S. Song

Prognostic significance of c-Met expression in glioblastomas

The authors investigated whether expression of c‐Met protein in glioblastomas is associated with overall survival and biologic features representing tumor invasiveness in patients with glioblastomas.

Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhoea‐predominant irritable bowel syndrome

Abstract  The objective of this study was to determine whether or not the number of enteroendocrine cells (ECs) in the gut is related to visceral hypersensitivity in patients with diarrhoea‐predominant irritable bowel syndrome (D‐IBS). Twenty‐five subjects with D‐IBS (mean, 43.1 years; 16 women, nine men) were recruited into our study, along with 13 healthy controls (mean, 40.7 years; nine women, four men). Maximally tolerable pressures were evaluated via barostat testing, and the levels of ECs were immunohistochemically identified and quantified via image analysis. The numbers of ECs between the D‐IBS subjects and the controls were not significantly different in the terminal ileum, ascending colon and rectum. However, the maximally tolerable pressures determined in the D‐IBS subjects were significantly lower than those of the control subjects (P < 0.01), and we detected a significant relationship between the maximally tolerable pressures and the numbers of ECs in the rectum (r = −0.37, P < 0.01). Rectal sensitivity was enhanced to a greater degree in D‐IBS patients exhibiting an elevated level of rectal ECs. This study provides some evidence to suggest that ECs play an important role in visceral hypersensitivity.

Promoter Hypermethylation of the p16 Gene Is Associated with Poor Prognosis in Recurrent Early-Stage Hepatocellular Carcinoma

Despite significant advances in the detection and treatment of hepatocellular carcinoma, the prognosis of patients with hepatocellular carcinoma remains very poor, in part due to the high incidence of recurrence. This study was aimed at identifying a prognostic indicator of recurrence in patients with hepatocellular carcinoma. We retrospectively analyzed CpG island hypermethylation of the p14, p15, p16, GSTP1, integrin α4, SYK, and CDH1 genes in fresh-frozen tissues from 265 patients with hepatocellular carcinoma using the methylation-specific PCR. The expression levels of p16 and p53 were evaluated by immunohistochemistry. CpG island hypermethylation was detected in 6% for p14, 21% for p15, 67% for p16, 75% for GSTP1, 23% for integrin α4, 12% for SYK, and 57% for CDH1. Recurrence was observed in 102 (38%) of the 265 patients. There was no association between the risk for recurrence and hypermethylation of any gene studied. However, p16 methylation was associated with a poor survival after surgery for recurrent stage I to II hepatocellular carcinomas (hazard ratio, 4.05; 95% confidence interval, 1.15-14.20; P = 0.03). In addition, the hazard of failure after recurrence was about 3.80 (95% confidence interval, 1.03-14.20; P = 0.04) times higher in patients with p16 methylation than in those without. Negative expression of p16 at a protein level was also associated with poor survival in recurrent stage I to II hepatocellular carcinomas, but p53 expression did not have a synergistic effect on the poor prognosis. In conclusion, the present study suggests that p16 methylation may be associated with a poor prognosis in recurrent early-stage hepatocellular carcinomas. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2260–7)

Can Immune Function Assay Predict Infection or Recovery

BACKGROUND Recently, the ImmuKnow assay (Cylex Inc., Columbia, Md) has been reported to be a global immune monitoring tool for organ transplants recipients. We assessed whether immunKnow ATP values predicted infectious syndromes. METHODS We prospectively enrolled 71 kidney transplant patients between September 2008 and May 2011. lmmuKnow assay monitoring was performed at one dav before as well as 4, 8, 12, 16, 20, 24, 36, and 52 weeks after the operation. ImmuKnow assay values were compared as well as BK viral infection pre-infection(PI), at first detection of infectious syndrome (DI), 4 weeks there after (4W), 8 weeks there after (8W) and 12 weeks there after (12W) and pre-recovery (PR), recovery (R) times. RESULTS Serial ImmuKnow assays showed significant differences over time and BK viral infectious state (P = .026). Interestingly, PI was significantly lower than DI and PR but PR significant greater than PI, 8W and 12W. However, we did not observe an adequate or absolute cutoff value of ImmuKnow by ROC curve: 377 ng/mL ImmuKnow showed 0.471 of AUC and 57.1% and 56.2%, of sensitivity and specificity. CONCLUSION Longitudinal evaluation and adjustment of the value of ImmuKnow assay seemed to be a favorable modality to monitor infectious syndromes especially those involving BK virus.

Clinical significance of molecular genetic changes in sporadic invasive pituitary adenomas.

Several molecular and genetic changes have been found in pituitary adenomas. We looked for correlations between these changes and the degree of invasiveness of the tumors. The invasiveness of 11 pituitary adenomas was graded by Hardy classification. We examined the retinoblastoma gene (RB1.20 on chromosome 13q) and the region around the MEN1 locus (chromosome 11q13.1-5) for loss of heterozygosity. Also examined are p53 mutations using single strain conformation polymorphism, p53 protein overexpression using immuno cytochemistry, homozygous deletions of p15 and p16 by polymerase chain reaction, and cellular proliferative activity using MIB-1 antibody. Six tumors (54.5%) had an LOH at either RB1.20 or the MEN1 locus. LOHs were found more frequently in Grade 4 and stage E tumors (72% and 67%) than in Grade 3 and stage D tumors (25% and 40%). However, no mutation or overexpression of p53 was found. No homozygous deletions of p15 or p16 were identified. The cell proliferative index ranged from 0 to 3%. LOH at 11q13 and 13q may be valuable in predicting the invasiveness of pituitary adenomas.

Steroid Withdrawal in Adult Liver Transplantation: Occurrence at a Single Center

BACKGROUNDS Steroids are the predominant immunosuppressive agent used after liver transplantation even though patients may experience steroid-related side effects. AIMS The objective of this study was to determine whether steroid use influenced the outcomes of liver transplantations. METHODS Three hundred forty-four adult patients underwent liver transplantation between May 2002 and December 2007. We reviewed the medical records of these patients, excluding those younger than 18 years old or those who died within the first month. The protocol withdrawal group (group 1) ceased steroid use within 5 months after transplantation, while the late withdrawal group (group 2) continued steroid use beyond this 5-month posttransplantation period. RESULTS All patients were classified according to the onset of steroid withdrawal (group 1: n = 243; group 2: n = 99). The incidences of biopsy-confirmed and treated acute rejection episodes (ARE) at 12 and 24 months posttransplantation were 7.8% and 12.3% in group 1, but 25.3% and 27.3% in group 2, respectively (P = .001). The incidence of hepatitis B virus (HBV) recurrence in group 2 was higher than that in group 1 (P = .007). The HBV-free survival rates at 1 and 2 years posttransplantation were 99.0% and 97.1% in group 1 and 96.1% and 92.1% in group 2, respectively. New-onset diabetes, avascular necrosis of the femoral head, corticosteroid-resistant ARE, hepatocellular carcinoma recurrence, as well as graft and patient survivals did not differ between the two groups. CONCLUSIONS Acute rejection episodes and HBV recurrence occurred less frequently when steroids were discontinued within 5 months after liver transplantation.

Kidney Donation after Cardiac Death in Korea

Organ donation after cardiac death (DCD) has been suggested due to the shortage of allografts in Korea. We investigated the outcomes of 446 deceased donor kidney transplant recipients in our center between September 1, 1995, and December 31, 2009. Twenty-four (5.4%) of those patients received DCD kidney grafts. The DCD group had a long intensive care unit stay, frequent inotropics use (such as norepinephrine and dopamine), low mean blood pressure and estimated glomerular filtration rate, and high serum creatinine and deceased donor scores compared to the standard criteria donor (SCD) group and the expanded criteria donor (ECD) group. Mean true warm ischemic time of the DCD group was 59.7 minutes based on asystole time. The DCD group had a long hospital stay after transplantation, but there was no statistically significant difference in delayed graft function and primary nonfunction. Serum creatinine levels at 3 months after transplantation in the ECD and DCD group were significantly higher than the SCD group (P < .001) but lower in the DCD group than in the ECD group at 6 months and 9 months (P < .001 and P = .004) posttransplantation. There were no statistically significant differences in serum creatinine levels or in the graft survival rates between groups at 12 months (P = .160 and P = .737). The use of DCD attracted Korean surgeons because DCD allografts are equivalent to a heart-beating donor. Donors who die during the evaluation of brain death should not be abandoned for procurement, and we need to try to harvest allografts after cardiac death (type 4 DCD) to expand donor pools.

Optimal Device and Method for Transportation of Isolated Porcine Islet

INTRODUCTION We investigated the optimal method for transportation of isolated porcine islets from an isolation facility to a transplant hospital or research center in terms of temperature, oxygen supply, and shaking effect. METHODS Commercially available insulator boxes with thermoregulators exposed for 5 hours under two external temperatures (4°C and 37°C) were monitored using HOBO temperature loggers. To find the optimal transport device, we compared islet counts, viability, quality, and function in conical tubes, gas-permeable bags (GPB) and gas-permeable flasks (GPF) after 1, 3 and 5 hours. To evaluate the effects of shaking on islets, we also analyzed the difference between a control and a shaking group in each device with time. RESULTS Commercially available Styrofoam insulators with thermoregulators maintained the internal temperature near the target. Islet recovery rate for GPF, which was higher than other devices, was maintained, while those decreased with time for conical tube and GPB containers adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio for GPF was lower than other devices, albeit not significantly fluoroscein acrimide/propidium iodide (AO/PI) ratio for GPF was higher than other devices after 5 hours. Glucose stimulated index was not different among the devices. In comparison with the control group, shaking yielded comparable islet survival, viability and function. CONCLUSION Our study demonstrated that the use of commercially available insulator boxes with thermoregulators maintained internal temperature close to the target value and that GPF was more favorable for islet oxygenation during transportation. This study also suggested negligible impact of shaking on isolated porcine islets during transportation.

Kidneys from deceased donors with oliguria are feasible for kidney transplantation.

BACKGROUND Since kidneys from deceased donors with oliguria have not been widely used, compared their outcomes with those in recipients of kidneys without oliguria at the time of organ procurement. METHODS We reviewed the deceased donors and kidney recipients between January 1999 and December 2009, all of whom were defined as standard criteria donors (SCD). RESULTS The group included 26 recipients whose terminal serum creatinine level (P < .001), estimated glomerular filtration rates (P < .001), and deceased donor scores (P < .001) were higher than those of the control group. Delayed graft function (P = .044) occurred more often among recipients with donor kidneys with oliguria than those without oliguria, and their hospitalization period was longer (P = .012). The serum creatinine levels in both groups were comparable posttransplantation; there was no significant difference in graft survivals. CONCLUSION Deceased donors with oliguria at organ procurement appeared to be poor predictors of outcomes in the early posttransplantation period. Kidneys from deceased donors with oliguria should not be discarded for transplantation. The present study suggested that it is acceptable to use kidneys from selected deceased donors with oliguria.

Pad -- a new self-collection device for human papillomavirus.

This study was designed to determine the accuracy and agreement of a self-collection method using pad for human papillomavirus (HPV) DNA. One hundred and thirty-four patients at university hospitals voluntarily participated in the accuracy study, and 314 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers designed for the direct sequencing. In the accuracy study, all samples were probed via histological examinations. With regard to the detection of squamous intraepithelial lesion (SIL), self-collection pad sampling displays sensitivity, of 76.9%, and specificity, of 93.3%. Three hundred and fourteen self-collection pad samples and the concurrent physicians’ samples showed a 97.8% agreement, with a Kappa value of 0.9200. A new self-collection pad for the detection of HPV DNA appears to constitute an easy, rapid, and convenient alternative method for the cervical cancer screening of many women with the virtue of being incredibly readily accessible.