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Biomedical subjects

M D Mignogna

Publications and source records attributed to M D Mignogna.

At least 19 recordsLinked to original sources

Field cancerization in oral lichen planus.

BACKGROUND: The concept of field cancerization describes the tendency of patients with premalignant and malignant lesions of head and neck mucosal sites to develop multiple carcinomas of the upper aerodigestive tract. Here we address whether this concept should be extended also to patients affected by oral lichen planus (OLP), an inflammatory disorder associated with an increased risk of cancer development. METHODS: Data from a cohort of 45 patients with OLP who subsequently developed severe dysplastic changes and/or oral squamous cell carcinoma were retrospectively reviewed. Patients who presented more than one oral neoplastic event were considered for further data analysis as regards incidence, localization, management and prognosis. RESULTS: Twenty (44.4%) patients were affected by one single neoplastic event while 25 (55.6%) developed multiple and often multifocal oral dysplastic and/or malignant events. In most cases, a careful surveillance programme led to diagnosis and effective treatment of oral neoplasias at an early intraepithelial and microinvasive stage, leading to long-term survival. In some patients, however, additional primary tumours occurred suddenly with rapid invasion, leading to advanced stage diagnosis and poor prognosis. Overall, three patients (12%) died due to malignant oral disease. CONCLUSIONS: Patients with OLP and subsequent development of dysplasia/ oral squamous cell carcinoma are at risk of having multiple and multifocal neoplastic events of the oral cavity, a phenomenon which parallels the concept of field cancerization of traditional head and neck cancers. If detected at an early stage, these neoplasias can be managed with superficial and complete resection. However a small number of patients have loco-regional tumour spread despite a standard surveillance protocol.

Adult↗

Treatment of Gorham's disease with zoledronic acid.

Gorham's disease (GD) is a rare disorder characterized by spontaneous and progressive osteolysis of one or more bones and thought to belong to lymphangiomatoses spectrum of diseases. Surgical, radiation and medical therapies have been performed with variable and often discouraging outcomes and currently there is no recognized effective treatment. In this paper we describe a 24-year-old girl with GD localized to mandible who was effectively managed with zoledronic acid, a nitrogen-containing high-potency bisphosphonate.

Adult↗

Sjögren's syndrome: the diagnostic potential of early oral manifestations preceding hyposalivation/xerostomia.

Sjögren's syndrome (SS) is a systemic autoimmune exocrinopathy that affects mainly the salivary and lacrimal glands, leading to progressive reduction in saliva and tear flow. Although the underlying immuno-mediated glandular destruction is thought to develop slowly over several years, a long delay from the start of the symptoms to final diagnosis has been frequently reported. A limited knowledge concerning SS natural history is among the major causes of the actual diagnostic delay. Although very few studies have been focused on the analysis of SS early clinical onset, a series of oral features preceding xerostomia/hyposalivation development in patients eventually diagnosed as having SS have been reported. Sialochemistry alterations, salivary gland swelling, early dental loss and sialorrhea have been observed before the onset of typical signs and symptoms (namely xerostomia and/or hyposalivation), which usually lead to SS clinical presentation and diagnosis. Here we suggest, after evaluating available data, that the traditional 'untouchable' association between SS and xerostomia/hyposalivation might probably be reconsidered, and that astute clinicians should not underestimate the possible presence or development of SS in patients without xerostomia/hyposalivation and presenting these atypical early oral features.

Early Diagnosis↗

Number II. Pemphigus vulgaris.

Pemphigus is a group of potentially life-threatening autoimmune diseases characterized by cutaneous and/or mucosal blistering. Pemphigus vulgaris (PV), the most common variant, is characterized by circulating IgG antibodies directed against desmoglein 3 (Dsg3), with about half the patients also having Dsg1 autoantibodies. There is a fairly strong genetic background to pemphigus with linkage to HLA class II alleles and ethnic groups such as Ashkenazi Jews and those of Mediterranean and Indian origin, are especially liable. Oral lesions are initially vesiculobullous but readily rupture, new bullae developing as the older ones rupture and ulcerate. Biopsy of perilesional tissue, with histological and immunostaining examination are essential to the diagnosis. Serum autoantibodies to either Dsg1 or Dsg3 are best detected using both normal human skin and monkey oesophagus or by enzyme-linked immunosorbent assay. Before the introduction of corticosteroids, PV was typically fatal mainly from dehydration or secondary systemic infections. Current treatment is largely based on systemic immunosuppression using corticosteroids, with azathioprine or other adjuvants or alternatives but newer therapies with potentially fewer adverse effects, also appear promising.

Adrenal Cortex Hormones↗

Effectiveness of small-volume, intralesional, delayed-release triamcinolone injections in orofacial granulomatosis: a pilot study.

BACKGROUND: Orofacial granulomatosis (OFG) is an idiopathic disorder characterized by chronic orofacial swellings causing significant cosmetic and functional problems. Treatment with high-volume triamcinolone injections has been shown to be effective but requires nerve block anesthesia and causes a dramatic temporary increase of lip swelling. OBJECTIVE: We have performed a noncomparative open-label pilot study in 7 patients with OFG in order to evaluate the effectiveness of small volumes of extended-release high-concentrate triamcinolone injections in reducing lip swelling and preventing recurrences. METHODS: Seven patients with OFG were studied. Small-volume, intralesional, high-concentrate, extended-release triamcinolone was injected on the basis of a weekly schedule. A standard cycle consisted of 2 or 3 injection sessions over 14 or 21 days, depending on the clinical response. RESULTS: After cycle completion, all patients remained without recurrences or with cosmetically acceptable slight lip enlargement for a mean time of 19 months (range, 8-30 months). No side effects were observed, except in one patient with hypopigmentation of the skin of the upper lip. CONCLUSIONS: Slow-volume, intralesional, high-concentrate, extended-release triamcinolone injections appear to be effective in reducing lip enlargement in patients with OFG and do not require nerve block anesthesia or cause a temporary troublesome increase of swelling. A long disease-free period is generally obtained.

Adult↗

The World Cancer Report and the burden of oral cancer.

The WHO has recently provided the most comprehensive global examination of cancer to date, through the publication of the World Cancer Report (WCR). According to IARC-WHO estimates, cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000, to 15 million in 2020. However, the report states that we have the opportunity to stem the predicted sharp increase in new cancer cases by taking action now, especially through planning effective cancer control strategies, such as reducing tobacco consumption, suggesting healthy lifestyle and diet, and performing early detection through screening. Although cancer of the oral cavity is largely related to lifestyle and can be easily detected and diagnosed at early stages through a 5 min visual inspection of the oral mucosa, actual figures concerning its prevention and early detection are dismal. Most oral cancers are detected at a late stage, requiring complex, costly and often ineffective therapies. Similarly, current research, educational and financial resources are focused on procedures burdened by high cost, high morbidity and unacceptable high mortality. Here we suggest that it is time to change this common point of view towards this disease and to alter this trend, stressing that there is no other oncologic specialty in which the WCR preventive guidelines could be applied in such an easy and effective manner, as in the field of oral cancer.

Cost-Benefit Analysis↗

HCV infection and oral lichen planus: a weak association when HCV is endemic.

Oral lichen planus (OLP), an immune-mediated disorder, has been reported as an extra-hepatic manifestation of Hepatitis C virus (HCV) infection, especially in HCV hyperendemic areas such as southern Europe and Japan. The aim of this study was to investigate from an epidemiological standpoint whether HCV infection is an important factor affecting the relative risk of OLP in a Mediterranean population or whether this relates to the degree of HCV endemicity. Two cohorts of OLP patients resident in two different regions of southern Italy (Campania and Sicily; n = 859) were evaluated for HCV infection status and categorized into five age classes to respective region-matched controls. No significant difference was found between OLP patients and the general population in this area, when data were corrected by the age-stratified prevalence of HCV. Therefore, the age-specific prevalence of HCV infection in OLP patients shows a close trend of direct association with increasing age, without significant differences with the general population of each geographical area. An aetiological link between OLP and HCV cannot be inferred solely by epidemiological data.

Adult↗

Anorexia/bulimia-related sialadenosis of palatal minor salivary glands.

In patients affected by alimentary disorders sialadenosis is frequently observed. This non-inflammatory condition is described to affect major salivary glands, leading to the characteristic parotid and/or submandibular swelling. Thus fine-needle aspiration cytology or parotid open biopsy are generally required to diagnose histologically the disorder. We report the case of a 28-year-old patient affected by bulimia/anorexia nervosa who presented, in addition to parotid enlargement, a bilateral symmetric painless soft swelling of the hard palate. The lesion was biopsied and histopathological examination showed the classical features of sialadenosis. To our knowledge, this is the first case of sialadenosis affecting palatal minor salivary glands. It underlines that when sialadenosis is clinically suspected, clinicians could check also patients' oral cavity for minor salivary glands involvement, in order to potentially avoid invasive extra-oral procedures and to easily confirm diagnosis with an intra-oral biopsy.

Adult↗

P-cadherin expression predicts clinical outcome in oral squamous cell carcinomas.

P-cadherin, a transmembrane molecule similar to E-cadherin involved in the cell-cell adhesion, and catenins form complexes between its cytoplasmic domain and the cytoskeleton. Five cell lines, 108 specimens of oral squamous cell carcinomas (OSCC), 9 metastasis and 10 of normal oral mucosa were examined to evaluate P-cadherin expression and cellular localization by immunohistochemistry and western-blotting. In normal oral mucosa there was a membranous expression only in basal and parabasal layers. 91 cases (84%) showed membranous/cytoplasmic positivity, whereas 17 cases (16%) were negative. In particular, while well-differentiated carcinomas showed P-cadherin upregulation, the protein was homogeneously hypo- or unexpressed in low-differentiated carcinomas. There was a statistically significant correlation between P-cadherin expression and tumour grading: G3 tumours had a lower score than G1-G2 tumours (P<0.05). When analysed for prognostic significance, patients with no P-cadherin expression (score 0) had poorer overall and diseases-free survival rates than the P-cadherin-expressing group (score 1) (P=0.0463 and P=0.0471, respectively). Western blotting analysis of cell lines and tissue samples confirmed immunohistochemical findings. When cell staining pattern of positive cases was examined, 52 cases showed a prevalent membranous pattern, while 39 had a prevalent cytoplasmic pattern. Cases with prevalent cytoplasmic staining showed high rates of lymph node metastases (P>0.05), and regional relapse (P <0.05) and poorer survival rates than the group with prevalent membranous expression (P<0.0001). An absent P-cadherin expression could constitute a hallmark of aggressive biological behaviour in oral squamous cell carcinoma.

Adult↗

HSP 27 as possible prognostic factor in patients with oral squamous cell carcinoma.

UNLABELLED: HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stress-induced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. MATERIALS AND METHODS: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. RESULTS: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor ("mosaic" pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. CONCLUSION: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.

Adult↗

Survivin expression in oral squamous cell carcinoma.

A series of 110 cases of oral squamous cell carcinoma (SCC) together with six lymph node and one distant metastatic lesions was analysed for expression of survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven cases, 100%) were positive for survivin expression, with weighted survivin scores ranging from 1 to 4. In contrast, normal oral epithelium did not express survivin. There was no significant correlation between survivin expression and age, sex, tumour size, the presence of lymph node and distant metastases. Survivin expression was increased in poorly differentiated tumours, even if differences were not statistically significant. In contrast, when analysed for prognostic significance, patients with low survivin expression had statistically significant better survival rates than the group with high survivin expression (P<0.05). These data suggest that survivin expression may identify cases of oral SCC with more aggressive and invasive phenotype.

Adult↗

Survivin, a potential early predictor of tumor progression in the oral mucosa.

Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.

Adult↗

p120(cat) Delocalization in cell lines of oral cancer.

UNLABELLED: p120(cat) is a novel component of the catenin family, a cytoplasmic molecule closely associated with the cell-cell adhesion molecule E (epithelial)-cadherin, by forming complexes between the cytoplasmic domain of E-cadherin and the cytoskeleton. Recent studies suppose a role for this molecule in human cancers and to date none report its expression in oral squamous cell carcinomas (SCCs). The goal of this study was to evaluate the role of this protein in the oral carcinogenetic process. A linked streptavidin-biotin-alkaline phosphatase technique was used to examine the immunoreactivity and cellular localisation of p120(cat) in five oral epithelial cell lines (NCTC 2544, normal and immortalized keratinocytes; KB, a poorly differentiated SCC cell line; OSC 20, a well differentiated oral SCC cell line; CAL 33 and CAL 27, moderately differentiated oral SCC cell lines) and 10 normal oral epithelium biopsies. RESULTS: As already reported for E-cadherin, beta- and gamma-catenin, p120 expression showed a homogeneous membranous localization in normal oral specimens. The intensity of staining for p120 progressively increased from basal and parabasal layers toward the intermediate spinous layer. No staining for p120 was observed in the upper layer. NCTC showed a membranous positivity. OSC 20, CAL 33 and CAL 27 showed a membranous positivity, even if polarized to cell-cell adhesion sites, in 40-50% of cells. OSC 20, CAL 33 and CAL 27 cells showed also a cytoplasmic delocalization. All positive KB cells showed a prevalent cytoplasmic staining and 10% of these cells showed a nuclear delocalization. In cancer cells, p120 showed an inverse relationship with the degree of differentiation for a progressive displacement of the signal toward the cytoplasm or nucleus in dedifferentiated cells. In conclusions, this nuclear delocalization for p120 could suppose its potential involvement in signalling and cancer transformation.

Carcinoma, Squamous Cell↗

Clinical behaviour of malignant transforming oral lichen planus.

AIMS: At present oral lichen planus (OLP) is classified among precancerous conditions but very few data are available in literature regarding prognosis of OLP-related cancers. The aim of this paper is to evaluate clinical long-term behaviour of OLP-related oral squamous cell carcinomas (OSCCs). METHODS: Clinical history and data from follow-up regarding 21 patients undergoing malignant transformation of OLP have been critically revised. RESULTS: In a mean time of 2.6 years from diagnosis of OLP, patients developed OSCCs. Histopathologically, two carinomas showed a moderate degree of differentiation, while the others were well differentiated. Six (28.5%) were in situ OSCC, in eight (30%) was found a microinvasive pattern of infiltration, one was a stage II tumour and the remaining (6 cases) were stage I tumours. During follow up, four patients (19%) have developed another OSCC in a mean time of 11 months from the first occurrence. In two men (10% of cases), multiple OSCCs occurred and in five cases (24%) lymph nodal metastases were detected. CONCLUSIONS: Our study points out an alarming tendency in developing second primary metachronous tumours (33.3%) of the oral cavity and nodal metastases (23.8%), especially if we consider their early stages. Thus we always recommend a strict follow-up of OLP patients with clinical oral and neck examination every 2 months for 6-9 months since OSCC diagnosis is made and, after, three times a year.

Adult↗

Costs and effectiveness in the care of patients with oral and pharyngeal cancer: analysis of a paradox.

Oropharyngeal cancer is estimated to be the ninth most common cancer worldwide. Its prognosis is largely dependent upon tumour-stage at the time of diagnosis. Stage I and II oropharyngeal cancers are characterized by a 5-year survival rate ranging from 70% to 90%, and the management of these early carcinomas is usually of short duration, easy and very cost-effective. On the other hand, the diagnostic evaluation, treatment and management of complications and recurrences of advanced stage oral tumours (stage III and IV) are often very long, complex and costly. They also have very poor prognosis with survival figures dropping to about 20%. Nowadays, most oropharyngeal cancers are detected at a late stage with an overall 5-year survival rate of around 45-50%, and with a conspicuous increase in treatment costs and a worsening of prognosis. Even if formal and comprehensive cost-effectiveness and cost-benefit analyses are not currently available in the oropharyngeal cancer literature, it seems clear that, in the care of these patients, the enormous consumption of resources is not associated with acceptable outcomes. New initiatives should be evaluated, planned and developed for the care of patients with oral and pharyngeal cancer. These strategies should be directed at prevention and early diagnosis in order to increase patient survival and quality of life and decrease the consumption of health care resources.

Cost-Benefit Analysis↗

Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma.

Deregulated expression of inhibitors of apoptosis (programmed cell death) may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to therapy. In this study, we investigated the potential expression and prognostic significance of the apoptosis inhibitor survivin in squamous cell carcinoma (SCC). A series of 135 cases of SCC including 46 oral SCC and 89 cutaneous SCC was analyzed for survivin expression by immunohistochemistry and Western blotting. Survivin was found in 57 cases (64%) of skin SCC and 26 cases (56%) of oral SCC, with weighted survivin scores ranging from 1 to 12. In contrast, normal oral epithelium, normal skin epithelium, and skin annexa did not express survivin. Survivin expression significantly (P < 0.05) segregated with high-grade and undifferentiated tumors with size >1.5 cm and invariably associated with lymph node metastasis. These data suggest that survivin expression may predictively identify cases of SCC with more aggressive and invasive clinical phenotype, potentially warranting closer follow-up protocols.

Apoptosis↗