Direct visualization of oral-cavity tissue fluorescence as novel aid for early oral cancer diagnosis and potentially malignant disorders monitoring.

Direct visualization of the oral tissue autofluorescence has been recently reviewed in several studies as a possible adjunctive tool for early recognition and diagnosis of potentially malignant and malignant oral disorders. The aims of this study were to assess: a) the value of a simple handheld device for tissue auto-fluorescence visualization of potentially malignant oral lesions; and b) the sensitivity, specificity and diagnostic accuracy of tested device, using histological examination as the gold standard. 175 consecutive patients, with at least one clinical oral lesion, were enrolled in the study. Clinical conventional inspections were performed for each patient by two blind operators. Then, oral biopsy and histological examination were performed. Pathologist was blind with respect to the autofluorescence results. The 175 histological assessments revealed no dysplasia, mild dysplasia, moderate/severe dysplasia and OSCC, in the 67.4%, 8.6%, 8%, 16% of cases, respectively. Oral lesions diagnosed as OSCC were found as positive under fluorescent light in the 96.4% of cases. Statistically significant correlation was observed between oral dysplastic lesions and the loss of tissue fluorescence (p-value=0.001). Low sensitivity values (60% and 71%) were recorded about the ability of the device in differentiating mild dysplasia vs. lack of dysplasia and moderate/severe dysplasia vs absence of dysplasia, respectively. The device tested in our study was found to not replace the histopathology procedure. However, we assessed its usefulness for oral tissue examination, especially within an oral medicine secondary care facility, before performing a biopsy and in monitoring oral lesions.

Lipoma of the fossa femoralis mimicking a femoral hernia. Report of 2 cases.

INTRODUCTION: Lipoma of the femoral fossa is uncommon. Often asymptomatic, femoral lipoma may growth within the circumscribed space of the femoral fossa causing pain and discomfort. A worsening pain caused by a lipomatous mass in the femoral area is a clinical feature that can mislead the diagnosis, resembling the more common condition of femoral hernia. METHODS: Two cases of symptomatic lipomas of the femoral fossa mimicking an incarcerated femoral hernia are presented. In both, Caucasian female, patients clinical examination and ultrasound of the femoral region revealed a painful neoplasm suspected for incarcerated femoral hernia. RESULTS: Intraoperatively, a mass of encapsulated fat arising from the bottom of the fossa femoralis was found. No visceral protrusion through the femoral ring could be documented. The neoplasms were removed in toto. Histology of the excised specimens evidenced the diagnosis of femoral lipomas suffering by chronic compressive damages. In a midterm postoperative follow up, both patients were symptom- free. DISCUSION: A correct preoperative diagnosis of femoral lipoma is challenging, even following an accurate diagnostic pathway. The cases highlighted herewith seem to confirm that lipoma of the femoral fossa can be mistaken with a femoral hernia. CONCLUSIONS: The clinical and histological features evidenced could result helpful in the differentiation of a lipomatous mass of the femoral fossa from a genuine femoral hernia.

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.

AIMS: To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. METHODS: Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in 'naïve' patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. RESULTS: Forty-eight patients were included (M/F 28/20; mean age 50.0 +/- 12.6 years; 62.5% genotype-1). Body mass index was 26.4 +/- 4.0 kg/m(2), and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis model assessment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. CONCLUSIONS: Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.

Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.

Prognostic and predictive factors in colorectal cancer: Kirsten Ras in CRC (RASCAL) and TP53CRC collaborative studies.

Mutations in the Ki-ras and TP53 genes are the most frequently observed genetic alterations in colorectal cancer (CRC). Ki-ras mutations are mostly found in codons 12 and 13, and less in codon 61. The majority of the TP53 mutations occur in the core domain which contains the sequence-specific DNA binding activity of the protein, and they results in loss of DNA binding. Few centres have sufficient patients to collect detailed information in the large numbers required to determine the impact of individual ki-ras and TP53 genotypes on outcome. Moreover, it has been reported that specific genetic alterations, and not any mutation, might play a different biological role in cancer progression. For these principal reasons, two collaborative studies have been conducted (the RASCAL and the TP53-CRC Collaborative Studies) with the aim of investigating the prognostic role of any, and specific, Ki-ras and TP53 mutations in CRC progression. The results obtained from the RASCAL studies suggest that Ki-ras mutations might have an effect on the survival rate of CRC patients, and that the specific codon 12 glycine/valine mutation might play a role in the progression of this neoplasia. The results of the TP53-CRC International Collaborative Study demonstrate the importance of primary tumor site when analyzing the prognostic value of TP53 mutations in CRC. In addition, different types of TP53 mutation might play a pivotal role in determining the biological behavior of CRC from different sites and hence the prognosis of patients. This meta-analysis produced evidence for interesting tumor site differences in the predictive value of TP53 mutation for survival benefit from 5FU chemotherapy.

High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C.

BACKGROUND: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective. AIM: To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients. METHODS: Patients were retreated for 6 months with 6 MU alphaIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months. RESULTS: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001). CONCLUSIONS: High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment.

Prognostic value of clinicopathologic variables and DNA ploidy in stage I cutaneous malignant melanoma.

We studied a consecutive series of 78 stage I cutaneous malignant melanoma in order to identify variables which might predict development of metastases. Anatomical site, sex, tumor thickness, Clark level, microscopic ulceration, growth phase, histologic type, cell type, and DNA ploidy were investigated. Lesions with tumor thickness 1.5 mm, Clark level IV-V, microscopic ulceration and DNA aneuploidy were at high risk for the development of metastases. This study showed the prognostic importance of DNA ploidy in stage I cutaneous malignant melanoma and the strong relationship between DNA ploidy and classic prognostic factors. This variable can be used in routine diagnosis for selecting a high-risk group of patients who may benefit from a more aggressive therapeutic approach.

Prognostic factors in oral squamous cell carcinoma. A review of the literature.

Despite diagnostic and therapeutic progress, the overall prognosis of oral squamous cell carcinoma remains poor and prognostic information is essential for the evaluation and optimal treatment of patients. The prognosis of oral carcinoma depends primarily on clinicopathological factors, that however, have showed a limited predictive value for the identification of patients with high risk of disease relapse. In recent years, the analysis of DNA ploidy, cellular proliferation and oncogenes amplification have been used in attempt to identify new prognostic indicators. The review of the literature shows that TNM stage, tumor grading evaluated at the deep invasive margins and maximal tumor thickness effect on the prognosis. Moreover, the assessment of DNA ploidy and proliferative activity can be used to obtain additional prognostic informations. In contrast, additional studies are needed to understand the prognostic value of oncogenes expression in oral carcinoma.

Malignant myoepithelioma of the minor salivary glands arising in a pleomorphic adenoma.

This paper reports a case of carcinoma expleomorphic adenoma of the minor salivary glands, where the carcinomatous component was a malignant myoepithelioma (myoepithelial carcinoma). Immunohistochemical investigation showed that the carcinoma cells were positive for cytokeratin, S-100 protein and vimentin, and focally positive for actin and desmin. A moderate level of positivity was found fo laminin and collagen IV around the neoplastic islands. These data are the confirmation that the carcinoma cells were myoepithelial. The number of mitoses, the istotype, the minimal extent of extracapsular infiltration and the absence of vascular invasion made it possible to include this particular case among those with a better prognosis.

Epithelial-myoepithelial carcinoma of the salivary glands: a clinico-pathologic, immunohistochemical and DNA flow cytometric study of three cases.

Epithelial-myoepithelial carcinoma is a rare neoplasia of the salivary glands. Histologic, immunohistochemical and flow cytometry analysis were used to study three new cases involving the major salivary glands of two women and one man. The mean age was 66.7 years. Immunohistochemistry confirmed the epithelial-myoepithelial dualism of the tumors: the predominant growth pattern showed ducts made up of an external myoepithelial layer and an internal epithelial layer. Proliferative activity, assessed by means of the PCNA and Ki-67 immunostaining and the study of the S-phase with flow cytometric analysis, proved to be higher in a recurrent case. All three cases were diploid. The use of immunohistochemical and flow cytometric techniques for the assessment of proliferative activity would seem to be an efficient method for the selection of a subgroup of epithelial-myoepithelial carcinomas with unfavorable prognosis.

Node status in lower lip squamous cell carcinoma in relation to tumor size, histological variables and DNA ploidy.

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following variables were investigated: tumor size, histologic grading, tumor maximal thickness, perineural infiltration and DNA ploidy, in a group of patients undergoing surgical treatment for LLSCC, and to show which of these might be predictive of the development of lymph node metastases.

Prognosis in lower lip squamous cell carcinoma: assessment of tumor factors.

We studied a consecutive series of 54 cases of lower lip squamous cell carcinoma (LLSCC) in order to identify any variables which might predict the development of lymph node metastases. The cases were divided into 38 tumors without metastases (group I) and 16 tumors with lymph node metastases (group II). The following factors were investigated: tumor size, histologic grading maximal thickness, perineural invasion, DNA ploidy and PCNA expression. In conclusion, we found that LLSCC greater than 2 cm in diameter, with histological grading G3-G4, thickness of more than 6 mm, DNA aneuploidy and high PCNA expression (PCNA LI > 0.48), were at high risk for the development of lymph node metastases.

[Synchronous carcinoma of the colorectum]. / Il carcinoma sincrono del colon-retto.

The incidence of synchronous carcinoma of the large intestine is rising in relation to a greater oncogenic environmental charge and increased average life expectancy. There is also a constant risk of not recognising the disease, especially in the case of small carcinoma and, to a greater extent, in patients operated during the occlusive phase. Having underlined the diagnostic value of a correct preparation of the colon prior to instrumental tests, the authors emphasise the importance of a careful intraoperative exploration of the viscera, its preliminary confinement in occluded subjects and repeated surgery in the event of doubts regarding the monolocation of the tumour. Lastly, they underline the importance of postoperative radiological and endoscopic controls since these tests mark both the successful outcome of treatment and the start of follow-up.

Biopsy vs. brushing: comparison of two sampling methods for the detection of HPV-DNA in squamous cell carcinoma of the oral cavity.

BACKGROUND: HR HPV infection was proposed as aetiological factor of oral squamous cell carcinomas (OSCC). HPV frequency in OSCC is highly variable, due to the discrepancy in oral sampling procedures, HPV testing methods and inclusion criteria regarding tumour site (strictly oral cavity vs. nearby structures). Our aim was to compare HPV DNA frequency and type-specific distribution in paired cytological and histological samples of SCC strictly located in oral cavity. The correlation between HPV detection rate by each method of sampling and demographical, behavioural and clinical-pathological variables was also examined. PATIENTS AND METHODS: HPV DNA was detected in brushed cells and formalin-fixed paraffin-embedded biopsies obtained from 83 consecutive unselected immunocompetent adults with OSCC. HPV DNA detection was performed in all samples by nPCR followed by direct DNA sequencing and the assay INNO-LiPA HPV Genotyping. Univariate and multivariate statistics were used, including Cohen κ index to evaluate agreement between two methods and association between HPV infection and demographical, behavioural and clinical-pathological variables for each method of sampling (p<0.05 statistically significant). RESULTS: HPV DNA was detected in 15.7% (13/83) of brushings and 12.1% (10/83) of biopsies (p>0.05). High risk HPV 51, 16 and 39 were genotypes more frequently detected, especially among biopsies; no concordance between two methods was found (Cohen κ index=0.04, p=0.34). CONCLUSION: A fraction of OSCC could be linked to HR HPV infection in the Mediterranean area. Although without a statistical significance, biopsy specimen demonstrated more accurate for HR HPV detection than brushing in OSCC.

Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy.

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by damage of large bowel mucosa and frequent extra-intestinal autoimmune comorbidities. The role played in IBD pathogenesis by molecular chaperones known to interact with components of the immune system involved in inflammation is unclear. We previously demonstrated that mucosal Hsp60 decreases in UC patients treated with conventional therapies (mesalazine, probiotics), suggesting that this chaperonin could be a reliable biomarker useful for monitoring response to treatment, and that it might play a role in pathogenesis. In the present work we investigated three other heat shock protein/molecular chaperones: Hsp10, Hsp70, and Hsp90. We found that the levels of these proteins are increased in UC patients at the time of diagnosis and decrease after therapy, supporting the notion that these proteins deserve attention in the study of the mechanisms that promote the development and maintenance of IBD, and as biomarkers of this disease (e.g., to monitor response to treatment at the histological level).