Locally advanced rectal cancer: Preliminary results of rectal preservation after neoadjuvant chemoradiotherapy. / Cáncer de recto localmente avanzado: resultados preliminares de la preservación del recto después de quimiorradioterapia neoadyuvante.

INTRODUCTION: The standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumors with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. METHODS: This is a retrospective cohort study (2005-2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. RESULTS: A total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 «Watch and Wait¼ and 7 local resections). Median follow-up was 46 months (interquartile range: 30-68). In the group of «Watch & Wait¼, 4 patients had local recurrence before 12 months (actuarial local recurrence rate=18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9-100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. CONCLUSION: The strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results.

[New method of hepatic regeneration]. / Nuevo Metodo de Regeneracion hepatica.

Postoperative liver failure (PLF) is the most feared and serious complication after extensive liver resections. We present an innovative surgical technique for the treatment of a patient with colorectal cancer and initially unresectable liver metastases. After completing neoadjuvant chemotherapy, it was decided to perform simultaneous surgery. A left hemicolectomy and cleaning of the metastases in the left liver was performed. As the future liver remnant (FLR) was insufficient, it was decided to perform an in situ liver split and a right portal vein ligation. On the 6(th) day after the surgery a volumetric CT showed an increase greater than 40% of the FLR. The right hepatectomy was completed and the patient was discharged on the 11(th) day after surgery. The technique induced a rapid growth of the FLR, exceeding that reported using portal occlusion. If these findings are corroborated in future studies, this revolutionary technique could enable surgery to be performed in two stages on patients with initially unresectable liver disease during the same hospital admission and without PLF.

The neural cell adhesion molecule is involved in the metastatic capacity in a murine model of lung cancer.

Neural cell adhesion molecule (NCAM) is involved in cell growth, migration, and differentiation. Its expression and/or polysialylation appear to be deregulated in many different cancer types. We employed the lung tumor cell line LP07, syngeneic in BALB/c mice to investigate the role of NCAM in malignant progression. LP07 cells express the three main NCAM isoforms, all of them polysialylated. This cells line, pretreated with an anti-NCAM antibody and inoculated intravenously (i.v.) into syngeneic mice, developed less and smaller lung metastases. In vitro studies showed that NCAM bound antibody inhibited cell growth, mainly due to an increase in apoptosis, associated with a decrease of cyclin D1 and enhanced expression of active caspase 3 and caspase 9. Anti-NCAM-treated LP07 cells showed impairment in their ability to migrate and adhere to several extracellular matrix components. Secreted uPA activity was also reduced. NCAM-140 knocked-down by siRNA in LP07 cells pretreated or not with anti-NCAM showed an impaired metastasizing ability upon i.v. inoculation into mice. These results suggest that anti-NCAM treatment could be mimicking homophilic trans-interactions and NCAM-140 knocked-down impairs heterophilic interactions, both leading to inhibition of metastatic dissemination. The involvement of NCAM in lung tumor progression was confirmed in human NSCLC tumors. Sixty percent of the cases expressed NCAM at tumor cell level. A multivariate analysis indicated that NCAM expression was associated with a shorter overall survival in this homogeneous series of Stages I and II NSCLC patients. NCAM may be able to modulate mechanisms involved in lung carcinoma progression and represents an attractive target to control metastatic progression.

Multidisciplinary approach to COVID-19 and cancer: consensus from scientific societies in Argentina.

INTRODUCTION: The world is living through an outbreak of an acute respiratory syndrome caused by a new betacoronavirus known as coronavirus 2 (SARS CoV-2), which has been declared an international public health emergency by the World Health Organisation. Cancer patients are a very special population in this setting since they are more susceptible to viral infections than the general population. Several recommendations have been made on this issue, most of them based on expert opinion and institutional experience. It is essential to gather the evidence available for decision making. OBJECTIVE: To review the evidence available in order to create a multi-institutional position from the perspective of scientific societies in Argentina involved in the management of cancer patients. METHODOLOGY: The review included two phases: 1) search and systematic revision of the medical literature; 2) consensus and revision of the document drafted by national scientific societies involved in the management and care of cancer patients using the modified Delphi method. The final results were presented at a videoconference with all the participants. Also, additional comment and recommendations were discussed. The final document was revised and approved for publication by the members of the panel. RESULTS: The consensus panel included 18 representatives from scientific societies from Argentina who assessed the evidence and then made recommendations for the management of cancer patients in our country. International guidelines (CDC; ASCO, NCCN and ESMO) were considered as a background for analysis, as well as institutional guidelines and an open ad hoc survey administered to 114 healthcare professionals from the scientific societies involved in this study.The recommendations are grouped as follows: 1) general care interventions-training of the personnel, cleaning and disinfection of the hospital premises and patient scheduling; 2) treatment decisions-patient care, surgeries, immunosuppressive therapy, radiotherapy and screening; 3) ethical considerations-optimisation of resources, end-of-life care for critically-ill patients; 4) management of hospitalised patients; and 5) wellbeing of the healthcare team.The general recommendation arising from the study is that the management of cancer patients must adapt to the exceptional pandemic status quo without disregarding treatment or cure options. Moreover, healthcare professional accompaniment of all patients should not be neglected. All healthcare professionals must make a significant joint effort to create multidisciplinary teams to discuss the most appropriate measures for each particular situation. CONCLUSIONS: The scientific evidence available on this topic worldwide is in progress. This together with the epidemiologically shifting scenario poses unprecedented challenges in the management of cancer amidst this global pandemic. Furthermore, the key role of the healthcare structural organisation appears evident, such as the drafting of clear guidelines for all the stakeholders, adaptability to constant change and an interdisciplinary shared vision through consensus to provide adequate care to our cancer patients in the light of uncertainty and fast-paced change.

Pneumo-PET-CT: Initial Results of This Novel Technique on the Evaluation of Esophageal and Gastric Tumors with Anatomic-Surgical Correlation.

We present the initial results of a novel hybrid scanning-based technique that combines pneumo-computed tomography (PNCT) with positron emission tomography (PET) using 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG). We denominate it pneumo-PET-CT. The focus of our discussion will be on the description of the pneumo-PET-CT technique and the interpretation criteria with emphasis on its benefits and applications in the presurgical and postneoadjuvant therapy evaluation of esophageal, esophagogastric junction (EGJ), and gastric tumors.

[Retinoid expression (RARbeta and CRBP1) in non-small-cell lung carcinoma]. / Retinoides (RARbeta y CRBP1) en carcinoma de pulmón a celulas no pequeñas.

Although early-stage non-small-cell lung carcinoma (NSCLC) patients have a relative by favorable prognosis, the risk of a bad outcome remains substantial. Identification of reliable prognostic markers for disease recurrence and death has meaningful clinical application. Retinoids are involved in cell growth and differentiation and may antagonize cancer progression. Their effects are mediated through nuclear receptors called Retinoic Acid Receptor (RAR) and regulated by molecules such as Cellular Retinol-Binding Protein 1 (CRBP1) that function in retinol storage. The aim of this work was to analyze by immunohistochemistry the expression patterns of RARbeta and CRBP1, involved in retinoid-mediated signaling, in the tumoral tissue of a cohort of stage I/II NSCLC patients (n = 49) who underwent a successful surgical resection. Prognostic evaluation was performed with the multivariate Cox proportional hazard model: 44.9% of tumors were positive for RARbeta staining at cytoplasmic level, while 34.7% showed nuclear staining. CRBP1 staining was observed in 61.2% of the lung tumors. No relationship was found between the number of cells expressing the studied molecules and clinical pathological features, including sex, T and N (stage), histopathology and p53 expression. Univariate analysis showed a significant association between positive cytoplasmatic expression of RARbeta with shorter overall survival (Log-rank test 4.17, p = 0.0412). Multivariate studies indicated that RARbeta expression was not influenced by other clinical pathological parameters. In conclusion, in this cohort of stage I and II NSCLC, only the expression of RARbeta at cytoplasmatic level is a significant independent unfavorable prognostic factor.

Expression of CD44s and CD44 splice variants in human melanoma.

The ability of tumor cells to adhere and detach from extracellular matrix and endothelial cells, is a crucial step in the metastatic process and may alter the clinical prognosis of some human tumors such as melanomas. CD44, the major cell surface receptor for hyaluronate, has been implicated in cell adhesion and in tumor progression. We studied the expression of standard CD44 molecule (CD44s) and its variants v3 and v6 in 57 human primary melanoma biopsies, without previous treatment. We analyzed the association between CD44 expression and the principal clinicopathological features, including survival. Fifty-six of 57 tumors expressed CD44s, associated to the cytoplasmic membrane. No expression of CD44v3 or CD44v6 was detected. No association between CD44s expression and prognostic factors such as tumor thickness, growth type, stage or anatomic site of the lesion was found. However, a positive correlation between CD44s expression and Clark level (Spearman, p<0.001) was found. While only 33.3% of melanomas Clark I + II showed high expression of CD44s (more than 50% of positive cells), 82.6% of melanomas Clark IV + V did so. Kaplan-Meier analysis revelead that patients whose melanomas had high expression of CD44s showed a reduced relapse free survival (RFS) rate, though without statistical significance. No difference between the level of CD44 expression and overall survival (OS) was found. We conclude that melanomas only expressed CD44s, and that its level was associated with Clark's stage. CD44s seems not to be useful as a tumor marker, because it does not predict either RFS or OS.

[Predictive response variables to recombinant human erythropoietin treatment in patients with anemia and cancer]. / Variables predictivas de respuesta a la eritropoyetina recombinante humana en pacientes con anemia y cáncer.

The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5% patients an increase in the level of hemoglobin was registered, and in 64.7% its normalisation was attained. Transfusional requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

Cáncer de cavum. Experiencia institucional / Cancer of cavum. Institutional experience

Los carcinomas epidermoides de cabeza y cuello son un grupo poco frecuente de neoplasias, en los Estados Unidos representan aproximadamente el 3% de todos los tumores. El cáncer de cavum se diferencia de otros tumores de cabeza y cuello por su epidemiología, histología, historia natural y respuesta al tratamiento. Presenta una marcada variación geográfica debido a su etiología multifactorial. En las áreas endémicas, la incidencia y la mortalidad han disminuido en los últimos 30 años. Esto probablemente se deba a cambios en el estilo de vida y avances en la radioterapia (RT) y quimioterapia (QT) sistémica (AU)

Epidermoid carcinomas of the head and neck are a rare group of tumors, in the United States they account for 3% of all cancers. Nasopharyngeal carcinoma differs from others head and neck squamous cells carcinomas in epidemiology, natural history, and response to treatment. Nasopharyngeal carcinoma displays a distinct racial and geographic distribution, which is reflective of its multifactorial etiology. The incidence and mortality has declined over the past 30 years in many endemic areas. This finding is probably a result of a combination of lifestyle modification and advances in radiotherapy and effective systemic agents (AU)

Carcinoma epidermoide de orofaringe. Experiencia institucional / Squamous cell carcinoma of the oropharynx. Institutional experience

Los carcinomas epidermoides de cabeza y cuello (CECC), son un grupo poco frecuente de neoplasias, en los Estados Unidos representan el 3.2% de todos los cánceres1,2. Si bien su frecuencia global se encuentra en disminución, los tumores localizados en la orofaringe han aumentado de forma considerable2. El virus del papiloma humano (HPV) es responsable de este aumento. Se ha descripto que los tumores de orofaringe, asociados al HPV, ocurren en pacientes más jóvenes, con enfermedad de bajo volumen a nivel del tumor primario, pero elevada incidencia de metástasis ganglionares, con adenopatías quísticas2,3. La detección del virus del HPV, por inmunohistoquímica (IHQ) o por reacción en cadena de la polimerasa (PCR) son factores pronósticos importantes que siempre deben ser tenidos en cuenta para el tratamiento de estos tumores (AU)

Epidermoid carcinomas of the head and neck are a rare group of tumors, in the United States they account for 3.2% of all cancers. Although their overall frequency is decreasing, tumors located in the oropharynx have increased considerably. Human papillomavirus (HPV) is responsible for this increase. It has been described that oropharyngeal tumors, associated with HPV, occur in younger patients, with low volume disease at the primary tumor level but a high incidence of lymph node metastases, with cystic lymphadenopathy. Detection of HPV virus by immunohistochemistry (IHC) or polymerase chain reaction (PCR) are important prognostic factors that should always be taken into account for the treatment of these tumors (AU)

Cáncer de recto localmente avanzado: resultados preliminares de la preservación del recto después de quimiorradioterapia neoadyuvante / Locally advanced rectal cancer: Preliminary results of rectal preservation after neoadjuvant chemoradiotherapy

Introducción: El estándar de tratamiento del cáncer de recto localmente avanzado es la escisión total del mesorrecto. Sin embargo, la preservación del órgano ha sido propuesta para los tumores con buena respuesta al tratamiento neoadyuvante. El objetivo de este estudio es investigar los resultados oncológicos de esta estrategia. Métodos: Se realizó un estudio de cohorte retrospectivo, en el que se analizó a los pacientes con adenocarcinoma de recto tratados con intención curativa entre 2005 y 2014 que, después de recibir quimiorradioterapia neoadyuvante, presentaron una respuesta clínica completa o casi completa y fueron tratados con preservación del recto. Resultados: Durante el periodo de estudio, 204 pacientes con cáncer del recto recibieron neoadyuvancia. Treinta (14,7%) presentaron una respuesta clínica completa o casi completa y se trataron según una estrategia de preservación de órgano (23 watch & wait y 7 resecciones locales). La mediana de seguimiento fue de 46 meses (rango intercuartil: 30-68). En el grupo de watch & wait, 4 casos presentaron recurrencia local antes del año (tasa actuarial 18,5%). Todos pudieron ser rescatados (2 con cirugía radical y 2 con resecciones locales) sin presentar nuevas recurrencias. El índice de supervivencia libre de enfermedad a distancia a 3 años fue de 94,1% (IC 95%: 82,9-100). De los 7 casos que se trataron mediante resección local, ninguno presentó recurrencia local. Considerando toda la muestra, la proporción de conservación de órgano fue del 93%. Conclusiones: La estrategia de preservación de órgano en el cáncer rectal localmente avanzado es factible en casos con buena respuesta a la neoadyuvancia. Implementada en un grupo altamente seleccionado de pacientes, se asocia con resultados oncológicos satisfactorios (AU)

Introduction: The standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumors with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. Methods: This is a retrospective cohort study (2005-2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. Results: A total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 «Watch and Wait» and 7 local resections). Median follow-up was 46 months (interquartile range: 30-68). In the group of «Watch & Wait», 4 patients had local recurrence before 12 months (actuarial local recurrence rate = 18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9-100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. Conclusion: The strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results (AU)

Mast cell phenotypes and microvessels in non-small cell lung cancer and its prognostic significance.

The impact of interstitial inflammatory cells, such as mast cells, and angiogenesis on the prognosis of cancer patients has been reported in many solid tumors, although there is disagreement about their role. We undertook a retrospective study with tissue samples from 65 patients with stage I and II non-small cell lung cancer to assess the clinical pathologic role and prognostic significance of mast cells. Mast cell phenotypes were identified by immunohistochemistry for tryptase and chymase. In addition, we identified microvessels using the endothelial marker CD34. Mast cell and microvessel density was quantified by assessing immunopositive cells in the intratumoral and peritumoral zones of tumor specimens. Both mast cell and microvessel density was higher in the peritumoral zone than the intratumoral zone (P

Estrogen receptor ß and epidermal growth factor receptor as early-stage prognostic biomarkers of non-small cell lung cancer.

As 20% of stage I NSCLC patients develop recurrent and often incurable cancer, the identification of prognostic markers has a meaningful clinical application. The biological significance of steroid hormone and EGF receptors, able to regulate key physiological functions, remains elusive in NSCLC. Our aim was to investigate the prognostic input of estrogen receptors (ERα, ERß), progesterone receptors (PR) and EGFR in tumors from 58 stage I NSCLC patients. Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate Cox model. We found that about 70 and 40% of samples expressed ERα or ERß at cytoplasmic or nuclear level, respectively. Besides, only 12.1% of samples weakly expressed nuclear PR and 62.7% showed membrane EGFR staining. Correlation studies indicated an inverse association between EGFR expression and smoking status (p<0.01). Multivariate studies showed that the lack of nuclear ERß or the loss of EGFR expression were independent prognosis markers associated with shorter overall survival. We also found that patients whose tumors were negative for these two biomarkers presented the worst outcome. In conclusion, our findings could be useful for selecting stage I NSCLC patients with poor prognosis to apply an earlier treatment that impacts on survival.

Association between mast cells of different phenotypes and angiogenesis in colorectal cancer.

It is known that mast cells proliferate in solid tumours and increase tumour angiogenesis. Nevertheless, there is no consensus regarding their role in colorectal cancer (CRC). In this study, we aimed to clarify the relationship of mast cells positive for tryptase (MCts) and tryptase-chymase (MCtcs) with microvessel density (MVD) in the intratumoral zone and the invasive edge of 80 CRC patient tumours. We evaluated these parameters and associated their expression with clinicopathological parameters, including survival rate. Tumour sections from each patient were immunostained for tryptase to evaluate MCts, chymase to evaluate MCtcs, and CD34 to evaluate microvessel counts under x100 microscopy. The number of MCs of both phenotypes and the MVD counts were higher in the invasive edge than in the intratumoral zone (p<0.001). MCt numbers were higher than those of MCtcs in all Astler-Coller stages in both regions. A positive correlation between MVD and MCts or MCtcs was observed (Pearson's test p<0.001). Neither the number of MCs nor MVD was associated with overall survival (log rank test). However, only 8.3% of patients with low numbers of MCtcs in the invasive edge succumbed to the disease, compared to 32% with high numbers of MCtcs. Our results indicate that angiogenesis and MC hyperplasia are events which appear early during CRC development. The correlation of MC phenotypes with MVD is in agreement with the role attributed to MCs, that of angiogenesis enhancement. Collectively, these findings suggest that screening during the early malignization of CRC can provide valuable clinical information.

Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors.

The neural cell adhesion molecule (NCAM) is involved in the intercellular junctions of neurons and glial cells. We investigated its relevance as a biomarker in gliomas which main characteristic is their high invasiveness. We studied by Western blot the pattern of serum NCAM bands in patients with gliomas (n = 34), with brain metastasis of different primary cancers (n = 27) and with benign brain tumors (n = 22)] compared with healthy controls (n = 69). For densitometric analysis NCAM bands > or = 130 kDa (HMW) and <130 kDa (LMW) were clustered. We observed that glioma patients presented higher NCAM HMW and lower NCAM LMW levels than control subjects (P < 0.01). A similar pattern was found in patients with brain metastasis or brain benign tumors, suggesting that the pattern of serum NCAM bands would be useful to detect brain tumor pathology. On the other hand, serum NCAM expression was not associated with the main clinicopathological features of gliomas, including overall survival. Interestingly, we found that 9/12 patients with glioma showed a significant decrease in NCAM HMW/LMW ratio between 1-3 months after successful tumor removal. Thus, serum NCAM could be a useful marker for monitoring treatment.NCAM expression was also analyzed at tissular level in 59 glioma sections from paraffined tumors. We observed that NCAM immunostaining was inversely correlated with the histological grade of malignancy, remaining this association in a multivariate analysis. Besides, loss of NCAM staining was significantly associated with bad prognosis in an univariate analysis.

Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2) in patients with colorectal carcinoma.

BACKGROUND AND OBJECTIVES: Therapy of colorectal tumors (CRC) based on histology and clinical factors is insufficient to predict the evolution of each patient. The finding of molecular abnormalities able to differentiate subgroups of patients with bad prognosis will improve our ability to treat them successfully. Our purpose was to analyze retrospectively the prognostic input of E-cadherin, beta-catenin, metalloproteinases (MMPs) (7 and 9), and tissue inhibitors of metalloproteinases (TIMPs) (1 and 2) in patients with a follow-up period of 5 years. METHODS: Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate proportional hazards model. RESULTS: We demonstrated a concomitant loss of E-cadherin and beta-catenin at membranous level and an abnormal accumulation of nuclear beta-catenin. Besides, we found that all MMPs and TIMPs studied were overexpressed in CRC tissue. There was no association between the expression of any of these molecules and the known clinical-pathological parameters employed in CRC pathology. A multivariate analysis demonstrated that the overall survival could be independently predicted by the loss of E-cadherin and the overexpression of TIMP-2. CONCLUSIONS: The expression of E-cadherin and TIMP-2 could be relevant in determining the prognosis of CRC patients and providing a more accurate mechanism for their classification.

CD44 expression in human gliomas.

BACKGROUND AND OBJECTIVES: Glioma invasiveness involves the attachment of tumor cells to the brain extracellular matrix, rich in hyaluronic acid (HA). CD44, the principal receptor for HA is found as a standard molecule (CD44s) or as variants (CD44v). We undertook a retrospective study to evaluate the expression pattern of CD44s, the isoforms CD44v3, v4/5 and v6 and to correlate their expression with clinical-anatomopathological parameters and survival rate. METHODS: The expression of these molecules was evaluated immunohistochemically in 84 gliomas. RESULTS: No expression of CD44v was detected in any tumors. CD44s staining of tumor cells was found in 70 of 84 (83.3%) of the gliomas. In 23 of 39 (59.0%) of the GBM more than the 70% of the cells were stained, while only 2 of 21 (9.5%) of LGA showed high expression. The association between CD44 and histological grade remained when the prognostic variables were considered in a multivariate analysis. Higher expression of CD44 was associated with worse overall survival rate; however, the Cox analysis indicated that survival was not associated with CD44. CONCLUSIONS: Our results suggest that overexpression of CD44s could be relevant in determining the highly invasive behaviour of gliomas, though it does not behave as an independent prognostic factor for survival.

Colorectal cancer staging: reappraisal of N/PN classification.

PURPOSE: Current American Joint Committee on Cancer and the Union Internationale Contre le Cancer TNM classification disregards location of positive nodes, discontinuing N3 category, which constitutes a major modification to 1987 version. This study was designed to assess the impact of the recategorization of former N3 cases and the reliability of the current N1-N2 subcategorization of Stage III patients. METHODS: Prospectively collected data from 1,391 patients (55.8 percent males; median age, 64 (range, 21-97) years), operated on with curative intent between 1980 and 1999, were analyzed. The median follow-up was 60 (interquartile range, 27-97) months with 129 cases lost to follow-up. RESULTS: Of positive node cases, 25.3 percent were former N3. Among them, 30.5 percent migrated to the N1 group and 69.5 percent to the N2 group. The proportions of former N3 cases in N1 and N2 groups were 12.5 percent and 46.1 percent, respectively (P<0.001). Node-positive patients had an actuarial five-year survival rate of 56.7 percent (95 percent confidence interval, 53-59), with a significant difference between N1/N2 categories (63.6 vs. 44.1 percent, respectively; P<0.001). Although apical node involvement and more than three positive nodes were associated with poorer outcomes in univariate analysis, only the number of positive nodes had independent association (hazard ratio, 1.6 (range, 1.2-2.2); P<0.001). Integration of former N3 cases did not modify outcomes. CONCLUSIONS: The recategorization of former N3 involved a high proportion of positive node cases. Current N1/N2 categories clearly defined different outcomes and were not modified by the integration of former N3.

Prognostic value of Mdm2, p53 and p16 in patients with astrocytomas.

Surgical cure of gliomas infiltrating into the brain is practically impossible and their clinical course is primarily determined by the biological behavior of the tumor cell. The purpose of this study was to analyze retrospectively prognostic input of p53, Mouse double minute-2 (Mdm2) and p16 in 103 uniformly treated patients with astrocytic tumors. The expression of these molecules was measured by immunohistochemical procedure. Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5-122) months for the survivors. We observed that 66% of gliomas showed mutated p53, while only 17% overexpressed Mdm2, the p53-regulatory molecule. Besides, almost 50% of gliomas lost p16 immunopositivity. Only p53 labeling showed a positive correlation with the grade of malignancy, according with the WHO classification. The association between mutated p53 and histological grade remained when prognostic variables were considered in a multivariate analysis. No association between p53 status and overall survival was found. On the other hand, Mdm2 overexpression and, unexpectedly, p16 immunopositivity were associated with a shorter survival in an univariate analysis. However, Cox-regression analysis showed that only Mdm2 in female patients was an independent prognostic factor, associated with shorter survival. In conclusion, our results suggest that Mdm2 could be a relevant marker in determining the evolution of glioma patients and could provide a more objective way to classify astrocytomas.

EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas.

BACKGROUND AND OBJECTIVES: Therapy of malignant glioma tumors is based on histology and clinical factors. However, comparable lesions may correspond with important prognostic differences. Our purpose was to analyze retrospectively the prognostic input of platelet-derived growth factor receptor (PDGF-R), epidermal growth factor (EGF-R), and bcl-2 expression in 103 malignant gliomas from uniformly treated patients. METHODS: The expression of the antigens was analyzed by immunohistochemistry (IHC). Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5-122) months for survivors. RESULTS: We observed that almost 50% of gliomas showed high expression of PDGF-R, while a lower expression of EGF-R and bcl-2 was found. No association between the main prognostic factors in malignant glioma (sex, age, histological grade, and Karnofsky score) and the labeling index (LI) of these antigens was observed. We found that only PDGF-R and EGF-R overexpression were associated with a shorter survival in patients with World Health Organization (WHO) II astrocytomas, being both associations independent of known prognostic factors, as shown by Cox model. Besides, we confirmed other authors' results that high histological grade and low performance score were associated with worse prognosis. CONCLUSIONS: PDGF-R and EGF-R expression could be relevant in determining the prognosis of low-grade astrocytomas (LGAs) and in providing a more objective mechanism for their classification.