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Objective: Tumor associated macrophages (TAMs) are among the most abundant cells of the tumor microenvironment. Several studies have been performed to investigate whether TAM markers, namely CD68 and CD163, could serve as prognostic factors in patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this systematic review and meta-analysis was to synthetize the available evidence of the literature about the role of CD68+ and CD163+ TAMs as prognostic factors in SCCHN., Materials and Methods: This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Meta-analysis of overall survival, disease-free survival and progression-free survival was performed using the inverse of variance test. A random- or a fixed- effect model was used on the basis of the presence of heterogeneity. Risk of bias assessment and subgroup analysis were also performed., Results: High stromal expression of CD163+ TAMs correlated with both poor overall survival (HR, 2.26; 95% CI: [1.47, 3.47]; P < 0.001) and progression-free survival (HR, 2.29; 95% CI: [1.11, 4.71]; P = 0.03). Conversely, abundance of CD68+ TAMs was not associated with overall survival (HR, 1.25; 95% CI: [0.86, 1.80]; P = 0.24) and disease-free survival (HR, 2.06; 95% CI: [0.84, 5.05]; P = 0.11)., Conclusions: Findings from this study revealed that whilst IHC analysis of the generic macrophage marker CD68+ has no prognostic utility in patients with SCCHN, the M2-like marker CD163+ predicts poor prognosis. Our data suggest that assessment of CD163+ TAMs in SCCHN has potential for future clinical use. Further well-standardized studies should be performed to confirm these results., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cell-cell and cell-matrix interactions regulate important cellular functions; they involve a number of specialised molecules and the corresponding receptors, among which a key role is played by cadherins and the associated catenins. Deregulation of these molecules has been associated with tumour progression in many human malignancies. While catenins expression has been extensively studied in many human cancers, including oral carcinoma (OSCC), less is known about their expression in oral epithelial dysplasia. The objective of this study was to evaluate the expression of these proteins in a large group of displastic lesions of the oral mucosa and their relation with subsequent malignant transformation. Expression of beta- and gamma-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and 10 samples of normal oral mucosa. The presence and absence of beta- and gamma-catenin staining was expressed differently in relation to dysplasia grade; while the degree of dysplasia became more severe, we observed a statistically significant loss and/or reduction of catenins expression, the loss of the exclusive membranous expression and a cytoplasmic delocalisation. Progression to OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed a concurrent and concordantly located beta- and gamma-catenin staining even, if no statistically significant differences were found between cases progressed to invasive OSCC or not. Catenins physiology alterations may be involved in the transformation process; however, the role of catenins expression as possible prognostic markers in precancerous oral lesions seems to be limited. Nonetheless, further studies on larger series of samples are necessary in order to clarify the role of catenins expression in oral carcinogenesis from both a biological and clinical point of view.

Objectives: The protective role of saliva in the case of oesophageal exposition to gastric acid has long been studied but some contradictions still remain. The main end-point of this study was to evaluate if a qualitative and quantitative alteration in salivary secretion exists in patients affected by GERD., Methods: One hundred and twenty patients (T group) with clinically and endoscopically diagnosed GERD, and 98 healthy subjects (C group) have been evaluated; salivary tests (i.e. basal flow rate, stimulated flow rate, pH, [Na(+)] and [K(+)]) were performed, socio-demographical variables and oral GERD-related symptoms were taken into account. SPSS 10.5 software was used for statistical univariate and multivariate analyses., Results: GERD patients and controls were found to have a similar basal flow rate but different stimulated salivary function [T group mean value 0.989 ml/min (+/-0.48718) vs. C group 1.2197 ml/min (+/-0.6108), pH [T group mean value 8.935 (+/-0.471) vs. C group 7.879 (+/-0.526)] and a higher K(+) concentration. In GERD patients we also registered a significant association with xerostomia [69/120 (57.5%) vs. 28/98 (28.7%)] and an oral burning sensation [58/120 (48.3%) vs. 19/98 (19.3%)]., Conclusions: Our findings assess that salivary secretion is altered in GERD patients and highlight the need for further investigations in order to define the role of saliva in the etiopathogenesis of GERD.

Objectives: Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition., Study Design: Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation., Results: Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern)., Conclusions: Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.

Background: Careful endoscopic classification of macroscopic appearance of superficial neoplasias of the gastrointestinal tract is essential in the early detection and appropriate treatment of cancer. It has contributed to introduce minimally invasive endoscopic surgery and has significantly improved survival of patients with colon and gastric cancers. Squamous cell carcinoma of the oral cavity has been characterized, in past and present times, by poor prognosis and lack of progress in treatment outcome. Failure in diagnosing oral malignancy at an early stage is a major culprit, and the lack of a worldwide adopted classification of its macroscopic appearance, similar to that of gastrointestinal neoplasias, may have contributed to it., Aim: To test the hypothesis that is possible to extend the diagnostic benefit of a classification based upon the macroscopic appearance of superficial tumours of the digestive tract to superficial carcinoma of the oral mucosa., Methods: We retrospectively examined a group of patients who developed multiple intraepithelial and early invasive malignant oral neoplasias, applying a modified version of the Paris classification of superficial GI neoplastic lesions., Results: One hundred and ten out of 116 (94.9%) of the study lesions had morphological features that accorded with the prepared classification., Conclusions: These preliminary data suggest that most superficial early neoplastic lesions of the oral cavity can be easily detected using a well-defined classification system similar to that employed in the diagnosis of early gastrointestinal malignancy.

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.

The concept of dysplasia/neoplasia surveillance has been applied to long-standing conditions associated with an increased risk of cancer. Although still controversial, periodic direct clinical examination as well as endoscopic techniques are currently performed in patients with inflammatory bowel diseases, Barrett's esophagus, and melanocytic skin lesions in order to detect and treat dysplastic or early malignant changes and therefore improve the patients' prognosis. It is not known if patients with oral lichen planus (OLP), a chronic inflammatory condition associated with an increased risk of cancer development, might benefit from such surveillance as well, nor how this should be performed. Here we present the clinical criteria we have adopted over a 12-year period to detect early malignant transformation of OLP, and report on their impact on the management and prognosis of patients. Overall data from 45 patients affected by 117 neoplastic events arising from OLP have been evaluated. Our dysplasia/neoplasia surveillance has led us to diagnose most episodes (94.9%; n.: 111) of OLP malignant transformation in early intraepithelial and microinvasive phases, namely stage 0 and I oral cancers (T(is) N0M0 or T1N0M0). The 5-year survival rate, where applicable, has been 96.7%. Advanced stage oral cancers have been diagnosed in six patients, three of whom have died. We suggest that the application of strict and rigorous clinical criteria in dysplasia/neoplasia surveillance could help clinicians to detect and treat early OLP malignant transformation and therefore improve long-term survival rates. Nevertheless, a small subgroup of patients has been shown not to benefit from such surveillance and to be characterized by a rapid development of advanced-stage oral carcinomas, with consequent poor prognosis.

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.

The association of chronic inflammation with a variety of epithelial malignancies has been recognised for centuries. Well established examples include, among many others, oesophageal adenocarcinoma associated with chronic oesophagitis and bowel cancer associated with chronic inflammatory bowel diseases. By now no data, other than clinical observation, have been available in understanding the pathogenesis of these inflammation-related tumours. However, recent molecular studies on the relationship between solid malignancies and the surrounding stroma have given new insights. There is now enough evidence to accept that the chronic inflammatory process per se is able to provide a cytokine-based microenvironment which is able to influence cell survival, growth, proliferation, differentiation and movement, hence contributing to cancer initiation, progression, invasion and metastasis. Here it is discussed whether also oral lichen planus (OLP), being a chronic inflammatory autoimmune disease which has been clinically associated with development of oral squamous cell carcinoma, might be categorised among these disorders. With this aim, we critically reviewed and detailed the presence, in OLP subepithelial infiltrate, of inflammatory cells and cytokine networks that might act to promote squamous tumorigenesis.

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.

In recent years, studies on the malignant potential of oral lichen planus (OLP) provided clinical evidence that patients affected by OLP have an increased risk to develop oral squamous cell carcinoma (OSCC); nevertheless, controversies still exist as to whether OLP has inherent predisposition to become malignant, or not. We believe extremely careful management of OLP patient is mandatory, and the aim of this paper is to illustrate our clinical guidelines in evaluating the possible risk of transformation in OLP lesions. Five-hundred and two patients (311 women and 191 men) affected by OLP regularly undergo follow-up examination in our Department. Patients' ages range from 18 to 83 years, with a mean of 55.4 years (57.5 for women and 53.9 for men); minimal follow-up period is 4 months, with a maximum of 12 years. In our group of OLP patients in the past 5 years we detected 24 carcinomas: excluding three cases in which diagnoses of OLP and OSCC were synchronous and three patients who had a history of tobacco use, thus possible malignant transformation of OLP would appear to be 3.7%. Clinical criteria used in our follow-up allowed us to detect 28.5% of tumours as in situ OSCC, 38% as microinvasive OSCC, 28.5% as stage I OSCC and 4.7% as stage II OSCC, with a remarkable improvement in prognosis compared to our previous study in which we adopted different criteria.