P16 Hypermethylation Predicts Surgical Outcome Following Curative Resection of Mid/Distal Bile Duct Cancer

Background

Bile duct cancer has very poor prognosis. Important prognostic factors include the TNM stage, cell differentiation, and histologic type; however, we often observe patients whose prognosis is not consistent with the TNM stage. Additional prognostic indicators are mandatory to complement those used presently. We evaluated the hypermethylation status of genes for the power to predict overall survival following curative resection of mid/distal bile duct cancer.

Methods

Pyrosequencing hypermethylation status at the loci of interest was analyzed in 65 mid/distal bile duct carcinoma specimens obtained at Severance Hospital of Yonsei University College of Medicine from January 2000 to December 2006.

Results

Significant methylation frequencies (MtI >5 %) were obtained for 5 genes (which P16 [17 %], DAPK [54 %], E-cadherin [60 %], RASSF-1 [46.2 %], and hMLH1 [43.1 %]). MtI status of P16, DAPK, and RASSF-1 were correlated with perineural invasion, tumor depth, and age, respectively. In the multivariate analysis of overall survival, the presence of lymph node metastasis and P16 methylation status were identified as independent prognostic factors for overall survival. Patients with unmethylated of P16 had the 3- and 5-year survival rates of 60.8 and 54.9 %, respectively. In patients with hypermethylated P16, the 3- and 5-year survival rates were 27.3 and 0.0 %, respectively.

Conclusions

P16 hypermethylation and lymph node metastasis may predict overall survival in curative resected mid/distal bile duct cancer. Classification of mid/distal bile duct cancer by both genetic and epigenetic profiles may improve the accuracy in predicting outcome and the effectiveness of tailored therapy in these diseases.     

Comparison of Lateral Opening Wedge Calcaneal Osteotomy and Medial Calcaneal Sliding-opening Wedge Cuboid-closing Wedge Cuneiform Osteotomy for Correction of Planovalgus Foot Deformity in Children

The purpose of the present study was to compare the clinical and radiographic results between 2 procedures, lateral opening wedge calcaneal osteotomy (LCL) and medial calcaneal sliding-opening wedge cuboid-closing wedge cuneiform osteotomy (3C) in patients with planovalgus foot deformity. A total of 38 patients who underwent either LCL (18 patients, 28 feet) or 3C (20 patients, 32 feet) were included in the present study. The etiology of the planovalgus foot deformity was idiopathic in 16 feet and cerebral palsy in 44 feet. The 2 procedures used in the present study were indicated in symptomatic (pain or callus) children in whom conservative treatment, such as shoe modifications or orthotics, had been applied for more than 1 year but had failed. The patients were evaluated preoperatively, postoperatively, and at the last follow-up visit, both clinically and radiologically, and the interval to union and postoperative courses were compared between the 2 groups. In the LCL group, 19 of the 28 feet (68%) showed a satisfactory outcome and 9 (32%) an unsatisfactory outcome. In the 3C group, 28 of the 32 feet (88%) showed a satisfactory outcome and 4 (12%) an unsatisfactory outcome. The clinical results were not significantly different between the 2 groups, with mild to moderate pes planovalgus deformity. However, the clinical results were better in the 3C group with severe pes planovalgus deformity than in the LCL group with severe pes planovalgus deformity. All 4 radiographic parameters were improved at the last follow-up visit in both groups. In particular, the talar–first metatarsal angle and the calcaneal pitch angle on the weightbearing lateral radiographs were significantly improved in the 3C group with mild to moderate planovalgus foot deformity. All 4 parameters were significantly improved in the 3C group with severe planovalgus foot deformity. No significant differences were observed between the 2 groups in terms of the interval to union and postoperative care. No case of postoperative deep infection or nonunion was encountered in either group. 3C is a more effective procedure than LCL for the correction of pes planovalgus deformity in children, especially severe pes planovalgus deformities.     

Prognostic Value of Early Postoperative Tumor Marker Response in Gastric Cancer

Background

The clinical usefulness of tumor markers as predictors of treatment outcome in patients with stomach cancer after radical gastrectomy has been poorly defined. The purpose of this study was to evaluate a comprehensive understanding of the impact of early postoperative tumor marker normalization on survival after gastrectomy.

Methods

Between January 2001 and December 2007, we enrolled 206 patients who had received radical gastrectomy as an initial treatment and had elevated carcinoembryonic antigen (CEA) (>5 ng/mL) or carbohydrate antigen (CA) 19-9 (>37 U/mL) levels. Early tumor marker response was defined as a normalization of preoperative CEA or CA19-9 values 1–2 months after gastrectomy.

Results

The mean patient age was 61 years (range 29–84 years), and 139 patients (67.5 %) were male. Early tumor marker response was identified in 150 of 206 (72.8 %) patients. Of the patients, 49 (23.8 %), 41 (19.9 %), and 116 (56.4 %) were stages I, II, and III, respectively, according to the seventh edition of the American Joint Commission on Cancer (AJCC) staging system. Both disease-free survival (DFS) and overall survival (OS) were significantly longer in patients with tumor marker response compared with nonresponse (61.5 vs. 37.6 months; P = 0.010 and 71.3 vs. 50.9 months; P = 0.008, respectively). Multivariate analyses showed that high CA19-9 level, early tumor marker response, and tumor, node, metastasis classification system stage were independent predictors of DFS and OS (P < 0.05).

Conclusions

Early CEA or CA19-9 normalization after radical gastrectomy is a strong prognostic factor for gastric cancer, especially in patients with high preoperative levels of tumor markers.     

Conversion of Twice‐Daily Tacrolimus to Once‐Daily Tacrolimus Formulation in Stable Pediatric Kidney Transplant Recipients: Pharmacokinetics and Efficacy

The pharmacokinetics, efficacy and safety of once‐daily tacrolimus formulation (Tac‐OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice‐daily tacrolimus formulation (Tac‐BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac‐OD on a 1:1 basis and maintained on a once‐daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C₀ concentrations (4.10 ± 1.16–3.53 ± 1.10 ng/mL, p = 0.004), and AUC_0–24 (151.8 ± 41.6–129.8 ± 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac‐OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac‐BID can be safely converted to Tac‐OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated.

     

Acute spinal subdural hematoma with hemiplegia after acupuncture: a case report and review of the literature

Background context

Subdural spinal hematoma (SDH) is a very rare entity; however, it can lead to serious complications resulting from injuries to the spinal cord and roots. Although acupuncture has been a popular method for the management of pain control, we encountered the first case of SDH after acupuncture.

Purpose

The purpose of this case report was to present the first case of subdural hematoma after acupuncture and the reasons for the risks of blind cervical acupuncture.

Study design

A case report and review of the previous literature are presented.

Methods

A 69-year-old man complained of progressive weakness in the right upper and lower extremities 2 hours after acupuncture on the cervical spine and back. The diagnosis was delayed because of unilateral weakness, and the symptom was initially misinterpreted as a transient ischemic attack because of no sensory change and pain and normal findings of two brain magnetic resonance imaging (MRI).

Results

Cervical MRI 36 hours after onset revealed acute hematoma from the C3–C5 level; hematoma showed an isointensity on T1-weighted image (WI) with the preservation of epidural fat and a hypointensity on T2WI. A decompressive surgery was scheduled to perform within 2 days after the cervical MRI scan because of a previous anticoagulation therapy, but the patient refused it. Finally, 9 days after the onset, surgical decompression and removal of hematoma were performed. Three months postoperatively, the patient had fully recovered demonstrating fine hand movement and good ability to walk up and down the stairs.

Conclusions

Our study indicates that it is essential to perform cervical MRI when a patient does not show an improvement in the neurologic deficit and has a negative brain MRI after acupuncture. In addition, blind acupuncture if not correctly practiced may be harmful to the cervical structures.