Surgical Indication for Non-curative Endoscopic Resection in Early Gastric Cancer

Background Endoscopic resection (ER) is an effective treatment for early gastric cancer (EGC) without lymph node metastasis. However, after ER additional surgery may be needed to manage the risks presented by residual cancer or lymph node metastasis. Methods ER was performed on 344 gastric adenocarcinomas between November 2001 and April 2006 at the Korean National Cancer Center under the strict pre-procedural indication. The authors performed operations in 43 patients due to: residual mucosal cancer, a mucosal cancer larger than 3 cm, or a submucosal cancer regardless of size or margin involvement. ER and surgical specimens were reviewed and analyzed for residual cancer and lymph node metastasis. Results Based on examinations of ER specimens, cancer was confined to the mucosal layer in 15 patients (34.9%) and invaded the submucosal layer in 28 patients (65.1%). Surgical specimens showed residual cancer in 17 patients (39.5%) and lymph node metastasis in four (9.3%). Neither residual cancer nor lymph node metastasis was found in patients with less than 500 μm submucosal invasion without margin involvement in ER specimens. In three of four patients with lymph node metastasis, the depth of submucosal invasion was 500 μm or more; the remaining patient had a 4-cm-sized differentiated mucosal cancer. Conclusions When a pathologic evaluation of an ER specimen reveals more than 500 μm of submucosal invasion or a mucosal cancer of larger than 3 cm, surgery should be considered due to the risk of lymph node metastasis.     

Transduodenal local resection for low-risk group ampulla of vater carcinoma

BACKGROUND: Carcinoma of the ampulla of Vater has a more favorable prognosis, compared to other malignant tumors of the periampullary region, because it usually presents with symptoms in the early stage. However, treatment by local resection only of the ampullary carcinoma remains controversial. The aim of this study was to evaluate the treatment results of the ampulla of Vater carcinoma according to different types of operation in low-risk-group patients. METHODS: We retrospectively reviewed the medical records of 17 low-risk-group patients among a total of 102 patients with ampulla of Vater carcinoma who had underwent curative surgery from 1992 to 2002. All specimens were critically reviewed by a single expert pathologist, and the relationship between surgical outcomes and operation type was assessed. RESULTS: The low-risk group was comprised of 10 men and 7 women with a median age of 57.8 years. Thirteen of 17 patients underwent a pancreaticoduodenectomy (PD) or a pylorus preserving pancreaticoduodenectomy (PPPD), while 4 patients underwent a transduodenal local resection (TDLR). The operation time was significantly shorter in the TDLR group, compared to the PD or PPPD groups. Among the 17 patients, there was only 1 case of recurrence in the inguinal area 33 months after the pancreaticoduodenectomy. CONCLUSIONS: Transduodenal local resection is a comparable mode of operation for low-risk-group patients with Ampulla of Vater carcinoma. In particular, it is essential to evaluate the invasion depth in preoperative endoscopic ultrasonography, cell differentiation in preoperative biopsy, and positivity of resection margin accurately by using frozen section during the operation.     

Thoracic ossification of ligamentum flavum caused by skeletal fluorosis

Thoracic ossification of ligamentum flavum (OLF) caused by skeletal fluorosis is rare. Only six patients had been reported in the English literature. This study reports findings from the first clinical series of this disease. This was a retrospective study of patients with thoracic OLF due to skeletal fluorosis who underwent surgical management at the authors' hospital between 1993 and 2003. Diagnosis of skeletal fluorosis was made based on the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis was present. Neurological status was evaluated preoperatively, at the third day postoperatively, and at the end point of follow-up using the Japanese Orthopaedic Association (JOA) scoring system of motor function of the lower extremities. A total of 23 cases were enrolled, 16 (69.6%) males and 7 (30.4%) females, age ranging from 42 to 72 years (mean 54.8 years). All patients came from a high-fluoride area, and 22 (95.7%) had dental fluorosis. Medical imaging showed OLF together with ossification of many ligaments and interosseous membranes, including interosseous membranes of the forearm (18/23 patients 78.3%), leg (14/23 patients 60.9%), and ribs (11/23 patients 47.8%). OLF was classified into five types based on MRI findings: localized (4/23 patients 17.4%), continued (12/23 patients 52.2%), skip (3/23 patients 13.0%), combining with anterior pressure (2/23 patients 8.7%), and combining with cervical and/or lumbar stenosis (2/23 patients, 8.7%). Urinalysis showed a markedly high urinary fluoride level in 14 of 23 patients (60.9%). Patients were followed up for an average duration of 4 years, 5 months. Paired t-test showed that the JOA score was slightly but nonsignificantly increased relative to preoperative measurement 3 days after surgery (P = 0.0829) and significantly increased at the end of follow-up (P = 0.0001). In conclusion, Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. Comparing with other OLF series, a larger number of spinal segments were involved. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptom, imaging study findings, and urinalysis. En bloc laminectomy decompression was an effective method.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.     

Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats

The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5x10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1x10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p<0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p<0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo.     

Immediate interlocking nailing versus external fixation followed by delayed interlocking nailing for Gustilo type IIIB open tibial fractures

PURPOSE: To compare immediate interlocking nailing with external fixation followed by delayed interlocking nailing, for Gustilo type IIIB open tibial fractures. METHODS: 23 patients with Gustilo IIIB open tibial fractures were treated with either immediate unreamed interlocking nailing (n=9) or external fixation followed by delayed unreamed interlocking nailing (n=14). Patient age, sex ratio, fracture site, fracture type, and severity were similar in both groups. The time to union, deep infection rate, and nonunion rate in the 2 groups were compared. RESULTS: In the immediate and delayed nailing groups, respective mean times to union were 21 (standard deviation [SD], 14) months and 14 (SD, 8) months; nonunion rates were 44% (4/9) and 36% (5/14), and deep infection rates were 22% (2/9) and 7% (1/14). All corresponding differences were not statistically significant. CONCLUSION: Prospective, randomised, multicentre studies are needed to assess whether there are significant differences between the 2 treatment methods.     

Porcine PD-L1: cloning, characterization, and implications during xenotransplantation

BACKGROUND: Effective intervention achieved by manipulating cell-mediated xenogeneic immune responses would critically increase the clinical feasibility of xenotransplantation as immediate hyperacute rejections become controllable through genetic modulations of donor organs. Endogenous negative regulatory signals like the programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) system are candidate targets for the control of cell-mediated xenogeneic immune response. METHODS: A porcine PD-L1 molecule was cloned using RACE (rapid amplification of cDNA ends) technology based on the human PD-L1 sequence. The functional effects of cloned porcine PD-L1 were tested on human CD4(+) T cell activation using porcine PD-L1-transfected bystander cells. Cellular proliferation was monitored by [3H] thymidine incorporation, and human T cell apoptosis was measured by flow cytometry. RESULTS: Porcine PD-L1 (GenBank accession number AY837780) was found to have 73.8% sequence homology with human PD-L1 and to contain two immunoglobulin domains in its extracellular region. Moreover, porcine PD-L1 expressed on Chinese hamster ovary (CHO) cells inhibited human CD4(+) T cell proliferation stimulated with anti-CD3 only or anti-CD3 plus anti-CD28. Percentages of apoptotic activated human T cells increased by over 30% in the presence of porcine PD-L1/CHO cells, and the addition of recombinant human PD-1-Fc fusion proteins during human T cell activation reversed the inhibitory effects of porcine PD-L1. CONCLUSIONS: Cloned porcine PD-L1 showed high sequence homology with human PD-L1 and a similar molecular structure. Moreover, porcine PD-L1 inhibited human CD4(+) T cell activation in human PD-1-dependent manner, and this involved activated T cell apoptosis. The authors suggest that PD-1-PD-L1 might play an important endogenous immune regulatory role during xenogeneic transplantation, and that the effective application of this system would improve transplanted xenogeneic organ survival.     

The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol.

OBJECTIVE: To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol. STUDY DESIGN: Hep-2 cells were exposed in stepwise escalating concentration of Taxol to develop the resistant cell line-Hep-2T. Cell cycle distribution, apoptosis, and rhodamine accumulation were studied through flow cytometry. The MDR1 and MRP1 genes were detected through real-time quantitative RT-PCR, and the corresponding proteins were detected through Western blotting. RESULTS: The drug resistance of Hep-2T cells to Taxol, doxorubicin, gemcitabine, 5-FU, and cisplatin all increased. The percentage of G0/G1 phase and the antiapoptosis ability increased significantly compared with Hep-2 cells. Both MDR1 and MRP1 also increased at gene and protein level, though MDR1 was more prominent. CONCLUSION: More emphasis should be laid on MDR1/Pgp, the non-Pgp substrate chemotherapeutic agents, and the changes of cell cycle distribution to prevent MDR induced by Taxol. SIGNIFICANCE: These findings may provide theoretical support for the reverse of MDR.