Search

"Oligoastrocytoma" disappeared as of the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System, except where appended with "not otherwise specified (NOS)". However, histopathological and genetic backgrounds of cases with dual features of astrocytoma/oligodendroglioma have been sparsely reported. We encountered a 54-year-old man with right frontal glioma comprising two distinct parts on imaging and histopathological examination: grade 4 astrocytoma with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q; and oligodendroglioma with IDH1-R132H, intact ATRX, p53-negativity and partially deleted 1p/19q. At recurrence, histopathology showed low-grade mixed astrocytic and oligodendroglial features: the former with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q and the latter showing IDH1-R132H, intact ATRX, p53-negativity and 1p/19q codeletion. At second recurrence, histopathology was astrocytoma grade 4 with IDH1-R132H, ATRX loss, p53-positivity and intact 1p/19q. Notably, 1p/19q codeletion was acquired at recurrence and CDKN2A was deleted at second recurrence. These findings suggest insights into tumorigenesis: (1) gliomas with two distinct lineages might mix to produce "oligoastrocytoma"; and (2) 1p/19q codeletion and CDKN2A deletion might be acquired during chemo-radiotherapy. Ultimately, astrocytic and oligodendroglial clones might co-exist developmentally or these two lineages might share a common cell-of-origin, with IDH1-R132H as the shared molecular feature., (© 2022. The Author(s), under exclusive licence to The Japan Society of Brain Tumor Pathology.)

One of the reasons for groove pancreatitis is caused by the leakage of pancreatic juice into the space between the pancreatic head, descending duodenum, and common bile duct. Endoscopic drainage of Santorini's duct (SD) via the minor papilla is reportedly efficacious but can be difficult due to duodenal stenosis. We report Santorini's duct drainage using endoscopic ultrasonography-guided pancreaticogastrostomy (EUS-PGS) for a case of groove pancreatitis with gastric outlet obstruction. Gastric outlet obstruction was improved after 7 months of EUS-PGS with internal drainage through the Santorini's duct/minor papilla. EUS-PGS may be effective for treating groove pancreatitis with duodenal stenosis. This is the first report of groove pancreatitis with duodenal stenosis, the symptoms of which were improved by EUS-PGS., Competing Interests: Isayama H is supported by honoraria from the Fujifilm Corp., Tokyo, Japan., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP), proposed in a recent NIH consensus overview, is a rare precursor entity of malignant peripheral nerve sheath tumor (MPNST) in neurofibromatosis type 1 (NF1) patients. Only one report on imaging findings of ANNUBP is available. Herein, we present the case of a 19-year-old female, diagnosed with a mediastinal tumor by chance, who visited to our hospital. She had café-au-lait spots on her trunk and a past history of resected neurofibroma. Her family also had café-au-lait spots; therefore, an NF1-induced tumor was strongly suspected. MRI revealed a paravertebral mass of 7.5 cm in size consisting of an inner rim with low T2 signal intensity and an outer rim with high T2 intensity, which was similar to a target sign, adjacent to the pulmonary veins; the center of the tumor was well enhanced by gadolinium, and the peripheral region was myxoid and slightly enhanced. FDG-PET showed high FDG uptake, SUVmax of 8.5, although the peripheral region represented low FDG accumulation. CT-guided needle biopsy was repeated because of the suspicion of an MPNST, which resulted in the histopathological diagnosis of ANNUBP. Marginal tumor resection was performed, and the final post-resection histopathological diagnosis was ANNUBP transformed from neurofibroma; the region of ANNUBP lost p16 immunostaining, although it was retained in the peripheral region of the neurofibroma. There has been no recurrence or metastasis 1 year after treatment. In conclusion, ANNUBP could be represented as a well-enhanced homogeneous mass on MRI and a high FDG accumulated region on FDG PET/CT, as seen in MPNST, in NF1 patients., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

There have recently been a few case reports of cutaneous T-cell lymphomas following treatment of atopic dermatitis with dupilumab, which works binding to the interleukin (IL)-4 receptor and inhibiting the JAK/ STAT cascade located downstream of both IL-4 and IL-13. Here, we report the first case of Hodgkin lymphoma (HL) in a patient treated with dupilumab for one year. Based on multiple biopsies, this case was diagnosed as a rare combination of discordant lymphomas of HL and peripheral T-cell lymphoma. As both lymphomas are known to overexpress IL-13, future studies should carefully evaluate the effect of anti-IL-13 therapy. A literature review showed that dermatitis persisted or worsened in all reported lymphoma cases following dupilumab and cutaneous T-cell lymphoma was diagnosed within 2 years of the start of treatment with dupilumab. In these cases, with the addition of our own, the median interval was 12 months, and 31% needed multiple biopsies for diagnosis of lymphomas. Our results demonstrate a need to be alert to potential development of lymphomas associated with the IL-13 and IL-4 pathways in patients with poorly responsive atopic dermatitis receiving dupilumab, and to consider the possibility of composite or discordant lymphomas in diagnosis and treatment of lymphomas., (© 2022. Japanese Society of Hematology.)

Background: Endometriosis is assumed to be involved in ovarian cancer development, which is called endometriosis-associated ovarian cancer (EAOC). Uterine endometrial cells may be the cell of origin of EAOC. Accumulated carcinogenic changes in the uterine endometrial cells may increase the risk of developing EAOC. To further understand the pathogenesis of EAOCs, we focused on the clinicopathological characteristics of EAOCs in endometrial cancer patients with concomitant endometriosis., Methods: We retrospectively reviewed 376 patients who were surgically treated for stage I-III endometrial cancer. Clinicopathological characteristics were compared between patients with and without endometriosis. Furthermore, the incidence of simultaneous endometrial and ovarian cancer (SEOC) and the histological characteristics of SEOC were compared between the two groups., Results: Among 376 patients with endometrial cancer, 51 had concomitant endometriosis. Patients with endometriosis were significantly younger and more frequently had endometrioid G1/G2 tumors than those without endometriosis. The incidence of SEOCs was significantly higher in endometrial cancer patients with endometriosis than those without it (p < 0.0001); notably, 12 of 51 endometrial cancer patients with endometriosis (24%) had SEOCs. All of the ovarian cancers in endometrial cancer patients with endometriosis were endometrioid carcinomas. Moreover, even in those without endometriosis, endometrioid carcinoma was the most common histological type of SEOC., Conclusion: We revealed that endometrial cancer patients with endometriosis had a high probability of SEOC and that endometrioid carcinoma was the most common histological subtype of SEOC regardless of the presence of endometriosis. For patients with endometrial cancer and endometriosis, careful examination of ovarian endometriotic lesions may be important to detect EAOCs., (© 2022. The Author(s).)

Stereotactic frame-based brain tumor biopsy (SFB) is a potent diagnostic tool considering its minimal invasiveness, though its diagnostic power and safety for brainstem lesions remain to be discussed. Here, we aimed to examine the usefulness of SFB for brainstem tumors. Twenty-two patients with brainstem tumors underwent 23 SFBs at our institution during 2002-2021. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including surgery-related complications and the diagnostic value. Seven (32%) tumors were located from the midbrain to the pons, eleven (50%) in the pons only, and four (18%) from the pons to the medulla oblongata. The target lesions were in the middle cerebellar peduncles in sixteen procedures (70%), the cerebellum in four (17%), the inferior cerebellar peduncles in two (9%), and the superior cerebellar peduncles in one (4%). A definitive diagnosis was made in 21 patients (95%) at the first SFB. The diagnoses were glioma in seventeen (77%) cases, primary central nervous system lymphoma in four (18%), and a metastatic brain tumor in one (5%). The postoperative complications (cranial nerve palsy in three [13%] cases, ataxia in one [4%]) were all transient. SFB for brainstem tumors yields a high diagnostic rate with a low risk of morbidity.

NF2 alteration is the most commonly-found genetic abnormality in meningiomas and is known to initiate events for aggressive-type meningiomas. Whereas the prognosis of meningiomas differs depending on their epigenomic/transcriptomic profile, the effect of NF2 alteration on the prognosis of benign meningiomas is not fully elucidated. This study aimed to probe the importance of NF2 alteration in prognosis of WHO grade I meningiomas. A long-term retrospective follow-up (5.3 ± 4.5 years) study involving 281 consecutive WHO grade I meningioma patients was performed. We assessed tumour recurrence in correlation with extent of resection (EOR), histopathological findings, tumour location, and NF2 alteration. "NF2 meningioma" was defined as meningiomas with presence of NF2 mutation and/or 22q loss. Overall, NF2 meningioma per se was not a predictor of prognosis in the whole cohort; however, it was a predictor of recurrence in supratentorial meningiomas, together with EOR and Ki-67. In a striking contrast, NF2 meningioma showed a better prognosis than non-NF2 meningioma in infratentorial lesion. Supratentorial NF2 meningiomas had higher Ki-67 and forkhead box protein M1 expression than those of others, possibly explaining the worse prognosis in this subtype. The combination of NF2 alteration, high Ki-67 and supratentorial location defines subgroup with the worst prognosis among WHO grade I meningiomas. Clinical connotation of NF2 alteration in terms of prognosis of WHO grade I meningioma differs in an opposite way between supratentorial and infratentorial tumors. Integrated anatomical, histopathological, and genomic classifications will provide the best follow-up schedule and proactive measures., (© 2022. The Author(s).)

Background: Solitary plasmacytoma is a localized lesion comprising monoclonal neoplastic proliferation of plasma cells. This disease is rarely encountered and few reports have described primary intracranial solitary plasmacytoma (PISP)., Case Description: We report a case of PISP that presented initially as status epilepticus and exhibited massive intratumoral hemorrhage at the subcortical area. To the best of our knowledge, this is the first recorded presentation of this pathology in this manner. Following evacuation of the hematoma and decompressive craniectomy, the patient underwent radiation therapy and showed no sign of tumor recurrence at 3 years after diagnosis., Conclusion: This case reveals that PISP can present as subcortical intraparenchymal hemorrhage. It should be emphasized that the precise diagnosis of this disease is of utmost importance, because solitary plasmacytoma without a background of multiple myeloma responds well to radiation therapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Background: Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals., Case Presentation: We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period., Conclusions: Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus., (© 2022. The Author(s).)

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words)., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We encountered HPV6-positive cervical papillary squamous cancer (PSCC) that was difficult to diagnose. The case was initially diagnosed and treated for condyloma. To the best of our knowledge, this is the first report of HPV6 infection in PSCC., Competing Interests: We have no conflicts of interest to declare regarding this case., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The emergency declaration (ED) associated with the coronavirus disease-2019 (COVID-19) pandemic in Japan had a major effect on the management of gastrointestinal endoscopy. We retrospectively compared the number of pancreaticobiliary endoscopies and newly diagnosed pancreaticobiliary cancers before (1 April 2018 to 6 April 2020), during (7 April to 25 May 2020), and after the ED (26 May to 31 July). Multiple comparisons of the three groups were performed with respect to the presence or absence of symptoms and clinical disease stage. There were no significant differences among the three groups (Before/During/After the ED) in the mean number of diagnoses of pancreatic cancer and biliary cancer per month in each period (8.0/7.5/7.5 cases, p = 0.5, and 4.0/3.5/3.0 cases, p = 0.9, respectively). There were no significant differences among the three groups in the number of pancreaticobiliary endoscopies (EUS: endoscopic ultrasonography/ERCP: endoscopic retrograde cholangiopancreatography) per month (67.8/62.5/69.0 cases, p = 0.7 and 89.8/51.5/86.0 cases, p = 0.06, respectively), whereas the number of EUS cases decreased by 42.7% between before and during the ED. There were no significant differences among the three groups in the presence or absence of symptoms at diagnosis or clinical disease stage. There was no significant reduction in the newly diagnosed pancreaticobiliary cancer, even during the ED. The number of ERCP cases was not significantly reduced as a result of urgent procedures, but the number of EUS cases was significantly reduced.

A decrease in carbohydrate antigen (CA) 19-9 levels has been proposed as a prognostic marker for survival and recurrence in patients with pancreatic cancer. We evaluated the association between duration of reduced CA 19-9 levels during 6 months after treatment and long-term survival for 79 patients with unresectable locally advanced pancreatic cancer (LAPC). We calculated the differences between pretreatment and monthly CA19-9 levels. We categorized 71 patients with decreases in CA19-9 levels into three groups based on the duration of these reduced levels (>2, >3, and >4 months). The cut-off level for long-term (more than 2 years) survival was identified as a 44% reduction from the baseline, using a ROC curve. A reduction duration >2 months was not associated with overall survival ( p = 0.1), while >3 months was significantly associated with survival ( p =.04). In multivariate analysis, a reduction duration >3 months predicted a good long-term prognosis (odds ratio = 5.75; 95% confidence interval = 1.47-22.36; p < 0.01). In patients with unresectable LAPC, the duration of reduced CA19-9 levels for more than 3 months, rather than the rate of reduction in CA19-9 levels, during 6 months after treatment was significantly associated with good prognosis.

Purpose: This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ., Methods: The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline., Results: Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024)., Conclusion: The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

Aberrant DNA methylation in the BRCA1 promoter region causes epigenetic silencing of BRCA1 gene expression, which is critical for breast cancer development. However, how BRCA1 promoter methylation status alters histological features remains poorly understood. Here, we investigated the possibility to predict BRCA1 promoter methylation status based on the morphological and immunohistochemical features of triple-negative breast cancers (TNBCs). The morphological features of 53 TNBCs were evaluated with hematoxylin-eosin staining, with immunohistochemical staining of BRCA1, androgen receptor, p53, cytokeratin 5/6, and epidermal growth factor receptor. BRCA1 promoter methylation status was used to distinguish BRCA1 promoter-methylated tumors (BPMTs) from BRCA1 promoter-unmethylated tumors (BPUTs) dependent on pathological characteristics. BPMTs comprised approximately 26% of the TNBCs. Immunohistochemical analysis found that BRCA1 protein expression was significantly lower in BPMT compared with BPUT (p = 0.016). Morphologically, BPMTs were associated with high mitotic index (p = 0.017), pushing margin (p = 0.017), a circumscribed growth pattern (p = 0.014), and a syncytial growth pattern (p = 0.034) compared with BPUTs. We then assessed the potential of predicting BRCA1 promoter methylation status by using published score systems based on these morphological characteristics. A receiver operating characteristic analysis showed an area under the curve of 0.80. This study found that BRCA1 promoter methylation status could be derived from morphological features and lower BRCA1 expression of TNBCs, which may help identify suitable cases for target treatment with PARP inhibitors., (© 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Postmortem computed tomography (CT) is currently a well-known procedure and helps in postmortem investigations. In this case report, we report a unique postmortem CT finding: delayed cerebral enhancement associated with the antemortem infusion of contrast medium. A 72-year-old female lost consciousness at a restaurant and was taken to a hospital in an ambulance. Despite resuscitation efforts, she died of hypoxic-ischemic encephalopathy caused by cardiac arrest. About 6 h before her death, she underwent enhanced antemortem CT of the head. No abnormal enhancement was observed in the cerebral parenchyma. Then, 11 h after her death, she underwent unenhanced postmortem CT, which showed bilateral hyperdense caudate nucleus and putamina, due to residual iodinated contrast medium, in addition to other characteristic findings of hypoxic-ischemic encephalopathy. The mechanism underlying this phenomenon could be the destruction of the blood-brain barrier, and/or selective vulnerability, due to hypoxic-ischemic changes in the gray matter. Enhancement of basal ganglia on postmortem CT due to antemortem infusion of iodinated contrast medium might suggest hypoxic-ischemic encephalopathy, which should be noted in postmortem CT interpretations., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background and Aims: The goals of the management of benign biliary stricture (BBS) are to relieve symptoms and resolve short-/long-term stricture. We performed fully covered self-expandable metallic stent (hereafter, FCSEMS) placement for BBS using various methods and investigated the treatment outcomes and adverse events (AEs)., Methods: We retrospectively studied patients who underwent FCSEMS placement for refractory BBS through various approaches between January 2017 and February 2020. FCSEMS were placed for 6 months, and an additional FCSEMS was placed if the stricture had not improved. Technical success rate, stricture resolution rate, and AE were measured., Results: A total of 26 patients with BBSs that were difficult to manage with plastic stents were included. The mean overall follow-up period was 43.3 ± 30.7 months. The cause of stricture was postoperative (46%), inflammatory (31%), and chronic pancreatitis (23%). There were four insertion methods: endoscopic with duodenoscopy, with enteroscopy, EUS-guided transmural, and percutaneous transhepatic. The technical success rate was 100%, without any AE. Stricture resolution was obtained in 19 (83%) of 23 cases, except for three cases of death due to other causes. Stent migration and cholangitis occurred in 23% and 6.3%, respectively. Stent fracture occurred in two cases in which FCSEMSs were placed for more than 6 months (7.2 and 10.3 months)., Conclusion: FCSEMS placement for refractory BBS via various insertion routes was feasible and effective. FCSEMSs should be exchanged every 6 months until stricture resolution because of stent durability. Further prospective study for confirmation is required, particularly regarding EUS-guided FCSEMS placement.

There have been only a limited number of reports on primary adult T cell lymphoma/leukemia (ATL) in the bone. This is a case report of a 75-year-old patient initially reporting multiple bone pains that were attributed to osteolytic ATL. The patient developed spontaneous chest/back pain and visited a local hospital. Laboratory tests showed high levels of alkaline phosphatase (ALP), and computed tomography (CT) revealed skeletal lesions with osteolysis. Although multiple myeloma was initially suspected, the results of bone marrow aspiration and bone biopsy were inconsistent. After he was referred to our hospital, mild hypercalcemia (10.4 mg/dL) with low-normal intact parathyroid hormone (PTH) (27 pg/mL), low parathyroid hormone-related protein (PTHrP), and elevated 1,25-dihydroxy vitamin D (1,25OH 2 D) levels (136 pg/mL) narrowed the differential diagnosis down to lymphomatous and granulomatous diseases, and then, the high serum soluble IL-2 receptor (3,450 U/mL) and the flower cells recognized in the peripheral blood sample suggested the involvement of ATL. Finally, the reevaluation of the iliac bone biopsy sample led us to the histological diagnosis of ATL infiltration in the bone. The subsequent two courses of chemotherapy in addition to denosumab resulted in an objective partial metabolic response indicated in 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Although very rare, the bone involvement of ATL could be used for the differential diagnosis for local osteolytic bone pain in addition to multiple myeloma and metastatic bone diseases.

Lewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson's disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by non-motor symptoms (NMSs) including gastrointestinal dysfunctions such as constipation. Its relationship to Lewy body-related α-synucleinopathy (Lewy pathology) of the enteric nervous system (ENS) is attracting attention because it can precede the motor symptoms. To clarify the role of ENS Lewy pathology in disease progression, we performed a clinicopathological study using the Brain Bank for Aging Research in Japan. Five-hundred and eighteen cases were enrolled in the study. Lewy pathology of the CNS and PNS, including the lower esophagus as a representative of the ENS, was examined via autopsy findings. Results showed that one-third of older people (178 cases, 34%) exhibited Lewy pathology, of which 78 cases (43.8%) exhibited the pathology in the esophagus. In the esophageal wall, Auerbach's plexus (41.6%) was most susceptible to the pathology, followed by the adventitia (33.1%) and Meissner's plexus (14.6%). Lewy pathology of the esophagus was significantly associated with autonomic failures such as constipation (p < 0.0001) and among PNS regions, correlated the most with LBD progression (r = 0.95, p < 0.05). These findings suggest that the propagation of esophageal Lewy pathology is a predictive factor of LBD.

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics., Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy., (© 2020 The Authos(s) Published by S. Karger AG, Basel.)

Background: Ganglion cysts mostly occur in the knuckles and wrists, but they rarely present in the odontoid process and can cause neurological symptoms by compressing the spinal cord. They are mostly localized in the epidural space, but may very rarely appear in the intradural space. There are no reports of cases of intradural ganglion cyst involving syringobulbia., Case Description: We report the presentation and management of 2 cases of an intradural ganglion cyst of the odontoid process. Several treatment options for ganglion cysts of the odontoid process have been reported, such as rest and use of a neck collar, posterior decompression and fusion, and transoral anterior decompression. Because our 2 cases progressed rapidly and had severe neurological symptoms, surgical treatment was performed for rapid decompression and definitive pathological diagnosis. The mass was resected as much as possible using the lateral occipital fossa approach, and the operation was completed without dissection of the brain stem or manipulation of the syringobulbia. Postoperatively, neurological symptoms promptly improved, and the syringobulbia reduced., Conclusions: For intradural ganglion cysts with syringobulbia, we suggest relief of the compression by resection of the mass and treatment of the syringobulbia in 2 stages, if necessary, to avoid the risk of damage to the brainstem., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the threshold of serum memantine for prevention of spinal cord injury (SCI) in a rabbit paraplegic model., Methods: Forty-two New Zealand white rabbits were divided into 7 groups. Preoperatively, oral memantine was given starting from 60 mg OD for 7 days in the initial group, then reducing the dose and/or duration to 60 mg OD for 5 days, 30 mg OD for 5 days, 30 mg OD for 3 days, 15 mg OD for 3 days, 30 mg single dose, and 60 mg single dose, in subsequent 6 groups. A paraplegic model was created by clamping both infrarenal aorta and inferior vena cava (IVC) for 45 min. Motor evoked potentials (MEPs), modified Tarlov score (0-5), serum memantine concentration, and histopathology of the spinal cord were evaluated., Results: Half of all rabbits (21/42) showed spinal protection. Receiver operating characteristic (ROC) curve analysis showed serum level of 4.5 ng/ml as a cutoff value for spinal protection (sensitivity 86%, specificity 62%, area under the curve (AUC) 0.785, P  = .002). Sixteen rabbits had serum level ≥ 4.5 ng/ml (group A), with 26 rabbits having < 4.5 ng/ml (group B). Further comparison was done between groups A and B. The mean modified Tarlov score at 6, 24, 48, and 72 h was 4.5 ± 0.9 and 2.4 ± 1.6, in groups A and B, respectively ( P  < .001). The modified Tarlov score showed positive correlation with serum memantine level (Spearman's rho = 0.618, P  = .01). Results of MEP and histopathology were significantly better for group A., Conclusions: We showed that memantine is protective against SCI at serum levels ≥ 4.5 ng/ml in a rabbit model; thus, it can be a potential adjunct for spinal protection during thoracic/thoracoabdominal aortic surgeries., Competing Interests: Conflict of interestH Suzuki received some grant support from Daiichi Sankyo Co. Ltd. for measurement of serum level of memantine., (© Indian Association of Cardiovascular-Thoracic Surgeons 2020.)

Background: With more prevalent gastroesophageal reflux disease comes increased cases of Barrett's esophagus and esophageal adenocarcinoma. Image-enhanced endoscopy using linked-color imaging (LCI) differentiates between mucosal colors. We compared LCI, white light imaging (WLI), and blue LASER imaging (BLI) in diagnosing reflux esophagitis (RE)., Methods: Consecutive RE patients (modified Los Angeles [LA] classification system) who underwent esophagogastroduodenoscopy using WLI, LCI, and BLI between April 2017 and March 2019 were selected retrospectively. Ten endoscopists compared WLI with LCI or BLI using 142 images from 142 patients. Visibility changes were scored by endoscopists as follows: 5, improved; 4, somewhat improved; 3, equivalent; 2, somewhat decreased; and 1, decreased. For total scores, 40 points was considered improved visibility, 21-39 points was comparable to white light, and < 20 points equaled decreased visibility. Inter- and intra-rater reliabilities (Intra-class Correlation Coefficient [ICC]) were also evaluated. Images showing color differences (ΔE*) and L* a* b* color values in RE and adjacent esophageal mucosae were assessed using CIELAB, a color space system., Results: The mean age of patients was 67.1 years (range: 27-89; 63 males, 79 females). RE LA grades observed included 52 M, 52 A, 24 B, 11 C, and 3 D. Compared with WLI, all RE cases showed improved visibility: 28.2% (40/142), LA grade M: 19.2% (10/52), LA grade A: 34.6% (18/52), LA grade B: 37.5% (9/24), LA grade C: 27.3% (3/11), and LA grade D: 0% (0/3) in LCI, and for all RE cases: 0% in BLI. LCI was not associated with decreased visibility. The LCI inter-rater reliability was "moderate" for LA grade M and "substantial" for erosive RE. The LCI intra-rater reliability was "moderate-substantial" for trainees and experts. Color differences were WLI: 12.3, LCI: 22.7 in LA grade M; and WLI: 18.2, LCI: 31.9 in erosive RE (P < 0.001 for WLI vs. LCI)., Conclusion: LCI versus WLI and BLI led to improved visibility for RE after subjective and objective evaluations. Visibility and the ICC for minimal change esophagitis were lower than for erosive RE for LCI. With LCI, RE images contrasting better with the surrounding esophageal mucosa were more clearly viewed.

We report a case of atypical type A thymoma variant manifesting polymyalgia rheumatica. A 68-year-old man underwent extended thymectomy with concomitant resection of the pericardium and right lung for an anterior mediastinal tumor. He was diagnosed with atypical type A thymoma variant with pericardial invasion. He developed pain in his extremities 1 year and 2 months after surgery. Detailed examinations resulted in a diagnosis of polymyalgia rheumatica and bone metastasis of thymoma. He was treated with oral prednisolone for polymyalgia rheumatica. His symptoms and bone lesion have been stable up to the present time of 3.5 years post-surgery., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)-positive ALCL have been reported so far, with no reported cases of a small cell variant., Case Description: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE)., Conclusions: In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We aimed to investigate the clinical and magnetic resonance imaging (MRI) characteristics of uterine adenomyosis, in which there is an extensive area of high signal intensity in the myometrium on T2-weighted MRI., Methods: This retrospective radiographic study reviewed a case series of six patients (mean age, 36 years) with adenomyosis. These patients were selected because, unlike in classical adenomyosis, T2-weighted images showed a larger area of high signal intensity than that of low signal intensity in the myometrium. The morphology of the myometrial lesions, patterns of contrast enhancement (n=4), intramyometrial hemorrhaging, diffusion restriction (n=5), endometrial lesions, and imaging findings after treatment (n=3) were evaluated on MRI., Results: The patients' clinical symptoms included vaginal bleeding and severe anemia. Four were administered hormonal therapy, one underwent hysterectomy, and one underwent enucleation. On T2-weighted images, all showed endometrial thickening and a high signal intensity area in the myometrium that was divided up by a mesh of low signal intensity bands, with an appearance reminiscent of a fish caught in a net. Other findings included gradual centripetal enhancement with contrast defects in multicystic areas (4/4), an intramyometrial hemorrhage (1/6), and increased diffusion (5/5). Following hormonal therapy, the uteruses decreased in size and were similar to those of classical adenomyosis on MRI (3/3). The lesions were diagnosed as adenomyosis with a proliferation of adenomyotic glandular tissue and a proliferative endometrial polyp., Conclusion: This case series suggests that there is a subgroup of uterine adenomyosis that shows a characteristic "fish-in-a-net" appearance on T2-weighted images.

To evaluate the utility of unenhanced postmortem computed tomography (PMCT) for the investigation of in-hospital nontraumatic death in children up to 3 years of age.This study included the cadavers of children who died from intrinsic diseases before 3 years of age. The major underlying disease and the main organ-disease systems associated with the immediate causes of death were determined by clinical evaluation, PMCT, and autopsy, which were used as a reference standard. The rates of concordance between the former two methods and autopsy were calculated for all cases.In total, 22 cadavers (12 male and 10 female; mean age, 6.1 ± 8.2 months) were included. The rates of concordance between clinical evaluation/PMCT and autopsy for diagnosis of the major underlying disease and main organ-disease systems associated with the immediate causes of death were 100%/36% (P = .0015) and 59%/41% (P = .37), respectively. In cases where the respiratory system was associated with the immediate cause of death, PMCT showed greater diagnostic sensitivity (90%) than did clinical evaluation (20%). In contrast, the diagnostic sensitivity of PMCT was lower than that of clinical evaluation in cases involving disorders of the cardiac system and multiple organ systems (0% vs 100% for both).The findings of this study suggest that the use of unenhanced PMCT with clinical evaluation can result in improved detection of the immediate cause of death in select cases of in-hospital nontraumatic death before 3 years of age.

Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm 3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems.

What Is Known and Objective: Daptomycin-induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (C trough ; breakpoint of 24.3 μg/mL). However, even with high-dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of C trough above 24.3 μg/mL. Therefore, we questioned the clinical significance of C trough levels of 24.3 μg/mL. In this study, we retrospectively evaluated the significance of C trough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records., Methods: Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including C trough and peak (C peak ), were measured by high-performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients' characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system., Results and Discussion: A total of 52 therapeutic cases for 46 patients were identified; of these, C trough and C peak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19-88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a C trough of above 24.3 μg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured C trough (of 10.9 μg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured C trough levels; these were 8.6 and 8.1 μg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited C trough levels lower than 24.3 μg/mL. In this study, two patients receiving high-dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed C trough levels similar to patients who received doses of daptomycin < 9 mg/kg., What Is New and Conclusions: The safety of daptomycin treatment was suggested in this study. C trough level of 24.3 μg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher C trough levels than 24.3 μg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high-dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved., (© 2019 John Wiley & Sons Ltd.)

Background: While prior studies reporting de novo arteriovenous malformations after birth are not uncommon, reports of ectopic recurrence of arteriovenous malformation after radiotherapy are scarce., Case Description: An 8-year-old girl with a ruptured cerebellar arteriovenous malformation was treated with stereotactic radiosurgery. The nidus was completely obliterated 17 months after stereotactic radiosurgery; however, 20 years later she had a rupture of a recurrent nidus that occurred adjacent to the original nidus, accompanied by a radiation-induced cyst. Surgical resection was performed, and subsequent pathologic examination revealed 2 different compartments: a typical nidus and a postirradiated degenerated nidus with an encapsulated hematoma. Immunohistochemical stains showed increased expression of Ki-67 and decreased expression of endoglin in endothelial cells in the recurrent nidus., Conclusions: Depletion in endoglin may lead to the formation of vessel malformations in the presence of angiogenic stimuli. This case serves as a strong reminder of the importance of long-term follow-up after stereotactic radiosurgery, especially for pediatric cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Uterine adenomyosis is a benign disorder that often co-occurs with endometriosis and/or leiomyoma, and impairs quality of life. The genomic features of adenomyosis are unknown. Here we apply next-generation sequencing to adenomyosis (70 individuals and 192 multi-regional samples), as well as co-occurring leiomyoma and endometriosis, and find recurring KRAS mutations in 26/70 (37.1%) of adenomyosis cases. Multi-regional sequencing reveals oligoclonality in adenomyosis, with some mutations also detected in normal endometrium and/or co-occurring endometriosis. KRAS mutations are more frequent in cases of adenomyosis with co-occurring endometriosis, low progesterone receptor (PR) expression, or progestin (dienogest; DNG) pretreatment. DNG's anti-proliferative effect is diminished via epigenetic silencing of PR in immortalized cells with mutant KRAS. Our genomic analyses suggest that adenomyotic lesions frequently contain KRAS mutations that may reduce DNG efficacy, and that adenomyosis and endometriosis may share molecular etiology, explaining their co-occurrence. These findings could lead to genetically guided therapy and/or relapse risk assessment after uterine-sparing surgery.

We report a case of giant solitary fibrous tumor( SFT) of the pleura postoperatively complicated with probable reexpansion pulmonary edema and atrial fibrillation. An 85-year-old woman was diagnosed to have a 13 cm sized intrathoracic neoplasm. Upon thoracotomy, the tumor was found to pedunculate from the right lung with no direct invasion to the surrounding structures. Complete resection of the tumor and expansion of the right lung was obtained. Histopathology revealed the tumor was a benign SFT arising from the visceral pleura. An infiltrative shadow in the right lower lung field soon after the surgery suggested a reexpansion pulmonary edema, which eventually recovered within a week. The patient suffered from a refractory atrial fibrillation that led to a congestive heart failure requiring an intensive medical treatment. It is emphasized that thoracic surgeons should be aware of these postoperative complications in treating such a case like this.

Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.

Glomeruloid hemangioma is a rare cutaneous lesion that has been considered as a specific cutaneous marker of POEMS syndrome. Herein, we present the first case of glomeruloid hemangioma associated with TAFRO syndrome, a unique variant of idiopathic multicentric Castleman disease. The patient is a 74-year-old woman presented with fever, cervical lymphadenopathy, thrombocytopenia, bilateral pleural effusions and ascites. Biopsy of the lymph node revealed multicentric Castleman disease-like histology and bone marrow biopsy showed mild reticulin fibrosis, consistent with TAFRO syndrome. The patient simultaneously developed multiple skin lesions, which were histologically confirmed as glomeruloid hemangioma. Multiple immunoglobulin-positive granules were detected in the proliferating endothelial cells. Glomeruloid hemangioma is not specific to POEMS syndrome and can be a manifestation of TAFRO syndrome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with marked variety in its clinical manifestations. While characteristic neuroimaging and skin biopsy findings are important clues to the diagnosis, autopsy studies are still important for confirming the exact disease features. We herein report the case of a patient who received an antemortem diagnosis of familial NIID with dementia-dominant phenotype that was later confirmed by an autopsy. Our report is the first to document a case of autopsy-confirmed NIID involving both cognitive impairment and sensorimotor neuropathy.

In the female genital tract, extrauterine leiomyomas such as those that arise in the ovary and paraovarian/paratubal regions are rare. Currently, little is known about the background genetic changes in such adnexal leiomyomas. Recent studies have found that the MED12 mutation is common in uterine leiomyomas, which suggests that such mutations may play an oncogenic role in smooth muscle neoplasms in females. Herein, we examined a series of ovarian and other adnexal leiomyomas in terms of MED12 mutational status to investigate possible MED12 involvement in the pathogenesis of extrauterine smooth muscle tumors. We evaluated 10 cases of adnexal leiomyomas (5 ovarian, 3 paraovarian, and 2 paratubal) and 49 cases of ovarian sex cord-stromal tumors as controls. We performed polymerase chain reaction followed by direct sequencing of exon 2 of MED12, and immunohistochemical staining for smooth muscle actin and desmin. We identified somatic MED12 mutations in 90% (9/10) of the adnexal leiomyomas. None of the sex cord-stromal tumors in the control group harbored MED12 mutations. Diffuse immunoreactivity for both smooth muscle actin and desmin was characteristic of adnexal leiomyomas only. Thus, we conclude that ovarian leiomyomas are distinct from sex cord-stromal tumors. MED12 mutations are key molecular features of ovarian and other adnexal leiomyomas. We speculate that the pathogenesis of adnexal leiomyoma is similar to that of its uterine counterpart., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification. The strategic integration of optimal chemical cocktails provided a series of CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) protocols, which efficiently clear mouse organs, mouse body including bone, and even large primate and human tissues. The updated CUBIC protocols are scalable and reproducible, and they enable three-dimensional imaging of the mammalian body and large primate and human tissues. This strategy represents a future paradigm for the rational design of hydrophilic clearing cocktails that can be used for large tissues., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Direct-acting antivirals (DAAs) are known to improve tolerability and have higher efficacy and shorter treatment durations compared with conventional interferon (IFN)-based treatments for hepatitis C virus (HCV) infection. Management of drug interactions and maintenance of patient adherence are important to achieve adequate therapeutic effects, sustained virological response (SVR). In order to maximize the benefits of oral DAA therapy, we established an ambulatory care pharmacy practice, a model of integrated collaboration between physicians and pharmacists, for patients receiving IFN-free DAA therapy. In this study, we evaluated pharmaceutical intervention for patients visiting the ambulatory care pharmacy practice., Methods: HCV-infected outpatients who visited our ambulatory care pharmacy practice between September 2014 and May 2017 were eligible for inclusion in the study. When IFN-free DAAs were first prescribed, the physicians recommended all patients to visit the ambulatory care pharmacy practice after their clinical examination. Subsequently, at the second visit or later, the patients visited the pharmacy service before the physician's examination. The primary endpoint was SVR, defined as HCV RNA below the lower limit of quantification after the completion of treatment. We also evaluated the adherence rate to DAAs, suggestions to the physicians by the pharmacists, and questions from the patients. All data were obtained retrospectively using an electronic medical record system., Results: Among the 401 study subjects, 386 patients completed the IFN-free DAA therapy. A total of 365 patients have reached 12 or 24 weeks after completing the treatment. The overall SVR rate was 98.1% (358/365). The proportion of patients with adherence ≥90% was 99.3% (398/401). Two-hundred and sixty-seven (84%) among 318 suggestions of prescription made by the pharmacists mainly to manage the adverse events were accepted by the physicians. The pharmacists received and answered 1072 questions on DAA therapy from the patients., Conclusions: This study indicates that the pharmaceutical intervention may contribute to enhanced adherence to DAAs and higher SVR rates in comparison with previous reports. This study also demonstrates that collaboration between physicians and pharmacists in an ambulatory setting provides favorable outcomes for patients receiving IFN-free DAAs., Competing Interests: This study was approved by the Institutional Review Board of Kobe City Medical Center General Hospital and the Board waived the need for patients’ consent (No. zn170408).The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Pancreatic masses consisting of lipomatous components clinically include lipoma, liposarcoma, lipomatous pseudohypertrophy of the pancreas, fat-containing neoplasms such as perivascular epithelioid cell tumor, and malignant neoplasm with lipoid degeneration. We present pancreatic lipomatous hamartoma, which has not been reported hitherto. A solid pancreatic mass was detected from a computed tomographic scan check-up in each of 3 cases of Japanese men. Macroscopically, well-demarcated solid lipomatous masses were detected at the uncus, body, and tail of the pancreas, respectively. Microscopically, the masses predominantly consisted of mature adipocytes with no atypia, but contained characteristics components of pancreatic hamartoma, such as small ducts, a well-preserved acinar structure, and/or fibrous stroma. On the basis of the unique features, lack of islets and absence of periductal elastic fibers, these tumors are a distinct variant of pancreatic hamartoma. Furthermore, high-mobility group AT-hook 2 expression in the fibro-adipocytes of this tumor indicated that these cells are an integral component of the pancreatic lipomatous hamartoma. Consequently, the unique tumors described herein are pancreatic lipomatous hamartoma, which must be discriminated from other lipomatous lesions of the pancreas.

Objectives: Although lymphovascular space invasion is a prognostic factor for the recurrence of resectable endometrial cancer, the differential impacts of lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) on the recurrence of endometrial cancer are poorly described. We investigated the prognostic significance of LVI and BVI on the recurrence of endometrial cancer and their association with patterns of recurrence., Methods: We retrospectively reviewed 376 patients with stage I to III endometrial cancer who underwent surgery with curative intent at our institution between 2007 and 2015. The associations of the presence of lymphovascular space invasion or LVI and BVI with recurrence-free survival and patterns of recurrence were evaluated., Results: Lymphovascular space invasion positivity was an independent prognostic factor for recurrence-free survival (hazards ratio [HR], 3.070; 95% confidence interval [CI], 1.404-6.824; P = 0.0048). However, when categorized by LVI versus BVI, the latter was a strong independent prognostic factor (HR, 2.697; CI, 1.288-5.798; P = 0.0081), whereas the former was not (HR, 1.740; CI, 0.795-3.721; P = 0.1637). Hematogenous metastasis was the most prevalent form of recurrence in endometrial cancer (24 [50%] of all 48 recurrent cases). Notably, 17 (19.5%) of 87 patients with BVI developed hematogenous metastases, compared with 7 (2.4%) of 289 without BVI (χ test, P < 0.0001)., Conclusions: Blood vessel invasion rather than LVI was a strong predictor of postoperative recurrence in stage I to III endometrial cancer, probably due to its predisposition to hematogenous metastases.

Background: Cholesterol crystal embolism (CCE) is caused by small crystals of cholesterol dispersed from atherosclerotic plaques of the aorta. There is an increasing interest in CCE because of the increased use of endovascular treatments. Here, we report a rare case of intestinal stenosis caused by CCE after functional end-to-end anastomosis (FEEA). To our knowledge, this is the first report of CCE causing such an anastomotic stenosis., Case Presentation: A 77-year-old male patient underwent laparoscopy-assisted low anterior resection and protective ileostomy for rectal carcinoid tumor. He was admitted to our hospital with ileus 1 year after stoma closure. Eosinophils and creatine kinase level were slightly elevated. Computed tomography revealed a stricture with thickened intestinal wall just distal to the anastomosis site of the ileostomy. The wall of the descending aorta appeared shaggy due to thrombosis. The patient underwent laparoscopic small-bowel resection because ileus reoccurred after any oral intake. Histopathological findings of the resected specimen showed fibrotic changes distal to the anastomosis site, and needle-shaped cholesterol embolus was observed in the submucosal layer. Thus, the stenosis was considered to be caused by CCE., Conclusion: This appears to be the first published report of stenosis due to CCE at such an anastomotic site. Intestinal CCE is difficult to diagnose preoperatively and is associated with poor prognosis. If eosinophilia is present or shaggy aorta is observed, CCE should be suspected to make correct diagnosis and prevent recurrence of CCE.

Although an increasing number of cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have been reported, there are few pathological reports, and no clear consensus has been established. Oligodendroglia or oligodendroglia-like cells (OLCs) have recently attracted attention in epilepsy studies. Here, we report the clinical and pathological findings of a 40-year-old male TLE patient with AE and hippocampal sclerosis, in whom histopathological study demonstrated remarkable clustering of OLCs around the uncus. The patient began to have refractory seizures at the age of 14, and preoperative MRI revealed left amygdala enlargement and left hippocampal atrophy. Other examinations were consistent with left mesial temporal epileptogenicity. He underwent surgical resection and achieved seizure freedom. Histopathological study of the amygdala showed swollen neurons with relatively large bodies and thick neurites, accompanied by vacuolar degeneration in the background. Additionally, there were marked clusters of OLCs with round nuclei and densely stained chromatin around the uncus. The OLCs were Olig2-positive. In the hippocampus, severe cell loss in CA1 and granule cell dispersion in the dentate gyrus were found. These findings may provide some insights for further pathological investigations of TLE with non-neoplastic AE., (© 2017 Japanese Society of Neuropathology.)

A 16-year-old boy with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (HLH) underwent allogeneic hematopoietic stem cell transplantation after conditioning with fludarabine, melphalan, total body irradiation, and rabbit antithymocyte globulin (ATG). A severe, persistent infusion reaction occurred after the initial administration of ATG. Investigations showed a rapid increase in the levels of liver enzymes and ferritin, and the reactivation of HLH was confirmed by marked hemophagocytosis in the bone marrow. Treatment with pulse glucocorticoid therapy resulted in the improvement of HLH. This is the first case of HLH reactivation triggered by ATG. Physicians should therefore be cautious of HLH reactivation, especially when a severe and prolonged infusion reaction occurs.

Although high-resolution three-dimensional imaging of endoscopically resected gastrointestinal specimens can help elucidating morphological features of gastrointestinal mucosa or tumor, there are no established methods to achieve this without breaking specimens apart. We evaluated the utility of transparency-enhancing technology for three-dimensional assessment of gastrointestinal mucosa in porcine models. Esophagus, stomach, and colon mucosa samples obtained from a sacrificed swine were formalin-fixed and paraffin-embedded, and subsequently deparaffinized for analysis. The samples were fluorescently stained, optically cleared using transparency-enhancing technology: ilLUmination of Cleared organs to IDentify target molecules method (LUCID), and visualized using laser scanning microscopy. After observation, all specimens were paraffin-embedded again and evaluated by conventional histopathological assessment to measure the impact of transparency-enhancing procedures. As a result, microscopic observation revealed horizontal section views of mucosa at deeper levels and enabled the three-dimensional image reconstruction of glandular and vascular structures. Besides, paraffin-embedded specimens after transparency-enhancing procedures were all assessed appropriately by conventional histopathological staining. These results suggest that transparency-enhancing technology may be feasible for clinical application and enable the three-dimensional structural analysis of endoscopic resected specimen non-destructively. Although there remain many limitations or problems to be solved, this promising technology might represent a novel histopathological method for evaluating gastrointestinal cancers., (© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: The Currarino triad is a rare hereditary syndrome comprising anorectal malformation, sacral bony defect, and presacral mass. Most of the patients are diagnosed during infancy., Case Presentation: A 44-year-old man was diagnosed with Currarino triad, with a huge presacral teratoma and meningocele. One-stage surgery via posterior approach was successful., Conclusions: Treatment of the presacral mass in the Currarino triad, diagnosed in adulthood, is challenging. Multidisciplinary management and detailed planning before surgery are important for a satisfactory outcome.

Background: A dry powder inhaled formulation is used for the anti-influenza drug laninamivir octanoate hydrate (laninamivir). Although two successive inhalations (puffs) are recommended to minimize residual amounts of active ingredients, previous reports suggest that pediatric patients with low peak inspiratory flow are unable to inhale the active ingredient adequately. In the present study, we prospectively investigated the appropriate number of repeated inhalations of laninamivir dry powder and factors influencing the residual amount of ingredients in pediatric patients with influenza., Methods: The study enrolled 64 patients receiving laninamivir dry powder inhaler (Inavir®) between January and March 2016 at Tsu emergency medical center/pediatric clinic and dental clinic. All patients enrolled used a laninamivir dry powder inhaler in four repeated inhalations, as instructed by a pharmacist. The residual amount of laninamivir dry powder was calculated by measuring the device weight before and after each inhalation and a residual amount of >20% was defined as an unsuccessful inhalation., Results: The inadequate inhalation rate after two successive inhalations was 45%, and it decreased as number of inhalation repeats increased, reaching 23% after four successive inhalations. Peak inspiratory flow in patients with inadequate inhalation was significantly lower than that in patients with adequate inhalation, for all numbers of inhalation repeats analyzed. Receiver operating characteristic analyses indicated peak inspiratory flow cut-off values of 140, 120, 100, and 100 L/min at 1-4 successive inhalations, respectively., Conclusions: The present findings suggest that a proportion of patients with low peak inspiratory flow were unable to inhale the active ingredient adequately when laninamivir dry powder inhaler was administered as two successive inhalations, as recommended in the instruction manual. Three or four repeated inhalations of laninamivir dry powder inhaler should be administered to pediatric patients with low peak inspiratory flow.