Gunter Hafiz

Frequencies of gap- and tight-junction mutations in Turkish families with autosomal-recessive non-syndromic hearing loss

Mutations in genes encoding gap‐ and tight‐junction proteins have been shown to cause distinct forms of hearing loss. We have now determined the GJB2[connexin 26 (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families with autosomal‐recessive inherited non‐syndromic sensorineural hearing loss (NSSHL). GJB2 mutations were found in 31.7% of the families, and the GJB2–35delG mutation accounted for 73.6% of all GJB2 mutations. The carrier frequency of GJB2–35delG in the normal Turkish population was found to be 1.17% (five in 429). In addition to the described W24X, 233delC, 120delE and R127H mutations, we also identified a novel mutation, Q80R, in the GJB2 gene. Interestingly, the Q80R allele was inherited on the same haplotype as V27I and E114G polymorphisms. As little is known about the mutation frequencies of most other recently identified gap‐ and tight‐junction genes as a cause for hearing loss, we further screened our patients for mutations in GJB3 (Cx31), GJA1 (Cx43), ΔGJB6–D13S1830 (Cx30) and the gene encoding the tight‐junction protein, claudin 14 (CLDN14). Several novel polymorphisms, but no disease‐associated mutations, were identified in the CLND14 and GJA1 genes, and we were unable to detect the ΔGJB6–D13S1830 deletion. A novel putative mutation, P223T, was found in the GJB3 gene in heterozygous form in a family with two affected children. Our data shows that the frequency of GJB2 mutations in Turkish patients with autosomal‐recessive NSSHL and the carrier rate of the GJB2–35delG mutation in the Turkish population, is much lower than described for other Mediterranean countries. Furthermore, mutations in other gap‐ and tight‐junction proteins are not a frequent cause of hearing loss in Turkey.

The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: Review of 30 cases

BACKGROUND Thirty adult patients with head and neck soft tissue sarcoma (HNSTS) treated between 1987 and 2000 were retrospectively analysed. PATIENTS AND METHODS The most frequent histopathological subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm received postoperative radiotherapy. RESULTS Five-year local control rates for patients with negative surgical margins (n=9), microscopically positive disease (n=10), gross residual disease (n=6) and inoperable cases (n=5) were 64, 70, 20 and 0%, respectively. However, there was no significant difference in local control between patients with negative or microscopically positive disease who received postoperative radiotherapy (71 vs. 70%). The patients who received doses>or=60 Gy had significantly higher local control rates than the ones who received doses lower than 60 Gy (p=0.048). The local control rates were lower in patients with grade 2-3 tumours when compared with grade 1 tumours (44 vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 vs. 13.3 months). CONCLUSION Our results confirm that the optimal treatment of HNSTSs is complete surgical excision, and that postoperative adjuvant radiotherapy clearly improves local control.

MYO15A (DFNB3) mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation.

Myosin XVA is an unconventional myosin which has been implicated in autosomal recessive nonsyndromic hearing impairment (ARNSHI) in humans. In Myo15A mouse models, vestibular dysfunction accompanies the autosomal recessive hearing loss. Genomewide homozygosity mapping and subsequent fine mapping in two Turkish families with ARNSHI revealed significant linkage to a critical interval harboring a known deafness gene MYO15A on chromosome 17p13.1‐17q11.2. Subsequent sequencing of the MYO15A gene led to the identification of a novel missense mutation, c.5492G → T (p.Gly1831Val) and a novel splice site mutation, c.8968 − 1G → C. These mutations were not detected in additional 64 unrelated ARNSHI index patients and in 230 Turkish control chromosomes. Gly1831 is a conserved residue located in the motor domains of the different classes of myosins of different species. Molecular modeling of the motor head domain of the human myosin XVa protein suggests that the Gly1831Val mutation inhibits the powerstroke by reducing backbone flexibility and weakening the hydrophobic interactions necessary for signal transmission to the converter domain.

Management of Carotid Artery Invasion in Advanced Malignancies of Head and Neck Comparison of Techniques

The objective of this study was to retrospectively investigate a single institutions experience with carotid artery resection performed as part of an oncological procedure and to determine acute and convalescent complication and survival rates. We performed a record review of 28 patients with head and neck malignancy invading the carotid artery. Immediate carotid artery resection and ligation on an emergent basis was performed on 12 patients (group 1), elective resection and ligation was performed on 8 patients (group 2), and elective resection and revascularization was performed on 8 patients (group 3). In group 1, although 1 patient survived for 1 year and 1 patient survived for 2 years, 1 patient died of severe neurologic deficit, 2 patients experienced neurologic deficit with good recovery, and 1 patient was moderately disabled. In group 2, 2 patients survived without disease for 5 years, and 2 patients experienced neurologic deficit, 1 with good recovery and the other with complete recovery. In group 3, only 1 patient survived for 5 years, and within this group, 1 patient died of severe neurologic deficit, 1 patient had neurologic deficit with moderate recovery, and 1 patient had neurologic deficit with complete recovery. No significant difference in mortality and morbidity rate was observed between the “resection and ligation” group and the “resection and revascularization” group (p = .52, χ2 = 0.79). We conclude that the surgical treatment of patients with an invaded carotid artery, including carotid resection, provides a small but real chance of 5-year survival. The methods of carotid resection and repair should be guided by clinical presentation and by preoperative and intraoperative investigations.

A more reliable method for incudostapedial rebridging ossiculoplasty: bone cement and wire.

Polymaleinate glass ionomer cement is a commercially available bone cement (Ketac Cem Radiopaque, ESPE, Germany) that can be used to reconstruct a discontinuity between the incus and the stapes. The popularity of bone cement in otologic surgery is increasing. If the missing part of the incus is too long, the results in the long term could be unsatisfying. Under such circumstances, a new method of incudostapediopexy that uses wire and involves remodeling of the long process of the incus with bone cement is introduced. A retrospective analysis of the outcomes of incudostapedial rebridging ossiculoplasty (ISRO) procedures carried out in 21 patients between June 1999 and September 2003 was performed. A total of 17 patients were treated with bone cement only; in 4 of these patients, hearing loss reoccurred within 6 months. The procedure was repeated in 2 of these patients using both bone cement and wire with satisfactory hearing results (air-bone gaps, 7.5 and 8.8 decibels hearing level [dB HL]) after 1 year. Four patients underwent ISRO wire and bone cement initially. The long-term results of these 6 “wire-and-cement” cases, which were followed for a mean of 21 months, were satisfactory (air-bone gap, 9.8 dB HL). The postoperative air-bone gap in the 15 patients who were treated by ISRO with bone cement only excluding the 2 reoperation cases was 12.1 dB HL. ISRO with bone cement is a cost-effective and safe procedure that yields good hearing results in selected cases. If the distance between eroded incus and stapes is too long to be reconstructed with bone cement alone, the surgeon should consider using wire with bone cement.

Robotic thyroidectomy using a transaxillary approach can be performed by experienced surgeons in selected surgical clinics

We read the article by Kang et al. [1] entitled RobotAssisted Endoscopic Surgery for Thyroid Cancer: Experience With the First 100 Patients with a great interest. These authors emphasized that robot-assisted endoscopic thyroid operations using a gasless transaxillary approach is a feasible, safe, and effective method for selected patients with thyroid cancer [1]. However, this robotic approach has several disadvantages. The surgeon must be experienced before performing the robotic operation. This new technique needs a da Vinci Surgical System, and its set of instruments requires excessive time. Moreover, the procedure may not be suitable for removing large thyroid tumors. Management complications due to this new technique may be require additional neck incisions and thus a longer operation time due to the narrow surgical area with transaxillary approach. Consequently, robotic thyroidectomy with a transaxillary approach is not a simple method. It can be performed by experienced surgeons in selected surgical clinics.

Serum and tissue c-erb B2, bcl-2, and mutant p53 oncoprotein levels in nasopharyngeal cancer.

To date there are no prognostic factors that can account for the biology and disease behavior in nasopharyngeal cancer. Therefore, identification of new factors that can help in predicting the behavior of the disease and characterizing the subgroup with more aggressive tumors more likely to benefit from chemotherapy is important. In this study, c-erb B2, bcl-2, and mutant p53 protein levels were investigated in sera and tumor tissue of patients with nasopharyngeal cancer. Serum c-erb B2 levels were significantly higher in the patients than in the healthy subjects. No meaningful difference was observed between the serum and tissue levels of the mutant p53 protein. Tissue bcl-2 concentrations were considerably high. Our results suggest that serum c-erb B2 levels may aid in identifying a subgroup of patients with a poorer response rate to first-line treatment.

Effectiveness of brachytherapy in the treatment of lip cancer : A retrospective study at the Istanbul university oncology institute

Stage T1 through T3 lip cancers can be treated primarily by brachytherapy (BRTX), with or without external radiotherapy (ERT), with adequate safety margins and good results. In this study, the outcomes of BRTX were reviewed for patients treated at the Brachytherapy Department of the Istanbul University Oncology Institute (IUOE). The medical records of 41 patients registered at IUOE with a diagnosis of lip cancer between 1988 and 2003 were reviewed. The median follow-up time was 88 months (24–160 mo). Among these patients, 21 patients with a primary tumor, 14 with tumors arising postoperatively, and 6 with postoperative recurrence of tumor were treated using BRTX. A total of 33 patients (80%) received BRTX alone and 8 (20%) received BRTX and ERT. The 10-year local control rate was 100%, 93%, and 67% for patients treated with BRTX alone, BRTX and surgery, and those treated for postoperative recurrence, respectively (P < .02). For patients treated with BRTX only and BRTX plus surgery, specific disease-free survival was 95% and 94%, respectively, and overall survival was 93% and 100%, respectively; these differences were not statistically significant. One patient with a postoperative recurrence who had been treated with BRTX died as a result of lip cancer. No patients developed any ulcerations, intra-oral complications, or mandibular necrosis. In the BRTX only group, 83% had excellent or good cosmetic results. In the surgery group, 62% had a contour deformity. In lip cancer management, BRTX results were comparable for local control, survival, and minimal late effects in normal tissue. This is in accordance with current reports in the medical literature. Satisfactory results were observed in patients with stage T1 and T2 lesions who had been treated with BRTX only and in patients with stage T3 lesions who had been treated with BRTX plus ERT, without a need for additional treatment modalities.