Duodenal gastric heterotopia,sporadic or fundic gland polyp-associated,frequently carries β-catenin mutation

Duodenal gastric heterotopia (DGH) is a benign asymptomatic condition assumed to be of congenital origin. Since DGH is often associated with fundic gland polyps (FGPs) that frequently carry a somatic β-catenin gene mutation, we examined whether DGH, either sporadic or FGP-associated, is attributable to alterations of the Wnt/β-catenin pathway. Genetic analysis revealed frequent somatic β-catenin gene mutations in DGH; some of which showed the same mutation pattern as coexisting FGPs. All missense mutations were confined to codons 32, 33, and 37. No such mutations were observed, however, in any of the specimens from focal gastric foveolar metaplasia (GFM). Therefore, DGH is not a mere congenital lesion due to aberrant migration of normal gastric mucosa or a simple reactive metaplasia after regenerative stimuli of the duodenal mucosa, but a distinct condition based upon molecular genetic changes in the Wnt/β-catenin pathway.     

Clinical utility of treatment method conversion during single-session endoscopic ultrasound-guided biliary drainage

BACKGROUND Although several techniques for endoscopic ultrasound-guided biliary drainage(EUS-BD)are available at present,an optimal treatment algorithm of EUS-BD has not yet been established.AIM To evaluate the clinical utility of treatment method conversion during single endoscopic sessions for difficult cases in initially planned EUS-BD.METHODS This was a single-center retrospective analysis using a prospectively accumulated database.Patients with biliary obstruction undergoing EUS-BD between May 2008 and April 2016 were included.The primary outcome was to evaluate the improvement in EUS-BD success rates by converting the treatment methods during a single endoscopic session.Secondary outcomes were clarification of the factors leading to the conversion from the initial EUS-BD and the assessment of efficacy and safety of the conversion as judged by technical success,clinical success,and adverse events(AEs).RESULTS A total of 208 patients underwent EUS-BD during the study period.For 18.8%(39/208)of the patients,the treatment methods were converted to another EUSBD technique from the initial plan.Biliary obstruction was caused by pancreatobiliary malignancies,other malignant lesions,biliary stones,and other benign lesions in 22,11,4,and 2 patients,respectively.The reasons for the difficulty with the initial EUS-BD were classified into the following 3 procedures:Target puncture(n=13),guidewire manipulation(n=18),and puncture tract dilation(n=8).Technical success was achieved in 97.4%(38/39)of the cases and clinical success was achieved in 89.5%of patients(34/38).AEs occurred in 10.3%of patients,including bile leakage(n=2),bleeding(n=1),and cholecystitis(n=1).The puncture target and drainage technique were altered in subsequent EUSBD procedures in 25 and 14 patients,respectively.The final technical success rate with 95%CI for all 208 cases was 97.1%(95%CI:93.8%-98.9%),while that of the initially planned EUS-BD was 78.8%(95%CI:72.6%-84.2%).CONCLUSION Among multi-step procedures in EUS-BD,guidewire manipulation appeared to be the most technically challenging.When initially planned EUS-BD is technically difficult,treatment method conversion in a single endoscopic session may result in successful EUS-BD without leading to severe AEs.     

Case Report: Trypanosoma cruzi Meningoencephalitis in a Patient with Acquired Immunodeficiency Syndrome

As a result of global migration, a significant number of people with Trypanosoma cruzi infection now live in the United States, Canada, many countries in Europe, and other non-endemic countries. Trypanosoma cruzi meningoencephalitis is a rare cause of ring-enhancing lesions in patients with acquired immunodeficiency syndrome (AIDS) that can closely mimic central nervous system (CNS) toxoplasmosis. We report a case of CNS Chagas reactivation in an AIDS patient successfully treated with benznidazole and antiretroviral therapy in the United States.Trypanosoma cruzi meningoencephalitis is a rare cause of ring-enhancing lesions in patients with acquired immunodeficiency syndrome (AIDS) that can closely mimic central nervous system (CNS) toxoplasmosis. Diagnosis is often delayed and mortality is 79–100% despite treatment^1,2; to our knowledge, only four cases of T. cruzi meningoencephalitis in human immunodeficiency virus (HIV)-infected patients have been reported in the United States.^3–6 None of the four patients have survived. We report a case of CNS Chagas reactivation in an AIDS patient successfully treated with benznidazole and antiretroviral therapy in the United States.A 49-year-old right-handed woman originally from Honduras was admitted to our hospital with a 3-week history of progressive altered mental status, headache, and right-sided weakness. On the day of symptom onset, she presented to an outside hospital and magnetic resonance imaging (MRI) of the brain revealed two ring-enhancing lesions associated with edema. She was also diagnosed with AIDS (CD4 count of 38 cells/μL and an HIV viral load of 375,000 copies/mL). The patient underwent an MRI-guided biopsy of the left parietal lesion and was diagnosed with cerebral Toxoplasmosis. After 14-days, she was discharged to continue treatment of cerebral toxoplasmosis with sulfadiazine and pyrimethamine; however, she was nonadherent with her medications.On admission to our hospital, she was afebrile and physical examination was notable for altered mental status and weakness of the right upper and lower extremities (3/5, Medical Research Council scale) without sensory deficit. The MRI of the brain showed worsening ring-enhancing lesions within the right superior frontal gyrus (1.4 × 1.2 cm) and left parietal lobe (2.4 × 2.2 cm) with moderate vasogenic edema and regional mass effect and adjacent leptomeningeal enhancement. She was started on oral sulfadiazine, pyrimethamine, and glucocorticosteroids. On hospital Day 5, the patient had worsening mental status and a computed tomography of the head showed enlargement of the right frontal lesion with increased edema. A lumbar puncture was performed. Cerebrospinal fluid (CSF) contained three white blood cells/μL and one red blood cell/μL. The CSF protein was 78 mg/dL and glucose was 55 mg/dL. The CSF Gram stain was negative for bacteria but Wright-Giemsa stain revealed numerous flagellated parasites consistent with T. cruzi trypomastigotes (Figure 1). Fungal and acid fast bacilli stain and cultures and CSF cryptococcal antigen were negative. Serologic studies were negative for Toxoplasma IgG and IgM but positive for T. cruzi antibody by the indirect fluorescent antibody test and enzyme immunoassay. The CSF and serum polymerase chain reaction studies were positive for T. cruzi and negative for Toxoplasma. Electrocardiogram and transthoracic echocardiogram were negative for findings to suggest Chagas cardiomyopathy.Open in a separate windowFigure 1.Trypanosoma cruzi trypomastigotes in cerebrospinal fluid (CSF) (Giemsa stain, ×1,000).The brain biopsy histopathology slides were obtained from an outside hospital, which revealed numerous intracellular organisms with rod-shaped kinetoplast, consistent with T. cruzi amastigotes (Figure 2).Open in a separate windowFigure 2.Trypanosoma cruzi amastigotes with rod-shaped kinetoplasts in glial cells (Giemsa stain, ×1,000).Treatment with benznidazole 5 mg/kg/day was started for Chagasic meningoencephalitis and brain abscesses. Her mental status improved gradually, although her right-sided weakness remained unchanged. Antiretroviral therapy was started 17 days after initiation of antitrypanosomal therapy. Repeat MRI of the brain 2 weeks after treatment showed a decrease in the size of the two lesions and surrounding edema. She completed a 60-day induction therapy. At last follow-up 5 months after initial diagnosis, she was clinically stable without evidence of recurrence and her CD4 count was 359 cells/μL with HIV viral load of 162 copies/ml.Chagas disease, or American trypanosomiasis, is estimated to affect ∼8–10 million people in the world, primarily in Latin America and the Caribbean.^7,8 As a result of global migration, a significant number of people with T. cruzi infection now live in the United States, Canada, many countries in Europe, and other non-endemic countries.⁹ In the United States alone, it is estimated that ∼0.3 to 1 million people are infected with T. cruzi.¹⁰Reactivation of chronic T. cruzi infection can occur in immunosuppressed patients such as those with hematologic malignancies, organ transplantation, and AIDS. In Chagas-endemic countries, T. cruzi and HIV coinfection rate ranges from 1.3% to 7.1%.¹¹ Although the chronic phase of Chagas disease in non-immunosuppressed patients most commonly manifests as cardiac disease or gastrointestinal dysfunction, the most common manifestations of T. cruzi reactivation in patients with AIDS are CNS lesions and menigoencephalitis. Most of the reported cases have occurred in HIV-infected patients with a CD4 count < 200 cells/μL.^1,2,12 T. cruzi reactivation in patients with AIDS can closely mimic cerebral toxoplasmosis clinically and radiographically, thus patients are often misdiagnosed resulting in a delay in appropriate treatment.¹²Identification of T. cruzi trypomastigote in CSF is diagnostic of chagasic encephalitis. However, a negative CSF smear does not rule out the disease. In a report of 15 cases from Argentina, CSF direct examination for T. cruzi was positive in 11 of 13 patients.² A brain biopsy may be necessary when the diagnosis remains unclear. The recommended treatment of CNS Chagas reactivation in HIV patients is benznidazole 5 mg/kg daily divided into two doses for 60–90 days and some authors recommend secondary prophylaxis with benznidazole 5 mg/kg three times per week.¹² Nifurtimox is considered an alternative treatment but clinical experience is limited. Immune reconstitution with highly active antiretroviral therapy likely plays an important role in the control of Chagas reactivation but optimal timing for initiation of antiretroviral therapy remains unclear.¹² Chagasic menigoencephalitis should be considered in HIV-infected patients with CNS lesions who are from T. cruzi-endemic areas.     

Comprehensive lipid profiling of bleomycin‐induced lung injury

Drug‐induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting‐edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug‐induced lung injury. We used a mouse model of bleomycin‐induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory‐to‐fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment. In the lung, the levels of ether‐type phosphatidylethanolamines decreased, while those of phosphatidylcholines, bismonophosphatidic acids and cholesterol esters increased on days 7 and 21. In BALF, the global lipid levels increased on days 7 and 21, but only those of some lipids, such as phosphatidylglycerols/bismonophosphatidic acids and phosphatidylinositols, increased from day 2. The lung levels of prostaglandins, such as prostaglandin D₂, were elevated on day 2, and those of 5‐ and 15‐lipoxygenase metabolites of docosahexaenoic acid were elevated on day 7. In BALF, the levels of 12‐lipoxygenase metabolites of polyunsaturated fatty acids were elevated on day 7. Our comprehensive lipidomics approach suggested anti‐inflammatory responses in the inflammatory phase, phospholipidosis and anti‐inflammatory responses in the inflammatory‐to‐fibrosis phase, and increased oxidative stress and/or cell phenotypic transitions in the fibrosis phase. Understanding these molecular changes and potential mechanisms will help develop novel drugs to prevent or treat drug‐induced lung injury.     

Distributions of calcitonin gene-related peptide and substance P in the human maxillary sinus of Japanese cadavers

BackgroundSubstance P (SP) and calcitonin gene-related peptide (CGRP) are released by the nociceptive sensory nerve and are involved in blood flow, pain and inflammation in the nasal mucosa. The purpose of this study was to assess the distribution of the SP and CGRP nerve fibres related to blood supply within human Schneiderian membrane of the maxillary sinus (MS).Material and methodsIn this study, the MS from Japanese cadavers was examined by whole-mount immunohistochemistry. Human male cadavers (ranging in age from 80 to 90 years) were used in this study.ResultsSP- and CGRP-positive fibres were found around large vessels of the medialis superior alveolar branches and also within the floor region of the MS. The floor region of the MS was composed of complex branches of these fibres.ConclusionOur results give useful information for surgical sinus floor elevation in this region of the MS. These anatomical features may assist in the execution of a successful surgical procedure.     

Intrahepatic cholangiojejunostomy (Longmire procedure) for recurrent bilioenteric anastomotic stricture with hepatolithiasis

Interventional procedure via percutaneous transhepatic route is often performed, as an initial treatment, in patients with benign bilioenteric anastomotic stricture. However, surgical management is required in most cases in which radiological intervention is unsuccessful. In this report, we describe a case of a 67-year-old woman with recurrent bilioenteric anastomotic stricture, accompanying bilateral hepatolitiasis after several times of transhepatic interventions. The patient underwent intrahepatic cholangiojejunostomy (Longmire procedure) and cholangioscopic lithotomy after resection of an atrophic left lateral segment resulting from hepatolithiasis. Although the damaged hilar bile duct had to be isolated and divided from the corresponding vasculature for re-anastomosis, it was quite impossible due to severe inflammatory change at the hepatic hilus. We, therefore, anastomosed the intact biliary stump on the cut surface of the left lateral segment to the jejunal loop with a stent tube. The patient's postoperative course was uneventful and she exhibited no evidence of cholangitis during follow-up period of 1 year after surgery. At present, the indications for intrahepatic cholangiojejunostomy for biliary obstruction, are quite limited, but biliary surgeons should keep this procedure in mind at the time of biliary reconstruction for benign proximal bile duct stricture, particularly in cases of multiply operated hilum.     

Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome‐wide SNP array

Prader–Willi syndrome is caused by the loss of paternal gene expression on 15q11.2–q13.2, and one of the mechanisms resulting in Prader–Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader–Willi syndrome. We report on two infants with Prader–Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome‐wide single‐nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post‐fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome‐wide single‐nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader–Willi syndrome. © 2012 Wiley Periodicals, Inc.