Acoustic analysis of voice in Parkinson's disease: a systematic review of voice disability and meta-analysis of studies. / Análisis acústico de la voz en la enfermedad de Parkinson: revisión sistemática de la discapacidad vocal y metaanálisis de estudios.

AIM: To systematically review all the literature, focusing on instrumental quantitative assessment of voice in patients with Parkinson's disease (PD). Furthermore, a meta-analysis was performed to identify the main characteristics of voice disturbances in PD. PATIENTS AND METHODS: Literature searches with the keywords «Parkinson¼ and «voice¼ were conducted in PubMed, EMBASE, Cochrane Library and Web of Science. Main inclusion criteria were: clinically confirmed PD and instrumented measurement of voice parameters with acoustic analysis of voice. RESULTS: Fourteen publications met the inclusion criteria and were included in the meta-analysis. The data within the meta-analysis revealed that several voice parameters including jitter, shimmer and fundamental frequency variation presented significant variations between patients with EP and healthy controls. Significant variations of fundamental frequency, maximum phonation time, harmonic to noise ratio, standard deviation of fundamental frequency were observed, but with a high heterogeneity between the studies. On the other hand, significant variations of noise to harmonic ratio, s/z ratio, variation of amplitude were not observed. CONCLUSION: Acoustic analysis of voice, using an electronic system, allows the identification of changes in voice parameters for predicting the worsening of disease and for targeting specific intervention. Among the voice parameters, jitter and shimmer significantly increased in patients with PD.

TITLE: Análisis acústico de la voz en la enfermedad de Parkinson: revisión sistemática de la discapacidad vocal y metaanálisis de estudios.Objetivo. Revisar de manera exhaustiva la bibliografía referente a la evaluación instrumental cuantitativa de la voz en pacientes con enfermedad de Parkinson (EP) y realizar un metaanálisis para definir las principales características de los trastornos de la voz en la EP. Pacientes y métodos. Búsquedas bibliográficas con las palabras clave «Parkinson¼ y «voice¼ en PubMed, EMBASE, Cochrane Library y Web of Science. Los principales criterios de aceptación fueron: EP con confirmación clínica y medición instrumentada de los parámetros de la voz mediante análisis acústico. Resultados. Catorce publicaciones cumplieron los criterios de aceptación y se incluyeron en el metaanálisis. De los datos incorporados al metaanálisis, se dedujo que varios parámetros vocales, como el jitter, el shimmer y la variación de la frecuencia fundamental, presentan variaciones significativas en los pacientes con EP frente a los controles sanos. Se hallaron variaciones significativas de la frecuencia fundamental y de su desviación estándar, del tiempo máximo de fonación y de la razón armónicos-ruido, si bien con una alta heterogeneidad entre los estudios. En cambio, no se observaron variaciones sustanciales de la razón ruido-armónicos, en el índice s/z ni en la variación de la amplitud. Conclusión. El análisis acústico de la voz por medio de un sistema electrónico permite detectar los cambios de los parámetros vocales de cara a predecir el empeoramiento de la enfermedad y elegir una intervención específica. Entre dichos parámetros, el jitter y el shimmer aumentaron significativamente en los pacientes con EP.

Rare cases reports of gastrointestinal stromal tumour (GIST).

The GISTs are rare tumours but even rarer is the localization in some districts. We reported two GISTs of the duodenum, two of the omentum and peritoneum, one of the rectum and one of a Meckel's diverticulum. These exceptional locations are confirmed by the relative difficult diagnosis, obtained in some cases only by the surgical treatment despite the CT and MR. The endoscopy is useful in hemorrhagic and duodenum forms, only for the diagnosis and for the control of blood loss. Surgical treatment in all cases was decisive without the need to make use of adjuvant therapy, with positive long-term results, which excluded the disappearance of relapses or secondary lesions.

Traumatic labyrinthine concussion in a patient with sensorineural hearing loss.

Blunt head trauma without any temporal bone fracture or longitudinal temporal bone fracture, with an associated fracture of the labyrinth may cause labyrinthine injury with sensor neural hearing loss and vertigo because of a concussive injury to the membranous labyrinth. Sudden sensory neural hearing loss is relatively frequent. In most cases, the etiology is not discovered. One of the possible causes for sudden deafness is inner labyrinth bleeding or concussion, which were difficult to diagnose before the advent of magnetic resonance imaging. Vertigo without a demonstrable fracture may also be the result of labyrinthine concussion, cupololithiasis and perilymphatic fistula. We describe the clinical case of a patient with acute traumatic hearing loss and vertigo, without skull base fracture detected on computed tomography. Magnetic resonance study was also performed. We have integrated the discussion with features that allow the differential diagnosis from other similar conditions.

Developmental venous anomaly responsible for hemifacial spasm.

Hemifacial spasm (HFS) is a facial movement disorder characterized by involuntary, unilateral and intermittent contractions of the facial muscles. It is one of the syndromes related to neurovascular conflict, first described by Jannetta et al. in 1979. Typically, HFS is due to pulsatile compression by the anterior inferior cerebellar artery. We describe a rare case of left developmental venous anomaly in a 59-year-old man referred to us with a six-month history of left-sided HFS. We performed an MR study of the brain and cerebellopontine angles, which demonstrated a compression of the ipsilateral facial nerve by the developmental venous anomaly.

Respiratory failure and pharyngeal hematoma as presenting signs of Moschcowitz's syndrome: a case report and literature review.

Moschcowitz's syndrome or thrombotic thrombocytopenic purpura is a quite rare pathology in childhood, being, as a matter of fact, more frequent among adult people. Often it is hard to distinguish from other pathologies in children both for its rare incidence and for the presence of clinical forms that are very heterogeneous and difficult to be classified. We report on a 13 year-old girl suffering from Moschcowitz's syndrome, in whom respiratory failure and pharyngeal hematoma were the first sign of the disease follone by jaundice, hematoma of the arm and limbs. The girl was treated with plasmapheresis with an improvement of her general condition. Since then we have followed up the girl for two years without any reappearance of the symptomatology. To our knowledge this is the first report of this peculiar presentation in children.

A rare location of benign osteoblastoma: case study and a review of the literature.

Osteoblastoma is a solitary, benign bone tumor that is rarely localized in the frontal sinus. It consists of hypocellular mineralized tissue that may form large masses or irregular trabeculae. A 31 year old man came to our attention with a 7 month history of diplopia, photophobia, frontal headhaches and progressive exophthalmos with proptosis of the left eye. The patient was submitted to computed tomography (CT) which allowed to appraise the extension of the lesion. The mass expanded inside the left frontal sinus and the upper ethmoidal cells invading the left orbital roof. Considering the extension of the tumor, the site and the connections with contiguous structures, a combination of endoscopic endonasal technique with intraorbital approach was performed. At histological examination typical features of benign osteoblastoma were observed. The sites of predilection for the tumor are the long bones, vertebral column, and small bones of hands and feet. Its occurrence in the skull and jaw bones is relatively rare and represents only 15% of all osteoblastomas. To our knowledge, only 5 cases of osteoblastoma of the frontal sinus have been previously reported in the English-language literature. This report describes a case of benign osteoblastoma in a rare site, namely, the frontal sinus with particular attention about the differential diagnosis and the treatment.    

Tracheostomy in childhood: new causes for an old strategy.

INTRODUCTION: A review of the available literature has shown that the indications, epidemiology, and complications for tracheostomies are changing, and that no definite guidelines have been established. In the 1970s, the most common indication for tracheostomies in children was acute inflammatory airway obstruction. Modern neonatal intensive care units (ICU) have turned long-term intubation into an alternative to a tracheostomy. Currently, long-term intubation has become the most important indication for tracheostomies in children. PATIENTS AND METHODS: We present our series involving tracheostomies performed in paediatric patients between 2004 and 2008 at our hospital. Sixteen patients underwent tracheostomies for respiratory failure and upper airway obstruction. RESULTS: The total complications rate was 37.5%. In children < 1 year of age, the complications rate was 25%, while in children > 1 year of age, the complications rate was 12.5%. CONCLUSIONS: Long-term intubation and its sequelae have now become one of the most important indications for tracheostomies in the paediatric age group.

High-dose fluconazole therapy in Intensive Care Unit.

AIM: Fungal infections have become one of the emerging complications in intensive care patients and the morbidity and mortality linked to these infections underlines the importance of managing these pathologies. METHODS: The clinical and laboratory difficulties of diagnosing candidiasis prompted us to identify patients at risk and to intervene as soon as possible, where there was the "suspicion" of active infection, using adequate, so-called "empiric" treatment. The major risk factors include the use of invasive devices (central venous catheters), the administration of multiple antibiotic treatment and parenteral nutrition. In our Intensive Care ward (multi-purpose), we examined 1933 patients who had undergoing 1211 urine cultures (following consolidated clinical criteria). "Empiric treatment" was used in 378 high-risk patients with unstable clinical symptoms and positive urinary fungal colonisations using high-dose fluconazole (800 mg/die) according to the guidelines set down by BSAC. The mean duration of treatment was 12+2 days and urine cultures became negative in all patients after 1 or 2 weeks of treatment. RESULTS: We observed that fluconazole was generally well tolerated: only 10% of patients presented augmented hepatic transaminase. This phenomenon was always transient. Renal function remained unchanged (creatinine clearance). A severe infection with hematogenous dissemination was reported in 6 cases: "empiric treatment" was used in 5 cases with 800 mg/die of fluconazole and 1 case received amphotericin B 1 mg/kg/die (because no clinical improvement was observed after 48-72 hours of fluconazole treatment). Three of these 6 cases died, 2 of which were not directly linked to fungal infection, and 3 patient were discharged from the ward. CONCLUSIONS: We found that fluconazole offers a treatment option that is less toxic, less expensive and equally effective for these infections, provided that it is used at an adequate dose and that high-risk patients are identified for "empiric treatment". No significant increases in resistance were noted, as is demonstrated by the fact that only 1 case of candidemia required conversion to amphotericin B.

[Superextended lymphadenectomy (D4) in the treatment of gastric adenocarcinoma]. / La linfadenectomia superestesa (D4) nel trattamento dell'adenocarcinoma gastrico.

BACKGROUND: The incidence of paraaortic lymph node metastasis (N4) in relation with the site of the tumour, and survival in patients with gastric cancer who underwent gastric resection and superextended lymphadenectomy (D4), have been analyzed. METHODS: The frequency of paraaortic lymph node metastasis was studied in 132 patients who underwent gastrectomy with D4 lymphadenectomy during the period June 1988 - December 2000. Six patients with plastic linitis and 3 with carcinoma of the gastric stump were excluded from the analysis. RESULTS: In personal experience the most frequent postoperative morbidity were respiratory complication (7.6%) and pancreatic fistula (6.8%). Among the 132 patients the total number of dissected nodes was 6362 and the mean number of dissected nodes per case was 48.2. The total number of retrieved lymph nodes from the paraaortic station was 755 with a mean number 5.7 per patients. N4 nodal involvement was found in 25 (19%) of 132 patients: 14 (36%) patients with carcinoma located in the proximal third, 5 (13%) with tumour located in the middle third and 6 (11%) with carcinoma of the distal third of the stomach. The median survival time and the overall cumulative 5-year survival rate for curatively (R0) resected patients were 74 months and 52% respectively. CONCLUSIONS: The presence of metastasis in paraaortic lymph nodes in 19% of our patients, the low morbidity and mortality, the good survival after superextended lymphadenectomy, suggest that this lymphadenectomy should be considered in the curative surgical treatment of advanced gastric cancer, especially if located in the proximal third of the stomach (N4 in 36% of cases).

[Goseki classification in adenocarcinoma of the cardia]. / La classificazione di Goseki nell'adenocarcinoma del cardias.

BACKGROUND: To assess an additional prognostic value of Goseki histological classification to TNM staging system in adenocarcinoma of the cardia. METHODS: Sixty-one patients curatively resected for advanced (T2, T3 and T4) cardia cancer at the I Division of General Surgery, University of Verona were classified in four different grades according to Goseki. Survival curves were estimated with Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed by Cox regression model. c2 test was used to compare Goseki to Lauren classification and grading. After discharge from hospital all patients were followed with a mean follow-up of 39.5 months. RESULTS: Lauren classification and grading were significantly related to tubular differentiation (p<0.01). Kaplan-Meier estimates of survival showed a better 5-year outcome for tumors with good tubular differentiation (19%), even though the difference with poor tubular differentiated tumors was not statistically significant (p'0.06). Diffuse type carcinomas and tumors with poor cytological differentiation showed a worse prognosis at univariate analysis (p<0.01). Multivariate analysis showed no additional prognostic significance of any of the histological classification analyzed. Only T (p<0.02; RR 2.2; IC 1.2-4) and N (p<0.01; RR 5; IC 2.4-11) were independent prognostic factors. CONCLUSIONS: In adenocarcinoma of the cardia, Goseki classification did not add any information to Lauren classification and to TNM staging system.

Metastases to the para-aortic lymph nodes in adenocarcinoma of the cardia.

OBJECTIVE: To find out the extent of involvement of the para-aortic nodes in patients with adenocarcinoma of the gastric cardia. DESIGN: Open prospective study. SETTING: Teaching hospital, Italy. SUBJECTS: 23 patients with advanced adenocarcinoma of the cardia (type II, n = 10, and type III, n = 13) who were treated by total gastrectomy with resection of the distal oesophagus and extended lymphadenectomy (D4) between January 1997 and June 1999. These were compared with 21 patients with advanced carcinoma of the proximal third of the stomach who had total gastrectomy with D4 lymphadenectomy during the same period. Lymph nodes were retrieved immediately postoperatively and assigned to the appropriate station according to the classification of the Japanese Research Society for Gastric Cancer. MAIN OUTCOME MEASURES: Number of para-aortic and other nodes involved. RESULTS: 22 of the 23 patients had lymph node metastases, and in 5 the para-aortic nodes were involved (N4). N3 lymph nodes were involved in only 1 patient, despite involvement of para-aortic nodes. Among the 5 patients with N4 metastases, 1 had only N1 metastases in addition, with no involvement of N2 or N3 nodes. Patients with involved N4 nodes had more nodes involved overall than those who did not (mean (SD) 17 (5) compared with 8 (12)). CONCLUSIONS: 5/23 patients with advanced carcinoma of the cardia had involved para-aortic nodes. This may have some prognostic value, but larger studies of D4 lymphadenectomy specimens is required.

[Para-aortic lymph node involvement in gastric adenocarcinoma]. / Envahissement des ganglions para-aortiques dans les adénocarcinomes de l'estomac.

AIMS: To determine the significance of superextended lymphadenectomy (D4) in patients with gastric cancer. The incidence of para-aortic lymph node metastases (N4) was analysed as well as its relationship to the site of the tumour. PATIENTS AND METHODS: The frequency of para-aortic lymph node metastases was assessed in 110 patients who underwent gastrectomy with D4 lymphadenectomy during the period from June 1988 to October 1999; five patients with plastic linitis and three with carcinoma of the gastric stump were excluded from the study. RESULTS: The postoperative mortality rate was 2.7% (n = 3) and the postoperative morbidity rate was 29.1% (n = 32). In our experience the most frequent postoperative complications were pancreatic fistulas (7.3%) and respiratory complications (6.4%). Among the 110 patients, the total number of dissected nodes was 5245 and the mean number of dissected nodes per case was 47.7. The total number of retrieved lymph nodes from the para-aortic station level was 639, with a mean number of 5.8 per patient. N4 nodal involvement was found in 20 (18.2%) out of 110 patients: 12 (33%) patients with a carcinoma located in the proximal third, two (6%) with a tumour located in the middle third and six (15%) with a carcinoma of the distal third of the stomach. CONCLUSION: The presence of para-aortic lymph node involvement in 18.2% of the patients suggests that D4 lymphadenectomy should be considered in the curative surgical treatment of advanced gastric cancer, especially if located in the proximal third of the stomach (N4 + in 33% of the patients).

[Results of the surgical treatment of primary gastric lymphoma]. / Risultati del trattamento chirurgico del linfoma gastrico primitivo.

The aim of the study was to verify the long term results obtained in primary gastric lymphoma with a strategy consisting in surgery as first-line treatment. Over the period from January 1988 to December 1999, 44 patients with histologically proven primary gastric lymphoma underwent surgical treatment in the First Department of General Surgery of the University of Verona. Tumours were staged according to the Ann Arbor classification and divided, according to the Kiel classification, into high- and low-grade lymphoma. Patients received adjuvant chemotherapy depending on the grade of malignancy and/or completeness of resection. Of the 44 patients, 40 (90.9%) underwent curative resections, i.e. with complete macroscopic and microscopic tumour removal (R0), consisting in total gastrectomy in 34 cases and subtotal gastrectomy in 6. Twenty-five of 40 patients had stage IE and 15 stage IIE tumours. Adjuvant chemotherapy was given to 33 patients (30 high-grade lymphomas and 3 low-grade lymphomas with N2 metastases). The overall cumulative 10-year survival rate in patients who underwent R0 resection was 79% without any significant differences in 10-year survival between patients with high- and low-grade malignancy (both 79%; P = 0.582) or between patients with or without lymph node metastases (91% and 70%, respectively; P = 0.426). In conclusion, the present investigation suggests that surgery yields prolonged complete remission in a high percentage of patients affected by gastric lymphoma irrespective of histopathologic grade of the disease and nodal involvement.

Rhesus D-phenotype does not provide prognostic information additional to TNM staging in gastric cancer patients.

Recently, the Rhesus D-negative phenotype was identified in multivariate analysis as an important independent risk factor in gastric cancer patients who underwent curative resection. The distribution of Rhesus (Rh) D phenotype was investigated in a group of 268 patients who underwent gastrectomy for gastric cancer from June 1988 to April 1999. After excluding patients with short, potentially guaranteed follow-up or who deceased in the postoperative period, the prognostic significance of Rh D phenotype was evaluated in a subgroup of 239 patients by Cox regression model controlling for gender, age, site, histology, depth of tumor invasion (T), node metastasis (N), and type of resection (R). Two hundred and thirty-six patients (88.1%) presented an Rh+ phenotype and 32 (11.9%) presented an Rh- phenotype. A significant association was found between Rh D- phenotype and the presence of residual tumor after surgery (P = .01). The cumulative 5-year survival rate (95% confidence interval) was 37.3% (18.1-56.6) in patients with Rh- phenotype and 47.0% (39.2-54.4) in patients with Rh+ phenotype. The Rh D phenotype did not affect survival independently either in univariate analysis (P = .27) or in multivariate analysis (P = .55). The relative risk of death in D-negative versus D-positive patients decreased from 1.36 (95% confidence interval, 0.80-2.30) in univariate analysis to 0.84 (0.47-1.49) in multivariate analysis after controlling for depth of tumor invasion, lymph node metastases, and type of resection. Our study did not confirm the prognostic significance of Rh D phenotype in gastric cancer patients.

[Advanced gastric adenocarcinoma with RER+ phenotype presents a good prognosis after 5 years of curative resection]. / L'adenocarcinoma gastrico avanzato con fenotipo RER+ presenta una buona prognosi a cinque anni dalla resezione curativa (R0).

Microsatellite instability (MIN) has been found both in advanced and early gastric cancer. To find out the step played by MSI in gastric carcinogenesis, links between RER+ phenotype and clinical and pathological aspects have been studied. In this work our purpose is to analyze the relationship between MIN+ advanced gastric cancer and prognosis at 5 years after radical surgery. We investigated 34 patients affected by gastric cancer who underwent R0 surgical resection from February 1991 to October 1994. After that, they underwent a four-monthly follow-up for a minimum of 5 years. Genetic abnormalities have been searched including (a) those occurring in common-type CIN carcinomas and (b) those characteristic of MIN cancers. DNA extraction showed the presence of microsatellite instability (MIN) in 9 (26%) of the samples (vs. 74% of chromosomal instability CIN); none of them was M+ (vs. 12% of CIN cancers). Recurrence occurred in 2 out of 9 of the MIN cancers (22%) and in 21 out of 25 CIN cancers (84%). In conclusion, our data suggest that advanced gastric cancers with mutator phenotype show a better outcome at 5 years than the CIN phenotype.

[Abdominal metastasis of cardias adenocarcinoma]. / Studio della diffusione neoplastica addominale nell'adenocarcinoma del cardias.

BACKGROUND: The aim of the present study was to evaluate the incidence of abdominal lymph node involvement of adenocarcinoma of the gastric cardia in relationship with the site and depth of tumor invasion. METHODS: From July 1988 to April 1998, 79 patients with adenocarcinoma of the gastric cardia underwent surgical curative resection and D2 lymphadenectomy at the 1st Department of General Surgery of Verona University. Among these 79 patients, 16 had an adenocarcinoma of the distal esophagus (type I), 26 patients had an adenocarcinoma of the anatomic cardia (type II) and 37 had a subcardial adenocarcinoma (type III). The frequency of lymph node involvement in each of the lymph nodes as classified by the JRSGC were analyzed. RESULTS: In type I carcinoma positive lymph nodes occurred in 20% of pT1, 33% of pT2 and 100% of pT3. Positive nodes along the lower half of the stomach were never found. In type II carcinoma positive lymph nodes occurred in 57% of pT1, 86% of pT2 and 83% of pT3. Metastasis along the greater curvature in 18% of advanced cancers were found. In type III carcinoma positive lymph nodes occurred in 83% of pT2, 94% of pT3 and in 100% of pT4. Nodes along greater curvature were involved in 21% of advanced cases and also infrapyloric lymph nodes involved in 13% of cases. The type II and III advanced tumors had involved paraortic lymph node in 33% of cases. CONCLUSIONS: These results suggest that for tumors of the cardia an extended lymphadenectomy is necessary to ensure the removal of all metastatic nodes.

Experience of endoscopic ultrasound in staging adenocarcinoma of the cardia.

AIM: The introduction of endoscopic ultrasonography (EUS) has generally resulted in a more accurate assessment of gastrointestinal regional tumour stage. Knowing the stage and the extent of oesophageal involvement is extremely important as a guide to the choice of surgical approach in cardia cancer. The aim of this study was to evaluate the ability of EUS to accurately predict depth of tumour invasion (T), node involvement (N) and the tumour's invasion length along the oesophagus. MATERIAL AND METHODS: Thirty-five patients with adenocarcinoma of the cardia were studied by EUS and the EUS pre-operative findings were compared with the pathology findings. RESULTS: The overall accuracy in T staging was 55.2% (16/29 cases). The sensitivity in evaluating T1, T2 and T3 classes was 80%, 38.5% and 70%, respectively. The sensitivity was excellent in evaluating N0 class (100%) (5 cases), but it fell to 66.7% in N1 cases. EUS correctly determined the extent of oesophagus invasion in 75.9% (22/29) of cases; moreover, it had a very high accuracy in distinguishing between tumours with an oesophageal invasion greater or lower than 2 cm (93.1%) (27/29 cases). CONCLUSION: EUS proved to be useful in pre-operative staging of cardia adenocarcinoma and, in particular, in the pre-operative identification of the extent of oesophageal invasion.

[Immunohistochemical study on the prognostic value of the expression of laminin and Ki-67 receptors in advanced gastric cancer]. / Studio immunoistochimico sul valore prognostico dell'espressione del recettore per la laminina e del Ki-67 nel cancro gastrico avanzato.

The expression of 67-KDa laminin receptor (LR) was investigated in a group of 75 patients who underwent curative gastrectomy for advanced gastric cancer, with special reference to the possible role in the tumor progression and in the overall survival. In 56 out of these 75 patients also the prognostic significance of proliferative activity was investigated using the monoclonal antibody Ki-67. The tumor LR expression and the Ki-67 labeling index (Ki-67 LI) were immunohistochemically determined in paraffin-embedded sections using the avidin-biotin immunoperoxidase method. The cumulative 5-years survival rate was 75.1% for patients without expression of LR, 52.6% for those with positive LR expression. Significant association between LR expression and depth of tumor invasion (p = 0.022) was found. By univariate analysis the presence of laminin receptor seemed to be associated with an higher risk of death (RR1.73-95% C.I. 0.71-4.20), but this effect disappeared after controlling for depth of tumor invasion. There was no significant relationship between the Ki-67 LI and wall invasion (p = 0.80) or nodal status (p = 0.73). The cumulative 5-year survival rates (95% CI) were 61.0% (35.3-79.2) in patients with Ki-67 index < 10%, 52.4% (29.7-70.9) with Ki-67 index = 10%-40%, 52.9% (27.6-73.0) with Ki-67 index > 40% and the differences were not statistically significant (p = 0.93). Also in multivariate analysis the proliferative activity did not independently affect survival (p = 0.98). An interaction between Ki-67 index and age was found and Ki-67 index > 40% was significantly associated with a poor prognosis in patients over 70 years old old (p = 0.002). In conclusion, tumor expression of laminin receptor could be correlated with gastric cancer aggressiveness, however its prognostic significance is already provided by depth of tumor invasion. The proliferative activity, determined with the monoclonal antibody Ki-67, does not seems to influence the survival except in elderly patients (> or = 70 years old).