Search

Aim: To better define clinically relevant non-classic radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with small hepatocellular carcinoma (HCC)., Methods: We retrospectively evaluated the influence of acute liver toxicities on fatal hepatic failure in HCC patients treated with SBRT. Between April 2006 and February 2012, 194 HCC were treated with SBRT. Among them, patients followed up for more than 6 months were eligible. Laboratory results and Child-Pugh (CP) scores were obtained before treatment and at monthly follow-up visits. Toxicities were evaluated by the Common Terminology Criteria for Adverse Events version 4.0. Possible definitions of RILD were evaluated with respect to fatal hepatic failure within 12 months., Results: One hundred and eighty HCC were evaluated with a median follow-up of 28.2 months. Fatal hepatic failure within 12 months occurred in eight patients (4%). On univariate analysis, grade 3 or more elevated transaminases, CP score of 8 or more, and/or grade 3 or more decreased platelet count significantly predicted fatal hepatic failure within 12 months. Combinations of these factors (i.e. having at least one criterion) also predicted fatal hepatic failure within 12 months (16% with criteria vs 1% without criteria). Two-year overall survival rates for patients with and without RILD was 64.9% and 83.8% (P < 0.001), respectively., Conclusion: We identified three criteria that affected overall survival in HCC patients treated with SBRT. Further prospective studies are warranted to validate the safety and effect of SBRT for HCC., (© 2014 The Japan Society of Hepatology.)

Background: Since 2005, we have treated hepatocellular carcinoma (HCC) with stereotactic body radiotherapy (SBRT) uniformly at two dose levels, according to baseline liver function and normal liver dose. We retrospectively examined the outcomes for these patients., Material and Methods: Between 2005 and 2012, 221 HCC patients were treated with SBRT. Eligibility criteria for SBRT included a single (either solitary or recurrent) HCC lesion; unfeasible, difficult or refusal to undergo other surgery or percutaneous ablative therapies; Child-Pugh Classification (CPC) A or B; tumors ≤ 5 cm; dose to the bowels < 25 Gy/5 fractions; curative intent. Patients followed up ≥ 6 months were eligible. The prescribed dose depended on liver function and liver dose: 40 Gy for CPC-A and 35 Gy for CPC-B, in 5 fractions, requiring a 5-Gy dose reduction if the proportion of the liver receiving ≥ 20 Gy exceeded 20%. Treatment outcomes and safety were analyzed., Results: A total of 185 patients (n = 48 in the 35-Gy group; n = 137 in the 40-Gy group) were eligible, with a median follow-up duration of 24 months (range 3-80). The three-year local control and overall survival rates were 91% and 70%, respectively. There were no significant differences in outcomes between dose levels: the three-year local control and overall survival rates in the 35-Gy and 40-Gy groups were 91% and 89% (log-rank p = 0.99) and 66% and 72% (p = 0.54), respectively. Acute toxicities ≥ grade 3 were observed in 24 (13.0%) patients, and 19 (10.3%) patients had worsening of CPC score by two points. All but three (1.6%) patients promptly recovered to grade 1-2. Grade 5 liver failure occurred in two patients in the 35-Gy group., Conclusion: SBRT for HCC was safe and provided equivalent outcomes when administered either in 35 or 40 Gy/5 fractions.

Purpose: Focal liver reaction (FLR) appears on radiographic images after stereotactic ablative body radiation therapy (SABR) in patients with hepatocellular carcinoma (HCC) and chronic liver disease. We investigated the threshold dose (TD) of FLR and possible factors affecting the TD on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI)., Methods and Materials: In 50 patients who were treated with SABR for small HCC and followed up by MRI for >6 months, FLR, seen as a hypointense area, was evaluated on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. The follow-up MRI with the largest extent of FLR was fused to the planning computed tomography (CT) image, and patients with good image fusion concordance were eligible. After delineating the border of the FLR manually, a dose-volume histogram was used to identify the TD for the FLR. Clinical and volumetric factors were analyzed for correlation with the TD., Results: A total of 45 patients were eligible for analysis with a median image fusion concordance of 84.9% (range, 71.6-95.4%). The median duration between SABR and subsequent hepatobiliary phase MRI with the largest extent of FLR was 3 months (range, 1-6 months). The median TD for FLR was 28.0 Gy (range, 22.3-36.4 Gy). On univariate analysis, pre-treatment Child-Pugh (CP) score and platelet count were significantly correlated with the TD. On multiple linear regression analysis, CP score was the only parameter that predicted TD. Median TDs were 30.5 Gy (range, 26.2.3-36.4 Gy) and 25.2 Gy (range, 22.3-27.5 Gy) for patients with CP-A and CP-B disease, respectively., Conclusion: The TD was significantly correlated with baseline liver function. We propose 30 Gy for CP-A disease and 25 Gy for CP-B disease in 5 fractions as TDs for FLR after SABR for patients with HCC and chronic liver disease. Use of these TDs will help to predict potential loss of liver tissue after SABR., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Aims: Stereotactic ablative body radiotherapy (SABR) is a relatively new treatment for hepatocellular carcinoma (HCC). The outcomes of SABR for previously untreated solitary HCC unfit for ablation and surgical resection were evaluated., Methods: Untreated solitary HCC patients treated with SABR were retrospectively studied. Between 2005 and 2012, 221 HCC patients underwent SABR. Among them, patients with untreated solitary HCC, treated with only SABR or SABR preceded by transarterial chemoembolization, were eligible. Based on baseline liver function and liver volume receiving ≥ 20 Gy, 35-40 Gy in five fractions was prescribed to the planning target volume surface., Results: Sixty-three patients were eligible, with a median follow-up duration of 31.1 (range 12.0-88.1) months. No patients were lost to follow-up. Twenty patients were treated with only SABR. In 43 patients treated with SABR preceded by transarterial chemoembolization, accumulation of lipiodol in the tumor remained complete in five, a partial defect in 38 on pre-SABR computed tomography. The 1-, 2-, and 3-year local control rates were 100%, 95%, and 92%, respectively; the intrahepatic recurrence-free rates were 76%, 55%, and 36%, respectively; and the overall survival rates were 100%, 87%, and 73%, respectively. Grade 3 laboratory toxicities in the acute, subacute, and chronic phases were observed in 10, 9, and 13 patients, respectively, and ascites occurred in one patient., Conclusions: Local control and overall survival after SABR for untreated solitary HCC were excellent despite the candidates being unfit for resection and ablation. SABR is safe and might be an alternative to resection and ablation., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Enriched environments reportedly show neuroprotective effects. Here, we evaluated the effect of an enriched environment prior to cerebral ischemia on neuronal cell death and neurogenesis in rats. Male SD rats were housed under standard conditions (SC) or in an enriched environment (EE), then subjected to global ischemia. The Y-maze test and novel object cognition test were used to evaluate cognitive function before and after ischemia. At 7 days post-ischemia, we evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding protein (phospho-CREB) was also evaluated immunohistochemically. The EE + ischemia group showed a significant decrease of cell death post-ischemia compared with the SC + ischemia group. There was no difference in neurogenesis post-ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed a significant increase of performance before and after ischemia compared with the SC + ischemia group. Phospho-CREB-positive cells were significantly increased post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed hippocampal cell death due to global ischemia. Additionally, enhancement of cognitive function before and after ischemia and prevention of cognitive impairment associated with ischemia were observed compared with the controls (rats housed in SC without ischemia). The CREB pathway may play an important role in protection of cognitive ability.

Purpose: To assess optimal relative prescribed dose values in stereotactic ablative body radiation therapy (SABR) using dynamic conformal multiple arc therapy (DCMAT) for liver tumors., Methods and Materials: We generated SABR plans for 8 typical liver tumors that received SABR with 50 Gy in 5 fractions. The prescribed dose had previously been defined as 80% of the maximal dose ("80% isodose plan"). Alternatively, 20%-90% isodose plans were created to compare dosimetric factors., Results: The mean liver volume values (%) that received >20 Gy (V20) and the mean liver dose were both the lowest with a 70% isodose plan and were the second lowest with a 60% isodose plan. The V20 dose was 5.19% lower (11.14%) with a 70% isodose plan and 4.51% lower (11.22%) with a 60% isodose plan compared with the value with an 80% isodose plan (11.75%). Mean planning target volume (PTV) dose increased as the % isodose decreased. The mean PTV dose was 10% higher (62.4 Gy) with a 70% isodose plan and 21% higher (68.9 Gy) with a 60% isodose plan compared with the value with an 80% isodose plan (56.8 Gy)., Conclusions: During SABR treatment planning using DCMAT for liver tumors, target doses increased as the percentage isodose value decreased, which could result in better outcomes. In contrast, a 70% isodose plan had the lowest normal liver dose and a 60% isodose plan had the second lowest. An optimal percentage isodose level might be adjusted depending on tumor radiation sensitivity and liver function reserve. Further investigation is warranted to determine whether these dosimetric advantages result in improved outcomes., (Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS., (Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Objective: The purpose of this study is to evaluate the CT appearances of tumor responses following hypofractionated stereotactic ablative body radiotherapy for small hypervascular hepatocellular carcinomas (HCCs) and to assess the relationship between tumor responses and local control., Materials and Methods: Among 277 HCC tumors treated with stereotactic ablative body radiotherapy (35 or 40 Gy per five fractions), we selected enhanced lesions on arterial phase CT performed before stereotactic ablative body radiotherapy. Radiographic findings after stereotactic ablative body radiotherapy were evaluated during a 2-year follow-up period with the modified Response Evaluation Criteria in Solid Tumors. Local control and survival rates were calculated with the Kaplan-Meier method., Results: Forty-two tumors with a median size of 2.1 cm (range, 1.0-3.8 cm) were selected with a median follow-up of 23.3 months (range, 9-56 months). Local recurrence was observed in two tumors after achieving a complete response (CR). The 2-year local control rate was 97%, and the overall survival rate was 81%. CR increased from 10 (24%) to 28 (67%) to 30 (71%) tumors at 3, 6, and 12 months after stereotactic ablative body radiotherapy. Overall CR at maximum follow-up was 39 tumors (93%), yet three enhanced tumors persisted for more than 2 years. The median time to achieve CR was 5.9 months (range, 1.2-34.2 months)., Conclusion: The CR rate in hypervascular HCCs after hypofractionated stereotactic ablative body radiotherapy increased during the 2-year follow-up period. Cautious and continuous observation until tumor regrowth is considered relevant to evaluate a true effect of this treatment. Further studies for the optimal evaluation of treatment outcome after stereotactic ablative body radiotherapy are warranted.

Background: For isolated postsurgical local recurrences (IPSLR) of lung cancer, salvage resection is often unfeasible due to a high risk of morbidity and death. Stereotactic ablative body radiotherapy (SABR) provides excellent therapeutic effects, with mild toxicities, for patients with medically inoperable lung cancer. However, the outcomes of SABR for IPSLR have not been reported., Methods: Patients with IPSLR who were treated with SABR between 2005 and 2012 were retrospectively identified. The prescribed doses were 40 to 60 Gy per 5 to 10 fractions. Treatment outcomes and toxicities were evaluated., Results: We identified 23 patients with IPSLR, including 21 with bronchial stump or staple line recurrences and 2 with chest wall recurrences. During follow-up, IPSLR occurred at a median of 36.7 months (range, 5.0 to 190 months) after resection. All patients were N0 M0, and the T stages at recurrence were T1a, T1b, T2a, and T4 in 6, 5, 3, and 9 patients, respectively. The initial pathologic diagnoses were adenocarcinoma in 17 patients and squamous cell carcinoma in 6. At a median follow-up duration of 17.0 months (range, 6.0 to 89.6 months) after SABR, there were 2 local recurrences. Local control and overall survival rates at 1 and 2 years were 94.7% and 86.8% and 84.0% and 76.4%, respectively. Grade 3 to 5 radiation pneumonitis occurred in 1 patient each. Grade 3 temporary but repeated obstructive pneumonia occurred in 2 patients., Conclusions: SABR for IPSLR achieved high local control with limited toxicities. SABR may lead to a potential cure and should be considered as a salvage treatment option for IPSLR., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The target volume for postoperative breast irradiation is the remaining breast tissue, and the axillary region is not an intentional target volume., Patients and Methods: Between 2001 and 2009, eligible women with pT1-2cN0/pN0(sn) breast cancer underwent breast-conserving therapy without axillary dissection. Treatment outcomes between 2 radiotherapy planning groups, high tangent fields with 2-dimensional (2-D) simulation-based planning and 3-dimensional (3-D) computed tomography-based planning with a field-in-field technique, were compared. The correlating factors for axillary failure were also calculated., Results: In total, 678 patients were eligible. As of May 2009, the median follow-up times for the 2-D (n = 346) and 3-D (n = 332) groups were 94 and 52 months, respectively. Patient characteristics were balanced, except for a younger population in the 2-D group and more lymphovascular invasion in the 3-D group. On multivariate analysis, 2-D planning was the only risk factor for axillary failure. In the 2-D and 3-D groups, the 5-year cumulative incidences of axillary failure were 8 (3.1%) and 1 (0.3%) (log-rank p = 0.009), respectively. The respective 5-year overall survival rates were 97.4 and 98.4% (p = 0.4)., Conclusion: High tangent irradiation with 3-D planning improved axillary control compared to that with 2-D planning, suggesting that optimizing axillary dose distribution may impact outcomes.

Purpose: To retrospectively investigate treatment outcomes of stereotactic ablative body radiation therapy (SABR) for octogenarians with non-small cell lung cancer (NSCLC)., Methods and Materials: Between 2005 and 2012, 109 patients aged ≥80 years with T1-2N0M0 NSCLC were treated with SABR: 47 patients had histology-unproven lung cancer; 62 patients had pathologically proven NSCLC. The prescribed doses were either 50 Gy/5 fractions for peripheral tumors or 40 Gy/5 fractions for centrally located tumors. The treatment outcomes, toxicities, and the correlating factors for overall survival (OS) were evaluated., Results: The median follow-up duration after SABR was 24.2 (range, 3.0-64.6) months. Only limited toxicities were observed, except for 1 grade 5 radiation pneumonitis. The 3-year local, regional, and distant metastasis-free survival rates were 82.3%, 90.1%, and 76.8%, respectively. The OS and lung cancer-specific survival rates were 53.7% and 70.8%, respectively. Multivariate analysis revealed that medically inoperable, low body mass index, high T stage, and high C-reactive protein were the predictors for short OS. The OS for the operable octogenarians was significantly better than that for inoperable (P<.01)., Conclusions: Stereotactic ablative body radiation therapy for octogenarians was feasible, with excellent OS. Multivariate analysis revealed that operability was one of the predictors for OS. For medically operable octogenarians with early-stage NSCLC, SABR should be prospectively compared with resection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Several single institution phase I and phase II trials of stereotactic ablative body radiotherapy (SABR) for liver tumors have reported promising results and high local control rates of over 90%. However, there are wide variations in dose and fractionation due to different prescription policies and treatment methods across SABR series that have been published to date.This study aims to assess and minimize inter-institutional variations in treatment planning using SABR for hepatocellular carcinoma (HCC) in preparation for a prospective multi-institutional study., Methods: Four institutions (A-D) participated in this study. Each institution was provided with data from four cases, including planning and diagnostic CT images and clinical information, and asked to implement three plans (a practice plan and protocol plans 1 and 2). Practice plans were established based on the current treatment protocols at each institution. In protocol plan 1, each institution was instructed to prescribe 40 Gy in five fractions within 95% of the planning target volume (PTV). After protocol plan 1 was evaluated, we made protocol plan 2, The additional regulation to protocol plan 1 was that 40 Gy in five fractions was prescribed to a 70% isodose line of the global maximum dose within the PTV. Planning methods and dose volume histograms (DVHs) including the median PTV D50 (Dm50) and the median normal liver volume that received 20 Gy or higher (Vm20) were compared., Results: In the practice plan, Dm50 was 48.4 Gy (range, 43.6-51.2 Gy). Vm20 was 15.9% (range, 12.2-18.9%). In protocol plan 1, the Dm50 at institution A was higher (51.2 Gy) than the other institutions (42.0-42.2 Gy) due to differences in dose specifications. In protocol plan 2, variations in DVHs were reduced. The Dm50 was 51.9 Gy (range, 51.0-53.1 Gy), and the Vm20 was 12.3% (range, 10.4-13.2%). The homogeneity index was nearly equivalent at all institutions., Conclusions: There were notable inter-institutional differences in practice planning using SABR to treat HCC. The range of PTV and normal liver DVH values was reduced when the dose was prescribed to an isodose line within the PTV. In multi-institutional studies, detailed dose specifications based on collaboration are necessary.

Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors., Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ., Results: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient., Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: We analyzed whether axillary nodal irradiation could control clinically node-negative disease, including those patients with a positive sentinel lymph node biopsy (SLNB), most of whom received regional nodal irradiation. We also evaluated toxicity profiles that resulted from nodal irradiation., Patients and Methods: From 1988 to 2011, 2107 patients with cT1-T2N0M0 breast cancer underwent breast conservation therapy in the absence of axillary dissection: nx group (n = 1548), without any axillary surgery; the sn(-) group (n = 518), with a negative SLNB; and sn(+) group (n = 104), with a positive SLNB., Results: The median follow-up times were 88, 56, and 55 months for the nx, sn(-), and sn(+) groups, respectively. The nx group had more risk factors than did the other 2 groups in terms of age, grade, or T stage. Ninety-eight percent of the sn(-)group received only tangent irradiation, and 100% and 83% of the sn(+) and nx group, respectively, received additional regional nodal irradiation. The 5-year cumulative incidences of axillary failure and regional nodal failure were 34, 3, and 0 (2.7%, 0.7%, and 0%; P = .02, log-rank test) and 57, 4, and 0 (4.4, 1%, and 0; P = .04), respectively. Overall survival rates in 5 years were 96.4%, 98.9%, and 97.6% (P = .03), respectively. Symptomatic but transient radiation pneumonitis developed in 31, 16, and 6 (2.0%, 3.1%, and 5.7%). Mild arm edema was observed in 1, 4, and 0 (0.06%, 0.8%, and 0%) in the nx, sn(-), sn(+) groups, respectively., Conclusions: Treatment without axillary dissection showed excellent outcomes with negligible toxicity for patients with clinically node negative, including those with a positive SLNB. Regional nodal irradiation after a positive SLNB is a reasonable alternative to axillary dissection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Psychological distress is a risk factor of stroke in humans and worsens the behavioral and neurological outcomes. In rats, acute stress exposure preceding ischemic events attenuates learning and memory. The retrosplenial cortex (RS) plays an important role in these functions, and global brain ischemia (GBI) or acute stress exposure can induce a decrease in expression of the immature neuronal marker, doublecortin (DCX), in the RS. However, little is known about the DCX expression in the RS after stress exposure prior to GBI., Methods: Eighteen male Sprague-Dawley rats were used. Acute stress exposure was applied as the forced swim paradigm and GBI was induced by bilateral common carotid arterial occlusion for 10 min. The rats were divided into three groups: GBI model preconditioned by stress (n = 6, Group P), GBI model preconditioned by non-stress (n = 6, Group G), and controls (n = 6, Group C). We performed immunohistochemistry to observe and analyze the DCX-expressing cells and Fluoro-Jade B (FJB) staining to detect cell death in the RS after GBI in each group., Results: The total number of DCX-expressing cells was 1,032, 1,219, and 1,904 in Group P, Group G, and Group C, respectively. The mean number of DCX-expressing cells per unit area was significantly lower in Group P and Group G than in Group C (P < 0.001). Moreover, the number was significantly lower in Group P than in Group G (P < 0.05). In each group, no FJB positive cells were observed., Conclusion: DCX plays an important role in various cytoskeletal changes. Preconditioning by acute stress exposure accelerated the decrease in DCX expression in the RS after GBI.

Many studies have demonstrated cognitive function disorders including space learning disorders after global brain ischemia (GBI). Previous research on space perception and learning has indicated that the retrosplenial cortex (RS) is strongly involved. We performed immunostaining with doublecortin (DCX) for neurons with plasticity potential in the RS and investigated the neuronal numbers to assess the changes of plasticity in the RS following GBI. We employed male Sprague-Dawley rats and carried out bilateral carotid arterial occlusion for 10 min as a GBI model (control, n = 5; GBI model, n = 5). We counted the right and left hemispheres separately on two serial sections, for a total of four regions per animal to examine the differences in expression related to GBI. Additionally, we performed Fluoro-Jade B (FJB) staining to investigate the cause of any DCX-expressing neuron decrease. The total number of DCX-expressing neurons was 1,652 and 912 in the controls and GBI model, respectively. The mean number of DCX-expressing neurons per unit area was significantly lower in the GBI model than in the controls. FJB positive neurons were not found in the RS, while many were present in the -hippocampus CA1 after GBI. The decrease of DCX-expressing neurons in the RS indicated a plasticity decrease following GBI. The lack of FJB positive neurons in the RS after GBI suggested that the decrease of DCX-expressing neurons in the RS was not due to neuronal cell death in contrast to the hippocampus CA1, while the FJB positive neurons in the hippocampus indicated a delayed neuronal cell death as observed in many previous studies.

A 44-year-old male with a history of diabetes mellitus and alcoholism for 20 years, was admitted to our hospital complaining of urinary retention and high fever. The scrotum was swollen and became necrotic partially. The inflammation and emphysema was around the anus, bilateral inguinal region, and right flank. The laboratory data showed disseminated intravascular coagulation (DIC). According to the clinical and radiological findings, we diagnosed the illness as Fournier's gangrene. Cystostomy and surgical debridment were performed in conjunction with the use of broad-spectrum antibiotics and anti-DIC therapy. After the general condition improved, the broad defect of perineal skin was covered with a free skin graft by using the negative-pressure bolster method. The graft was successful.

We report the very rare case of bilateral spermatoceles concurrent with bilateral scrotal hydrocele presenting huge scrotal swelling. A 52-year-old man came to our hospital because of large scrotal swelling. Ultrasonography and magnetic resonance imaging showed bilateral large scrotal hydroceles concurrent with bilateral multicystic spermatoceles above the hydrocele. He had no history of vasectomy or scrotal injury, and the semen examination was normal. The contents of the hydroceles and spermatoceles were first aspirated, but hydrocelectomy and spermatocelectomy were eventually done because after the aspiration the fluid increased more rapidly. Bilateral spermatocele is very rare; moreover, this is the first report of bilateral spermatocele concurrent with bilateral hydrocele.

A 49-year-old female visited to our department with complaints of gross hematuria and micturition pain. Cystoscopic examination revealed a 5-cm diameter solid broad-based tumor located at the front wall of the bladder. Histologically, the tumor was composed of grade 2 urothelial carcinoma (UC) element and sarcomatous spindle cell element. Immunohistochemical examination demonstrated that both UC and spindle cells were positive for cytokeratin. In addition, spindle cells did not stain for S-100 protein or smooth muscle actin. We diagnosed the tumor as sarcomatoid carcinoma and performed total cystectomy and ileal conduit without chemotherapy and radiation. The patient has remained without any evidence of recurrence for 14 months after operation. Sarcomatoid carcinoma of the bladder has aggressive malignant potential and poor prognosis. An appropriate adjuvant therapy for sarcomatoid carcinoma with metastasis has not been established. Total cystectomy is recommended as soon as possible after pathological diagnosis in the same manner as conventional high grade UC.