Akinori Iwasaki

Adjunct teriparatide therapy with monitoring of bone turnover markers and bone scintigraphy for bisphosphonate-related osteonecrosis of the jaw

The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still difficult in many cases that do not respond to conservative treatments. We report a case of BRONJ treated by adjunctive teriparatide therapy for 6 months with monitoring of bone turnover markers (at baseline, at 1, 3, and 6 months of treatment, and after 9 months off therapy) and bone scintigraphy (at baseline, 3 and 6 months, and after 9 months off therapy). The patient was a 78-year-old woman with osteoporosis and BRONJ. She had not responded to previous conventional treatment. Teriparatide was added for resolution of BRONJ. The pain disappeared after 1 month, and remarkable bone regeneration was obtained after 6 months, with significantly increasing bone formation and resorption markers. Bone scintigraphy showed regression of the uptake area. This case suggests the usefulness of monitoring bone turnover markers and using bone scintigraphy to increase the effectiveness of teriparatide therapy.

Multivariate analysis of factors influencing oral mucositis in allogeneic hematopoietic stem cell transplantation

Little information is available regarding the effect of oral intervention on the outcome of hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the incidence of oral mucositis after allogeneic HSCT with or without oral intervention among 96 consecutive patients in our hospital between January 1988 and March 2006. We combined two oral intervention strategies: cryotherapy and oral health care. The former was applied beginning in 2003 for patients being treated with melphalan, and the latter, which was the study’s main strategy, was applied to all HSCT recipients beginning in 2004. Oral mucositis was evaluated according to NCI CTCAE v3.0. The incidence of oral mucositis was 30.9% (17/55) in reduced-intensity stem cell transplantation (RIST), which was significantly lower than the 90.2% (37/41) in conventional stem cell transplantation (CST; P < 0.001). Among these 96 patients, severe oral mucositis was observed in 19 (46.3%) CST cases and in 6 (10.9%) RIST cases (P < 0.001). The occurrence of oral mucositis apparently decreased after oral health care instructions were given. Multiple logistic analysis revealed that the conditioning regimen and oral health care were independent risk factors for the incidence of oral mucositis. The cryotherapy did not exert enough potency to prevent oral mucositis in patients who had undergone CST or RIST. We concluded that oral health care improved tissue damage due to an overall upgrade in oral hygiene during chemotherapy.

Correlation of (18)F-fluoromisonidazole PET findings with HIF-1α and p53 expressions in head and neck cancer: comparison with (18)F-FDG PET.

ObjectiveWe evaluated tumor hypoxia using 18F-fluoromisonidazole (18F-FMISO) PET in relation to the expression of hypoxia-inducible factor-1&agr; (HIF-1&agr;) and p53 in patients with head and neck cancer and compared the results with those obtained using 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) PET. Materials and methodsA total of 28 tumors (23 primary tumors and five metastatic lymph nodes) from 24 patients with newly diagnosed head and neck cancer were examined with 18F-FMISO PET and 18F-FDG PET. The 18F-FMISO PET images were scaled to the venous blood concentration of 18F-FMISO activity to produce tumor-to-blood (T/B) values. Hypoxia was defined as a region with a T/B ratio greater than or equal to 1.2. The maximum T/B (T/Bmax) and hypoxic volumes were calculated by region-of-interest analysis. For 18F-FDG PET, the maximum standardized uptake value (SUVmax) and hypermetabolic volume were calculated by region-of-interest analysis. The expressions of HIF-1&agr; and p53 using immunohistochemistry were estimated in tumor tissue samples. ResultsA weak correlation was observed between hypoxic volume and T/Bmax (r=0.53, P=0.003) on using 18F-FMISO PET and between hypermetabolic volume and SUVmax (r=0.38, P=0.046) on using 18F-FDG PET. The hypoxic volume using 18F-FMISO PET and hypermetabolic volume using 18F-FDG PET also showed a weak correlation (r=0.44, P=0.020). The values of 18F-FMISO hypoxic volume showed a weak correlation with HIF-1&agr; (r=0.40, P=0.037) and p53 (r=0.47, P=0.012) obtained on immunohistochemical examination. ConclusionThis study demonstrates a weak correlation between hypoxic volume measured by 18F-FMISO PET and expressions of HIF-1&agr; and p53 in head and neck cancer.

Comparison of 201Tl- with 67Ga single photon emission tomography in the diagnosis of head and neck cancer recurrence

The purpose of this study was to evaluate the usefulness of 201Tl single photon emission tomography (SPET) in comparison with 67Ga SPET for distinguishing recurrent tumours in patients previously treated for head and neck cancer. A total of 37 patients with suspicion of recurrent cancer were investigated. SPET images with 201Tl were acquired 10 min (early) and 3 h (delayed) and SPET images with 67Ga were acquired 72 h, after injection. The visual and semiquantitative (T/N ratio) analysis were performed. On visual analysis, results from early 201Tl SPET were the same as those from delayed 201Tl SPET. The sensitivity, specificity and accuracy of the diagnosis of local recurrence using 201Tl SPET were all 100%. The three values using 201Tl SPET for neck lymph node metastases were 73%, 100% and 91%. The corresponding values using 67Ga SPET for local recurrence were 57%, 100% and 89%, respectively, and those using 67Ga SPET for neck lymph node metastases 55%, 100% and 84%, respectively. In the semiquantitative analysis, there was a statistically higher T/N ratio obtained using 201Tl when compared with 67Ga. 201Tl early SPET, especially, has the potential to replace 67Ga SPET in the follow-up of patients with head and neck cancer.

Monitoring of bone turnover markers and bone scintigraphy for teriparatide therapy in bisphosphonate related osteonecrosis of the jaw

Treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains an intractable problem in many cases. Recent literatures have shown that the new treatment modality using teriparatide may be beneficial to BRONJ. However, the teriparatide therapy was not effective in all cases. It would be necessary to assess the therapeutic effectiveness of teriparatide with predictable procedures to treat BRONJ. We report here two cases of BRONJ treated by adjunctive teriparatide therapy for 6 months while simultaneously performing the monitoring of changes of bone turnover markers and the quantitative assessment of bone scintigraphy. Six months after the combination of teriparatide and conservative treatment, CT showed evidence of bone regeneration and the intraoral wound was completely healed. Biochemical bone formation markers were monitored at the time points of 0, 1, 3 and 6 months. Almost of all the markers related to the bone formation and resorption revealed an increase during the teriparatide treatment. The uptake area and quantitative value of technetium-99m-methylene diphosphonate showed a reduction after the administration of teriparatide. It was strongly suggested that teriparatide therapy is one of the useful treatments for BRONJ based on monitoring bone turnover results and employing bone scintigraphy.