RESUMO
The management of patients with locally advanced mid/low rectal cancer with resectable liver metastases is complex because of the need to combine the optimal treatment of both tumors. This study aims to review the available treatment strategies and compare their outcome, focusing on radiotherapy (RT) and liver-first approach (LFA). A systematic review was performed in PubMed, Embase, and web sources including articles published between 2000 and 02/2023 and reporting mid-/long-term outcomes. Overall, twenty studies were included (n = 1837 patients). Three- and 5-year overall survival (OS) rates were 51-88% and 36-59%. Although several strategies were reported, most patients received RT (1448/1837, 79%; > 85% neoadjuvant). RT reduced the pelvic recurrence risk (5.8 vs. 13.5%, P = 0.005) but did not impact OS. Six studies analyzed LFA (n = 307 patients). LFA had a completion rate similar to the rectum-first approach (RFA, 81% vs. 79%) but the interval strategy-an LFA variant with liver surgery in the interval between radiotherapy and rectal surgery-had a better completion rate than standard LFA (liver surgery/radiotherapy/rectal surgery, 92% vs. 75%, P = 0.011) and RFA (79%, P = 0.048). Across all series, LFA achieved the best survival rates, and in one paper it led to a survival advantage in patients with multiple metastases. In conclusion, different strategies can be adopted, but RT should be included to decrease the pelvic recurrence risk. LFA should be considered, especially in patients with high hepatic tumor burden, and RT before liver surgery (interval strategy) could maximize its completion rate.
Assuntos
Neoplasias Hepáticas , Neoplasias Retais , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Humanos , Taxa de Sobrevida , Resultado do Tratamento , Terapia Neoadjuvante , Hepatectomia/métodos , Terapia Combinada , Recidiva Local de Neoplasia , Ablação por Radiofrequência/métodos , Masculino , FemininoRESUMO
Finding effective ways to perform cancer sub-typing is currently a trending research topic for therapy opti-mization and personalized medicine. Stemming from genomic field, several algorithms have been proposed. In the context of texture analysis, limited efforts have been attempted, yet imaging information is known to entail useful knowledge for clinical practice. We propose a distant supervision model for imaging-based cancer sub-typing in Intrahepatic Cholangiocar-cinoma patients. A clinically informed stratification of patients is built and homogeneous groups of patients are characterized in terms of survival probabilities, qualitative cancer variables and radiomic feature description. Moreover, the contributions of the information derived from the ICC area and from the peri tumoral area are evaluated. The findings suggest the reliability of the proposed model in the context of cancer research and testify the importance of accounting for data coming from both the tumour and the tumour-tissue interface. Clinical relevance - In order to accurately predict cancer prognosis for patients affected by ICC, radiomic variables of both core cancer and surrounding area should be exploited and employed in a model able to manage complex information.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/genética , Diagnóstico por Imagem , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The histopathological growth pattern (HGP) of colorectal liver metastases (CLM) has been associated with prognosis. This study was designed to elucidate if the HGP is associated with local recurrence risk and impacts the adequate width of surgical margin. METHODS: All consecutive patients resected for CLM in 2018-2019 were considered. HGP was prospectively classified as follows: desmoplastic, pushing, and replacement. Surgical margin was classified as follows: R0 (margin ≥ 1 mm), R1vasc (0-mm margin, tumor detachment from intrahepatic vessels), and R1par (tumor exposure along transection plane). R0 resections were further distinguished in R0min (1-mm margin) and R0wide (> 1-mm margin). RESULTS: A total of 340 resection areas in 136 patients were analyzed (70 R0min, 143 R0wide, 31 R1vasc, 96 R1par). HGP was desmoplastic in 26 cases, pushing in 221, and replacement in 93. Thirty-six local recurrences occurred (11%, median follow-up 21 months): 1 after R0wide, 4 after R0min, 3 after R1vasc, and 28 after R1par resection. In R1par group, local recurrence rate was high independently of HGP (29%). In R1vasc and R0min groups, local recurrence risk was higher in the replacement group (R1vasc: 29% vs. 4% if pushing/desmoplastic; R0min: 11% vs. 4%). In R0wide group, local recurrence risk was low for all HGP ( < 1%). Independent predictors of local recurrence were replacement HGP (odds ratio = 1.654, P = 0.036), and R1par resection (odds ratio = 57.209, P < 0.001 vs. R0). CONCLUSIONS: Replacement HGP is associated with an increased risk of local recurrence. In these patients, a wide surgical margin should be pursued, because R1vasc and R0min resections could be insufficient. R1par resection is inadequate, independently of the HGP.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgiaRESUMO
Guillain-Barré syndrome (GBS) incidence can increase during outbreaks of infectious illnesses. A few cases of GBS associated with coronavirus disease 2019 (COVID-19) infection have been reported. The aim was to identify specific clinical features of GBS associated with COVID-19. PubMed, Embase and Cochrane were searched from 1 November 2019 to 17 May 2020 and included all papers with full text in English, Spanish, French or Italian, reporting original data of patients with GBS and COVID-19. Data were extracted according to a predefined protocol. A total of 18 patients reported in 14 papers were included in this review. All the patients were symptomatic for COVID-19, with cough and fever as the most frequently reported symptoms. The interval between the onset of symptoms of COVID-19 and the first symptoms of GBS ranged from -8 to 24 days (mean 9 days; median 10 days). Most of the patients had a typical GBS clinical form predominantly with a demyelinating electrophysiological subtype. Mechanical ventilation was necessary in eight (44%) patients. Two (11%) patients died. Published cases of GBS associated with COVID-19 report a sensorimotor, predominantly demyelinating GBS with a typical clinical presentation. Clinical features and disease course seem similar to those observed in GBS related to other etiologies. These results should be interpreted with caution since only 18 cases have been heterogeneously reported so far.
Assuntos
COVID-19/complicações , Síndrome de Guillain-Barré/etiologia , COVID-19/mortalidade , Doenças Desmielinizantes/etiologia , Síndrome de Guillain-Barré/mortalidade , HumanosRESUMO
BACKGROUND: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. METHODS: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). RESULTS: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). CONCLUSION: A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.
ANTECEDENTES: Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimallyinvasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes. RESULTADOS: Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumenresultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.
Assuntos
Hepatectomia/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Idoso , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Itália/epidemiologia , Neoplasias Hepáticas/cirurgia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/mortalidade , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Análise de SobrevidaRESUMO
BACKGROUND: The impact of chemotherapy-associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres. METHODS: PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords 'chemotherapy', 'liver resection', 'outcome' and 'colorectal metastases' to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo-Clavien grade III-V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery-specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery-specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001). CONCLUSION: An increase in postoperative major morbidity and liver surgery-specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/complicações , Neoplasias Colorretais , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/mortalidade , Feminino , Hepatectomia/mortalidade , Humanos , Tempo de Internação , Falência Hepática Aguda/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal liver metastases (CLM), but 25-35% of patients fail to complete the scheduled procedure (drop-out). To elucidate if drop-out of TSH is a patient selection (as usually considered) or a loss of chance. METHODS: All the consecutive patients scheduled for a TSH at the Paul Brousse Hospital between 2000 and 2012 were considered. TSH patients were matched 1:1 with patients receiving a one-stage ultrasound-guided hepatectomy (OSH) at the Humanitas Research Hospital in the same period. Matching criteria were: primary tumor N status; timing of CLM diagnosis; CLM number and distribution into the liver. RESULTS: Sixty-three pairs of patients were analyzed. Demographic and tumor characteristics were similar (median 7 CLM), except for more chemotherapy lines and adjuvant chemotherapy in TSH. Drop-out rate of TSH was 38.1% (0% of OSH). The two groups had similar R0 resection rate (19.0% OSH vs. 15.9% TSH). OSH and completed TSH had similar five-year survival (from CLM diagnosis 49.8% vs. 49.7%, from liver resection 36.1% vs. 44.3%), superior to drop-out (10% three-year survival, p < 0.001). OSH and completed TSH had similar recurrence-free survival (at three years 21.7% vs. 20.5%) and recurrence sites. The completion of resection (drop-out vs. OSH/completed TSH) was the only independent prognostic factor (p = 0.003). CONCLUSIONS: Drop-out of TSH could be a loss of chance rather than a criteria for patient selection. "Unselected" OSH patients had the same outcomes of selected patients who completed TSH. A complete resection is the main determinant of prognosis.
Assuntos
Quimioterapia Adjuvante/estatística & dados numéricos , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Seleção de Pacientes , Idoso , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , França , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosAssuntos
Neoplasias dos Ductos Biliares/cirurgia , Colectomia/efeitos adversos , Ducto Colédoco/cirurgia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Gastrectomia/efeitos adversos , Hepatectomia , Pancreaticoduodenectomia/efeitos adversos , Feminino , Humanos , MasculinoRESUMO
AIM: This study aimed to evaluated prognostic factors of patients with GEP-NETs after primary tumor resection comparing pancreatic and gastro-enteric locations. METHODS: Patients undergone surgery for primary GEP-NETs between 01/2000 and 03/2012 were considered. All specimens were reclassified according to the WHO 2010 scheme. RESULTS: A total of 83 patients were considered: 37 pancreatic NETs (pNET) and 46 gastroenteric NETs (GE-NET). The two groups were similar in terms of age, sex and tumors size. A higher rate of patients with pNETs had Ki67 score ≥3 (64.8% vs. 39%, p = 0.027) while the rates of Mitotic Index ≥2x10HPF (62% pNET vs. 50% GE-NET, p = 0.374) and diagnosis of neuroendocrine carcinoma NEC (16.2% pNET vs. 17.3% GE-NET, p = 0.100) were similar. The rates of distant metastases (GE-NETs 30.4% vs. p-NETs 29.7%, p = 0.944) and liver metastases (19.5% GE-NET vs. 27% pNET, p = 0.421) were comparable. Radical resection was achieved in a similar proportion in both groups [33 patients (89.1%) pNET vs. 36 (78.2%) GE-NET, p = 0.393]. After a median follow-up of 47.1 months overall 3, 5 and 10-years survival rates of whole patients were 88.1%, 81.2% and 76.7%. There was not difference on 5-years overall survival between pNET (81.4%) and GE-NET (81%, p = 0.901). At multivariate analysis age ≥70 [OR 4.177 (CI 95% 1.26-13.8), p = 0.019] and NEC [OR 5.932 (CI 95% 1.81-19.40), p < 0.001] were negative prognostic factors of survival. CONCLUSION: Overall survival of GEP-NET after resection of primary tumors seems to be correlated to patient's age and WHO 2010 staging system but not to primary tumor site.
Assuntos
Carcinoma/cirurgia , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adulto , Fatores Etários , Idoso , Carcinoma/química , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/mortalidade , Humanos , Antígeno Ki-67/análise , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Estadiamento de Neoplasias , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/mortalidade , Taxa de Sobrevida , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Patients with large numbers of colorectal liver metastases (CRLMs) are potential candidates for resection, but the benefit from surgery is unclear. METHODS: Patients undergoing resection for CRLMs between 1998 and 2012 in two high-volume liver surgery centres were categorized according to the number of CRLMs: between one and seven (group 1) and eight or more (group 2). Overall (OS) and recurrence-free (RFS) survival were compared between the groups. Multivariable analysis was performed to identify adverse prognostic factors. RESULTS: A total of 849 patients were analysed: 743 in group 1 and 106 in group 2. The perioperative mortality rate (90 days) was 0.4 per cent (all group 1). Median follow-up was 37.4 months. Group 1 had higher 5-year OS (44.2 versus 20.1 per cent; P < 0.001) and RFS (28.7 versus 13.6 per cent; P < 0.001) rates. OS and RFS in group 2 were similar for patients with eight to ten, 11-15 or more than 15 metastases (48, 40 and 18 patients respectively). In group 2, multivariable analysis identified three preoperative adverse prognostic factors: extrahepatic disease (P = 0.010), no response to chemotherapy (P = 0.023) and primary rectal cancer (P = 0.039). Patients with two or more risk factors had very poor outcomes (median OS and RFS 16.9 and 2.5 months; 5-year OS zero); patients in group 2 with no risk factors had similar survival to those in group 1 (5-year OS rate 44 versus 44.2 per cent). CONCLUSION: Liver resection is safe in selected patients with eight or more metastases, and offers reasonable 5-year survival independent of the number of metastases. However, eight or more metastases combined with at least two adverse prognostic factors is associated with very poor survival, and surgery may not be beneficial.
Assuntos
Neoplasias Colorretais , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Resultado do TratamentoRESUMO
This study aimed at evaluating whether the administration of symbiotic therapy in jaundiced patients could reduce their postoperative infectious complications. The study was conducted between November 2008 and February 2011. Jaundiced patients scheduled for elective extrahepatic bile duct resection without liver cirrhosis, intestinal malabsorption or intolerance to symbiotic therapy were randomly assigned to receive [Group A] or not [Group B] symbiotics perioperatively. The primary endpoint was the infectious morbidity rate. Forty patients were included in the analysis (20 in each group). The patients in Group B presented a higher overall morbidity (70 vs 50%) and infectious morbidity rate (50 vs 25%), but the differences were not significant. Eleven patients in Group A (Group ndA) and 13 in Group B (Group ndB) did not receive preoperative biliary drainage. The results of the two groups were comparable. Infectious complications were higher in Group B [5 (34%) vs 0, p = 0.030], while the prevalence of natural killer (NK) cells was higher in Group ndA the day before surgery (17% ± 5.1 vs 10% ± 5.3, p < 0.01) and on post-operative day (POD) 7 (13.1% ± 4.1 vs 7.7% ± 3.4, p < 0.01). The rates of lymph node colonization were similar. The symbiotic therapy failed to reduce the rate of infectious morbidity in jaundiced patients. Further studies investigating the place of symbiotic in no-drainage patients are required.
Assuntos
Ductos Biliares Extra-Hepáticos/cirurgia , Icterícia/cirurgia , Probióticos/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Probióticos/administração & dosagem , Sepse/prevenção & controleRESUMO
BACKGROUND: Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221). METHODS: Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m(-2), day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)). RESULTS: Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation. CONCLUSIONS: Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m(-2)) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias da Mama/metabolismo , Dano ao DNA , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Histonas/metabolismo , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: Patients with T3-4 gallbladder cancers (GBCs) often require extended surgical procedures, and up to 30% of patients have N2 metastases. This study investigated which patients with T3-4 GBC benefit from resection. METHODS: Consecutive patients (n = 78) with T3-4 GBC who underwent resection between 1990 and 2011 were analysed (38 before 2003, 40 in 2003-2011). Forty patients required common bile duct (CBD) resection, 10 pancreatoduodenectomy, 4 right colectomy and 2 gastric resection. Fifty-two (67%) patients had LN metastases, including 22 with N2 metastases. RESULTS: The in-hospital mortality rate was 8%, 11% before 2003 vs. 5% in 2003-2011. The morbidity rate (47%) remained stable during the study. Undergoing liver and pancreatic resection did not increase severe morbidity (0%) or mortality (10%). Sixty-seven (86%) patients had R0 resection. The 5-year survival rate was 17% (median follow-up, 65 months). Survival improved after 2002 (26% vs. 9%, p = 0.04). R1 patients had poor 3-year survival (0% vs. 32%, p = 0.001). N+ patients also had low survival (5-year survival, 10% vs. 32% in N0, p = 0.019), but N1 and N2 patients had similar outcomes. CBD resection and major hepatectomy did not worsen prognosis. Patients requiring pancreatoduodenectomy, gastric or colonic resection had 0% 3-year survival (p = 0.036 in multivariate analysis). CONCLUSIONS: Resection of T3-4 GBC is worthwhile only if R0 surgery is achievable. Outcomes improved in most recent years. N2 metastases should not preclude surgery. Good results are possible even with CBD resection or major hepatectomy, while benefits from surgery are doubtful if pancreatoduodenectomy or other organ resection is needed.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colectomia/efeitos adversos , Ducto Colédoco/cirurgia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Gastrectomia/efeitos adversos , Hepatectomia , Pancreaticoduodenectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Colectomia/mortalidade , Feminino , Neoplasias da Vesícula Biliar/patologia , Gastrectomia/mortalidade , Mortalidade Hospitalar , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia/mortalidade , Seleção de Pacientes , Prognóstico , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The lymph node status is one of the strongest prognostic determinants in rectal cancers. After chemoradiotherapy (CRT), lymph nodes are difficult to detect. This study aims to evaluate the feasibility of lymph node mapping in the mesorectum after CRT to analyze the pattern of metastasis spread and to assess the reliability of blue dye injection in sentinel lymph node detection. METHOD: Ten patients with cN+ mid/low RCs after CRT were prospectively enrolled. The protocol scheduled intraoperative blue dye injection, surgery, and specimen examination with fat clearance technique. The mesorectum was divided into three equal "levels" (upper, middle, and lower); each level was divided into three equal "sectors" (right anterolateral, posterior, and left anterolateral). Lymph nodes were defined "small" if ≤5 mm. RESULTS: Two hundred seventy-six lymph nodes were retrieved in ten patients; 76.5 % were small lymph nodes. Six patients were pN+ (33 metastatic lymph nodes, 76 % small); small lymph node analysis upstaged one patient from N0 to N1 and four patients from N1 to N2. Metastasis distribution across sectors was continuous, without "skip sectors." The blue dye detected the sentinel lymph node in all patients; in half of the cases, it was out of the tumor sector. Blue dye identified 69.7 % of metastatic lymph nodes; its sensitivity decreased together with the metastatic deposit size (84 % macrometastases, 28.6 % micrometastases, 0 % occult tumor cells; p = 0.004). CONCLUSION: The fat clearance technique should be the standard pathological examination in patients with RCs after CRT; N staging was improved by small lymph node identification. Lymph node metastases have a continuous spread through mesorectal sectors. Blue dye injection is effective in sentinel lymph node detection.
Assuntos
Quimiorradioterapia , Linfonodos/patologia , Metástase Linfática/patologia , Terapia Neoadjuvante , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapiaRESUMO
BACKGROUND: Laparoscopic liver surgery must reproduce open surgical steps. Intraoperative ultrasonography (IOUS) is mandatory, but reliability of laparoscopic IOUS has been poorly evaluated. The aim of this study was to compare laparoscopic versus open IOUS in staging liver tumours. METHODS: All patients scheduled for liver resection between September 2009 and March 2011 were considered. Inclusion criteria were primary and metastatic tumours. Exclusion criteria were: hilar/gallbladder cholangiocarcinoma, ten or more lesions, repeat resection, laparoscopic hepatectomy, adhesions and unresectability. Following percutaneous ultrasonography and thoracoabdominal computed tomography (CT), and on indication contrast-enhanced (CE) liver magnetic resonance imaging (MRI) and/or positron emission tomography (PET)-CT, patients were scheduled for laparoscopy, laparoscopic IOUS, then laparotomy, open IOUS and Partial hepatectomy. Data were collected prospectively. Reference standards were final pathology and 6-month follow-up results. RESULTS: Sixty-five patients were included, who had a median of 3 preoperative imaging studies (ultrasonography/CT 100 per cent, CE-MRI 67 per cent, PET-CT 54 per cent). A total of 119 lesions were diagnosed. Laparoscopic IOUS detected 22 additional lesions (+18·5 per cent) in 14 patients. Open IOUS detected two additional lesions, but did not confirm four lesions; overall 20 additional lesions (+16·8 per cent) were detected in ten patients. Pathology confirmed 14 newly detected malignant nodules (+11·8 per cent) in eight patients. After 6 months ten new nodules were identified in six patients. The sensitivity of preoperative imaging, laparoscopic IOUS and open IOUS was 83·1, 92·3 and 93·0 per cent respectively; accuracy was 79, 82 and 88 per cent. In comparison with open IOUS, the sensitivity and accuracy of laparoscopic IOUS were 98·6 and 94 per cent. CONCLUSION: Laparoscopic IOUS is a reliable tool for staging liver tumours with a performance similar to that of open IOUS in detecting new nodules.
Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/patologia , Adulto , Idoso , Neoplasias Colorretais , Humanos , Achados Incidentais , Cuidados Intraoperatórios/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Padrões de Referência , Ultrassonografia de Intervenção/métodos , Adulto JovemRESUMO
BACKGROUND: This study assessed the feasibility and outcomes of combined colorectal and hepatic resection as the first step of two-stage hepatectomy in patients with bilobar synchronous colorectal liver metastases. METHODS: All patients with bilobar synchronous colorectal liver metastases who were considered for two-stage hepatectomy, combining resection of the primary tumour with the first stage of hepatectomy, between 2000 and 2008 were selected from a prospectively collected database at two institutions. Data were analysed retrospectively on an intention-to-treat basis. RESULTS: Thirty-three patients were studied. Twenty patients received neoadjuvant chemotherapy. Combined colorectal resection and clearance of left-sided liver metastases was the first-stage procedure in all but one patient, in whom right clearance was performed. In 17 patients right portal vein ligation was undertaken at the same time. No patient died. Two patients had anastomotic leakage. Interval chemotherapy was given to 25 patients, five of whom also had percutaneous portal vein embolization. Twenty-five patients had the second-stage hepatectomy, but not eight patients with disease progression. There was one postoperative death after the second stage, and eight patients experienced morbidity. Median follow-up from the first stage was 28.7 months. Overall and disease-free survival rates for patients who completed the procedure were 80 and 44 per cent respectively at 3 years, and 48 and 22 per cent at 5 years. CONCLUSION: In patients with bilobar synchronous colorectal liver metastases who are candidates for two-stage hepatectomy, combined resection of the primary tumour and first-stage hepatectomy reduces the number of procedures, optimizes chemotherapy administration and may improve outcome.