Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

Background: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. Patients and methods: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student’s t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson’s correlation coefficient. Results: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP(p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. Conclusions: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy (AU)

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SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases

Purpose. Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. Patients and methods. A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient’s outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. Results. Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422–0.944) and SMAD4 (HR 1.680, 95 % CI 1.047–2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. Conclusions. The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence (AU)

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Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

Complete response with pegylated liposomal doxorubicin as a second-line therapy in metastatic ovarian carcinosarcoma: Significance of assessment of the response by FDG-PET.

► We present a case report of a patient with an ovarian carcinosarcoma who achieve a complete response with PLD as a second-line therapy. ► There is little evidence regarding the effectiveness of second-line therapies in ovarian carcinosarcoma. ► Our case illustrates that the RECIST criteria is unreliable in predicting the histopathological treatment response in carcinosarcomas. ► FDG-PET was significantly more accurate than size-based criteria.

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes (AU)

Different patterns of toxicity after sequential administration of two anti-EGFR monoclonal antibodies

A 40-year-old woman with liver metastasis resulting from colorectal adenocarcinoma suffered from a severe hypersensitivity reaction to cetuximab. She also experienced grade 3 skin toxicity. The administration of cetuximab was suspended, and she was offered panitumumab as an alternative treatment. Whereas she did not experience another infusion reaction, her skin rash worsened with the administration of panitumumab, a fully human anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb) (AU)

Primary intracranial malignant peripheral nerve sheath tumour responding to chemotherapy

Malignant peripheral nerve sheath tumours (MPNST) are a rare variety of soft tissue sarcomas (STS) arising from major peripheral nerve branches and typically located in the lower extremity, chest wall or the retroperitoneum. It is a biologically aggressive neoplasm for which the treatment of choice is surgery, but usually requires a multimodality approach, having been generally labelled as chemoresistant. We present a case of MPNST located intracranially with a good response to chemotherapy (AU)

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Sarcoidosis as a diagnostic pitfall of pancreatic cancer

Sarcoidosis (SA) is accompanied by malignancy more than can be explained by chance. Cancer can occur in patients with an established diagnosis of SA and SA can subsequently develop in a cancer patient. Malignancy can also be associated with the occurrence of sarcoid reactions (SR), which are typically restricted to the regional lymph nodes. Problems may also arise in distinguishing between tumour-related SRs and true systemic SA. Here we present a case with both SA and pancreatic cancer, and we discuss the result of distinguishing between SA and SRs in a patient with concurrent cancer (AU)

Interposición yeyunal esofagogástrica por vía combinada, abdominal y torácica derecha / Esophagogastric jejunal interposition by right thoraxic and abdominal combined via

Se describe una innovación técnica para la interpretación yeyunal, que está indicada en las estenosis benignas extensas del tercio del esófago. Ella consiste en la realización de este procedimiento por una vía combinada, abdominal y torácica derecha, para lo cual fue necesario desarrollar una técnica original que permitiera el ascenso del segmento yeyunal aislado hacia el tórax, una vez suturada la incisión abdominal. La técnica descrita se practicó en dos pacientes, y se demostró que facilita extraordinariamente la resección del segundo morboso del esófago y la realización de la anastomosis esofagoyeyunal en el tercio medio del esófago torácico. El resultado funcional de la interposición yeyunal fue satisfactorio en ambos pacientes (AU)

Pleurectomía parietal como tratamiento del neumotórax espontáneo. Resultados inmediatos en 15 años / Parietal pleurectomy as treatment for spontaneous pneumothorax. Immediate results within 15 years

Se hace un estudio de los resultados inmediatos de la pleurectomía parietal como tratamiento del neumotórax espontáneo, en un período de 15 años, con 69 pacientes; se analizan las causas que dieron origena la indicación de la operación, los hallazgos operatorios, y las complicaciones, se da una explicación a la posible causa de la manifiesta predominación de las vesículas subpleurales y bullas en el lóbulo superior derecho; se hacen conclusiones (AU)

Pleurectomía parietal en el tratamiento del neumotórax espontáneo / Parietal pleurectomy for spontaneous pneumotorax treatment

Se define el concepto, se precisan las indicaciones, así como algunos detalles de la técnica de la pleurectomía parietal. Se analizan 49 historias clínicas de pacientes operados en nuestro servicio en un lapso de 10 años. Se exponen resultados inmediatos de la totalidad de los pacientes, y tardíos de 17 de ellos(AU)

Páncreas aberrante / Aberrant pancreas

Se estudiaron en un período de diez años en el hospital docente "Enrique Cabrera", 24 casos de pacientes que presentaban páncreas aberrante, de los cuales 8 resultaron diagnóstico biópsico y el resto fueron por hallazgo necrópsico. Se trató de establecer su frecuencia en nuestro medio y se realizaron comparaciones entre todos los casos. Se determinaron los medios diagnósticos indispensables para obtener elevado índice de sospecha, así como su tratamiento quirúrgico definitivo, sin dejar de omitir el estudio hístico intraoperatorio (AU)

Indicaciones y resultados del método de fluorescencia en la cirugía del tracto digestivo / Indications and results of the fluorescence method in digestive tract surgical procedures

Se precisan las indicaciones y la técnica del método de fluorescencia con la fluoresceína sódica, para comprobar introperatoriamente la vascularización de segmentos del tracto digestivo. Se presentan los excelentes resultados obtenidos en los primeros 17 pacientes en quienes se utilizó, durante transposiciones gastrointestinales pediculadas y en la cirugía del colon (AU)

Interposición yeyunal esofagogástrica / Esophagogastric jejunal interposition

Se analizan los objetivos, las indicaciones, la técnica quirúrgica, el tratamiento durante el período posoperatorio y los resultados de la interposición yeyunal esofagogástrica, basándose en una experiencia de 20 pacientes operados en el servicio de cirugía general del hospital docente "General Calixto García", de La Habana, con los cuales dicha técnica tuvo, en general, buenos resultados (AU)

Características clínicas, radiológicas y anatomopatológicas de los tumores insulares no funcionantes del páncreas / Clinical, radiologic and anatomopathologic characteristics of nonfunctionatig isletcell tumors of the pancreas

Se presentan 5 tumores insulares no funcionantes del páncreas, revisándose la frecuencia de esta patología y los elementos clínicos, evolutivos, radiológicos y anatomopatológicos que constribuyen a realizar su diagnóstico precoz y la determinación de su grado de malignidad. Se exponen los caracteres diferenciales con los tumores insulares funcionantes y con los que se originan en el páncreas exocrino (AU)

Tumores malignos no funcionantes de los islotes del páncreas. A propósito de tres observaciones / Malignant non-functionating islet-cell tumors of the pancreas

Se exponen los aspectos clínicos, diagnósticos y terapéuticos de tres pacientes portadores de nesidioblastomas malignos no funcionantes del páncreas. Se destaca lo difícil del diagnóstico clínico e histopatológico de estos tumores. Se señala el valor diagnóstico de la larga evolución desde el punto de vista clínico y la necesidad de realizar estudios histoquímicos y ultramicrocópicos para llegar al diagnóstico de tipo celular de estos tumores insulares. Se enfatiza la importancia del tratamiento quirúrgico aún en presencia de metástasis, debido al buen pronóstico que ofrecen estas lesiones (AU)

Reporte sobre treinta casos experimentales de trasplante de riñón

Una técnica operatoria correcta no produce alteraciones funcionales ni morfológicas en el riñón trasplantado. Los riñones autotrasplantados, a perros, a pesar de haber perdido sus conexiones nerviosas y linfáticas, funcionaron normalmente. El lavado renal empleado por nosotros, tuvo efectos deletéreos sobre el riñón trasplantado, debido posiblemente a no poseer Procaína. La Azathiorine no produjo baja apreciable del número de leucocitos, aunque empleamos una dosis mayor que la reportada, evitando la reacción de rechazo. Solamente en dos perros, que mantuvieron funcionando sus trasplantes durante 20 y 68 días respectivamente (AU)

Incisión abdominal en la anastomosis portocava

Se hace un análisis de las diversas incisiones utilizadas para realizar las anastomosis portocava y se explica la preferencia mantenida durante muchos años por las tóracoabdominales debido al falso concepto de que ellas facilitaban la técnica operatoria. Se demuestra, de acuerdo con los conceptos de Hunt, que la toracofrenolaparotomía aumenta las dificultades técnicas en la realización de esta anastomosis y se exponen las múltiples ventajas de la vía de acceso abdominal. Se describe la técnica empleada por nosotros, que consiste en la posición inclinada del paciente a 45º, la incisión de altura variable de acuerdo con el volumen del hígado y el respeto a la integridad de los ligamentos redondos y falciforme, para evitar la sección de vías venosas colaterales que pueden ser de vital importancia(AU)