Anna Patrikidou

Bisphosphonate-Related Osteonecrosis of the Jaws: A Case-Control Study of Risk Factors in Breast Cancer Patients

PURPOSE Osteonecrosis of the jaws (ONJ) was initially described in 2001 in patients receiving intravenous bisphosphonate (BP) treatment. The objective of the present study was to determine whether routine dental procedures can be considered as possible risk factors for the development of ONJ in breast cancer patients receiving BP. PATIENTS AND METHODS Twenty breast cancer patients who developed ONJ receiving BP treatment were included in group A, whereas group B consisted of 40 matched controls (breast cancer patients who did not progress to ONJ receiving BP treatment). Routine dental care, smoking habits, history of tooth extraction, use of dentures, and root canal therapy were recorded. RESULTS Our results indicate that history of tooth extraction during zoledronic acid treatment (adjusted odds ratio [OR] = 16.4; 95% CI, 3.4 to 79.6) and the use of dentures (adjusted OR = 4.9; 95% CI, 1.2 to 20.1) increase the risk of developing ONJ. CONCLUSION The outcome of the present study suggests early referral by oncologists for dental evaluation for every patient to be treated with BP. These results raise the current American Society of Clinical Oncology Level of Evidence linking certain dental procedures with ONJ from V to III. Further studies are needed to assess other possible risk factors and also to highlight the etiopathogenesis mechanism of ONJ.

Cutaneous squamous cell carcinoma (SCC) of the head and neck: risk factors of overall and recurrence-free survival.

BACKGROUND Head and neck cutaneous squamous cell carcinoma (HNCSCC) although rarely fatal has significant adverse public health effects due to high medical costs, compromised quality of life, functional impairment and other serious consequences. The present longitudinal cohort study of HNCSCC was designed to determine whether certain clinical-pathologic features of HNCSCC are associated with reduced overall and recurrence-free survival, as suggested by previous data. PATIENTS The cohort sample consisted of 315 consecutive patients presenting with primary HNCSCC of the head and neck. Life-table analysis and Kaplan-Meier survival analysis were performed. Multivariate Coxs proportional hazards regression models were used to assess the effects of covariates on the length of the interval. RESULTS There were 145 male and 170 female Caucasian patients. At the time of analysis, 222 patients were alive. The mean follow-up time of a patient after enrolment has been 46.7 months (range, 12-124 months). Broders differentiation grade, perineural involvement, the presence of inflammation and T-stage were independent adjusted predictors for overall survival. pT and N-stage, inflammation and perineural involvement were significant predictors for recurrence-free survival while adjuvant irradiation was associated with a 92% reduced risk for recurrence. Life-table analysis showed that 87% and 69% study patients were free from recurrence at years 3 and 5, respectively. CONCLUSIONS Certain clinico-pathological predictors can be used to discriminate subsets of high-risk patients that could benefit from long-term follow-up. After excision in negative margins, patients with HNCSCC should be referred to specialised multidisciplinary oncology clinics for counselling on adjuvant radiotherapy and follow-up.

Non-AIDS Kaposi's sarcoma in the head and neck area

Kaposis sarcoma is classified into 4 types: classic (sporadic), African (endemic), iatrogenic (transplant recipients), and epidemic (acquired immunodeficiency syndrome [AIDS]‐associated). This article aims to feature a comprehensive review of non‐AIDS Kaposis sarcoma, including literature review and report of 3 cases. Case material was from our hospitals archive. Literature review was conducted via electronic and manual medical database searches. Biological aspects, diagnostic difficulties, investigation protocols, and management modalities are discussed.

Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group.

BACKGROUND The added value of tumoural genomic profiles to conventional clinico-biological factors to predict progression-free survival (PFS) and overall survival (OS) was prospectively investigated in patients with advanced gastrointestinal stromal tumours (GIST) treated in the BFR14 study. METHODS Of the 434 included patients, mutational analysis was performed in 322 patients. Survival analysis was performed in patients with validated mutational status. RESULTS Mutational status was validated in 228 patients. We identified 196 patients with tumours harbouring 200 KIT alterations (exon 11: 173 patients, exon 9: 22 patients, exon 17: 3 patients, exon 13: 2 patients; 4 patients had double KIT mutations), 6 patients with PDGFRA mutations and 26 patients with wild-type (WT) GIST genotype. On a median follow-up of 73 months, median PFS/OS were 12.3/54.9 months for WT GIST, 12.6/55 months for KIT exon 9, and 39.4 months/not reached (69.1% at 5 years) for KIT exon 11. Tumour size, female gender, KIT exon 11 mutations and CD34 positivity were independent prognostic factors for a higher PFS. A higher OS was predicted by performance status (PS) <2, low neutrophil and normal lymphocyte counts, KIT exon 11 mutations, non-advanced tumour and female gender. KIT exon 11 mutations at codons 557-558 showed better tumour response (p=0.028) but shorter PFS (p=0.0176). CONCLUSIONS In GIST patients, presence of a KIT exon 11 mutation is an independent prognostic factor for PFS and OS, along with gender, PS, tumour size, lymphocyte and neutrophil counts. Subsets of exon 11 mutations are associated with significantly different response patterns and PFS.

Inverse baseline expression pattern of the NEP/neuropeptides and NFκB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells

BackgroundCastration-resistance in prostate cancer (PC) is a critical event hallmarking a switch to a more aggressive phenotype. Neuroendocrine differentiation and upregulation of NFκB transcriptional activity are two mechanisms that have been independently linked to this process.MethodsWe investigated these two pathways together using in vitro models of androgen-dependent (AD) and androgen-independent (AI) PC. We measured cellular levels, activity and surface expression of Neutral Endopeptidase (NEP), levels of secreted Endothelin-1 (ET-1), levels, sub-cellular localisation and DNA binding ability of NFκB, and proteasomal activity in human native PC cell lines (LnCaP and PC-3) modelling AD and AI states.ResultsAt baseline, AD cells were found to have high NEP expression and activity and low secreted ET-1. In contrast, they exhibited a low-level activation of the NFκB pathway associated with comparatively low 20S proteasome activity. The AI cells showed the exact mirror image, namely increased proteasomal activity resulting in a canonical pathway-mediated NFκB activation, and minimal NEP activity with increased levels of secreted ET-1.ConclusionsOur results seem to support evidence for divergent patterns of expression of the NFκB/proteasome pathway with relation to components of the NEP/neuropeptide axis in PC cells of different level of androgen dependence. NEP and ET-1 are inversely and directly related to an activated state of the NFκB/proteasome pathway, respectively. A combination therapy targeting both pathways may ultimately prove to be of benefit in clinical practice.

Baseline Plasma Levels of Interleukin-8 in Stage IV Non-Small-Cell Lung Cancer Patients: Relationship With Nutritional Status and Prognosis

Interleukin (IL)-8 promotes cellular proliferation and angiogenesis in patients with non-small-cell lung cancer (NSCLC) and may be related to cachexia. Our aim was to investigate the relationship of IL-8 levels with nutritional status, and clinical outcome of patients with NSCLC. Patients with metastatic NSCLC referred for first-line therapy were eligible. Baseline IL-8 levels were measured in plasma. The Mini Nutritional Assessment (MNA) was used for the evaluation of the nutritional status, and patients were classified into 3 groups: A (score 24–30) “well nourished,” B (score 17–23.5) “risk of malnutrition,” and C (0–16.5) “malnourishment.” Response to first-line chemotherapy, time-to-tumor progression (TTP), and overall survival (OS) were also recorded. In total, 114 patients (101 males, 88.5%; mean age = 67.5 yr) were evaluated. Performance status was 0–1 in 62% of the patients. According to the MNA, the majority of patients (71%) was either at nutritional risk or malnourished. IL-8 levels were significantly different between MNA groups (P = 0.023) and correlated with TTP (P = 0.013) and OS (P = 0.001) in univariate analysis. Baseline IL-8 levels correlate with the nutritional status of patients with metastatic NSCLC, suggesting that this cytokine may be related with cachexia.

Benign Fibrous Histiocytoma of the Buccal Mucosa: Case Report and Literature Review

Benign fibrous histiocytoma is an interesting and challenging entity even in its most usual, cutaneous presentation. Noncutaneous presentation is extremely limited, even more so for the mucosa of the head and neck area. We herein report such a case, describing the clinical characteristics of the lesion, complete diagnostic evaluation, management, and follow-up. Diagnostic histopathological challenges are specifically illustrated. A complete review of the relevant literature is also included.

Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells.

Objectives:  Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin‐proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasome inhibitor bortezomib in neuropeptides signaling effects on prostate cancer cells.

Metastasis of a ductal breast carcinoma to the buccal mucosa of the mandible with tooth involvement

BackgroundWe present a metastatic tumour from the breast to the gingiva, with the rare finding of tooth invasion. Metastatic tumours to the oral region are uncommon. The breast is the most common primary site for metastatic tumours to the jawbones in women, with the mandible being most often affected.Case reportWe report the case of a 52-year-old Caucasian woman who presented with a swelling of the buccal mucosa in the molar region of the left mandible. Biopsy revealed a metastatic lesion, with involvement of the two adjacent molars. Immunohistochemical analysis ruled out other malignancies and confirmed the diagnosis of a ductal breast carcinoma origin.DiscussionManagement in such cases should be in the context of the treatment of a metastatic disease that could prolong survival and improve quality of life, but is not curative. Tooth invasion has been described since 1910 for different primary malignancies with distant metastases to the oral cavity. This report seems to describe the second case in the literature of a metastatic breast carcinoma to the mandible with tooth invasion. Management in such cases should be in the context of the treatment of a metastatic disease that could prolong survival and improve quality of life, but is not curative.

Key messages from the BFR14 trial of the French Sarcoma Group

The BRF14 trial is a prominent study that investigated the effect of prolonged imatinib treatment in advanced gastrointestinal stromal tumor patients. The key messages deduced from this study are as follows: imatinib drastically improved progression-free and overall survival in advanced gastrointestinal stromal tumor patients. Treatment ought to be maintained indefinitely in nonprogressing patients, as interruption entails a high risk of progression, even in patients in complete response. Imatinib rechallenge is effective, achieving new disease control in patients progressing after imatinib interruption. Rechallenge response profiles reflect the initial responses, albeit of poorer quality. Imatinib interruption does not affect the incidence of secondary resistance; however, the imatinib-free interval influences the time to secondary resistance. Specific clinical, biological and molecular characteristics seem to identify the patients who are long responders to imatinib. Surgery of residual disease after maximal imatinib response improves progression-free and overall survival.