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1.
Ann Surg Oncol ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586069

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33278573

RESUMO

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy was hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, p<0.001) and AJCC 8th edition T-stage (r = 0.586, p<0.001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs. 31%, p<0.001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs. 32%, p<0.001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs. 36%, p<0.001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (p=0.007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

3.
Clin Cancer Res ; 26(13): 3126-3134, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32156749

RESUMO

PURPOSE: We hypothesized that autophagy inhibition would increase response to chemotherapy in the preoperative setting for patients with pancreatic adenocarcinoma. We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel. PATIENTS AND METHODS: Participants with potentially resectable tumors were randomized to two cycles of nab-paclitaxel and gemcitabine (PG) alone or with hydroxychloroquine (PGH), followed by resection. The primary endpoint was histopathologic response in the resected specimen. Secondary clinical endpoints included serum CA 19-9 biomarker response and margin negative R0 resection. Exploratory endpoints included markers of autophagy, immune infiltrate, and serum cytokines. RESULTS: Thirty-four patients in the PGH arm and 30 in the PG arm were evaluable for the primary endpoint. The PGH arm demonstrated statistically improved Evans grade histopathologic responses (P = 0.00016), compared with control. In patients with elevated CA 19-9, a return to normal was associated with improved overall and recurrence-free survival (P < 0.0001). There were no differences in serious adverse events between arms and chemotherapy dose number was equivalent. The PGH arm had greater evidence of autophagy inhibition in their resected specimens (increased SQSTM1, P = 0.027, as well as increased immune cell tumor infiltration, P = 0.033). Overall survival (P = 0.59) and relapse-free survival (P = 0.55) did not differ between the two arms. CONCLUSIONS: The addition of hydroxychloroquine to preoperative gemcitabine and nab-paclitaxel chemotherapy in patients with resectable pancreatic adenocarcinoma resulted in greater pathologic tumor response, improved serum biomarker response, and evidence of autophagy inhibition and immune activity.

4.
AJR Am J Roentgenol ; 214(2): 362-369, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31799875

RESUMO

OBJECTIVE. The goal of this study was to assess the correlation between CT-derived texture features of pancreatic ductal adenocarcinoma (PDAC) and histologic and biochemical markers of response to neoadjuvant treatment as well as disease-free survival in patients with potentially resectable PDAC. SUBJECTS AND METHODS. Thirty-nine patients completed this prospective study protocol between November 2013 and December 2016. All patients received neoadjuvant chemotherapy, underwent surgical resection, and had histologic grading of tumor response. Similar CT protocol was used for all patients. Pancreatic (late arterial) phase of pre- and posttreatment CT scans were evaluated. Histogram analysis and spatial-band-pass filtration were used to extract textural features. Correlation between textural parameters, histologic response, biochemical response, and genetic mutations was assessed using Mann-Whitney test, chi-square analysis, and multivariate logistic regression. Association with disease-free survival was assessed using Kaplan-Meier method and Cox model. RESULTS. Pretreatment mean positive pixel (MPP) at fine- and medium-level filtration, pretreatment kurtosis at medium-level filtration, changes in kurtosis, and pretreatment tumor SD were statistically different between patients with no or poor histologic response and favorable histologic response (p < 0.05). Changes in skewness and kurtosis at medium-level filtration significantly correlated with biochemical response (p < 0.01). On the basis of multivariate analysis, patients with higher MPP at pretreatment CT were more likely to have favorable histologic response (odds ratio, 1.06; 95% CI, 1.002-1.12). The Cox model for association between textural features and disease-free survival was statistically significant (p = 0.001). CONCLUSION. Textural features extracted from baseline pancreatic phase CT imaging of patients with potentially resectable PDAC and longitudinal changes in tumor heterogeneity can be used as biomarkers for predicting histologic response to neoadjuvant chemotherapy and disease-free survival.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/terapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Meios de Contraste , Intervalo Livre de Doença , Feminino , Humanos , Iopamidol , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Neoplasias Pancreáticas/patologia , Estudos Prospectivos
5.
Surgery ; 167(2): 352-357, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31272813

RESUMO

BACKGROUND: Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy. METHODS: Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis. RESULTS: In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P < .001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P < .001) and metastasectomy (36.9 vs 17.3 months, P = .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections (P = .008). Margin status at metachronous metastasectomy was not associated with survival (P = .452). CONCLUSION: Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/secundário , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Estados Unidos/epidemiologia
6.
Surg Clin North Am ; 99(2): 231-244, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30846032

RESUMO

Gallstone disease is a leading cause of morbidity in the United States and usually requires surgical or endoscopic interventions for diagnosis and/or treatment. Although gallstone disease is classically associated with the inflammatory sequela of cholecystitis, gallstones can also contribute to other clinical presentations such as gallstone ileus, Mirizzi syndrome, and Bouveret syndrome. This article explores the common-and uncommon-causes of surgical pathology owing to gallstones with an emphasis on clinical identification, diagnostics, and management options.


Assuntos
Colecistite/diagnóstico , Cálculos Biliares/diagnóstico , Cálculos Biliares/terapia , Íleus/diagnóstico , Síndrome de Mirizzi/diagnóstico , Colecistite/etiologia , Colecistite/terapia , Cálculos Biliares/etiologia , Humanos , Íleus/etiologia , Íleus/terapia , Síndrome de Mirizzi/etiologia , Síndrome de Mirizzi/terapia
7.
Ann Surg Oncol ; 25(8): 2308-2315, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29868977

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy. METHODS: Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study. Factors associated with en bloc resection were assessed by uni- and multivariate analysis. The primary end point was overall survival. RESULTS: In this study, 167 patients were included and categorized as adrenalectomy with en bloc resection (AdEBR) if they had extra-adrenal organs removed or adrenalectomy (Ad) if they did not. The demographics were similar between the AdEBR (n = 68, 40.7%) and Ad groups, including age, gender, race, American Society of Anesthesiology (ASA) class, and body mass index (BMI). The AdEBR group had larger tumors (13 vs. 10 cm), more open operations (97.1 vs. 63.6%), and more lymph node dissections (LNDs) (36.8 vs. 12.1%). The most common organs removed were kidney (55.9%), liver (27.9%), and spleen (23.5%). Multiple organs were removed in 38.2% (n = 26) of the patients. Margin-negative resections were similar between the two groups. In the multivariate Cox regression adjusted for T and N stages, LND, margin, size, and hormone hypersecretion, en bloc resection was not associated with improved survival (hazard ratio [HR], 1.42; p = 0.323). CONCLUSION: The study findings validated current practice by showing that en bloc resection should occur at index adrenalectomy for ACC when a T4 lesion is suspected pre- or intraoperatively, or when it is necessary to avoid tumor rupture. However, in this study, when a negative margin resection was otherwise achieved, removal of extra-adrenal organs en bloc was not associated with additional survival benefit.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia/mortalidade , Carcinoma Adrenocortical/cirurgia , Bases de Dados Factuais , Excisão de Linfonodo/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
Ann Surg Oncol ; 25(2): 520-527, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29164414

RESUMO

BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Adrenalectomia/mortalidade , Carcinoma Adrenocortical/secundário , Neoplasias do Córtex Suprarrenal/classificação , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/classificação , Carcinoma Adrenocortical/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral , Estados Unidos
9.
Am Surg ; 83(7): 761-768, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28738949

RESUMO

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/cirurgia , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
10.
J Gastrointest Surg ; 21(2): 352-362, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27770290

RESUMO

BACKGROUND AND OBJECTIVES: Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery. METHODS: Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA. RESULTS: A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p < 0.001). There was no difference in rates of intraoperative tumor rupture (p = 0.612) or R0 resection (p = 0.953). Only EBL (p = 0.038) and T stage (p = 0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival. CONCLUSION: MIS adrenalectomy may be utilized for preoperatively determined ACC ≤ 10.0 cm; however, OA should be utilized for adrenal masses with either preoperative or intraoperative evidence of local invasion or enlarged lymph nodes, regardless of size.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Carcinoma Adrenocortical/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
11.
Ann Surg ; 265(1): 197-204, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28009746

RESUMO

OBJECTIVE: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC). BACKGROUND: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery. METHODS: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x). RESULTS: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%). CONCLUSIONS: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto Jovem
12.
J Surg Oncol ; 114(8): 971-976, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27633419

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported. METHOD: Patients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2-5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded. RESULTS: Among the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P < 0.05). The need for multi-visceral resection, perioperative blood transfusion, and adjuvant therapy correlated with early mortality. However, nodal involvement, distant metastasis, and R1 resection did not preclude patients from becoming actual 10-year survivors. Ten of twelve actual 10-year survivors were women, and of the seven 10-year survivors who experienced disease recurrence, five had undergone repeat surgery to resect the recurrence. CONCLUSION: Surgery for ACC can offer a 1 in 4 chance of actual 5-year survival and a 1 in 15 chance of actual 10-year survival. Long-term survival was often achieved with repeat resection for local or distant recurrence, further underscoring the important role of surgery in managing patients with ACC. J. Surg. Oncol. 2016;114:971-976. © 2016 Wiley Periodicals, Inc.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/cirurgia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
13.
Ann Surg Oncol ; 23(Suppl 5): 708-713, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27590329

RESUMO

BACKGROUND: Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear. METHODS: Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon's effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups. RESULTS: Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p < .001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p = .72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection. CONCLUSIONS: In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon's effort to dissect peritumoral lymph nodes was independently associated with improved overall survival.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/secundário , Excisão de Linfonodo , Linfonodos/cirurgia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia/efeitos adversos , Carcinoma Adrenocortical/cirurgia , Adulto , Feminino , Mortalidade Hospitalar , Humanos , Excisão de Linfonodo/efeitos adversos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
14.
J Am Coll Surg ; 222(4): 480-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26775162

RESUMO

BACKGROUND: Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. STUDY DESIGN: Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. CONCLUSIONS: When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/cirurgia , Antineoplásicos Hormonais/uso terapêutico , Mitotano/uso terapêutico , Neoplasias do Córtex Suprarrenal/mortalidade , Adrenalectomia , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
15.
Am J Surg ; 211(6): 1106-13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26810939

RESUMO

BACKGROUND: We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC). METHODS: The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed. RESULTS: The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01). CONCLUSIONS: Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia/métodos , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/cirurgia , Neoplasias do Córtex Suprarrenal/diagnóstico , Adrenalectomia/efeitos adversos , Carcinoma Adrenocortical/diagnóstico , Adulto , Análise de Variância , Causas de Morte , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Hidrocortisona/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
16.
Surgery ; 159(1): 267-73, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26435431

RESUMO

BACKGROUND: Adrenal venous sampling is an important lateralization study for primary aldosteronism, but inability to cannulate the right adrenal vein is not uncommon and interpreted as a failed study. We challenged this notion by examining whether data from incomplete left-sided adrenal venous sampling could accurately predict lateralization. METHODS: Sixty-two adrenal venous sampling studies from 2007 to 2014 at 2 tertiary-care institutions were reviewed. For this analysis, data from the right adrenal vein were excluded. The study variable was the aldosterone:cortisol ratio of the left adrenal vein compared with the inferior vena cava (LAV/IVC). Scatterplot analysis identified high and low LAV/IVC cutoffs that predicted accurately unilateral disease in 1 institutional cohort and validated in the second cohort. RESULTS: Thirty-six studies of adrenal venous sampling were evaluated at the first institution and divided into 3 diagnostic categories: unilateral-left (n = 14), unilateral-right (n = 12), and bilateral (n = 10). Cutoff values of the ratios of LAV/IVC of ≥ 5.5 and ≤ 0.5 accurately predicted left- and right-sided disease, respectively, and were validated in 26 studies from the second institution (100% PPV). The "5.5-0.5 criteria" salvaged accuracy for predicting lateralization in 50% of cases. CONCLUSION: Even in the setting of failed cannulation of the right adrenal vein, the actual data from the remaining adrenal venous sampling can predict lateralization accurately in many patients. A "failed" adrenal venous sampling study may be of greater predictive utility than believed traditionally.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Aldosterona/sangue , Hidrocortisona/sangue , Hiperaldosteronismo/sangue , Adulto , Idoso , Cateterismo , Feminino , Humanos , Hiperaldosteronismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Veias Renais , Estudos Retrospectivos , Veia Cava Inferior
17.
World J Surg ; 40(3): 706-714, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26546184

RESUMO

BACKGROUND: The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival. METHODS: Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed. RESULTS: A total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8%). A postoperative complication occurred in 99 patients for a morbidity of 37.4%; five patients (1.9%) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95% CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95% CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95% CI 2.24-13.80; P < 0.001). CONCLUSION: Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia/efeitos adversos , Carcinoma Adrenocortical/cirurgia , Previsões , Complicações Pós-Operatórias/epidemiologia , Neoplasias do Córtex Suprarrenal/mortalidade , Adrenalectomia/mortalidade , Carcinoma Adrenocortical/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
18.
JAMA Surg ; 151(4): 365-73, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26676603

RESUMO

IMPORTANCE: Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES: To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS: Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES: The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS: In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS). CONCLUSIONS AND RELEVANCE: Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Adrenalectomia , Carcinoma Adrenocortical/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Nomogramas , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/cirurgia , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
19.
Ann Surg Oncol ; 23(1): 134-41, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26286195

RESUMO

BACKGROUND: The influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC. METHODS: A total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1. RESULTS: R0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04). CONCLUSIONS: A positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
20.
Ann Surg Oncol ; 23(1): 126-33, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26282907

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC. METHODS: Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence. RESULTS: A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01). CONCLUSIONS: Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.


Assuntos
Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Complicações Pós-Operatórias , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Estados Unidos/epidemiologia
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