Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma.

The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P<0.001), progression free-survival (PFS) (P<0.009) and overall survival (OS) (P<0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-κB and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.

[A retrospective study about 11 cases of Esthesioneuroblastomas treated in Hospital Santa Creu i Sant Pau between 2000 and 2008 and literature review]. / Estudio retrospectivo de 11 casos de estesioneuroblastomas tratados en el Hospital Santa Creu i Sant Pau entre los años 2000 y 2008 más revisión de la literatura.

INTRODUCTION. Esthesioneuroblastoma (ENB) is a very uncommon malignant tumor with a neuroectodermal origin that usually involves the anterior cranial fossa and nasal cavity. OBJECTIVES. To review our experience in the management of ENB and assess the validity of the histopathological diagnosis, modality of treatment and prognostic factors of the disease comparing our findings with the literature. METHODS. A retrospective study of 11 cases with the diagnosis of esthesioneuroblastoma treated in our hospital between 2000 and 2008. Statistical analysis was performed in search for prognostic factors. The bibliography about ENB published between 1990 and 2009 was reviewed RESULTS. There were 3 women and 8 men, with a mean age of 42 years old (range 20-71y). Their symptoms upon admission were nasal obstruction (81%), epistaxis (27%), visual loss (18%), headache and others. According to the Kadish Stage, 2 were stage B and 9 were stage C. Dulguerov and Calcaterra Classification was also used: 2 were T2, 3 were T3 and 6 were T4. The hystopathological result according to the Hyams classification was: 2 cases in stage I, 4 in stage II, 3 in stage III and 2 in stage IV. The two cases classified in stage IV changed the diagnosis to undifferenciate tumor in the second biopsy. A subcranial approach was performed in 8 cases combined with endonasal endoscopy to confirm the total removal, followed by radiotherapy in all and chemotherapy in one case, resulting on 62% (5 patients) being alive without disease, 12,5% (1 p) alive with disease, and 25% (2 p) dead of disease. Another patient was operated by a single endonasal endoscopic approach and a subtotal removal was achieved. This patient is alive without disease. The other 2 patients were treated by biopsy plus radiotherapy and chemotherapy, because they were considered unresectable, and one of them is alive with disease and the other one is dead of disease. Radiotherapy was performed in all cases and chemotherapy in 5 cases. The hystopathological grading system of Hyams was considered statistically significant as a prognostic factor of disease-free survival. CONCLUSIONS. When the hystopathological diagnosis of ENB is considered, the Hyams classification can be valid considering grade IV as an advanced stage that is sometimes difficult to differentiate from other undiferentiated tumors. The subcranial approach or craneofacial resection in advanced stages (Kadish C and some B) should be considered as the first treatment of choice. Radiotherapy is indicated in all cases and chemotherapy in selected cases. Hyams' classification was the only staging system that proved useful as a prognostic factor in our series.

Estudio retrospectivo de 11 casos de estesioneuroblastomas tratados en el Hospital Santa Creu i Sant Pau entre los años 2000 y 2008 más revisión de la literatura / A retrospective study about 11 cases of Esthesioneuroblastomas treated in Hospital Santa Creu i Sant Pau between 2000 and 2008 and literature review

Introducción. El estesioneuroblastoma (ENB) es un tumor maligno de origen neuroectodérmico poco habitual que afecta principalmente a la fosa craneal anterior y cavidad nasal. Objetivos. Revisar nuestra experiencia en el manejo de los ENB, evaluar la validez del diagnóstico anatomopatológico, el tipo de tratamiento y factores pronósticos de la enfermedad comparando nuestros hallazgos con los descritos en la literatura. Material y métodos. Estudio retrospectivo de 11 casos de ENB tratados en nuestro hospital en el periodo comprendido entre 2000 y 2008. Se realiza análisis estadístico sobre la existencia de factores pronósticos. Se revisa la bibliografía publicada sobre el ENB entre 1990 y 2009.Resultados. Se trataron 3 mujeres y 8 hombres, cuya edad media fue 42 años (rango 20-71 años). El síntoma inicial fue la obstrucción nasal (81%), epistaxis (27%), disminución de agudeza visual (18%), cefalea y otros. Según la clasificación de Kadish, 2 son estadío B y 9 estadío C; según la clasificación de Dulguerov, 2 son T2, 3 son T3 y 6 son T4. El resultado histológico según la clasificación de Hyams fue de 2 casos en grado I, 4 en grado II, 3 en grado III y 2 en grado IV. Dos de los casos inicialmente catalogados en grado IV cambiaron de diagnóstico en la segunda (..) (AU)

Introduction. Esthesioneuroblastoma (ENB) is a very uncommon malignant tumor with a neuroectodermal origin that usually involves the anterior cranial fossa and nasal cavity. Objectives. To review our experience in the management of ENB and assess the validity of the histopathological diagnosis, modality of treatment and prognostic factors of the disease comparing our findings with the literature. Methods. A retrospective study of 11 cases with the diagnosis of esthesioneuroblastoma treated in our hospital between 2000 and 2008. Statistical analysis was performed in search for prognostic factors. The bibliography about ENB published between 1990 and 2009 (..) (AU)

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis.

Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n=24) or allogeneic (n=35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 micromol/g dry weight (7.7 mg/g; range 31-631 micromol/g). In total, 4/32 (12%) patients with HIC <150 micromol/g and 10/27 (37%) with hepatic iron > or =150 micromol/g showed invasive aspergillosis at autopsy (P=0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P=0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.

Endometriosis umbilical con estudio de receptores hormonales / Umbilical Endometrosis with Study of Hormonal Receptors

La endometriosis es la presencia de tejido endometrial extrauterino, su localización habitual es intrapélvica, sin embargo puede localizarse a nivel cutáneo de forma espontánea o secundaria. La localización umbilical es la más frecuente de las endometriosis espontáneas alcanzando al 1 por ciento del total de las endometriosis. Se presenta el caso de una paciente con endometriosis umbilical espontánea, en la que se realiza un estudio inmunohistoquímico para receptores hormonales de estrógeno y de progesterona resultando ambos positivos (AU)

Parálisis del plexo braquial como traumatismo obstétrico / Paralysis of the brachial plexus as an obstetric trauma

La parálisis obstétrica del plexo braquial es el traumatismo obstétrico más frecuente después de la fractura de clavícula, y consiste en un traumatismo o lesión por elongación del plexo braquial en el momento del parto (AU)

Selective dissection of levels II-III with intraoperative control of the upper and middle jugular nodes: a therapeutic option for the N0 neck.

BACKGROUND: Selective neck dissections are accepted elective treatment in N0 patients. We present the results of a dissection of levels II to III and intraoperative pathologic control of a sample of subdigastric and supraomohyoid nodes in a group of patients with laryngeal carcinoma. When intraoperative analysis was positive, dissection of levels IV and V was completed. METHODS: Between 1991 and 1997, 145 neck dissections with intraoperative control were carried out in 79 patients with laryngeal carcinomas. Postoperative radiotherapy was used in 49 patients. RESULTS: There were occult metastases in 29 neck dissections (20%). In 22 cases (15%), tumor was found in the nodes sent to intraoperative pathologic study, and dissection of levels IV and V was completed. In 7 additional cases tumor was found in the postoperative study. The sensitivity of the use of frozen sections in the detection of occult metastases was 76%. In no case were positive nodes found at level V. There was no regional relapse in any of the 145 selective neck dissections. CONCLUSIONS: The lateral selective neck dissection is an effective method in the elective treatment of the neck of N0 laryngeal carcinoma patients. Dissection of level IV can be spared when intraoperative biopsy specimens of a sample of the subdigastric and supraomohyoid nodes are negative. According to our results, at present we do not consider it necessary to dissect level V in selective neck dissections in patients with laryngeal carcinoma.

Redefining the significance of aneuploidy in the prognostic assessment of colorectal cancer.

The aberrant content of DNA, or aneuploidy, is a hallmark of tumor cells and may be associated with malignant potential. Based on the hypothesis that aneuploidy, as a form of genetic instability, results in an increased capability to generate cell heterogeneity, we investigated whether a comprehensive assessment of aneuploidy extent and degree might be a reliable indicator of tumor aggressiveness. DNA content was determined by flow cytometry in the infiltrating front of 131 paraffin-embedded primary colorectal carcinomas collected in a prospective design. Enrichment of tumor cells by sample microdissection resulted in neoplastic cell contents above 75%. An estimate of aneuploidy, the aneuploidy index (AI), was calculated as the tumor DNA content adjusted by the percentage of diploid and aneuploid cells in G0/G1. Thirty-nine tumors were diploid, 90 hyperdiploid, and 2 hypodiploid. The mean AI in aneuploid tumors was 1.20+/-0.17 and correlated with Dukes' stage and metastasis (p < 0.05). A high AI (receiver operating characteristic curve cutoff value greater than 1.14) predicted a poorer outcome in univariate (p = 0.004) and multivariate (p = 0.01) analyses. Based on these results, we postulate that aneuploidy is the molecular engine of progression in a subset of colorectal cancers, in which the AI seems to be a sensible and independent gauge of malignant potential. The AI determination may have prognostic application in colorectal cancer, especially in low-grade tumors, which might benefit from coadjuvant therapies.

Histologically negative specimens after induction therapy: frequency and impact on survival.

BACKGROUND: Occasionally in head and neck cancer patients treated surgically after induction chemotherapy, the histologic analysis of the excised tissue does not show evidence of viable tumor cells, a situation that the authors named "negative specimen." The objective of this study was to quantify the frequency of negative specimens in surgery after induction chemotherapy and to analyze the repercussions of this situation. METHODS: A retrospective study of prospectively collected data on 245 patients treated surgically after induction chemotherapy was made to calculate the frequency of negative specimens. An individualized review of the patients with negative specimens was made. The actuarial survival was calculated in relation to the existence of residual tumor. RESULTS: Twenty-five patients (10%) had negative specimens. Five-year adjusted survival for patients with negative specimens was 96%, significantly better than 62% survival in patients with residual tumor. CONCLUSIONS: Ten percent of patients treated surgically after induction chemotherapy had no residual tumor. These patients had a favorable prognosis.

[Identification of 2 families with hereditary nonpolyposis colonic cancer (HNPCC) and the Amsterdam criteria. Relevance of the genealogic tree and follow-up]. / Identificación de dos familias con cáncer de colon hereditario no polipósico (CCHNP) y criterios de Amsterdam. Relevancia del árbol genealógico y las medidas de seguimiento.

Hereditary nonpolyposis colorectal cancer (HNPCC) diagnosis is based either on the so-called "Amsterdam 1 criteria" or "Amsterdam 2 criteria", which includes extracolonic neoplasms associated with Lynch II syndrome. Many families are suspected of having a hereditary predisposition to cancer and may benefit from close surveillance. We describe a family (family 1) with suspected HNPCC at the beginning who fulfilled the Amsterdam 1 criteria over the course of its follow-up. We also describe an Amsterdam 2 family (family 2) with a very young affected individual. Both of them received genetic counseling and screening recommendations. A total colonoscopy was done to an asymptomatic member of family 1 and he was diagnosed with an early-stage colon cancer. He underwent subtotal colectomy because of the high risk of metachronous lesion. Screening recommendations must be the same in Amsterdam 2 families as in Amsterdam 1. Both families show the importance of considering the family history when hereditary criteria are suspected.

A highly sensitive method for K-ras mutation detection is useful in diagnosis of gastrointestinal cancer.

Detection of molecular features such as K-ras mutations has been used to evaluate potential tumour markers in a wide variety of clinical samples. Here we have applied a recently developed highly sensitive method for detection of K-ras codon 12 mutations to colorectal and pancreatic cancer diagnosis. We analysed 67 faecal samples from patients undergoing diagnostic colonoscopy under suspicion of colorectal cancer. PCR products were obtained in 62 of 67 (93%) faecal samples. Mutations were detected in exfoliated cells in 6 of 22 (27%) of the adenomas and in 6 of 11 (55%) of adenocarcinomas. No false positives were observed. Agreement between faecal samples and corresponding tissues was 100% for adenocarcinomas and 65% for adenomas. Mutations were also analysed in 61 pancreatic fine-needle aspirates. Mutations were detected in 36 of 45 (80%) of the pancreatic aspirates diagnosed as pancreatic cancer without false positives. Our findings suggest that, when colorectal cancer is suspected, detection of K-ras codon 12 mutations in faecal samples using this new method is specific for colorectal tumours. Additionally, this technique is a good alternative for evaluation of pancreatic masses.

PCR analysis in the pathological diagnosis of Whipple's disease: emphasis on extraintestinal involvement or atypical morphological features.

PCR analysis of species-specific bacterial 16S rRNA gene of Tropheryma whippelii was performed in biopsies from 10 cases of Whipple's disease (WD). In seven patients showing the typical clinical picture of WD, PCR was performed on the diagnostic intestinal biopsy. In the remaining three cases (an autopsy case of disseminated WD and two patients showing lymphadenopathy as the initial clinical presentation), PCR was done on lymph node specimens. In one of the lymph node biopsies, an unusual sarcoidlike granulomatous reaction had led to the diagnosis of sarcoidosis. The specific bacterial DNA was detected in all cases, both in intestinal biopsies and in lymph node specimens. Follow-up biopsies after antibiotic therapy were evaluated in two patients. The two follow-up biopsies were negative, although in both of them scattered nests of PAS-positive macrophages remained. The results of this study suggest that PCR analysis of species-specific sequences of the 16S rRNA of Tropheryma whippelii is a very useful tool for the pathological diagnosis of WD. It confirms the diagnosis of WD in intestinal biopsies as well as in extraintestinal sites, even when the morphological appearance is not typical. It is also the most precise technique for monitoring therapeutic effects.

p53 and K-ras gene mutations correlate with tumor aggressiveness but are not of routine prognostic value in colorectal cancer.

PURPOSE: p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer. PATIENTS AND METHODS: One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate. RESULTS: p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance. CONCLUSION: p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.

Orthotopic xenografts of human pancreatic carcinomas acquire genetic aberrations during dissemination in nude mice.

Orthotopic transplantation of human tumors in nude mice reproduces the pattern of local growth and distal dissemination. The aim of our study was to determine the pattern of genetic alterations in human carcinomas of the exocrine pancreas orthotopically implanted and perpetuated in nude mice. Eight of the sixteen orthoimplanted human pancreatic carcinomas were perpetuated through several passages. Four perpetuated tumors followed distinct patterns of distal dissemination. Point mutations in the K-ras gene, genetic aberrations in the p53 and p16 genes, and allelic losses at retinoblastoma, adenomatous polyposis coli, and deleted in colorectal cancer loci were analyzed. Perpetuated tumors maintained the pattern of genetic alterations present in primary tumors. Five perpetuated tumors contained K-ras mutations, and all tumors contained p53 and/or p16 genetic aberrations. Allelic losses were present in four of the perpetuated tumors. Additional genetic alterations were detected in 6 of 35 metastases analyzed. Five of 9 peritoneal metastases or malignant ascitic cells acquired either K-ras or second p53 mutations. In contrast, only 1 of 25 liver metastases and none of the lymph node metastases acquired additional mutations. No additional p16 gene aberrations or other allelic losses were evidenced during tumor dissemination. We conclude that orthotopically implanted pancreatic carcinomas xenografted in nude mice show a high degree of genetic stability. Mutations in K-ras and p53 genes can occur in this model system in the more advanced stages of pancreatic tumor progression, mainly during peritoneal dissemination.

K-ras and p53 mutations in hamster pancreatic ductal adenocarcinomas and cell lines.

K-ras and p53 gene alterations are frequently found in human pancreatic carcinomas and cell lines. The aim of this study was to analyze for the presence of K-ras and p53 gene mutations in hamster pancreatic tumors and cell lines. Mutations at the first coding exon of the K-ras gene and in exons V to VIII of the hamster p53 gene were analyzed in six cell lines (H2T, PC1, PC1.2, PC1.0, WD, and PD) and in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic (n = 9) and extra-pancreatic (n = 4) tumors. K-ras mutations were present in seven of the nine pancreatic tumors and in all extra-pancreatic tumors. No p53 mutations were detected in the tumors. All cell lines analyzed contained K-ras mutations. Moreover, four of the six cell lines contained single amino acid substitutions in the p53 gene. Cell lines derived from nitrosamine-induced pancreatic tumors in the hamster contained K-ras and p53 alterations similar to those found in cell lines derived from human pancreatic carcinomas.

[Atypical ossifying hemangioma of the temporal bone]. / Hemangioma osificante de hueso temporal. Caso atípico.

Over the last decade, the hemangioma of the temporal bone has become clinically recognized as the benign tumor most commonly involving the facial nerve in its intratemporal portion. Its locally aggressive nature affects the VIIth cranial nerve at a very early stage, usually before the tumor reaches a 10 mm diameter. We present a case of ossifying hemangioma of the temporal bone which, in spite of being located in the region of the geniculate ganglion and of measuring over 20 mm, only caused hearing conductive loss. The atypical clinical course of this case contrasts with those described in the literature.

[Focal nodular hyperplasia of the liver with malignant endoscopy appearance]. / Hiperplasia nodular focal del hígado con apariencia endoscópica maligna.

We report the case of a male patient, 49 years of age, who was admitted to our hospital to clarify the diagnosis of a solid liver tumor of the left lobe of the liver which had been made by image methods (U.S., scan and scintigraphy). Laparoscopy showed an isolated tumor emerging from the left lobe of the liver featuring hypervascularity and umbilication at the top. A visual diagnosis of malignancy was made which was not confirmed neither by biopsy nor the cytological examination. Liver resection was undertaken, and a diagnosis of nodular hyperplasia was made by the pathologist. We have never encountered before this endoscopic appearance of focal nodular hyperplasia either in our own experience or in the search of the literature.