Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly 1 higher predictive accuracy than any single biomarker (p < 0.001.). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p < 0.001) and cancer specific mortality (4.3%, p < 0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p < 0.001). Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

Group psychotherapy: An additional approach to burning mouth syndrome

Introduction: Glossodynia or burning mouth syndrome (BMS) is a common and poorly understood disorder. Its treatment is uncertain. Otherwise, there is some evidence of the importance of psychological factors in the genesis of this disease. Objectives: Verify the usefulness of group psychotherapy as an adjuvant therapeutic method in the treatment of BMS. Casuistics and Methods: The study group consisted of 64 consecutive patients with a clinical diagnosis of BMS seen at the Stomatology Outpatient Clinic, ENT Department, Sao Paulo University Medical School, between May 2002 and May 2007. All the patients were submitted to physical examination, laboratorial screening tests, psychological assessment (Crown-Crisp Experimental Inventory), and answered a short form of the McGill Pain Questionnaire. Only 44 patients who did not show any abnormality in the protocol exams entered the study. Twenty-four of them underwent group psychotherapy. Twenty patients received placebo. Chi-square test was applied to compare the results of treatment with or without psychotherapy. Results: There were 15 men and 29 women in the study group. Tongue burning was the main complaint of the patients. Improvement of symptoms was reported by 17 (70.8%) of the patients undergoing psychotherapy, while among those who did not eight (40%) had improvement of symptoms (P=.04). Conclusion: Psychological assessment demonstrated a close correlation between symptoms and psychological factors, suggesting that group psychotherapy is an important alternative to conventional treatment methods. (C) 2009 Elsevier Inc. All rights reserved.

Dental Evaluation of Kabuki Syndrome Patients

Kabuki syndrome is a genetic disorder of unknown etiology characterized by mental retardation, growth deficiency, and peculiar face (i.e., long palpebral fissures, eversion of the lateral third of the lower eyelids, prominent ears, and broad and depressed nasal tip). Oral manifestations commonly observed in Kabuki syndrome may comprise cleft lip/palate, bifid tongue and uvula, malocclusion, and dental abnormalities. We evaluated the dental findings of eight patients with Kabuki syndrome. One presented cleft palate; three presented caries; and seven had missing teeth, with the upper lateral incisors and inferior central incisors being the most commonly absent. All missing teeth were permanent, and there was no alteration of dental chronology or morphology. Because most patients had mixed dentition, the presence or absence of primary teeth was assessed through the parents` reports. One patient presented an absent upper canine, which had not been reported previously in the literature. Dental findings may be helpful for clinical diagnosis, or they may be an additional finding to substantiate the diagnosis of Kabuki syndrome in children with mild phenotype.

Extent of Pelvic Lymphadenectomy in Women With Squamous Cell Carcinoma of the Uterine Cervix: Is There Any Prognostic Value?

Background and Objectives: Some authors states that the removal of lymph node would only contribute towards assessing the lymph node status and regional disease control, without any benefit for the patients` survival. The aim of this paper was to assess the influence of the number of surgically dissected pelvic lymph nodes (PLN) on disease-free Survival. Methods: Retrospective cohort study on 42 women presenting squamous cell carcinoma (SCC) of the uterine cervix, with metastases in PLN treated by radical surgery. The Cox model was used to identify risk factors for recurrence. The model variables were adjusted for treatment-related factors (year of treatment, surgical margins and postoperative radiotherapy). The cutoff value for classifying the lymphadenectomy as comprehensive (15 PLN or more) or non-comprehensive (<15 PLN) was determined from analysis of the ROC curve. Results: Fourteen recurrences (32.6%) were recorded: three pelvic, eight distant, two both pelvic and distant, and one at an unknown location. The following risk factors for recurrence were identified: invasion of the deep third of the cervix and number of dissected lymph nodes <15. Conclusions: Deep invasion and non-comprehensive pelvic lymphadenectomy are possible risk factors for recurrence of SCC of the uterine cervix with metastases in PLN. J. Surg. Oncol. 2009;100:252-257. (C) 2009 Wiley-Liss, Inc.

Laparoscopic resection of uncinate process of the pancreas

Solid pseudopapillary neoplasm of the pancreas is an uncommon but distinctive pancreatic neoplasm with low metastatic potential [1]. Therefore, whenever feasible, an organ-preserving operation should be performed. As previously reported, women with solid pseudopapillary neoplasm of the pancreas may be best treated by more conservative procedures [2]. Recently, laparoscopic pancreatic resections became more common and are being performed in highly specialized centers. There are only six cases of laparoscopic resection for solid pseudopapillary neoplasm of pancreas published in the English literature and, to our knowledge, laparoscopic resection of uncinate process of the pancreas has never been reported [3-6]. This video demonstrates the technical aspects of a totally laparoscopic resection of the uncinate process of the pancreas in a patient with solid pseudopapillary neoplasm. A 26-year-old woman with a 4-cm solid pseudopapillary pancreatic neoplasm was referred for surgical treatment. According to preoperative echoendoscopy, there was a safe margin between neoplasm and main pancreatic duct. The patient was placed in supine position with the surgeon standing between her legs. Four trocars, one 10-mm and three 5-mm, were used. At inspection, the inferior vena cava, transverse colon, duodenum, and pancreas are clearly identified. A Kocher maneuver was performed with complete exposure of pancreatic head and uncinate process. The uncinate process was dissected from the superior mesenteric vein and venous branches were divided between metallic clips or by use of laparoscopic coagulation shears (LCS; Ethicon Endo Surgery Industries, Cincinnati, OH, USA). Blood supply of the duodenum was preserved by ligature of small pancreatic branches from inferior pancreatoduodenal artery. Transection of pancreatic parenchyma was performed using laparoscopic coagulation shears, which is an effective tool for cutting the pancreas [7, 8]. Surgical specimen was removed through a suprapubic incision inside a retrieval bag. A hemostatic absorbable tissue (Surgicel; Ethicon Inc., Cincinnati, OH) was placed in the cutting pancreatic surface, and one round 19F Blake abdominal drain (Ethicon) was left in place. Operative time was 180 minutes and blood loss estimated in 40 ml with no blood transfusion. Hospital stay was 4 days. The patient did not have postoperative pancreatitis or pancreatic leakage, and the abdominal drain was removed on the tenth postoperative day. Final pathology confirmed the diagnosis of solid pseudopapillary neoplasm of pancreas with free surgical margins. The patient was well and asymptomatic 2 months after the procedure. Laparoscopic resection of uncinate process of the pancreas is safe and feasible and should be considered for patients suffering from pancreatic neoplasms.

Effects of Oropharyngeal Exercises on Patients with Moderate Obstructive Sleep Apnea Syndrome

Rationale: Upper airway muscle function plays a major role in maintenance of the upper airway patency and contributes to the genesis of obstructive sleep apnea syndrome (OSAS). Preliminary results suggested that oropharyngeal exercises derived from speech therapy may be an effective treatment option for patients with moderate OSAS. Objectives: To determine the impact of oropharyngeal exercises in patients with moderate OSAS. Methods: Thirty-one patients with moderate OSAS were randomized to 3 months of daily (similar to 30 min) sham therapy (n = 15, control) or a set of oropharyngeal exercises (n = 16), consisting of exercises involving the tongue, soft palate, and lateral pharyngeal wall. Measurements and Main Results: Anthropometric measurements, snoring frequency (range 0-4), intensity (1-3), Epworth daytime sleepiness (0-24) and Pittsburgh sleep quality (0-21) questionnaires, and full polysomnography were performed at baseline and at study conclusion. Body mass index and abdominal circumference of the entire group were 30.3 +/- 3.4 kg/m(2) and 101.4 +/- 9.0 cm, respectively, and did not change significantly over the study period. No significant change occurred in the control group in all variables. In contrast, patients randomized to oropharyngeal exercises had a significant decrease (P < 0.05) in neck circumference (39.6 +/- 3.6 vs. 38.5 +/- 4.0 cm), snoring frequency (4 [4-4] vs. 3 [1.5-3.5]), snoring intensity (3 [3-4] vs. 1 [1-2]), daytime sleepiness (14 +/- 5 vs. 8 +/- 6), sleep quality score (10.2 +/- 3.7vs. 6.9 +/- 2.5), and OSAS severity (apnea-hypopnea index, 22.4 +/- 4.8 vs. 13.7 +/- 8.5 events/h). Changes in neck circumference correlated inversely with changes in apnea-hypopnea index (r = 0.59; P < 0.001). Conclusions: Oropharyngeal exercises significantly reduce OSAS severity and symptoms and represent a promising treatment for moderate OSAS. Clinical trial registered with www.clinicaltrials.gov (NCT 00660777).

Genetic Polymorphisms of Matrix Metalloproteinases: Susceptibility and Prognostic Implications for Prostate Cancer

Purpose: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer. Materials and Methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by realtime polymerase chain reaction using TaqMan (R) fluorescent probes. Results: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042). Conclusions: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

Gingival juvenile xanthogranuloma in an adult patient: case report with immunohistochemical analysis and literature review

Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis (nonLCH). It is a benign and self-healing disorder that generally affects infants and children. Oral lesions in adult patients are rare, although the microscopic findings are similar to those observed in other locations. A 56-year-old white man presented with a chief complaint of a gingival mass that had appeared 6 months before and had grown slowly. An intraoral examination revealed the presence of a solitary, softened gingival mass affecting the mandibular lingual gingiva at the right central incisor area. A biopsy of the lesion showed multiple large macrophages and numerous giant cells of Touton type. The immunohistochemistry positivity for CD68, fascin, factor XIIIa, alpha-antitrypsin and negativity for S-100, beta-actin, CD1a, and desmin confirmed the diagnosis of JXG. The occurrence of adult oral JXG is extremely rare. It is a nonLCH that may present variable clinical and microscopic aspects, which leads to a diversity of clinical misdiagnoses. A precise diagnosis of these lesions requires an accurate evaluation of clinical, microscopic, and immunohistochemical features.

USE OF ANTIBIOTIC SPACERS FOR KNEE ENDOPROSTHESIS INFECTIONS TREATMENT

Objective: The aim of this study is to evaluate the use of cement spacers impregnated with antibiotics for the treatment of infections in the nonconventional endoprostheses of the knee. Methodology: We have treated seven patients since 2004 (of which six were submitted to surgery in our service and one patient had been submitted to a primary tumor surgery in another removal service) with deep infection in knee tumor prosthesis. All patients were submitted to endoprosthesis removal and reconstructed with antibiotic cement spacer All patients were monitored both clinically and by lab tests as for monitoring the evolution, being considered able for reviews after 6 (six) months without infections signs. Results: We have noted a small predominance of infectious processes on the prosthesis inserted on proximal tibia as compared with distal femur (57.1% x 42.9%). The mean follow-up time of patients was 68.2 months. During the follow up, one patient died as a result of the root disease. Six patients out of seven were regarded as cured and one persisted with infection signs and symptoms. Conclusion: The results obtained up to date have motivated us to continue using this method of treatment.

Carcinoid syndrome - Case report

Carcinoid tumors are rare neoplasms with, an estimated incidence of I to 2 cases per 100, 000 inhabitants. The malignant carcinoid syndrome, characterized by flushing, diarrhea, abdominal pain and, less frequently, pellagra, bronchospasm and valvular disease, occurs in less than 10% of patients. Nevertheless, in advanced stages of the disease, the incidence is about 40 to 50%. Retrospective studies and descriptive case series have shown that cutaneous involvement is relatively common but has rarely been reported. We present a case of carcinoid syndrome diagnosed with basis on skin findings on clinical examination.

Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific antigen expression in unusual subtypes of prostate cancer

There are some unusual histologic variants of prostate carcinoma, including mucinous, signet-ring cells, and ductal carcinomas that can metastasize in a problematic way and simulate lung, colorectal, or bladder primaries. Currently, antibodies that are organ-specific have been used in the routine surgical pathology practice. Our aim is to study the profile of expression of Cdx2, thyroid transcription factor 1 (TTF1), and cytokeratin 20 (CK20) in prostate cancer with unusual histologic finding. Twenty-nine prostate adenocarcinomas with unusual histologic findings were submitted to immunohistochemistry with prostate-specific antigen (PSA), CK20, Cdx2, and TTF1 antibodies. There were 7 mucinous, 5 ductal, 2 signet-ring cells, and 15 usual acinar adenocarcinomas with focal mucinous differentiation. To compare the results with usual acinar adenocarcinomas, we studied 10 primary and their respective lymph node metastases in a tissue microarray, 2 unusual metastatic adenocarcinomas, and 6 usual acinar high-grade carcinomas. For tumors with special histologic finding, Cdx2 was expressed by 9 (31.0%) mucinous, signet-cell, or with focal mucinous differentiation. Thyroid transcription factor I was moderately positive in mucinous differentiation areas of 2 (6.9%) adenocarcinomas. Cytokeratin 20 was expressed by 9 (31.0%) tumors, among them, 3 ductal adenocarcinomas. Prostate-specific antigen was positive in 28 (96.6%) cases and negative in I ductal adenocarcinoma. There was only I worrisome ductal adenocarcinoma that was strongly CK20 positive and PSA negative. Almost one third of mucinous prostate carcinomas express Cdx2. Cytokeratin 20 can be positive also in one third of prostate carcinomas, especially the ductal type. Pathologist should be alert when evaluating immumohistochemical profiles of unusual histologic findings of prostate cancer, mostly in distant sites. (C) 2008 Elsevier Inc. All rights reserved.

Skin cancer in Taubate (SP) - Brazil, from 2001 to 2005: a prevalence study

BACKGROUND - Cancer represents the third principal cause of death in Brazil. Skin is the most frequent location and about 50% of caucasian patients older than sixty years will develop some type of cutaneous cancer OBJECTIVE - To describe the profile of the individuals with skin cancer assisted at the University Hospital of Taubate in the period between 2001 and 2005. METHODS - A hospital-based cross-sectional study involving individuals assisted at the Dermatology Department at the University Hospital of Taubate in the period between January 2001 to December 2005 was performed. Study variables were gender, age, skin color, location and clinical type of the tumor basal cell carcinoma, squamous cell carcinoma, combined and melanoma. Statistical analyses were performed using qui-square, Student`s t-test and ANOVA. RESULTS - A total of 639 individuals were included in the study. Prevalence was 50 cases/100.000 inhabitants. The most prevalent age group was that of individuals older than sixty years of age, gender distribution was higher among females than males (57.2% / 42.8%) and the proportion of white to non-white was of 4:1. CONCLUSION - This study fills a gap that was due to the inexistence of studies in the region and also to the small number of studies in the state of Sao Paulo, and its results are in accordance with, those in the literature.

Clinico-pathological discrepancies in the diagnoses of solid malignancies

Autopsy is a valuable tool in evaluating diagnostic accuracy. Solid malignancies may have a protracted presentation, and diagnosis frequently requires imaging and deep-sited biopsies; clinical and postmortem diagnosis discrepancies may occur in a high rate in these diseases. Here, we analyzed the occurrence of clinico-pathological discrepancies in the diagnoses of solid malignancies in a Brazilian academic hospital. We reviewed charts and autopsy reports of the patients that died from 2001 to 2003 with at least one solid neoplasm. Patients were classified in concordant and discordant cases regarding cancer diagnosis. Discordant cases were categorized in undiagnosed cases (no suspicion of cancer) and in misdiagnosed cases (clinical suspicion of cancer but incompletely diagnosed). Among the 264 patients with a single non-incidental solid neoplasm, the clinico-pathological discrepancy rate was 37.1%. Liver (22.5%), lung (19.4%), and pancreatic cancer (15.3%) were the most frequent malignancies in the discordant group. Misdiagnosis category comprised 68% of the discordant cases, i.e., there was no correct knowledge about the tumor primary site and/or the histological type during life. Our data show that a high rate of discrepancies occurs in solid malignancies. Autopsies may provide the basis for a better understanding of diagnostic deficiencies in different circumstances. (C) 2008 Elsevier GmbH. All rights reserved.

Vestibular rehabilitation with biofeedback in patients with central imbalance

Central Nervous System disorders may cause important functional unbalance in the maintenance of balance and posture. There is no effective rehabilitation for these symptoms until now. Objective: The aim of this paper is to evaluate the use of tongue electrotactile stimulation on patients with central imbalance using BrainPort. Materials and Methods: This is a prospective case series study. We evaluated 8 patients with central imbalance, 6 men and 2 women, with mean age of 67.75 years. The patients were submitted to Computed Dynamic Posturography (CDP) and then received 18 sessions of electrotactile stimulation by BrainPort (R) device for 20 minutes, twice a day. Then they were submitted to a new CDP test and to a self-perception scale to assess symptom remission, partial improvement and no improvement at all. Results: 75% of the patients reported being more stable. There was no improvement in the balance control of the mass center in these patients. Conclusion: The patients were able to use the electrotactile stimulus to improve their balance control.

Oral lesions in HIV infected individuals from Ribeirao Preto, Brazil

Objectives: The aim of this study was to diagnosis oral lesions related to HIV infection in individuals followed in the General Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. The presence of oral lesions was correlated with gender, age, smoking habit, levels of CD4 lymphocytes, HIV load, time of HIV seropositivity, AIDS condition, use of removable dental prosthesis, and use of HAART. Materials and Methods: 340 HIV infected individuals were selected for this study, all participants of the study were examined by only one practiced dentist which performed anamnesis, peribuccal and oral examination. Results: Oral lesions were observed in 113 of 340 (33.2%) HIV infected individuals. These oral lesions included: oral candidiasis (17.7%) of pseudomembranous (10.8%) and of erythematous types (6.9%), angular cheilitis (13.9%), hairy leukoplakia (11.8%), and oral ulcers (2.1%). Oral candidiasis lesions were more frequently observed in women (p. 033). Smoking addict participants presented a high frequency of tongue hairy leukoplakia (p. 038) and a reduced frequency of oral ulcers (p. 018). Hairy leukoplakia and pseudomembranous candidiasis were inversely correlated to CD4+ L levels and directly correlated with HIV load, behaving as immune depression markers. Hairy leukoplakia and pseudomembranous candidiasis also showed an inverse correlation with HAART use (p < .0001). Patients using mobile dental prosthesis presented a high frequency of erythematous candidiasis (p. 003). Conclusion: The inverse correlation with CD4+ L level and the direct correlation with HIV load suggest that oral lesions could be used as alternative clinical markers for poor immune condition in HIV infected individuals.