Parameters and outcomes in 525 patients operated on for oral squamous cell carcinoma.

PURPOSE: This report analyzed the outcomes of patients undergoing surgery for oral squamous cell carcinoma (OSCC) to identify the value of prognostic factors. MATERIAL AND METHODS: A total of 525 patients were studied who had undergone surgery for oral squamous cell carcinoma (OSCC) between 2000 and 2011, of whom 222 had received postoperative radiation-therapy (PORT) and or chemoradiation-therapy (PORTC). For each patient, personal data, histological findings, treatment and outcome were recorded and analyzed statistically. Survival curves were calculated using the Kaplan-Meier algorithm, and the difference in survival among subgroups was examined. RESULTS: The overall survival (OS) and disease-specific survival (DSS) 5-year survival rate in the 525 patients were respectively 71.38% and 73.18%. The differences in the overall survival and disease-specific 5-year survival were significant (p < 0.05) for age < 40 years, site of origin, N status, staging, grading, osseous medullar infiltration, and perineural invasion. In patients undergoing radiation therapy, only perineural invasion negatively influenced the survival prognosis. In 150 pT1 cases of tongue and floor-of-mouth cancer, an infiltration depth (ID) > 4 mm was statistically correlated with poorer prognosis. CONCLUSIONS: The results demonstrate an improvement in the 5-year OS and DSS rates during the past decade compared with the previous decade. Univariate analysis revealed that age, tumor staging, and lymph node involvement, extracapsular spread, grading, perineurial invasion, infiltration depth, and osseus medullary invasion were associated significantly with overall survival and disease-specific survival.

Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial.

AIMS: Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single-stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients' compliance compared with standard-dose cisplatin with similar outcome results. MATERIALS AND METHODS: Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m(2)) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck. RESULTS: Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively. CONCLUSIONS: Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in 'unfit' patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded.

Correlation between Skp2 expression and nodal metastasis in stage I and II oral squamous cell carcinomas.

PURPOSE: The aim of this study was to investigate the role of S-phase kinase associated protein (Skp2) in the development of nodal metastasis and to assess its influence on prognosis in stage I and II oral squamous cell carcinomas (OSCCs). EXPERIMENTAL DESIGN: Seventy-one patients affected by OSCC (stage I-II) were observed in the period ranging from March 2003 to December 2006. The research was performed using immunohistochemical and histopathological analysis. RESULTS: The overall survival rate was 89.6% at 3 years, 87% at 5 years and 80.7% at 10 years. Patients with vascular or perineural invasion showed no statistically significant survival difference when compared with the ones with no invasion. The tumour depth of invasion did not prove to be related to the metastatic potential. Nine of the seventeen patients with Skp2 positive nuclei (≥20%) developed nodal metastasis. Conversely, only 6 of the 54 patients with a nuclear positivity lower than 20% developed a laterocervical metastasis (P=0.001). When comparing survival curves of Skp≥20% and Skp2<20% OSCCs, no significant P value emerged from the statistical analysis. CONCLUSIONS: This study is the first to report an important correlation between an Skp2 expression lower than 20% and the capability of the tumour not to develop nodal laterocervical metastases (P=0.001).

[Incidence of psychopathologic symptoms in patients treated for mouth cancer]. / Valutazione dell'incidenza dei sintomi psicopatologici in pazienti trattati per carcinoma del cavo orale.

BACKGROUND: The first aim of the study is to evaluate the possible onset of anxiety, major or minor forms of depression and delirium in patients treated for head and neck malignancies. The second aim is to study the possible association between the psychological conditions and the different parameters connected with the treatment (site of tumor, time of hospitalisation and surgery, kind of reconstruction). METHODS: The study included 35 patients (21 males; 14 females) with diagnosis of head and neck squamous cell carcinoma (HNSCC). All the patients were examined before surgery, during the preoperative phase, and after surgery. Three evaluation questionnaires were used during the interview: Spielberg's StaiY1 and Y2 test, to evaluate anxiety, and Zung Self-Rating Depression scale, to evaluate depression. RESULTS: Patients revealed anxiety before surgery, while after intervention the level was normal. There was a prevalence of anxiety over depression. There was no correlation between diagnosis, site of tumor, time of hospitalisation and psychological symptoms. An association between time of surgery, kind of reconstruction, anxiety and depression was found. The patients with a higher degree of anxiety were more tending to delirium. CONCLUSIONS: Malignancy of the head and neck causes considerable physical and psychological problems which may adversely affect the quality of life during and after treatment. The better reconstruction is correlated with the lower psychopathological problems. The study underlines the need to offer psychological support during diagnostic and therapeutic procedures.

Oral lichen planus in patients infected or noninfected with hepatitis C virus: the role of autoimmunity.

Serum proteins, serum immunoglobulins, anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA), anti-liver-kidney antibodies (LKM), anti-parietal-cell gastric antibodies (APCA), anti-epithelial antibodies and concomitant autoimmune disease were studied in 27 OLP-HCV+ve subjects and in a comparable group of 23 who were OLP-HCV-ve. In addition, all the patients with chronic liver disease who were sero-positive for ANA, AMA or LKM were scored using the new aggregate scoring system to detect those with the accepted criteria for the diagnosis of autoimmune hepatitis (AIH). Hypergammaglobulinemia was more frequent in OLP-HCV+ve than in OLP-HCV-ve (P = 0.008) subjects. Serum IgG and IgM levels were higher in HCV+ve than in HCV-ve (respectively, P = 0.017 and P = 0.018) individuals. However, there was no difference in the frequency of any autoantibody between OLP-HCV+ve and OLP-HCV-ve patients. Overall, immunologically-related abnormalities were found in 17(63%) OLP-HCV+ve and 11(48%) OLP-HCV-ve (P = 0.43) patients. Three OLP-HCV-ve and no OLP-HCV+ve patients had score criteria of probable AIH. The present and our previous data suggest that OLP patients with HCV infection neither had evidence of autoimmune liver damage nor had abnormal humoral immune-responses, with the exception of higher than control levels of serum immunoglobulins. Cryoglobulins may be responsible.

[An increase in gingival volume induced by drugs (phenytoin, cyclosporine and calcium antagonists). A review of the literature]. / Aumento di volume gengivale indotto da farmaci (fenitoina, ciclosporina, e calcioantagonisti). Revisione della letteratura.

The aim of this review is to evaluate the side effects of some drug therapies on the gingival tissue in certain susceptible individuals. Phenytoin, cyclosporine-A and a variety of calcium channel blockers have been shown to produce gingival overgrowth. In this paper the pharmacodynamics and pharmacokinetics of these drugs, the pathogenesis, the clinical aspect of the enlargement and its treatment are examined. Several of the reviewed theories on pathogenesis are well documented in the literature, while others are controversial and less described. The old term gingival hyperplasia is not exact because histologically an increase in the number of fibroblasts has not been demonstrated, but an increase has been found out in the amount of collagen fibers and noncollagenous proteins in the connective tissue. The clinical findings have the same characteristics both in location and growth pattern while prevention is primarily directed at the removal of local irritant factors. The prevalence and severity of gingival enlargement increase in heart transplant patients who are often medicated with cyclosporin and channel blockers.

Altered expression of alpha 6 integrin subunit in oral squamous cell carcinoma and oral potentially malignant lesions.

The expression and distribution of integrin chains alpha 2, alpha 3, alpha 5, alpha 6, beta 1, beta 4, collagen type IV, laminin 1 and laminin 5 in oral squamous cell carcinoma (SCC) and oral keratoses with and without dysplasia (OL) have been studied by immunochemistry and western blotting. Focal interruptions of basement membrane protein staining were detected in SCC indicating a loss of continuity, whereas tumour nests were apparently completely surrounded by laminin 1, type IV collagen and laminin 5; the loss of basement membrane components in OL was found in only one specimen showing severe dysplasia. The localisation of integrins showed altered suprabasal and pericellular expression of the alpha 6 chain in all but one SCC, as well as in many OL samples, whereas the beta 4 subunit showed only a faint pericellular redistribution in SCC. In OL, beta 4 was often seen in a normal basally polarised distribution. Western blotting analysis confirmed that alpha 6 protein levels were abnormally high in cancerous lesions, whereas quantitative recovery of the beta 4 subunit in SCC was only minimal, suggesting a dissociation in the synthetic ratios of the two chains of the alpha 6 beta 4 heterodimer in SCC. Because alterations in the polarised expression of integrin alpha 6 beta 4 have been seen during epithelial tumour progression and wound healing, we suggest that the lack of restricted basal polarisation of alpha 6 could be an early but non-specific marker of oral malignancy, indicating that the generation of abnormal signals from the extracellular matrix may be involved.

[Topical treatment of atrophic-erosive oral lichen planus with clobetasol in bioadhesive gel as well as chlorhexidine and miconazole in oral gel]. / Il trattamento topico del lichen planus orale atrofico-erosivo con clobetasolo in gel bioadesivo, soluzione di clorexidina e miconazolo gel orale.

The study was performed to evaluate the efficacy of the combination of a topical corticosteroid with topical antimicrobic drugs in the therapy of the atrophic-erosive forms of oral lichen planus. Clobetasol propionate, a very potent corticosteroid in the Miller and Munro classification, was used in a 4% hydroxy ethylcellulose bioadhesive gel and applied twice daily for the first four months and once daily for the last two months. Because of the high frequency of candidal infections during corticosteroid therapy, chlorhexidine 0.12%, 3 mouthwashes daily, and miconazole gel, once daily, were added for the whole period of the treatment. Twenty-five patients (17 female, 8 male) participated in the study; 20 concluded the six months of therapy and the six months of follow-up. All 20 patients (100%) had an improvement, while 75% had a complete remission of oral signs. No cases of oral candidiasis were seen. After six months from therapy suspension, 65% of patients were stable in their oral conditions. Our study confirms the efficacy of the combination of a topical corticosteroid with topical antimicrobic drugs in the therapy of the atrophic-erosive forms of oral lichen planus. The stability of our results suggests that, extending the therapy, control of the disease is better.

[Melanoma of the oral cavity. Review of the literature]. / Melanomi nel cavo orale. Revisione della letteratura.

The location of melanoma in the oral cavity is extremely rare: its frequency varies between 0.2 and 8%. Oral melanoma strikes mainly male subjects and is more frequently seen at the level of the hard palate and gingiva. Today the clinicopathological classification of oral melanoma is not yet clearly outlined, and that is why the skin form is often taken as a reference. The acral lentiginous subtype proves to be the most common in this seat. In many cases (up to 50%) the diagnosis of melanoma is made on lesions which have evolved from the pre-existing pigmented lesions: as a consequence, every pigmented lesion of undetermined origin must be biopsied as a routine. The prognosis often proves poor and the surgical approach, combined with the chemotherapeutic one, is the first choice treatment. Lymph node dissection is not routinely practiced.

[Therapeutic management of mucous membrane pemphigoid. Report of 11 cases]. / Il trattamento del pemfigoide delle membrane mucose. Descrizione ed analisi di 11 casi.

In the present study the efficacy of systemic and topical steroid treatment in the management of 11 patients with mucous membrane pemphigoid (MMP) confirmed histologically and immunologically has been evaluated. Eight patients were treated with a topically applied clobetasol in a bioadhesive gel (2-3 times/daily) and with chlorexidine mouth-washes (3 times/daily) and myconazole gel (1 time/daily) as antimycotics. The remaining 3 were treated with systemic prednisone (25 to 100 mg/daily) followed by a topical therapy with clobetasol, chlorexidine and myconazole. In 6 cases (54%), 4 topically treated and 2 systemically plus topically treated, we observed a complete clearance of signs and symptoms of MMP in an average period of 5.7 months. In the remaining 5 cases (46%), 4 topically treated and 1 systemically plus topically treated, we observed partial healing of the oral lesions. One patient treated with a high dose of prednisone (100 mg/daily) showed side-effects (insomnia, fluid retention and gastralgia) whereas other 3 subjects had oral candidiasis. In a mean follow-up time of 13 months (range 6 to 27) 6 patients (54%) were free of disease, 3 (27%) had a marked improvement and 2 (18%) had new active lesions of MMP. These results suggest that often in the treatment of MMP a systemic corticosteroid therapy followed by a treatment with high potency topical steroids is useful to obtain a good control of MMP.

Hepatitis C virus infection in Italian patients with oral lichen planus: a prospective case-control study.

To assess the aetiology of liver disease associated with lichen planus, we prospectively studied 70 consecutive newly diagnosed patients with oral lichen planus (OLP) living in northwest Italy (Piemonte) and 70 controls matched for age and sex with other oral keratoses coming from the same district. Twenty-two patients with OLP (31.4%) and 9 controls (12.9%) were found to be affected by chronic liver disease (CLD) (P = 0.014). In sixteen of the 22 OLP patients with CLD the liver disease was hepatitis C virus (HCV)-related, whereas 2 of the 9 controls had a HCV-related CLD (P = 0.016). In another OLP case, liver damage was related to a combination of HCV and alcohol abuse. The prevalence of HCV antibodies in the whole OLP group (27.1%) was significantly higher than in controls (4.3%) (P = 0.014), whereas no difference was found between the OLP and control groups regarding hepatitis B virus markers and other common causes of CLD. HCV infection was more frequently found in patients with erosive OLP (58.8%) than in patients with non-erosive OLP (13.2%) (P = 0.004). Serum HCV-RNA was detected by polymerase chain reaction (RT-PCR) in the majority (93.7%) of OLP patients who had HCV antibodies. Excluding OLP and control patients with HCV markers, there was no difference between the two groups regarding frequency of CLD. Our data show that HCV is probably the main pathogenic factor in liver disease of Italian patients with OLP, and suggests that HCV could be involved in the pathogenesis of OLP.

[Pemphigoid of the mucous membranes. The clinical, histopathological and immunological aspects and current therapeutic concepts]. / Il pemfigoide delle membrane mucose. Aspetti clinici, istopatologici, immunologici ed attuali concetti terapeutici.

Mucous membrane pemphigoid (MMP) is a chronic disease of unknown etiology frequently involving oral cavity and eye and sometimes also pharyngeal, laryngeal, oesophageal and genital mucosae. It is characterized histologically by a sub-epithelial blister and by a typical direct immunofluorescence feature showing linear binding of IgG and C3 to the basement membrane zone (BMZ). The predominance of mucosal involvement or the lack of skin lesions distinguish MMP from bullous pemphigoid. Oral mucosal presentation of MMP is quite variable from chronic erythematous lesions to erosions covered by a fibrinous slough produced by bullae rupture involving mainly gingiva, buccal mucosa and palate. Because eye manifestations of MMP are common and blindness may develop, an ophthalmological examination is mandatory in these patients, although recent data suggest that pure ocular pemphigoid, oral pemphigoid and MMP with cutaneous lesion could be different diseases. Further immunological and biochemical studies are needed to better characterize these pathologies. It is generally considered that blister formation in MMP is the result of immunoglobulin deposition leading to complement activation in the BMZ, but there are not specific pathogenetic data regarding oral pemphigoid. Multiple therapeutic options exist including topical and systemic corticosteroids associated or not to other immunosuppressive drugs, dapsone and tetracycline but there do not exist treatment modalities generally accepted.