Pathological fracture and pyogenic osteomyelitis in a patient with type 2 Gaucher disease

In Gaucher disease (GD), enzyme replacement therapy (ERT) results in the alleviation of hematological abnormalities and visceral infiltration as well as improvement in quality of life and life-span. However, several years may be required for skeletal manifestations, which are usually observed in type 1 and 3 GD, to respond to ERT. Infants with type 2 GD rarely present skeletal manifestations because most of these patients die within the first 2 years of life before they develop skeletal involvement. The use of ERT may prolong the lifespan of these patients and influence the natural history of the disease. The present study reports a new natural history of treated GD in which a 2-year and 7-month-old girl with type 2 GD who was receiving ERT developed valproate-induced Fanconi syndrome, pathological fractures, and pyogenic osteomyelitis. In conclusion, skeletal disease may occur in any type of GD, and Fanconi syndrome may lead to severe skeletal complications in patients with GD.     

Objective evaluation of cerebrovascular reactivity for acetazolamide predicts cerebral hyperperfusion after carotid artery stenting: Comparison with region of interest methods

Background and purpose

Hemodynamic impairments are considered risk factors of cerebral hyperperfusion after carotid artery stenting (CAS); measurement by Single-photon emission computed tomography (SPECT) using a subjective region of interest (ROI) method lacks consistency and reproducibility.

Accurate localization of rectal cancer using near infrared ray-guided surgery with intra-operative colonoscopy and da Vinci Firefly technology

Surgery Today - Accurate localization of the tumor during robot-assisted laparoscopic surgery for rectal cancer is crucial. Several techniques have been described, but each has its shortcomings. We...     

Efficacy of an Anti-Semaphorin 3A Neutralizing Antibody in a Male Experimental Retinal Vein Occlusion Mouse Model

PurposeSemaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction.MethodsWe examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-α and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer.ResultsInduction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-α and semaphorin-related proteins.ConclusionsThese findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.     

Thallium-201 scintigraphy for the assessment of long-term prognosis in patients with osteosarcoma

Objective

The aim of this study was to confirm the prognostic value of ²⁰¹Tl scintigraphy in the midcourse of preoperative chemotherapy in patients with osteosarcoma.

Methods

The 28 patients with biopsy-proven osteosarcoma were enrolled retrospectively in this study. Planar scintigraphy was performed 15?min after injection of 111?MBq ²⁰¹Tl before preoperative chemotherapy and after third course (midcourse) of chemotherapy in all patients. The ²⁰¹Tl uptake ratio was calculated by dividing the count density of the lesion by that of the contralateral normal area. The percentage reduction of the ²⁰¹Tl uptake ratio calculated by 100?×?[(pre-chemotherapy ratio??C?mid-chemotherapy ratio)/pre-chemotherapy ratio] was compared with the histopathological response and long-term survival rate.

Results

Good histopathological response was observed in 16 patients. Mean follow-up period was 58.0?±?41?months. Both overall and event-free survival rates of histopathologically good responders were significantly higher than that of poor responders (P?=?0.018 and P?=?0.0076). There was also significant correlation between pre-chemotherapeutic effect evaluated with ²⁰¹Tl scintigraphy and overall and event-free survival rate in all patients (P?=?0.045 and P?=?0.017, respectively), and in patients without metastasis at initial diagnosis (P?=?0.043 and P?=?0.031, respectively).

Conclusion

²⁰¹Tl scintigraphy performed in the middle of neoadjuvant chemotherapy can predict overall survival and event-free survival in patients with osteosarcoma.     

Pleomorphic Carcinoma with Exophthalmos and a Subsequent Diagnosis of Paraneoplastic Syndrome

The patient was a 75-year-old man who developed polyopia and exophthalmos. Chest computed tomography (CT) revealed a mass in the left upper lobe. A CT-guided biopsy suggested lung adenocarcinoma. He was treated by neoadjuvant chemotherapy followed by left upper lobectomy. He was diagnosed with stage IIB pleomorphic carcinoma postoperatively. Preoperative head magnetic resonance imaging revealed exophthalmos and bilateral swelling of the extraocular muscles. The thyroid function of the patient was within the normal range, and he tested negative for autoantibodies. As his symptoms and swelling of the extraocular muscles improved postoperatively, he was diagnosed with paraneoplastic syndrome.     

Chemical constituents and diversity of Ligularia lankongensis in Yunnan Province of China

The chemical constituents of the roots of Ligularia lankongensis collected at seven different places in Yunnan Province, China, were investigated together with the DNA sequence of the atpB- rbcL intergenic region. All the samples contained a new, highly oxygenated bisabolane-type sesquiterpene ( 1). Four other oxygenated bisabolanes ( 2 and the new 3, 4, and 5) were also obtained. Intraspecific diversity was observed in the composition of the compounds, but not in the DNA sequence.     

Priming Therapy with Alpha-Interferon in Chemotherapy-Resistant Multiple Myeloma

Nine patients with multiple myeloma were treated with alpha-interferon (IFN) priming followed by the previous chemotherapy regimen to which the patients had been resistant. Natural human leukocyte IFN (8 patients) or recombinant human IFN-2b (1 patient) at a dose of 5-6 × 10⁶ IU s.c. was given for 1-2 weeks before chemotherapy, after which IFN was used either cyclically or continuously (3-6 × 10⁶ ID every other day). Four patients responded; three had a good response based on reduction of the paraprotein level, and one patient had no further progress of his bone lesions. Two of the patients have had a prolonged response lasting 21 and 13+ months, respectively. IFN increased chemotherapy-related myelotoxicity considerably, and three patients died of granulocytopenic sepsis. The use of IFN priming may possibly offer an alternative for the treatment of some patients with resistant multiple myeloma.     

Anti-tumor cytotoxicity of γδ T cells expanded from peripheral blood cells of patients with myeloma and lymphoma

In order to establish an efficient gammadelta T cell-mediated immunotherapy for hematological malignancies, we attempted to evaluate cytotoxicity against tumor cells by gammadelta T cells, which were generated from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and a low dose of IL-2. Although gammadelta T cells were expanded in patients with myeloma and lymphoma as well as normal persons, the amplification rates of gammadelta T cells before and after culturing varied from patient to patient in myeloma and lymphoma. gammadelta T cells generated in patients with myeloma and lymphoma showed a potent cytotoxic ability against myeloma/lymphoma cell lines as shown in gammadelta T cells generated in normal subjects. In addition, gammadelta T cells generated in a patient with myeloma showed a cytotoxic ability against self myeloma cells freshly prepared from bone marrow. However, the same gammadelta T cells were demonstrated to be non-cytotoxic to normal cells of the patient. These data demonstrated that gammadelta T cells, which could be expanded in vitro from blood cells of patients with myeloma and lymphoma by culturing with zoledronate and IL-2, possess a sufficient cytotoxic ability against tumor cells. These findings suggested that in vitro generated patients' gammadelta T cells could be applied to gammadelta T cell-mediated immunotherapy for hematological malignancies.