HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients.

The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously associated to tumor progression and angiogenesis; here we investigated the potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM) cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at the diagnosis related to high bone marrow angiogenesis and overexpressed in about 40% of myeloma cell lines compared with normal plasma cells. Enforced HOXB7 expression in MM cells by a lentiviral vector significantly modified their transcriptional and angiogenic profile, checked by combined microarray and angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene signature was also validated in a large independent dataset of MM patients. Accordingly, MM-induced vessel formation was significantly increased by HOXB7 overexpression both in vitro angiogenic and chorioallantoic membrane assays, as well as the HOXB7 silencing by small interfering RNA inhibited the production of angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor growth, increased MM-associated angiogenesis and the expression of pro-angiogenic genes by microarray analysis supporting the critical role of HOXB7 in the angiogenic switch in MM.

[Non-endoscopic minimally invasive thyroidectomy in papillary carcinoma. Our experience]. / La tiroidectomia mini-invasiva non endoscopica nel carcinoma papillifero. Nostra esperienza.

INTRODUCTION: Minimal access thyroid surgery, using various techniques, is increasingly being reported. The present study reviews our experience with thyroid surgery using a minimally invasive approach in a group of patients with papillary thyroid carcinoma. METHODS: A total of 15 female patients with a thyroid nodule, not exceeding 2 cm, proven to be a papillary thyroid carcinoma at preoperative evaluation, underwent a total thyroidectomy with non endoscopic minimally invasive approach. RESULTS: None of the patients presented intraoperative central lymphnode involvement. The cytologic preoperative diagnosis was confirmed by histology in all cases. One case of transient recurrent nerve palsy was observed immediately after surgery. No permanent nerve lesions were documented at 4 months. The hospital stay ranged from 48 to 72 hours. The iodine 131 uptake ranged from 0 to 2.13%, similar to that obtained with open thyroidectomy. All patients were satisfied for cosmetic result. CONCLUSIONS: The preliminary results of this study showed that non endoscopic minimally invasive thyroidectomy could be proposed in patients with T1 papillary carcinoma. In our experience the results obtained with this technique are similar to that obtained with open thyroidectomy, with the great advantage of a minimal neck wound and shorter hospital stay. However a higher number of cases and a longer follow-up are needed to confirm the safety of this procedure on the management of papillary cancer of the thyroid.

[Atypical partial tracheolaryngectomy associated with circular pharyngectomy followed by flap reconstruction for dedifferentiated papillary carcinoma of the thyroid gland]. / Tracheolaringectomia parziale atipica associata a faringectomia circolare seguita da ricostruzione con lembo alt per carcinoma papillifero dedifferenziato della tiroide.

The management of the extensive malignancy of the hypopharynx generally combines with total laryngectomy. The authors report a case of scanty differentiated papillary thyroid carcinoma, extended to the hypopharynx, with partial involvement of thyroid, cricoid and first tracheal ring cartilage and unilateral vocal fold palsy treated with an "atypical" partial tracheo-laringectomy combined with total circular pharyngectomy. The defect has been replaced with an antero lateral tight free flap suitably modeled to restore the pharyngeal and laryngeal lumen. A modified Montgomery T- tube has been inserted to avoid larynges-tracheal stenosis. This unusual technique allowed to restore a stable airway and satisfying deglutition and an adequate voice. With this case presentation the authors want to subline that when the tumor type is less aggressive than squamous cell carcinoma, it is possible to perform a partial larynx preservation also in the case of circular pharyngectomy. Obviously the residual laryngeal skeleton have to be sufficient to restore laryngeal lumen.

Cell proliferation as an independent predictor of survival for patients with advanced nasopharyngeal carcinoma.

Commonly used clinical and pathologic criteria are often of limited value in predicting the outcome of patients with undifferentiated nasopharyngeal carcinoma, and new parameters related to the biology of growth of neoplastic cells are still required for better definition of the aggressiveness of these tumors. The prognostic significance of DNA ploidy, measured by image cytometry on isolated cells, and of the mitotic index, proliferating cell nuclear antigen, and p53 protein, all measured by image cytometry in histologic sections, were evaluated on archival tumor tissues from 53 patients with Stage III or IV nasopharyngeal carcinomas. Patients were staged according to the criteria of the International Union Against Cancer and were irradiated according to a conventional radiotherapy schedule. No significant associations were found between biologic parameters and clinical features. Only the stage and the mitotic index were related to patient survival, and, when examined in a proportional hazard regression analysis, both provided independent information. When patients with compromised skull and/or cranial nerves (T4 tumors), who had a very short survival, were eliminated from the analysis, only the mitotic index and proliferating cell nuclear antigen allowed discrimination of a subset of patients with poor prognoses. This study shows that the assessment of cell proliferative activity can provide useful information for better predicting the clinical course of high-risk patients with nasopharyngeal carcinomas and improve therapeutic strategies.

[Cytokeratin and vimentin expression in laryngeal squamous cell carcinoma]. / Espressione delle citocheratine e della vimentina nel carcinoma della laringe.

The present study employed immunohistochemical methods to study the cytokeratin (ck) and vimentin expression in 40 cases of laryngeal squamous cell carcinoma. Specific monoclonal isoform antibodies and mixes of antibodies vs. a specific molecule were used in order to determine what cytokeratins were present as accurately as possible. In this sampling two ck patterns were identified based on whether the ck pair 8/18 was present or not. The ck 8/18 positive cases were further broken down into three sub-groups based on the expression of one of the following: the ck 4/13 pair, ck 1/10 pair or vimentin. A statistically significant relationship was found between these sub-groups, the site at which the neoplasm arose and the tendency toward regional metastases. Moreover, it was found that the presence of ck 13 in a squamous cell carcinoma is correlated with the less aggressive forms, as indicated in the literature.

[External radiotherapy in early stage squamous cell carcinoma of the supraglottic larynx. Report of 28 cases]. / Il trattamento radiante nel carcinoma iniziale (T1-T2N0) sopraglottico. Revisione di una casistica di 28 casi.

The Authors reviewed a group of 28 pts with early-stage supraglottic carcinoma (T1-T2N0), classified according to UICC (1987), and treated exclusively with radiotherapy (RT) between 1980 and 1991. Until 1990 RT was employed for such tumors when surgery was refused or controindicated, while since 1991 primary irradiation (with surgery in reserve) has been considered the treatment of choice. The total dose ranged from 66 to 70 Gy on the larynx and up to 50 Gy on neck nodes. RT was applied in a daily fraction of 2 Gy five times a week. No significant early complications were observed. Only 1 pt showed residual cronical oedema in the arytenoid region. In none of the pts was tracheostomy necessary. The local control rate obtained after 30 months was 85.7% (24/28). Salvage surgery (horizontal supraglottic laringectomy, HSL) was performed in 3 out of 4 pts with local failure and achieved complete control of the disease. In the last pt the surgery was controindicated because of poor general health conditions. The actuarial survival rate after 5 years is 86.2%. The present series was compared to a group of 152 pts with T1-T2N0 supraglottic cancer treated surgically (HSL) at the same Istitution. In these pts local control and the actuarial survival rates are 85.6% and 89% respectively. According to recent Literature data, the present findings confirm that RT may be administered for the treatment of selected early stage (T1-T2N0) supraglottic squamous cell carcinoma of the larynx with oncologic results equivalent to those obtained with radical surgery. The importance of imaging techniques (TC, MRI) in the correct staging of the tumor is emphasised.

[Non-Hodgkin's lymphomas of the salivary gland: analysis of prognostic factors in 28 cases]. / I linfomi non Hodgkin delle ghiandole salivari: analisi dei fattori prognostici su 28 casi.

Primary malignant lymphomas of the major salivary glands are rare and usually arise in the parotid gland (2% of all neoplastic disorders). In this report clinical records of 28 cases of NHL of salivary glands (27 in the parotid gland and one in the submandibular gland) are reviewed and problems related to diagnosis and management strategies are discussed. The 5-year overall survival rate was 72% and did non differ from the survival of other NHL of the head and neck. Statistical evaluation of prognostic factors (age, histology, clinical stage, grading, bulky and surgical approach--biopsy versus parotidectomy), are presented. Analysis of these factors showed that prognosis was not influenced by age, histology, clinical stage and grading of disease. Poor survival was significantly correlated to bulky lesions (tumor size greater than 6 cm). In our experience surgical treatment did not significantly affect survival rate. It is concluded that diagnostic surgical procedures in case of suspected NHL of the parotid gland are fine needle aspiration biopsy. (FNAB) or incisional biopsy. The treatment of choice is radiotherapy associated with chemiotherapy in cases of localized-bulky or disseminated disease.

Invasive mycotic and actinomycotic oropharyngeal and craniofacial infection in two patients with AIDS.

Two cases of invasive oropharyngeal and craniofacial infection caused by fungal and actinomycotic pathogens are described in HIV-infected patients. Two women with a previous diagnosis of AIDS, one with non-Hodgkin's lymphoma and one with Candida oesophagitis, developed a subacute, invasive inflammatory process characterized by ulcerative necrotizing lesions spreading from the oropharynx up to the soft and hard palate, maxillary sinuses and nasal cavity, with extensive soft-tissue necrosis. Although presenting with a very similar clinical picture, infection was due to Actinomyces spp. in the first case, while an apparent dual fungal aetiology (Aspergillus flavus and Candida spp.) was demonstrated in the second patient. Both cases were characterized by remarkable diagnostic difficulties leading to a late final recognition (confirmed by histological examination), and by a partial response to antimicrobial treatment.

A case of Merkel-cell carcinoma metastatic to the tonsil.

Metastatic tumours are rare in the tonsil. We describe a 69-year-old male patient who had previously undergone a resection of a Merkel-cell tumour of the left forearm and subsequently presented with a left tonsillar tumour. Biopsy revealed a metastatic Merkel-cell carcinoma. Our patient is the first described case of Merkel-cell carcinoma metastasizing to the tonsil. The clinical and histopathological picture of this rare tumour is presented, along with a review of literature.

Laryngeal metastasis from colonic adenocarcinoma.

Metastases to the larynx from distant primaries are very rare. Usually the secondary lesion comes from an hypernephroma or malignant melanoma. A case of metastatic laryngeal tumour from a colonic adenocarcinoma, occurring in a 59-year-old woman, is presented and the routes for laryngeal spread are discussed. The poor survival-rate of these patients justified only conservative surgery.

[Intraparotid lesions in HIV infection]. / Lesioni intraparotidee in infezione da HIV.

HIV-related lesions of the parotid region. A case of parotid enlargement in a 43-year-old male with unsuspected HIV infection is reported. Lesions consisted in lymphonodal changes, epi-myoepithelial islands and cysts lined by squamous epithelium. It is suggested that it is possible to recognize an unsuspected HIV infection, when the first clinical involvement is in the parotid region.

The use of microfluorometry to study DNA in nasopharyngeal carcinomas: a possible prognostic tool?

A microfluorometric method was used to determine the nuclear DNA content in the nasopharyngeal carcinomas (NPC) of 25 patients treated before 1983. Eleven patients are still alive with no evidence of disease (NED), while the rest died of their disease (DOD). All of the patients received a cycle of radiotherapy, while some also received chemotherapy or neck dissections. The neoplastic cells studied were taken from the original biopsy blocks, deparaffinized, isolated by enzymatic treatment and mechanical fragmentation, and then Feulgen-stained. The cytofluorometric measurement was carried out by a microphotometer equipped for fluorescence excitation and connected to a computer. This method allowed us to construct a histogram of the DNA content in the neoplastic cells. Different neoplastic classes were identified and represent the heteroclonality of the tumor, which can be expressed by the heteroclonality index (HCT). From the collected data it appears that the NED patients all had a low HTC (less than 1) and only 7 of the DOD patients had low HTCs (less than 1). Six of the DOD patients with a low HTC were in advanced stages of their tumor at the time of diagnosis, while the remaining patient did not complete his treatment. Our results show that the DNA analysis of the NPC cell population may offer a useful tool in predicting the biological behavior of this tumor and also improving its treatment.