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BACKGROUND: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC. PATIENTS AND METHODS: Patients with completely resected p-stage IB-IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs. RESULTS: We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73-1.23; P = 0.69). CONCLUSION: Although GEM-based adjuvant therapy for patients with completely resected stage IB-IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Desoxicitidina/análogos & derivados , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Tegafur , Uracilo/uso terapéutico , GemcitabinaRESUMEN
BACKGROUND: This study was aimed to examine the significance of fluorodeoxyglucose positron emission tomography in predicting prognosis after segmentectomy in lung cancer. METHODS: This was a retrospective cohort study, including 227 patients with cT1N0M0 nonsmall cell lung cancer who underwent positron emission tomography followed by segmentectomy between 2012 and 2019. Significance of tumor histology, T-stage, tumor size, and standardized uptake value on positron emission tomography in relation to recurrence-free survival were examined using Cox's proportional hazard analysis. Median follow-up period was 56 months (range: 1-95 months). RESULTS: Tumor stages were Tis in 25 patients, T1mi/T1a in 51, T1b in 98, and T1c in 53. Twenty-six patients (11%) experienced recurrences, including local (n = 8) and distant (n = 18). Multivariate analysis showed that the significant variables for recurrence-free survival were T-stage and standardized uptake value (p = 0.002 and 0.015, respectively), whereas tumor histology and tumor size were not significant (p = 0.28 and 0.44, respectively). When tumor size was divided into ≤2 cm and >2 cm for analysis, it was not significant again (p = 0.49), whereas standardized uptake value remained significant (p = 0.008). While standardized uptake value of tumors with recurrences was significantly higher than those without (4.9-2.8 and 2.6-2.5, respectively, p < 0.001), there was no significant difference between local and distant recurrences (p = 0.32). Cut-off value of standardized uptake value for recurrences was 3.2. Five-year recurrence-free survival rates in tumors with standardized uptake value <3.2 and ≥3.2 were 86 and 65%, respectively (p < 0.001). CONCLUSION: Positron emission tomography could predict the prognosis after segmentectomy better than tumor size.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía , Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Valor Predictivo de las Pruebas , Radiofármacos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga TumoralRESUMEN
For extrahepatic recurrence after primary hepatocellular carcinoma resection, molecular targeted therapy is the first- choice and no consensus is reached on the indication of surgical resection of extrahepatic metastasis. However, when the extrahepatic lesion extends to vena cava, tumor thrombus can cause acute pulmonary embolism that can lead to fatal consequences. Here, we experienced a case of multiple metachronous metastases from hepatocellular carcinoma to thoracic spine and right adrenal invading right kidney with tumor thrombus in the inferior vena cava. Local radiation therapy to thoracic vertebra, molecular targeted therapy, and transcatheter arterial chemoembolization were performed but tumor thrombus still occluded vena cava. Therefore, to prevent pulmonary embolism and to bridge to immunotherapy, right adrenalectomy, right nephrectomy, thrombectomy and replacement of inferior vena cava were performed. The patient remains healthy 6 months after the surgery and still receiving immunochemotherapy.
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Carcinoma Hepatocelular , Carcinoma de Células Renales , Quimioembolización Terapéutica , Neoplasias Renales , Neoplasias Hepáticas , Trombosis , Carcinoma Hepatocelular/cirugía , Carcinoma de Células Renales/cirugía , Humanos , Riñón , Neoplasias Renales/cirugía , Neoplasias Hepáticas/cirugía , Nefrectomía , Columna Vertebral , Trombectomía , Trombosis/cirugía , Vena Cava InferiorRESUMEN
S-1 plus oxaliplatin(SOX)chemotherapy is now widely used for the treatment of unresectable gastric cancer but there are few case reports about conversion surgery following SOX. Hereby, we report a case of type 4 gastric cancer with peritoneal dissemination successfully treated with conversion surgery after intensive SOX chemotherapy. A 69-year-old female was diagnosed of type 4 gastric cancer by upper endoscopy(por1, HER2 negative)and peritoneal disseminations were identified on left diaphragm and mesentery under direct vision. After 11 courses of SOX chemotherapy, CT revealed that primary tumor markedly decreased in size. Therefore, staging laparoscopy was performed and peritoneal disseminated lesions disappeared. Peritoneal cytology also turned negative. Subsequently, total gastrectomy and splenectomy were performed. Histology revealed that tumor was categorized as por2, ypT2N3M0, ypStage â ¢A, and Grade 2 in histological evaluation criteria. SOX was continued as an adjuvant chemotherapy for another 6 months and the patients remain healthy without recurrence. Unresectable gastric cancer with peritoneal dissemination can be successfully treated with conversion surgery following SOX chemotherapy and staging laparoscopy was useful to evaluate peritoneal dissemination. When conversion surgery is indicated for gastric cancer with peritoneal dissemination, downstaging should be confirmed by staging laparoscopy.
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Neoplasias Gástricas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Combinación de Medicamentos , Femenino , Gastrectomía , Humanos , Recurrencia Local de Neoplasia , Oxaliplatino/uso terapéutico , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Tegafur/uso terapéuticoRESUMEN
PURPOSE: Non-small cell lung cancer (NSCLC) involving the chest wall is usually treated with en bloc rib resection or parietal pleurectomy; however, the former causes chest wall deformity and the latter is associated with local recurrence. To prevent both these sequalae, we performed the "ribcage" procedure for tumors involving the chest wall after induction chemoradiotherapy. METHODS: This was a single center retrospective study conducted from 2012 to 2018. The "ribcage" procedure is designed to preserve the ribs of patients with lung tumors involving chest wall and involves peeling the intercostal muscles and periosteum from the ribs, resulting in a birdcage-like appearance. Seventeen patients with NSCLC clearly involving the chest wall, but not destroying the ribs, were treated with induction chemoradiotherapy, followed by the ribcage procedure. A negative margin at the ribs was confirmed by intraoperative frozen sections in 16 of these patients, who then underwent the ribcage procedure. RESULTS: Complete resection was achieved in all 16 patients, none of whom experienced major postoperative complications. After a median follow-up period of 37 months, there was no evidence of local recurrence in any of the patients. CONCLUSION: Our findings suggest that the ribcage procedure is the preferable surgical option as it can prevent chest wall deformities as well as local recurrence.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioradioterapia Adyuvante , Neoplasias Pulmonares/cirugía , Terapia Neoadyuvante , Pleura/cirugía , Costillas/cirugía , Procedimientos Quirúrgicos Torácicos/métodos , Pared Torácica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSES: To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. METHODS: Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. RESULTS: In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 ± 8 and -53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 ± 5 and -58 ± 3 °C, respectively. CONCLUSION: Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.
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Criocirugía/instrumentación , Criocirugía/métodos , Geles , Pulmón/patología , Pulmón/cirugía , Nitrógeno/uso terapéutico , Animales , Frío , Neoplasias Pulmonares/cirugía , Modelos Animales , PorcinosRESUMEN
PURPOSES: To assess whether a video-assisted thoracoscopic surgery (VATS) procedure is superior to limited thoracotomy (LT) for segmentectomy; postoperative pain was compared between VATS-lobectomy (VATS-L) and LT-segmentectomy (LT-S). Widely opened anterolateral thoracotomy segmentectomy (WT-S) was used as a control. METHODS: This study was a retrospective analysis of prospectively collected data for 220 consecutive patients with stage I NSCLC treated between 2012 and 2015 at a single institute using VATS-L (n = 58), LT-S (n = 93), or WT-S (n = 69). Pain scores from postoperative days (POD) 1-4 were measured using a visual analog scale three times a day. Chronic pain was assessed by the need for analgesics at 1, 2, and 3 months postoperatively. RESULTS: No significant differences in pain from POD 1 to 4 were observed between VATS-L and LT-S, whereas WT-S showed significantly higher pain scores than these two procedures (p = 0.0001-0.02). Chronic pain did not differ significantly among the procedures. CONCLUSION: Postoperative pain does not differ significantly between VATS-L and LT-S. LT may be preferable to VATS for segmentectomy to identify the anatomy, dissect the hilar nodes, and establish surgical margins.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Márgenes de Escisión , Dolor Postoperatorio/prevención & control , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Toracotomía/métodos , Anciano , Femenino , Humanos , Pulmón/anatomía & histología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSES: Sentinel node identification using indocyanine green (ICG) is not only simpler, but also more cost-effective, than using radioisotope tracers. We herein examined the utility and pitfalls of sentinel node (SN) identification using ICG during segmentectomy in patients with cT1N0M0 non-small cell lung cancer (NSCLC). METHODS: ICG was injected around the tumor after thoracotomy, followed by segmentectomy and lymph node dissection, in 135 patients with cT1N0M0 NSCLC. The dissected nodes were examined using an ICG fluorescence imaging system. RESULTS: SNs could be identified in 113 patients (84 %). The mean number of SNs was 2.3 ± 1.3. The percentages of being an SN were 57 % for both stations #12 and #13, which was significantly higher than the 18 % for #10 and 22 % for #11 (p < 0.001). Fourteen patients had N1 or N2 disease. Of these, the SNs were true positive (i.e., SNs contained metastasis) in 11 patients (79 %) and false negative (i.e., SNs did not contain metastasis, while non-SNs contained metastasis) in three patients (21 %). Of the three patients with false-negative results, all non-SNs containing metastases were at station #12 or #13. CONCLUSION: While ICG makes it simple to identify SNs during segmentectomy for cT1N0M0 NSCLC, stations #12 and #13 should be submitted for frozen sections along with the identified SNs to avoid missing true SNs.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Verde de Indocianina , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/patología , Anciano , Reacciones Falso Negativas , Femenino , Fluorescencia , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
PURPOSES: One of the limitations of fluorodeoxyglucose-positron emission tomography (PET) for N-staging in non-small cell lung cancer (NSCLC) is false-positive results due to lymphadenitis. This study was performed to examine whether DWI can correctly identify false-positive nodes on PET in NSCLC. METHODS: Both PET and DWI were performed in 157 patients before surgery, which involved dissection of 1033 nodal stations. Of the 157 patients, 26 patients had pathological N1 or N2 disease. Each nodal station was classified as positive or negative on PET and DWI according to the cutoff value determined by the receiver operating characteristic curve. Short-axis diameters of lymph nodes were measured on computed tomography. RESULTS: While hilar nodes did not show significant differences in the number of false-positives between PET and DWI, DWI showed fewer false-positives than PET in the mediastinum (p = 0.011). Of the 43 false-positive mediastinal nodes on PET, 35 (81 %) were negative on DWI. The mean size of the 43 false-positive nodes on PET was 9 ± 1 mm, which was significantly larger than mean size of 7 ± 3 mm of the 24 false-positive nodes on DWI (p = 0.002). CONCLUSIONS: DWI can correctly identify false-positive nodes on PET in the mediastinum. The larger size of false-positive nodes on PET could be due to enlargement by lymphadenitis.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Imagen de Difusión por Resonancia Magnética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Ganglios Linfáticos/diagnóstico por imagen , Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Reacciones Falso Positivas , Femenino , Humanos , Linfadenitis/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana EdadRESUMEN
PURPOSES: To examine whether diffusion-weighted magnetic resonance imaging (DWI) is as useful as fluorodeoxyglucose positron emission tomography (FDG-PET) for discriminating between malignant and benign pulmonary nodules measuring less than 3 cm in size, as well as for predicting tumor aggressiveness. METHODS: PET and DWI were carried out on 87 pulmonary nodules measuring from 1 to 3 cm in size (66 NSCLCs and 21 benign nodules). The signal intensity (SI) of DWI was measured by the contrast ratio (CR) between the lesions and spinal cord, i.e., SI-CR. The maximum standard uptake value (SUV) of PET was measured by CR between the lesions and contralateral lung, i.e., SUV-CR. RESULTS: DWI and PET showed sensitivities of 0.86 and 0.71, and specificities of 0.90 and 0.81, respectively. While there was no significant difference in the specificity between the two, DWI showed a significantly higher sensitivity than PET (p = 0.013). While the difference in the sensitivity was significant in lung adenocarcinoma (p = 0.012), there was no difference in the other histological types. Both the SI-CR and SUV-CR were significantly higher in the tumors with either histological invasiveness or lymphatic metastasis than in those without. CONCLUSIONS: DWI is thus considered to be useful, not only to diagnose NSCLCs, especially in lung adenocarcinoma, but also for predicting tumor aggressiveness as well as FDG-PET.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Imagen de Difusión por Resonancia Magnética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Nódulos Pulmonares Múltiples/diagnóstico , Nódulos Pulmonares Múltiples/patología , Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
While the use of segmentectomy to treat lung cancer remains controversial, it has recently gained status as a radical surgery for cT1aN0M0 non-small cell lung cancer. I herein review the literature regarding segmentectomy and present my data to discuss the following issues: the prognosis after segmentectomy; local recurrence; the area required for lymph node dissection at the hilum and mediastinum; the technique used to cut the intersegmental plane; the selection of the lymph nodes for frozen sections; the postoperative pulmonary function; the role of completion lobectomy after radical segmentectomy for cT1N0M0/pN1-2; expectations and concerns regarding the randomized controlled trial JCOG0802; and the future of segmentectomy.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Escisión del Ganglio Linfático , Masculino , Mediastino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neumonectomía/mortalidad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Resistance to erlotinib in lung cancer cases includes T790M mutant epidermal growth factor receptor and c-Met gene amplification, but other unknown mechanisms account for about 30% of the resistance. Activation of the nuclear factor kappa B (NFkappaB)-related pathways in association with the reduction in ikappaB level may be one of such potential mechanisms. It is known that curcumin inhibits the inducible activation of NFkappaB at least in part by sustaining ikappaB expression level. Therefore, we evaluated the effects of coadministration of erlotinib and curcumin on lung cancer cells. We found that erlotinib and curcumin augmentatively reduced cell viability. Studies in PC9 cells showed that induction of apoptosis was involved. Expression of ikappaB was elevated in PC9 cells by curcumin administration, and pretreatment with siRNAs for ikappaB significantly attenuated the reduction in cell viability after coadministration of erlotinib and curcumin. Furthermore, coadministration of erlotinib and/or curcumin augmentatively attenuated the growth of PC9 tumors in mice. These results suggested the existence of an augmentative tumor growth inhibitory effect between erlotinib and curcumin, and this effect was at least in part mediated by the increase in the expression of ikappaB induced by curcumin.
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Supervivencia Celular/efectos de los fármacos , Curcumina/farmacología , Neoplasias Pulmonares/patología , Quinazolinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Clorhidrato de Erlotinib , Humanos , Proteínas I-kappa B/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Interferencia de ARNRESUMEN
Chest computed tomography (CT) revealed a focal ground glass opacity (GGO) with a minimal solid area in a 75-year-old man. The shadow was located in the periphery of the right upper lobe and measured 11 mm in diameter. The patient had a medical history of metachronous prostate and gastric cancers. The patient had been treated with androgen deprivation therapy for prostate cancer for 12 years and underwent subtotal gastrectomy for triple gastric cancers 7 months before. Since primary lung adenocarcinoma was suspected, CT-assisted percutaneous needle biopsy was performed. Histology revealed the sheet-like and trabecular proliferation of atypical cells, suggesting that the lesion was moderately to poorly differentiated adenocarcinoma. Adenocarcinoma cells showed subepithelial extension causing the thickening of alveolar walls. A tumor thrombus was not detected in the blood or lymphatic vessels. Immunohistochemistry revealed that carcinoma cells were negative for cytokeratin 7 (CK7), CK20, thyroid transcription factor-1 and CDX2 and positive for prostate-specific antigen and P504S. Based on these findings, the patient was diagnosed with metastatic carcinoma from prostate cancer. The disease remained stable for 4 months after the diagnosis, and no new lesions were observed on chest CT. Metastatic carcinoma rarely presents with focal GGO. Lung biopsy is necessary to identify the pathology of the lesion, and the primary site needs to be confirmed by immunohistochemistry with specific markers, particularly in a case of metachronous multiple cancers. A tumor thrombus, which is suggestive of lymphangitic carcinomatosis or pulmonary tumor thrombotic microangiopathy, also needs to be evaluated.
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OBJECTIVE: We aimed to identify prognostic factors after pulmonary metastasectomy for colorectal cancer and propose the clinical application of them. Furthermore, we endeavored to provide a rationale for pulmonary metastasesectomy. BACKGROUND: Several prognostic factors have been proposed, but clinical application of them remains unclear. Moreover, there is no theoretical evidence that pulmonary metastasectomy is indicated for colorectal cancer. METHODS: We retrospectively analyzed 1030 patients who underwent pulmonary metastasectomy for colorectal cancer from 1990 to 2008. Prognostic factors were identified and the relationship of recurrent sites after pulmonary resection to pulmonary tumor size was assessed. RESULTS: Overall 5-year survival was 53.5%. Median survival time was 69.5 months. Univariate analysis showed tumor number (P < 0.0001), tumor size (P < 0.0001), prethoracotomy serum carcinoembryonic antigen (CEA) level (P < 0.0001), lymph node involvement (P < 0.0001), and completeness of resection (P < 0.0001) to significantly influence survival. In multivariate analysis, all remained independent predictors of outcome. In patients whose recurrent sites extended downstream from the lung via hematogenous colorectal cancer spread, pulmonary tumor size was significantly larger than in those with recurrent sites confined to the lung and regions upstream from the lung. CONCLUSIONS: We should utilize these prognostic factors to detect patients who might benefit from surgery. Therefore, we should periodically follow up advanced colorectal cancer patients by chest computed tomography to detect small pulmonary metastases before serum CEA elevation. Metastases to the lung or organs upstream from the lung are regarded as semi-local for colorectal cancer. This concept provides a rationale for validating surgical indications for pulmonary metastases from colorectal cancer.
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Neoplasias Colorrectales/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estadísticas no Paramétricas , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: Reduction in the level of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of pulmonary emphysema. To this end, pharmacological VEGF receptor blockade, and the Cre-lox system models have been utilized to study the effects of VEGF depletion in the lung. These models generally reproduce air space enlargement resembling clinical emphysema. Here we report a potentially more readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides (siRNAs) in mice. METHODS: Airway administration of VEGF siRNAs were done in C57BL/6 mice. The lungs were removed for histology and protein analysis 2, and 4 days later. Airspace enlargement was evaluated by lung volume measurement, and histological analyses. VEGF levels were analyzed by western blot and immunohistochemistry. RESULTS: Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. VEGF expression was significantly reduced in the lung, particularly in the alveolar septal cells. We also found that in this particular model, sequential airway administration of recombinant VEGF protein attenuated this air space enlargement. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3'-5'-cyclic adenosine monophosphate, and isobutylmethylxanthine attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression. CONCLUSIONS: The pathogenesis of pulmonary emphysema is likely to be multifaceted, but the present mouse model may be useful in dissecting the involvement of VEGF in pulmonary emphysema.
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Enfisema Pulmonar/genética , Enfisema Pulmonar/patología , ARN Interferente Pequeño/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Apoptosis/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/genética , Humanos , Pulmón/metabolismo , Pulmón/patología , Ratones , Enfisema Pulmonar/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
PURPOSE: To describe the computed tomographic (CT) appearance of lung tumors treated with cryoablation to establish a reliable reference profile. MATERIALS AND METHODS: CT images of 56 patients who underwent follow-up CT for at least 1 year for treatment with cryoablation of 79 tumors from 2003 to 2010 were retrospectively reviewed. Patients had a follow-up CT scan immediately after the procedure; 1 day, 1 week (two-phase dynamic CT), and 1 month later; and then at 3-month intervals. The appearance of ablation zones on CT images was classified into five patterns, and bidimensional diameters and other imaging features were evaluated. RESULTS: Seventy-eight percent of ablation zones (62 of 79) showed transformation similar to the following: a consolidation or nodular pattern was seen within the 1-week follow-up, involution and a "stripe" pattern was shown at 1 month or later, and zones later became indistinct. Eighty percent of cases of local progression (eight of 10) arose from the stripe pattern on follow-up CT 6 months or later, after the ablation zones showed a transformation opposite the aforementioned pattern. Ice balls could not always be visualized exactly because of dense peritumoral hemorrhage. Internal and marginal enhancement of the ablation zone within the 3-month follow-up did not show a direct relationship with local progression. In total, cavitation and peritumoral ground-glass opacity were seen in 35% (n = 28) and 85% (n = 66) of ablation zones, respectively. CONCLUSIONS: The reference profile of CT appearance, which is mandatory for follow-up, has been established. No single indicator of complete ablation was proven throughout this study. Careful long-term follow-up with CT is indispensable.
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Criocirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Tomografía Computarizada Multidetector , Criocirugía/normas , Humanos , Japón , Tomografía Computarizada Multidetector/normas , Valor Predictivo de las Pruebas , Valores de Referencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the safety and feasibility of cryoablation for lung tumors as well as the incidence of, and risk factors for, complications. MATERIALS AND METHODS: This study included 193 cryoablation sessions for 396 lung tumors in 117 consecutive patients. Univariate and multivariate analyses were performed to assess risk factors for common complications. Changes in laboratory values were analyzed the day after cryoablation. RESULTS: Pneumothorax, pleural effusion, and hemoptysis occurred after 119 (61.7%), 136 (70.5%), and 71 (36.8%) sessions, respectively. Phrenic nerve palsy, frostbite, and empyema occurred after one session each (0.52%). Proximal tumor implantation was observed in one of 471 punctures (0.20%). Of 119 sessions with pneumothorax, 21 (17.6%) required chest tube insertion and two (1.7%) required pleurodesis. Delayed and recurrent pneumothorax occurred in 15 of 193 sessions each (7.8%). A greater number of cryoprobes was a significant (P = .001) predictor of pneumothorax. Male sex (P = .047) and no history of ipsilateral surgery (P = .012) were predictors for the need for chest tube insertion, and no history of ipsilateral surgery (P = .021) was a predictor for delayed/recurrent pneumothorax. Greater number of cryoprobes (P = .001) and no history of ipsilateral surgery (P = .004) were predictors for pleural effusion. Greater number of cryoprobes (P < .001) and younger age (P = .034) were predictors for hemoptysis. Mean changes in white blood cell count, platelet count, hemoglobin level, and C-reactive protein level were 2,418/µL ± 2,260 (P < .001), -2.0 × 10(4)/µL ± 3.2 (P < .001), -0.77 mg/dL ± 0.89 (P < .001), and 3.0 mg/dL ± 2.9 (P < .001), respectively. CONCLUSIONS: Percutaneous cryoablation could be performed minimally invasively with acceptable rates of complications.
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Criocirugía , Neoplasias Pulmonares/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Criocirugía/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Japón , Modelos Logísticos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/etiología , Radiografía Intervencional/métodos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Malignant pleural mesothelioma is known to be widely resistant to therapy and new treatment strategies are needed. Curcumin, which has a long history as a dietary spice is known to suppress the growth of multiple cancer lines, but the effects on mesothelioma cells are not well defined. In the present study we examined the effects of curcumin on ACC-MESO-1, which is a human derived mesothelioma cell line. We found that curcumin dose-dependently reduced cell viability but did not induce apoptosis. Curcumin administration increased LC3B-II/LC3B-I expression, and induced the formation of autophagosomes on electron microscopy. These changes were attenuated by RNA silencing of atg5. From these findings it was speculated that induction of autophagy was at least in part involved in the reduction of cell viability by curcumin.
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Autofagia/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/farmacología , Mesotelioma/patología , Proteína 5 Relacionada con la Autofagia , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Silenciador del Gen , Humanos , Microscopía Electrónica de Transmisión , Proteínas Asociadas a Microtúbulos/genética , ARN Interferente PequeñoRESUMEN
We report a case of lung cancer producing granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient, a 55-year-old woman, was found to have leukocytosis (leukocytes 28.8 × 10(3)/mm3) with eosinophilia (eosinophils 24.5%) without any evidence of infection or allergy. The serum concentration of GM-CSF was elevated to 44 pg/ml (normal range <2.0 pg/ml), which might have induced the leukocytosis and eosinophilia. We performed left pneumonectomy and diagnosed a pleomorphic carcinoma with p-T2bN0M0, based on histological examination of the resected tumor. Immunohistochemical examination revealed GM-CSF. The serum level of GM-CSF decreased to within the normal range 8 days after surgery. At the time of writing, 16 months after the surgery, she was alive without disease. To our knowledge, this represents the first case report of a GM-CSF-producing tumor effectively treated by surgical resection.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Persona de Mediana Edad , NeumonectomíaRESUMEN
We describe our innovative technique for performing segmentectomy of the posterior segment of the lower lobe of the lung, being segment number 10 (S¹°). In segmentectomy of S¹°, it is difficult to identify A¹° from the interlobar fissure because the pulmonary artery to S¹° (A¹°) branches from A(9+10) and runs dorsally and deeply into the lung tissue. Moreover, to reach S¹° from the interlobar fissure, the lung tissue should be cut between S6 and S8, because S¹° is not located beside the interlobar fissure. However, it is difficult to identify the boundary between the S6 and S8 without a route marker. To solve these difficulties, we divided S6 and S¹° from each other at the beginning of the procedure, which enabled A¹° to be identified easily from the dorsal side. Because S6 and S(8-10) should be divided in S¹° segmentectomy at the end, the division between S6 and S(8-10) at the beginning of procedure is not only reasonable, but makes the procedure simple.