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Neural networks play a growing role in many scientific disciplines, including physics. Variational autoencoders (VAEs) are neural networks that are able to represent the essential information of a high dimensional data set in a low dimensional latent space, which have a probabilistic interpretation. In particular, the so-called encoder network, the first part of the VAE, which maps its input onto a position in latent space, additionally provides uncertainty information in terms of variance around this position. In this work, an extension to the autoencoder architecture is introduced, the FisherNet. In this architecture, the latent space uncertainty is not generated using an additional information channel in the encoder but derived from the decoder by means of the Fisher information metric. This architecture has advantages from a theoretical point of view as it provides a direct uncertainty quantification derived from the model and also accounts for uncertainty cross-correlations. We can show experimentally that the FisherNet produces more accurate data reconstructions than a comparable VAE and its learning performance also apparently scales better with the number of latent space dimensions.
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BACKGROUND: Ramucirumab is a VEGFR-2 antibody that has proven to prolong overall survival (OS) in patients with pretreated metastatic gastric/gastrooesophageal junction (GEJ) adenocarcinoma. We present data from patients treated with ramucirumab and paclitaxel or FOLFIRI after failure of at least one platinum- and 5-FU-containing chemotherapy (CHT) regimen. METHODS: In this retrospective two-center study, 56 patients with metastatic gastric cancer (47%) or adenocarcinoma of the GEJ (53%) were treated with paclitaxel and ramucirumab (n=38) as second-line (75%) or beyond second-line (25%) therapy. FOLFIRI-ramucirumab (FOLFIRI-R) (n=16) was given to patients with a short interval between taxane-based perioperative CHT and occurrence of metastatic disease or to those ineligible for paclitaxel. RESULTS: The median progression-free survival (PFS) and OS for patients treated with paclitaxel-ramucirumab (pacl-R) were 2.9 (95% CI: 2.3-3.6) and 4.4 (4.1-4.7) months, respectively, and those for patients treated with FOLFIRI-R were 5.9 (95% CI: 0.35-11.4) and 8.3 (6.6-10) months, respectively (P=0.05). We observed a trend towards prolonged PFS after perioperative taxane-based FLOT CHT (n=12) with FOLFIRI-R compared with pacl-R. Adverse events were manageable, with neutropenia and polyneuropathy (PNP) being the most common events. More than two treatment lines were given to 48.2% of patients. CONCLUSIONS: The use of ramucirumab in combination with FOLFIRI showed favourable PFS and OS in patients with prior treatments with platinum and/or taxane-based agents and allows further treatment lines after progression. In patients with taxane pretreatment or persistent high-grade PNP, the combination of FOLFIRI-R might be a promising combination.
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Central venous port devices are indicated for patients, who need long-term intravenous therapy. Oncologic patients may require intermittent administration of chemotherapy, parenteral nutrition, infusions, or blood transfusions. A venous port system is composed of a port chamber attached to a central catheter, which is implanted into the central venous system. The subcutaneous location of the catheter chamber improves the patients' quality of life and the infection rate is lower than in non-totally implantable central venous devices. However, proper implantation, use, and care of a port system are important to prevent short- and long-term complications. Most common early complications (< 30 days) include venous malpositioning of catheter and perforation with arterial injury, pneumothorax, hemothorax, thoracic duct injury, or even cardiac tamponade. Delayed complications include infection, catheter thrombosis, vessel thrombosis and stenosis, catheter fracture with extravasation, or fracture with migration or embolization of catheter material. Radiologic imaging has become highly relevant in intra-procedural assessment and postoperative follow-up, for detection of possible complications and to plan intervention, e.g., in case of catheter migration. This pictorial review presents the normal imaging appearance of central venous port systems and demonstrates imaging features of short- and long-term complications.
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BACKGROUND: The minimally invasive esophagectomy (MIE) for esophageal cancer was introduced assuming a reduction of morbidity and operation time. After implementation of MIE at our institution, a randomized controlled trial was designed. METHODS: This is a prospective randomized controlled study comparing open (OE) and laparoscopic gastric tube (MIE) formation in Ivor Lewis esophagectomy. Primary endpoints were morbidity and 30-day mortality. Secondary endpoints included the duration of intensive care unit stay, length of hospital stay, operative time as well as relapse-free and overall survival. RESULTS: Twenty patients (76.9%) were male, median age was 63 years (40-77). Median operation time was 290 (215-385) minutes in OE and 292.5 (200-450) minutes in MIE group, pâ¯=â¯0.421. Major complications occurred in 4 (33.3%) patients in the OE group and in 6 (35.7%) patients in the MIE group. Anastomotic leakage was seen in 2 (16.6%) and 3 (21.4%) patients, respectively (OR 1.364; CIâ¯= 0.188-9.912; pâ¯= 0.759). Due to an alarming number of consecutive anastomotic leakages, the trial was stopped after inclusion of 26 patients. Median follow-up was 41.5 (1-62.6) months. 5year survival rate was 50%. Thirty-eight percent developed recurrence of disease in the study period. There was no significant difference in overall and relapse-free survival regarding the type of surgery. CONCLUSION: This study shows that hybrid MIE is a feasible alternative for esophageal resection. Morbidity, mortality, and oncological long-term results were equal in both groups, but the interpretation has to be done carefully due to premature termination of the trial. Interrupting a trial because of patient benefit should not be a reason to discard results but rather to improve technical aspects and strive for novel studies.
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BACKGROUND: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The ⢠Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies. METHOD: Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study. RESULTS: From 2007-2012, the ⢠Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%. CONCLUSION: Due to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the ⢠Pancho trial is now awaited.
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BACKGROUND: Both long-term proton pump inhibitor (PPI) use and surgical fundoplication have potential drawbacks as treatments for chronic gastroesophageal reflux disease (GERD). This multi-center, prospective study evaluated the clinical experiences of 69 patients who received an alternative treatment: endoscopic anterior fundoplication with a video- and ultrasound-guided transoral surgical stapler. METHODS: Patients with well-categorized GERD were enrolled at six international sites. Efficacy data was compared at baseline and at 6 months post-procedure. The primary endpoint was a ≥ 50 % improvement in GERD health-related quality of life (HRQL) score. Secondary endpoints were elimination or ≥ 50 % reduction in dose of PPI medication and reduction of total acid exposure on esophageal pH probe monitoring. A safety evaluation was performed at time 0 and weeks 1, 4, 12, and 6 months. RESULTS: 66 patients completed follow-up. Six months after the procedure, the GERD-HRQL score improved by >50 % off PPI in 73 % (48/66) of patients (95 % CI 60-83 %). Forty-two patients (64.6 %) were no longer using daily PPI medication. Of the 23 patients who continued to take PPI following the procedure, 13 (56.5 %) reported a ≥ 50 % reduction in dose. The mean percent of total time with esophageal pH <4.0 decreased from baseline to 6 months (P < 0.001). Common adverse events were peri-operative chest discomfort and sore throat. Two severe adverse events requiring intervention occurred in the first 24 subjects, no further esophageal injury or leaks were reported in the remaining 48 enrolled subjects. CONCLUSIONS: The initial 6-month data reported in this study demonstrate safety and efficacy of this endoscopic plication device. Early experience with the device necessitated procedure and device changes to improve safety, with improved results in the later portion of the study. Continued assessment of durability and safety are ongoing in a three-year follow-up study of this patient group.
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Endoscopia Gastrointestinal , Fundoplicatura/instrumentação , Refluxo Gastroesofágico/cirurgia , Grampeadores Cirúrgicos , Ultrassonografia de Intervenção , Cirurgia Vídeoassistida , Adolescente , Adulto , Idoso , Terapia Combinada , Monitoramento do pH Esofágico , Feminino , Seguimentos , Fundoplicatura/métodos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/diagnóstico por imagem , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a p53-dependent apoptosis pathway. The TP53 gene is frequently mutated in esophageal cancer. OBJECTIVE: To test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer. PATIENTS AND METHODS: The investigation included 36 patients with primary operable esophageal cancer who were treated neoadjuvantly with cisplatin and fluorouracil. The TP53 genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a standardized gene-specific TP53 sequencing protocol (mark53 kit; mark53 Ltd, Vienna, Austria). RESULTS: Mutations in the TP53 gene were present in 50% of tumors. Two-year overall survival rates were 55.6% in patients with a normal TP53 marker status, compared with 16.7% in those with a mutant TP53 gene. In patients with normal TP53, neoadjuvant treatment resulted in significant advantages in terms of tumor-associated survival (P=.0049) and overall survival (P=.0304) compared with those with mutant TP53. The median tumor-associated survival was 34.2 months for patients with normal TP53, compared with 8.9 months for those with mutant TP53. The latter had a 3-fold higher risk of dying (hazard ratio, 3.01; 95% confidence interval, 1.359-6.86). CONCLUSIONS: The biomarker TP53 divides esophageal cancer patients into 2 categories with markedly different outcomes: patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those with a mutant TP53 marker status appear to be at risk for lack of response.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Mutação , Terapia Neoadjuvante , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Áustria , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Análise Mutacional de DNA , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Fluoruracila/administração & dosagem , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Treatment of locally advanced resectable esophageal cancer is challenging. In the past three decades surgical treatment has become safer, chemotherapy more powerful and radiation techniques more precise. Today's stage-dependent treatment relies on modern diagnostic tools such as multidetector helical CT, high-frequency endoscopic ultrasound, PET, image fusion techniques and MRI. Specialists cooperate on multidisciplinary tumor boards that follow transparent decision trees based on the newest evidence. METHODS: Results of recent randomized controlled trials are examined with emphasis on their reliability and comparability. RESULTS: Patients with esophagogastric cancer undergoing neoadjuvant chemotherapy, perioperative chemotherapy and neoadjuvant radiochemotherapy plus esophagectomy had a higher R-0 resection rate, fewer involved lymph nodes and better overall survival than with esophagectomy alone. While perioperative morbidity and mortality were not remarkably enhanced by neoadjuvant chemotherapy, several trials showed an increase of mortality after neoadjuvant radiochemotherapy. Adenocarcinoma seems to respond better to chemotherapy than squamous cell cancer, and squamous cell cancer seems to respond better to radiochemotherapy than adenocarcinoma. CONCLUSION: On the basis of the results of randomized trials, preoperative treatment of esophageal cancer shows a survival benefit and should be recommended as the standard treatment strategy in advanced esophageal cancer. While preoperative radiochemotherapy is the standard for advanced squamous cell cancer, both chemotherapy and radiochemotherapy may be adopted for neoadjuvant/perioperative treatment of adenocarcinoma depending on the patient's general condition. Markers to predict response are urgently needed since only responders benefit from multimodal treatment and nonresponders suffer potential harm when surgery is delayed.
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Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Biomarcadores Tumorais/metabolismo , Quimiorradioterapia , Terapia Combinada , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Humanos , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Discovery of the molecular pathogenesis of Gastrointestinal stromal tumors led to the development of targeted therapies, revolutionizing their treatment. However, surgery is still the mainstay of GIST therapy and the only chance for cure. AIM: Here we present a single institutional consecutive case series of 159 GIST-patients. METHODS AND PATIENTS: A total of 159 GIST-patients who underwent resection between 1994 and 2011 were reviewed for clinicopathohistological data, informations on surgical and medical therapy and further follow-up, outcome and survival data. RESULTS: Laparoscopic (25.2%) and open (71.1%) GIST surgery achieved complete resection rates of 97.5% and 85.2%, whereas 44.4% of incomplete and 6.6% of complete resected patients died from GIST. Compared to open surgery laparoscopy significantly reduced duration of operation (183.4 vs. 130.6 min), length of hospitalization (16.1 vs. 8.3 d) and morbidity (23% vs. 7.5%). Mean survival time was 3.7 ± 2.7 years (R0: 5.1 a and R1: 2.6 a) and the mean overall survival was 4.5 ± 3.8 years. CONCLUSION: Complete surgical resection is the primary goal and laparoscopy can be performed safely in a subset of GIST-patients with potential perioperative advantages. Although not proven by the present study the authors assume that multimodal GIST-treatment, as performed in reference-centers, is required for advanced or high risk disease. Our data suggest the potential for minimally invasive GIST resection to achieving comparable oncological outcomes as after open surgery while providing low morbidity rates.
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Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The efficacy of triple-drug combination regimens such as docetaxel, cisplatin and 5-fluorouracil (DCF), and epirubicin, oxaliplatin and capecitabine (EOX), is superior to standard cisplatin/5-fluorouracil in patients with upper gastrointestinal adenocarcinoma. In this analysis, we compare DCF and EOX regarding toxicity and efficacy. PATIENTS AND METHODS: Patients received either intravenous docetaxel at 75 mg/m(2), cisplatin at 75 mg/m(2), both given on day 1, and 5-fluorouracil at 750 mg/m(2), on days 1 to 5, or epirubicin at 50 mg/m(2) i.v. on day 1, oxaliplatin at 130 mg/m(2) i.v. on day 1 and capecitabine at a twice-daily dose of 1000 mg/m(2) p.o. for two weeks; both regimens were repeated every three weeks. RESULTS: Response rates for DCF and EOX were 28% and 10%, time-to-progression was 26 and 20 weeks, and overall survival were 54 and 52 weeks, respectively. CONCLUSION: We conclude that further investigations within comparative prospective clinical trials of these regimens are warranted.
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Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Cuidados Paliativos , Trato Gastrointestinal Superior/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Docetaxel , Epirubicina/efeitos adversos , Epirubicina/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Estudos Retrospectivos , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Esophagectomy represents the gold standard in the treatment of resectable esophageal cancer. Despite significant improvements in perioperative care, postoperative morbidity and mortality rates remain high. Minimally-invasive surgical techniques introduced to the surgical treatment of esophageal malignancies have been shown to successfully diminish surgical trauma and postoperative morbidity. AIM: In the present report we present the stepwise implementation of minimally-invasive techniques in the treatment of esophageal cancer at a high-volume center and its influence on overall patient outcome. PATIENTS AND METHODS: A total of 165 consecutive patients with esophagectomy, in two 4-year periods, namely that before (period A) and that after (period B) the implementation of minimally-invasive esophagectomy (MIE) for cancer, were compared. Patients' characteristics, and perioperative, surgical, oncological and survival outcomes were compared. RESULTS: In time period A, 73 patients were treated with open esophagectomy (OE), whereas in time period B 37 patients (40.2%) underwent an OE and 55 (59.8%) a minimally-invasive esophagectomy. Surgical and non-surgical complications did not differ significantly between groups (B: 44.6% vs. A: 54.8%; B: 38% vs. A: 35.6%; p>0.05). Duration of ventilation (B: 1.8 days vs. A: 6.7 days), ICU (B: 5.7 days vs. A: 12.2 days) and hospital stay (B: 20.5 days vs. A: 28.4 days) were significantly reduced in patients of time period B. The number of lymph nodes removed and complete resection rates were comparable (mean=18.1 ± 10.1 lymph nodes; B: 87% R0 vs. A: 93.2% R0). No significant differences between the groups were detectable regarding short-term disease-free or overall survival. CONCLUSION: The implementation of minimally-invasive esophagectomy is feasible, safe and has the potential to reduce perioperative morbidity without compromising oncological outcome.
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Adenocarcinoma/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Optimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.
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Assistência ao Convalescente , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Adulto , Áustria , Benzamidas/uso terapêutico , Biópsia , Criança , Terapia Combinada , Comportamento Cooperativo , Diagnóstico Diferencial , Diagnóstico por Imagem , Progressão da Doença , Endoscopia Gastrointestinal , Seguimentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Trato Gastrointestinal/patologia , Trato Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib , Indóis/uso terapêutico , Comunicação Interdisciplinar , Índice Mitótico , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Nomogramas , Cuidados Paliativos , Compostos de Fenilureia/uso terapêutico , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , SunitinibeRESUMO
BACKGROUND: The efficacy of triple-drug combination regimens such as epirubicin, oxaliplatin and capecitabine (EOX) is superior to standard cisplatin/5-fluorouracil, but considerable toxicity needs to be taken into account in patients with upper gastrointestinal adenocarcinoma. Therefore, we aimed to establish a modified version of the EOX regimen with improved tolerability for these patients. PATIENTS AND METHODS: Patients received palliative first-line chemotherapy with a modified EOX regimen repeated every three weeks (epirubicin 50 mg/m(2) i.v., day 1; oxaliplatin 130 mg/m(2) i.v., day 1; capecitabine at a twice-daily dose of 1000 mg/m(2) p.o. for two weeks). RESULTS: Out of 51 patients, partial remission was observed in five (10.2%) and stable disease in 31 (60.8%). Progression-free survival was four months, and overall survival twelve months. CONCLUSION: Modified EOX was generally well-tolerated and, therefore, further investigation within prospective clinical trials is warranted.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica , Cuidados Paliativos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the clinical impact of lymphangiogenesis (measured by lymphatic microvessel density [LMVD]) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer. METHODS: For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed. RESULTS: Patients with high LMVD had a significant increased risk to develop LVI (P = .00123; coefficient of regression [CR] 0.27) and lymph node metastasis (P = .00233), independent of the tumor's histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS (P < .001; 5-year OS 14% vs 60%) and DFS (P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions (P = .008). The amount of ISR correlated significantly with LMVD. CONCLUSION: Our data provide evidence for a clinically significant role of specific lymphangiogenesis in esophageal cancer. Patients with high lymphangiogenic tumor activity represent candidates for lymphangiogenesis-associated therapies.
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Adenocarcinoma/fisiopatologia , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias Esofágicas/fisiopatologia , Linfangiogênese , Metástase Linfática , Vasos Linfáticos/fisiopatologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Humanos , Imuno-Histoquímica , Vasos Linfáticos/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
PURPOSE: Squamous cell cancer (SCC) of the pharyngoesophageal junction area has a poor prognosis mainly due to late symptom manifestation and diagnosis. Treatment of choice is still pharyngolaryngoesophagectomy, substantially affecting quality of life. Limited surgical procedures have been adopted as well. The aim of this retrospective study was to evaluate whether the extent of resection influences postoperative safety and mortality. METHODS: From 1984 to 2006, 66 patients were operated at a single tertiary referral center. Nineteen patients (28.8 %) had SCC of the hypopharynx and 47 patients (71.2 %) had SCC of the cervical and cervicothoracic esophagus. Thirty-five patients (53.0 %) underwent cervical esophageal resection (CE) and 31 underwent total esophagectomy (TE). In 39 patients (59.1 %), the larynx was preserved. Thirteen patients (19.7 %) underwent multimodal treatment. RESULTS: Overall postoperative morbidity was 69.7 % and reoperation rate reached 28.8 %. TE (P = 0.03) and larynx preservation (P = 0.02) were followed by a higher rate of non-lung infections compared with CE and pharyngolaryngectomy, respectively. Pulmonary complications have been observed more frequently after larynx preservation (P = 0.02). Hospital mortality was 9.1 %. Four patients died after TE (12.9 %) and two patients died after CE (5.7 %). In all of them, the larynx had been preserved (15.4 %). Overall, 53 patients (80.3 %) died until follow-up. One-year and 5-year survival in patients with the major tumor burden at the cervicothoracic site was 35.7 and 0 %. CONCLUSIONS: CE can be recommended as long as R0 resection is warranted. The advantage of larynx preservation is gained by higher morbidity and mortality rates and may not be recommended as standard procedure. Surgery may not be appropriate for advanced SCC in the cervicothoracic region.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Faringectomia/métodos , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Faringectomia/mortalidade , Complicações Pós-Operatórias , Prognóstico , Qualidade de Vida , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AIMS: Podoplanin overexpression is associated with worse prognosis in several human cancers. In gastrointestinal stromal tumors (GISTs) very few data on the expression of podoplanin exist, but it seems to be frequently overexpressed in pediatric/syndromic GISTs. We investigated podoplanin expression and its clinical relevance in a large series of sporadic GISTs. METHODS: Podoplanin expression was determined immunohistochemically in 145 sporadic adult GISTs. Aneuploidies of 1p36 and 1q25 were investigated using FISH, and KIT and PDGFRA genes were investigated by sequencing. RESULTS: Overexpression of podoplanin was observed in eight (5.6%) GISTs and no association with amplification of 1p36 or KIT or PDGFRA mutations was seen. The amount of podoplanin expression was not associated with clinical risk factors or patient survival. CONCLUSION: Overexpression of podoplanin is a rare event in sporadic GISTs and is not associated with amplification of 1p36 or with KIT or PDGFRA mutations, which indicates limited pathobiological or clinical relevance.
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Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/metabolismo , Glicoproteínas de Membrana/metabolismo , Adulto , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 1 , Feminino , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
INTRODUCTION: Liver metastases originating from various types of sarcoma are a rare reason for hepatic resection. So far, even multicentre studies do hardly provide statistically relevant sample sizes. Thus, review of available data can provide surgeons with useful information in similar cases. Therefore, this study can be regarded more as a contribution to this pool of data than as a stand-alone paper. PATIENTS AND METHODS: The study includes 10 women and five men who underwent subtotal hepatic resection for solitary (n = 4) and multiple (n = 11) liver metastases originating from sarcoma. The median tumour diameter was 60 mm (range 20-200 mm). RESULTS: Morbidity was 33%. One patient died within 30 days after surgery. Resection was complete (R0) in 67%. Median overall survival was 33.6 months, 5-year survival 27%. The use of Pringle manoeuvre was significantly associated with poorer outcome (p = 0.014) and shorter period of recurrence-free survival (p = 0.012). Diameter of liver lesion over 50 mm showed significantly shorter recurrence-free survival (p = 0.042). CONCLUSION: Hepatic resection may be beneficial in patients with isolated sarcoma metastasis in the liver.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Sarcoma/secundário , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Invasividade Neoplásica/patologia , Medição de Risco , Sarcoma/mortalidade , Sarcoma/terapia , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: A retrospective analysis was carried out to evaluate toxicity and efficacy of the combination chemotherapy of docetaxel, cisplatin and 5-fluorouracil (DCF) plus granulocyte colony-stimulating factor prophylaxis (G-CSF) in patients with metastatic gastric and gastroesophageal junction adenocarcinoma. PATIENTS AND METHODS: Eighteen patients received intravenous 75 mg/m2 docetaxel, 75 mg/m2 cisplatin, both given on day 1 and 750 mg/m2 5-fluorouracil, on days 1 to 5 plus G-CSF on day 6, all repeated every 3 weeks. RESULTS: Response rate was 28%, time to progression and overall survival were 26 and 54 weeks, respectively. The most common hematological WHO toxicities were anemia and leukocytopenia, which occurred in 18/18 and in 12/18 patients. WHO Grade 4 neutropenia occurred in one patient whereas nonhematological toxicity was generally mild. CONCLUSION: We conclude that DCF combination plus G-CSF prophylaxis is a safe and active regimen for patients with metastatic gastric and gastroesophageal junction adenocarcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Taxoides/efeitos adversosRESUMO
OBJECTIVE: To evaluate the accuracy of multidetector computed tomography with water filling (Hydro-MDCT) in the T-staging of patients with oesophageal cancer. MATERIALS AND METHODS: There were 131 consecutive patients who were preoperatively and prospectively examined in the prone position on arterial phase contrast-enhanced MDCT, after ingestion of 1,000-1,500 ml tap water and effervescent granules. Two readers staged the local tumour growth (T-staging) independently. They assessed tumour location, size, presence of stenosis, and morphology of the outer border of the oesophageal wall and perioesophageal fat planes on CT. CT findings were compared with histopathological results from resected specimens. Data were analyzed using the SPSS statistical package. RESULTS: Both readers obtained a high sensitivity of 95% and a high positive predictive value of 96%. Accurate local staging was achieved in 76.3% and 68.7% for readers 1 and 2, respectively. Inter-reader agreement was excellent (weighted κ value of 0.93 and un-weighted κ of 0.89). CONCLUSION: Using the hydro-technique and applying specific assessment criteria, MDCT appears to be an accurate, non-invasive diagnostic tool for local tumour staging of oesophageal cancer.