Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria.

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it. METHODS: Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration. RESULTS: Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution. CONCLUSIONS: Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.

Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora.

BACKGROUND: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. METHODS: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model. RESULTS: IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion. CONCLUSIONS: Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions).

[Successful resection of a gastric aberrant pancreas causing gastrointestinal bleeding by laparoscopy and endoscopy cooperative surgery].

A man in his 50s was admitted to our hospital for treatment of hematemesis. Endoscopy revealed arterial bleeding from a gastric submucosal tumor and endoscopic hemostasis was successful. However, surgical resection was contemplated to prevent recurrent bleeding and for making a definitive diagnosis. Surgical resection was eventually performed by laparoscopy and endoscopy cooperative surgery (LECS), and the tumor was pathologically diagnosed to be a gastric aberrant pancreas. We think that LECS is suitable for a gastric aberrant pancreas causing gastrointestinal bleeding, because the procedure is effective for tumor resection with minimal removal of the stomach wall.

Blockade of SIRPα-CD47 axis by anti-SIRPα antibody enhances anti-tumor activity of DXd antibody-drug conjugates.

Signal regulatory protein alpha (SIRPα) is an immune inhibitory receptor on myeloid cells including macrophages and dendritic cells, which binds to CD47, a ubiquitous self-associated molecule. SIRPα-CD47 interaction is exploited by cancer cells to suppress anti-tumor activity of myeloid cells, therefore emerging as a novel immune checkpoint for cancer immunotherapy. In blood cancer, several SIRPα-CD47 blockers have shown encouraging monotherapy activity. However, the anti-tumor activity of SIRPα-CD47 blockers in solid tumors seems limited, suggesting the need for combination therapies to fully exploit the myeloid immune checkpoint in solid tumors. Here we tested whether combination of SIRPα-CD47 blocker with antibody-drug conjugate bearing a topoisomerase I inhibitor DXd (DXd-ADC) would enhance anti-tumor activity in solid tumors. To this end, DS-1103a, a newly developed anti-human SIRPα antibody (Ab), was assessed for the potential combination benefit with datopotamab deruxtecan (Dato-DXd) and trastuzumab deruxtecan (T-DXd), DXd-ADCs targeting human trophoblast cell-surface antigen 2 and human epidermal growth factor receptor 2, respectively. DS-1103a inhibited SIRPα-CD47 interaction and enhanced antibody-dependent cellular phagocytosis of Dato-DXd and T-DXd against human cancer cells. In a whole cancer cell vaccination model, vaccination with DXd-treated cancer cells led to activation of tumor-specific T cells when combined with an anti-mouse SIRPα (anti-mSIRPα) Ab, implying the benefit of combining DXd-ADCs with anti-SIRPα Ab on anti-tumor immunity. Furthermore, in syngeneic mouse models, both Dato-DXd and T-DXd combination with anti-mSIRPα Ab showed stronger anti-tumor activity over the monotherapies. Taken together, this study provides a preclinical rationale of novel therapies for solid tumors combining SIRPα-CD47 blockers with DXd-ADCs.

Differences in gaze behaviors between trainees and experts during endovascular therapy for cerebral aneurysms: a preliminary study using a cerebral aneurysm model.

In the neuroendovascular field, the training of operators has become an important issue. Recently, eye-tracking technology has been introduced into various fields of medical education. This study aimed to apply eye-tracking technology to the training of neuroendovascular therapy. Six neurosurgeons, including three neuroendovascular specialists and three trainees, at our institution and related facilities participated in the study. Eye movement was recorded by the eye-tracking device during the microcatheter navigation and coil placement into the silastic aneurysm model under biplane X-ray fluoroscopy. Eye-tracking analysis during neuroendovascular therapy was feasible in all six subjects. In microcatheter navigation, specialists tended to more frequently switch their attention between frontal and lateral images than trainees. In coil embolization, the overall gaze frequency tended to increase, and the average fixation duration tended to decrease as the number of experienced cases increased. Inexperienced operators tend to fix their gaze when they are operators than when they are assistants. More experienced operators tended to look at the microcatheter longer in the coil insertion task. The eye-tracking analysis may be useful for operator training in neuroendovascular therapy. Experts may have moved their eyes more frequently than trainees to gaze at the right place. In the future, it will be necessary to collect gaze data for more operators in various tasks.

Usefulness of arrival time parametric imaging in evaluating the degree of liver disease progression in chronic hepatitis C infection.

OBJECTIVE: To determine whether the degree of liver disease progression in chronic hepatitis C infection can be evaluated by arrival time parametric imaging using contrast-enhanced sonography with Sonazoid (perfluorobutane; GE Healthcare, Oslo, Norway). METHODS: In this study, 60 patients with liver disease in chronic hepatitis C infection were examined and compared with 10 healthy volunteers who served as controls. A recommended dose of the sonographic contrast agent Sonazoid was intravenously infused, and the S5 or S6 region of the liver and right kidney were observed concurrently while movies of the procedure were saved. Arrival time parametric images of liver parenchymal blood flow were created, with red pixels to indicate an arrival time of 0 to 5 seconds and yellow pixels to indicate an arrival time of 5 to 10 seconds. From the obtained images, the ratio of the red area to the entire enhanced area of the liver was calculated using image-processing software. Each participant was subsequently subjected to liver biopsy for liver fibrosis staging according to Metavir scores, and the determined fibrosis stage was compared with the ratio of red. The serum albumin level, platelet count, and prothrombin time were also compared with the ratio of red for each participant. RESULTS: The ratio of red increased significantly as liver fibrosis stage advanced (P < .01 for F1 versus F2; P < .01 for F1 versus F3; P < .01 for F1 versus F4; and P < .01 for F2 versus F4). As the ratio of red increased, significant decreases were observed in the serum albumin level (r = -0.29; P = .027), platelet count (r = -0.46; P = .0003), and prothrombin time (r = -0.46; P = .0002). CONCLUSIONS: Arrival time parametric imaging using Sonazoid-enhanced sonography enables noninvasive evaluation of the degree of progression of liver disease in chronic hepatitis C infection and is thus considered clinically useful.

Clinical evaluation of hemorrhagic gastroduodenal ulcer in the elderly: is Helicobacter pylori infection a risk factor for hemorrhage?

AIM: In this study, the aim was to determine the demographic characteristics of elderly patients with gastroduodenal ulcer who had undergone endoscopic hemostasis by comparing them with younger patients. METHODS: A total of 353 patients with Forrest class I-IIa hemorrhagic gastroduodenal ulcer who underwent endoscopic hemostasis at our hospital between December 2004 and May 2010 were divided into two groups: one for those 75 years or older (old-old group; n = 71; age ≥75 years) and one for those younger than 75 years (younger group; n = 282; age <75 years). Then, their demographic characteristics were compared. RESULTS: There were significantly more female patients, patients with underlying chronic renal failure and patients using non-steroidal anti-inflammatory drugs in the old-old group than in the younger group. In addition, the prevalence of open-type atrophy in the background gastric mucosa was significantly higher in the old-old group. Although more than half the patients in each group were infected with Helicobacter pylori, the prevalence was significantly higher in the younger group. Of the patients who underwent endoscopic hemostasis only once, those in the old-old group constituted a significantly higher medical cost than those in the younger group. Comparison of deaths between the two groups revealed that the old-old patients were more likely to develop severe complications associated with hematemesis, such as aspiration pneumonia. CONCLUSIONS: The observed lower prevalence of Helicobacter pylori infection among the elderly patients compared to the younger patients with hemorrhagic gastroduodenal ulcer suggests that other factors, such as non-steroidal anti-inflammatory drugs use and chronic renal failure, predispose the elderly to hemorrhagic ulcer.

Abnormal foreshortening of a Flow Re-Direction Endoluminal Device caused by in-stent thrombosis immediately after deployment.

Thromboembolic complications are a concern in the treatment of cerebral aneurysms using a flow diverter. In this study, we report a case of abnormal foreshortening of a Flow Re-Direction Endoluminal Device (FRED) caused by in-stent thrombosis immediately after its deployment. A 72-year-old woman had a large cavernous carotid aneurysm, which caused ptosis and diplopia. FRED deployment was planned, and dual antiplatelet therapy was initiated 2 weeks before the procedure. Under systemic heparinization, FRED was deployed with local compaction over the aneurysm orifice. Cone-beam computed tomography subsequently revealed slightly poor wall apposition at the proximal side. While the balloon catheter was prepared for angioplasty, the stent became abnormally foreshortened, the proximal side slipped into the aneurysm, and the internal carotid artery became occluded. FRED was removed using a snare wire, and recanalization was obtained. The lumen of the removed FRED was filled with thrombus. The antiplatelet therapy was changed to triple regimen, and a Pipeline Flex embolization device was placed 1 month later. At that time, no thromboembolic complications were noted. It was considered that thrombotic occlusion was followed by foreshortening of FRED on the distal side because of antegrade blood flow. Multiple factors, such as increased mesh density by locally compacted stent deployment, slightly poor wall apposition, clopidogrel resistance, and the dual-layer structure of FRED, may have been involved in thrombus formation.

Evaluation of the differences in pressure applied to the vessel wall by different types of balloon remodeling microcatheters in an experimental model.

BACKGROUND: We examined compliance differences among balloon remodeling microcatheters, which have not been established previously. METHODS: Straight and 120° angulated vascular models were created in a 3 mm diameter tube with 3 mm hole (vascular model A), a tube with a 4 mm hole (vascular model B), and a 4 mm diameter tube (vascular model C). We compared the pressure exerted when each balloon was herniated 1 or 2 mm between three compliant balloons (SHOURYU SR, TransForm C, and Scepter C) and four super-compliant balloons (HyperForm, SHOURYU HR, TransForm SC, and Scepter XC). RESULTS: In vascular model A, there was a significant difference in the pressure exerted by compliant balloons and super-compliant balloons in both the straight and angulated models. In the straight model (1 and 2 mm), the lowest pressure was exerted by HyperForm (super-compliant balloons group) and SHOURYU SR (compliant balloons group). The lowest pressure was exerted in the angulated model by HyperForm (super-compliant balloons group) and Scepter C (compliant balloons group). The Scepter balloon exerted higher pressure in the straight model than other balloon remodeling microcatheters but less in the angulated model. In vascular model B, the pressure decreased in all balloons compared with model A. In vascular model C, the pressure increased in all balloons compared with model A. CONCLUSIONS: Pressure differed across balloon remodeling microcatheters. In addition, vessel shape and diameter, and hole size, affected the results. Our findings can help select balloon remodeling microcatheters.

Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. METHODS: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. RESULTS: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). CONCLUSIONS: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.

Streak Metal Artifact Reduction Technique in Cone Beam Computed Tomography Images after Endovascular Neurosurgery.

Cone beam computed tomography (CBCT) images are degraded by artifacts due to endovascular implants. We evaluated the use of streak metal artifact reduction technique (SMART) in non-contrast CBCT images after endovascular neurosurgery obtained from 148 patients (125 with aneurysm and 23 with dural arteriovenous fistula [dAVF]). Three neurosurgeons evaluated the cistern and brain surface visibility in CBCT images with and without SMART correction based on a 4-point scale (1, excellent; 2, good; 3, limited; and 4, insufficient). Significant improvement in visibility was achieved when the median scores improved from 4 or 3 to 2 or 1 or from 2 to 1. Metal artifact reduction in adjacent slices without metal and new artifacts after SMART correction was also examined. A significant improvement was achieved regarding the visibility of the cistern in 90 (60.8%) images and of the brain surface in 108 (73.0%) images. Metal size (cistern: odds ratio [OR], 0.91 per 1 mm increase; 95% confidence interval [CI], 0.83-0.99), irregular metal shape (cistern: OR, 0.18; 95% CI, 0.05-0.60 and brain surface: OR, 0.15; 95% CI, 0.05-0.45), and infratentorial lesions (cistern: OR, 0.37; 95% CI, 0.14-0.96 and brain surface: OR, 0.30; 95% CI, 0.11-0.80) were negatively correlated with improved visibility. Metal artifact reduction in adjacent slices without metal was obtained in 25.6% and 34.8% of images with aneurysm and dAVF, respectively. New artifacts after SMART correction were found in 4.8% and 13.0% of images with aneurysm and dAVF, respectively. SMART is especially effective for supratentorial small aneurysms.

Management of Asymptomatic Vertebral Artery Injury Caused by a Cervical Pedicle Screw Malposition: Two Case Reports.

Iatrogenic vertebral artery (VA) injury in cervical fusion is an extremely rare complication but can lead to serious sequelae. We present two successful cases of internal trapping for preventing delayed-onset ischemic stroke after iatrogenic VA stenosis caused by a cervical pedicle screw. A 34-year-old female underwent posterior cervical fusion for C4/C5 dislocation fracture. No neurological deficits were observed after the operation. However, the postoperative images revealed that the left C5 pedicle screw perforated the transverse foramen, and the left VA was suspected to be occluded at the screw insertion site. Before revision surgery, we tried to embolize the injured VA with coils. A microcatheter could be navigated from the ipsilateral VA to the distal of the screw, and internal trapping was performed with coils. Another case is that of a 50-year-old male with cervical spondylosis, who underwent posterior decompression and cervical fusion. The neurological symptoms did not deteriorate after the operation. However, the postoperative computed tomography images revealed the perforation of the right C3 transverse foramen by the pedicle screw. In right vertebral angiography, about 70% stenosis was observed at the screw insertion site. Although revision surgery was not planned due to good stability, we embolized the right VA after balloon occlusion test, to prevent the delayed-onset thromboembolic complications. Both the patients recovered without any neurological deficits. Iatrogenic VA injuries, even if asymptomatic immediately after surgery, can lead to serious sequelae in case of delayed-onset ischemic stroke. Therefore, careful attention should be paid when the screw perforates the transverse foramen.

Direct Vertebral Artery Puncture During Open Surgery for the Endovascular Treatment of a Recurrent Vertebro-Vertebral Arteriovenous Fistula.

BACKGROUND: Vertebro-vertebral arteriovenous fistula (VVAVF) is a condition in which there is an arteriovenous shunt directly connecting the extracranial vertebral artery to the vertebral venous plexus. Many reports have described fistula occlusion or vertebral artery trapping as treatments for VVAVF. Here, we describe a case in which endovascular treatment for recurrent VVAVF using a transfemoral approach was unsuccessful; thus, the vertebral artery (VA) was directly punctured during open surgery and the treatment was successful. CASE DESCRIPTION: The patient was a 47-year-old female who had undergone endovascular treatment for VVAVF. The patient developed subarachnoid hemorrhage. Digital subtraction angiography revealed a left VVAVF. The left VA was trapped with coils at the C2 and C3 levels and an arteriovenous shunt formed from the VA between the 2-coil mass to the vertebral venous plexus. In addition, reflux was observed in the spinal vein. Endovascular treatment was attempted with a transfemoral approach, but we could not reach the shunt. Five days post-treatment, the patient had a second subarachnoid hemorrhage and surgery was performed to occlude the radiculomedullary vein; however, residual reflux went into the spinal vein from another spinal level. Later, the VA was directly punctured and treated with N-butyl cyanoacrylate, and the shunt disappeared. CONCLUSIONS: Direct puncture of the vertebral artery was useful in this case, where it was difficult to reach the lesion. Although direct VA puncture is associated with more complications than the transfemoral or transbrachial approach, it may be an option when other methods are difficult.

Short-Term and Long-Term Outcomes of Infliximab and Tacrolimus Treatment for Moderate to Severe Ulcerative Colitis: Retrospective Observational Study.

BACKGROUND/AIMS: While some studies have shown that IFX and TAC exhibit similar efficacy against UC in the short-term, it is unclear which drug produces better long-term outcomes. In this study, we compared the long-term efficacy of IFX and TAC in patients with moderate to severe UC. METHODS: This retrospective study was conducted from 2009 to 2017. It included patients with no history of IFX or TAC treatment. We analyzed the clinical response and remission rates at 12 and 52 weeks, and colectomy-free and relapse-free survival were evaluated until the end of the study. RESULTS: At 12 weeks, 94.4% and 77.8% of the patients in the IFX group (n = 18) had demonstrated clinical responses and clinical remission, respectively, whereas 72.7% of the patients in the TAC group (n = 11) exhibited clinical responses and clinical remission. The clinical response, clinical remission, and colectomy-free rates did not differ significantly between the groups. At 52 weeks, clinical responses and clinical remission had been achieved in 76.5% and 70.6% of the patients both in the IFX group, respectively. In the TAC group, clinical responses and clinical remission were achieved in 50.0% of patients. Relapse-free and colectomy-free survival were estimated significantly better in IFX group evaluated by Kaplan-Meier curves. CONCLUSION: This study indicates that IFX and TAC produce similar short-term outcomes in UC patients, but IFX produces better long-term outcomes than TAC especially with avoidance of colectomy. Our data suggest that IFX therapy may be prioritized over TAC for the treatment of moderate to severe UC.

Suppressive effects of fruit-juice concentrate of Prunus mume Sieb. et Zucc. (Japanese apricot, Ume) on Helicobacter pylori-induced glandular stomach lesions in Mongolian gerbils.

Helicobacter pylori (Hp) infection is an important factor in human gastric disorders, including chronic active gastritis, peptic ulcers, intestinal metaplasia and cancer. Since epidemiologic studies overwhelmingly agree on a protective influence of fruits and vegetables in reducing the risk of gastric neoplasia and processed foods made from Prunus mume Sieb. et Zucc. (Japanese apricot or "Ume" in Japanese) are traditionally known for their miscellaneous medical effects, in the present study we investigated the efficacy of a fruit-juice concentrate of Japanese apricot (CJA) in the glandular stomach of Hp-infected Mongolian gerbils. Hp-inoculated gerbils were given CJA in their drinking water at concentrations of 1 and 3% for 10 weeks. The microscopic scores for gastritis and mucosal hyperplasia in the CJA groups were significantly lower than in the Hp-inoculated control group, with dose-dependence. Real-time PCR was performed to quantitate Hp by demonstrating urease A gene amount using gerbils glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene as an internal control. Average relative urease A gene dosage in the glandular stomach in the 1 and 3% CJA and Hp-inoculated control groups was 26.6 +/- 11.6% (average +/- SE), 30.3 +/- 10.5%, 100 +/- 40.9%, respectively, the fruit-juice concentrate causing significant lowering (P<0.01 and P<0.05, respectively, with 1 and 3%). These findings suggest that suppressive effects on gastric cancer development might also be expected as a result of decreased numbers of Hp and improvement of Hp-induced chronic active gastritis on administration of CJA.

Effect of obstructive jaundice on hepatic hemodynamics: use of Sonazoid-enhanced ultrasonography in a prospective study of the blood flow balance between the hepatic portal vein and hepatic artery.

PURPOSE: To prospectively clarify the effects of obstructive jaundice (OJ) on hepatic hemodynamics using contrast-enhanced ultrasonography (US). METHODS: Subjects comprised 14 patients admitted to our hospital for OJ between April 2013 and March 2014. Contrast-enhanced US was performed using the LOGIQ E9 ultrasound device during the jaundice phase, before biliary drainage, and again after improvement of jaundice. After injecting the Sonazoid contrast agent, contrast dynamics were recorded in the right kidney and liver segments 5 or 6. Prototype software was used to calculate mean arrival time (AT) of the contrast agent in the liver parenchyma. Statistical analysis was performed to compare the mean AT in the jaundice and improved jaundice phases. RESULTS: We were unable to follow up three of the 14 patients after biliary drainage; thus, we included 11 patients for further analysis. The mean AT of the contrast agent was 2.0 ± 1.8 and 6.1 ± 2.3 s in the jaundice and improved jaundice phases, respectively, showing significantly shorter AT in the jaundice phase (p = 0.0033). CONCLUSION: Our findings indicate that OJ may influence the blood flow balance between the hepatic portal vein and hepatic artery.

Spontaneous complete necrosis of hepatocellular carcinoma: A case report and review of the literature.

The present study reports the case of a 68-year-old male patient who presented to Tokyo Rosai Hospital for the treatment of alcoholic liver disease. A high density was observed in liver segment S2, while a tumor, 30 mm in size, exhibiting a low density was observed in the delayed phase upon contrast-enhanced computed tomography (CT), which was performed prior to admission. The tumor appeared slightly poorly defined upon abdominal ultrasound and was observed as a 30 mm low-echoic nodule that was internally heterogeneous. A 5-mm thick contrast enhancement effect was observed in the tumor border in the vascular phase on Sonazoid contrast-enhanced ultrasonography, while a defect in the entire tumor was observed in the post-vascular phase. Dysphagia had commenced three months prior to presentation and a weight loss of ~3 kg was observed. Therefore, the patient was admitted to Tokyo Rosai Hospital due to the presence of a hepatic tumor, and to undergo a close inspection of the cause of the tumor. Upon close inspection, it was determined that the weight loss and aphagia were caused by progressive bulbar paralysis. A contrast-enhanced CT was performed on post-admission day 29 as a follow-up regarding the hepatic tumor. As a result, although no change in the tumor size was observed, the contrast enhancement in the tumor borderline had disappeared. Necrosis of the tumor was considered. However, as viable persistence of the malignant tumor could not be excluded, a hepatic left lobe excision was performed. The patient was diagnosed with hepatocellular carcinoma (HCC) based on the morphology of the cellular necrosis. In addition, occlusion due to thrombus was observed within the blood vessels passing inside the fibrous capsule. It was hypothesized that the formation of a thick fibrous capsule and occlusion due to thrombus in the feeding vessel were possibly involved as the cause of complete spontaneous necrosis. Written informed consent was obtained from the patient.

Endoscopic nasobiliary drainage improves jaundice attack symptoms in benign recurrent intrahepatic cholestasis: A case report.

A 66-year-old male with unbearable pruritus and jaundice was admitted for detailed examination. Blood tests on admission showed increased bilirubin with a dominant direct fraction. Ultrasonography and computed tomography performed subsequent to admission showed no narrowing or distension of the bile ducts. As the jaundice symptoms were not improved by the oral administration of ursodeoxycholic acid (300 mg/day) that had been started immediately after admission, endoscopic retrograde cholangiopancreatography (ERCP) was performed on hospital day 14. This also showed no abnormalities of the bile ducts. After considerating its potential effects for improving jaundice, endoscopic nasobiliary drainage (ENBD) was performed on the same day and was followed by immediate improvements in pruritus and jaundice. Detailed examinations were performed to identify the cause of the jaundice, which was suspected to be viral hepatitis, autoimmune hepatitis or drug-induced liver injury, however, there were no findings suggestive of any of these conditions. Following a further increase in bilirubin levels, confirmed by additional blood tests, a liver biopsy was performed. Histological findings were consistent with the histological features of benign recurrent intrahepatic cholestasis (BRIC). Although ursodeoxycholic acid is used as a first-line treatment in most cases of BRIC, ENBD should also be considered for patients not responding to this treatment.

A case of branch duct type intraductal papillary neoplasm of the bile duct treated by open surgery after 11 years of follow-up.

The intraductal papillary neoplasm of the bile duct (IPNB) is a novel disease concept that was recently classified as a biliary cystic tumor by the revised World Health Organization classification. This is the case report of a 70-year-old female patient who experienced repeated episodes of obstructive jaundice and cholangitis since 2000, attributed to a mucus-producing hepatic tumor. Surgery was advised due to the repeated episodes; however, the patient refused. In May, 2011, the patient developed jaundice and fever and was treated with antibiotics. Since there was no improvement, the patient was admitted to the Tokyo Rosai Hospital. Abdominal computed tomography (CT) revealed a 50-mm cystic mass with an internal septum in the left hepatic lobe. Although the tumor size had remained almost unchanged compared to the initial CT scan performed in 2000, intra- and extra-hepatic bile duct dilation was more prominent on the second CT scan. Following admission, endoscopic retrograde cholangiopancreatography was performed and revealed an expanded papilla of Vater due to a mucous plug. A balloon catheter was inserted into the bile duct to remove the mucous plug, resulting in the drainage of copious amounts of mucus and infected bile. The patient finally consented to surgery and left hepatic lobectomy was performed. Consequently, the diagnosis of low-grade IPNB was made. Branch duct type IPNB, which is characterized by imaging appearance of a cystic mass and slow progression, is attracting increasing attention. In the present case, a cystic mass was identified in the left hepatic lobe, with no significant change in size after 11 years of follow-up, leading to the diagnosis of branch duct type IPNB. Considering the fact that IPNB is usually treated surgically at the time of diagnosis, the present case, due to the long-term follow-up, provides valuable insight into the natural history of the tumor.

Mucinous cystadenocarcinoma of the appendix in which contrast-enhanced ultrasonography was useful for assessing blood flow in a focal nodular lesion in the tumor cavity: A case report.

A 63-year-old woman was admitted to hospital with pain in the right lower quadrant. Abdominal computed tomography (CT) revealed a 60-mm cystic mass at a site corresponding to the appendix. The mass wall on the appendicular ostium was thickened and enhanced by contrast, while calcification was observed in the mass wall on the appendicular tip. No projection was observed in the mass cavity. On abdominal ultrasonography (US), the mass wall on the appendicular ostium was thickened and projections were observed at two sites in the mass cavity. On contrast-enhanced US (CEUS), only one of these projections was enhanced. Based on the thickened and contrast-enhanced wall of the mass on the appendicular ostium on CT and US, as well as the contrast enhancement of a projection on US, the mass was diagnosed as mucinous cystadenocarcinoma of the appendix. Ileocecal resection was subsequently performed on day 10. A detailed examination of the surgical specimen revealed carcinoma cells in the mass wall on the appendicular ostium. The contrast-enhanced projection was identified as granulation tissue that had grown to come into contact with the tumor, while the non-contrast-enhanced projection was identified as solidified mucus. US enabled successful visualization of projections in the mass cavity that were not visible on abdominal CT. CEUS also proved useful for assessing blood flow in these projections.