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.

Analysis of microvascular density in early gastric carcinoma using magnifying endoscopy with narrow-band imaging.

BACKGROUND AND STUDY AIMS: Intramucosal vascular density differs between differentiated and undifferentiated type gastric carcinomas. This study aimed to evaluate the microvascular density characteristics of these two types of carcinoma using magnifying endoscopy with narrow-band imaging (ME-NBI). PATIENTS AND METHODS: In total, 42 differentiated and 10 undifferentiated types were evaluated. The microvessels observed using ME-NBI were extracted from stored still images and the microvascular density in the two carcinoma types was analyzed. Histological vascular density in resected specimens was also evaluated using CD34 immunostaining. RESULTS: There were significant differences between the microvascular density in the differentiated and undifferentiated types of carcinoma (10.02 ±â€Š4.72 % vs 4.02 ±â€Š0.40 %; P < 0.001) using ME-NBI. Vascular density assessed histologically also differed significantly between differentiated and undifferentiated types in both the whole mucosal (5.81 ±â€Š3.17 % vs 3.25 ±â€Š1.21 %) and the superficial mucosal layers (0 - 100 µm) (6.38 ±â€Š3.73 % vs 3.66 ±â€Š1.46 %). However, the vascular density in the surrounding non-carcinomatous mucosa assessed using ME-NBI and histologically, was significantly lower in the differentiated than in the undifferentiated types (P < 0.001). There was good agreement between ME-NBI and histologically assessed microvascular density in both the whole (r = 0.740; P < 0.001) and superficial mucosal layers (r = 0.764; P < 0.001). White opaque substance (WOS) was seen in eight patients who had the differentiated type carcinoma. In almost all cases with WOS, the appearance of the carcinoma was discolored. CONCLUSIONS: There was a close relationship between ME-NBI assessed microvascular density and histologically assessed vascular density in the mucosal layer. Microvascular density differed significantly between the differentiated and undifferentiated types of carcinoma assessed using ME-NBI.

[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.

Characteristics of Small Bowel Polyps Detected in Cowden Syndrome by Capsule Endoscopy.

Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2-5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.

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.

Relationship between tumor necrosis factor-α release and granulocyte and monocyte adsorption to cellulose acetate beads.

Tumor necrosis factor-α, (TNF)-α, a proinflammatory cytokine, is produced by activated granulocytes and monocytes (GMs) and implicated as a major factor in inflammatory bowel disease (IBD) pathogenesis. Reduction of TNF-α should improve IBD pathology. GM adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including IBD. GM adsorption to cellulose acetate (CA) beads induces anti-inflammatory cytokine release, although these effects on TNF-α release are not clarified. We hypothesized that GMA may inhibit TNF-α release. The aim of the present study was to clarify the effects of GM adsorption to CA beads on TNF-α release in vitro. Peripheral blood was incubated with and without CA beads and TNF-α was measured. For comparison, TNF-α was measured in another lipopolysaccharide (LPS)-containing peripheral blood sample incubated similarly. The amount of TNF-α in blood samples incubated with CA beads was significantly higher than in those incubated without beads, although it was significantly lower than TNF-α incubated with LPS-containing sample without beads. The amount of TNF-α after incubation with CA beads positively correlated with GM adsorption ratio. GM adsorption to CA beads induced a small amount of TNF-α release. This is the first report on TNF-α release induced via GM adsorption stimuli. The biological effects of TNF-α release during GM adsorption need to be clarified.

[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.

Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas.

Mitogen-activated protein kinase phosphatase 5 (MKP-5)/DUSP10 acts as a phosphatase of stress-activated kinases (JNK and p38), but its activity towards ERK has not been demonstrated. In the present study we observed that MKP-5 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription. These data suggested a novel MKP-5 function as a scaffold protein for the ERK pathway. We analyzed MKP-5 gene expression in several tumors, and found that it is frequently upregulated in colorectal but not in lung and breast cancer, suggesting its association with the malignant phenotype of colon cancer.

[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 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.

[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.

Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias.

STUDY DESIGN: The mechanisms responsible for the spontaneous regression of lumbar disc herniation (LDH) were studied by examining herniated tissue collected at operation from patients with LDH. OBJECTIVE: The aim of the present study was to investigate the role of neovascularization and macrophages in hernias when spontaneous regression of LDH occurred. SUMMARY OF BACKGROUND DATA: Spontaneous regression of LDHs has already been demonstrated by diagnostic imaging with tools such as magnetic resonance imaging. However, there have been few studies on the mechanisms of spontaneous regression based on pathologic examination of herniated tissue. In particular, there has been no detailed work on the role of macrophages, which are thought to be closely associated with spontaneous regression. METHODS: The magnetic resonance imaging and operative findings of 73 patients who underwent surgery were investigated, and specimens collected during surgery were examined by light and transmission electron microscopy. RESULTS: Capillaries that invade the hernia and macrophages derived from monocytes migrating out of these capillaries are considered to be important factors in the regression of the herniated disc. Macrophages contain lysosomes filled with collagen-degrading enzymes that break down substances after phagocytosis, whereas primary lysosomes are secreted by these cells and break down intercellular substances such as collagen. Both of these mechanisms are closely involved in the regression of herniation. CONCLUSION: The inflammatory response that occurs around hernia tissue in the epidural space is believed to play an important role in herniated disc resorption, although it may also have a harmful effect on the adjacent nerve root. Therefore, control of the inflammatory reaction is an important challenge when treating patients with disc herniation.

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.

Synapse involvement of the dorsal horn in experimental lumbar nerve root compression: a light and electron microscopic study.

STUDY DESIGN: This study was aimed at investigating changes in the dorsal horn of the lumbar cord induced by mechanical compression using an in vivo model. OBJECTIVE: To determine the effect of axonal flow disturbance in the dorsal horns induced by nerve root compression. SUMMARY OF BACKGROUND DATA: Few studies have looked at changes of synapses within the dorsal horn caused by disturbance of axonal flow and the axon reaction as a result of mechanical compression of the dorsal root. METHODS: In mongrel dogs, the 7th lumbar nerve root was compressed for 1 week, or 3 weeks using a clip. After intravenous injection of Evans blue albumin, they were observed under a fluorescence microscope for the purpose of clarifying the function of the blood-spinal cord barrier. Morphologic changes of the synapses in the dorsal horns secondary to the nerve fiber degeneration were examined by light and electron microscope. Changes on immuno-staining for substance P, calcitonin gene-related peptide, and somatostatin in the dorsal horn were also examined. RESULTS: Light microscope observation conducted 1 week after compression of the nerve roots revealed Wallerian degeneration of the myelinated nerve in the dorsal horn, and fluorescence microscope observation of these areas demonstrated edema formation resulting from damage of the blood-spinal cord barrier. Three weeks after the compression, electron microscope observation revealed shrinkage of the axon terminals, ubiquitous presence of high electron density degeneration and presence of synapses whose contact with synapses was disrupted. Immuno-histochemical studies showed a marked decrease of substance P, calcitonin gene-related peptide, and somatostatin staining in substance gelatinosa with Wallerian degeneration after compression of nerve root. CONCLUSION: It is important to recognize that compressive disturbance of the nerve roots caused Wallerian degeneration not only at the site of compression of nerve roots but also at the synapses of spinal cord dorsal horns.

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.

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.

Long-term follow-up and knee osteoarthritis change after medial patellofemoral ligament reconstruction for recurrent patellar dislocation.

BACKGROUND: Proximal or distal realignment procedures have long been selected as treatment for recurrent patellar dislocation, but associated knee osteoarthritis has been a substantial problem that leads to poor results. A new approach, medial patellofemoral ligament reconstruction, has recently started, but there have been no reports on the long-term follow-up. HYPOTHESIS: Anatomical medial patellofemoral ligament reconstruction can lead to satisfactory long-term outcome and a low association rate of knee osteoarthritis. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-four knees from 22 patients who underwent medial patellofemoral ligament reconstruction for recurrent patellar dislocation were reviewed at a mean follow-up of 11.9 years (range, 8.5-17.2 years). A lateral release was done on 14 of 24 knees. The clinical/physical outcome and the association of knee osteoarthritis were investigated. Patellofemoral and femorotibial osteoarthritis on the radiographs was evaluated using the Crosby/Insall and the Kellgren/Lawrence grading systems. RESULTS: According to the Crosby/Insall criteria, 11 knees (46%) were classified as excellent, 10 (42%) as good, 3 (12%) as fair/poor, and none as worse at follow-up. Further lateral subluxation or dislocation occurred in only 2 knees. The mean Kujala score improved significantly from 63.2 points preoperatively to 94.2 points at follow-up (P < .0001). According to the Crosby/Insall grading system, patellofemoral osteoarthritis was none to mild in 23 of the 24 knees and moderate in 1 knee, pre-operatively. At the final follow-up, 21 knees were none to mild, and 3 knees were moderate. There were only 2 knees that had definite progression from none to mild to a moderate grade. CONCLUSION: The association of definite knee osteoarthritis in medial patellofemoral ligament reconstruction with or without lateral release was small in the long-term follow-up. The conclusion is that medial patellofemoral ligament reconstruction not only prevents further patellar dislocation but also shows no or only slight progression of knee osteoarthritis.

An algorithm guiding the evaluation and treatment of acute primary patellar dislocations.

Primary patellar dislocation continues to be a common problem facing clinicians today. These injuries are associated with significant morbidity and a substantial recurrence rate. A myriad of operative and nonoperative options have been described to treat these injuries though the evidence-based literature is sparse. As a result, much controversy exists regarding the ideal management of the primary patellar dislocation. This article reviews the literature on this topic, from the initial examination and management to definitive treatment. Furthermore, an algorithm is presented to help the clinician approach and treat these patients.