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Pouchitis is the most common long-term complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Although several agents, including probiotics, steroids, and immunomodulators, have been used, the treatment of pouchitis remains challenging. Owing to the proven efficacy of biological therapy in inflammatory bowel disease, there is now growing evidence suggesting the potential benefits of biological therapy in refractory pouchitis. Here, we report the case of a 64-year-old woman with pouchitis due to ulcerative colitis who was successfully treated with ustekinumab (UST). The patient developed ulcerative pancolitis at the age of 35. Total colectomy and IPAA with J-pouch anastomosis were performed when the patient was 47 years old. Ileotomy closure was performed 6 months later. Postoperatively, the patient developed steroid-dependent pouchitis. Three years later, she developed steroid-induced diabetes. The patient has been taking 3mg of steroid for 20 years;therefore, her lifetime total steroid dose was 21g. The patient had over 20 episodes of bloody diarrhea a day. The last pouchoscopy in 20XX-9 revealed inflammatory stenosis with deep ulcerations of the afferent limb just before the ileoanal pouch junction. In July 20XX, when we took over her treatment, the policy of treatment was to withdraw her from steroids. Pouchoscopy revealed a widened but still tight afferent limb through which the scope could easily pass, and the ileoanal pouch still showed erosive ileitis without ulcers. Thiopurine administration and steroid tapering were initiated. Steroid tapering increased the erythrocyte sedimentation rate (ESR). As ESR increased, her arthritis exacerbated. Six months after the end of steroid administration, the patient consented to UST treatment. On April 20XX+1, the patient received her first 260-mg UST infusion. At this point, she experienced 14-15 episodes of muddy bloody stools. She had no abdominal pain;however, she experienced shoulder pain. Gradually, UST affected both pouchitis and arthritis. UST treatment was continued at 90mg subcutaneously every 12 weeks without abdominal pain recurrence. Eight months after the first UST infusion, nonsteroidal anti-inflammatory drugs were no longer necessary for shoulder pain. Follow-up pouchoscopy performed 14 months after UST optimization revealed a normal afferent limb without ulcerations in either segment. Pouchitis remission was maintained for over 2 years.

The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).

A 51-year-old male presented with swelling on the left side of his neck. A diagnosis of thoracic esophageal cancer(Lt type 5a, squamous cell carcinoma, T3N4[16LN]M1[skin, bone, retroperitoneum, lung], cStage Ⅳb)was made, and treatment with a combination of 5-FU plus CDDP and pembrolizumab was initiated. After the 1st round of chemotherapy, there was an increase in metastases in the left cervical lymph node and skin, along with the development of back pain because of an L3 lumbar spine metastasis. Palliative radiotherapy(Σ24 Gy/6 Fr)was administered for all lesions. Subsequently, pembrolizumab was administered for the persistent decline in white blood cell and neutrophil counts. After 6 courses of pembrolizumab, computed tomography(CT)revealed an absence of lesions. Positron emission tomography/CT demonstrated no significant accumulation, prompting a diagnosis of complete response(CR). The patient is currently under pembrolizumab therapy and continues to remain in a state of CR.

Immune checkpoint inhibitor(ICI)combination therapy is the first-line of treatment for unresectable or recurrent esophageal cancer. The frequency and mechanism of immune-related adverse events(irAEs)associated with ICI are still unclear and may require differentiation from other diseases. The present study examined a patient with unresectable, advanced esophageal cancer treated with cisplatin plus 5-fluorouracil(CF)plus nivolumab as the first-line treatment. CF therapy was discontinued after 1 course owing to adverse events. Nivolumab was continued, but progressive anemia stemming from pure red cell aplasia(PRCA), an irAE of nivolumab administration, was observed. Nivolumab was discontinued, but later, interstitial pneumonia also developed, and pulse steroid therapy was begun. After steroid tapering, both the PRCA and interstitial pneumonia improved. At present, about 6 months have elapsed since the last nivolumab administration without any PRCA recurrence or evidence of tumor progression.

Recently, mammography systems equipped with digital breast tomosynthesis (DBT) have become widely used in Japan. Therefore, it is urgently necessary to establish a quality control method for DBTs. So far, we have been studying acceptance tests for DBTs with reference to EUREF. In 2020, IEC 61223-3-6 was published, which provides not only acceptance tests but also constancy test methods. Therefore, we conducted data collection using DBTs sold in Japan and examined the feasibility of conducting constancy tests. Although there were some items that were difficult to implement in each device, we were able to confirm quality control items that could be implemented in many devices. In addition, we were able to confirm routine tests that enable rapid evaluation. Based on these results, we have developed a "Digital Breast Tomosynthesis Quality Control Manual". In this paper, we report an overview of the manual and the results of routine tests.

A 69-year-old woman was referred to our hospital for the treatment of a left renal tumor found by computed tomography (CT) during examination for microscopic hematuria. Contrast-enhanced CT showed a 5 cm tumor in the inferior pole of the left kidney. Left renal cell carcinoma (RCC) (cT1bN0M0) was suspected. In addition, the left renal and gonadal veins were dilated and enhanced in an arterial phase; renal arteriovenous fistula (RAVF) was suspected. Moreover, there were multiple focal arterial dilatations, suggesting the presence of multiple vascular malformation. Hereditary aortic disease, including vascular Ehlers-Danlos syndrome (vEDS), was a concern. In general, surgery is not recommended for patients with vEDS, due to vascular fragility. As such, a panel analysis of genes for hereditary aortic diseases, including vEDS, was performed; no pathogenic variants in candidate genes including COL3A1 were identified. After detailed discussions with the patient, she underwent a left nephrectomy, following transcatheter arterial embolization (TAE) of the left renal artery. We prepared a balloon catheter for aortic occlusion as a preventative measure for massive bleeding; this was not the case, as only a small amount of intraoperative bleeding occurred. Thus, the nephrectomy was performed successfully without using the balloon catheter. The patient recovered uneventfully and was discharged on day 8. Pathological examination showed clear-cell RCC (pT1a) and a RAVF near the tumor. Herein we report this case of left RCC with RAVF and multiple arterial malformation, which was successfully managed by evaluating preoperative risks with a genetic test, followed by TAE of the renal artery and open nephrectomy.

Esophagectomy is a highly invasive surgery for elderly patients. The incidence of esophageal cancer is relatively high among the aging population in Japan. Therefore, it is crucial to determine the indications for esophagectomy and implement effective pre- and post-operative management strategies, considering the reduced physical function often observed in elderly patients. In our study, approximately 20% of patients with stageⅡ/Ⅲ esophageal cancer underwent esophagectomy. When we assessed thesepatients using the estimation of physiologic ability and surgical stress (E-PASS) scoring system, we found that the E-PASS score was significantly lower in the group that underwent surgery compared to those who received chemotherapy, radiation, or palliative treatment. Evaluating the risk of esophagectomy using tools such as E-PASS or others is crucial in establishing appropriate indications and ensuring patient safety. Regarding the perioperative period, our study revealed that the complication rate did not differ significantly between patients aged 74 years or younger and those aged 75 years or older. However, patients aged 75 years or older experienced significantly longer total and post-hospital stays. This prolonged postoperative stay in elderly patients can be attributed to a decline in activities of daily living (ADL) following esophagectomy, primarily due to their lower physical function. These results emphasize the importance of considering the potential decline in ADL resulting from lower physical function in elderly patients during perioperative management. Establishing multidisciplinary perioperative teams and rehabilitation programs can enhance the quality of life for patients after esophagectomy.

The monoamine hypothesis has been common hypotheses for the pathophysiology of major depressive disorder (MDD). Since mainstream antidepressants are selective serotonin (5-HT) reuptake inhibitors, hypo-serotonergic function has been implicated in the MDD. However, one-third of patients are refractory to the treatment with antidepressants. Tryptophan (TRP) is metabolized via the kynurenine (KYN) and 5-HT pathways. Indoleamine 2,3-dioxygenase 1 (IDO1) is the first metabolizing enzyme in the TRP-KYN pathway which is inducible by pro-inflammatory cytokines, involved depression-like behavior via 5-HT depletion due to decreased level of TRP in the 5-HT pathway. Kynurenine 3-monooxygenase (KMO) is the enzyme in the metabolism of KYN to 3-hydroxykynurenine. KMO deficiency increases level of kynurenic acid (KA), a KYN metabolite by kynurenine aminotransferases (KATs) and induces depression-like behavior. Interestingly, Chronic unpredictable mild stress (CUMS) is associated with a disruption of the hypothalamus-pituitary-adrenocortical (HPA) system and increases KA level with decreased KMO expression in the prefrontal cortex. The decrease of KMO may be related to the reduction in expression of microglia, since KMO is mainly found in microglia in the nervous system. CUMS increases KA level via alternation of enzymes from KMO to KAT. KA is α7 nicotinic acetylcholine receptor (α7nAChR) antagonist. Activation of α7nAChR by nicotine or galantamine attenuates CUMS-induced depression-like behaviors. Taken together, depletion of 5-HT by induction of IDO1 and α7nAChR antagonism by KA via decreased KMO expression cause depression-like behavior, suggesting that metabolic alterations in TRP-KYN pathway are highly involved in the pathophysiology of MDD. Therefore, TRP-KYN pathway is expected to be an attractive target for the development of novel diagnosis of MDD and antidepressants.

We analyzed 4 cases who experienced extravasation of anthracyclines and had dexrazoxane therapy in our hospital. Concerned drugs were 2 adriamycin and 2 amrubicin cases and all cases received steroid ointment therapy, and no cases showed severe condition such as skin ulcer. As dexrazoxane is known to enhance bone marrow suppression of anti-cancer drugs, the nadir of neutropenia and thrombocytopenia was observed from day 10 to 17 in our cases. We made a domestic manual and have used in various professionals. Dexrazoxane would contribute to the reduction of skin damage due to extravasation if we could manage bone marrow suppression successfully.

An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.

The patient was a 42-year-old woman. After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she underwent pleurodesis using OK-432 for increased right pleural effusion. On the 12th day after pleurodesis diffuse infiltrative shadows in the right lung, and frosted shadows in both lungs, were observed, and she was diagnosed with drug-induced lung injury. About 3 weeks after administration of prednisolone 1 mg/ kg a tendency for improvement in lung injury was observed, but the patient died of breast cancer progression. Drug- induced lung injury by pleurodesis carries the risk of delaying resumption of chemotherapy. We report this case with a review of the literature.

A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.

(Objective) Pregnancy in kidney transplant recipient continues to remain challenging due to a high rate of cesarean section along with preterm delivery, and concern for worsening renal function. This study examined the prognosis and perinatal management of post-transplant pregnancies. (Patients and methods) A total of nine post-transplant recipients at Niigata University Medical and Dental Hospital between 2007 and 2021 were retrospectively examined. (Results) All pregnancies were planned. Calcineurin inhibitors and steroids were continued, and antimetabolites were changed to azathioprine. The mean age at delivery was 33±3.8 years, and the mean time from renal transplantation to delivery was 6.5±3.5 years. Five patients (55.5%) had cesarean sections, while four (44.5%) patients had normal vaginal deliveries. The mean gestational age was 35±3.0 weeks, and the mean birth weight was 2,336±565.4 g. No congenital malformation was observed. The most common reason for early delivery was worsening renal function, seen in six (66.7%) patients. The mean serum creatinine level before pregnancy was 1.11±0.23 mg/dL and then worsened to 1.59±0.37 mg/dL during pregnancy. However, it recovered to 1.14±0.40 mg/dL after delivery. One patient had antibody-mediated rejection with donor specific antibody (DSA) prior to pregnancy, and her renal graft function worsened slightly after delivery. Another patient had a de novo DSA after delivery, which was not detected before pregnancy. (Conclusions) In our hospital, pregnancy in kidney transplant recipients were safe and renal graft function after delivery was relatively stable. Patients may require adjustment of calcineurin inhibitors during pregnancy, and the appearance of DSA after delivery should be noted.

The patient was a man in his 70s. During the treatment for acute myeloid leukemia, abdominal pain and bloody stools appeared. A diagnosis of small intestinal ileus was made by computed tomography scan. Treatment with an ileus tube did not improve his condition, and enteroscopy revealed the presence of ileal ulcers. Based on histological examination, small intestinal mucormycosis was suspected, and thus, antifungal drugs were administered. However, the patient developed perforated peritonitis and underwent small intestine resection. He was finally diagnosed with small intestinal mucormycosis with the help of the resected specimen. The gastrointestinal form of mucormycosis rarely occurs, and small intestinal lesions are very rare. Enteroscopy was helpful in its diagnosis and treatment.

Purpose: Lung cancer accounts for the largest number of deaths among malignant tumors. Recently, more and more patients are concerned about their own life expectancy. CT examination is essential for the diagnosis of lung cancer. However, it is difficult to accurately predict the prognosis using CT images. In this study, we developed a method to predict the prognosis of lung cancer patients from CT images using a convolutional neural network (CNN) and a machine learning method., Methods: In this study, the CT images of 173 lung cancer patients were collected. First, we selected the slice with the largest tumor size in each case and extracted features using a CNN. Next, we performed feature selection using information gain and predicted alive or death by classifiers. An artificial neural network or Naïve Bayes was used as a classifier and alive and death were predicted at one-year intervals from one year to five years later., Results: We evaluated the prediction accuracy via the three-fold cross-validation method and found that the prediction accuracies were around 80% for all periods from 1 to 5 years. In the evaluation of the survival curve, the shape of the curve was close to the actual curve., Conclusion: These results indicate that feature extraction by a CNN and classification by the machine learning method may be effective in predicting the prognosis of lung cancer patients using CT images.

Thrombotic microangiopathy (TMA) is a pathological condition characterized by platelet thrombi-induced generalized microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. TMA includes the life-threatening diseases thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TTP is different from HUS in that it has a severe deficiency in ADAMTS13 activity. Congenital TTP is caused by a lack of plasma ADAMTS13 activity caused by genetic mutations, and acquired TTP is caused by a secondary deficiency caused by autoantibodies. In Japan the only product approved for the treatment of congenital TTP is fresh frozen plasma containing ADAMTS13. Recombinant ADAMTS13 may provide a new treatment option for congenital TTP. The first-line treatment for acquired TTP is plasma exchange. Rituximab treatment should be considered for patients who are refractory or have relapsed. Caplacizumab is a nanobody that specifically targets von Willebrand factor. ISTH recently published guidelines recommending that caplacizumab be added to the initial treatment for acquired TTP. Atypical HUS (aHUS) is related with the dysregulation of the complement alternative pathway. Eculizumab, a monoclonal antibody that inhibits C5, was the first drug approved for aHUS, and it was found to be well-tolerated by patients and effective in clinical use. TMA is classified based on its etiology, and specific treatments for targeting various etiologies are now available.

A 65-year-old man was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia with no initial central nervous system (CNS) involvement. Complete remission was achieved after the induction therapy. However, during consolidation therapy, he developed septic shock and pneumocystis pneumonia, leading to interruption in chemotherapy and allogeneic transplantation. Subsequently, he achieved complete molecular remission and ponatinib maintenance therapy was initiated. Two years later, he developed left leg paralysis and was diagnosed with isolated CNS relapse; however, radiation therapy improved CNS lesions and paralysis. Thus, ponatinib maintenance therapy alone is inadequate in preventing CNS relapse in patients who have not completed systemic chemotherapy for CNS relapse prevention.

We experienced a case of solitary liver tumor that developed after renal cancer surgery. Before the surgery, the tumor was suspected to be hepatocellular carcinoma and was subsequently diagnosed as renal cancer liver metastasis. An 81-year-old man underwent retroperitoneal laparoscopic nephrectomy for left renal cancer in January 2017. After that, the cancer had not recurred, but a follow-up CT examination 1 year after the operation revealed a 42 mm-sized tumor in the liver S6. Liver biopsy was performed for diagnosis, but in histopathological findings, the diagnosis was difficult to make. Eventually, the preoperative final diagnosis was hepatocellular carcinoma. Laparoscopic partial hepatectomy was performed in June 2018, and in the histopathological findings of the resected specimen, the final diagnosis was the liver metastasis from renal cancer. Generally, the prognosis of renal cancer with liver metastasis is poor, but if complete resection is possible, it is recommended in the Clinical Practical Guideline for Renal Cancer. In recent years, the number of minimally invasive laparoscopic surgeries for hepatectomy has increased, and its safety has also improved. Therefore, resection is diagnostic treatment for cases where, like this case, preoperative diagnosis for solitary liver tumor is difficult. Laparoscopic hepatectomy could be one of the effective treatment strategies.

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

Maximum safe resection is the principal goal of glioma surgery to improve patient prognosis, and various skills and techniques are available to achieve this. First, detailed preoperative image assessment of the tumor, arteries, veins, and white matter is helpful in developing the surgical plan. Second, surgical supporting technology, such as a navigation system, electrophysiological monitoring, awake craniotomy, and fluorescence-guided surgery, are vital for glioma surgery. Third, and most importantly, neurosurgeons should develop surgical techniques. In this review, we will focus on the following points: how to determine and dissect the tumor boundary, how to preserve passing arteries and veins, how to identify and preserve the eloquent cortex and fibers, and how to treat bleeding during tumor removal. Dissection of the tumor margin includes sharp dissection and subpial dissection. Subpial dissection using a suction tube or Cavitron Ultrasonic Surgical Aspirator(CUSA)is often effective in glioma surgery, not only for achieving better resection, but also for the preservation of passing vessels. Using these techniques, excessively small vessels, such as perforating arteries, can be finely exposed and preserved during tumor resection. In this way, we should achieve an ideal balance between maximum tumor resection and patient quality of life.

Perampanel is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist that has been marked as an antiepileptic drug for partial-onset and primary generalized tonic-clonic seizures. There have been some recent reports of perampanel being effective against cortical myoclonus by Lafora disease and Unverricht-Lundborg disease. We herein report a 49-year-old man who presented with myoclonus due to Lance-Adams syndrome (LAS) after cardiopulmonary arrest caused by a severe bronchial asthma attack. Perampanel was very effective against myoclonus induced by LAS even in the chronic state, over 10 years after the remote onset. Perampanel should be considered for the treatment of extremely refractory myoclonus due to LAS.

Antibody-drug conjugates (ADCs) combine the specific antibody and cytotoxic agent by a linker and represent a promising drug class with a wider therapeutic window than conventional chemotherapeutic agents by substantiating efficient and specific drug delivery to antigen-expressing tumor cells. However, there are rooms for improvement in terms of efficacy, safety, physicochemical property; therefore, the development of promising ADC drugs across multiple indications are eagerly awaited. In 2015, Daiichi Sankyo initiated the first-in-human study of HER2 ADC, trastuzumab deruxtecan (T-DXd, ENHERTU ® ) which possesses DNA topoisomerase I inhibitor, exatecan derivative and proprietary linker, in Japan. Based on the provocative results in phase 1 study, the global development program has been accelerated to show the high and durable efficacy in patients with HER2 positive breast cancer pretreated with trastuzumab emtansine. As a result, T-DXd was approved based on single arm phase 2 study in the US (Dec 2019) and Japan (March 2020) by leveraging the breakthrough designation and conditional early approval system, respectively, at the first time for the HER2 positive breast cancer. In addition, T-DXd was recently approved in gastric cancer through Sakigake designation in Japan based on a randomized phase 2 study. T-DXd is also being developed in the earlier lines or other indications where no anti-HER2 therapies were approved to date. Combination studies with other agents, such as immune checkpoint inhibitors are underway. In the near future, we hope that more patients worldwide can enjoy the therapeutic benefits of T-DXd through our continuous efforts to expand its indications.

(Objective) Nocturia, an important male lower urinary tract symptom (LUTS), is often difficult to treat. Herein, we report our experience of the initial treatment of nocturia with the novel drug desmopressin. (Subjects and methods) Subjects included 25 patients with LUTS treated with desmopressin who had the chief complaint of nocturia. Before treatment, the frequency of nocturnal urination (≥2) and nocturnal polyuria index (≥0.33) were confirmed based on the urination diary for ≥ 72 h. Before sleep, 25 or 50 mg desmopressin (Minirin ® Melt OD tablets) was administered once daily. The frequency of nocturnal urination, volume of nocturnal urine, time from falling asleep to first urination, first urinary volume after falling asleep, nocturnal polyuria index, International Prostate Symptom Score (IPSS), quality of life index, Overactive Bladder Symptom Score, and residual urine volume were comparatively evaluated before and 4 weeks after treatment. Treatment effect was self-evaluated by patients 4 weeks after the treatment. Safety was evaluated by interview and blood testing 1 and 4 weeks after the treatment. (Results) Decrease in the frequency of nocturnal urination and improvement in IPSS were observed. According to self-evaluation of the treatment, 72.6% of the patients considered the treatment efficacious. Regarding safety, adverse events were observed in 28% of the patients, particularly hyponatremia (12% of the patients). (Conclusion) Desmopressin is a potential key drug for the treatment of nocturia caused by nocturnal polyuria.

(Purpose) To conduct a prospective study on the efficacy and safety of desmopressin for nocturnal polyuria. (Materials and methods) We selected 51 Japanese men, aged ≥50 years, with complaints of nocturia and a nocturnal polyuria index of ≥0.33. We administered 25 or 50 μg desmopressin (Minirinmelt Orally Disintegrating Tablet ® ), once daily at bedtime. We evaluated the nighttime urinary frequency and urine volume, nocturnal polyuria index, time to the first urination after falling asleep, and International Prostate Symptom Score (IPSS) at baseline and at 4, 8, and 12 weeks after administration. In addition, they underwent clinical examinations and blood tests at 1, 4, and 12 weeks to evaluate the safety of the drug. (Results) We observed a decrease in the nighttime urinary frequency and urine volume, and nocturnal polyuria index, increased prolonged time to the first urination after falling asleep, and improved IPSS at and after 4 weeks, compared to baseline data. Furthermore, the drug remained effective even at 12 weeks for all parameters. We observed adverse events in 31.3% of the patients. The incidence of hyponatraemia was particularly high in 15.7% of the patients. Those with a lower serum sodium level and lesser body weight at baseline were more likely to develop hyponatraemia. (Conclusion) Desmopressin was identified as a potential drug for the treatment of nocturnal polyuria. However, hyponatraemia, an important adverse event, resulted in treatment discontinuation in several patients. A sodium level lower than the normal level and low body weight at baseline were the risk factors for hyponatraemia.

Alexander disease (AxD) is a rare neurodegenerative disorder caused by the mutations in glial fibrillary acidic protein (GFAP) gene. Rosenthal fiber formations in astrocytes are the pathological hallmarks of AxD. Astrocyte dysfunction in the AxD brain is considered to be involved in its pathogenesis. We have previously reported that in AxD model mice aberrant Ca 2+ signals in astrocytes were associated with the upregulation of reactive phenotype. Reactive astrocytes are conditions that lead to morphological, functional, and molecular changes by responding to various pathological insults (trauma, inflammation, ischemia), and environmental stimuli. Recent technological advances in single-cell gene expression analysis have revealed that astrocytes have heterogeneity by indicating that they form sub population with different characteristics depending on the brain region, the growth development, aging stage, and the pathological condition. AxD astrocytes are also thought to constitute a heterogeneous population with diverse properties and functions. Moreover, it is presumed that AxD pathogenesis occur due to interactions with neurons and other glial cells, as well as the microenvironment in tissues. Research strategies based on these perspectives will help us understand AxD pathology better and may lead to the elucidation of disease modifiers and clinical diversity.

An ependymoma of the sella turcica and the suprasellar region has been described by only 10 reports in the available literature. We describe similar pathology in a 70-year-old woman who presented with dementia and visual disturbance. Magnetic resonance imaging with gadolinium revealed a mixed contrast-enhanced lesion(maximum diameter 3.5 cm)in the sella turcica and suprasellar area associated with a noncommunicating hydrocephalus. The patient was preoperatively presumptively diagnosed with a craniopharyngioma. The lesion was adherent to the hypothalamus, and the third ventricular floor was completely resected via an endoscopic endonasal transsphenoidal approach. Histopathological findings confirmed an ependymoma. Although her visual disturbance improved, the patient developed postoperative panhypopituitarism. She has had no recurrence for 7 years postoperatively. An ependymoma of the sella turcica and the suprasellar region is extremely rare; establishing the preoperative diagnosis is challenging in such patients. Maximum tumor resection and long-term follow-up are essential for good prognosis.

Patients with refractory ascites that develops >3 months after allogenic stem cell transplantation typically have a poor prognosis. We present the case of a 61-year-old man who developed refractory massive ascites approximately 3 months after cord blood transplantation (CBT) and showed complete and spontaneous remission from ascites after 18 months. The patient complained of severe bloating and needed weekly paracentesis to manage the fluid levels. Laboratory tests indicated that the ascites was caused by liver fibrosis. After the patient underwent Keisuke-Matsusaki cell-free and concentrated ascites reinfusion therapy (KM-CART), we were able to decrease the frequency of paracentesis treatments. We planned a transjugular liver biopsy, but the patient contracted pneumocystis pneumonia before the procedure could be performed. Although the pneumonia improved, the ascites worsened again. However, weekly paracentesis spontaneously stopped the progression of ascites and eventually resolved it completely, resulting in the patient's survival.

Malignant melanoma is an aggressive tumor with a high potential for distant metastases. Autopsy studies have shown that gallbladder metastases are found in 15% of patients. However, metastatic melanoma of the gallbladder is rarely discovered in living patients. A 73-year-old man was reported. The patient underwent surgical removal of malignant melanoma on his back and lymphadenectomy of the axillary lymph nodes. In addition, the patient developed cutaneous metastases to the right axillary and the middle of the chest 1.5 years after the surgery. Consequently, nivolumab chemotherapy was started. A computed tomography (CT) scan showed a well-enhanced mass in the gallbladder 4 months after. Abdominal ultrasonography revealed a 13-mm hypoechoic heterogeneous mass in the gallbladder with a hyperechoic layer on the mass surface. Magnetic resonance imaging demonstrated that the gallbladder tumor showed high signal intensity on T1-weighted images, low signal intensity on T2-weighted images, and high signal intensity on diffusion-weighted images. Positron emission tomography-CT revealed the slight uptake of fluorodeoxyglucose at the tumor. Endoscopic ultrasonography showed a hypoechoic tumor infiltrating the submucosal layer. The patient underwent open cholecystectomy. Examination of the resected specimens revealed a black, nodular-type tumor in the gallbladder body. The histopathological diagnosis was malignant melanoma. It was judged as metastatic melanoma of the gallbladder.

The case is a 59-year-old woman. A medical examination revealed a high CA19-9, she visited a nearby hospital. Abdominal echo showed thickening of the gallbladder wall, and she was referred to our hospital for further examination. EUS-FNA was performed and a biopsy of #12 lymph node revealed undifferentiated cancer, which was diagnosed as gallbladder cancer. FDG-PET showed accumulation of FDG in the gallbladder lumen and swollen lymph nodes around the aorta. Therefore, the cancer was considered unresectable and chemotherapy was performed. FDG-PET was re-examined after 4 courses of gemcitabine plus cisplatin combination chemotherapy. As a result, the lymph node swelling contracted, the accumulation of FDG disappeared, and surgery was scheduled. Extended cholecystectomy and extrahepatic bile duct resection were performed. She was discharged 22 days after the surgery without complications. Histopathological examination showed fibrotic tissue at the gallbladder and lymph nodes, but no residual tumor cells. There are no recurrences 11 months after surgery. Although the prognosis of gallbladder cancer with para-aortic lymph node metastasis is generally poor, it is suggested that conversion surgery with multimodality treatment including preoperative chemotherapy may be a useful therapeutic strategy.

A 60's man came to our hospital for jaundice. Contrast-enhanced CT showed irregular thickening of the hilar bile duct, and the lymph nodes(LN)were swollen from the hilar to the abdominal aorta. These LNs showed similar findings in endoscopic ultrasonography(EUS), and fine needle aspiration cytology(FNA)was performed on the enlarged No.13LN to diagnose LN metastasis of hilar cholangiocarcinoma. Since the peri-aortic LN was also markedly enlarged, it was considered to be metastasis, and was diagnosed as unresectable hilar cholangiocarcinoma with distant LN metastasis. When gemcitabine/cisplatin therapy(GC therapy)was started, tumor markers normalized and LN decreased in 4 months. We performed GC therapy for a total of 12 cycles and did not re-exacerbate. Cholangioscopy revealed that bile duct stenosis at the hilar portion had improved. We have determined that curative resection is possible and performed surgery. We confirmed that No.16b1LN was negative by pathological diagnosis during surgery and performed left hepatic caudate lobectomy, extrahepatic cholangectomy, and biliary reconstruction. Diagnosis was pT2aN1(n8a)M0, fStage ⅢB, and pR0. After surgery, adjuvant chemotherapy with S-1 was continued.

We report a case of anterior cranial fossa dural arteriovenous fistula(ACF-DAVF)in a patient whose diagnosis was made according to characteristic findings on arterial spin labeling(ASL)MRI. CASE:A 68-year-old man was admitted to our hospital because of intractable epilepsy. Based on the initial MRI findings, an initial diagnosis of limbic encephalitis was made. Steroids and anticonvulsant drugs were administered;however, the seizures could not be controlled. A second MRI with ASL revealed abnormal vessel signals in the base segments of the left frontal and temporal lobes toward the basal vein of Rosenthal. Digital subtraction angiography(DSA)revealed an arteriovenous shunt in the left anterior cranial fossa, which drained toward the medial side of the left temporal lobe. A diagnosis of ACF-DAVF with status epilepticus was made, and the main drainer was cauterized. After the surgical procedure, the epilepsy was controlled with antiepileptic drugs, and postoperative MRI revealed obliteration of ACF-DAVF, disappearance of the high-intensity area on FLAIR sequences, and disappearance of the high-intensity signal area on ASL.

The case presented is a 72-year-old male with no history of hepatitis B or C. Dynamic CT revealed a 2 cm mass in the liver (S8), with arterial phase hyperenhancement and delayed phase washout. The patient underwent an open S8 subsegmentectomy. The mass was pathologically diagnosed as well-to-moderately differentiated hepatocellular carcinoma(T2N0M0, Stage Ⅱ). At 2 years 10 months postoperatively, MRI showed a 4 cm mass in contact with the pancreatic head, inferior vena cava, and duodenum. The mass had moderate FDG uptake on PET scan, and early phase hyperenhancement and delayed phase washout on dynamic CT. We performed laparoscopic mass resection, suspecting lymph node metastasis of the hepatocellular carcinoma, which was confirmed by the pathological diagnosis. The patient has survived for 1 year without recurrence. Lymph node metastasis of hepatocellular carcinoma is rare. It is unclear whether surgical resection is feasible in such cases. Here, we report a case of lymph node metastasis of hepatocellular carcinoma resected by laparoscopic surgery.

Double functional pituitary adenomas are rare, and only a few cases of excessive clinical symptoms of both adrenocorticotropic hormone(ACTH)and growth hormone(GH)have been reported. We herein report a case of symptomatic ACTH-and GH-producing double pituitary adenomas, which were discretely located within the same pituitary gland. A 38-year-old woman presented with general malaise, facial and lower limb edema, unexplained weight gain, facial redness, acne, and nasal enlargement. Endocrinological findings matched with the diagnostic criteria for both acromegaly and Cushing's disease. Preoperative magnetic resonance imaging showed a 15-mm cyst-like lesion on the right side of the sellae surrounded by what was thought to be the normal contrast-enhancing pituitary gland. We assumed that the cyst-like lesion was an adenoma and performed endoscopic endonasal transsphenoidal surgery. However, the cyst-like lesion was a parenchymal tumor. Furthermore, the region we considered to be a normal pituitary gland was also found to be an adenoma. Both adenomas were completely resected. The postoperative blood analysis showed ACTH<1.0pg/dL, cortisol 1.8μg/dL, and insulin-like growth factor-1 60ng/mL, all of which were below reference levels. The histopathological examination confirmed the coexistence of two adenomas, a GH-producing adenoma and an ACTH-producing adenoma. We concluded that these adenomas were endocrinologically active within the pituitary gland. Thus, a diagnosis of double pituitary adenomas was made. When treating a patient with symptoms caused by hypersecretion of multiple anterior pituitary hormones, the possibility of coexisting multiple pituitary adenomas should be considered.

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.

Spontaneous cerebrospinal fluid(CSF)rhinorrhea may have multiple leakage sites, and occasionally, may become difficult to manage. A 46-year-old man was admitted to our hospital presenting with bacterial meningitis that occurred after CSF rhinorrhea. The CSF leak had stopped following conservative medical treatment;however, it recurred immediately. The leakage was assumed to be in the left lateral recess of the sphenoid sinus based on the location of fluid accumulation on the CT and MR images and the nasal endoscopic findings. First, we performed an endoscopic endonasal repair of the CSF leakage sites. There were multiple defects in the roof of the sphenoid sinus, including the left lateral sphenoid recess. These bone defects were repaired with abdominal fat;however, this did not stop the CSF leak. Therefore, he underwent a craniotomy and nasal endoscopy, which were performed simultaneously using a galeal flap. The galeal flap was inserted from the middle of the skull base to the sphenoid sinus to cover the bone defects, and the position was adjusted under the guidance of nasal endoscopy. Moreover, intraoperatively, another meningocele with CSF leak was discovered in the cribriform plate and was repaired using abdominal fat. The CSF leak stopped after the second surgery. It is important to be mindful of possible multiple leakage sites when treating cases of idiopathic CSF leakage;moreover, the determination of the leakage sites can be difficult. A repair surgery using a galeal flap is preferable in cases of multiple CSF leakage sites, such as in this case, because it allows for all defects to be covered and repaired simultaneously.

(Background) It has become evident in recent year that aldosterone has a pathogenic role in hypertension, heart failure and renal disease. Elevation of aldosterone occurs in a certain fraction of hemodialysis patients, and the adverse effects of hyperaldosteronism could pose a problem after kidney transplantation. Long-term effects of aldosterone level in renal transplant recipients remain unknown. (Materials and methods) All recipients underwent transplantation between 1996 and 2018 in Niigata university hospital were included in the study. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were retrospectively analyzed in 210 recipients before and after kidney transplantation. (Results) Sixty percent of recipients had higher PRA than normal upper limit before and after transplantation. The use of angiotensin receptor blocker (ARB) or angiotensin-converting-enzyme inhibitor (ACEI) was significantly more frequent in the patients with hyperreninemia than those without one after transplantation. Sixty percent of recipients had higher PAC than normal upper limit before transplantation and it spontaneously decreased to normal level after transplantation in most of them. There was no significant correlation between PAC and blood pressure, recipient age, and renal graft function after transplantation. We divided the patients into two groups, with and without post-transplant hyperaldosteronemia. The patients with post-transplant hyperaldosteronemia (n=29) had higher diastolic blood pressure and less use of renin-angiotensin-aldosterone system (RAAS) inhibitors than those with normal PAC level. (Conclusions) The use of RAAS inhibitors should be considered in post-transplant hyperaldosteronemia patients to control blood pressure and to save their long-term renal graft and heart function.

A 56-year-old man underwent distal pancreatectomy due to pancreatic body carcinoma in 2009, at the age of 46. There had been no sign of metastasis and recurrence until levels of tumor markers began to increase in January 2014. PET scan, CT scan, and other examinations showed a possible carcinoma in the pancreas head. The patient underwent total remnant pancreatectomy. The tumor was located in the uncinate process of the pancreas with infiltration of the portal vein. The pathological diagnosis of the tumor was moderately differentiated adenocarcinoma. The ductal lumen structure was relatively maintained and the cytoplasm was comparatively clear. Since its pathological findings were similar to those observed in 2009, the tumor appeared to be a recurrence of the tumor resected at that time. The patient had received postoperative chemotherapy and remains alive in 2019 without recurrence. While there is evidence that surgical resection for the recurrence of other cancers such as colon cancer may improve patient survival, it remains unclear if surgical resection of recurrence in the remnant pancreas after pancreatectomy of pancreatic cancer is feasible. We report a case with long survival after surgical resection of a pancreatic carcinoma recurrence in the remnant pancreas.