Prognostic Role of Methylation Status of the MGMT Promoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients

Objective

This study investigated whether pyrosequencing can be used to determine the methylation status of the MGMT promoter as a clinical biomarker using relatively old archival tissue samples of glioblastoma. We also examined other prognostic factors for survival of glioblastoma patients.

Methods

The available study set included formalin-fixed paraffin-embedded (FFPE) tissue from 104 patients at two institutes from 1997 to 2012, all of which were diagnosed histopathologically as glioblastoma. Clinicopathologic data were collected by review of medical records. For pyrosequencing analysis, the PyroMark Q96 CpG MGMT kit (Qiagen, Hilden, Germany) was used to detect the level of methylation at exon 1 positions 17–39 of the MGMT gene, which contains 5 CpGs.

Results

Methylation of the MGMT promoter was detected in 43 (41.3%) of 104 samples. The average percentage methylation was 14.0±16.8% overall and 39.0±14.7% for methylated cases. There was no significant pattern of linear increase or decrease according to the age of the FFPE block (p=0.687). In multivariate analysis, age, performance status, extent of surgery, method of adjuvant therapy, and methylation status estimated by pyrosequencing were independently associated with overall survival. Additionally, patients with a high level of methylation survived longer than those with low methylation (p=0.016).

Conclusion

In this study, the status and extent of methylation of the MGMT promoter analyzed by pyrosequencing were associated with overall survival in glioblastoma patients. Pyrosequencing is a quantitative method that overcomes the problems of MSP and a simple technique for accurate analysis of DNA sequences.     

Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

Objective

This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method.

Methods

Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later.

Results

There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups.

Conclusion

These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA.     

Direction selectivity of neurons in the visual cortex is non‐linear and lamina‐dependent

Neurons in the visual cortex are generally selective to direction of movement of a stimulus. Although models of this direction selectivity (DS) assume linearity, experimental data show stronger degrees of DS than those predicted by linear models. Our current study was intended to determine the degree of non‐linearity of the DS mechanism for cells within different laminae of the cat's primary visual cortex. To do this, we analysed cells in our database by using neurophysiological and histological approaches to quantify non‐linear components of DS in four principal cortical laminae (layers 2/3, 4, 5, and 6). We used a DS index (DSI) to quantify degrees of DS in our sample. Our results showed laminar differences. In layer 4, the main thalamic input region, most neurons were of the simple type and showed high DSI values. For complex cells in layer 4, there was a broad distribution of DSI values. Similar features were observed in layer 2/3, but complex cells were dominant. In deeper layers (5 and 6), DSI value distributions were characterized by clear peaks at high values. Independently of specific lamina, high DSI values were accompanied by narrow orientation tuning widths. Differences in orientation tuning for non‐preferred vs. preferred directions were smallest in layer 4 and largest in layer 6. These results are consistent with a non‐linear process of intra‐cortical inhibition that enhances DS by selective suppression of neuronal firing for non‐preferred directions of stimulus motion in a lamina‐dependent manner. Other potential mechanisms are also considered.     

A prospective short-term outcome study of a short metaphyseal fitting total hip arthroplasty

The purpose of this study was to determine whether the short, metaphyseal fitting femoral stem would achieve stable fixation without diaphyseal fixation. A total of 126 patients (144 hips) were included in the study, and their mean age was 53.9 years (26-65 years). The mean duration of follow-up was 4.5 years (4-5 years). The predominant diagnosis was osteonecrosis of femoral head (88 of 144 hips, or 61%). The mean preoperative Harris hip score was 45 points, which improved to 96 points by the final follow-up. Western Ontario and McMaster Universities Osteoarthritis score and patient's activity score were improved substantially at the final follow-up. This short, metaphyseal fitting cementless femoral component achieved stable fixation without diaphyseal fixation, and there was minimal stress-shielding bone resorption in the calcar region.     

Endoscopic thyroidectomy via bilateral axillo-breast approach (BABA): review of 512 cases in a single institute

Background

Various techniques for endoscopic thyroidectomy have been introduced in the past decade, and the cosmetic superiority of these techniques has been universally acknowledged. We developed the endoscopic thyroidectomy via bilateral axillo-breast approach (BABA) and have performed more than 500 operations. The aims of this study are to analyze the surgical outcomes and to evaluate the effectiveness and safety of BABA endoscopic thyroidectomy.

Patients and methods

Between February 2004 and March 2008, 512 patients with thyroid diseases underwent BABA endoscopic thyroidectomy. The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, tumor–node–metastasis (TNM) stage on the basis of the 7th edition of the American Joint Committee on Cancer (AJCC), results after radioactive ablation therapy, and recurrence of disease in these patients.

Results

Of 512 patients, 397 had a malignant tumor and 115 had benign thyroid disease. Eight patients were diagnosed with Graves’ disease, and nine patients underwent completion thyroidectomy. Three cases were subjected to open thyroidectomy due to uncontrolled bleeding. Mean operation time was 151.2?±?38.1?min for total and near-total thyroidectomy, and 141.7?±?50.1?min for subtotal thyroidectomy and lobectomy. Regarding postoperative complications, transient hypocalcemia occurred in 31.1% of patients and permanent hypoparathyroidism occurred in 4.2% of patients. Transient hoarseness occurred in 20.3% of patients, and permanent vocal cord palsy occurred in 1.7%. Mean hospital stay after operation was 3.34?±?0.8?days (range 3–7?days), and mean follow-up period was 57.1?±?17.6?months (range 38.5–71.7?months). There were eight cases of recurrent thyroid carcinoma, and no mortality has occurred up to the present time.

Conclusions

Endoscopic thyroidectomy via bilateral axillo-breast approach is a safe and effective method that gives good surgical completeness, a low rate of postoperative complications and recurrence, and an excellent cosmetic result. Therefore, this method is a good choice for patients with surgical thyroid diseases.     

Reappraisal of Percutaneous Transhepatic Biliary Drainage Tract Recurrence After Resection of Perihilar Bile Duct Cancer

Background

The high incidence of percutaneous transhepatic biliary drainage (PTBD) tract recurrence after resection of perihilar bile duct cancer (BDC) at a reference single center has suggested the need for endoscopic biliary drainage (EBD) to prevent PTBD-related tumor recurrence. To determine the general applicability of these findings, we validated the risk of PTBD tract recurrence in patients with resected BDC in our high-volume center.

Methods

The medical records of 306 patients with perihilar BDC who underwent hepatobiliary resection with curative intent over 10?years were reviewed retrospectively.

Results

Of the 306 patients, 293 (95.8%) underwent biliary decompression, 171 (56.1%) by preoperative PTBD, 62 (20.3%) by EBD alone, and 60 (19.7%) by both. Of the 231 patients who underwent PTBD, 160 (69.3%), 62 (26.8%), and 9 (3.9%) had one, two, or three catheters, respectively (mean of 1.3 catheters per patient for a median 23?days). No patient experienced synchronous PTBD tract metastasis, whereas 4 (1.7%) experienced PTBD tract recurrence a median 13.5?months after surgery, with 3 of these patients having an intraabdominal recurrence soon afterward. Only one patient had a solitary tract recurrence without intraabdominal metastasis. These patients survived for a median 25?months, which is comparable to survival outcomes after noncurative resection. No risk factor was significantly associated with PTBD tract recurrence.

Conclusions

We think that the risk of PTBD tract recurrence after resection of perihilar BDC is not negligible but is much lower than previously reported. There is no definitive reason to avoid PTBD when it is indicated.     

Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation

A characteristic pattern of hemodynamic changes that may occur in reperfusion phase of liver transplantation (LT) is known as post-reperfusion syndrome (PRS). In this study, we determined the frequency of PRS and evaluated possible predictors of PRS. The medical records of 152 patients who underwent living donor LT were reviewed. PRS was defined as a decrease in mean arterial pressure of more than 30% from the baseline value for more than one min during the first five min after reperfusion. The frequency of PRS was determined, and patients were divided into two groups: PRS group and non-PRS group. Donor factors, preoperative and intraoperative recipient factors, and postoperative outcomes were compared between the two groups. PRS occurred in 58 recipients (34.2%). Preoperative model for end-stage liver disease scores of recipients and percentage of graft steatotic changes were higher in PRS group. PRS group showed higher heart rates and lower hemoglobin values preoperatively. Before reperfusion, PRS group received more transfusion and their urine output was less than that of non-PRS group. Postoperatively, peak bilirubin during the first five d after LT was higher in PRS group. In conclusion, both severity of liver disease and graft steatosis may increase risk for PRS in LT. Further prospective studies of PRS in its relationship to outcome are indicated.     

Long-term outcomes after laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective study

Background

Recently, the number of laparoscopic procedures for gastric cancer has increased rapidly. Laparoscopic surgery is reported to have many advantages over open gastrectomy with oncologic safety in early gastric cancer. However, there were few reports on long-term outcomes of laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer (AGC). The aim of this study was to investigate long-term survival outcomes after LAG for AGC.

Methods

The data of 1,485 patients who underwent LAG between April 1998 and December 2005 by ten surgeons at ten hospitals were collected retrospectively. Among them, 239 patients who were diagnosed with AGC on final pathologic examination were enrolled in the present study to investigate long-term clinical outcomes.

Results

The ratio of male to female patients was 151:88 and the mean age was 57.1?years. One hundred ninety-three subtotal gastrectomies, 41 total gastrectomies, and 5 proximal gastrectomies were performed. D1?+?α, D1?+?β, and D2 lymph node dissections were performed for 14, 62, and 163 cases, respectively. The median follow-up period was 55.4?months. The overall 5-year survival rate of the 239 AGC patients was 78.8% and the disease-specific 5-year survival rate was 85.6%. The 5-year survival rates of the TNM staging system’s (7th ed.) stages were 90.5% (stage Ib, n?=?86), 86.4% (stage IIa, n?=?53), 78.3% (stage IIb, n?=?44), 52.8% (stage IIIa, n?=?24), 52.9% (stage IIIb, n?=?24), and 37.5% (stage IIIc, n?=?8) (p?Conclusion The long-term survival outcome rates of LAG for AGC in the present study were comparable to those previously reported for open gastrectomy. Based on the present results, a well-designed phase III trial comparing LAG and open gastrectomy for AGC will be needed to affirm the validity of LAG for AGC.