SEOM—GECOD clinical guideline for unknown primary cancer (2021)

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.

SEOM-GECOD clinical guideline for unknown primary cancer (2021).

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.

Formulation and attributes of gluten-free cakes of Andean corn improved with green banana flour.

The aim of this work was obtaining layer and sponge cakes formulated with corn flour replaced by green banana flour and to determine the best substitution proportions to achieve nutritionally improved products and with texture and sensory characteristics acceptable. The replacement of corn flour by GB flour increased the density in layer cake batters, while in sponge cake batters the density decreased. The batters were influenced by the increase in the flow properties, the viscoelastic behaviour, and the decrease in the thixotropic properties. The thermal analysis of batters determined a partial gelatinization of the starch, which together with its rheological properties influenced the cakes' texture parameters. The substitution of 30% corn flour by GB flour in sponge and layer cakes produced a decrease in cohesiveness and an increase in hardness. In sponge cakes, incorporation of up to 30% of GB flour improved the sensory attributes and the textural properties, while in layer cakes a 30% substitution did not significantly deteriorate the quality of cakes.

Adjuvant chemoradiation in gastric cancer: long-term outcomes and prognostic factors from a single institution.

BACKGROUND: Adjuvant chemoradiotherapy (CRT) improves relapse-free (RFS) and overall survival (OS) in patients with resected gastric cancer. However, difficulties in standardizing an optimal surgical approach and a perceived higher toxicity compared with the perioperative approach have limited its widespread application in Europe. The aim of our study was to assess toxicity and long-term outcomes of adjuvant CRT at our institution. METHODS: A retrospective review (September 2001-January 2012) was completed of patients with resected gastric cancer who received adjuvant CRT (Macdonald regimen). Adverse events and completion rates, RFS and OS were estimated. Univariate and multivariate analyses of prognostic factors for OS were performed. RESULTS: Eighty-seven patients were included. Most had diffuse (52%) and locally advanced tumors (stage III-IV; 66.7%). D2 lymphadenectomy was performed in 80.5%. The most frequent grade 3-4 toxicities were gastrointestinal (28%) and stomatitis (20%), with 78.2% completing treatment. With a median follow-up of 115 months, 58.5% had relapsed, most of them distantly. Median RFS and OS were 9 and 24 months, respectively. Univariate analysis showed that performance status, stage and lymph node burden were significant factors for OS. In the multivariate study, only stage and lymph node burden remained as independent OS predictors. CONCLUSIONS: Our implementation of the Macdonald regimen achieved worse outcomes than those reported in the INT-0116 trial. The rate of distant relapse remains unacceptably high. Higher rate of positive lymph nodes and of diffuse tumors could explain some differences. The use of perioperative chemotherapy, especially in patients with a poorer prognosis, might improve these results.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

CONTEXT: The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. METHODS: Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. MAIN OUTCOME MEASURES: Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. RESULTS: Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. CONCLUSIONS: Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Characterisation of nutrient profile of quinoa (Chenopodium quinoa), amaranth (Amaranthus caudatus), and purple corn (Zea mays L.) consumed in the North of Argentina: proximates, minerals and trace elements.

Quinoa, amaranth and purple corn are Andean cereals largely consumed in North of Argentina. Nutrient analysis with the purpose of inclusion in the Argentinean FCDB and e-search EuroFIR has become urgent matter. In this work proximate and mineral profile of Andean cereals cultivated in the North of Argentina were determined and compared with rice. Proximate analysis showed that Andean cereals have similar profile but significantly higher (p<0.05) than rice. Andean cereals are rich sources of iron, copper, manganese and zinc and better than rice. Phosphorus and magnesium quinoa content could contribute up to 55% of consumers DRI. Andean cereals and rice are poor sources of potassium. To guarantee the interchange of data among users and producers of FCDB component values were obtained in compliance with EuroFIR guidelines for compilation process. Present work provides necessary information to FCDB users who wish to have access to food reference analytical parameters.

Importancia del pan blanco como fuente de nutrientes: reducción de sodio y fortificación con calcio / Importance of white bread as a source of nutrients: sodium reduction and fortification with calcium

Los hábitos alimenticios son importantes oportunidades que impulsan la elaboración de productos fortificados para satisfacer necesidades nutricionales específicas y carencias detectadas. El pan es uno de los productos que brinda la posibilidad de incorporar ingredientes funcionales y/o suplementarlo mejorando la dieta sin modificar los hábitos alimentarios, y las modificaciones que se produzcan en su composición tendrán importante repercusión en la ingesta de factores de protección y de riesgo. Actualmente las diferentes variedades de pan son también importantes contribuyentes de la ingesta de sodio. El exceso de sodio en la dieta es un determinante de la presión arterial elevada, principal causa de enfermedad y muerte en muchos países. El objetivo del presente trabajo fue investigar el impacto de la reducción de la sal y sustitución por sales de calcio en las características organolépticas y la aceptabilidad de los panes. Se formularon tres recetas con diferentes proporciones de sales de sodio y calcio (20:80; 30:70; 50:50), con un contenido total de 1,8 g sales/100 g harina. El suplemento de calcio consistió en mezcla de CaCl2 y CaCO3 (50:50). El análisis sensorial descriptivo realizado por un panel entrenado indicó que 16 de los 26 atributos sensoriales mostraron diferencias significativas entre el control y los panes sustituidos analizados. Aunque los rasgos sensoriales presentaron diferencias significativas, el panel indicó que aquéllos producidos con la sustitución de 50% NaCl por sales de calcio fueron comparables al control en términos de aceptabilidad. Tecnológicamente es posible sustituir hasta 80% el NaCl por la mezcla de sales de calcio, sin embargo, la aceptabilidad indica que es conveniente reducir solo hasta 50% el NaCl para mantener las características organolépticas. (AU)

Importancia del pan blanco como fuente de nutrientes: reducción de sodio y fortificación con calcio / Importance of white bread as a source of nutrients: sodium reduction and fortification with calcium

Los hábitos alimenticios son importantes oportunidades que impulsan la elaboración de productos fortificados para satisfacer necesidades nutricionales específicas y carencias detectadas. El pan es uno de los productos que brinda la posibilidad de incorporar ingredientes funcionales y/o suplementarlo mejorando la dieta sin modificar los hábitos alimentarios, y las modificaciones que se produzcan en su composición tendrán importante repercusión en la ingesta de factores de protección y de riesgo. Actualmente las diferentes variedades de pan son también importantes contribuyentes de la ingesta de sodio. El exceso de sodio en la dieta es un determinante de la presión arterial elevada, principal causa de enfermedad y muerte en muchos países. El objetivo del presente trabajo fue investigar el impacto de la reducción de la sal y sustitución por sales de calcio en las características organolépticas y la aceptabilidad de los panes. Se formularon tres recetas con diferentes proporciones de sales de sodio y calcio (20:80; 30:70; 50:50), con un contenido total de 1,8 g sales/100 g harina. El suplemento de calcio consistió en mezcla de CaCl2 y CaCO3 (50:50). El análisis sensorial descriptivo realizado por un panel entrenado indicó que 16 de los 26 atributos sensoriales mostraron diferencias significativas entre el control y los panes sustituidos analizados. Aunque los rasgos sensoriales presentaron diferencias significativas, el panel indicó que aquéllos producidos con la sustitución de 50% NaCl por sales de calcio fueron comparables al control en términos de aceptabilidad. Tecnológicamente es posible sustituir hasta 80% el NaCl por la mezcla de sales de calcio, sin embargo, la aceptabilidad indica que es conveniente reducir solo hasta 50% el NaCl para mantener las características organolépticas.

Long-term results with oral fluoropyrimidines and oxaliplatin-based preoperative chemoradiotherapy in patients with resectable rectal cancer. A single-institution experience.

INTRODUCTION: Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new agents such as oxaliplatin may improve efficacy and tolerance. MATERIAL AND METHODS: Between 1999 and 2009, 126 RC patients with T3-T4 and/or N+ disease were given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine-oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4-6 weeks after. Adjuvant treatment was given in all patients. The primary objective was pathologic complete response (pCR). RESULTS: Preoperative therapy was well tolerated, with no toxic deaths and a 15% grade 3-4 toxicity rate. Eighty-five percent of patients received the full chemotherapy dose, 56% had an abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5 years of followup, 92% of relapses had occurred. Median follow-up was 73 months, 5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year overall survival rates were 79% and 66% respectively. There was no benefit from the use of oxaliplatin regarding survival or pCR rates. Older patients had worse long-term outcomes. CONCLUSIONS: Neoadjuvant chemoradiotherapy with oral fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of early progression is low. However, there was no added benefit with the use of oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant chemotherapy is unclear.

Primary meningeal lymphoma of T-cell origin: a rare presentation of primary central nervous system lymphomas.

Primary meningeal lymphoma is a rare clinical entity. Central nervous system infiltration by systemic lymphoma should always be excluded. Diagnosis can be difficult, and prognosis is usually poor. Most are of B-cell origin. We present the case of a young man with a primary meningeal lymphoma of T-cell origin. He was treated with systemic chemotherapy with high-dose methotrexate and cytarabine and intraventricular chemotherapy. He had a clinical improvement and a complete remission, with a long overall survival. There is no standard treatment for this rare disease. Traditionally, treatment has been based in craniospinal radiation therapy and intrathecal chemotherapy, with poor overall results. More recently, systemic chemotherapy with high-dose methotrexate has been advocated, which could avoid the long-term toxicity of craniospinal radiation therapy, and could improve the prognosis of these patients.

Disfunción endotelial, enfermedad coronaria y diabetes mellitus / Endothelial dysfunction, coronary heart disease and diabetes mellitus

Fundamento y objetivo: La diabetes mellitus es un factor de riesgo cardiovascular que propicia la aparición de una lesión endotelial, fundamental en la fisiopatología de la cardiopatía isquémica, por lo que sería útil la investigación de marcadores que indiquen la lesión en pacientes diabéticos. Pacientes y método: Estudio observacional, realizado con 25 pacientes diagnosticados de cardiopatía isquémica y alteración endotelial confirmada mediante coronario grafía, cuyo único factor de riesgo cardiovascular es la diabetes mellitus (grupo I). Tomamos 2 grupos control, uno de 10 sujetos diabéticos sin más factores de riesgo ni clínica de cardiopatía isquémica (grupo II), y otro de 17 sujetos sanos sin factores de riesgo cardiovascular (grupo III). Comparamos entre los grupos la actividad del factor de von Willebrand (FvW) antigénico, como marcador de lesión endotelial. Empleamos como herramientas estadísticas la prueba de la t de Student y la de la 2, el coeficiente de correlación y análisis de regresión múltiple, con un intervalo de confianza del 95%.Resultados: Los pacientes diabéticos tienen mayores concentraciones de FvW que los sujetos sanos; además, los sujetos con cardiopatía isquémica presentan valores más elevados que los diabéticos sin complicaciones vasculares. Se comprueba cierto grado de relación entre las concentraciones de FvW y fibrinógeno en el grupo I. Conclusiones: El FvW es un factor de riesgo de lesión endotelial en diabéticos, y un marcador de riesgo de complicaciones vasculares (AU)

Background and objective: Diabetes mellitus is a cardiovascular risk factor that promotes the development of endothelial injury, which is fundamental in the physiopathology of ischemic heart disease. Therefore, investigation of markers indicating the presence of endothelial injury in diabetic patients would be useful. Patients and method: We performed an observational study of 25 patients with ischemic heart disease and coronary atherosclerosis, diagnosed by coronary angiography, whose only cardiovascular risk factor was diabetes mellitus (group I). There were 2 control groups, one with 10 diabetic controls without ischemic heart disease or other cardiovascular risk factors (group II) and another group with 17 healthy controls (group III). Activity of von Willebrand factor (vWf) antigen, as a marker of endothelial injury, was compared among the groups. Student’s ttest, the 2 test, the coefficient of correlation, and multiple regression analysis, with a 95% confidence interval, were used in the statistical analysis. Results: Diabetic patients had higher vWf levels than healthy controls. Diabetic patients with coronary atherosclerosis had higher vWf levels than diabetics without vascular complications. There was a correlation between vWF and fibrinogen concentrations in group I. Conclusions: vWf is a risk factor for the development of endothelial injury in diabetics and is also a marker of risk for the development of vascular complications in these patients (AU)

Clinical predictors of severe toxicity in patients treated with combination chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer: a single center experience.

INTRODUCTION: Little has been published regarding clinical predictors of severe toxicity in patients with metastatic colorectal cancer (CRC) treated with combination chemotherapy (CT) with oxaliplatin and/or irinotecan. MATERIAL AND METHODS: We analyzed retrospectively 142 patients treated between 1996 and 2004 in our center with these regimes with regards to grade 3-4 toxicity and overall survival (OS) rates. Köhne's prognostic classification could be applied in all patients. RESULTS: Köhne classification: good (54.2%), intermediate (26.8%), and poor prognosis (19%). 50.4% received irinotecan-based CT. Median number of cycles 6 with a total response rate of 38.9%. 23.2% stopped first-line CT due to toxicity. 50.7% suffered grade 3-4 toxicity: digestive (28.2%), hematologic (19.7%), and fatigue (25.4%). 7.7% episodes of neutropenic fever with 4.9% toxic deaths. 70.9% of grade 3-4 episodes occurred in the first four cycles. Median follow-up of 33.9 mo; median OS of 15.9 mo. For Köhne classification: good (20 mo), intermediate (15.8 mo), and poor (6.8 mo). Toxicity analysis: female sex and age > 70 yr predicted higher overall grade 3-4 toxicity, with no differences in CT efficacy; age > 70 yr and PS > 1 predicted higher grade 3-4 fatigue. No relationship could be found between baseline laboratory characteristics and higher toxicity, except baseline hemoglobin and grade 3-4 hematologic toxicity. CONCLUSIONS: Female and elderly patients have a higher grade 3-4 toxicity rate when treated with combination CT with oxaliplatin or irinotecan. Prognostic classifications such as Köhne's can help differentiate subgroups of patients who benefit little with the use of combination CT.

Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis.

Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to the development of tumours. The aim of this work was to investigate HO-1 expression and localization along the different stages of chemically induced hepatocarcinogenesis (HCC) and the occurring morphological changes. To provoke sustained oxidative stress and chronic inflammation, CF1 mice received dietary p-dimethylaminoazobenzene (DAB, 0.5%, w/w) during a whole period of 14 months. HO-1 expression increased along the experimental trial in morphologically normal hepatocytes in DAB-treated animals. HO-1 expression diminished in altered hepatic foci (AHF) and oval cells and early preneoplastic lesions. Otherwise, marked HO-1 overexpression was detected in Kupffer cells and macrophages surrounding necrotic and nodular areas. Adenomas showed decreased HO-1 immunostaining. In hepatocellular carcinomas, an inverse relationship was found between the immunohistochemical expression of HO-1 and the degree of tumour differentiation, being negative in poorly differentiated tumours. In our experimental model, down modulation of HO-1 expression correlated with malignancy progression. Thus, our data point to activation of HO-1 as a potential therapeutic tool.

[Molecular pathogenesis of carcinoma of the esophagus]. / Patogénesis molecular del carcinoma de esófago.

Carcinoma of the esophagus is present in two distinct morphological cell types: squamous or pavimentous cell carcinoma and adenocarcinoma. In this article, the main genetic alterations found in both types of carcinomas and their implications are described. The sequence of these alterations is related to histogenesis, making it possible to understand tumor progression from normal epithelium to invasive carcinoma. A comparison is attempted between the molecular development of esophagus carcinomas and that of colorectal carcinoma.

Patogenesis molecular del carcinoma de esofago / Molecular pathogenesis of carcinoma of the esophagus

El carcinoma de esófago existe en dos formas principales: el carcinoma de células escamosas o pavimentoso y el adenocarcinoma. En este artículo se describen las principales alteraciones genéticas halladas en ambos tipos de carcinomas y la implicancia de éstas en la patogénesis de los mismos. La secuencia de estas alteraciones se correlaciona con la histogénesis, lo que permite comprender la progresión tumoral desde el epitelio normal al carcinoma invasor. Se establece también una comparación entre la patogénesis molecular delcáncer de esófago y del desarrollo de estos carcinomas con el modelo de la patogénesis molecular del cáncer colorrectal.

Patogénesis molecular del carcinoma de esófago. / [Molecular pathogenesis of carcinoma of the esophagus]

Carcinoma of the esophagus is present in two distinct morphological cell types: squamous or pavimentous cell carcinoma and adenocarcinoma. In this article, the main genetic alterations found in both types of carcinomas and their implications are described. The sequence of these alterations is related to histogenesis, making it possible to understand tumor progression from normal epithelium to invasive carcinoma. A comparison is attempted between the molecular development of esophagus carcinomas and that of colorectal carcinoma.

Patogenesis molecular del carcinoma de esofago / Molecular pathogenesis of carcinoma of the esophagus

El carcinoma de esófago existe en dos formas principales: el carcinoma de células escamosas o pavimentoso y el adenocarcinoma. En este artículo se describen las principales alteraciones genéticas halladas en ambos tipos de carcinomas y la implicancia de éstas en la patogénesis de los mismos. La secuencia de estas alteraciones se correlaciona con la histogénesis, lo que permite comprender la progresión tumoral desde el epitelio normal al carcinoma invasor. Se establece también una comparación entre la patogénesis molecular delcáncer de esófago y del desarrollo de estos carcinomas con el modelo de la patogénesis molecular del cáncer colorrectal.(AU)

Análisis molecular del gen P53 y microsátelites en muestras endoscópicas de adenomas y carcinomas de colon / Molecular analysis of P53 gene and microsatellites in endoscopic samples of colonic adenomas and carcinomas

Uno de los eventos moleculares que participa en la secuencia adenoma-carcinoma colorrectal es la presencia de mutaciones en el antioncogen p53, cuyo producto proteico regula el ciclo celular. Asimismo, el análisis de microsatélites es un indicador indirecto de inestabilidad génica en tejido tumoral, permitiendo realizar un screening rápido de todo el genoma. En tejidos frescos y mucosa normal de ocho pacientes, se analizaron molecularmente por PCR-SSCP los exones 4 a 8 del gen p53 y microsatélites. Estos datos fueron correlacionados con el diagnóstico morfológico-inmunohistoquímico (IHQ). Fueron observadas alteraciones del gen p53 en el tejido tumoral en tres de ellos; se encontraron mutaciones puntuales en el exón 6 en dos pacientes: uno portador de un adenoma tubular y otro con un adenoma mixto (túbulo-velloso) ambos con displasia de alto grado y p53+IHQ tenía ua mutación en el exón 7. En un adenocarcinoma con sobreexpresión de p53 por IHQ no se detectaron alteraciones de dicho gen. La presencia de mutación sería un indicador de transformación tumoral y corroboraría el seguimiento más estricto en pacientes con lesiones de alto grado. El análisis de microsatélites en los 8 pacientes no determinó la existencia de anomalías génicas. (AU)

Análisis molecular del gen P53 y microsátelites en muestras endoscópicas de adenomas y carcinomas de colon / Molecular analysis of P53 gene and microsatellites in endoscopic samples of colonic adenomas and carcinomas

Uno de los eventos moleculares que participa en la secuencia adenoma-carcinoma colorrectal es la presencia de mutaciones en el antioncogen p53, cuyo producto proteico regula el ciclo celular. Asimismo, el análisis de microsatélites es un indicador indirecto de inestabilidad génica en tejido tumoral, permitiendo realizar un screening rápido de todo el genoma. En tejidos frescos y mucosa normal de ocho pacientes, se analizaron molecularmente por PCR-SSCP los exones 4 a 8 del gen p53 y microsatélites. Estos datos fueron correlacionados con el diagnóstico morfológico-inmunohistoquímico (IHQ). Fueron observadas alteraciones del gen p53 en el tejido tumoral en tres de ellos; se encontraron mutaciones puntuales en el exón 6 en dos pacientes: uno portador de un adenoma tubular y otro con un adenoma mixto (túbulo-velloso) ambos con displasia de alto grado y p53+IHQ tenía ua mutación en el exón 7. En un adenocarcinoma con sobreexpresión de p53 por IHQ no se detectaron alteraciones de dicho gen. La presencia de mutación sería un indicador de transformación tumoral y corroboraría el seguimiento más estricto en pacientes con lesiones de alto grado. El análisis de microsatélites en los 8 pacientes no determinó la existencia de anomalías génicas.

Infectados HIV de 15 a 49 años durante el período 1986-1992 con residencia en el Partido Gral. Pueyrredón - Bs. As. Argentina / HIV infected patients during the lapse 1986-1992 homebound in the General Pueyrredón County , province Buenos Aires, Argentina

Se estudiaron 506 infectados de HIV en el período entre 1987 y 1992, residentes en el Partido de Gral. Pueyrredón, Pcia. de Bs. As. Se observaron distribución por edad, sexo, tendencia, prevalencia de período, comportamiento sexual, adicción a drogas, vías utilizadas y motivo de la consulta. Los datos secundarios se obtuvieron a través de los registros de notificación de la Zona Sanitaria VIII. La tendencia del proceso se presentó en aumento con incremento mayor en el año 1991. La prevalencia fue de 200 por 100 habitantes de 15 a 49 años. El grupo más afectado el de 20 a 39 años, y la relación entre sexos fue uniforme globalmente, aumentando en algunas edades en las mujeres. En el grupo donde pudo establecerse el mecanismo de transmisión de la infeccion se observó una importante proporción de embarazadas hecho relevante por la implicancia que ello tiene tanto para la madre como para el hijo y la sociedad