Wei-Hsin Lin

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.

Unusual causes of carpal tunnel syndrome: space occupying lesions

Space occupying lesions found at surgery caused or contributed to carpal tunnel syndrome in 23 of 779 patients operated for carpal tunnel syndrome from January 1999 to December 2008. The mean age of these 23 patients was 52.9 years, and in patients who had a local swelling or palpable mass, ultrasonography or magnetic resonance imaging (MRI) was done. All had open release of the transverse carpal ligament and lesions were removed. Histopathology showed tophaceous gout in 10 men, tenosynovitis in seven patients and tumors in eight. The tumors included ganglion cysts in two, lipoma in three and fibroma of the tendon sheath in one. The neurological symptoms subsided after surgery in all. In patients with gout, one had an infected wound and another had recurrence of symptoms 1 year after later. Carpal tunnel syndrome caused by a space occupying lesion is rare and more complicated than idiopathic carpal tunnel syndrome.

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.

Diverse Targets of β-Catenin during the Epithelial–Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse

Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that are activated by epithelial-mesenchymal transition (EMT). However, the mechanistic relationship between EMT and the Wnt pathway in CSC is not entirely clear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex, the latter of which then binds to CSC-related gene promoters. Tandem coimmunoprecipitation and re-ChIP experiments with epithelial-type cells further revealed that Sox15 associates with the β-catenin/E-cadherin complex, which then binds to the proximal promoter region of CASP3. Through this mechanism, Twist1 cleavage is triggered to regulate a β-catenin-elicited promotion of the CSC phenotype. During EMT, we documented that Twist1 binding to β-catenin enhanced the transcriptional activity of the β-catenin/TCF4 complex, including by binding to the proximal promoter region of ABCG2, a CSC marker. In terms of clinical application, our definition of a five-gene CSC signature (nuclear β-catenin(High)/nuclear Twist1(High)/E-cadherin(Low)/Sox15(Low)/CD133(High)) may provide a useful prognostic marker for human lung cancer.

Polarized cell migration induces cancer type-specific CD133/integrin/Src/Akt/GSK3β/β-catenin signaling required for maintenance of cancer stem cell properties

CD133 is widely used as a surface marker to isolate cancer stem cells (CSCs). Here we show that in CSCs CD133 contributes to β-catenin-mediated transcriptional activation and to the self-renewal capacity of sphere-forming and side-population (SP) cells in cell lines from brain, colon and lung cancers, but not gastric or breast cancers. In chromatin immunoprecipitation assays, β-catenin binding to the proximal promoter regions of ITGA2-4 and ITGA10-11 in brain, colon and lung cancer cell lines could be triggered by CD133, and β-catenin also bound to the proximal promoter regions of ITGB6 and ITGB8 in cell lines from gastric and breast cancers. CD133 thus induces β-catenin binding and transcriptional activation of diverse targets that are cancer type-specific. Cell migration triggered by wounding CD133+ cells cultured on ECM-coated dishes can induce polarity and lipid raft coalescence, enhancing CD133/integrin signaling and asymmetric cell division. In response to directional cues, integrins, Src and the Par complex were enriched in lipid rafts, and the assembly and activation of an integrated CD133-integrin-Par signaling complex was followed by Src/Akt/GSK3β signaling. The subsequent increase and nuclear translocation of β-catenin may be a regulatory switch to increase drug resistance and stemness properties. Collectively, these findings 1) indicate that a polarized cell migration-induced CD133/integrin/Src/Akt/GSK3β/β-catenin axis is required for maintenance of CSC properties, 2) establish a function for CD133 and 3) support the rationale for targeting CD133 in cancer treatment.

An aberrant nuclear localization of E-cadherin is a potent inhibitor of Wnt/β-catenin-elicited promotion of the cancer stem cell phenotype.

Several studies suggest that Wnt signaling contributes to reprogramming and maintenance of cancer stem cell (CSC) states activated by loss of membranous E-cadherin expression. However, E-cadherin’s exact role in Wnt/β-catenin-mediated promotion of the CSC phenotype remains unclear. Recently, a significant positive correlation has been observed between the expression of nuclear (an aberrant nuclear localization) E-cadherin and β-catenin in gastric and colorectal carcinomas. Here we conducted a series of in-vitro and in-vivo studies to show that the β-catenin/TCF4 interaction was abolished by E-cadherin and was correlated with its nuclear localization, and consequently decreased β-catenin/TCF4 transcriptional activity. Nuclear E-cadherin was a negative regulator of Wnt/β-Catenin-elicited promotion of the CSC phenotype. Using immunohistochemistry on lung cancer tissue microarrays, we found that changes in subcellular location of E-cadherin may be described by tumor grade and stage, suggesting cellular redistribution during lung tumorigenesis. Furthermore, nuclear E-cadherin expression was more significantly inversely correlated with CD133 (a lung CSC marker) expression (P<0.005) than total E-cadherin expression (P<0.05), suggesting that lung cancer as defined by nuclear E-cadherinLow/nuclear β-cateninHigh/CD133High biomarkers has superior prognostic value over total E-cadherinLow/nuclear β-cateninHigh/CD133High.

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.

Slipped capital femoral epiphysis in an adult with panhypopituitarism.

Slipped capital femoral epiphysis usually occurs in children going through a pubertal growth spurt, possibly because the immature proximal femoral physis is unable to bear the shear stress. It commonly occurs in adolescents between 10 and 16 years. Slipped capital femoral epiphysis in adults is uncommon, with only 10 cases reported in the literature. This article presents a case of a 29-year-old man with craniopharyngioma diagnosed when he was 19. He underwent surgery with subtotal tumor excision and postoperative radiotherapy, but received no further treatment for the panhypopituitarism concomitant with the tumor. He reported sudden onset of left hip pain after riding a bicycle and underwent surgical fixation 5 days later. He also underwent hormone replacement therapy, including prednisolone, thyroxin, desmopressin, and testosterone, and regular clinical follow-up. His hip function recovered with a painless gait. At 18-month follow-up, neither osteonecrosis nor contralateral slipped capital femoral epiphysis was noted. Furthermore, bilateral proximal femoral physes were also closed. For stable slippage as in this case, in situ pinning fixation is a commendable method. A high index of suspicion of endocrinal disorder and proper management are essential for successful treatment of adult slipped capital femoral epiphysis.

Traumatic Femoral Vein Rupture Resulting in Compartment Syndrome with Concomitant Closed Femoral Diaphyseal Fracture

Compartment syndrome of the thigh after an isolated femoral shaft fracture is a rare finding1. Schwartz et al.2 found only twenty-one cases of thigh compartment syndrome in more than 6000 patients with femoral shaft fracture. Arterial injury has been reported to cause compartment syndrome either directly or indirectly after arterial repair2-5. To our knowledge, acute thigh compartment syndrome secondary to femoral vein rupture has not previously been reported. We present a patient with acute thigh compartment syndrome caused by bleeding from a rupture of the femoral vein with a concomitant traumatic femoral diaphyseal fracture. The fracture and compartment syndrome were successfully treated with an extensive lateral fasciotomy and open reduction and internal fracture fixation with locked intramedullary nailing, followed by primary reconstruction of the ruptured femoral vein with a saphenous vein graft. The patient was informed that data concerning his case would be submitted for publication, and he provided consent. A twenty-four-year-old healthy man was involved in a motor vehicle accident. He was seen in our emergency department immediately following the accident without initial loss of consciousness. Tachycardia (heart rate, 140 beats per minute) and hypotension (systolic/diastolic blood pressure [BP], 90/50 mm Hg) were noted. The initial physical examination revealed a profoundly swollen left thigh with ecchymosis. Although the left leg and foot were also swollen, the dorsalis pedis pulse was strong. The posterior tibial, popliteal, and femoral pulses were palpable. An expanding nonpulsatile mass was palpated over the medial side of the left thigh. The preoperative radiograph showed a femoral diaphyseal fracture (Fig. 1-A). After volume-replacement intravenous therapy, the vital signs were stabilized. Computed tomography angiography (CTA) was done to evaluate for an arterial injury. However, neither an arterial injury nor a large blush caused by local hemorrhage was detected (Fig. 1-B …