Nicholas S. Mastronikolis

Gorlin-Goltz syndrome: incidental finding on routine ct scan following car accident.

IntroductionGorlin-Goltz syndrome is a rare hereditary disease. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Multiple basal cell carcinomas (BCCs), odontogenic keratocysts, skeletal abnormalities, hyperkeratosis of palms and soles, intracranial ectopic calcifications of the falx cerebri and facial dysmorphism are considered the main clinical features. Diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by DNA analysis. Because of the different systems affected, a multidisciplinary approach team of various experts is required for a successful management.Case presentationWe report the case of a 19 year-old female who was involved in a car accident and found to present imaging findings of Gorlin-Goltz syndrome during a routine whole body computed tomography (CT) scan in order to exclude traumatic injuries.ConclusionRadiologic findings of the syndrome are easily identifiable on CT scans and may prompt to early verification of the disease, which is very important for regular follow-up and better survival rates from the co-existent diseases.

Alterations in the Content and Composition of Glycosaminoglycans in Human Laryngeal Carcinoma

Glycosaminoglycans in normal and cancerous human laryngeal cartilage were isolated and characterized by means of enzyme susceptibility and high performance liquid chromatography. The known mammalian glycosaminoglycans were identified in all samples but their content and composition varied between normal and malignant samples. Chondroitin/ dermatan sulphate was the major glycosaminoglycan in all cases, but its relative proportion was decreased in malignant samples. Its sulphation pattern showed that in normal samples it was sulphated mainly at the C6 position of galactosamine, whereas in malignant samples it was sulphated mainly at C4. Dermatan sulphate, expressed as a result of the different digestion of samples with chondroitinases, was present in very small amounts in normal samples (2.7% of total sulphated glycosaminoglycans) but increased in proportion up to 27.7% in malignant samples. The content of oversulphated chondroitin/dermatan was increased twofold in malignant samples. The content of heparan sulphate was increased almost fivefold in malignant samples as compared to normal ones. The content of hyaluronan was increased in malignant samples 3.5-fold, amounting to up to 11.4% of total glycosaminoglycans. These dramatic changes in the content and composition of glycosaminoglycans seemed to be characteristic of the tumour and independent of its status.

A phase II study with vinorelbine, gemcitabine and cisplatin in the treatment of patients with stage IIIb-IV non-small cell lung cancer (NSCLC).

In our phase II study an acceptable and effective agent like cisplatin was used in combination with vinorelbine and gemcitabine in patients with non-small cell lung cancer (NSCLC). These two new cytostatic drugs have demonstrated, when used as a single-agent treatment, effective response rates (vinorelbine) and minimum toxicity (gemcitabine). The following schedule was used: (i) vinorelbine 25 mg/m2 on days 1 and 8; (ii) gemcitabine 1000 mg/m2 on days 1 and 8; and (iii) cisplatin 75 mg/m2 on day 8. The schedule was repeated every 21 days, with a maximum of six cycles per patient. A total of 31 patients with a mean Karnofsky performance status of 90% were evaluated and 29 of them were finally eligible. Of the patients, five (16.1%) were at stage IIIb and the remainder (83.9%) were at stage IV. The overall response rate was 65% (20 patients); six patients (19.4%) had complete response (CR) and 14 (45.2%) had partial response (PR). Two patients (6.5%) had stable disease and seven (22.6%) had progressive disease. The most notable toxicity was hematologic. Leukoneutropenia was mainly revealed after the third or fourth cycle and granulocyte-colony stimulating factor (G-CSF) was administered in 24 patients (77.4%). Mild anemia was found in almost all patients after the third or fourth cycle (Hb 10-11 g/dl) and eight patients (25.8%) required erythropoietin (EPO). Thrombocytopenia was more often observed compared with other known chemotherapeutic regimens; six patients (19.4%) had grade I thrombocytopenia and therapy was delayed in another four patients (12.9%) due to this complication. Non-hematologic toxicity was mild and well tolerated and consisted of alopecia (54.8%), nausea and vomiting (12.9%), constipation (12.9%), peripheral neuropathy (9.6%), diarrhea (6.5%), stomatitis (3.2%) and local phlebitis (3.2%). The examined combination provides us with one of the best overall responses rates reported, however at the cost of remarkable hematologic toxicity. Therefore, it would be better applied in patients with good performance status. The high response rates give us hope of using this combination as a neoadjuvant regimen.

Extramedullary plasmacytoma of the nasal cavity

medullary neoplasms. The latter are rare tumors, more commonly presenting in the submucosal tissue of the upper respiratory tract. A mass or swelling causing nasal or pharyngeal symptoms is by far the most common presentation of this entity in the head and neck region. We report a case of nasal extramedullary plasmacytoma in a 75-year-old female with left nasal obstruction, epiphora, and hearing loss. A review of the symptoms presentations, diagnosis, treatment, survival, and prognostic factors in the affected patients, is also presented. The most common symptoms of nasal tumors, whether benign or malignant, consist of nasal obstruction, blood-tinged mucus, and epistaxis. Facial asymmetry, loose teeth, and sensory changes around the nose are late symptoms and occur less frequently. Differential diagnosis of a nasal mass includes both benign and malignant tumors. Benign tumors of the nose are rare in comparison with malignant growths. In decreasing order of frequency, the benign tumors are osteoma, hemangioma, papilloma, and angiofibroma. Squamous cell carcinoma is the most common malignant tumor of the nose. Other malignant neoplasms include adenocarcinoma, adenoid cystic carcinoma, sarcoma, and malignant melanoma. A rare malignant tumor of the nasal cavity is extramedullary plasmacytoma. According to Willis,1 plasmacytomas are classified into 3 groups: 1. Multiple myeloma characterized by generalized bone involvement and characteristic radiographic findings, with frequently abnormal serum protein and Bence-Jones proteinuria. 2. Solitary plasmacytoma of the bone, with no evidence of generalized disease. 3. Primary plasmacytoma of the soft tissues that can be single or multiple. Extramedullary plasmacytoma represents less than 1% of all head and neck malignancies and less than 0.4% of upper respiratory malignancies. In 1997, Pahor2 reported on a series of 943 cases of plasmacytomas in the period 1963 to 1972. Twenty-two of these cases were extramedullary plasmacytomas, 14 of which were in the head and neck region. Clinical presentation is that of a submucosal mass or swelling with a polypoid configuration often without bone destructions and causing nasal or pharyngeal symptoms.

Bilateral ossification of the auricles: an unusual entity and review of the literature

BackgroundTrue ossification of the auricle with cartilage replacement by bone, is a very rare clinical entity and can result in an entirely rigid auricle.Case presentationWe present a rare case of bilateral ossification of the auricles in a 75-years old man with profound progressive rigidity of both auricles. His main complaint was a mild discomfort during resting making sleeping unpleasant without any other serious symptoms. His medical history was significant for predisposing factors for this condition such as, Addisons disease and diabetes mellitus. Excisional biopsy was performed confirming the ossified nature of the auricles. Further treatment deemed unnecessary in our case due to his mild clinical picture.ConclusionTrue auricular ossification is a quite rare clinical entity with unclear pathogenesis and one should have in mind that there is always the possibility of a serious co-existed disease like endocrinopathy.

Chronic rhinocerebral mucormycosis: a rare case report and review of the literature

Rhinocerebral mucormycosis is an invasive infection caused by filamentous fungi of the Mucoraceae family. The rhinocerebral form of the disease represents the most common form and has two distinct clinical entities. The common presentation consists of a rapidly progressive infection with high mortality rate, while the other presentation is that of a chronic infection with lower mortality. In the present paper we report a rare case of chronic rhinocerebral mucormycosis. An 85‐year‐old male with a 6‐month history of purulent and odorous nasal discharge, and sporadic episodes of epistaxis and anosmia, presented to the outpatient department of our clinic. Initial cultures were positive only for Pseudomonas aeruginosa. The patient was unresponsive to ciprofloxacin treatment, developing necrotic areas of the nasal septum suspicious for rhinocerebral mucormycosis. Admission to the ENT clinic followed, with histopathologic evaluation of the vomer bone confirming the diagnosis. The patient was treated with amphotericin B and was discharged 3 weeks later on oral posaconazole therapy. Chronic rhinocerebral mucormycosis may present with atypical symptoms or coinfection with another agent. A high degree of clinical suspicion is required for correct diagnosis and prompt initiation of appropriate treatment.

The chondroitin/dermatan sulfate synthesizing and modifying enzymes in laryngeal cancer: Expressional and epigenetic studies

BackgroundSignificant biochemical changes are observed in glycosaminoglycans in squamous cell laryngeal carcinoma. The most characteristics are in chondroitin/dermatan sulfate fine structure and proportion, which might be due to differential expression of the enzymes involved in their biosynthesis. The aim of the present work was the investigation in expressional and epigenetic level of the enzymes involved in chondroitin/dermatan sulfate biosynthesis in laryngeal cancer.MethodsTissues subjected to total RNA and DNA isolation, and protein extraction. The techniques used in this study were RT-PCR analysis, western blotting and methylation specific PCR.ResultsWe identified that many enzymes were expressed in the cancerous specimens intensively. Dermatan sulfate epimerase was expressed exclusively in the cancerous parts and in minor amounts in healthy tissues; in the macroscopically normal samples it was not detected. Furthermore, chondroitin synthase I and chondroitin polymerizing factor were strongly expressed in the cancerous parts compared to the corresponding normal tissues. Sulfotransferases, like chondroitin 6 sulfotransferase 3, were highly expressed mainly in healthy specimens.ConclusionsThe study of the various chondroitin/dermatan synthesizing enzymes revealed that they were differentially expressed in cancer, in human laryngeal cartilage, leading to specific chondroitin/dermatan structures which contributed to proteoglycan formation with specific features. The expression of the examined enzymes correlated with the glycosaminoglycan profile observed in previous studies.

A solid phase assay for the determination of heparan sulfate and its application to normal and cancerous human cartilage samples.

A sensitive and accurate quantitative assay for the measurement of minor amounts of chondroitin/dermatan sulfate and heparan sulfate that does not require specific apparatus or reagents is described. The assay involves labeling of chondroitin sulfate A following reaction of carboxyl groups with biotin hydrazide in the presence of carbodiimide. ELISA plate wells were coated with glutaraldehyde and then spermine was coupled to it via a Schiffs base bond. In such activated wells, the biotinylated molecules were readily bound and detected after the interaction with avidin-peroxidase conjugates and the subsequent enzymic assay. Chondroitin/dermatan sulfate and heparan sulfate competed this interaction in a linear manner. Disaccharides derived from chondroitin sulfate A did not act as competitors, while heparan sulfate disaccharides showed significant competition. From the competition, before and after digestion with either chondroitinase ABC or heparitinases, the amounts of chondroitin sulfate and heparan sulfate in a sample could be calculated. The assay was applied for the determination of sulfated glycosaminoglycans in normal and cancerous human laryngeal cartilage samples. By using this procedure, the accurate determination, especially, of heparan sulfate in a mixture of glycosaminoglycans was achieved, which otherwise would require the use of very expensive technology.

Pharyngocutaneous Fistula Complicating Laryngectomy: Can Metronidazole Help?

Aim: To evaluate the use of metronidazole as a prophylactic agent against pharyngocutaneous fistula (PCF) formation. Patients and Methods: Seventy patients who underwent total laryngectomy between 2000 and 2008 in our department were divided into two groups. The first group (M+ group) was placed on a 10-day metronidazole regimen (2 days prior to surgery and 7 days following). The second group (M– group) received only regular preoperative chemoprophylaxis. Results: In total, 17 (24.3%) incidents of PCF were reported, 3 of which were in the M+ group, with the remainder in the M– group. A statistically significant reduction in the PCF rate was noted in favor of metronidazole in the overall population (p = 0.005), as well as in the patient group that had received radiotherapy prior to surgery (p = 0.03). Conclusion: Metronidazole administered for a total of 10 days pre- and postoperatively seems to lower the incidence rate of PCF formation.

Sinus fluid penetration of oral clarithromycin and azithromycin in patients with acute rhinosinusitis.

Background The aim of this study was to investigate the extracellular concentration and the degree of sinus fluid penetration of newer macrolides, within the first 24–48 hours of treatment in patients with acute bacterial rhinosinusitis (ABRS), choosing clarithromycin and azithromycin as model antibiotics. An open, noninterventional pharmacokinetic study was performed at a tertiary teaching hospital. Methods In 36 outpatients with ABRS, sinus fluid aspirates and serum samples were collected 2, 4, 6, 8, and 12 hours or 2, 6, 12, and 24 hours after the administration of three doses of oral clarithromycin, 500 mg, twice daily or two doses of oral azithromycin, 500 mg, once daily, respectively. Drug concentrations were determined in both matrices by high-performance liquid chromatography with fluorometric detection, and the pH was estimated for all sinus fluid samples. Results The average clarithromycin sinus fluid concentration was found to be significantly higher than the corresponding azithromycin concentration (2.47 mg/L versus 0.65 mg/L), while the extent of the average sinus fluid penetration, expressed by the ratio of drug concentration in tissue versus serum, was similar for both drugs (115 and 120%, respectively). Conclusion In patients with ABRS, clarithromycin and azithromycin present adequate penetration into sinus fluid to eradicate erythromycin-sensitive strains of Streptococcus pneumoniae. Considering their comparative in vitro activity, the sinus fluid pH effect, and their sinus fluid penetration profile, we may conclude that among the erythromycin-resistant S. pneumoniae strains, clarithromycin might be advantageous over azithromycin in eradicating some of the low-level resistant strains.