Independent Poor Prognostic Factors for True Progression after Radiation Therapy and Concomitant Temozolomide in Patients with Glioblastoma: Subependymal Enhancement and Low ADC Value

BACKGROUND AND PURPOSE:Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide.MATERIALS AND METHODS:Forty-two patients with glioblastoma multiforme with newly developed or enlarged enhancing lesions on the first follow-up MR images obtained within 2 months of concurrent chemoradiotherapy completion were included. Subependymal enhancement was analyzed for the presence, location, and pattern (local or distant relative to enhancing lesions). The mean ADC value and the fifth percentile of the cumulative ADC histogram were determined. A multiple logistic regression analysis was performed to identify independent factors associated with true progression.RESULTS:Distant subependymal enhancement (ie, extending >1 cm or isolated from the enhancing lesion) was significantly more common in true progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth percentile of the cumulative ADC histogram was significantly lower in true progression than in pseudoprogression (P = .014). Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were independent factors associated with true progression (P = .041 and P = .033, respectively). Sensitivity and specificity for the diagnosis of true progression were 83% and 67%, respectively, by using both factors.CONCLUSIONS:Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were significant independent factors predictive of true progression.

Glioblastoma multiforme (GBM) is the most common form of malignant primary brain tumor in adults,¹ which is notorious for its intrinsic aggressiveness and a dismal prognosis.^2,3 The current standard treatment for GBM is maximal safe tumor resection followed by radiation therapy with concurrent temozolomide (TMZ) and adjuvant TMZ.⁴Recently, the criteria for assessing therapeutic responses in high-grade gliomas have been updated by the Response Assessment in Neuro-Oncology (RANO) Working Group to address the limitations of the previous guideline.⁵ For instance, contrast enhancement, which has been regarded as a surrogate marker for tumor progression, has been reassessed as a nonspecific finding merely reflecting the passage of contrast material across a disrupted blood-tumor barrier.^6–11 In particular, radiologists and clinicians have increasingly recognized the occurrence of progressive MR imaging lesions immediately after completion of concurrent chemoradiotherapy (CCRT) with TMZ, which spontaneously improved without further treatment other than the adjuvant TMZ.^12–14 The treatment-related reaction is termed pseudoprogression and has received attention as a potential pitfall in the response evaluation. At present, owing to the lack of established findings in conventional contrast-enhanced MR imaging for the differential diagnosis of true progression from pseudoprogression,^9,10 RANO stresses that the diagnosis of true progression can be made within the first 12 weeks after completion of radiation therapy only if most of the new enhancement is located outside the radiation field or if there is pathologic confirmation of progressive disease.⁵During the past few decades, there has been extensive effort to identify imaging biomarkers for tumor progression. Among the many parameters derived from advanced MR imaging techniques, DWI has been consistently reported to be helpful in differentiating tumor progression from treatment-related changes or necrosis.^15–22 Meanwhile, most previous studies pertaining to the role of conventional MR imaging have not shown promising results.^9,23 Nevertheless, a recent study focusing on the conventional MR imaging findings has proposed subependymal enhancement as a useful MR imaging marker for differentiating true progression from pseudoprogression.²⁴ To our knowledge, however, no previous studies have conducted in-depth analysis of the subependymal enhancement, and its potential as an independent predictor for true progression remains elusive.The purpose of the present study was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with GBM treated with radiation therapy and concomitant TMZ.     

Differences in activities of the lower extremity muscles with and without heel contact during stair ascent by young women wearing high-heeled shoes

Background  The purpose of this study was to identify any differences in the activity patterns of lower extremity muscles with and without heel contact during stair ascent by women in their twenties wearing high-heeled shoes. Methods  Twenty healthy female subjects wearing high-heeled shoes walked up a step with a height of 20 cm with and without heel contact, during which the activities of the vastus medialis oblique, vastus lateralis, and gastrocnemius were recorded using surface electromyography. Results  During stair ascent the activities of the vastus lateralis and vastus medialis oblique were significantly higher and that of the gastrocnemius significantly lower with high-heel contact than without high-heel contact. Conclusion  We suggest that young women wearing high-heeled shoes should step up with heel contact on the stair surface during stair ascent to activate the quadriceps muscle.     

The 7‐year outcome of the tension‐free vaginal tape procedure for treating female stress urinary incontinence

OBJECTIVE

To evaluate the long‐term results and predictive risk factors for efficacy after the tension‐free vaginal tape (TVT) procedure for treating female stress urinary incontinence (SUI).

PATIENTS AND METHODS

Inall, 306 women (mean age 50.7 years, sd 8.7) who had a TVT procedure for SUI were selected and followed ≥7 years (mean 92.3 months, range 84–110) after surgery. We analysed the long‐term results, the variables predictive of cure rates, and patient satisfaction.

RESULTS

The overall 7‐year cure rate was 84.6%, with a satisfaction rate of 69.3%. The cure rates were lower in patients with high‐grade SUI (50% in grade III, 82.8% in grade II and 90.7% in grade I; P < 0.001). On multivariate analysis, there were no independent risk factors related to cure rate, and urgency was the only factor independently associated with patient satisfaction (P = 0.008; odds ratio 2.47). Seventy‐one patients (23.2%) had complications at the 1‐month follow‐up after surgery, but only eight (2.6%) had complications at the 7‐year follow‐up, including mesh exposure in six and de novo urgency in two.

CONCLUSION

The absence of long‐term adverse events associated with the TVT procedure, and high subjective and objective 7‐year success rates with no independent predictive factors affecting the long‐term cure rate, make the TVT procedure a recommendable surgical treatment for female SUI.     

Effects of obesity on lower urinary tract symptoms in Korean BPH patients

We analyzed the effects of obesity on lower urinary tract symptoms （LUTSs） in Korean benign prostatic hyperplasia （BPH） patients. This is a multicenter, cross-sectional, prospective study conducted in four centers in Korea. A total of 602 men with LUTSs secondary to BPH were included. BPH/LUTSs cases were men aged ≥ 40 years with intemational prostate symptom scores （IPSS） ≥ 8 points. Height, weight and waist circumference were measured. Among the 602 patients, 156 patients had a waist circumference above 90 cm, representing central obesity, and 215 patients had a body mass index above 25 kg m2. Waist circumference was positively correlated with prostate volume （P = 0.034）. Men with waist circumference 〉 90 cm experienced a 1.36-fold increased risk of severe LUTSs （95% CI 0.82-2.41） compared with men with waist circumference ≤ 90 cm. Prostate volume was positively correlated with urgency and nocturia in men with central obesity. In this population of Korean men diagnosed with BPH, central obesity rather than overall obesity seems to be the more important predictor of LUTSs correlated with BPH.     

Learning curve of office-based ultrasonography for rotator cuff tendons tears

Purpose

To compare the accuracy of ultrasonography and MR arthrography (MRA) imaging in detecting of rotator cuff tears with arthroscopic finding used as the reference standard.

Methods

The ultrasonography and MRA findings of 51 shoulders that underwent the arthroscopic surgery were prospectively analysed. Two orthopaedic doctors independently performed ultrasonography and interpreted the findings at the office. The tear size measured at ultrasonography and MRA was compared with the size measured at surgery using Pearson correlation coefficients (r). The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and false-positive rate were calculated for a diagnosis of partial-and full-thickness rotator cuff tears. The kappa coefficient was calculated to verify the inter-observer agreement.

Results

The sensitivity of ultrasonography and MRA for detecting partial-thickness tears was 45.5 and 72.7 %, and that for full-thickness tears was 80.0 and 100 %, respectively. The accuracy of ultrasonograpy and MRA for detecting partial-thickness tears was 45.1 and 88.2 %, and that for full-thickness tears was 82.4 and 98 %, respectively. Tear size measured based on ultrasonography examination showed a poor correlation with the size measured at arthroscopic surgery (r = 0.21; p < 0.05). However, tear size estimated by MRA showed a strong correlation (r = 0.75; p < 0.05). The kappa coefficient was 0.47 between the two independent examiners.

Conclusions

The accuracy of office-based ultrasonography for beginner orthopaedic surgeons to detect full-thickness rotator cuff tears was comparable to that of MRA but was less accurate for detecting partial-thickness tears and torn size measurement. Inter-observer agreement on the interpretation was fair. These results highlight the importance of the correct technique and experience in operation of ultrasonography in shoulder joint.

Level of evidence

Diagnostic study, Level II.     

Parametric Cerebrovascular Reserve Images Using Acetazolamide 99mTc-HMPAO SPECT: A Feasibility Study of Quantitative Assessment

Purpose

Basal/acetazolamide stress ^99mTc-HMPAO single-photon emission computed tomography (SPECT) has been widely used for evaluation of hemodynamics; however, qualitative and subjective visual assessment of cerebrovascular reserve (CVR) has been performed in clinical settings. The aim of this study was to generate parametric CVR images and evaluate its feasibility of quantification.

Methods

Basal/acetazolamide stress ^99mTc-HMPAO SPECT data from 17 patients who underwent bypass surgery or percutaneous transluminal angioplasty were used. Spatial normalization was performed and parametric CVR images were generated using relative CVR (rCVR) of each voxel proportional to CVR of the whole brain. Binary parametric maps to show area of relatively reduced CVR were generated also using threshold of rCVR < 90 %. We calculated rCVR of internal carotid artery (ICA) using the parametric CVR images and probabilistic maps for ICA territory. Pre- and postprocedural parametric CVR images were obtained and quantitative rCVRs were compared. The rCVRs were evaluated according to visual grades for regional decreased CVR.

Results

Postprocedural rCVR obtained from parametric CVR images increased significantly from preprocedural rCVR. The rCVR was significantly correlated with visual grades of reduced CVR for each side of ICA territories.

Conclusions

We generated parametric CVR images for basal/acetazolamide stress ^99mTc-HMPAO SPECT. As a quantitative measurement, rCVR obtained from the parametric image was feasibly assessed hemodynamic abnormalities with preserved anatomical information.     

Sexual function and psychological characteristics of penile paraffinoma

Aim:To identify the sexual, emotional and psychological status of men who augmented their penis with mineral oil injection for their small penis. Methods: Men who had penile paraffin were asked to answer the semi-structured questionnaire. The questionnaire was designed to assess the motivation, method of penile injection, changes in erectile function and satisfaction after penile injection. SCL (Symptom checklist)-90-R, STAI (State and Trait Anxiety Inventory) and Zung SDS (Self-rating depression scale) were also included in the questionnaire for psycho-logical evaluation. Results: A total of 357 men completed the questionnaire. The first-ranked motivation of the injection was recommendation by their acquaintances (48.9 %). The majority of the respondents had the procedure by non-medical person (78.0 %). Before injection, 17.2 % had a sense of inferiority in their penis and 32 % worried about their weak erectile function. After injection, 33.0 % have found relief from their sense of inferiority and 17.8 % wish to feel improvement in their cr~tile function. Most of the respondents (91%) were not satisfied with their penis and 74 % of them replied that they want to remove the injected material. Only 15.6 % did not experience side effects.Most of the subjects have suffered from various side effects such as inflammation, skin necrosis, pain, etc. No evidence of psychiatric pathology was found in psychological evaluation. Conclusion: The motivations of mineral oil injection were recommendation by their acquaintances or desire to be more mannish. Most of them had suffered from various side effects and only a small number of them felt improvement in their sense of inferiority, in their penis and erectile function. Increased public awareness is needed for the prevention of this physically and psychologically debilitating problem. (Asian J Andro12003 Sep; 5:191-194 )     

A case of delayed recurrent hemarthrosis after posterolateral reconstruction of the knee with a staple fixation at the lateral femoral epicondyle

We present a case of delayed recurrent hemarthrosis after posterolateral reconstruction of the knee with staple fixation of the tendon graft at the lateral femoral condyle. A 20-year-old man had undergone a reconstructive surgery of the knee with allogeneic Achilles tendon aimed to reinforce lateral collateral ligament and popliteofibular ligament. At 4 months after surgery, recurrent swelling of the operated knee after minor exertion developed. The radiographs showed prominent staples at the lateral side of lateral femoral condyle. The arthroscopy revealed that the staples were salient intra-articularly at lateral gutter of the knee, and the adjacent lateral capsule seemed abraded, through which the longitudinal fibers of iliotibial band were seen. Iatrogenic iliotibial band syndrome owing to the prominent staple was speculated. The staples were removed under arthroscopic guidance, and there has been no recurrence thereafter. A staple fixation over bony prominence is not advisable and the interference screw might be a better alternative method of fixation.     

The flavonoid quercetin induces apoptosis and inhibits migration through a MAPK-dependent mechanism in osteoblasts

The present study was undertaken to evaluate effects of quercetin, a major dietary flavonoid occurring in foods of plant origin, on cell viability and migration of osteoblastic cells. Quercetin inhibited cell viability, which was largely attributed to apoptosis, in a dose-and time-dependent manner in osteoblastic cells. Similar cytotoxicity of quercetin was observed in adipose tissue-derived stromal cells. Quercetin exerted a protective effect against H₂O₂-induced cell death, whereas it increased TNF-α-induced cell death. Western blot analysis showed that quercetin induced activation of ERK and p38, but not JNK. Quercetin-induced cell death was prevented by the ERK inhibitor PD98059, but not by inhibitors of p38 and JNK. Quercetin increased Bax expression and caused depolarization of mitochondrial membrane potential, which were inhibited by PD98059. Quercetin induced caspase-3 activation, and the quercetininduced cell death was prevented by caspase inhibitors. Quercetin inhibited cell migration, and its effect was prevented by inhibitors of ERK and p38. Taken together, these findings suggest that quercetin induces apoptosis through a mitochondria-dependent mechanism involving ERK activation and inhibits migration through activation of ERK and p38 pathways. Quercetin may exert both protective and deleterious effects in bone repair.     

Tumor Necrosis Rate Adjusted by Tumor Volume Change Is a Better Predictor of Survival of Localized Osteosarcoma Patients

Background We assessed whether new parameter that considers both tumor volume change and necrosis rate predicts metastasis-free survival of localized osteosarcoma patients. We also evaluated relationship between tumor volume change and necrosis rate or metastasis-free survival. Methods We retrospectively reviewed 151 patients with stage II osteosarcoma who were treated with surgery and neoadjuvant chemotherapy. The tumor volume change was measured and calculated based on pre- and postchemotherapy magnetic resonance images. The mean metastasis-free interval was 83.1 months. We calculated adjusted tumor necrosis rate as following formula: 100–(100–necrosis rate) × postchemotherapy/prechemotherapy tumor volume. Survival and logistic regression analyses were used to evaluate the correlation among size parameters, tumor necrosis rate and survival. Results The 5-year metastasis-free survival rate of 151 patients was 71.4% (95% CI, 67.7–75.1%). American Joint Committee on Cancer (AJCC) stage IIB (RR 2.27; 95% CI, 1.11–4.62; P = 0.025) and poor adjusted tumor necrosis rate (RR 2.02; 95% CI, 1.05–3.89; P = 0.035) independently correlated with metastasis-free survival period. Further, tumor volume change independently correlated with necrosis rate. Decreased tumor volume could predict good response, with sensitivity of 80.2%, specificity of 68.6%, and positive predictive value (PPV) of 74.7%. Increased or stable tumor volume could predict poor response, with sensitivity of 68.6%, specificity of 80.2%, and PPV of 75.0 %. Conclusion The necrosis rate adjusted by the tumor volume change is an independent prognostic factor in osteosarcoma. This adjusted tumor necrosis rate may serve as a basis for risk-adapted therapy in combination with other prognostic factors.