Pablo Varela-Centelles

Is diagnostic delay related to advanced-stage oral cancer? A meta-analysis

Diagnostic delay in oropharyngeal cancer may be associated with poor prognosis. As controversy exists on this topic because of contradictory results, the aim of this study was to perform a systematic review of the relationship between total diagnostic delay and advanced disease stages. A systematic search of MEDLINE, EMBASE, and ISI proceedings was made to identify observational studies that provided relative risks (RRs) and 95% confidence intervals (CIs) for patients with confirmed pathological diagnosis. The outcome of interest was disease stage (TNM classification), while the exposure of interest was the total diagnostic delay. The study-specific adjusted log RRs for cohort studies were weighted by the inverse of their variance to compute a pooled RR and its 95% CI. The fixed-effects pooled RR of advanced stages of oropharyngeal cancer when diagnostic delay is present was 1.32 (95% CI: 1.07-1.62). This association was stronger when the analysis was restricted to oral cancer (pooled RR: 1.47; 95% CI: 1.09-1.99) and when delay was longer than 1 month (pooled RR: 1.69; 95% CI: 1.26-2.77). The probability for patients with delayed diagnosis to present an advanced-stage tumour at diagnosis was significantly higher than that of patients with no delay in diagnosis. However, new prospective studies with strict methodology are needed to shed more light on this association.

Oral lichen planus: a clinical and morphometric study of oral lesions in relation to clinical presentation

Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical presentations that can be classified as reticular or atrophic-erosive. Sixty-two OLP patients were studied to evaluate the clinical-pathologic characteristics of their OLP lesions and to investigate possible differences in their biological behavior. The most common clinical presentation was the reticular type (62.9% vs 37.1%). Atrophic-erosive presentations showed significantly longer evolution (chi square=4.454; p=0.049), more extensive lesions (chi square=16.211; p=0.000) and more sites affected than reticular ones (chi square=10.048; p=0.002). Atrophic-erosive OLP was more frequently found on the tongue, gingiva and floor of the mouth. No statistically significant differences could be identified between reticular and atrophic-erosive clinical presentations in terms of age, sex, tobacco habit, plasma cortisol level and depth of inflammatory infiltrate. We concluded that the classification of OLP lesions as reticular vs atrophic-erosive is a simple, easy to use classification that can identify clinical presentations with different biological behavior.

Impact of delay in diagnosis on survival to head and neck carcinomas: a systematic review with meta‐analysis

Clin. Otolaryngol. 2012, 37, 99–106

Metastatic tumours to the oral cavity: a survival study with a special focus on gingival metastases

AIMS To describe survival from oral metastases, particularly gingival metastases, and to identify clinical prognostic variables. MATERIALS AND METHODS A series of 39 patients were studied, analysing age, gender, primary tumour site, oral metastases site and histological type. RESULTS Mean age: 62.3+/-9.2 years, with similar prevalence by gender. The most frequent sites for primary tumours were the kidney (20.5%), lung (20.5%) and breast (20.5%). Gingival metastases represented 63.6% of all oral soft tissue metastases (7/11). The average time between primary tumour diagnosis and appearance of the gingival metastases was 9.7+/-13.4 months. The median survival time since gingival metastases appearance was 5.2 months [95% confidence interval (CI)=0-13.6]; no statistically significant difference with other oral locations was found by the Kaplan-Meier curves (log rank: 0.29; p>0.05). Oral metastases involving the gingiva were more frequently found in the maxilla (85.7%versus 14.3%), whereas intra-osseous metastatic tumours were more frequent in the mandible (77.8%versus 22.2%; p<0.05; odds ratio=21; 95% CI=2.0-210.1). None of the variables considered had a prognostic value as indicated by the Kaplan-Meier test. PRACTICAL IMPLICATIONS The data in this paper show that 25% (and in other studies up to 37%) of oral metastases came from unknown primary tumours; thus a biopsy with histopathologic analysis is mandatory for every patient with a gingival mass. CONCLUSIONS This study reinforces the significance of gingival metastases as a poor prognosis indicator. Dental practitioners should suspect that gingival masses mimicking benign or inflammatory lesions may represent a sign of underlying malignant tumours.

Factors related to late stage diagnosis of oral squamous cell carcinoma.

Aims: To identify factors related to advanced-stage diagnosis of oral cancer to disclose high-risk groups and facilitate early detection strategies. Study design: An ambispective cohort study on 88 consecutive patients treated from January 1998 to December 2003. Inclusion criteria: pathological diagnosis of OSCC (primary tumour) at any oral site and suffering from a tumour at any TNM stage. Variables considered: age, gender, smoking history, alcohol usage, tumour site, macroscopic pattern of the lesion, co-existing precancerous lesion, degree of differentiation, diagnostic delay and TNM stage. Results: A total of 88 patients (mean age 60±11.3; 65.9% males) entered the study. Most patients (54.5%) suffered no delayed diagnosis and 45.5% of the carcinomas were diagnosed at early stages (I-II). The most frequent clinical lesions were ulcers (70.5%). Most cases were well- and moderately-differentiated (91%). Univariate analyses revealed strong associations between advanced stages and moderate-poor differentiation (OR=4.2; 95%CI=1.6-10.9) or tumour site (floor of the mouth (OR=3.6; 95%CI=1.2-11.1); gingivae (OR=8.8; 95%CI=2.0-38.2); and retromolar trigone (OR=8.8; 95%CI=1.5-49.1)). Regression analysis recognised the site of the tumour and the degree of differentiation as significantly associated to high risk of late-stage diagnosis. Conclusions: Screening programmes designed to detect asymptomatic oral cancers should be prioritized. Educational interventions on the population and on the professionals should include a sound knowledge of the disease presentation, specifically on sites like floor of the mouth, gingivae and retromolar trigone. More studies are needed in order to analyse the part of tumour biology on the extension of the disease at the time of diagnosis. Key words: Oral cancer, advanced-stage, diagnosis, cohort study.

Proliferative activity and diagnostic delay in oral cancer

Tumor stage may relate to the chronology of neoplasm growth and has been used as an outcome variable when studying diagnostic delay in oral cancer. However, tumor growth rate may act as a confounding factor.

Heat shock proteins (HSP70 and HSP27) as markers of epithelial dysplasia in oral leukoplakia.

Heat shock proteins (HSPs) play a significant role in cell proliferation, differentiation, and oncogenesis. HSP70 and HSP27 are constitutively and gradually expressed in a broad range of normal tissues and neoplasms, and their expression has been assessed as markers for oral epithelial dysplasia. The study involved 43 patients with oral leukoplakia (OL): 23 were categorized as nondysplastic and 20 as dysplastic OLs. Immunohistochemistry was carried out with the monoclonal antibodies HSP70 and HSP27. The presence of epithelial dysplasia and its histologic grading was evaluated according to the World Health Organization classification: mild, moderate, and severe squamous epithelial dysplasia. Expression of HSPs within the epithelium was also evaluated. The difference in the percentage of HSP70 positive nuclei in nondysplastic and dysplastic OL reached statistical significance95% confidence interval = 17.74-43.82; P = 0.000). None of the 43 specimens analyzed showed positive nuclear immunostaining for anti-HSP27 antibody. No significant difference for HSP27 cytoplasmic expression could be identified between OL with or without epithelial dysplasia95% confidence interval = 0.44-3.95; P = 0.89). It is concluded that the nuclear HSP70 immunoexpression could be an objective marker for the presence of the epithelial dysplasia in OL.

Use of chalazion forceps to ease biopsy of minor salivary glands.

INTRODUCTION Pathologic features of minor salivary glands are one of the six criteria for classification of Sjogren syndrome. The presence of one or more foci of 50 or more mononuclear cells within 4 mm of gland tissue is considered supportive of this diagnosis.1 Amyloidosis is diagnosed by demonstrating the presence of amyloid protein in the affected organ. It is possible to take biopsies of affected tissues from kidney, liver, or rectum. However, it causes far less morbidity to obtain a sample of tissue from minor salivary glands as a first step toward diagnosis of amyloidosis.2 Chalazion forceps (Moria Dugast, Paris, France) are used by ophthalmologists during chalazion excisions, but its particular design also makes the device useful for taking biopsies from mobile or oral tissues.3

Membrane perforation in sinus floor elevation - piezoelectric device versus conventional rotary instruments for osteotomy: an experimental study.

PURPOSE Sinus membrane perforation is the most common intraoperative complication of maxillary sinus floor elevation (MSFE) procedures and frequently causes postoperative problems. Piezoelectric devices have been claimed to reduce the frequency of membrane perforations although no clear evidence supports this view. MATERIALS AND METHODS Ten surgeons with different expertise levels performed 80 MSFEs in selected lamb heads, with rotary and piezoelectric instruments following standard protocols. After the procedures, specimens were coded and perforations or tears determined through a microscope. RESULTS No significant differences in terms of thickness either of the sinus lateral wall (xi -xj  = 73.2; 95% confidence interval [CI] = 45.3-191.8) or the membrane (xi -xj  = 24.2; 95% CI = -29.4 to 77.9) were identified between the specimens allocated to each group. Nine membrane perforations (11.2%) occurred during the study, all within the lower expertise group. Membrane elevation by hand instruments caused five perforations (40%) in the rotary instrument group and one in the piezoelectric group. Expert surgeons produced no membrane perforations, the size of the antrostomy that was smaller in the piezoelectric group being the only significant difference between the rotary and piezoelectric groups. CONCLUSIONS The use of piezoelectric material for MSFE reduces the frequency of membrane perforation among surgeons with a limited experience.

Predictors for Tumor Recurrence After Primary Definitive Surgery for Oral Cancer

PURPOSE The purpose of this study was to identify significant predictors for oral squamous cell carcinoma recurrence. PATIENTS AND METHODS This Ambispective cohort study was performed in consecutive metastasis-free patients treated for oral squamous cell carcinoma with curative intent from 1998 through 2003. Variables included gender, age, tumor site, macroscopic pattern of the lesion, coexisting disorders (diabetes, hepatic and heart disorders, other tumors/diseases), degree of differentiation, and pathologic TNM stage. Tumor recurrence was considered the dependent variable (outcome). The distribution of recurrences was assessed with χ(2) test. Survival times were estimated by Kaplan-Meier curves and differences were examined with log-rank test. Multiple Cox regression study was also performed. The significance level chosen for all tests was P < .05. RESULTS One hundred eighteen patients entered the study. Tumor recurrence was 44.9% during the follow-up period (10% local, 29.7% regional, and 5% distant). The mean period that had elapsed before recurrence was 15 months (1.5 to 81.8), with most recurrences (66%) during the first year after treatment (84.9% before 2 years). Multivariate Cox regression analysis indicated the presence of a coexisting disorder (P = .022) as the most relevant prognostic factor for relapse, because patients with associated diseases had a 2.43-fold risk of recurrence. Tumor stage (P = .037), degree of differentiation (P = .042), and macroscopic pattern of the lesion (P = .022) were also identified as prognostic factors for relapse. CONCLUSIONS The risk profile for oral cancer recurrence includes patients younger than 60 years with coexisting diseases whose primary tumor occurred as an ulcerated lesion, and diagnosed at an advanced stage with a poorly differentiated tumor.