Unique vascular structures of a radicular arteriovenous fistula at the craniocervical junction along the first cervical spinal nerve: A case report.

Background: An arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is a rare vascular malformation. Definitive diagnosis and curative treatment of CCJ AVF are challenging. Case Description: A 77-year-old man presented with subarachnoid hemorrhage. Cerebral angiography showed an AVF at the CCJ, which drained into a radicular vein. The lesion was fed by a vertebral artery, anterior and lateral spinal arteries (LSAs), and the occipital artery (OA). There were two unique structures: the LSA originating from the posterior inferior cerebellar artery of the extracranial V3 segment and the OA feeding the shunt. Curative treatment involved two steps: endovascular embolization of feeders using Onyx and surgical shunt disconnection. Feeding arteries were blackened by Onyx, which helped identify the location of the shunt. The shunt was located behind the first cervical (C1) spinal nerve, and the draining vein was confirmed on the deep side of the nerve. A clip was applied to the draining vein distal to the shunt. Tiny vessels supplying the shunt were then coagulated referring to blackened arteries. Conclusion: A radicular AVF at the CCJ along the C1 spinal nerve had unique vascular structures. Definitive diagnosis and curative treatment were achieved by combining endovascular embolization using Onyx and direct surgery.

Is a small-caliber or large-caliber endoscope more suitable for colonic self-expandable metallic stent placement? A randomized controlled study.

OBJECTIVES: The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. METHODS: Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. RESULTS: Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly (p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly (p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). CONCLUSION: Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. CLINICAL TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748).

Ninjin'yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression.

Purpose: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin'yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice. Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks. Results: Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution. Conclusion: NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.

Exercise Ameliorates Emphysema Of Cigarette Smoke-Induced COPD In Mice Through The Exercise-Irisin-Nrf2 Axis.

Background: Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice. Methods: Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined. Results: Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group. Conclusion: Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smoke-induced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.

Astaxanthin Suppresses Cigarette Smoke-Induced Emphysema through Nrf2 Activation in Mice.

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

Isoflavone Aglycones Attenuate Cigarette Smoke-Induced Emphysema via Suppression of Neutrophilic Inflammation in a COPD Murine Model.

Chronic obstructive pulmonary disease (COPD), a lung disease caused by chronic exposure to cigarette smoke, increases the number of inflammatory cells such as macrophages and neutrophils and emphysema. Isoflavone is a polyphenolic compound that exists in soybeans. Daidzein and genistein, two types of isoflavones, have been reported to have anti-inflammatory effects in various organs. We hypothesized that the daidzein-rich soy isoflavone aglycones (DRIAs) attenuate cigarette smoke-induced emphysema in mice. Mice were divided into four groups: the (i) control group, (ii) isoflavone group, (iii) smoking group, and (iv) isoflavone + smoking group. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and the airspace enlargement using the mean linear intercept (MLI) were determined 12 weeks after smoking exposure. Expressions of neutrophilic inflammatory cytokines and chemokines were also examined. In the isoflavone + smoking group, the number of neutrophils in BALF and MLI was significantly less than that in the smoking group. Furthermore, the gene-expressions of TNF-α and CXCL2 (MIP-2) in the isoflavone + smoking group were significantly less than those in the smoking group. Supplementation of the COPD murine model with DRIAs significantly attenuates pathological changes of COPD via suppression of neutrophilic inflammation.

Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: An exploratory pilot case-control study.

BACKGROUND: Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, human NDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. METHODS: As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDD patients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. RESULTS: Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), thus we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict NDE-related blood substances. Interleukin 34 (IL34)/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and tumor necrosis factor receptor 1 (TNFR1)/CD81 were positively correlated with severities of depression and/or various sub-symptoms. LIMITATIONS: We did not actually extract NDE from peripheral blood. CONCLUSIONS: Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.

Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours: analyses according to the WHO 2010 classification.

OBJECTIVE: Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications. MATERIAL AND METHODS: One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated. RESULTS: Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate. CONCLUSION: Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery.

Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors.

BACKGROUND AND AIM: Pancreatic neuroendocrine tumors (pNETs) are histologically categorized according to the WHO 2010 classification by their mitotic index or Ki-67 index as G1, G2, or G3. The present study examined the efficacy of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis and grading of pNET. METHODS: We retrospectively reviewed 61 pNETs in 51 patients who underwent EUS between January 2007 and June 2014. All lesions were pathologically diagnosed by surgical resection or EUS-FNA. We evaluated the detection rates of EUS for pNET and sensitivity of EUS-FNA, and compared the Ki-67 index between EUS-FNA samples and surgical specimens. EUS findings were compared between G1 and G2/G3 tumors. RESULTS: EUS showed significantly higher sensitivity (96.7%) for identifying pNET than CT (85.2%), MRI (70.2%), and ultrasonography (75.5%). The sensitivity of EUS-FNA for the diagnosis of pNET was 89.2%. The concordance rate of WHO classification between EUS-FNA and surgical specimens was 69.2% (9/13). The concordance rate was relatively high (87.5%, 5/6) in tumors <20 mm but lower (57.1%; 4/7) in tumors ≥20 mm. Regarding EUS findings, G2/G3 tumors were more likely to be large (>20 mm), heterogeneous, and have main pancreatic duct (MPD) obstruction than G1 tumors. Multivariate analysis showed large diameter and MPD obstruction were significantly associated with G2/G3 tumors. CONCLUSIONS: EUS and EUS-FNA are highly sensitive and accurate diagnostic methods for pNET. Characteristic EUS findings such as large tumor size and MPD obstruction are suggestive of G2/G3 tumors and would be helpful for grading pNETs.

Gastric gastrointestinal stromal tumor smaller than 20 mm with liver metastasis.

There have been no reports of gastric gastrointestinal stromal tumors (GISTs) <20 mm with distant metastasis. We report a case of a 15-mm gastric GIST with liver metastasis 1 year after surgical resection of the primary lesion. A 35-year-old man underwent routine esophagogastroduodenoscopy in July 2009. A submucosal tumor (SMT) <20 mm was incidentally detected at the posterior wall of the gastric body. Endoscopic ultrasound (EUS) indicated that it was a gastrointestinal mesenchymal tumor, including GIST, leiomyoma or schwannoma. He did not accept regular follow-up for this gastric SMT, therefore local laparoscopic excision was carried out in October 2009. The final pathological diagnosis after surgery was GIST, 15 mm in size, and a mitotic rate of 7/50 high-power fields, which did not indicate a high metastatic risk. The patient was followed up regularly without adjuvant chemotherapy. At 1 year after surgery, a space-occupying lesion ~15 mm was detected in the left lobe of the liver by abdominal ultrasound, where no mass lesion had been observed before surgery. To make a definite diagnosis of the hepatic mass lesion, EUS-guided fine-needle aspiration was performed, which demonstrated a metastatic liver tumor from a gastric GIST. Although this was a rare case, we should keep in mind that gastric GISTs do have a chance of malignant behavior, even if <20 mm.

[A case of postoperative recurrent gastric cancer resembling esophageal achalasia diagnosed by endoscopic ultrasound-guided fine-needle aspiration].

A 74 year-old man underwent subtotal gastrectomy for advanced gastric cancer in 2000. The histological type of the cancer was signet-ring cell carcinoma, and the clinical stage was stage II (T2, N1, M0). In June 2008 the patient was referred to our hospital complaining of dysphagia. Esophageal endoscopy revealed a circular stenosis with covered with normal mucosa between the lower esophagus and the esophago-gastric junction. Histologically, samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed signet-ring cell carcinoma. Our experience suggests that EUS-FNA was useful for the histological diagnosis of recurrence of gastric cancer.

Gastric mucosal cancer smaller than 7mm can be treated with conventional endoscopic mucosal resection as effectively as with endoscopic submucosal dissection.

BACKGROUND/AIMS: Recently, endoscopic submucosal dissection (ESD) has been accepted for the treatment of gastrointestinal mucosal neoplasms because of the higher en bloc resection rate. However, ESD is technically more difficult, requires a longer procedure time and has more frequent complications compared with conventional endoscopic mucosal resection (EMR). We evaluated retrospectively the clinical outcomes of ESD compared with EMR to determine the size of the lesion for choosing EMR rather than ESD. METHODOLOGY: Three hundred and sixty-five lesions of early gastric cancer were treated endoscopically (146 by EMR and 219 by ESD). We compared en bloc resection, residual tumor and recurrence-free rates between EMR and ESD. RESULTS: En bloc resection rate was significantly higher with ESD (88.5%) than EMR (45.2%). With regard to lesions < or = 7mm in size, en bloc resection, residual tumor and recurrence-free rates did not differ. CONCLUSIONS: Gastric mucosal cancer < or = 7mm can be treated with EMR as effectively as with ESD.

Immunoassay based on a polyclonal antibody for sex steroid hormones produced by a heterogeneous hapten-conjugated immunogen: estimation of its potentiality and antibody characteristics.

A method in which antibodies are produced by using an immunogen heterogeneously conjugated with two or more kinds of haptens having unlike chemical structures against a same carrier protein was offered as an efficient approach for development of antibody to low molecular compounds. To appreciate the potentiality of the approach, 17beta-estradiol (E2) and testosterone were selected as model compounds. The I(50) values of antiserum developed were 6 and 8 microg L(-1) with the detection limits of 0.02 and 0.15 microg L(-1) for E2 and testosterone, respectively. Antiserum owned an interesting characteristic that it was possible to independently analyze E2 and testosterone without mutual interference by making proper use of coating antigens. When using beta-estradiol 17-hemisuccuinate (EH) conjugated with bovine serum albumin (BSA) as a coating antigen, the enzyme-linked immunosorbent assay (ELISA) was very selective to E2 and some estrogen analogues. Therefore, if testosterone coexisted in the ELISA for E2 detection, it showed no interference with it. From these findings, it was suggested that the verified method was an efficient and rational approach in development of polyclonal antibody to low molecular compounds.

Determination of oxycodone and hydrocotarnine in cancer patient serum by high-performance liquid chromatography with electrochemical detection.

We developed an HPLC procedure using electrochemical detection for the quantitation of oxycodone and hydrocotarnine in cancer patients serum. An eluent of methanol:acetonitrile:5 mM pH 8 phosphate buffer (2:1:7) was used for the mobile phase. The calibration curve was linear in the range from 10 ng/mL to 100 ng/mL. The recovery of oxycodone and hydrocotarnine was 97.2% and 90.5%, respectively. The relative standard deviations within-runs and between-runs for the assay of oxycodone or hydrocotarnine were less than 4.8%. The method developed here was better than the method reported previously.

Preoperative diagnosis and staging of gallbladder carcinoma by EUS.

BACKGROUND: EUS has recently been shown to be efficacious for the preoperative assessment of depth of invasion of gallbladder carcinoma. This study assessed the value of EUS for determining T stage (International Union Against Cancer). METHODS: Preoperative EUS findings in 41 patients with gallbladder carcinoma were analyzed retrospectively. EUS images were classified according to the shape of the tumor and the adjacent gallbladder wall structure as follows: type A, pedunculated mass with preserved adjacent wall structures; type B, sessile and/or broad-based mass with a preserved outer hyperechoic layer of the gallbladder wall; type C, sessile and/or broad-based mass with a narrowed outer hyperechoic layer; type D, sessile and/or broad-based mass with a disrupted outer hyperechoic layer. EUS and histopathologic findings were compared, including the depth of invasion of the tumor in the resection specimen. RESULTS: The 4 categories of EUS images of gallbladder carcinoma correlated with the histologic depth of invasion and T stage. Accuracies for the EUS classification as type A corresponding to pTis, type B to pT1, type C to pT2, and type D to pT3-4 were, respectively, 100%, 75.6%, 85.3%, and 92.7%. CONCLUSIONS: Preoperative EUS imaging accurately depicts T stage of gallbladder carcinoma and allows for effective therapeutic decision making.