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BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placed in the pull through (PT) technique is a common procedure to restore enteral feeding in patients with swallowing disorders. Limitations of this technique are patients with obstruction of the pharynx or esophagus or with an esophageal stent. We report our experience with the direct puncture (DP) PEG device. METHODS: We included 154 patients (55 women). One hundred forty patients had cancer. After passing the endoscope into the stomach, 4 gastropexies were performed with a gastropexy device and the PEG was placed with the introducer method. After 1 month, the sutures were removed and a constant gastrocutaneous fistula had been created and the new catheter could be placed safely. RESULTS: The DP PEG was successfully placed in all patients. Overall complication rate was 11% (minor: 6%, major: 5%). The most common event was tube dislocation (40 cases). In 5 cases of dislocation, this resulted in a major complication with injuring the gastric wall and the necessity for surgical treatment. CONCLUSIONS: The DP PEG system is safe, and can be used in cases in which a standard PT PEG is not feasible. To avoid dislocation, strict adherence to a post-interventional protocol is highly recommended.
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Catéteres de Permanencia/efectos adversos , Gastrostomía/efectos adversos , Gastrostomía/métodos , Falla de Prótesis/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Nutrición Enteral , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Gastropexia , Gastroscopía , Gastrostomía/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estómago/lesiones , Adulto JovenRESUMEN
BACKGROUND: Clinical reasoning is based on the declarative and procedural knowledge of workflows in clinical medicine. Educational approaches such as problem-based learning or mannequin simulators support learning of procedural knowledge. Immersive patient simulators (IPSs) go one step further as they allow an illusionary immersion into a synthetic world. Students can freely navigate an avatar through a three-dimensional environment, interact with the virtual surroundings, and treat virtual patients. By playful learning with IPS, medical workflows can be repetitively trained and internalized. As there are only a few university-driven IPS with a profound amount of medical knowledge available, we developed a university-based IPS framework. Our simulator is free to use and combines a high degree of immersion with in-depth medical content. By adding disease-specific content modules, the simulator framework can be expanded depending on the curricular demands. However, these new educational tools compete with the traditional teaching OBJECTIVE: It was our aim to develop an educational content module that teaches clinical and therapeutic workflows in surgical oncology. Furthermore, we wanted to examine how the use of this module affects student performance. METHODS: The new module was based on the declarative and procedural learning targets of the official German medical examination regulations. The module was added to our custom-made IPS named ALICE (Artificial Learning Interface for Clinical Education). ALICE was evaluated on 62 third-year students. RESULTS: Students showed a high degree of motivation when using the simulator as most of them had fun using it. ALICE showed positive impact on clinical reasoning as there was a significant improvement in determining the correct therapy after using the simulator. ALICE positively impacted the rise in declarative knowledge as there was improvement in answering multiple-choice questions before and after simulator use. CONCLUSIONS: ALICE has a positive effect on knowledge gain and raises students' motivation. It is a suitable tool for supporting clinical education in the blended learning context.
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Educación Médica/métodos , Internet/estadística & datos numéricos , Simulación de Paciente , Aprendizaje Basado en Problemas/métodos , HumanosRESUMEN
PURPOSE: Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery. METHODS: In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996-2006) (pre-CTx) and b) after (2006-2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR). RESULTS: 737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65 years and the median follow-up was 27.5 months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (p < 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (p = 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (p = 0.357), age (p = 0.379), pT category (p = 0.817), pN stage (p = 0.074), cM stage (p = 0.112), Laurén classification (p = 0.158), and SRs (3-YSR: 60.3% vs 59.4%; p = 0.898) between the MAGIC and FLOT regimens. CONCLUSIONS: Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.
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Neoplasias Esofágicas , Neoplasias Gástricas , Anciano , Femenino , Humanos , Masculino , Neoplasias Esofágicas/patología , Unión Esofagogástrica/cirugía , Unión Esofagogástrica/patología , Gastrectomía , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Gástricas/patología , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: Residual tumor at the resection margins after surgery for gastric and gastroesophageal junction (GEJ) adenocarcinoma is a known prognostic factor. In this single-center, retrospective cohort study in a tertiary referral center, the authors aimed to evaluate the relevance of intraoperative pathology consultation (IOC) and consecutive extension of surgery on patient survival. STUDY DESIGN: Of 737 consecutive patients undergoing (sub)total gastrectomy for gastric or GEJ adenocarcinoma, 679 cases with curative intent surgery between 05/1996 and 03/2019 were included. Patients were categorized into: R0 without further resection (direct R0), R0 after positive IOC and extension of resection (converted R0), and R1. RESULTS: IOC was performed in 242 (35.6%) patients, in 216 (89.3%) at the proximal resection margin. Direct R0-status was achieved in 598 (88.1%), converted R0 in 26 (3.8%) of 38 (5.6%) patients with positive IOC and R1 in 55 (8.1%) patients. The median follow-up was 29 months for surviving patients. 3-year survival rate (3-YSR) was significantly higher for direct R0 compared to converted R0 with 62.3% compared to 21.8% (hazard ratio=0.298; 95% CI=0.186-0.477, P <0.001). 3-YSR was similar between converted R0 and R1 (21.8 vs. 13.3%; hazard ratio =0.928; 95% CI=0.526-1.636, P =0.792). In multivariate analysis, advanced T ( P <0.001), N ( P <0.001), R ( P =0.003), and M1 status ( P <0.001) were associated with worse overall survival. CONCLUSION: IOC and consecutive extended resection for positive resection margins in gastrectomy for the proximal gastric and GEJ adenocarcinoma does not achieve long-term survival benefits in advanced tumor stages.
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Adenocarcinoma , Márgenes de Escisión , Humanos , Estudios Retrospectivos , Gastrectomía , Adenocarcinoma/patología , Unión Esofagogástrica/cirugía , Unión Esofagogástrica/patología , Tasa de Supervivencia , PronósticoRESUMEN
BACKGROUND/AIM: Esophagectomy and gastrectomy are procedures with considerable physical burden and intense post-operative care of which the patient's physical condition seems to be a relevant predictor. The gold standard of the cardiorespiratory fitness is the peak oxygen consumption (VO2peak). This pilot study examined the prognostic value of VO2peak on post-surgery outcomes in esophageal and gastric cancer patients. PATIENTS AND METHODS: In this prospective cross-sectional study, patients scheduled for esophagectomy or gastrectomy were examined 24 h before the surgery regarding their VO2peak. The post-operative complications according to Clavien-Dindo grade IIIb/IV/V, Intensive-Care-Unit days, and overall hospital stay were documented following surgery. In a subset, body weight changes from surgery until hospital discharge and first aftercare visit were recorded. RESULTS: The functional capacity was significantly reduced in 34/35 of the included patients compared to matched norm-values (p<0.01). The only significant correlation was found between VO2peak values and body weight change from surgery to the first aftercare visit. A subgroup comparison of patients with a VO2peak <17 ml/min/kg and ≥17 ml/min/kg suggested small, non-significant differences in post-surgery outcomes and significant differences in the body weight change from surgery to hospital discharge, favoring the higher-VO2peak subgroup. CONCLUSION: The impaired functional capacity following esophagectomy or gastrectomy may strengthen the rational for exercise programs during neoadjuvant and pre-surgery phases. The prognostic value of VO2peak on post-operative outcomes remains uncertain due to noticeable descriptive differences, but no significant correlations, potentially limited by the smallsized population. Nonetheless, a correlation between VO2peak and body weight change post-surgery was observed and indicates a potential prognostic value of VO2peak.
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Neoplasias Esofágicas , Neoplasias Gástricas , Peso Corporal , Estudios Transversales , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Esofagectomía/métodos , Gastrectomía/efectos adversos , Humanos , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND AND AIMS: We evaluated the outcome of primarily resected rectal cancer patients immediately after the implementation of total meserectal excision (TME) based on potential quality indicators. PATIENTS AND METHODS: Following initial teaching of two staff surgeons (PMS and AHH) by RJ Heald, 164 consecutive patients were analyzed. The following quality indicators were evaluated: (a) frequency of local recurrence, (b) number of resected lymph nodes, (c) selection of operative technique depending on tumor localization, (d) use of a protective loop ileostomy, and (e) frequency and type of adjuvant therapy. RESULTS: Local recurrence rate was 8.5% after a minimum follow-up of 5 years. An increasing pT category (p < 0.02) and the presence of lymph node metastases (pN+, p < 0.05) were significantly associated with local recurrence rates. The number of resected lymph nodes was significantly associated with nodal metastases rate (p < 0.02). Patients with distal third rectal cancer underwent significantly more often an abdominoperineal amputation (p < 0.0001). Clinical course, but not the rate of anastomotic leakage (9.5%) itself was influenced by using a protective loop ileostomy. Forty-two (29.7%) patients received adjuvant therapy; however, local recurrence rate was higher in patients with adjuvant chemo-/radiotherapy (14.2% vs. 6.1%). CONCLUSIONS: The local recurrence rate of 8.5% demonstrates that through consequent implementation of TME excellent onclogical results can be achieved. The number of resected lymph nodes significantly influenced the pN category. The primary construction of a protective loop ileostomy after TME became standard. Neoadjuvant chemoradiation was systematically introduced in order to improve local tumor control and prevent abdominoperineal amputations. No conclusions can be drawn concerning adjuvant therapy.
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Indicadores de Calidad de la Atención de Salud , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Fuga Anastomótica , Quimioterapia Adyuvante , Demografía , Femenino , Humanos , Ileostomía , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Recto/tratamiento farmacológicoRESUMEN
BACKGROUND: We analyzed perioperative platelet counts as a potential clinical marker for survival after transthoracic en bloc resection for esophageal cancer. Recent data described preoperative thrombocytosis in malignancies to be associated with poor prognosis. METHODS: A retrospective analysis from a prospective database (1997-2006) was performed for 291 consecutive patients with esophageal cancer who underwent transthoracic en bloc esophagectomy and extended lymphadenectomy. Squamous cell cancer was found in 47.0% and adenocarcinoma in 50.9% (2.1% had rare histologies). Neoadjuvant chemoradiation was performed in 152 (52%) patients. Platelet counts before surgery and on postoperative days (PODs) 1, 10, and 30 were evaluated. We used the published cutoff value of 293 × 10(9)/l (mean of 80 healthy controls ± standard deviation) for platelet counts. RESULTS: High platelet counts before surgery missed significance for poorer survival (p = 0.054). Following a perioperative fall in thrombocytes, a significant rise at POD 10 after surgery was evident. Platelet counts of more than 293 × 10(9)/l at this time correlated with a significantly improved survival rate (p = 0.027). Patients with no increase in thrombocytes until POD 10 had significantly poorer survival (p = 0.012). Multivariate analysis confirmed that a thrombocyte increase between the preoperative count and that on POD 10 is an independent prognostic indicator (p = 0.035) for patients with completely (R0) resected tumors. CONCLUSIONS: An increase in platelet counts measured on POD 10 following transthoracic en bloc esophagectomy and extended lymphadenectomy is an independent prognostic indicator for improved survival in patients with esophageal cancer.
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Adenocarcinoma/cirugía , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Trombocitosis/fisiopatología , Adenocarcinoma/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/fisiopatología , Neoplasias Esofágicas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: DPD and TS expression have been shown to correlate with response of 5-FU based chemotherapy in colorectal cancer tissue. Little is known about mRNA expression levels of TS and DPD in peripheral blood. The goals of this study were to test the feasibility of DPD and TS detection in blood and their associations to TNM staging and complete surgical resection. METHODS: Whole blood was drawn 1 day pre- and 10 days post-operatively from 23 patients with rectal cancer. Either adjuvant (n = 15) or neoadjuvant (n = 8) treatment was performed. Tumor cells were enriched from whole blood by density gradient centrifugation prior to extraction of total cellular RNA and subsequent direct quantitative reverse transcriptase-PCR assays. RESULTS: DPD was detectable in 21/23 patients (91.3%) and TS in 14/23 (61.7%). Stepwise multiple linear regression models showed a significant association of DPD expression with distant metastases (P = 0.004) and residual tumor categories (P = 0.03). CONCLUSIONS: Quantitative analysis of TS and DPD mRNA expression in peripheral blood of rectal cancer patients is technically feasible. DPD expression levels appear to be associated with residual tumor categories and might serve as a molecular marker for complete tumor resection. Larger studies seem to be warranted to scrutinize our hypothesis.
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Adenocarcinoma/enzimología , Adenocarcinoma/cirugía , Biomarcadores de Tumor/sangre , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Neoplasia Residual/enzimología , Neoplasias del Recto/enzimología , Neoplasias del Recto/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Quimioterapia Adyuvante , Dihidrouracilo Deshidrogenasa (NADP)/genética , Estudios de Factibilidad , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Periodo Posoperatorio , ARN Mensajero/análisis , Curva ROC , Radioterapia Adyuvante , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Análisis de Regresión , Sensibilidad y Especificidad , Tasa de Supervivencia , Nucleótidos de Timina/metabolismoRESUMEN
BACKGROUND: The purpose of this study was to evaluate the significance of human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity as prognostic markers in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In a series of 69 curatively resected NSCLC specimens, telomerase activity was analyzed with the telomeric repeat amplification protocol (TRAP) assay and expression of hTERT mRNA by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Partitioning of gene expression levels and protein activities to construct prognostic groups was attempted. RESULTS: Human hTERT mRNA transcripts were detected in 62 (89.9%) cases of NSCLC. Seven (10.1%) tumors were completely negative for hTERT expression. Dichotomized hTERT levels (<0.42 versus > or =0.42) were associated with prognosis and Kaplan-Meier survival curves demonstrated a significant difference (log rank: p<0.01) with 5-year survival rates of 44.3% (+/-7.1%) for low as compared to 80% (+/-8.9%) for high hTERT mRNA expression. Low hTERT expression was also significantly associated with squamous cell histology (p<0.03). Telomerase activity was not associated with survival, stage, pT and pN categories, histological type or grading. Comparison of hTERT mRNA expression and telomerase activity was possible in 66 patients and showed a significant difference (p<0.0001) by Wilcoxon rank test. CONCLUSION: This is the first study which demonstrates that high hTERT mRNA expression is associated with improved 5-year survival rates. Expression patterns are distinct among histopathological subtypes of NSCLC and telomerase activity (TRAP) is significantly higher than hTERT mRNA expression.
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Adenocarcinoma/genética , Carcinoma de Células Grandes/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , ARN Mensajero/genética , Telomerasa/metabolismo , Adenocarcinoma/enzimología , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Grandes/enzimología , Carcinoma de Células Grandes/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Telomerasa/genéticaRESUMEN
OBJECTIVE: To prospectively assess the sensitivity (sens), specificity (spec), positive predictive value (ppv), negative predictive value (npv), and accuracy (acc) for clinical response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound (EUS) to determine histomorphologic regression UICC T-category downstaging after neoadjuvant chemoradiation for esophageal cancer. BACKGROUND: Histomorphologic regression is meanwhile established as objective parameter for response and prognosis after neoadjuvant chemoradiation for esophageal cancer. PATIENTS AND METHODS: Within a prospective observation trial, 80 patients with localized esophageal cancers (cT2-4,Nx,M0) received standardized neoadjuvant chemoradiation (cisplatin, 5-fluorouracil, 36 Gy) and were resected by transthoracic en bloc esophagectomy and two-field lymphadenectomy. Tumor regression was based on the percentage of vital residual tumor cells and classified in 4 categories as reported previously. Evaluation by endoscopy and EUS was performed based on WHO/UICC criteria before starting chemoradiation and before resection and rebiopsies were taken at the time of re-endoscopy. RESULTS: Histomorphologic response was of significant (log rank) prognostic importance (P < 0.001), whereas clinical response evaluation by endoscopy (P = 0.1), rebiopsy (P = 0.34), and EUS (P = 0.35) was not. The results of the 3 diagnostic modalities to assess histomorphologic regression by endoscopy and rebiopsy UICC ypT-category downstaging for EUS are summarized: Endoscopy: sens 60%, spec 34%, ppv 49%, npv 44%, acc 47%. Rebiopsy: sens 36%, spec 100%, ppv 100%, npv 24%, acc 47%. EUS: sens 7%, spec 79%, ppv 18%, npv 57%, acc 50%. CONCLUSIONS: Histomorphologic regression is an objective response parameter of significant prognostic importance. The diagnostic accuracy of endoscopy, rebiopsy, and EUS is inadequate for objective response evaluation after neoadjuvant chemoradiation and can be omitted for this purpose in the clinical practice.
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Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Terapia Neoadyuvante , Adulto , Anciano , Biopsia , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Endosonografía , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Esofagectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Dosificación Radioterapéutica , Radioterapia Adyuvante , Medición de Riesgo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Portal vein arterialization is performed in particular situations to guarantee sufficient blood flow in the portal vein. In addition, some authors have postulated a proliferation-promoting influence of portal vein arterialization on the liver tissue. However, portal vein arterialization is an unphysiological procedure: It increases portal blood flow and blood pressure as well as oxygenation of the liver tissue. On the other hand, it reduces the influx of hepatotrophic factors from the portal venous blood. The aim of these experiments was to investigate apoptosis and proliferation of hepatocytes during various conditions of the portal perfusion. MATERIALS AND METHODS: After 70% liver resection in Lewis rats, the following four experimental groups were formed differing in portal perfusion: (I) hyperperfused, nonarterialized; (II) flow-regulated, nonarterialized; (III) hyperperfused, arterialized; (IV) flow-regulated, arterialized. A warm ischemia of 30 min was kept in all groups. RESULTS: Portal vein arterialization of 70% reduced rat livers significantly reduced liver regeneration as shown by a significant reduction in liver weight, body weight, and liver function after 6 wk, in contrast to the group with 70% liver mass reduction and portal venous inflow of the portal vein. Furthermore, we found a significantly elevated number of apoptotic hepatocytes after portal vein arterialization. These results were independent from blood flow regulation of the arterialized portal vein, which caused no improvement of the results. CONCLUSIONS: Portal vein arterialization should be performed only temporarily and is clinically not recommended as a permanent option, because of the increased hepatocellular apoptosis and the very distinctive, negative long-term effects on liver weight.
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Apoptosis , Hepatocitos/fisiología , Regeneración Hepática , Derivación Portocava Quirúrgica , Vena Porta/fisiología , Animales , Proliferación Celular , Masculino , Vena Porta/cirugía , Ratas , Ratas Endogámicas LewRESUMEN
Pim kinases are emerging as important mediators of cytokine signalling pathways in hematopoietic cells, and contribute to the progression of certain leukemias and solid tumors. The mRNA expression of pim-1, a putative oncogenic serine-threonine kinase, was determined in non-small cell lung cancer (NSCLC) patients. Sixty-eight patients with potentially curative resections (R0 resections) for NSCLC in histopathological stages I-IIIA were included. An analysis of pim-1 mRNA expression was performed on paired tumor and normal lung tissue samples by quantitative real-time reverse transcriptase-PCR (RT-PCR) standardized for beta-actin. Pim-1 expression in the tumor (median 0.28) was significantly down-regulated (p<0.0001) compared to the paired normal tissue (median 4.96). Immunohistochemistry showed a strong expression of Pim-1 protein in the normal respiratory epithelium and a lower expression in the tumor cells. A significant association between the pim-1 down-regulation and occurrence of lymph node metastases (p=0.05) was detected. The down-regulation of pim-1 mRNA was demonstrated for 59 out of 68 lung cancer patients (86.8%). Down-regulation occurs already in the early stage of NSCLC and is either directly involved in the lymphatic progression in NSCLC or represents a surrogate marker.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ganglios Linfáticos/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/genética , ARN Mensajero/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Adulto , Anciano , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/secundario , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Regulación hacia Abajo , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Survivin suppresses programmed cell death and regulates cell division. To evaluate the prognostic importance of the apoptosis inhibitor survivin for non-small cell lung cancer (NSCLC), a study was performed in 64 patients with R0 resections for NSCLC and histopathological stages I-IIIA. PATIENTS AND METHODS: Analysis of survivin mRNA expression was performed on 64 paired tumor and normal tissues by quantitative real-time RT-PCR. RESULTS: Survivin expression in tumors (median 3.68, min. 0.19, max. 28.63) was significantly higher (p < 0.04) than in corresponding normal tissues (median 1.68, min. 0.03, max. 155.59). Survivin mRNA was up-regulated in tumors of 42 patients (66%). However, survivin overexpression did not correlate with survival of lung cancer patients. There was no significant association of survivin mRNA levels with histological type (p = 0.29), pT (p = 0.41) and pN categories (p = 0.57), grading of the primary tumor (p = 0.45), or histopathological stage (p = 0.87). CONCLUSION: Overexpression of survivin mRNA in NSCLC might be a marker for noninvasive tumor detection, but has no prognostic importance.
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Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Asociadas a Microtúbulos/biosíntesis , Proteínas de Neoplasias/biosíntesis , ARN Mensajero/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Survivin , Regulación hacia ArribaRESUMEN
PURPOSE: Anastomotic leakage is a major surgical complication following esophagectomy and gastric pull-up. Specific risk factors such as celiac trunk (TC) stenosis and high calcification score of the aorta have been identified, but no data are available on their relative prognostic values. This retrospective study aimed to compare and evaluate calcification score versus stenosis quantification with regards to prognostic impact on anastomotic leakage. PATIENTS AND METHODS: Preoperative contrast-enhanced computed tomography scans of 164 consecutive patients with primary esophageal cancer were evaluated by two radiologists to apply a calcification score (0-3 scale) assessing the aorta, the celiac axis and the right and left postceliac arteries. Concurrently, the presence and degree of stenosis of TC and superior mesenteric artery were recorded for stenosis quantification. RESULTS: Anastomotic leakage was noted in 14/164 patients and 12/14 showed stenosis of TC (n=11). The presence of TC stenosis was found to have a significant impact on anastomotic healing (p=0.004). The odds ratio for the prediction of anastomotic leakage by the degree of stenosis was 1.04 (95% CI, 1.02-1.07). Ten of 14 patients had aortic calcification scores of 1 or 2, but calcification scores of the aorta, the celiac axis and the right and left postceliac arteries did not correlate with the corresponding TC stenosis values and showed no influence on patient outcome as defined by the occurrence of anastomotic insufficiency (p=0.565, 0.855, 0.518 and 1.000, respectively). Inter-reader reliability of computed tomography analysis and absolute agreement on calcium scoring was mostly over 90%. No significant differences in preoperative comorbidities and patient characteristics were found between those with and without anastomotic leakage. CONCLUSION: Measurement of TC stenosis in preoperative contrast-enhanced computed tomography scans proved to be more reliable than calcification scores in predicting anastomotic leakage and should, therefore, be used in the risk assessment of patients undergoing esophagectomy and gastric pull-up.
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BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) expression was reported to be associated with tumor growth, progression and resistance to radio-/chemotherapy. Whether HIF-1alpha mRNA or protein expression is associated with histomorphological response or prognosis following neoadjuvant chemoradiation and surgery in resectable, locally-advanced esophageal cancer was analyzed. PATIENTS AND METHODS: Fifty-three patients received neoadjuvant chemoradiation (cisplatin, 5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. HIF-1alpha mRNA and protein expressions were analyzed by quantitative RT-PCR and immunostaining. RESULTS: In squamous cell carcinoma, HIF-1alpha mRNA expression was significantly higher than in paired normal epithelium (p < 0.001). Normal squamous epithelium showed significant elevated expression in adenocarcinomas, suggesting a field effect (p < 0.04). HIF-1alpha protein expression showed a significant regulation following chemoradiation. Neither HIF-1alpha mRNA nor protein expression was associated with histomorphological regression or prognosis. CONCLUSION: HIF-1alpha mRNA expression is differentially upregulated in esophageal squamous cell carcinoma compared to adenocarcinomas, but does not predict tumor regression or prognosis.
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Neoplasias Esofágicas/terapia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , ARN Mensajero/genética , Adulto , Anciano , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapy- and radiotherapy-induced apoptosis. We analyzed the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal cancer. EXPERIMENTAL DESIGN: Fifty-two patients with resectable esophageal cancers (cT2-4, Nx, and M0) received neoadjuvant radiochemotherapy (cisplatin, 5-5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumor cells. RNA was isolated from endoscopic biopsies (paired tumor and normal tissue) before neoadjuvant treatment and quantitative real-time reverse transcriptase-PCR (Taqman) assays were done to determine COX-2 mRNA expression levels standardized for beta-actin. COX-2 protein expression in pretreatment biopsies and post-therapeutic resection specimens was analyzed by immunostaining of tumor cells. RESULTS: Median COX-2 mRNA expression levels were significantly (P < 0.0001) different between paired tumor (median, 2.2) and normal tissues (median, 0.159). Comparison of pre-therapeutic and posttherapeutic specimens showed a significant difference (P < 0.006) in COX-2 protein expression. Twelve of 52 tumors showed down-regulation and 3 of 52 showed up-regulation of COX-2 protein expression during neoadjuvant radiochemotherapy. High COX-2 protein expression in post-therapeutic resection specimens was significantly associated with minor histopathologic response (P < 0.04) and poor prognosis (5-year survival probabilities: 26.3 +/- 8.2% for minor and 58.6% +/- 12.9% for major histopathologic response; P < 0.01). CONCLUSION: High COX-2 protein expression following neoadjuvant radiochemotherapy in resection specimens is significantly associated with minor histopathologic response to neoadjuvant therapy and very poor prognosis.
Asunto(s)
Ciclooxigenasa 2/genética , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/terapia , Regulación Enzimológica de la Expresión Génica , Terapia Neoadyuvante , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Cisplatino/administración & dosificación , Terapia Combinada , Ciclooxigenasa 2/metabolismo , Endoscopía , Neoplasias Esofágicas/patología , Esofagectomía , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , ARN Mensajero/metabolismo , Radioterapia Adyuvante , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
AIM: We examined quantitative mRNA expression of growth factor receptors (c-erbB-1, c-erbB-2) and the anti-apoptosis gene survivin known to be regulated in pancreatic adenocarcinomas and compared the expression pattern with that in carcinomas of the papilla of Vater. METHODS: Quantitative real-time reverse transcriptase-PCR (QRT-PCR, Taqman) was performed to analyze mRNA expression levels of c-erbB-1, c-erbB-2 and survivin in normal and corresponding tumor samples of 31 pancreatic adenocarcinomas and 8 cancers of the papilla of Vater. RESULTS: The overall median mRNA expression of survivin was significantly increased in both adenocarcinoma of the pancreas (P<0.01) and papilla of Vater (P<0.008) compared with uninvolved normal control tissue. In pancreatic cancer, expression of c-erbB-1 was significantly decreased compared with the normal pancreatic tissue (P<0.03), whereas in the cancer of the papilla of Vater expression of c-erbB-2 was significantly downregulated (P<0.05) compared with the paired normal samples. Gene expression was not associated with tumor stage, differentiation or prognosis. CONCLUSION: The common anti-apoptosis gene survivin is overexpressed both in the cancer of the papilla of Vater and pancreas. In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.
Asunto(s)
Adenocarcinoma/metabolismo , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/metabolismo , Receptores ErbB/metabolismo , Neoplasias Pancreáticas/metabolismo , ARN Mensajero/genética , Receptor ErbB-2/metabolismo , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Conducto Colédoco/genética , Receptores ErbB/genética , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis , Masculino , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/genética , ARN Mensajero/metabolismo , Receptor ErbB-2/genética , Estudios Retrospectivos , Tasa de Supervivencia , SurvivinRESUMEN
OBJECTIVE: Chylothorax is a major complication after esophagectomy. As recent studies refer to heterogeneous patient cohorts and surgical procedures, this study was conducted to report the incidence and evaluate the optimal management of chylous fistula in patients treated with transthoracic esophagectomy and 2-field lymphadenectomy for esophageal cancer. METHODS: From January 2005 to December 2013, a total of 906 patients underwent transthoracic esophageal resection for esophageal carcinoma at our institution. En bloc esophagectomy was performed with routine supradiaphragmatic ligation of the thoracic duct. The incidence of chylothorax, and associated morbidity and mortality, were analyzed, and subsequent therapeutic management was reviewed. RESULTS: Chylothorax after Ivor Lewis esophagectomy was observed in 17 (1.9%) patients. Fifteen patients required surgical intervention with rethoracotomy and repeat duct ligation. Thoracic duct ligation was successful in all patients. Two patients died within 90 days after primary esophageal resection. The median time between initial tumor resection and rethoracotomy was 13 days. Average daily chest-tube output at time of reoperation was 1900 mL. In 2 patients, pleural effusion did not exceed 1000 mL per day. In these cases, conservative management with additional thoracic drainage and total parenteral nutrition led to complete resolution of chylous fistula. CONCLUSIONS: Occurrence of chylothorax after prophylactic thoracic duct ligation during transthoracic esophagectomy for esophageal cancer is rare. In patients with high-output chylous fistula, an early rethoracotomy with repeat ligation of the thoracic duct is safe and helps to shorten recovery time. In cases of low-volume drainage, a conservative approach is feasible.
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Quilotórax/prevención & control , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Conducto Torácico/cirugía , Toracotomía/métodos , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Quilotórax/etiología , Estudios de Cohortes , Manejo de la Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Femenino , Estudios de Seguimiento , Alemania , Hospitales Universitarios , Humanos , Ligadura/métodos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Toracotomía/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Mitochondrial DNA (mtDNA) is known for high mutation rates caused by lack of protective histones, inefficient DNA repair systems, and continuous exposure to mutagenic effects of oxygen radicals. We examined the frequency of mutations in the mtDNA D-Loop region in 20 patients with Barrett's carcinoma and associated Barrett's epithelium by automated DNA sequencing. Mutations were detected in eight of 20 (40%) patients in tumor and/or tumor-associated Barrett's epithelium. In six of eight positive cases, the mutations were detected only in the tumor, one of eight showed mutations in tumor and Barrett's epithelium, and one of eight only in Barrett's epithelium. The degree of dysplasia in Barrett's epithelium was classified low-grade in one and high grade in the two specimens. There was no association of mtDNA D-Loop mutations with histopathological stage of disease or tumor grading. We present the first study of frequent occurrence of mutations in the mtDNA D-Loop regions in adenocarcinomas in Barrett's esophagus. Furthermore, this study supports the hypothesis that oxidative damage might be a mechanism for the induction of adenocarcinoma in Barrett's esophagus. Since mutations were identified in tumor-associated dysplastic Barrett's epithelium, they also might become a marker for the malignant potential of Barrett's epithelium.
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Adenocarcinoma/genética , Esófago de Barrett/genética , ADN Mitocondrial/genética , Mutación/genética , Secuencia de Bases , Análisis Mutacional de ADN , Humanos , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: To find out if neoadjuvant therapy could alter tumor response determinants that might affect tumor sensitivity to the treatment, we investigated intratumoral expressions of genes associated with chemosensitivity, radiosensitivity, or both before and after radiochemotherapy. STUDY DESIGN: Twenty-four patients with locally advanced, resectable esophageal cancer (cT2-4,Nx,M0) received neoadjuvant 5-FU/cisplatin/36 Gy treatment followed by transthoracic en bloc esophagectomy. Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, excision repair cross-complementing gene 1 , glutathione S-transferase Pi, epidermal growth factor receptor, and HER2 were measured in matched preradiochemotherapy endoscopic tumor biopsies and in postradiochemotherapy resection specimens. mRNA was isolated from formalin-fixed, paraffin-embedded, laser microdissected tumor tissues, and a quantitative fluorescent dye real-time reverse transcription polymerase chain reaction system was used for gene expression measurement. RESULTS: There was a significant reduction in the expression levels of thymidylate synthase (p < 0.01), dihydropyrimidine dehydrogenase (p = 0.03), excision repair cross-complementing gene 1 (p < 0.01), glutathione S-transferase Pi (p = 0.03), HER2 (p < 0.01), and epidermal growth factor receptor (p = 0.04). The change in the levels of epidermal growth factor receptor mRNA in post- compared with pretreatment specimens was significantly associated with the histopathologic grade of regression (p = 0.01). CONCLUSIONS: The expression levels of a set of genes that are possible determinants of 5-FU/cisplatin/radiation therapy antitumor activity are significantly downregulated by neoadjuvant radiochemotherapy in esophageal cancer.