Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions.

The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

Esophageal carcinoid tumor treated by endoscopic resection.

The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43-year-old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow-band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low-echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.

[Characteristics of group A patients according to the ABC classification for gastric cancer risk screening].

In the ABC classification for gastric cancer risk screening, group A (Helicobacter pylori infection-negative, pepsinogen [PG]-negative) patients are assumed to be at low risk, but some patients do have atrophic gastritis and H. pylori infection. This study aimed to identify the characteristics of group A patients. Healthy adults in Yamagata City who underwent barium radiography and ABC classification participated in the survey. Patient radiographs were randomly interspersed and reviewed by two gastroenterologists who were blinded to the H. pylori and PG statuses. Group A patients (n=1462) was subclassified as follows: atrophic gastritis group, 21.5%; intermediate group, 15.7%; and no atrophic gastritis group, 62.8%. Elderly subjects and those with H. pylori antibody titers of 3.0-9.9U/ml should be carefully evaluated while interpreting the results of the ABC classification for gastric cancer risk screening.

[Chylothorax in a patient with advanced gastric cancer and mediastinal lymph node metastasis causing thoracic duct obstruction].

We report the case of a 61-year-old female with advanced gastric cancer and mediastinal lymph node metastasis who developed chylothorax. The patient presented with cough, dyspnea and pain in the left lower limb, back, and hips. Her lower limb symptoms were attributed to cellulitis. Computed tomography revealed right-sided pleural effusion, multiple lymph node swelling, and thickening of the gastric wall. Following pleural aspiration, the effusion was identified to be chyle. Cytopathologically, numerous adenocarcinoma cells were detected in clumps, and subsequent esophagogastroduodenoscopy revealed type 3 gastric cancer. We diagnosed multiple lymph node metastases with pleural dissemination. Chemotherapy was administered; however, she eventually succumbed to disease progression. We suspected that the chylothorax resulted from the mediastinal lymph node metastasis that caused thoracic duct obstruction.

Small Bowel Endoscopic Features of Eosinophilic Gastroenteritis.

Eosinophilic gastroenteritis (EoGE) is a rare digestive disorder characterized by eosinophilic infiltration of the stomach and intestines. In the diagnosis of EoE, it is extremely important to recognize distinctive endoscopic findings and accurately detect increased eosinophilia in gastrointestinal tissues. However, endoscopic findings of EoGE in the small intestine remain poorly understood. Therefore, we conducted a literature review of 16 eligible papers. Redness or erythema was the most common endoscopic finding in the small bowel, followed by villous atrophy, erosion, ulceration, and edema. In some cases, stenosis due to circumferential ulceration was observed, which led to retention of the capsule during small bowel capsule endoscopy. Although many aspects of small bowel endoscopic findings in EoGE remain elusive, the findings presented in this review are expected to contribute to the further development of EoGE practice.

TNFSF15 transcripts from risk haplotype for Crohn's disease are overexpressed in stimulated T cells.

TNFSF15 is a susceptibility gene for Crohn's disease (CD). It remains to be elucidated how the associated single nucleotide polymorphisms (SNPs) in TNFSF15 affect the susceptibility to CD. Because there are no non-synonymous SNPs in TNFSF15, we speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells (PBMCs). When PBMCs stimulated by phytohemagglutinin (PHA) were examined, the allelic ratio of mRNA transcribed from the risk haplotype to the non-risk haplotype increased, compared with the ratio without stimulation. When peripheral blood T cells and Jurkat cells stimulated by phorbol 12-myristate 13-acetate + ionomycin were examined, an allelic expression imbalance similar to that observed in PBMCs stimulated by PHA was confirmed. The promoter assay in stimulated Jurkat cells showed that the luciferase activity of the promoter region (-979 to +35) of the risk haplotype was significantly higher than that of the non-risk haplotype, and deletion and mutagenesis analysis demonstrated that this difference resulted from the -358T/C SNP. The promoter activity of -358C (risk allele) was higher than that of -358T (non-risk allele) in stimulated T cells. This effect of -358T/C on the transcriptional activity in stimulated T cells may confer susceptibility to CD.

DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression.

The dual-specificity phosphatase (DUSP) 13 gene encodes two atypical DUSPs, DUSP13B/TMDP and DUSP13A/MDSP using alternative exons. DUSP13B protein is most highly expressed in testis, particularly in spermatocytes and round spermatids of the seminiferous tubules, while that of DUSP13A is restricted to skeletal muscle. Here, we show that DUSP13B inactivated MAPK activation in the order of selectivity, JNK = p38>ERK in cells, while DUSP13A did not show MAPK phosphatase activity. Reporter gene analysis showed that DUSP13B had significant inhibitory effect on AP-1-dependent gene expression, but DUSP13A did not. To our knowledge, DUSP13B is the first identified testis-specific phosphatase that inhibits stress-activated MAPKs. These data suggest an important role for DUSP13B in protection from external stress during spermatogenesis.

[A case of early cystic duct carcinoma concomitant with xanthogranulomatous cholecystitis (XGC)].

We reported a case of early cystic duct carcinoma concomitant with xanthogranulomatous cholecystitis (XGC). This case was a 72-year-old man in whom thickening of the gallbladder wall was pointed out an abdominal ultrasonography and elevation of the CA19-9 level was detected at a local clinic. Endoscopic ultrasonography and CT demonstrated a mass in the cystic duct. Mapping biopsy using peroral cholangioscopy (POCS) revealed a diagnosis of cystic carcinoma with superficial flat growth, therefore a pylorus-preserving pancreatoduodenectomy was performed. Histopathological diagnosis was well differentiated papillotubular adenocarcinoma with superficial flat spread and the thickening of the gallbladder wall was XGC. A case of early cystic duct carcinoma concomitant with XGC is extremely rare.

[Regression of MALT lymphoma of the rectum after Helicobacter pylori eradication therapy in a patient negative for Helicobacter pylori].

A 53-year-old woman was referred to our hospital for further examination of a rectal polypoid lesion. Colonoscopy revealed a submucosal tumor in the rectum (Ra) and a diagnosis of MALT lymphoma was made on the histological examination of the biopsy specimens and Southern blot analysis of the immunoglobulin heavy chain gene rearrangement. Although the patient was negative for Helicobacter pylori, H. pylori eradication therapy was performed. Colonoscopy 3 months after the eradication therapy showed disappearance of the rectal tumor. H. pylori eradication appears to be a useful treatment for not only H. pylori-positive colonic MALT lymphoma but H. pylori-negative colonic MALT lymphoma.

[A case of pancreatic endocrine tumor developing from intraductal papillary mucinous neoplasm (IPMN)].

In March, 2004, a 64-year-old man was given a diagnosis of IPMN of the pancreas in postoperative CT of left shoulder blade chondrosarcoma. In October, 2007, because a tumor in the pancreas body was found, distal pancreatectomy was performed a diagnosis of the poorly differentiated adenocarcinoma. Histopathologic diagnosis revealed as pancreatic endocrine tumor and immunity dyeing was useful for differential diagnosis. A case of pancreatic endocrine tumor developing from IPMN has a possibility not rare for frequency, but few reports are available so far.

[A case of primary gastric mantle cell lymphoma].

Endoscopic examination of a 60-year-old man revealed multiple erosions in the gastric antrum. After 6 months, erosions also formed in the duodenal bulb and systemic lymph nodes become enlarged. After 20 months, the gastroduodenal erosions developed into mucosal ulcers, and the systemic lymph node swelling progressed. Histological examination of the neck lymph node showed mantle cell lymphoma (MCL). This result agreed with the results of the gastroduodenal biopsy. This case was diagnosed as recurrent primary gastric MCL in other areas, with systemic lymph node metastasis and bone marrow invasion. Hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone), high-dose methotrexate and cytarabine in combination with Rituximab and stem cell transplantation was performed. The gastroduodenal lesions and atypical cells in the bone marrow disappeared after 2 cycles of the chemotherapy. Metastatic lymph node swelling regressed after stem cell transplantation. We have had no evidence of recurrence for 50 months. Primary gastric MCL is very rare and cyclin D1 immunohistochemistry and FISH assay were very useful for the diagnosis of MCL.

Two cases of SAPHO syndrome accompanied by classic features of Behcet's disease and review of the literature.

We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.

Fine structure of cartilage canal and vascular buds in the rabbit vertebral endplate. Laboratory investigation.

OBJECT: The vascular terminations (vascular buds) in the bone-disc junction area are structurally very similar to cartilage. In all previous studies to date, however, the roles of cartilage canals and vascular buds were mainly discussed using histological and transparent sections but not electron microscopic sections. The purpose of this study was to clarify the ultrastructure of the vascular bud seen in the bone-disc junction in comparison to the cartilage canal. METHODS: Japanese white rabbits from 2 days to 6 months of age were used in this study. The bone-disc junctions were examined by microangiogram and light and electron microscopy, and morphological changes and their association with the age of the animals were noted. RESULTS: The fine structure of the vascular bud was similar to that of the cartilage canal that nourished the growing cartilage. They were composed of arteries, veins, capillaries, cells resembling fibroblasts, and macrophages. The capillaries in the cartilage canal were all the fenestrated type. Vascular buds were seen over the entire bone-cartilage interface, with maximum density in the area related to the nucleus pulposus. They projected into the bone-disc junction area from the vertebral body contacting the cartilaginous endplate directly. CONCLUSIONS: The results of this study clarify the formation process and ultrastructure of the vascular bud seen in the bone-disc junction. The authors found a strong structural resemblance between the vascular bud and the cartilage canal and hypothesize that the immature cells seen surrounding the cartilage canal and vascular bud represent a common precursor for the 3 main types of connective tissue cells seen during early vertebral development.

Mapping of a disease susceptibility locus in the HLA region for Primary Biliary Cirrhosis in Japan.

AIMS: Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic disease of unknown pathogenesis. However, several reports have demonstrated the involvement of genetic backgrounds in this syndrome. The aim of this study is to examine the genetic disequilibrium in the HLA region in Japanese patients using six microsatellite markers. METHODS: Genomic DNAs were obtained from 73 patients with PBC (patient cohort) and 186 healthy volunteers (control cohort). Genetic polymorphisms at six microsatellite markers (D6S1568, DQ.CAR, D6S273, TNF-d, C1-2-A, C3-2-11) were determined using fluorescence-labeled polymerase chain reaction (PCR) genetic analyzer. Allele frequencies were estimated by direct counting and the genotypic differentiation test was performed by the Markov chain method using Genepop software. RESULTS: Among these six microsatellite markers, four markers in the patients significantly (P < 0.05) deviated from the Hardy-Weinberg equilibrium: DQ.CAR (P = 0.0278), D6S273 (P = 0.0168), TNF-d (P = 0.0089) and C1-2-A (P = 0.0005). Genotypic differentiation test between the patients and controls demonstrated that DQ.CAR (P = 0.0111), TNF-d (P = 0.0051) and C1-2-A (P = 0.0371) were significant. Finally, allelic association test revealed before correction for multiple testing demonstrated allele125 of TNF-d (P = 0.00065, Pc = 0.0052) and allele246 of C1-2-A (P = 0.0026 Pc = 0.033) had significant association after Bonferroni's correction. CONCLUSION: Disequilibrium mapping using microsatellite markers was a useful method to narrow a disease susceptibility locus. The possible susceptibility gene in the HLA region is thought to be localized around or in the TNF gene. Further studies seem feasible using more closely distributed microsatellite markers or single nucleotide polymorphisms (SNPs) to narrow the susceptibility locus in PBC in Japanese populations.

Atlantoaxial subluxation-induced myelopathy in cleidocranial dysplasia. Case report.

The authors describe the clinical course and treatment of a patient with cleidocranial dysplasia in whom spastic myelopathy developed due to atlantoaxial subluxation. This 27-year-old woman with cleidocranial dysplasia and a history of atlantoaxial subluxation presented with spastic myelopathy. Surgery was performed twice for cervical myelopathy and atlantoaxial subluxation, including laminectomy at the atlas and cervicooccipital fusion in which the Luque rod system was used, as well as C1-2 fusion via the transpharyngeal route. Solid bone fusion was achieved by 7 months postsurgery. Postoperative magnetic resonance imaging studies demonstrated that spinal cord compression was relieved, but atrophy persisted. At 2 years postsurgery there was no neurological disease progression, but spasticity persisted. The patient could walk with a cane. Cleidocranial dysplasia is an extremely rare cause of myelopathy in patients with atlantoaxial subluxation; the authors know of only two reports of this condition. When managing cleidocranial dysplasia, the practitioner should always be aware that atlantoaxial subluxation may be the cause of cervical myelopathy.

Bilateral recurrent patellar dislocation in a patient with isolated patella aplasia-hypoplasia.

Patella aplasia-hypoplasia is a rare condition characterized by the congenital absence or marked reduction of the patellar bone. It is well known that patella aplasia-hypoplasia occurs in nail-patella syndrome, small patella syndrome, and several other syndromes. However, isolated patella aplasia-hypoplasia without associated clinical or radiologic anomalies, first described by Kutz in 1949, is an extremely rare condition. This report describes 12 years' follow-up after medial patellofemoral ligament reconstruction surgery performed for bilateral recurrent patellar dislocation in a 29-year-old patient with isolated patella aplasia-hypoplasia. The patient had no radiographic findings of elbow abnormalities, exostoses of the ilia, or abnormal ossification of the ischiopubic junction. The right patella was severely subluxated, and the left patella was mildly subluxated. The preoperative Kujala score was 28 points for the right patella and 23 points for the left. Medial patellofemoral ligament reconstruction, wide lateral release, and patellaplasty with multiple drilling were done in July 1993 for the left knee and in August 1993 for the right. At 12 years' follow-up, the Kujala score was 68 points for the right patella and 73 points for the left, and the patient was satisfied with the result. Magnetic resonance images showed both patellae without subluxation and bulky regenerated ligaments.

Microvascular system of anterior cruciate ligament in dogs.

This study was done to investigate the microvascular system of anterior cruciate ligament (ACL) using dogs. The objective was to study the microvascular architecture and the status of the barrier function of the capillary wall in the ACL by using microangiogram, scanning (SEM), and transmission electron microscopy (TEM). The vascular system in the ACL has been intensively studied by a number of researchers, using several microangiographic techniques in dogs, rabbits, and humans. However, most of these microangiographic studies had significant shortcomings, including the lack of three-dimensional observations and function of the blood-joint barrier in the ACL. In this study, the microstructure of the ACL was examined using microangiogram, SEM, and TEM. We investigated the vasculature of the ACL with SEM of vascular corrosion casts. In addition, we examined the status of the barrier function of the capillary wall in the ACL using the protein tracer horseradish peroxidase (HRP). Feeding vessels of the ligament were predominantly coming from the synovial-derived vessels originating from the synovium attached to the ligament near the tibial and femoral bone insertions of the ACL. The anterior cruciate ligament was surrounded by synovium, which had abundant vessels. The branches of these synovial vessels were penetrating into the ligament and making the intrinsic vascular network. It was also ascertained under SEM that the perivascular space around the intrinsic vessels were communicating through the intrinsic ligament fiber bundles and the mesh-like synovial membrane. The capillaries in the ACL were all of the continuous type under TEM. The protein tracer that was injected into the joint space passed through the synovial membrane and entered into the capillary lumen in the ACL, but the tracer that was injected intravenously did not appear in the perivascular space. The existence of a blood-ACL barrier does not necessarily imply the existence of an ACL-blood barrier. We think that the blood flow in the ACL is definitely affected by the status of joint fluid and these barriers of endothelium. The clinical relevance of the fine vascular anatomy of the ACL in trauma surgery is considered. This deserves further consideration.

Hybrid medial patellofemoral ligament reconstruction using the semitendinous tendon for recurrent patellar dislocation: minimum 3 years' follow-up.

PURPOSE: The purpose of this study was to evaluate the results of a new hybrid medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation. METHODS: Hybrid MPFL reconstruction by use of the semitendinous tendon was performed in 12 knees with recurrent patellar dislocation. The results were evaluated at a minimum follow-up of 3 years (mean, 4.2 years). RESULTS: According to the grading system of Insall et al., the results were classified as excellent in 8 knees (66%), good in 2 (17%), and fair in 2 (17%), with none being classified as poor. The mean Kujala score was 56.3 points (range, 29 to 82) preoperatively and 96.0 points (range, 84 to 100) at follow-up. There were no patients with recurrent dislocation and subluxation. No knees had a positive apprehension sign, and there were no postoperative complications. CONCLUSIONS: At a midterm follow-up, hybrid MPFL reconstruction by use of the semitendinous tendon for recurrent patellar dislocation should be considered as an effective operation for cases without severe predisposing factors. LEVEL OF EVIDENCE: Level IV, therapeutic case series, no or historical control group.

Generalized joint laxity and contralateral patellar hypermobility in unilateral recurrent patellar dislocators.

PURPOSE: The purpose of this study was to assess the relation between generalized joint laxity and patellar hypermobility in unilateral recurrent patellar dislocators. TYPE OF STUDY: Case series. METHODS: A total of 82 patients (23 male and 59 female patients) with unilateral recurrent patellar dislocation were studied compared with an age- and sex-matched control group. The modified Carter and Wilkinson criteria for generalized joint laxity and lateral patellar hypermobility test were examined. RESULTS: Generalized joint laxity (score of 4 or 5) was present in 20 patients (24%) with recurrent patellar dislocation in 8 subjects (10%) of the control group. The mean total score was 2.5 (SD, 1.4) in the recurrent patellar dislocators and 1.7 (SD, 1.3) in the control group. The incidence of generalized joint laxity (P = .013) and the mean total score (P = .00004) were statistically significant between the two groups. A hypermobile patella was present in 42 patients (51%) and in 5 subjects (6%) of the control group. There was a large statistically significant difference between the two groups (P < .00001). CONCLUSIONS: Although a hypermobile patella and generalized joint laxity were significant between the recurrent patellar dislocators and the control group, a hypermobile patella was more significant than generalized joint laxity as the predisposing factors of patellar dislocation. LEVEL OF EVIDENCE: Level IV, prognostic case series.