Bevacizumab plus irinotecan in recurrent or progressive malign glioma: a multicenter study of the Anatolian Society of Medical Oncology (ASMO)

Purposes

The overall prognosis for recurrent malignant glioma (MG) is extremely poor, and treatment options are limited. We evaluated our multicenter retrospective experience for patients with recurrent MG administering bevacizumab and irinotecan in combination therapy.

Methods

A total of 115 patients with grade IV glial tumor (n = 93) and grade III glial tumor (n = 22) were retrospectively evaluated at 14 centers in Turkey. Primary objectives of the study were to evaluate the efficacy and toxicity of the bevacizumab and irinotecan as salvage treatment based on response to therapy, progression-free survival (PFS), 6 months of PFS, overall survival (OS), and 6 months of OS (OS6).

Results

Bevacizumab and irinotecan were performed as second line (79.1 %) and third line treatment (20.9 %). Median chemotherapy cycle was 6 (range 1–37), and median follow-up was 6 months (range 1–36 months). Objective response rate was 39.1 %. Six-month PFS and OS6 were 46.3 % and 67.5 %, respectively. Median PFS was 6 months (95 % CI 2.5–9.5) and 6 months (95 % CI 4.9–7.1) in the grade III and IV groups, respectively (p = 0.773). Median OS was 9 months (95 % CI 7.1–10.9) and 8 months (95 % CI 6.6–9.4) in the grade III and IV groups, respectively (p = 0.450). Serious toxicities were observed in 7.8 % of patients. Treatment-related toxic death was observed in 3 patients. There was no treatment related to central nervous system hemorrhage or other serious hemorrhages.

Conclusions

Present study results were consistent with previous studies. In addition, we detected similar outcomes in grade III and IV glial tumors.     

Repair of Furcal Iatrogenic Perforation with Mineral Trioxide Aggregate: Two Years Follow-up of Two Cases

Furcal perforation is usually an undesired complication that can occur during preparation of endodontic access cavities or exploring canal orifice of multirooted teeth. Inadequacy of the repair materials has been a contributing factor to the poor outcome of repair procedures. On the basis of the recent physical and biologic property studies of the relatively new introduced mineral trioxide aggregate, this material may be suitable for closing the communication between the pulp chamber and the underlying periodontal tissues. There are few reports on repair of furcal perforation with MTA in molar teeth. The purpose of this case report was to describe the treatment of two furcal perforation using MTA in molar teeth. The perforations were cleaned with NaOCl and saline solution and sealed with MTA without internal matrix. Finally, the teeth were endodontically treated and coronally restored with composite resin and ceramic veneer crown and bridge. After 2 years, the absence of periradicular radiolucent lesions, pain, and swelling along with functional tooth stability indicated a successful outcome of sealing perforations in two cases.     

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.     

Inhibition of L-arginine transport by reactive oxygen species in rat anococcygeus muscle

The effect of L-arginine on nitrergic transmission and its alteration with reactive oxygen species (ROS) were investigated. L-arginine potentiated the relaxation response induced by electrical field stimulation in rat anococygeus muscle. This effect was inhibited by L-lysine, a cationic amino acid using y+ L and y+ transport systems in a similar way with L-arginine. The neutral amino acid L-leucine, which uses only y+ L system as a transport mechanism, inhibited this potentiation at only low frequency stimulation. Electrolysis of the physiological solution did not change the responses to electrical field stimulation, but inhibited the potentiation elicited by L-arginine that was prevented in the presence of mannitol and N-acetyl-L-cysteine. In conclusion, L-arginine is transported via y+ system predominantly to potentiate the relaxation response to nitrergic nerve stimulation in rat anococcygeus muscle. ROS, primarily hydroxyl radicals inhibited L-arginine-induced potentiation probably by interacting with the y+ amino acid transport system.     

The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial

BACKGROUND: Among patients using GnRH analogues for endometriosis it has been postulated that peripheral and inflammation-induced in-situ aromatization of adrenal androgens are probably the main reasons for the high rates of failure during follow-up. We hypothesized that in cases with premenopausal severe endometriosis, use of a combination of anastrozole and goserelin to achieve almost maximal endocrine blockade of estrogen synthesis after conservative surgery may increase the pain-free interval and reduce the recurrence rates as compared to goserelin alone. METHODS: In a prospective randomized trial, we evaluated the efficacy of using either a combination of anastrozole and goserelin for 6 months or goserelin alone for 6 months after conservative surgery for severe endometriosis. The primary outcome measures were the symptom recurrence rates and the impact of treatment on endometriosis-related multidimensional score. The secondary outcome measures were the impact of allocated treatment regimens on menopausal quality of life and on lumbar spine bone mineral density (BMD). RESULTS: When we analyzed the Kaplan-Meier survival curves, we detected a statistically significant advantage of goserelin plus anastrozole as compared to goserelin only, in terms of the median time to detect symptom recurrence (>2.4 versus 1.7 months; log-rank test; P=0.0089). This statistically significant advantage occurred with a relative risk of 4.3 [95% confidence interval (CI) 1.3-9.8]. Three cases out of 40 recurred in the goserelin plus anastrozole arm (7.5%), whereas we detected recurrences in 14 cases out of 40 cases in the goserelin-only arm (35%) during the follow-up period of 24 months. Based on these data, the interpretation of Kaplan-Meier curves indicates that at the end of follow-up, 54.7 versus 10.4%, respectively, of the patients were free of recurrence. The mean of the differences in terms of Deltabaseline-24 months post-medical therapy multidimensional score were statistically significant in favour of goserelin and anastrozole (9.2 +/- 2.1 versus 6.7 +/- 2.8; paired t-test; P<0.0001; 95% CI 1.5-4.0). We observed a statistically significant difference in suppression of estradiol concentrations and a significantly greater BMD loss at the end of treatment in the goserelin and anastrozole arm as compared to goserelin-only arm. However, this did not elicit deterioration in menopausal quality of life and the observed bone loss was not significant in terms of DeltaBMD between the groups at 2 years of treatment withdrawal. CONCLUSIONS: Six months of treatment with anastrozole and goserelin as compared to goserelin alone increased the pain-free interval and decreased symptom recurrence rates in patients following surgery for severe endometriosis. Furthermore, menopausal quality of life and BMD at 2 years after medical therapy remained unaffected.     

Subclinical celiac disease with cerebellar ataxia

We report an unusual case of celiac disease with cerebellar ataxia. Gastrointestinal signs and malabsorption were not found in this patient. We suggested that celiac disease should be taken into consideration in differential diagnosis of patients with cerebellar ataxia with unknown etiology.     

Evaluation of nail involvement in patients with chronic cutaneous graft versus host disease: a single-center study from Turkey

Although graft versus host disease (GVHD) is associated with a myriad of cutaneous signs, nail involvement is rarely mentioned in the literature. This study was conducted at the Department of Dermatology and The Bone Marrow Transplantation Unit of Hematology. All patients were examined clinically for presence of nail abnormalities. Severity of nail involvement was assessed as mild or severe. Of 28 patients diagnosed with chronic cutaneous GVHD, 14 had nail manifestations. Longitudinal ridging was the most frequently observed nail change on both the fingernails and the toenails. Severe nail changes such as ptergyium and onicoatrophy were noted in a few patients. As a result we could not find any relationship between nail changes and clinical severity but there was a relationship between nail changes and duration of disease. Nail manifestations could be responsible for considerable morbidity.     

Designing appointment scheduling systems for ambulatory care services

The current climate in the health care industry demands efficiency and patient satisfaction in medical care delivery. These two demands intersect in scheduling of ambulatory care visits. This paper uses patient and doctor-related measures to assess ambulatory care performance and investigates the interactions among appointment system elements and patient panel characteristics. Analysis methodology involves simulation modeling of clinic sessions where empirical data forms the basis of model design and assumptions. Results indicate that patient sequencing has a greater effect on ambulatory care performance than the choice of an appointment rule, and that panel characteristics such as walk-ins, no-shows, punctuality and overall session volume, influence the effectiveness of appointment systems.     

Juvenile non-hyaline fibromatosis: juvenile hyaline fibromatosis without prominent hyaline changes

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease of the connective tissue. It is characterized by papulonodular skin lesions, soft tissue masses, gingival hypertrophy, osteolytic bone lesions and flexion contractures of the large joints. Here, we report a 14-year-old girl with characteristic clinical features of JHF with early fatal outcome. Dermatopathologic examination of the early lesions however constantly lacked the so-called hyalin changes in multiple skin biopsies. According to our experience; dermatopathological features of this entity is not often and always consists of classical hyalinisation. Only larger lesions with long duration should expected to be exhibiting those features. Therefore we suggest that; JHF may often present itself as Juvenile Non-Hyaline Fibromatosis: JHF without prominent hyaline changes. And thus this fact should not change the actual diagnosis and prognostic implications.