Youn-Soo Park

Early Osteolysis Following Second-Generation Metal-on-Metal Hip Replacement

BACKGROUND Total hip arthroplasty with use of metal-on-metal bearings has been reintroduced as an alternative to the use of metal-on-polyethylene bearings because of theoretical advantages such as reduced wear and a lower prevalence of osteolysis. However, we observed early osteolysis in a cohort of patients who had been managed with second-generation metal-on-metal hip replacements and investigated the possible etiologic role of metal hypersensitivity. METHODS We retrospectively analyzed 165 patients (169 hips) who had undergone primary cementless total hip replacement with a contemporary metal-on-metal total hip design between 2000 and 2002. After a minimum duration of follow-up of twenty-four months, nine patients (ten hips) had an osteolytic lesion localized to the greater trochanter. Skin-patch tests for hypersensitivity to metals were performed on the nine patients and on nine randomly selected patients with total hip replacements who did not have osteolytic changes and who were matched to the study cohort for age and gender. Microbiological cultures, histopathologic examinations, and immunohistochemical analysis were performed on samples of periprosthetic tissue that were collected during revision arthroplasty on two hips with early osteolysis. RESULTS The patients with early osteolysis had a significantly higher rate of hypersensitivity reaction to cobalt compared with controls (p = 0.031). The retrieved periprosthetic tissues showed no evidence of metallic staining, but histologic analysis revealed a perivascular accumulation of CD3-positive T-cells and CD68-positive macrophages and an absence of both particle-laden macrophages and polymorphonuclear cells. Immunohistochemical analysis demonstrated that bone-resorbing cytokines such as IL-1beta and TNF-alpha were produced mainly by infiltrating lymphocytes and activated macrophages. CONCLUSIONS These findings raise the possibility that early osteolysis in patients with this second-generation metal-on-metal hip replacement is associated with abnormalities consistent with delayed-type hypersensitivity to metal. A prospective study in which a large group of patients is evaluated with multiple diagnostic methods is needed in order to establish whether there is a causal relationship between metal hypersensitivity and osteolysis.

Ceramic failure after total hip arthroplasty with an alumina-on-alumina bearing.

BACKGROUND The mechanical properties of alumina ceramic, now in its third generation, have been markedly improved through the evolution of design features and manufacturing processes and the introduction of proof-testing. Nonetheless, because of the lack of ductility of alumina ceramic, there is concern regarding the risk of fracture during insertion or in vivo use. The purpose of the present study was to present a multicenter review of primary total hip arthroplasties performed with use of a polyethylene-ceramic composite liner combined with a ceramic femoral head, with particular attention to failure of the ceramic bearing. METHODS We evaluated 357 primary total hip arthroplasties that had been performed in 319 patients with use of a contemporary alumina-on-alumina bearing design incorporating a polyethylene-ceramic composite liner within a titanium-alloy shell coupled with a 28-mm-diameter ceramic femoral head. The procedures were performed at four participating centers from 1998 to 2001. Ceramic failure without trauma occurred in six hips (1.7%). All of these hips were revised, and the retrieved alumina implants were examined by means of visual inspection and scanning electron microscopy equipped with energy-dispersive x-ray spectrometry. RESULTS Two femoral heads fractured during the first postoperative year, and four alumina liners fractured after an average of 36.8 months in vivo. All four of the explanted alumina liners revealed evidence of rim contact with the metal neck of the femoral component. Composition analysis confirmed that surface-stain materials were titanium particles transferred from the femoral component. CONCLUSIONS Despite the theoretical improvement in the fracture toughness of a polyethylene-alumina composite liner, a relatively high rate of catastrophic ceramic bearing surface failure was still observed at the time of short-term follow-up. This finding prompted us to discontinue the use of this type of alumina bearing design.

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients

In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P=0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P=0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P=0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.

Nasal-type NK/T cell lymphoma: clinical features and treatment outcome.

Nasal-type NK/T cell lymphoma is an increasingly recognised disease entity of aggressive clinical behaviour. The objective of this study was to investigate clinical features and treatment outcomes in patients with nasal-type NK/T cell lymphoma. From January 1991 to December 2003, 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. One half of patients presented with poor performance status (ECOG ⩾2); 46% of patients were categorised as high intermediate or high-risk group according to IPI; and 46% of patients were diagnosed at advanced stage. The median survival for 26 patients with nasal-type NK/T cell lymphoma was 7.4 months (95% CI, 0.1, 16.9). The treatment outcome of primary anthracycline-based chemotherapy was poor: 60% CR rate in localised disease and 0% CR rate in advanced disease. After a median follow-up of 24.4 months (range 3.1–99.0) in patients with localised disease who had achieved a CR (range 29.6–165.7), three patients (50.0%) developed disease recurrence at 6.1, 21.8, and 52.1 months, respectively, and all patients presented with locoregional failure. The predictive factors for poor survival were of age greater than 60, advanced stage and poor performance in multivariate analysis. In conclusion, Nasal-type NK/T cell lymphomas showed a poor response to the conventional anthracycline-based chemotherapy, and thus an investigation for an innovative therapy is urgently needed to improve survival in these patients.

Changes in the epigenetic status of the SOX-9 promoter in human osteoarthritic cartilage.

Whether osteoarthritis (OA) is associated with alterations in the epigenetic status of anabolic factors is largely unknown. To answer the question, we investigated the DNA methylation and histone modification of SOX‐9 gene promoter, a typical anabolic gene, in the articular cartilage from nine patients with femoral neck fractures without OA and from nine hip OA patients. Methylation‐specific PCR (MSP) and bisulfite sequencing analysis (BSQ) showed that the methylation of SOX‐9 promoter was increased in OA cartilage compared to normal cartilage. The decreased SOX‐9 gene and protein expression in OA chondrocytes was reversed by the treatment of 5‐azacytidine (5‐AzaC), the demethylating agent. Methylation of SOX‐9 proximal promoters reduced the binding affinity of transcription factors CCAAT‐binding factor/nuclear factor‐Y and cyclic adenosine monophosphate (cAMP) response element–binding. There was a significant increase in H3K9 and H3K27 trimethylation and a significant decrease in the acetylation of H3K9, 15, 18, 23, and 27 at SOX‐9 promoters in OA chondrocytes. These findings suggest that hip OA is associated with a change in the epigenetic status of SOX‐9 promoter, including increased DNA methylation and altered histone modification.

A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer

Capecitabine plus oxaliplatin every 3 weeks (XELOX regimen) has proven efficacy in patients with colorectal carcinoma. We investigated this combination in patients with previously untreated advanced gastric carcinoma. The study population comprised patients with histologically confirmed nonresectable advanced gastric adenocarcinoma. Patients received intravenous oxaliplatin 130 mg m−2 over 2 h on day 1 plus oral capecitabine 1000 mg m−2 twice daily on days 1–14, every 3 weeks. Patients received a maximum of eight cycles. Twenty evaluable patients (17 men, 3 women) with a median age of 64 years (range 38–75) were enrolled. The overall response rate was 65% (95% confidence interval (CI), 44–86%), with complete responses in two patients and partial responses in 11 patients. Median progression-free survival was 7.5 months (95% CI, 3.2–11.7 months); median overall survival was not reached during the study period. There was no grade 4 and little grade 3 toxicity. The most common haematological adverse event was anaemia (65% of patients) and the most common nonhaematological toxicities were vomiting (65%), neuropathy (60%), diarrhoea (30%), and hand–foot syndrome (20%). In conclusion, XELOX is apparently as effective as triplet combinations and is well tolerated as first-line therapy for advanced gastric carcinoma. We are starting a large multi-institutional phase II study of XELOX in this setting.

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy

Background:With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy.Methods:The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed.Results:From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14%; P=0.04), and less severe hepatitis (0 vs 17%; P=0.002).Conclusion:Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.

Cementless Modular Total Hip Arthroplasty in Patients Younger than Fifty with Femoral Head Osteonecrosis: Minimum Fifteen-Year Follow-Up

This study aimed to report the outcome of total hip arthroplasty (THA) with a modular femoral component in patients younger than fifty years with osteonecrosis of femoral head. Sixty-four osteonecrotic hips in fifty-five patients were available for clinical and radiographic analyses at minimum follow-up of fifteen-years. The mean Harris hip score improved from 36 points preoperatively to 92.7 points at final follow-up. Sixty-two (95.3%) hips demonstrated stable bone ingrowth. No hips showed loosening or required revision for aseptic loosening. Survivorship with an end point of stem revision for any reason was 93.8% and for aseptic loosening was 100% at 16.8years. We believe that cementless THA with a modular stem is a promising procedure for young and active patients with osteonecrosis of the femoral head.

Clinical significance of CD151 overexpression in subtypes of invasive breast cancer.

Background:CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.Methods and results:The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.Conclusion:CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.

Treatment of periprosthetic hip infection caused by resistant microorganisms using 2-stage reimplantation protocol.

To determine the effectiveness of staged reimplantation for the treatment of periprosthetic hip infection caused by resistant microorganisms, we performed a retrospective case-control study on 37 consecutive patients who had a culture-proven periprosthetic hip infection treated using a 2-stage reimplantation protocol. Twenty-four patients infected by resistant microorganisms were compared with 13 patients infected by nonresistant microorganisms. The second-stage reimplantation procedure was possible in 34 (92%) of the 37 patients, but the remaining 3 required permanent resection because of persistent infection. At a mean follow-up of 4.4 years, there were 4 recurrent infections and 1 aseptic cup loosening. Overall treatment failure rate was 22%. All failures occurred only in the resistant microorganism group and none in the nonresistant microorganism group (33% vs 0%; P = .032). Current 2-stage reimplantation protocol showed a high rate of treatment failure in our patients with a periprosthetic hip infection caused by resistant microorganisms.