Endoscopic Resection of Tuberculum Sellae Meningiomas

Objective To evaluate the results of endoscopic transnasal resection of tuberculum sellae meningiomas (TSMs) as compared with transcranial approaches.Design We retrospectively analyzed five patients who underwent endoscopic endonasal resection of TSM and performed a comprehensive review of articles published between 2000 and 2012 describing the operative treatment of TSMs.Results Gross total resection (GTR) was achieved in four patients (80%). Transient diabetes insipidus occurred in three patients (60%). Preoperative visual field deficit resolved in all patients. Cerebrospinal fluid (CSF) leak occurred in one patient. Analysis of published studies included 1,026 transcranial and 144 transnasal cases. GTR was achieved in 85% of transcranial and 72% of transnasal cases. Visual field deficit improved in 65% of transcranial and 82% of transnasal cases. Rate of diabetes insipidus and CSF leak was higher in the transnasal series. Rate of GTR and visual improvement was higher in endoscopic endonasal as compared with microsurgical transnasal series.Conclusion The literature supports transsphenoidal surgery for the resection of TSMs with significant optic nerve compromise and limited lateral extension. This approach may have an equivalent if not superior outcome over transcranial surgery in visual outcome. CSF leaks are still a challenge but may improve with the use of vascularized nasoseptal flaps.     

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Background

The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.

Methods

A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C _max) were calculated by Bayesian analysis.

Results

In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C _max by age group. No relationship was observed between the administration method of MZR and serum concentration.

Conclusion

The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

     

Positive Lymph Node Ratio as an Indicator of Prognosis and Local Tumor Clearance in N3 Gastric Cancer

Background

Nodal metastasis is an important clinical issue in gastric cancer patients. This study was designed to investigate the clinical usefulness of the positive lymph node ratio (PLNR), which reflects both metastatic and retrieved lymph node numbers, in patients with pN3 gastric cancer.

Methods

We retrospectively analyzed the records of 138 consecutive pN3 patients who underwent curative gastrectomy with lymphadenectomy from 2000 to 2012.

Results

A PLNR of 0.4 was proved to be the best cutoff value to stratify the prognosis of patients with pN3 gastric cancer (P?<?0.001). Univariate and multivariate analyses revealed that older age, larger tumor size (≥10 cm), and PLNR?≥?0.4 [P?<?0.001, HR 3.1 (95 % CI 1.7–5.4)] were independent prognostic factors in pN3 gastric cancer. Regarding the recurrence, patients with PLNR <0.4 had a significantly lower rate of lymph node recurrence than those with PLNR ≥0.4 (P?=?0.020). There was no significant difference in the lymph node recurrence rate between N3a and N3b patients in the PLNR <0.4 group [P?=?0.546, 11.6 % (7/60) vs. 12.5 (1/8)], indicating a better local control regardless of pN3 subgroups.

Conclusions

PLNR is useful to stratify the prognosis and evaluate the extent of local tumor clearance in pN3 gastric cancer.

     

Conditional gene targeting on the pure C57BL/6 genetic background

Brain functions are the products of dynamic interactions between multiple genes and environments. Accordingly, there are large differences among mouse strains at the behavioral and neurobiological levels. Therefore, it is crucial to manipulate genes on the same and homogenous genetic background and then to analyze and compare the phenotypes of various genetically modified mice. Furthermore, a conditional gene targeting to restrict the gene knockout to specific cells and time is a powerful tool to investigate the molecular basis of higher brain functions such as learning and memory. We have developed a system employing Cre-progesterone receptor fusion recombinase for temporal regulation of gene targeting and Flp/frt recombination system for elimination of marker genes. Importantly, both the recombinase lines and target mice have been produced with embryonic stem cells derived from the C57BL/6 strain suitable for brain function analysis. Thus, we have established an inducible and neuron-specific gene targeting system on the pure C57BL/6 genetic background.     

Extramural cancer deposits without nodal structure in colorectal cancer: optimal categorization for prognostic staging

To establish an optimal categorization of cancer deposits without lymph node structure (extranodal cancer deposits [EX]) in a prognostic staging system, we analyzed 1,027 cases in which patients underwent potentially curative surgery for advanced colorectal adenocarcinoma. EX was classified as vascular invasion-type (VAS) or non-VAS.A total of 512 foci of EX were identified in 205 patients (20.0%), with VAS and non-VAS found in 68 and 182 patients, respectively. The hazard ratio for patients with nodal involvement was 3.6 and for patients with VAS and non-VAS, 2.5 and 4.7, respectively. Based on multivariate analysis of these 3 parameters, only nodal involvement and non-VAS were significant prognosticators. By using the Akaike information criterion, N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and non-VAS were treated together as an N factor and VAS was treated as a T factor ("new categorization"). The clinical significance of the TNM grading system for colorectal cancer would be enhanced if we treat EX as a new categorization.     

Development of a novel ELISA for detection of anti-A and anti-B antibodies in recipients of ABO-incompatible living donor liver grafts

The survival rate in ABO-incompatible (ABO-I) liver transplantation was much lower than that in ABO-compatible recipients for the early experiences. It is therefore essential to develop the precise and fast measurement of anti-A and anti-B antibodies (Abs) to prevent humoral rejection in ABO-I liver transplantation. Agglutination titer has been the standard method to measure these Abs, but the interpretation of the results is subject to bias. Here, we have developed an objective and quantitative enzyme-linked immunosorbent assay (ELISA) to measure anti-A and anti-B Abs. This test requires only a small amount (10 microl) of recipient's serum. We applied the newly developed ELISA to monitor living donor liver transplant recipients and investigated the correlation between ELISA and agglutination titer. The Spearman's correlation coefficient for Abs ranged from 0.461 to 0.812. Moreover, in one case of humoral rejection, the increase of Abs was detected by ELISA one day earlier than by the agglutination titer. In conclusion, our ELISA method proved useful to detect an increase of anti-A and anti-B Abs titers at an early stage, thereby contributing to a prompt treatment of humoral rejection due to ABO-I.