RESUMO
PURPOSE: No single reliable biomarker is available for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), seems to be a more accurate biomarker compared to its precursor. Primary aim was to investigate the ability of VS-1, compared to total-CgA, to assess the effectiveness of surgical resection performed for NF-PanNETs. Secondary aim was to evaluate two additional CgA-derived fragments, pancreastatin (PST) and vasostatin-2 (VS-2), as possible biomarkers for NF-PanNETs. METHODS: Consecutive patients who underwent surgery for NF-PanNETs at San Raffaele Scientific Institute were included (n = 35). Plasma levels of CgA and CgA-derived fragments were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA), preoperatively and postoperatively. RESULTS: Preoperative VS-1 was significantly higher compared to VS-1 measured on postoperative day 5 (POD5) (pre: 0.338 nM versus POD5: 0.147 nM, P < 0.001), whereas total-CgA significantly increased after surgery (pre: 1.123 nM versus POD5: 1.949 nM, P = 0.006). Overall, 24 patients showed ≥ 1 feature of tumor aggressiveness (T3-T4, nodal/distant metastases, Ki67 > 5%, microvascular/perineural invasion, necrosis). The median percentage decrease in VS-1 plasma levels was 63% (IQR 28-88%) among patients with aggressive tumors, compared to 13% (IQR 0-57%) in the remaining population (P = 0.033). No significant differences in terms of PST (P = 0.870) and VS-2 (P = 0.909) were observed between preoperative and postoperative time. CONCLUSION: VS-1 provides an early assessment of surgical efficacy in patients who undergo resection for NF-PanNETs, especially in those with aggressive neoplasms. Total-CgA, PST and VS-2 have no clinical utility in this setting.
Assuntos
Cromogranina A , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Biomarcadores Tumorais/sangue , Cromogranina A/sangue , Humanos , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgiaRESUMO
PURPOSE: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. METHODS: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. RESULTS: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15-26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence. CONCLUSION: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.
Assuntos
Carcinoma Neuroendócrino/cirurgia , Neoplasias Pancreáticas/cirurgia , Recidiva , Carcinoma Neuroendócrino/fisiopatologia , Humanos , Razão de Chances , Neoplasias Pancreáticas/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: Despite the low malignant potential of pancreatic mucinous cystic neoplasms (MCNs), surgery is still performed. The aim of this pragmatic study was to assess the outcome of surgery and surveillance for patients presenting with a presumed MCN at the first evaluation. METHODS: Data for patients with a presumed MCN observed from 2000 to 2016 at the Verona Pancreas Institute and San Raffaele Hospital were extracted from prospective databases. The endpoints were risk of malignancy at pathology and rate of misdiagnosis for the surgical series, expressed as an odds ratio (OR) with 95 per cent confidence interval, and disease-specific survival (DSS) for the surveillance cohort investigated by the Kaplan-Meier method. RESULTS: A total of 424 patients were identified. In the surgical series (229 patients), the rate of misdiagnosis was 19.2 per cent. The rate of malignant MCNs was 10.9 per cent (25 patients). The overall rate of malignancy, including misdiagnoses, was 11.3 per cent (26 patients). Predictors of malignancy were mural nodules (OR 27.75, 95 per cent c.i. 4.44-173.61; P < 0.001), size at least 50 mm (OR 13.39, 2.01 to 89.47; P = 0.007), and carbohydrate antigen 19.9 level (OR 3.98, 1.19 to 13.30; P = 0.025). In the absence of mural nodules and enhancing walls, none of the resected presumed MCNs smaller than 50 mm were malignant. Only patients with high-risk stigmata undergoing surgery experienced a significantly reduced 5-year DSS compared with all other patients (88 versus 100 per cent; P = 0.031). CONCLUSION: Presumed MCNs with mural nodules, enhancing walls or cysts of 50 mm or larger should be considered for upfront surgical resection owing to the high risk of malignancy. In the absence of these features, the incidence of malignancy is negligible, favouring surveillance in selected patients given the low risk of malignancy and the high rate of misdiagnosis. LAY SUMMARY: Malignant degeneration of presumed pancreatic mucinous cystic neoplasms takes several years, if it occurs at all. Mural nodules, enhancing walls or cysts of 50 mm or larger call for surgical resection owing to an increased risk of malignancy; otherwise, surveillance seems a good option.
Malignant degeneration of presumed pancreatic mucinous cystic neoplasms takes several years, if it occurs at all. Mural nodules, enhancing walls or cysts of 50 mm or larger call for surgical resection owing to an increased risk of malignancy; otherwise, surveillance seems a good option.
Assuntos
Cistadenocarcinoma Mucinoso/cirurgia , Pâncreas/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Medição de Risco/métodos , Adulto , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by complex biological features and poor prognosis. A prognostic stratification of PDAC would help to improve patient management. The aim of this study was to analyse the expression of Ki-67 in relation to prognosis in a cohort of patients with PDAC who had surgical treatment. Methods: Patients who had pancreatic resection between August 2010 and October 2014 for PDAC at two Italian centres were reviewed retrospectively. Patients with metastatic or locally advanced disease, those who received neoadjuvant chemotherapy, patients with PDAC arising from intraductal papillary mucinous neoplasm and those with missing data were excluded. Clinical and pathological data were retrieved and analysed. Ki-67 expression was evaluated using immunohistochemistry and patients were stratified into three subgroups. Survival analyses were performed for disease-free (DFS) and disease-specific (DSS) survival outcomes according to Ki-67 expression and tumour grading. Results: A total of 170 patients met the selection criteria. Ki-67 expression of 10 per cent or less, 11-50 per cent and more than 50 per cent significantly correlated with DFS and DSS outcomes (P = 0·016 and P = 0·002 respectively). Ki-67 index was an independent predictor of poor DFS (hazard ratio (HR) 0·52, 95 per cent c.i. 0·29 to 0·91; P = 0·022) and DSS (HR 0·53, 0·31 to 0·91; P = 0·022). Moreover, Ki-67 index correlated strongly with tumour grade (P < 0·001). Patients with PDAC classified as a G3 tumour with a Ki-67 index above 50 per cent had poor survival outcomes compared with other patients (P < 0·001 for both DFS and DSS). Conclusion: Ki-67 index could be of use in predicting the survival of patients with PDAC. Further investigation in larger cohorts is needed to validate these results.
Antecedentes: El adenocarcinoma ductal de páncreas (pancreatic ductal adenocarcinoma, PDAC) es una enfermedad agresiva con características biológicas complejas y pronóstico pobre. La estratificación pronóstica del PDAC ayudaría a mejorar el tratamiento del paciente. El objetivo de este estudio era analizar la expresión de Ki67 como marcador pronóstico en una cohorte de pacientes con PDAC tratados quirúrgicamente. Métodos: Se efectuó un análisis retrospectivo de pacientes sometidos a resección pancreática por PDAC en dos centros italianos entre agosto de 2010 y octubre de 2014. Se excluyeron los pacientes con enfermedad metastásica o localmente avanzada, los tratados con quimioterapia neoadyuvante, los pacientes con PDAC originado en una neoplasia papilar mucinosa intraductal y aquellos pacientes con datos incompletos. Se analizaron los datos clínicos y anatomopatológicos. La expresión de Ki67 se evaluó por inmunohistoquímica y los pacientes se estratificaron en tres grupos. Se calculó la supervivencia libre de enfermedad (diseasefree survival, DFS) y la supervivencia específica de la enfermedad (diseasespecific survival, DSS) según la expresión de Ki67 y el grado tumoral. Resultados: Un total de 170 pacientes cumplió los criterios de selección. La expresión de Ki67 del ≤ 10%, 1150% y > 50% mostró una correlación significativa con los resultados de DFS y DSS (P = 0,016 y P = 0,002, respectivamente). El índice Ki67 fue un predictor independiente de pobre DFS (cociente de riesgos instantáneos, hazard ratio, HR 0,52, i.c. del 95% 0,290,91; P = 0,022) y DSS (HR 0,53, i.c. del 95% 0,310,91; P = 0,022). Asimismo, el índice Ki67 se correlacionaba fuertemente con el grado tumoral (P < 0,001). Los pacientes con un PDAC clasificado como tumor grado G3 y con un índice Ki67 > 50% tenían peores resultados de supervivencia en comparación con otros pacientes (P < 0,001 para ambos DFS y DSS). Conclusión: El índice Ki67 se puede utilizar como predictor de supervivencia en pacientes con PDAC. Hace falta seguir investigando para validar estos resultados en cohortes más grandes.
Assuntos
Carcinoma Ductal Pancreático/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Although consensus guidelines suggest that patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) should have surgery, a non-operative strategy is often selected in patients who are poor surgical candidates. The aim was to determine the risk of disease-related death from IPMN in patients with worrisome features or high-risk stigmata who were kept under observation. METHODS: A PubMed literature search was undertaken of articles published from August 1992 to June 2016 (updated October 2017). The methodology was developed from PRISMA and MOOSE checklists. Incidence proportions and rates of overall and IPMN-related deaths were calculated, with subgroup analyses for main-duct/mixed-type and branch-duct IPMNs. Quality of the studies, publication bias and heterogeneity were explored. RESULTS: Six studies reported data on overall mortality and eight described disease-specific mortality for 556 patients during follow-up ranging from 24·9 to 60·0 months. Pooled rates of overall and IPMN-related mortality were 30·9 (95 per cent c.i. 19·6 to 45·1) and 11·6 (6·0 to 21·2) per cent respectively. The pooled incidence rate for overall mortality was substantially higher than that for IPMN-related mortality: 78 (95 per cent c.i. 44 to 111) and 23 (9 to 37) per 1000 patient-years respectively. The pooled incidence rate for disease-specific mortality was considerably lower for branch-duct than for main-duct or mixed-type IPMNs: 5 (0 to 10) and 32 (12 to 52) per 1000 patient-years respectively. CONCLUSION: In patients unfit for surgery, IPMN-related mortality among patients with worrisome features and high-risk stigmata is low, and the risk of death from other causes much higher.
Assuntos
Neoplasias Intraductais Pancreáticas/mortalidade , Conduta Expectante , Humanos , Neoplasias Intraductais Pancreáticas/diagnóstico , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/terapia , Risco , Resultado do TratamentoRESUMO
BACKGROUND: Patients with borderline (BL) or locally advanced (LA) pancreatic adenocarcinoma are usually treated with primary chemotherapy (CT), followed by resection when feasible. Scanty data are available about the criteria to candidate patients to resection after CT. PATIENTS AND METHODS: Between 2002 and 2016 overall 223 patients diagnosed with BL or LA pancreatic adenocarcinoma were primarily treated with Gemcitabine combination (4-drugs or nab-paclitaxel-gemcitabine) for 3-6 months followed by surgery and/or chemoradiation. Resection was carried out when radical resection could be predicted by imaging studies and intraoperative findings. The prognostic value of both pre-treatment factors and treatment response was retrospectively evaluated, searching for criteria that could improve the selection of patients for surgery. RESULTS: Median survival (MS) for the whole population was 18.3 months. Surgical resection was carried out in 61 patients; MS in resected patients was significantly longer (30.0 months) as compared with 162 non-resected patients (16.5 months) (P < 0.00001). According to response criteria, 48% had a radiological partial response, 47% a stable disease and 5% a disease progression); CA19.9 response (reduction >50%) was obtained in 77.8% of patients. Among resected patients, neither pre-treatment factors, including BL/LA distinction, nor radiological response, were able to prognosticate survival differences. Survival of resected patients having no CA19.9 response was significantly lower as compared with responders (MS 15.0 versus 31.5 months, P = 0.04), and was similar to non-responders patients that did not undergo resection (MS 10.9 months, P= 0.25). Multivariate analysis carried out on the overall population, showed that Karnofsky performance status, T3-T4 status, resection and CA19.9 response were independent prognostic factors, while radiological response, BL/LA distinction and baseline CA19.9 had not significant influence on survival. CONCLUSIONS: CA19.9 response may allow a better selection of patients who will benefit from resection after primary CT for BL or LA pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Seleção de Pacientes , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias PancreáticasRESUMO
BACKGROUND: The incidence of asymptomatic, sporadic, small non-functioning pancreatic neuroendocrine neoplasms (NF-PNENs) has increased in recent decades. Conservative treatment has been advocated for these tumours. The aim of this study was systematically to evaluate the literature on active surveillance and to compare this with surgical management for asymptomatic sporadic small NF-PNENs. METHODS: PubMed, Embase and the Cochrane Library were searched systematically for studies that compared the active surveillance of asymptomatic, sporadic, small NF-PNENs with surgical management. PRISMA guidelines for systematic reviews were followed. RESULTS: After screening 3915 records, five retrospective studies with a total of 540 patients were included. Of these, 327 patients (60·6 per cent) underwent active surveillance and 213 (39·4 per cent) had surgery. There was wide variation in the tumour diameter threshold considered as inclusion criterion (2 cm to any size). The median length of follow-up ranged from 28 to 45 months. Measurable tumour growth was observed in 0-51·0 per cent of patients. Overall, 46 patients (14·1 per cent) underwent pancreatic resection after initial conservative treatment. In most patients the reason was an increase in tumour size (19 of 46). There were no disease-related deaths in the active surveillance group in any of the studies. CONCLUSION: This systematic review suggests that active surveillance of patients affected by sporadic, small, asymptomatic NF-PNENs may be a good alternative to surgical treatment.
Assuntos
Doenças Assintomáticas , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Conduta Expectante , Tomada de Decisão Clínica , Humanos , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Preferência do Paciente , Complicações Pós-Operatórias , ReoperaçãoRESUMO
BACKGROUND: New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. METHODS: Retrospective analysis. EXCLUSION CRITERIA: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. RESULTS: 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). CONCLUSIONS: Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/mortalidade , Estudos RetrospectivosRESUMO
BACKGROUND: Preoperative biliary drainage (PBD) with stenting increases complications compared with surgery without PBD. Metallic stents are considered superior to plastic stents when considering stent-related complications. Aim of the present systematic review and meta-analysis is to compare the rate of endoscopic re-intervention before surgery and postoperative outcomes of metal versus plastic stents in patients with resectable periampullary or pancreatic head neoplasms. METHODS: We conducted a bibliographic research using the National Library of Medicine's PubMed database, including both randomized controlled trials (RCTs) and non-RCTs. Quantitative synthesis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Statistical heterogeneity was assessed using the I(2) tests. RESULTS: One RCT and four non-RCTs were selected, including 704 patients. Of these, 202 patients (29.5%) were treated with metal stents and 502 (70.5%) with plastic stents. The majority of patients (86.4%) had pancreatic cancer. The rate of endoscopic re-intervention after preoperative biliary drainage was significantly lower in the metal stent (3.4%) than in the plastic stent (14.8%) group (p < 0.0001). The rate of postoperative pancreatic fistula was significantly lower in the meta stent group as well (5.1% versus 11.8%, p = 0.04). The rate of post-operative surgical complications and of - post-operative mortality did not differ between the two groups. CONCLUSIONS: Although the present systematic review and meta-analysis demonstrates that metal stent are more effective than plastic stents for PBD in patients with resectable periampullary tumors, randomized controlled trials are needed in order to confirm these data with a higher level of evidence.
Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/instrumentação , Icterícia Obstrutiva/terapia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Stents/estatística & dados numéricos , Ampola Hepatopancreática , Drenagem/instrumentação , Humanos , Icterícia Obstrutiva/etiologia , Metais , Neoplasias Pancreáticas/complicações , Plásticos , Cuidados Pré-Operatórios/estatística & dados numéricos , Fatores de RiscoRESUMO
BACKGROUND: Recent evidence has shown that enhanced recovery after surgery (ERAS) protocols decrease hospital stay following pancreaticoduodenectomy (PD). The aims of this study were to assess the feasibility and to evaluate the effect of introducing ERAS principles after PD in elderly patients. METHODS: Patients ≥75 years were defined as elderly. Comparison of postoperative outcome was performed between 22 elderly patients who underwent ERAS (elderly ERAS + patients) and a historical cohort of 66 elderly patients who underwent standard protocols (elderly ERAS-patients). RESULTS: The lowest adherence with ERAS among elderly patients was observed for starting a solid food diet within POD 4 (n = 7) and early drains removal (n = 2). The highest adherence was observed for post-operative glycemic control (n = 21), epidural analgesia (n = 21), mobilization (n = 20) and naso-gastric removal in POD 0 (n = 20). Post-operative outcomes did not differ between elderly ERAS+ and elderly ERAS- patients. In patients with an uneventful postoperative course, the median intention to discharge was earlier in elderly ERAS + patients as compared to the elderly ERAS- patients (4 days versus 8 days, P < 0.001). CONCLUSION: An ERAS protocol following PD seems to be feasible and safe among elderly although it is not associated with improved postoperative outcomes.
Assuntos
Pancreaticoduodenectomia/reabilitação , Cuidados Pós-Operatórios/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Fidelidade a Diretrizes , Estudo Historicamente Controlado , Humanos , Tempo de Internação , Masculino , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/normas , Alta do Paciente , Cuidados Pós-Operatórios/efeitos adversos , Cuidados Pós-Operatórios/normas , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Guias de Prática Clínica como Assunto , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58â years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40â mm (2-200)), 9% had resection beyond 1â year of follow-up (3â years (1-20), size at diagnosis: 25â mm (4-140)) and 39% had no surgery (3.6â years (1-23), 25.5â mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1â year (n=1271), size increased in 37% (growth rate: 4â mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.
Assuntos
Cistadenoma Seroso , Neoplasias Pancreáticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/mortalidade , Cistadenoma Seroso/patologia , Cistadenoma Seroso/terapia , Europa (Continente) , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Sociedades Médicas , Adulto JovemRESUMO
BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con-PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. METHODS: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. RESULTS: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. CONCLUSION: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association.
Assuntos
Adenocarcinoma Mucinoso/patologia , Ampola Hepatopancreática , Carcinoma Adenoescamoso/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Primárias Múltiplas/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Dor Abdominal/etiologia , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/epidemiologia , Carcinoma Adenoescamoso/cirurgia , Carcinoma Ductal Pancreático/epidemiologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Neoplasias do Ducto Colédoco/epidemiologia , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Humanos , Achados Incidentais , Icterícia/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/cirurgia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Prevalência , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: The British system (Thy1-5), the Bethesda system for reporting thyroid cytopathology (BSRTC) and the Italian Society of Anatomic Pathology and Cytology (SIAPEC) classification represent the most important international classifications for thyroid cytopathology. Irrespective of the system used, the 'indeterminate' categories are still debated among cytopathologists, particularly with regard to diagnostic criteria, clinical impact of subclassification and role of molecular techniques. AIM: We aimed to find answers to the following questions: Are there shared criteria in cytological preparations that allow the division of indeterminate follicular lesions into subcategories? What is the true clinical impact of this possible subclassification? METHODS: Among 1150 consecutive thyroid fine needle aspiration (FNA) specimens, 80 patients had nodules with a final cytological report of Tir3 (SIAPEC)/Thy3. These 80 cases were re-evaluated and subclassified according to morphological criteria into three groups: pure follicular proliferations, Hürthle cell follicular lesions and atypical proliferations. RESULTS: Sixteen (20%) cases were categorized as pure follicular proliferations, 40 (50%) as Hürthle cell follicular lesions and 24 (30%) as atypical proliferations. Surgery was performed in 57 cases (71%). Cyto-histological correlation showed that follicular adenoma was the most frequent final diagnosis in the cases treated by surgery (24/57, 42%). The overall malignancy rate in the Tir3 category was 28% (16/57). Atypical proliferations were more often malignant than either of the follicular groups (53% versus 19%, P = 0.019). CONCLUSIONS: A five-tiered classification, subdividing the 'indeterminate for malignancy' class into 'follicular proliferations' and 'atypical lesions' could be adopted. As a result of their higher risk of malignancy, surgical management of the atypical lesions would be justified. In future, the introduction of a genetic panel might contribute to their stratification, to the determination of a more accurate risk of malignancy of the atypical lesions and to the verification of follicular proliferations that are benign.
Assuntos
Biópsia por Agulha Fina , Citodiagnóstico , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Reino UnidoAssuntos
Tumores Neuroendócrinos/classificação , Neoplasias Pancreáticas/classificação , Organização Mundial da Saúde , Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Everolimo , Humanos , Indóis/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Pirróis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , SunitinibeRESUMO
Among the animal models of Duchenne muscular dystrophy (DMD), the Golden Retriever muscular dystrophy (GRMD) dog is considered the best model in terms of size and pathological onset of the disease. As in human patients presenting with DMD or Becker muscular dystrophies (BMD), the GRMD is related to a spontaneous X-linked mutation of dystrophin and is characterized by myocardial lesions. In this respect, GRMD is a useful model to explore cardiac pathogenesis and for the development of therapeutic protocols. To investigate whether cardiac progenitor cells (CPCs) isolated from healthy and GRMD dogs may differentiate into myocardial cell types and to test the feasibility of cell therapy for cardiomyopathies in a preclinical model of DMD, CPCs were isolated from cardiac biopsies of healthy and GRMD dogs. Gene profile analysis revealed an active cardiac transcription network in both healthy and GRMD CPCs. However, GRMD CPCs showed impaired self-renewal and cardiac differentiation. Population doubling and telomerase analyses highlighted earlier senescence and proliferation impairment in progenitors isolated from GRMD cardiac biopsies. Immunofluorescence analysis revealed that only wt CPCs showed efficient although not terminal cardiac differentiation, consistent with the upregulation of cardiac-specific proteins and microRNAs. Thus, the pathological condition adversely influences the cardiomyogenic differentiation potential of cardiac progenitors. Using PiggyBac transposon technology we marked CPCs for nuclear dsRed expression, providing a stable nonviral gene marking method for in vivo tracing of CPCs. Xenotransplantation experiments in neonatal immunodeficient mice revealed a valuable contribution of CPCs to cardiomyogenesis with homing differences between wt and dystrophic progenitors. These results suggest that cardiac degeneration in dystrophinopathies may account for the progressive exhaustion of local cardiac progenitors and shed light on cardiac stemness in physiological and pathological conditions. Furthermore, we provide essential information that canine CPCs may be used to alleviate cardiac involvement in a large preclinical model of DMD.
Assuntos
Distrofia Muscular Animal/patologia , Miocárdio/citologia , Miocárdio/patologia , Células-Tronco/patologia , Animais , Diferenciação Celular/fisiologia , Linhagem da Célula , Modelos Animais de Doenças , Cães , Feminino , Citometria de Fluxo , Humanos , Masculino , Camundongos , Camundongos SCID , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Miocárdio/metabolismo , Ratos , Células-Tronco/metabolismo , TranscriptomaRESUMO
AIMS: Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information. METHODS AND RESULTS: Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway. CONCLUSIONS: These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.
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Neoplasias da Mama/química , Carcinoma/química , Receptores ErbB/análise , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/antagonistas & inibidores , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/patologia , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Dosagem de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , PTEN Fosfo-Hidrolase/análise , Seleção de Pacientes , Fosfatidilinositol 3-Quinases/genética , Reação em Cadeia da Polimerase , Medicina de Precisão , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas ras/genéticaRESUMO
Many surgeons have attempted to reduce the number and the size of ports in laparoscopic cholecystectomy to decrease parietal trauma and pain, and to improve cosmetic results. We report a series of laparoscopic cholecystectomies using a single-port technique (SILS) through an umbilical incision in a pilot group of 21 cases. Our goal was to validate and develop the single-port access as a viable option. All the operations were performed using an umbilical SILS port (Ethicon). Most reported techniques utilize special purpose-made instruments. This article provides a stepwise description of the procedure using all straight instruments. No special reticulating instruments or flexible telescopes were used. We report our early difficulties and concerns about the procedure and propose solutions to the problems. Patients' request for improved cosmesis impels surgeons toward the application of SILS, but the true advantage of the technique should be assessed by more evidences. For this reason, we are planning a single-institution, prospective randomized controlled trial to compare postoperative pain, operating time and cosmetic result between one port and standard laparoscopic surgery.
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Colecistectomia Laparoscópica/métodos , Colecistolitíase/cirurgia , Umbigo , Adolescente , Adulto , Colecistectomia Laparoscópica/instrumentação , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Brostallicin is a DNA minor groove binder which shows enhanced antitumor activity in cells which are resistant to several anticancer agents due to their high glutathione S-transferase (GST)/glutathione content. Phase I and II clinical trials of single-agent brostallicin have shown that myelotoxicity is the dose-limiting toxicity (DLT), while hints of antitumor activity were mainly observed in soft tissue sarcoma. Preclinical studies showing a more than additive antitumor effect of the cisplatin-brostallicin combination paved the way to clinical combination studies. In particular, we set up the first clinical combination study of brostallicin and cisplatin in patients with advanced solid tumors. This study was to be followed by a phase II study in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). METHODS: Escalating doses of brostallicin were administered in combination with a fixed dose of cisplatin (75 mg/m(2)) in patients with recurrent or metastatic advanced solid tumors who had previously received a cumulative dose of cisplatin not higher than 475 mg/m(2). The recommended dose of brostallicin was expanded in order to have a better estimate of antitumor activity and to better define the safety profile of the combination. RESULTS: Twenty-one patients were treated. Two DLTs (grade 3 fatigue and febrile neutropenia) were observed at dose level 3 (brostallicin 9 mg/m(2)). Dose level 2 (brostallicin 7 mg/m(2) and cisplatin 75 mg/m(2)) was recommended for future phase II studies. Main toxicity was hematologic; in fact, only 1 patient out of 21 did not develop neutropenia and only 2 patients did not have thrombocytopenia. Grade 3-4 neutropenia was observed in 90.5% of patients, grade 3-4 thrombocytopenia in 38.1%, grade 3-4 anemia in 23.8%. The cycle 1 nadir (ANC < 500 x 10(9)/L) for neutrophils was Day 14 (median; range 11-17) with recovery to an ANC of >1,500 3.5 days after nadir (median; range 2-4) at dose level 3. The cycle 1 nadir (median of 51,000 x 10(9)/L) for platelets occurred on Day 13 (median; range 10-15) with recovery to a platelet count of >100,000 4 days after nadir (median; range 2-8). No objective responses were observed, but seven patients had a long lasting (>18 weeks) stable disease. CONCLUSIONS: Further studies of the combination of brostallicin and cisplatin are warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Guanidinas/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pirróis/administração & dosagem , Caracteres SexuaisRESUMO
BACKGROUND AND OBJECTIVES: In recent years there has been an increase in the diagnosis of cystic tumors of the pancreas. In this setting, difficult diagnostic problems and different therapeutic management can be proposed. MATERIAL AND METHODS: A review of the literature and authors experience were undertaken. RESULTS: Cystic tumors of the pancreas include different neoplasms with a different biological behaviour. While most serous cystadenomas (SCAs) can be managed nonoperatively, patients with mucinous cystic neoplasms (MCNs), solid pseudopapillary tumors (SPTs), main-duct intraductal papillary mucinous neoplasms (IPMNs) should undergo surgical resection. Branch-duct IPMNs can be observed with radiological and clinical follow-up when asymptomatic, < 3 cm in size and without radiologic features of malignancy (i.e. nodules). CONCLUSIONS: Cystic tumors of the pancreas are common. Differential diagnosis among the different tumor-types is of paramount importance for appropriate management. Nonoperative management seems appropriate for most SCAs and for well-selected branch-duct IPMNs.
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Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Cistadenoma/classificação , Cistadenoma/patologia , Cistadenoma/cirurgia , Diagnóstico Diferencial , Humanos , Neoplasias Císticas, Mucinosas e Serosas/classificação , Neoplasias Císticas, Mucinosas e Serosas/epidemiologia , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/epidemiologia , PrognósticoRESUMO
Understanding stem cell commitment and differentiation is a critical step towards clinical translation of cell therapies. In past few years, several cell types have been characterized and transplanted in animal models for different diseased tissues, eligible for a cell-mediated regeneration. Skeletal muscle damage is a challenge for cell- and gene-based therapeutical approaches, given the unique architecture of the tissue and the clinical relevance of acute damages or dystrophies. In this review, we will consider the regenerative potential of embryonic and somatic stem cells and the outcomes achieved on their transplantation into animal models for muscular dystrophy or acute muscle impairment.