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BACKGROUND: Standard survival analysis fails to give insight into what happens to a patient after a first outcome event (like first relapse of a disease). Multi-state models are a useful tool for analyzing survival data when different treatments and results (intermediate events) can occur. Aim of this study was to implement a multi-state model on data of patients with rectal cancer to illustrate the advantages of multi-state analysis in comparison to standard survival analysis. METHODS: We re-analyzed data from the RCT FOGT-2 study by using a multi-state model. Based on the results we defined a high and low risk reference patient. Using dynamic prediction, we estimated how the survival probability changes as more information about the clinical history of the patient becomes available. RESULTS: A patient with stage UICC IIIc (vs UICC II) has a higher risk to develop distant metastasis (DM) or both DM and local recurrence (LR) if he/she discontinues chemotherapy within 6 months or between 6 and 12 months, as well as after the completion of 12 months CTx with HR 3.55 (p = 0.026), 5.33 (p = 0.001) and 3.37 (p < 0.001), respectively. He/she also has a higher risk to die after the development of DM (HR 1.72, p = 0.023). Anterior resection vs. abdominoperineal amputation means 63% risk reduction to develop DM or both DM and LR (HR 0.37, p = 0.003) after discontinuation of chemotherapy between 6 and 12 months. After development of LR, a woman has a 4.62 times higher risk to die (p = 0.006). A high risk reference patient has an estimated 43% 5-year survival probability at start of CTx, whereas for a low risk patient this is 79%. After the development of DM 1 year later, the high risk patient has an estimated 5-year survival probability of 11% and the low risk patient one of 21%. CONCLUSIONS: Multi-state models help to gain additional insight into the complex events after start of treatment. Dynamic prediction shows how survival probabilities change by progression of the clinical history.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Evaluación de Resultado en la Atención de Salud/métodos , Neoplasias del Recto/tratamiento farmacológico , Medición de Riesgo/métodos , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Medición de Riesgo/estadística & datos numéricos , Factores de RiesgoRESUMEN
Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted.
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Tumores del Estroma Gastrointestinal/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Tumores del Estroma Gastrointestinal/patología , Alemania , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Neoplasias Primarias Secundarias/diagnóstico , Evaluación de Resultado en la Atención de Salud , Pronóstico , Sistema de Registros , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Prevention programmes should only be recommended if they achieve what they promise to achieve. Therefore, we checked the variation and validity of recommendations for screening for colorectal cancer of nine organisations. METHODS: We analysed the information concerning recommended screening age, guaiac faecal occult blood test (gFOBT), faecal immunological test (FIT), faecal DNA test, sigmoidoscopy, colonoscopy, double-contrast examination/double-contrast barium enema, and virtual colonoscopy/CT colonography in the following three steps: 1) we gathered the references quoted by the nine organisations; 2) references were categorised according to mortality, incidence and sensitivity/specificity; 3) the validity of references that reported reduced mortality attributed to screening were evaluated. RESULTS: Evidence of occult faecal blood was the only screening method recommended by all nine organisations. Colonoscopy was recommended by seven organisations. Fifteen of the 33 references used endpoints other than mortality to justify screening. One publication was a meta-analysis. Eleven of 17 publications evaluated the gFOBT, three evaluated sigmoidoscopy, one FIT, one coloscopy, and one general diagnosis of the intestine. On average, two of nine validity criteria were completely fulfilled, five only partially, and two were not fulfilled. In two publications, none of the validity criteria were completely met. CONCLUSION: Analysis of screening for colorectal cancer revealed that nine organisations had different goals and different recommendations. Scrupulous and thorough evaluation of the scientific studies in relation to mortality, upon which these recommendations are based, revealed numerous shortcomings and therefore could not sufficiently substantiate the international recommendations for screening for colorectal cancer. It would be useful to establish a consensus about which data have to be collected to provide a reliable basis for health-care decisions.
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Neoplasias Colorrectales/prevención & control , Detección Precoz del Cáncer/métodos , Anciano , Sulfato de Bario , Colonografía Tomográfica Computarizada , Colonoscopía , Comparación Transcultural , Alemania , Adhesión a Directriz , Humanos , Sangre Oculta , SigmoidoscopíaRESUMEN
OBJECTIVES: During the last 15 years, there was tremendous progress in minimally invasive surgery and minimal-access surgery. Many conventional surgical procedures were replaced by these techniques, resulting in a wide range of benefits for the patients. In kidney transplantation, many centers choose an approach to the iliac fossa through an oblique or J-shaped incision. This might have possible disadvantages due to the extent of tissue trauma. Thus, we introduced a minimal-access kidney transplantation technique (MAKT) as a transplantation method in our center. We retrospectively analyzed this technique used for 11 living-donor kidney transplants and report here our experience. PATIENTS AND METHODS: From April 2008 to July 2011, 11 living-donor kidney recipients were subjected to the MAKT and were matched (age, sex) with a historical group from our center from 2000 to 2007. To analyze the assumption of noninferiority of the MAKT in comparison to the standard approach, a matched case-control study design was chosen, with creatinine level at 1 year after transplantation as the primary outcome variable. We used a Wilcoxon signed rank test; 1-sided significance level was 2.5%. RESULTS: Eleven recipients were included. Both groups were almost similar regarding age and body mass index. Characteristics of the procedure were significantly different only for cold ischemic time (114 minutes MAKT vs 77 minutes historical group). In the MAKT group, there were no reinterventions necessary, no wound infections, no incisional hernia, no acute rejection episodes, no graft losses, and 2 lymphoceles occurred. Further, no urinary leakage or ureteral stenosis and no vascular complications were observed. The statistical analysis of the primary endpoint revealed a noninferiority of the MAKT technique (P = .0005). CONCLUSIONS: Considering the fact that this is an initial series and a retrospective analysis, the applied MAKT technique seems to be safe in terms of both graft function after 1 year and surgical complications.
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Trasplante de Riñón/métodos , Donadores Vivos , Adulto , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: Our aim was to determine predictive factors for the diagnosis and postoperative complications of acute appendicitis. MATERIALS AND PATIENTS: Data sets of 1,439 consecutive adults and children who had an appendectomy between 1999 and 2008 were retrospectively analyzed. RESULTS: A mild acute appendicitis was present in 50 % (n = 722) and a severe acute appendicitis in 25 % (n = 355) of the patients. No signs of any pathology were found in 6 % (n = 82). Gender, white blood count (WBC), C-reactive protein (CRP), and ultrasound (US) examination were important indicators of mild acute and severe acute appendicitis in adults and children. Postoperative complications occurred in 16 % (237/1,439), mainly consisting of wound infections (8 %, n = 122) and bowel dysfunction (5 %, n = 76). Sixty-two patients (4.3 %) required reoperations. One patient died (1/1,439, 0.07 % mortality rate). Age, pathology, and the presence of bacteria in the intraoperative swab were important predictive factors for postoperative complications in adults and children. Time since onset of symptoms and type of operation were also associated with postoperative complications among adults. Complications developed in 21 and 9 % of the adults (155/754 and 10/125) who had open and laparoscopic surgery, respectively. CONCLUSIONS: Besides history and clinical examination, WBC, CRP, and US examination remain important factors for diagnosing acute appendicitis. Complications are related to the pathology, presence of bacteria, and type of operation. Early diagnosis within 48 h may be important. A laparoscopic procedure in adults may also cause fewer wound infections.
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Apendicectomía/efectos adversos , Apendicitis/diagnóstico , Apendicitis/cirugía , Complicaciones Posoperatorias/fisiopatología , Adolescente , Adulto , Factores de Edad , Apendicectomía/métodos , Proteína C-Reactiva/análisis , Niño , Estudios de Cohortes , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Laparotomía/efectos adversos , Laparotomía/métodos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Resultado del Tratamiento , Ultrasonografía Doppler/métodos , Adulto JovenAsunto(s)
Hernia Hiatal/complicaciones , Neumotórax/etiología , Choque Séptico/etiología , Gastropatías/complicaciones , Rotura Gástrica/complicaciones , Anomalía Torsional/complicaciones , Adulto , Tubos Torácicos , Ejercicio Físico , Femenino , Gastrectomía/métodos , Hernia Hiatal/congénito , Hernia Hiatal/diagnóstico , Hernia Hiatal/cirugía , Humanos , Isquemia/complicaciones , Isquemia/cirugía , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/etiología , Neumotórax/cirugía , Atelectasia Pulmonar/diagnóstico , Atelectasia Pulmonar/etiología , Rotura Espontánea/complicaciones , Rotura Espontánea/diagnóstico , Choque Séptico/cirugía , Estómago/irrigación sanguínea , Gastropatías/cirugía , Rotura Gástrica/diagnóstico , Rotura Gástrica/cirugía , Tomografía Computarizada por Rayos X , Anomalía Torsional/cirugíaRESUMEN
BACKGROUND: Intestinal anastomotic leakage represents a major complication in visceral surgery with relevant morbidity and mortality. MATERIAL AND METHODS: Based on a literature -search in Medline / PubMed the available data are presented, critically reviewed and summarised. RESULTS AND CONCLUSION: Beside optimisation of surgical technique, patient-dependent risk factors - such as relevant comorbidity, certain medications or previous radiochemotherapy - play a major role in the development of anastomotic leak-age. The effort for optimisation of these patient-dependent risk factors is not incorporated within the compensation scheme in German hospitals.
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Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Enfermedades Gastrointestinales/cirugía , Fuga Anastomótica/prevención & control , Fuga Anastomótica/cirugía , Enfermedades de las Vías Biliares/cirugía , Estudios Transversales , Humanos , Incidencia , Enfermedades Pancreáticas/cirugía , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Fístula Pancreática/cirugía , Cuidados Preoperatorios , Reoperación , Factores de Riesgo , Dehiscencia de la Herida Operatoria/epidemiología , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/prevención & control , Dehiscencia de la Herida Operatoria/cirugíaRESUMEN
Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostly observed in patients with severe subtypes of Fanconi anemia (FA) with or without VACTER-L association (VL). We investigated the hypothesis that early consequences of genomic instability result in shared regions with copy number variation in different precursor cells that originate distinct embryonal tumors. We observed a newborn girl with FA and VL (aplasia of the thumbs, cloacal atresia (urogenital sinus), tethered cord at L3/L4, muscular ventricular septum defect, and horseshoe-kidney with a single ureter) who simultaneously acquired an epithelial-type WT in the left portion of the kidney and a poorly differentiated adrenal NB in infancy. A novel homozygous germline frameshift mutation in PALB2 (c.1676_c1677delAAinsG) leading to protein truncation (pGln526ArgfsX1) inherited from consanguineous parents formed the genetic basis of FA-N. Spontaneous and induced chromosomal instability was detected in the majority of cells analyzed from peripheral lymphocytes, bone marrow, and cultured fibroblasts. Bone marrow cells also showed complex chromosome rearrangements consistent with the myelodysplastic syndrome at 11 months of age. Array-comparative genomic hybridization analyses of both WT and NB showed shared gains or amplifications within the chromosomal regions 11p15.5 and 17q21.31-q25.3, including genes that are reportedly implicated in tumor development such as IGF2, H19, WT2, BIRC5, and HRAS.
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A 31-year-old pregnant woman presented with refractory severe hypercalcemia due to an advanced neuroendocrine tumor masquerading as hyperemesis gravidarum. Octreotide therapy and extensive tumor debulking surgery resulted in symptom control. After a prolonged stay in the intensive care unit due to parapneumonic acute respiratory distress syndrome, the patient delivered a healthy child. Neuroendocrine tumors are a rare complication of pregnancy and a seldom cause of refractory hypercalcemia.
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Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Tumores Neuroendocrinos/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Adulto , Femenino , Humanos , Hipercalcemia/prevención & control , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/terapia , Embarazo , Complicaciones Neoplásicas del Embarazo/terapia , Resultado del TratamientoRESUMEN
Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is able to localize persistent or recurrent disease in differentiated thyroid carcinoma (DTC). The aim of the study was to correlate PET/CT results with precise intraoperative localization of persistent or recurrent papillary and follicular thyroid carcinoma. Patients with differentiated thyroid carcinoma who received FDG-PET scans were prospectively documented. The PET/CT results were correlated with other localization studies (neck ultrasound, ¹³¹I whole-body scan) and accurately compared to intraoperative findings and histopathological examinations. FDG-PET/CT scans were performed in 18 patients, between 16 and 84 years of age, from December 2008 to June 2011. Fourteen patients had papillary thyroid carcinomas and 4 had follicular thyroid carcinomas. All patients had a previous thyroidectomy and radioiodine ablation. Before cervical re-exploration, FDG-PET/CT-positive findings were reported in 14 individuals, whereas 4 PET scans provided no evidence of disease. Intraoperatively, 13 of 14 FDG-PET/CT-positive localizations of recurrent or persistent thyroid carcinomas were verified and confirmed by histopathology (sensitivity 93%). In another patient lymph node metastases of lung cancer were detected intraoperatively. However, FDG-PET/CT underestimated the number of lesions in 5 of 6 patients undergoing systematic lymphadenectomy. No lymph node or soft tissue metastases were found intraoperatively in 3 of the 4 patients with negative FDG-PET scans. A solitary cystic lymph node metastasis was found in the fourth patient but was not detected by FDG-PET/CT (specificity 75%). FDG-PET/CT has high sensitivity and specificity for the detection of persistent or recurrent differentiated thyroid carcinoma. FDG-PET/CT helps to select patients who might benefit from surgery because it provides precise anatomical details.
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Fluorodesoxiglucosa F18/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugía , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Adenocarcinoma Folicular/diagnóstico por imagen , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/secundario , Adenocarcinoma Folicular/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Carcinoma/secundario , Carcinoma/cirugía , Carcinoma Papilar , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Imagen Multimodal , Recurrencia Local de Neoplasia/patología , Neoplasia Residual , Tomografía de Emisión de Positrones , Estudios Prospectivos , Reoperación/efectos adversos , Sensibilidad y Especificidad , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Clinical economics strives to support healthcare decisions by economic considerations. Making economic decisions does not mean saving costs but rather comparing the gained added value with the burden which has to be accepted. The necessary rules are offered in various disciplines, such as economy, epidemiology and ethics. Medical doctors have recognized these rules but are not applying them in daily clinical practice. This lacking orientation leads to preventable errors. Examples of these errors are shown for diagnosis, screening, prognosis and therapy. As these errors can be prevented by application of clinical economic principles the possible consequences for optimization of healthcare are discussed.
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Atención a la Salud/economía , Costos de Hospital/estadística & datos numéricos , Programas Nacionales de Salud/economía , Procedimientos Quirúrgicos Operativos/economía , Conducta Cooperativa , Ahorro de Costo , Análisis Costo-Beneficio/economía , Errores Diagnósticos/economía , Alemania , Hospitales Universitarios/economía , Humanos , Comunicación Interdisciplinaria , Tamizaje Masivo/economía , Errores Médicos/economía , PronósticoRESUMEN
BACKGROUND: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. PATIENTS AND METHODS: Patients ≥18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. RESULTS: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14-15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≥90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT(>)(MIC) = 20%) and up to 0.25-0.5 mg/l for the near-maximal killing target (40% fT(>)(MIC)). CONCLUSION: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously.
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Colon/metabolismo , Recto/metabolismo , beta-Lactamas/farmacocinética , Adulto , Anciano , Colon/efectos de los fármacos , Ertapenem , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Unión Proteica , Recto/efectos de los fármacos , Distribución TisularRESUMEN
Schwannomas are rare tumors, usually benign, originating from the nerve sheath, and found only infrequently in the retroperitoneal space. We report on a 67-year-old woman who was initially misdiagnosed and treated for a liver hydatid cyst. After incomplete resection and recurrence of the tumor, we were able to diagnose a large retroperitoneal schwannoma that completely displaced the liver to the left abdomen. The patient underwent surgical resection of the schwannoma; pathological evaluation revealed a cystic tumor measuring 18.5 × 18 × 12.5 cm, with tumor cells staining strongly positive for S-100. Retroperitoneal schwannomas may mimic cystic hepatic tumors and should, therefore, be considered as a differential diagnosis in such cases. We describe the diagnostic modalities and difficulties in the approach of a cystic liver tumor.
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Neurilemoma/patología , Neurilemoma/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/cirugía , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Hepáticas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Standard adjuvant chemoradiotherapy of rectal cancer still consists of 5-fluorouracil (5-FU) only. Its cytotoxicity is enhanced by folinic acid (FA) and interferon-α (INFα). In this trial, the effects of FA and IFNα on adjuvant 5-FU chemoradiotherapy in locally advanced rectal cancer were investigated. METHODS: Patients with R(0)-resected rectal cancer (UICC stage II and III) were stratified and randomised to a 12-month adjuvant chemoradiotherapy with 5-FU, 5-FU+FA, or 5-FU+IFNα. All patients received levamisol and local irradiation with 50.4 Gy. RESULTS: Median follow-up was 4.9 years (n=796). Toxicities (WHO III+IV) were observed in 32, 28, and 58% of patients receiving 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. No differences between the groups were observed for local or distant recurrence. Five-year overall survival (OS) rates were 60.3% (95% confidence interval (CI): 54.3-65.8), 60.4% (54.4-65.8), and 59.9% (53.0-66.1) for 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. A subgroup analysis in stage II (pT3/4pN0) disease (n=271) revealed that the addition of FA tended to reduce the 5-year local recurrence (LR) rate by 55% and increase recurrence-free survival and OS rates by 12 and 13%, respectively, relative to 5-FU alone. CONCLUSIONS: Interferon-α cannot be recommended for adjuvant chemoradiotherapy of rectal cancer. In UICC stage II disease, the addition of FA tended to lower LR and increased survival. The addition of FA to 5-FU may be an effective option for adjuvant chemoradiotherapy of UICC stage II rectal cancer.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Terapia Combinada , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Adulto JovenRESUMEN
In patients with primary hyperparathyroidism (pHPT), positive preoperative localization studies enable to perform a minimally invasive approach for parathyroid surgery. However, current imaging techniques are not always successful. We therefore conducted a study to determine the sensitivity of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT) in localizing parathyroid adenomas in pHPT. Met-PET/CT scans of the neck and mediastinum of 33 patients undergoing parathyroidectomy for primary HPT were compared with intraoperative and histological findings. Primary HPT was caused by a single gland adenoma in 30 patients, while another 3 patients had multiglandular disease. Met-PET/CT scan correctly located a single gland adenoma in 25 out of 30 (83%) patients with pHPT, among them 2 patients with persistent disease, 7 patients with prior neck surgery, and 8 patients with concomitant thyroid nodules. In 3 patients with multiglandular disease, Met-PET/CT showed only one enlarged parathyroid gland in two individuals and was negative in the third patient. Statistical analysis found a significant correlation between true-positive results and the weight (2.42+/-4.05 g) and diameter (2.0+/-1.18 cm) of parathyroid adenomas while the subgroup with false negative findings had significantly smaller (0.98+/-0.54 cm) and lighter (0.5+/-0.38 g) glands. Sensitivity was 83% for single gland adenomas and 67% for multiglandular disease. Met-PET/CT correctly localized 83% of single gland parathyroid adenomas in patients with pHPT. However, preoperative localization of multiglandular disease due to double adenomas or parathyroid hyperplasia remained difficult.
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Adenoma/diagnóstico por imagen , Hiperparatiroidismo Primario/diagnóstico por imagen , Metionina , Neoplasias de las Paratiroides/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adenoma/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hiperparatiroidismo Primario/complicaciones , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Cuello/cirugía , Neoplasias de las Paratiroides/complicaciones , Cuidados Preoperatorios , Adulto JovenRESUMEN
The surgeon is the key "prognosis factor" for colorectal cancer. For this reason quality criteria were recently established (including minimum numbers) in order to treat patients who are entitled to the best quality of care and to improve the prognosis. The aim of this study was to critically discuss the existing demands on the surgeon based on the current literature and our own results and to formulate evidence-based quality criteria for surgical clinics. After reviewing the current literature criteria were compiled, discussed and finally presented in a summarized form. These are based on current developments on the diagnostic and therapy of large intestine and colorectal carcinoma. New developments of the German Cancer Society for planning of organ centers are incorporated. The quintessence of our study is that the number of cases alone is not decisive for the success of therapy. Important are the application of the correct surgical-oncology operation procedure, adherence to standards and the training of surgeons. Following the S3 guidelines stage-oriented therapy should additionally be carried out in a structured sequence. This includes an interdisciplinary decision making on the diagnostic and therapy strategy (tumor board). The organization structure of the hospital (teams, tumor board, emergency care with intensive care unit, emergency diagnostic and options for interventional measures) can be more important than the hospital case numbers alone. These demands which have been evaluated from published data and own results are designed to raise the therapy of colorectal cancer to the best possible level of quality and to effect a further improvement in the prognosis.
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Neoplasias Colorrectales/cirugía , Garantía de la Calidad de Atención de Salud/normas , Benchmarking/normas , Competencia Clínica/normas , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Vías Clínicas/normas , Medicina Basada en la Evidencia/normas , Alemania , Adhesión a Directriz/normas , Administración Hospitalaria/normas , Humanos , Estadificación de Neoplasias , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/normas , Pronóstico , Estándares de Referencia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell-cell and cell-matrix interactions. In cancer, SPARC can be not only associated with a highly aggressive phenotype, but also acts as a tumour suppressor. The aim of this study was to characterise the function of SPARC and its modulation by fibroblast growth factor receptor (FGFR) 1 isoforms in pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Exogenous SPARC inhibited growth, movement, and migration. ShRNA inhibition of endogenous SPARC in ASPC-1 and PANC-1 cells resulted in increased anchorage-dependent and -independent growth, transwell migration, and xenograft growth as well as increased mitogenic efficacy of fibroblast growth factor (FGF) 1 and FGF2. Endogenous SPARC expression in PANC-1 cells was increased in FGFR1-IIIb over-expressing cells, but decreased in FGFR1-IIIc over-expressing cells. The up-regulation of endogenous SPARC was abrogated by the p38-mitogen-activated protein kinase inhibitor SB203580. SPARC was detectable in conditioned medium of pancreatic stellate cells (PSCs), but not PDAC cells. Conditioned medium of PDAC cells reduced endogenous SPARC expression of PSCs. CONCLUSION: Endogenous SPARC inhibits the malignant phenotype of PDAC cells and may, therefore, act as a tumour suppressor in PDAC. Endogenous SPARC expression can be modulated by FGFR1-III isoform expression. In addition, PDAC cells may inhibit endogenous SPARC expression in surrounding PSCs by paracrine actions.
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Carcinoma Ductal Pancreático/patología , Regulación Neoplásica de la Expresión Génica/fisiología , Proteínas de Neoplasias/fisiología , Osteonectina/fisiología , Neoplasias Pancreáticas/patología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/fisiología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , División Celular/fisiología , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/metabolismo , Movimiento Celular/fisiología , Medios de Cultivo Condicionados/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Imidazoles/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Osteonectina/biosíntesis , Osteonectina/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Comunicación Paracrina , Fenotipo , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Piridinas/farmacología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Proteínas Recombinantes de Fusión/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/fisiologíaRESUMEN
Piwi proteins and their interaction with piRNAs have rapidly emerged as important contributors to gene regulation, indicating their crucial function in germline and stem cell development. However, data on the Hiwi 1 (Hiwi) gene, one of the four human Piwi homologues, are still scarce. Therefore, we investigated the Hiwi mRNA expression in microdissected PDAC tissues from patients with ductal adenocarcinoma of the pancreas (PDAC) by quantitative real-time PCR and the protein expression by immunohistochemistry. Elevated levels of Hiwi mRNA transcripts were measured in 40 out of 56 tissues and a positive immunostaining of Hiwi was detected in tumours of 21 out of 78 patients. There was no general impact of elevated Hiwi mRNA transcript levels or protein expression on survival, as tested by multivariate Cox regression and Kaplan-Meier analysis. However, men showed a significantly increased risk for tumour-related death in case of down- or upregulated expression of Hiwi mRNA (relative risk (RR)=2.78; P=0.034). In summary, we report the first analysis of Hiwi expression in PDAC and its impact on prognosis. We suggest that alterations in mRNA expression of Hiwi can increase the risk of tumour-related death in male PDAC patients.
Asunto(s)
Adenocarcinoma/genética , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/genética , Proteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Argonautas , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.
Asunto(s)
Neoplasias Colorrectales/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Recurrencia Local de Neoplasia/cirugía , Algoritmos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Terapia Combinada , Supervivencia sin Enfermedad , Embolización Terapéutica , Medicina Basada en la Evidencia , Estudios de Factibilidad , Humanos , Laparoscopía , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , PronósticoRESUMEN
Benign pancreatic tumors should undergo surgical resection when they are symptomatic or--in the case of incidental discovery--bear malignant potential. This is the case for the majority of benign pancreatic tumors, especially for intraductal papillary mucinous neoplasms or mucinous cystic adenomas. In addition, resection is indicated for all tumors where preoperative diagnostic fails to provide an exact classification.Several different operative techniques are available. The treatment of choice depends on the localization of the tumor, its size and on whether there is evidence of malignant transformation. Partial duodenopancreatectomy is the oncological treatment of choice for tumors of the pancreatic head whereas for tumors of the pancreatic tail a left-sided pancreatectomy is appropriate. Middle pancreatectomy or duodenum-preserving resection of the pancreatic head is not a radical oncologic procedure. They should only be performed in cases of tumors without malignant potential.