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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.

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.

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.

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.

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.

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.

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.

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 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.