-intent resection are generally dictated by the surgeon performing the operation. METHODS: A qualitative investigation using 1:1 interviews with 40 open-ended questions was conducted with a convenience sample of 10 high-volume pancreatic surgeons from across the country. The grounded theory approach was used for data analysis. RESULTS: A total of 10 interviews were conducted with expert pancreatic surgeons-6 males and 4 females. During preoperative counseling, all surgeons attempt to motivate patients by emphasizing hope, optimism, and the fact that surgery offers the only opportunity for cure. All surgeons discuss the possibility of recurrence as well as postoperative complications; however, a majority perceived that patients do not fully appreciate the likelihood of recurrence or postoperative complications. All surgeons acknowledged the importance of end-of-life conversations when death is imminent. Seventy percent of surgeons had mixed opinions regarding benefits of preoperative Advanced Care Planning in the preoperative setting, while 20% felt it was definitely beneficial, particularly that delivery of care aligned with patient goals. All surgeons emphasized that Advanced Care Planning should be led by a physician who both knows the patient well and understands the nuances of pancreatic ductal adenocarcinoma management. Most common barriers to in-depth Advanced Care Planning discussion reported by surgeons include taking away hope, lack of time, and concern for sending "mixed messages." CONCLUSION: We identified that surgeons experience a fundamental tension between promoting realistic long-term goals and expectations versus focusing on hope and enabling an overly optimistic perception of prognosis.


Assuntos
Planejamento Antecipado de Cuidados/organização & administração , Carcinoma Ductal Pancreático/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/psicologia , Aconselhamento/organização & administração , Feminino , Teoria Fundamentada , Esperança , Humanos , Masculino , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/psicologia , Pancreatectomia/psicologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/psicologia , Relações Médico-Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/psicologia , Prognóstico , Pesquisa Qualitativa , Cirurgiões/psicologia , Fatores de Tempo
20.
J Surg Case Rep ; 2021(5): rjab202, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34084448

RESUMO

Complications after pancreatoduodenectomy are common, and range widely in timing of presentation, relation to pancreatobiliary pathology, and necessity of operative intervention. We present a case of a 74-year-old male with history of pancreatoduodenectomy for pancreatic adenocarcinoma who presented 11 months after index operation with cecal volvulus and required emergent right hemicolectomy. Prior history of pancreatoduodenectomy with mobilization of the right colon likely predisposed him to development of this surgical emergency. Patients have altered gastrointestinal anatomy after pancreatoduodenectomy and special care is necessary to protect the afferent biliopancreatic limb during intraoperative exploration, and particularly if right colectomy is necessary.

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