Glioblastoma treated with postoperative radio-chemotherapy: Prognostic value of apparent diffusion coefficient at MR imaging

Purpose

To retrospectively evaluate whether the mean, minimum, and maximum apparent diffusion coefficient (ADC) of glioblastomas obtained from pretreatment MR images is of prognostic value in patients with glioblastoma.

Materials and methods

The institutional review board approved our study and waived the requirement for informed patient consent. Between February 1998 and January 2006, 33 patients (24 males, 9 females; age range 10-76 years) with supratentorial glioblastoma underwent pretreatment magnetic resonance (MR) imaging. The values of the mean, minimum, and maximum ADC (ADC_mean, ADC_MIN, and ADC_MAX, respectively) of each tumor were preoperatively determined from several regions of interest defined in the tumors. After surgical intervention, all patients underwent irradiation and chemotherapy performed according to our hospital protocol. The patient age, symptom duration, Karnofsky performance scale score, extent of surgery, and ADC were assessed using factor analysis of overall survival. Prognostic factors were evaluated using Kaplan-Meier survival curves, the log-rank test, and multiple regression analysis with the Cox proportional hazards model.

Results

Likelihood ratio tests confirmed that ADC_MIN was the strongest among the three prognostic factors. Total surgical removal was the most important predictive factor for overall survival (P < 0.01). ADC_MIN was also statistically correlated with overall survival (P < 0.05) and could be used to classify patients into different prognostic groups. Interestingly, ADC_MIN was also the strongest prognostic factor (P < 0.01) in the group of patients in whom total tumor removal was not possible.

Conclusion

The ADC_MIN value obtained from pretreatment MR images is a useful clinical prognostic biomarker in patients with glioblastoma.     

Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

Apparent diffusion coefficient of human brain tumors at MR imaging

PURPOSE: To determine if apparent diffusion coefficient (ADC) can be used to differentiate brain tumors at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Institutional review board approval or informed patient consent was not required. MR images were reviewed retrospectively in 275 patients with brain tumors: 147 males and 128 females 1-81 years old, treated between September 1997 and July 2003. Regions of interest were placed manually in tumor regions on MR images, and ADC was calculated with a five-point regression method at b values of 0, 250, 500, 750, and 1000 sec/mm2. ADC values were average values in tumor. All brain tumor subgroups were analyzed. Logistic discriminant analysis was performed by using ADC, age, and patient sex as independent variables to discriminate among tumor groups. RESULTS: A significant negative correlation existed between ADC and astrocytic tumors of World Health Organization grades 2-4 (grade 2 vs grades 3 and 4, accuracy of 91.3% [P < .01]; grade 3 vs 4, accuracy of 82.4% [P < .01]). ADC of dysembryoplastic neuroepithelial tumors (DNTs) was higher than that of astrocytic grade 2 tumors (accuracy, 100%) and other glioneuronal tumors. ADC of malignant lymphomas was lower than that of glioblastomas and metastatic tumors (accuracy, 83.6%; P < .01). ADC of primitive neuroectodermal tumors (PNETs) was lower than that of ependymomas (accuracy, 100%). ADC of meningiomas was lower than that of schwannomas (accuracy, 92.4%; P < .01). ADC of craniopharyngiomas was higher than that of pituitary adenomas (accuracy, 85.2%; P < .05). ADC of epidermoid tumors was lower than that of chordomas (accuracy, 100%). In meningiomas, ADC was not indicative of malignancy grade or histologic subtype. CONCLUSION: ADC is useful for differentiation of some human brain tumors, particularly DNT, malignant lymphomas versus glioblastomas and metastatic tumors, and ependymomas versus PNETs.     

Dipeptide monoester ganciclovir prodrugs for treating HSV-1-induced corneal epithelial and stromal keratitis: in vitro and in vivo evaluations.

PURPOSE: The aim of this study was to evaluate a series of dipeptide monoester ganciclovir (GCV) prodrugs with the goal of improving ocular bioavailability of GCV from topical ophthalmic solutions. METHODS: Solubility, logP, pH-stability profile, permeability, interaction with corneal peptide transporter, and in vivo efficacy against herpes simplex virus type 1 (HSV-1) ocular disease in the rabbit model were studied. RESULTS: Val-Val-GCV, Tyr-Val-GCV, and Gly-Val-GCV were more stable in aqueous solution than Val-GCV, showing no measurable degradation even after 7 d at 37 degrees C, within the pH range of 1.4-5.4. Tyr-Val-GCV and Val-Tyr-GCV were the most lipophilic among the prodrugs synthesized and were predicted to have an n-octanol/water partition coefficient 33 times greater than that of GCV. All of the prodrugs had a much higher aqueous solubility than the parent drug. Transcorneal permeability of Val-GCV and Val-Val-GCV was seven- to eightfold greater than that of GCV, in the presence of a proton gradient, and was significantly decreased in the presence of Gly-Pro. Val-Val-GCV (1% w/v) provided significantly better therapeutic activity than trifluorothymidine (1% w/v) against HSV-1 epithelial keratitis and equivalent therapeutic activity against stromal keratitis in the rabbit eye model. CONCLUSIONS: Val-Val-GCV demonstrates excellent corneal permeability and chemical stability, high aqueous solubility, and substantial in vivo antiviral activity against the HSV-1.     

ISOLATED WELL-FORMED INTESTINAL TISSUE IN THE UMBILICAL CORD: A Variant of Cyst of Omphalomesenteric Duct

An extremely rare abnormality, a variant of omphalomesenteric duct, was observed in the umbilical cord 1 cm from the entry point into the abdominal wall, which itself was as an isolated mass of well-formed intestinal tissue free of structural defects. This intestinal tissue seems to be the remnant of an intestinal loop from caudal limb of midgut following physiological herniation during the third month of gestation.     

Retrospective Study Using the Propensity Score to Clarify the Oncologic Feasibility of Thoracoscopic Esophagectomy in Patients with Esophageal Cancer

Background

The present study aimed to clarify the long-term prognostic impact and oncologic feasibility of thoracoscopic esophagectomy (TSE) in patients with esophageal cancer in comparison with open thoracic esophagectomy (OTE).

Methods

Patients with esophageal cancer underwent surgically curative esophagectomy without neoadjuvant therapy from January 1991 to December 2008 and were analyzed retrospectively. Of 257 patients, 91 underwent TSE and 166 had OTE. Relations between the long-term prognosis after surgery, the surgical procedure, and clinicopathologic parameters were analyzed statistically. The propensity scores were calculated for all patients through a multiple logistic regression model that was optimized with Akaike’s Information Criterion. Using Cox’s proportional hazard model with prognostic variables and the propensity scores, we implemented a multivariate analysis for comparing the performance of two surgical methods.

Results

Patient characteristics and the incidence of perioperative morbidity or hospital death were similar for the TSE and OTE groups. Significantly more lymph nodes were dissected in the TSE group than in the OTE group (total p = 0.013; thoracic p = 0.0094; recurrent laryngeal p < 0.0001). The TSE group exhibited a more favorable prognosis after surgery than the OTE group in terms of overall survival (p = 0.011) and disease-specific survival (DSS) (p = 0.0040). Particularly in subgroup analysis of DSS, the TSE group had a favorable prognosis in upper thoracic esophageal cancer (p = 0.0053), invasive cancer (p = 0.046), node-positive cancer (p = 0.020), progressive cancer (p = 0.0052), cancer with lymphatic vessel invasion (p = 0.0019), and cancer without blood vessel invasion (p = 0.0081). In terms of DSS, the TSE group exhibited a more favorable prognosis than the OTE group regardless of the presence or absence of metastasis to lymph nodes around the thoracic (p < 0.0001) or recurrent laryngeal (p < 0.0001) nerves. TSE (p = 0.0430), lymph node metastasis (p = 0.0382), lymphatic invasion (p = 0.0418), and p stage (p = 0.0047) were independent prognostic parameters in the Cox’s proportional hazard model with the propensity scores.

Conclusions

TSE can contribute to prolonged survival after surgery in patients with esophageal cancer by enabling precise thoracic lymph node dissection based on a magnified surgical field. TSE might have maximum oncologic benefit and minimum invasiveness for patients with esophageal cancer.     

Long-term efficacy of trilostane for Cushing's syndrome due to adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia

A 66-year-old man with Cushing's syndrome due to adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) was treated for 7 years with trilostane, a 3β-hydroxysteroid dehydrogenase inhibitor. Administration of trilostane reduced the serum cortisol level to around the upper limit of normal for 7 years, and symptoms of excessive glucocorticoid production (such as moon face and obesity) were gradually improved. On the other hand, the size of both adrenal glands gradually increased despite treatment with trilostane. Though trilostane therapy could not prevent adrenal growth, it did suppress cortisol secretion over the long term, so it might be a reasonable option for AIMAH in addition to adrenalectomy.     

Analysis and rearrangement of human karyotypes by computer

A system useful for the collection and analysis of a large number of abnormal karyotypes and for studies on the relationship between cytogenetic abnormalities and clinical features of diseases is reported. The program is based on the disintegration and rearrangement of abnormal karyotypes recorded according to the 1978 International System for Human Cytogenetic Nomenclature (ISCN).     

Health status of radiation exposed residents living near the Semipalatinsk Nuclear Test Site based on health assessment by interview

The purpose of the present paper is to examine the aftereffects of radiation exposure on residents of villages near the Semipalatinsk Nuclear Test Site (SNTS) in Kazakhstan. Our Hiroshima University (Japan) research team began field research in 2002 by means of health assessments conducted via interviews. We focus on persons who responded to questions concerning their medical conditions and symptoms. In this paper, we summarize and analyze, using multiple linear logistic regression analysis, the answers obtained by questionnaire survey. The results show: (1) 31% of the residents reported that they felt bad or were in very poor health. (2) Residents living in villages having higher radiation levels were more likely to report having poor or very poor health, minor complaints such as loss of sleep, headaches, nighttime sweating and swollen arms or legs, and the need for nursing care in performing activities of daily living. (3) Symptoms reported by over 40% of the respondents included high blood pressure, heart disease and arthralgia/ lower back pain/ arthritis. Our results suggest that radiation exposure in the Semipalatinsk area is one of the causes of poor health in general among residents. There is also a possibility that radiation exposure has influenced the incidence of some specific medical conditions.