Karl Wu

Prognostic Factors of Treatment Outcomes in Patients with Granulocytic Sarcoma

Purpose: To investigate the possible prognostic factors of survival outcomes in patients with granulocytic sarcoma (GS). Methods: We retrospectively investigated the prognostic factors determining survival in 24 patients with GS using Kaplan-Meier survival analysis followed by log rank tests. We evaluated gender, age, location, GS antedating leukemia, underlying disorders, treatment type and stem cell transplantation. Results: The 5-year survival rate for the patients with GS was 21%. The patients undergoing chemotherapy had a significantly longer survival time compared to those who did not (p = 0.0009). We found no difference in the 5-year survival rate among the patients undergoing chemotherapy combined with radiation or surgery. Patients with chronic myelogenous leukemia and myelodysplastic disorders had worse survival rates (p = 0.0028). Conclusion: Early diagnosis with biopsy and early chemotherapy can improve survival outcome. Local radiation or surgery can improve symptoms but does not influence survival outcomes.

Treatment of unicameral bone cyst: a comparative study of selected techniques.

BACKGROUND There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. METHODS From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. RESULTS The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 +/- 2.3 months compared with 23.4 +/- 14.9, 12.2 +/- 8.5, and 6.6 +/- 4.3 months in Groups 1, 2, and 3, respectively. CONCLUSIONS This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

The diagnostic and prognostic effectiveness of F-18 sodium fluoride PET-CT in detecting bone metastases for hepatocellular carcinoma patients.

BackgroundThe aim of this prospective study is to evaluate the diagnostic and prognostic usefulness of F-18 sodium fluoride (NaF) positron emission tomography-computed tomography (PET-CT) relative to Tc-99m methylene diphosphonate (MDP) planar bone scintigraphy with no CT (BS) for hepatocellular carcinoma (HCC) patients with suspicious bone metastasis. MethodsBoth Tc-99m MDP BS and F-18 NaF PET-CT were performed for 34 consecutive Taiwanese HCC patients (five female and 29 male; mean age, 61.0±12.0 years) within a time span of 1 month (mean: 11.3±10.4 days). The accuracies of BS and PET-CT were determined by comparing their results with the finalized clinical data in a lesion-by-lesion manner. ResultsAccording to the pathological and/or follow-up results, the accuracy for detecting metastatic bone lesions by Tc-99m MDP BS is 75.4% and that by F-18 NaF PET-CT is 95.7%, respectively. F-18 NaF PET-CT is significantly more accurate than Tc-99m MDP BS (P=0.0001). Furthermore, there is a significant correlation between the presence of F-18 NaF PET-CT-positive bone lesions and the survival time of HCC patients. On the other hand, the diagnostic results from BS are not correlated with the survival time of these HCC patients. ConclusionF-18 NaF using PET-CT system has significantly better sensitivity and specificity than conventional Tc-99m MDP BS in detecting metastatic HCC bone lesions that are predominantly osteolytic. The diagnostic result of PET-CT also serves as a more effective prognostic indictor for HCC patients.

15-deoxy-Δ12,14-prostaglandin-J2 and ciglitazone inhibit TNF-α-induced matrix metalloproteinase 13 production via the antagonism of NF-κB activation in human synovial fibroblasts

Collagenase‐3 (matrix metalloproteinase, MMP‐13) plays an important role in the degradation of cartilage in pathologic conditions. MMP‐13 is elevated in joint tissues in both rheumatoid arthritis (RA) and osteoarthritis (OA). In addition, inflammation‐stimulated synovial fibroblasts are able to release MMP‐13 and other cytokines in these diseases. The peroxisome proliferator‐activated receptor‐γ (PPARγ) ligands are recently considered as new anti‐inflammatory compounds and these ligands were reported to ameliorate inflammatory arthritis. The aim of this study is to evaluate the mechanisms how PPARγ ligands inhibit the inflammatory response in synovial fibroblasts. Two PPARγ ligands, cyclopentenone prostaglandin 15‐deoxy‐Δ12,14‐prostaglandin‐J2 (15d‐PGJ2) and synthetic thiazolidinedione compound ciglitazone were examined in this study. Here we found that 15d‐PGJ2 and ciglitazone markedly inhibited TNF‐α‐induced MMP‐13 production in human synovial fibroblasts. In addition, activation of nuclear factor κB (NF‐κB) is strongly associated with MMP‐13 induction by TNF‐α and the activation of NF‐κB was determined by Western blot, reporter assay, and immunofluorescence. It was found that 15d‐PGJ2 markedly attenuated the translocation of NF‐κB by direct inhibition of the activation of IKK via a PPARγ‐independent manner. Ciglitazone also inhibits TNF‐α‐induced MMP‐13 expression by suppressing NF‐κB activation mainly via the modulation of p38‐MAPK. Collectively, our data demonstrate that 15d‐PGJ2 and ciglitazone attenuated TNF‐α‐induced MMP‐13 expression in synovial fibroblasts primarily through the modulation of NF‐κB signaling pathways. These compounds may have therapeutic application in inflammatory arthritis. J. Cell. Physiol. 226: 3242–3250, 2011.

Thyroid Carcinoma with Bone Metastases: A Prognostic Factor Study

Objective Occult clinical presentations usually hinder the early detection and management of patients with bone metastases from thyroid carcinoma. We retrospectively investigated the clinical outcomes of such patients from 1993 to 2004 and analyzed the prognostic parameters. Design The basic demographic data and manifestations of 44 patients who had thyroid carcinoma with bone metastases were reviewed. We studied the gender, age, locations of metastases, histological types, treatment methods, hypercalcemic episodes and results of treatments. We used Kaplan-Meier survival analysis and log-rank tests to access the statistical significance. Main Outcome The incidence of bone metastasis from thyroid carcinomas in this series was 5.0%. Twenty patients (45.4%) had follicular, 16 (36.3%) had papillary, 3 (6.8%) had anaplastic, 3 (6.8%) had medullary, and 2 (4.5%) had Hurthel cell carcinomas. Twelve patients had hypercalcemic episodes, ranging from 2.6 to 2.9 mmolL−1 (mean ± SD: 2.68 ± 0.15 mmolL−1). Survival time after bone metastases ranged from 2 months to 8 years (mean ± SD: 5.3 ± 1.3 years). The 5-year survival rate was 79.4% and the 10-year survival rate was 52.9%. Regarding the histological cancer type, patients with papillary and follicular cancers survived significantly longer than those with anaplastic and medullary cancers (p < 0.05). In addition, the patients presenting with hypercalcemia had the worst survival (p < 0.05). Conclusions Thyroid carcinoma can present with bone metastases in its early stage. We found that both tumor type and hypercalcemia were significant prognostic factors for survival time.

Treatment of Unicameral Bone Cyst: Surgical Technique

BACKGROUND There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. METHODS From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. RESULTS The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 ± 2.3 months compared with 23.4 ± 14.9, 12.2 ± 8.5, and 6.6 ± 4.3 months in Groups 1, 2, and 3, respectively. CONCLUSIONS This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

Comparing hook plates and Kirschner tension band wiring for unstable lateral clavicle fractures.

The purpose of this study was to compare outcomes and complications of clavicular hook plate and Kirschner tension band wiring for fixation of unstable lateral clavicle fractures. The surgical outcomes of 92 consecutive patients (mean age, 49.30 ± 15.54 years) with unstable fractures of the lateral clavicle treated using AO clavicle hook plates were compared with those of 24 patients (mean age, 50.67 ± 17.58 years) treated using K-wire tension banding. Patients in the hook plate and K-wire groups were followed up for 22.76 ± 2.22 and 25.67 ± 2.75 months, respectively (P<.001). The time to hardware removal was significantly shorter (P<.001) in the hook plate group (5.20 ± 1.93 months) compared with the K-wire group (7.58 ± 2.00 months), whereas the Constant-Murley score was significantly higher (P<.001) in the hook plate group (90.43 ± 4.78) compared with the K-wire group (85.63 ± 5.38) at final follow-up. There were 12 complications in the hook plate group and 7 in the K-wire group (P=.069). Complications in the hook plate group included 7 periprosthetic fractures, 4 plate removals, and 1 plate malposition. Complications in the K-wire group included 3 K-wire migrations, 3 losses of reduction, and 1 wire breakage. We found that hook plate fixation of unstable lateral clavicle fractures was associated with statistically better shoulder function and earlier implant removal than K-wire tension band fixation, with an equivalent rate of complications. Our findings suggest that hook plates are useful for treating unstable lateral clavicular fractures.

Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation

SummaryDextromethorphan (DXM), a commonly used antitussive, is a dextrorotatory morphinan. Here, we report that DXM inhibits the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption by abrogating the activation of NF-κB signalling in vitro. Oral administration of DXM ameliorates ovariectomy (OVX)-induced osteoporosis in vivo.IntroductionDXM was reported to possess anti-inflammatory properties through inhibition of the release of pro-inflammatory factors. However, the potential role and action mechanism of DXM on osteoclasts and osteoblasts remain unclear. In this study, in vitro and in vivo studies were performed to investigate the potential effects of DXM on osteoclastogenesis and OVX-induced bone loss.MethodsOsteoclastogenesis was examined by the TRAP staining, pit resorption, TNF-α release, and CCR2 and CALCR gene expression. Osteoblast differentiation was analyzed by calcium deposition. Osteogenic and adipogenic genes were measured by real-time PCR. Signaling pathways were explored using Western blot. ICR mice were used in an OVX-induced osteoporosis model. Tibiae were measured by µCT and serum markers were examined with ELISA kits.ResultsDXM inhibited RANKL-induced osteoclastogenesis. DXM mainly inhibited osteoclastogenesis via abrogation of IKK-IκBα-NF-κB pathways. However, a higher dosage of DXM antagonized the differentiation of osteoblasts via the inhibition of osteogenic signals and increase of adipogenic signals. Oral administration of DXM (20 mg/kg/day) partially reduced trabecular bone loss in ovariectomized mice.ConclusionDXM inhibits osteoclast differentiation and activity by affecting NF-κB signaling. Therefore, DXM at suitable doses may have new therapeutic applications for the treatment of diseases associated with excessive osteoclastic activity.

Pelvic skeletal metastasis of hepatocellular carcinoma with sarcomatous change: a case report

Sarcomatoid hepatocellular carcinoma (HCC) is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum α-fetoprotein level was never elevated beyond normal limit (< 20 ng/mL) through the whole course of treatment. We considered sarcomatoid hepatocellular carcinoma bone metastasis a highly aggressive lesion with unusual metastatic pattern. Surgical treatment with adequate safe margin in such a huge tumor with hypervascularity and extensive invasion in the pelvis was difficult; and radiotherapy maybe refractory regarding the sarcomatous nature. Therefore, debulking operation with local symptoms control may provide a better quality of life. And the clinical course suggests sarcomatoid hepatocellular carcinoma is derived from the transition of an ordinary hepatocellular carcinoma.

High false negative rate of Tc-99m MDP whole-body bone scintigraphy in detecting skeletal metastases for patients with hepatoma

BACKGROUND/PURPOSE Technetium-99m methylene diphosphonate (Tc-99m MDP) whole-body bone scintigraphy (BS) has been widely used for detecting bone metastases. The aim of this study is to investigate the diagnostic accuracy of BS in detecting skeletal metastases for hepatocellular carcinoma (HCC) patients. In addition, the anatomic distribution of the metastatic bone lesions and the prognoses of the HCC patients are also analyzed. METHODS We retrospectively reviewed BS results of 179 consecutive HCC patients from January 2005 to December 2006 in our institution. The false negative (FN) rate, sensitivity, and specificity of BS were evaluated by patient-based and region-based analyses. RESULTS A total of 59 patients (33.0%) were confirmed of bone metastases. A total of 25 of these 59 patients (46.3%) had at least one lesion categorized as BS FN, and the bone metastatic status for 10 patients (17.0%) was underestimated by BS. The most observed metastatic site was spine while the most observed sites with FN of BS were the lower extremity. In total, there were 122 metastatic regions and 33 regions (27.0%) were FN of BS. Patients without any metastases survived significantly longer than any of other groups with metastases. CONCLUSION High FN rate of Tc-99m MDP BS in detecting metastatic bone lesions for HCC patients was observed. In our opinion, careful history taking, meticulous examination, and a high index of suspicion are important for HCC patients with unexplained progressive pain in the musculoskeletal system. Even with negative results from Tc-99m MDP BS, the possibility of skeletal metastases cannot be indiscriminately excluded.