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The poor prognosis after surgery for pancreatic cancer or extrahepatic bile duct cancer has mainly been attributed to early lymph node metastasis, as well as a high frequency of perineural invasion along the peripancreatic neural plexuses or extrahepatic bile duct plexus. However, there has been no detailed morphological description of the anterior and posterior hepatic plexuses (AHP and PHP). In addition, the concepts of the pancreatic plexus and PHP are confused by surgeons. To assess the relations of the pancreatic plexus and hepatic plexuses from the morphological, developmental, and clinical perspectives, these plexuses were dissected in 24 cadavers. The PHP was found to be completely independent of the AHP. The PHP ran behind the portal vein, with most nerve fibers ascending along the bile duct to the gallbladder and the liver or descending to the distal common bile duct and duodenal papilla. Some branches of the PHP contributed to the pancreatic plexus, corresponding to pancreatic head plexus I as defined by the Japan Pancreas Society. The differences between the PHP and pancreatic head plexus I should be understood, even though liver function is not obviously affected after PHP excision for pancreatic head cancer. Further study is needed to determine whether there are functional differences between the AHP and PHP. Clin. Anat., 33:630-636, 2020. © 2019 Wiley Periodicals, Inc.

A 59-year-old female experienced gross hematuria and right back pain, and she visited our hospital in March 2015. Abdominal computed tomography (CT) showed bilateral renal pelvic calculi; the right stone was 15 mm and the left stone was 18 mm in diameter. She had ulcerative colitis and had been taking salazosulfapyridine (SASP) for about 30 years. Urinalysis showed aciduria and deposition of urate crystals. An abdominal X-ray picture did not show a calculus shadow. We suspected uric acid calculus and started treatment with urinary alkalizer and uric acid production inhibitor.Three months later, abdominal CT showed enlargement of the bilateral renal pelvic calculi; the right stone was 25 mm and the left stone was 24 mm in diameter. She also complained of worse right back pain and underwent transurethral ureterolithotripsy for the right renal pelvic stone. The stone was orange, comparatively soft, and chipped down until it was approximately half of its original size. The stone analysis suggested suspected drug-induced urolithiasis, but not uric acid calculus. Thus, we investigated the stone and SASP using infrared spectroscopy, and the infrared absorption pattern was similar in both. The stone analysis demonstrated drug-induced urolithiasis induced by SASP.The patient's ulcerative colitis therapy was switched to mesalazine, and the amount of urinary alkalizer was increased. Abdominal CT 3 months thereafter showed dissipation of bilateral renal pelvic calculi. The patient did not take any preventative medication, and there was no recurrence of urolithiasis.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

Objective The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with α1 -adrenoceptor antagonists. Methods Patients with persistent storage symptoms refractory to α1 -adrenoceptor antagonists for benign prostatic hyperplasia were enrolled in the study. Patients were randomly assigned to either a 5 mg tadalafil or 5 mg solifenacin treatment group for 12 weeks. International Prostate Symptom Score, Overactive Bladder Symptom Score, urinary flow rates, residual urine volume, and blood pressure were measured prospectively before treatment and after 4 and 12 weeks of treatment. Changes from baseline were compared between groups. The rate of treatment discontinuation due to adverse effects was evaluated. Results Of the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups. Conclusions Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α1 -adrenoceptor antagonists.

(Background) Multiple renal angiomyolipoma (AML) may develop concurrently with tuberous sclerosis complex (TSC) and lung lymphangioleiomyomatosis (LAM). In recent years, an increase in subjects undergoing chest computed tomography examinations, including medical examinations, has been accompanied by an increase in LAM cases that are diagnosed while still asymptomatic. Surgical treatment may also be performed for renal AML to prevent bleeding. We clarified the clinical features of AML that is complicated by LAM, and discussed the significance of screening for LAM. (Methods) Between January 1, 2006 and April 30, 2014 two groups, comprising 7 patients with LAM (LAM-AML group) and another 26 patients without LAM (sporadic AML group), were compared with regard to findings for renal AML such as imaging examinations, pathological features, and treatment course. Screening for LAM was chest CT scanning. (Results) In the LAM-AML group, there were younger and more female cases and tumors tended to be multiple, large and bilateral. 85.7% of cases underwent surgery. On the other hand, in the sporadic group 73.1% of cases were followed up without treatment. There was no preoperative lung screening except the one TSC case and all 5 LAM cases were diagnosed postoperatively. One LAM patient was symptomatic and eventually required lung transplantation, while all other LAM cases were handled by monitoring the course, without treatment. (Conclusion) Many cases of asymptomatic LAM are untreated. However, the poor prognosis, risk of a need for general anesthesia, and potential for renal sparing by selection of pharmacotherapy must be taken into account. In that light-especially in the case of young women-patients with multiple renal AML should undergo preoperative screening for LAM.

Introduction To clarify the mechanisms responsible for running-induced asymptomatic gross hematuria. Case presentation We identified 12 patients who visited our outpatient clinic with hematuria after running as a chief complaint. In 9 of 12 patients (75%), cystoscopic findings revealed mucosal contusions at the center of the posterior wall. Our examination including cystoscopy and magnetic resonance imaging revealed that this bladder contusion development was caused by the repeated contact of the bladder posterior wall against the fixed bladder neck by vertical motion in the empty bladder lumen during running. All patients with bladder contusion were male because the bladder neck is more firmly fixed to the pelvic floor by the protruding prostate in men than women. Gross hematuria in all patients quickly resolved without treatment after running cessation. Conclusion This is the first report in which cystoscopic findings showed that running-induced macroscopic hematuria can be frequently caused by traumatic bladder contusion.

Developmentally, the uncinate process of the pancreas is derived from the ventral pancreatic anlagen, supplied by the superior mesenteric artery (SMA), and contains pancreatic polypeptide (PP)-rich islets of Langerhans. In contrast, the other parts of the pancreas originate from the dorsal anlagen supplied by the celiac system and contain PP-poor islets. This study was performed to investigate whether morphogenesis of the ventral pancreas anlagen is associated with the pattern of SMA branching. SMA branches to the pancreatic body were dissected in 44 cadavers. The cadavers were divided into two groups: the SMA group in which the SMA gave off branches to the pancreatic body and the General group in which it did not. In the SMA group, the ratio of the diameter of the SMA branch supplying the pancreatic body (SMA branch) to that of the SMA itself was calculated. After dissection was completed, tissues were collected from all pancreatic specimens for HE staining and for immunohistochemistry with PP and insulin antibodies. There were 25 cadavers in the General group and 19 in the SMA group. In 10/19 cadavers from the SMA group, PP-rich islets were confirmed in the pancreatic body. The SMA branch diameter ratio was significantly smaller in the SMA group cadavers with PP-poor islets (n = 9) than in cadavers with PP-rich islets (n = 10) (P < 0.001). These findings suggest a relation between the SMA branching pattern and the distribution of PP cells.

The visual acuity prognoses of patients with neuromyelitis optica (NMO) are worse than those with optic neuritis (ON) caused by other diseases. Predicting the prognoses of ON at the time of onset is important for selecting treatments for NMO patients.Twenty-three consecutive anti-aquaporin-4 autoantibody-positive NMO patients who presented with ON and had contrast-enhanced optic MRIs in the acute phase of their first ON episode were examined. Optical coherence tomographies (OCTs) were also examined for 22 of them. The visual acuity at the final follow-up, as assessed with the logMAR scale more than three years after ON onset, served as the outcome measure. These variables were also collected from 12 patients with serum anti-myelin oligodendrocyte glycoprotein antibody (anti-MOG-Ab).The strongest predictor of visual prognosis was the axial ON lesion length in the acute phase (R=0.747, p0.0001), which was not observed in patients with anti-MOG-Ab. Specifically, the ON lesion length within the intra-orbit and canalicular segments exhibited the strongest correlation with visual prognosis (R=0.783, p0.0001). The ON onset age was also correlated with visual prognosis (R=0.435, p=0.0338). OCT data in the chronic phase also showed a correlation with visual prognosis, but they were much weaker than the ON lesion length in the acute phase.The ON lesion length in the acute phase was an important predictor of the visual prognoses of NMO patients.

The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with αPatients with persistent storage symptoms refractory to αOf the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups.Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α

Chronic testicular pain remains an important challenge for urologists. Investigation of the innervation of male gonads thus becomes essential for deepening our understanding of their regulatory roles in male reproductive physiology and pathophysiology. Studies of testicular innervation are mainly limited to the intratesticular peptidergic nerves of the testis by immunohistochemical and acetylcholinesterase histochemical investigations in some animals. Little is known about the detailed, overall distribution in general experimental animal testis. In this study, the distribution of nerves supplying the testis, epididymis and accessory sex glands of Suncus murinus was investigated by whole mount immunohistochemistry staining using a neurofilament protein antibody. Testicular nerves arose through three routes: nerves deriving from the mesenteric and renal plexuses accompanied the testicular artery, entering into the testicular hilum through the superior ligament of the testis. The nerves originating from the hypogastric plexus then ran along the internal iliac artery, deferential artery, and passed through the mesoductus deferens or mesoepididymis, innervating the cauda and corpus of the epididymis, the vas deferens and the inferior pole of the testis. The third route arose from the pelvic plexus, distributed in the seminal vesicle and the prostate. The density of nerve fibers was higher in the cauda epididymidis than in the testis, and more abundant in the vas deferens. The different origins and distribution densities of testicular nerves in S. murinus may serve different neuronal regulatory functions, and, therefore, S. murinus may be an important model animal for understanding the different characteristics of testicular pain.

We report a patient with retroperitoneal myxoid liposarcoma recurrence who achieved remarkable improvements in performance status (PS) and maintained stable disease for approximately 5 months when treated with combination chemotherapy with gemcitabine (GEM) and docetaxel combination chemotherapy (GD). A 51-year-old woman was referred to our hospital with the chief complaint of a palpable mass in the left side of the abdomen. A retroperitoneal liposarcoma was diagnosed on the basis of magnetic resonance imaging and computed tomography results, and tumor resection was performed. The histopathological evaluation showed myxoid liposarcoma, which was classified as grade 2 according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system.Two months later, the tumor regionally recurred as peritoneal dissemination with rapid growth. Five months after the surgery, the growing tumor caused appetite loss and pleural effusion in the left lung. GD was administered (800 mg/m2 GEM on days 1 and 8, and 60 mg/m2 docetaxel on day 8) and 4 cycles were administered.The resulting decrease in abdominal girth and in the amount of pleural effusion allowed the patient to regain her appetite, and the patient's PS greatly improved from 3 to 1.Initially, GD was shown to be effective for the treatment of leiomyosarcoma and pleomorphic sarcoma, and it is now recommended as one of the first-line regimens in the National Comprehensive Cancer Network guidelines for soft tissue sarcoma treatment. The patient in this case showed remarkable improvement in PS after tumor recurrence and maintained stable disease for some time, without severe adverse effects.

Objectives To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. Methods A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. Results Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. Conclusions This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers.

This study investigated the significance of urological surgical intervention for viral hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 1, 024 patients underwent allo-HSCT at our medical center between January 2006 and July 2014. In the 6 patients (0.58%) who required urological surgical treatment for viral HC, we retrospectively analyzed patient characteristics and outcomes. Two patients underwent nephrostomy for bilateral hydronephrosis due to bladder tamponade. One of these patients showed no improvement in renal function, graft versus host disease worsened and he died on postoperative day (POD) 5. The other patient displayed improved renal function but hematuria did not improve, and total cystectomy was required. To control bleeding, we performed transurethral electrocoagulation (TUC) on 3 patients, and total cystectomy was performed on 2 patients. All 3 patients who underwent TUC had BK virus HC. Two of these patients experienced marked improvement in hematuria from immediately after surgery. Hemostasis was only temporary in the other patient, who eventually died due to septicemia on POD 24. The 2 patients who underwent total cystectomy had adenovirus HC. Both experienced secondary hemorrhage postoperatively and required further surgery. Eventually, one died due to postoperative bleeding on POD 1, and one died due to postoperative pneumonia on POD 57. Urological surgical treatment for HC was effective in some cases, but the ultimate outcome greatly depends on the general condition of the patient and treatment of the underlying hematological disorder. TUC may be considered for HC (particularly BK virus HC), but total cystectomy (especially inaden ovirus HC) should be avoided.

Acute optic neuritis (ON) typically presents with ocular pain and low visual acuity (VA), and there is a risk of permanent vision loss if ON is not managed properly.1 ON may be the first symptom of inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD). Recently, we reported some distinct characteristics between seropositive anti-aquaporin-4 (anti-AQP4) patients and seropositive antimyelin oligodendrocyte glycoprotein (anti-MOG) patients with NMOSD, using our in-house cell-based assays (CBA). However, patients with a single attack of unilateral ON were not included in our previous study. None of the previous studies of anti-MOG+ patients performed orbital MRI or optical coherence tomography (OCT) segmentation analyses, which may have diagnostic and prognostic implications. To address these issues, we evaluated the diagnostic utility of the anti-MOG assay and compared the MRI and OCT findings of anti-MOG+ and anti-AQP4+ patients with isolated ON. ### Patients We investigated 28 affected ON eyes from 21 consecutive anti-AQP4 seronegative patients aged 12 years or older who presented with isolated ON (4 cases with simultaneous bilateral ON, 3 cases with relapsing unilateral ON, and 14 cases with a single attack of unilateral ON) and were admitted to Tohoku University Hospital between 2011 and 2013. We excluded patients with ON already associated with brain and/or spinal cord MRI lesions. We compared anti-MOG+ ON eyes with nine affected ON eyes from eight anti-AQP4+ patients with isolated ON (one simultaneous bilateral ON). Severe VA loss was set at 0.1 in the decimal Japanese chart (equivalent to 20/200).2 ### Orbital MRI All patients performed orbital imaging using a 1.5 T MRI. We measured the short τ inversion recovery (STIR) and/or T2-weighted image hyperintense lesions …

Objectives To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. Methods and materials We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS). Results The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58–136) and 51 months (95% CI: 13–82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42–97) and 120 (95% CI: 52–120) months, respectively (P = 0.25). Conclusion Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC.

Background The role of lymph node dissection (LND) for upper tract urothelial carcinoma (UTUC) patients remains controversial. The aim of this study was to evaluate the effect of LND on clinical outcomes during radical nephroureterectomy (RNU) and to determine prognostic factors of survival. Patients and Methods From 1985 to 2013, 404 patients with UTUC underwent RNU; 5 patients who received neoadjuvant chemotherapy were excluded. Among them, 182 (46%) were pathologically negative for lymph node metastasis (pN0), 177 (44%) were non-LND (pNx), and 40 (10%) were positive for lymph nodes metastasis (pN1/2). Results The 5-year disease-free survival (DFS) and cancer-specific survival (CSS) rate were higher in pN0 patients than in pNx patients and in pN1/2 patients. According to multivariate analysis, non-LND was an independent predictive factor of DFS (hazard ratio [HR], 1.91; P = .004) and CSS (HR, 2.28; P = .003). In the subgroup with muscle-invasive UTUC, the 5-year DFS and CSS rates were higher in pN0 patients than in pNx patients. However, there was no statistical difference between pN0 and pNx groups in terms of DFS and CSS in the pT2 cases. DFS and CSS times were significantly prolonged in the pN0 group in the locally advanced UTUC patients (≥pT3). Conclusion In the ≥pT3 subgroup, the 5-year DFS and CSS were significantly prolonged in the pN0 group, but there were no statistical differences between pN0 and pNx groups in terms of DFS and CSS in the pT2 subgroup. LND for patients with locally advanced UTUC might improve disease prognosis.

Objective To compare myelin and astrocyte injury in patients with antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) or aquaporin-4 (anti-AQP4), and multiple sclerosis (MS). Methods Myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) levels were measured in the cerebral spinal fluid (CSF) from anti-MOG+ or anti-AQP4+ patients tested in both sera and CSF by cell-based assays with live transfected cells. Results In total, 75.6% (68/90) of the patients were positive for either anti-MOG or anti-AQP4 antibodies in both serum and CSF; 74.2% (23/31) were anti-MOG+, and 76.3% (45/59) were anti-AQP4+. No patients were only CSF positive or were positive for both anti-MOG and anti-AQP4 antibodies, and none of the MS patients or controls had these autoantibodies in the serum or CSF. MBP levels were elevated in the anti-MOG+ cases compared to the multiple sclerosis (MS) patients, and the levels found were similar between anti-MOG+ cases and anti-AQP4+ neuromyelitis optica spectrum disorder (NMOSD) cases. Meanwhile, GFAP was only elevated in the anti-AQP4+ NMOSD. Moreover, CSF pleocytosis, high protein levels, and oligoclonal IgG band negativity distinguished the anti-MOG+ cases from MS patients. Conclusions Myelin injury was more severe in the anti-MOG+ cases than in the MS cases, and anti-MOG+ cases have differences in the CSF characteristics compared to MS. GFAP elevation in anti-AQP4+ cases was absent in anti-MOG+ patients (even in cases with NMOSD phenotype), indicating that immune-mediated astrocytopathy is unique to anti-AQP4+ patients. Our study suggests that anti-MOG+ cases are distinct from MS and anti-AQP4+ NMOSD.

We analyzed the pathological findings, surgical margin, the first site of local or distant recurrence, treatment for postoperative recurrence and the characteristics of 25 patients who were surgically treated for retroperitoneal sarcomas between December 2000 and January 2014. The median tumor diameter was 11 cm. The pathological diagnosis was liposarcoma (n = 14), leiomyosarcoma (n = 7) and others (n = 4). Tumors were resected en-bloc with adjacent organs in 17 of the patients. In median follow up period of 39 months, 11 of the 14 patients with liposarcoma experienced local tumor recurrence and distant metastasis did not precede local recurrence in any of these patients. Leiomyosarcoma recurred in all patients and distant metastases appeared before local recurrence in four of them. The five-year recurrence-free and over all survival rates were 28 and 58%, respectively. The recurrence-free and overall survival rates significantly differed between well-differentiated and other subtypes of liposarcoma (both p0.05). The overall survival was significantly better for patients with a tumor diameter of11 cm than for those with ≥ 11 cm (p 0.05). Furthermore, overall survival was significantly better for patients who were able to undergo re-operation at the time of recurrence than for those who could not (p0.005). Although we resected adjacent organs when the margin was insufficient, the rate of local recurrence was high in liposarcoma. On the other hand, the rate of distant metastasis was high in leiomyosarcoma.

Introduction Neuromyelitis optica (NMO), an autoimmune astrocytopathic disease associated with anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions preferentially involving the optic nerves and spinal cord. However, previous in-vivo experimental models injecting human anti-AQP4 antibodies only resulted in mild spinal cord lesions compared to NMO autopsied cases. Here, we investigated whether the formation of severe NMO-like lesions occurs in Lewis rats in the context of experimental autoimmune encephalomyelitis (EAE), intraperitoneally injecting incremental doses of purified human immunoglobulin-G from a NMO patient (hIgGNMO) or a high affinity anti-AQP4 monoclonal antibody (E5415A), recognizing extracellular domain of AQP4 made by baculovirus display method. Results NMO-like lesions were observed in the spinal cord, brainstem, and optic chiasm of EAE-rats with injection of pathogenic IgG (hIgGNMO and E5415A), but not in control EAE. Only in higher dose E5415A rats, there were acute and significantly severer clinical exacerbations (tetraparesis or moribund) compared with controls, within half day after the injection of pathogenic IgG. Loss of AQP4 was observed both in EAE rats receiving hIgGNMO and E5415A in a dose dependent manner, but the ratio of AQP4 loss in spinal sections became significantly larger in those receiving high dose E5415A up to about 50 % than those receiving low-dose E5415A or hIgGNMO less than 3 %. These lesions were also characterized by extensive loss of glial fibrillary acidic protein but relatively preserved myelin sheaths with perivascular deposition of IgG and C5b-9, which is compatible with post mortem NMO pathology. In high dose E5415A rats, massive neutrophil infiltration was observed especially at the lesion edge, and such lesions were highly vacuolated with partial demyelination and axonal damage. In contrast, such changes were absent in EAE rats receiving low-dose E5415A and hIgGNMO. Conclusions In the present study, we established a severe experimental NMO rat model with highly clinical exacerbation and extensive tissue destructive lesions typically observed in NMO patients, which has not adequately been realized in in-vivo rodent models. Our data suggest that the pathogenic antibodies could induce immune mediated astrocytopathy with mobilized neutrophils, resulted in early lesion expansion of NMO lesion with vacuolation and other tissue damages. (350/350) Electronic supplementary material The online version of this article (doi:10.1186/s40478-015-0259-2) contains supplementary material, which is available to authorized users.

Objectives Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT). Material and methods Thirty-five patients with nonmetastatic ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical (IHC) analyses were performed for the expression of BAP1 protein, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate analyses of the associations between disease-free survival (DFS) and clinical variables including BAP1 protein expression, tumor size, Karnofsky performance status (KPS) score, and the extension level of the tumor thrombus were performed using a Cox proportional hazard model. Results The median follow-up time was 58.8 months (range: 2–130 months). The median age was 68 years (range: 37–80 years). The median size of the primary tumor was 9.6 cm (range: 3.0–15.0 cm). The IVCTT extended above and below the diaphragm in 10 (28.6%) and 25 (71.4%) patients, respectively. The KPS score was>80 in 23 patients (65.7%). BAP1 protein expression on IHC was positive in 24 cases (68.8%) and negative in 11 cases (31.2%). The median overall survival in cases with BAP1-negative and -positive tumor on IHC staining were 44.7 and 81.5 months, respectively (P = 0.052). BAP1-negative tumor on IHC staining was associated with a significantly shorter DFS than BAP1-positive tumor (median DFS = 10.0 vs. 26.0 months, respectively; P = 0.011). Multivariate analysis showed that only BAP1-negative tumor on IHC staining was significantly associated with shorter DFS (P = 0.004). Conclusions Patients whose tumors had loss of BAP1 protein expression were significantly associated with poor prognosis in patients with ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy.

OBJECTIVE To evaluate the effectiveness of adjuvant chemotherapy in patients with pathological Stage T3 bladder cancer who had undergone radical cystectomy, and to determine the prognostic survival factors for adjuvant chemotherapy treatment. METHODS From January 1990 to October 2013, 202 patients underwent radical cystectomy and pelvic lymphadenectomy. Among them, 65 patients with non-organ-confined disease (pT3, N0-3, M0) diagnosed were investigated in this study. Thirty-one patients (48%) were treated with adjuvant chemotherapy and the remaining 34 patients (52%) were not. RESULTS Median age of all patients was 66 years, and median follow-up was 26.1 months. For all pT3 patients, overall survival and disease-free survival times were similar in the adjuvant chemotherapy and non-adjuvant chemotherapy groups. However, in the pT3b subgroup, median overall survival (47.0 vs. 10.6 months) and median disease-free survival (35.5 vs. 5.3 months) times were significantly prolonged for those who underwent adjuvant chemotherapy (P = 0.009 and 0.025). In patients with pathological lymph node metastatic (pN+), median overall survival (30.1 vs. 6.4 months) and median disease-free survival (15.7 vs. 3.5 months) times were significantly prolonged in the adjuvant chemotherapy group (P = 0.016 and 0.027). In addition, according to multivariate analysis in pT3b and/or pN+ subgroup patients, adjuvant chemotherapy status was an independent predictive factor for overall survival and disease-free survival. CONCLUSION Adjuvant chemotherapy did not significantly improve overall survival and disease-free survival when compared with all patients with pT3 who had received radical cystectomy in the non-adjuvant chemotherapy group. However, in the pT3b and pN+ subgroup, adjuvant chemotherapy demonstrated statistically significant benefits regarding overall survival and disease-free survival. Although these results could not support adjuvant chemotherapy use for all pT3 patients, the pT3b substage and/or pN+ may help identify patients with pT3 who could benefit from adjuvant chemotherapy.

More than a century has passed since the first description of neuromyelitis optica (NMO) or Devic's disease. The relation between NMO and multiple sclerosis (MS) had long been debated, but the discovery of anti-aquaporin-4(AQP4) antibody, an NMO-specific autoantibody has accelerated clinical and experimental research of NMO, and contributed to estabilishing NMO spectrum disorder(NMOSD), a wider disease spectrum than a prototypic opticospinal phenotype and a new disease concept: autoimmune astrocytopathic disease. Clinical, MRI and laboratory findings and therapeutic response in NMOSD are different from those in MS. On the other hand, anti-AQP4 antibody-seronegative NMOSD has some distinct features from seropositive cases, and anti-myelin oligodendrocyte glycoprotein(MOG) antibody is detected in a fraction of cases of seronegative NMOSD. Unlike anti-AQP4 antibody-associated NMOSD, anti-MOG antibody-seropositive NMOSD may be a demyelinating desease. In this review, we provide an overview of how the concept of NMOSD has evolved in association with accumulated scientific evidences.

Aim: Hemodynamic changes with aging in the penile arterial circulation, including the helicine arteries, were evaluated with power Doppler imaging in erectile dysfunction patients with a normal response to prostaglandin injection. Methods: In 36 patients with erectile dysfunction and no definite vascular risk factors, 72 corpora were examined using power Doppler imaging. Patients were classified by age: younger than 40 years, from 40 to 49, or 50 and older. Hemodynamic variables in the cavernous arteries, helicine arteries and dorsal arteries were measured after intracavernous injection of prostaglandin E1 (20 µg). Results: All cavernous arteries had a maximum peak systolic velocity of greater than 35 cm/s and a minimum end-diastolic velocity of less than 0 cm/s. Mean peak systolic velocity in the cavernous artery differed between groups (P = 0.016), especially between the younger than 40 age group and the 40–49 age group. Peak systolic velocity correlated negatively with age (P = 0.0048). In the helicine arteries and dorsal arteries, peak systolic velocity did not differ between groups and showed no correlation with age. End-diastolic velocity, resistance index and acceleration time did not differ between groups, or correlate with age for any artery. Conclusions: Hemodynamic change with aging occurs predominantly in the cavernous arteries, where peak systolic velocity decreases. The arterial circulation beyond the cavernous arteries, including the helicine arteries, as well as veno-occlusive mechanisms, may have an important role in maintaining erectile function in aging.

e16080 Background: Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC), and affected patients have a poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts a poor prognosis. The aim of this study was to elucidate the association between BAP1 expression and clinicopathologic outcomes in patients with ccRCC with an IVC tumor thrombus. Methods: Thirty-nine patients with ccRCC with an IVC tumor thrombus who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical analyses were performed for the expression of BAP1, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Multivariate analyses of the associations between overall survival (OS) and clinical variables were performed using a Cox proportional hazard model. For all analyses, P < 0.05 was considered statistically significant. Results: The median follow-up time was 58.8 months (range, 2–130 months). The median age was 66 years (range, 37–80 years). Four patients (10.3%) had lung metastasis at the initial diagnosis. The primary tumor was right-sided in 27 (69.2%) patients and left-sided in 12 (30.8%). The IVC tumor thrombus extended above and below the diaphragm in 11 (28.2%) and 28 (71.8%) patients, respectively. The KPS score was > 80 in 23 patients (59.0%). BAP1 expression was positive in 26 (67.0%) cases and negative in 13 (33.0%). BAP1-negative tumors were associated with a significantly shorter OS than BAP1-positive tumors (median OS, 42.0 vs. 81.5 months, respectively; P = 0.019). The median disease-free survival in BAP1-negative and -positive tumors was 10.0 and 19.0 months, respectively (P = 0.019). Multivariate analysis showed that only a BAP1-negative status was significantly associated with shorter OS (P = 0.026). Conclusions: A BAP1-negative tumor status was significantly associated with a poor prognosis in patients with ccRCC with an IVC tumor thrombus who underwent radical nephrectomy and tumor thrombectomy.

To evaluate the clinicopathological features and identify predictive factors in patients with early and late recurrence following initial surgery for localized renal cell carcinoma. From April 1988 to January 2013, 486 patients without metastases at the initial diagnosis underwent either radical nephrectomy or partial nephrectomy and were followed up thereafter. Patients were divided into 3 groups; no recurrence, early recurrence (recurrence within 5 years), and late recurrence (recurrence after 5 years). Cancer-specific survival after recurrence was analyzed by using the Kaplan–Meier method. Multivariate logistic regression analysis was applied to define clinical and pathological factors correlated to early and late recurrence following surgery. Seventy-seven (15.8 %) and 18 (3.7 %) patients developed early and late recurrence, respectively. In multivariate logistic regression analysis, positive symptoms at diagnosis, ≥pT2, positive lymphovascular invasion, and grade 3 were independent predictive factors for early recurrence. Age at surgery and ≥pT2 were significantly correlated to late recurrence. The 5-year cancer-specific survival rate after recurrence was 72.4 and 52.9 % in the late and the early recurrence groups, respectively (P = 0.044). The risk factors for clinical recurrence differed according to the time that had elapsed between initial surgery and the first metastasis in patients with localized renal cell carcinoma. Our study showed age at initial surgery and the pT stage were independent predictive factors for late recurrence. Further investigation of a larger number of patients is required to predict which patients may develop recurrence in the future and to choose appropriate treatment.

The objectives of this study were to evaluate the efficacy and toxicity of maintenance intravesical instillation therapy with bacillus Calmette-Guerin (BCG) and epirubicin for non-muscle invasive bladder cancer. From April 1999 to March 2010, 27 eligible patients were enrolled in this study. After receiving one cycle of epirubicin (100 mg/100 ml) by intravesical instillation, all patients received 6 weekly alternate intravesical instillation of BCG (80 mg/50 ml) and epirubicin (50 mg/50 ml), followed by 10 monthly instillations. Among the 27 patients, 19 were men and 8 were women, with a median age of 62.4 years (range, 37-78 years). Tumor pathologic stage was pTa in 25 patients, pT1 in 2 and there were no concomitant carcinoma in situ cases. Median follow-up was 37.1 months (range, 11-82 months). The 3- year recurrence-free and progression-free survival rates were 75.3% and 96.1%, respectively. Furthermore, a high completion rate of 81.5% was achieved in this study. Adverse events of grade 3 or higher occurred in 3 patients (11.1%), 1 patient had anaphylaxis. There were no treatment-related deaths. Maintenance intravesical instillation therapy with BCG and epirubicin is a favorable therapeutic option for non-muscle invasive bladder cancer. Given the safety and benefit profile found in this study, appropriate patient selection is warranted in the future.

Between November 2008 and March 2010, we performed initial division of the left renal vein occluded by the tumor thrombus in six cases of left renal cancer at Toranomon Hospital. The left renal vein was completely occluded by the tumor thrombus in all cases. In order to ligate the left renal artery first behind the dilated left renal vein, we must dissect the left kidney with arterial blood flow. Massive bleeding from the numerous engorged collateral veins around the left kidney is inevitable. Furthermore, access to the left renal artery is difficult because of the large tumor. We therefore initially divided the left renal vein without arterial blood flow followed by division of the left renal artery. After nephrectomy by dissecting the tumor without blood flow we extirpated the intracaval tumor thrombus. The median time of the operation was 7 hours 35 minutes and the median amount of blood loss was 2,869 ml. The tumor stage was pT3b in four cases and pT3c in two cases. No complications were observed during and after surgery except for one case of lymphocele and another case of chylous ascites. The initial division of the left renal vein is considered to be a useful surgical approach in left renal cancer with occluded left renal vein, especially when the tumor is large.

A 30-year-old female was admitted to our hospital with a 3-month history of general fatigue and one month history of left flank mass. Computed tomography revealed a huge left renal tumor (20 × 13 × 10 cm) with intracaval tumor thrombus. The tumor thrombus extended into the right atrium. The left renal vein (lt-RV) was expanded 3.5 cm in diameter by the tumor thrombus. The tumor was surrounded by a tortuous dilated capsular vein. The strategic issue was how to ligate the left renal artery (lt-RA) behind the expanded lt-RV. We first divided the lt-RV occluded by the tumor thrombus using a Linear Cutter® and then divided the lt-RA before the dissection of the tumor to avoid excessive bleeding. Even transarterial embolization of lt-RA were to be performed,the tumor was too large to dissect without division of lt-RV and lt RA. After the left kidney was removed,the lower half of the tumor thrombus was excised,clamping the inferior vena cava,three right renal arteries,two right renal veins,and the lumber vein. Finally,we removed the upper half of the tumor thrombus extending to the right atrium through atriotomy and cavotomy under an extracorporeal cardiovascular bypass. Operation time was 9 h 22 m,and total blood loss was 1670 ml. Convalescence was uneventful except for abdominal lymphocele.

肝細胞における細胞内カルシウム動態の意義を明らかにするため,初代培養肝細胞を用いてホルモン刺激後のカルシウム動態を経時的に測定した.培養早期の肝細胞ではvasopressinおよびphenylephrineに対して細胞内カルシウムの著明な上昇を示したが,培養時間の経過にともなって反応性は低下,遅延し,12～24時間後には反応は消失した.これは肝細胞が増殖に向かうにつれ,これらのホルモンのreceptorが減少することによりphosphatidylinositol代謝系を介したカルシウムのシグナルが減衰したものと考えられ,このシグナルの変化が肝細胞の増殖分化と関連していることが示唆された.

A 43-year-old infertile man with oligozoospermia and normal serum gonadotropin and cytogenetic findings was treated with follicle-stimulating hormone for 1 year at our institution. Two years later, the patient presented with bilateral palpable testicular tumors. His beta-human chorionic gonadotropin and lactate dehydrogenase levels were elevated. Pathologic examination disclosed a pure seminoma in each testis (pT1N0M0). Adjuvant radiotherapy was administered. The tumors might have been induced by follicle-stimulating hormone treatment. Careful follow-up examination of the testis is necessary in men who have received hormonal treatment for infertility.

The children at the Minamihata, Asaka 3rd and Osato elementary schools were instructed in their diaries their tooth-brushing habits for one year. Careful analyses of the diaries revealed that, as compared with other months of June, August, October and December, the number of their tooth-brushings decreased per day in August.At the same time, it was confirmed that on Sundays the number of tooth-brushings was less than on week days.When analyzed in terms of different schools, at the Minamihata elementary school 35% accounted for the tooth-brushing after lunch, whereas at the Asaka 3rd and Osato elementary school more than half of the children brushed their teeth at getting up in the morning or before retiring for the night.This kind of differences may be ascribed to the teaching policy of the schools concerned.Those children who brushed their teeth more than once a day were observed to be unstable in their habit than those who regularly brushed their once a day.It has been difficult to infer their habit of tooth-brushing of a day for that of one month or the whole year.Although the taste and flavor of a tooth-paste liked by the children were factors to be considered in the formation of tooth-brushing habit, it seemed that a dental paste or dental powder could be easily changed. Therefore, it is necessary that, in the instruction of tooth-brushing in schools, many factors involved in the picture should be given a sufficient consideration.