Roles of Salmonella typhi and Salmonella paratyphi in Gallbladder Cancer Development.

BACKGROUND: Typhoid (Salmonella typhi and paratyphi) carriers and gall bladder cancer (GBC) are endemic in northern India. Results of previous studies about association of typhoid carriers with GBC are inconsistent. We studied antibodies against Salmonella typhi and paratyphi in serum samples of patients with GBC. METHODS: We performed modified Widal test for antibodies against Salmonella typhi (Vi and O) and Salmonella paratyphi (AO and BO) antigens in patients with GBC (n=100), xanthogranulomatous cholecystitis (XGC, n=24), chronic cholecystitis (CC, n=200) and healthy controls (HC, n=200). RESULTS: Serum antibodies against Salmonella were more frequently positive in GBC (22%) and XGC (29%), particularly in males in age ≥50 years (GBC: 47% and XGC: 50%) vs. HC (0) (p <0.01). Vi antibody was more common in GBC (13%, OR:9.8) and XGC (8%, OR:5.9) than HC (2%). O antibody was more common in GBC (8%, OR: 8.6) and XGC (8%, OR: 9.0) than HC (1%). O antibody was also more common in males with GBC (12%) than CC (1%) and HC (1%) (P=0.02 and p <0.001, respectively). AO (6%) and BO (4%) antibodies were detected in GBC, particularly in males, than HC (0), (p <0.01). Salmonella antibodies were more frequent in GBC with GS than those without GS (50% vs. 20%, OR=3.94, P=0.01). CONCLUSIONS: Salmonella carrier state was more common in GBC and XGC, particularly in elderly males than HC. The Vi antibody was more common in GBC and XGC than HC. Salmonella infection was more common in GBC with GS than those without GS.

Xanthogranulomatous Ureteritis Mimicking Ureteral Involvement by Cancer in a Radical Cystectomy Specimen.

Xanthogranulomatous pyelonephritis is well established as a renal mass-forming inflammatory process. However, a ureteral counterpart is minimally recognized. In this article, we present a case of xanthogranulomatous ureteritis in an 81-year-old woman, mimicking ureteral involvement by cancer in a radical cystectomy specimen for invasive urothelial carcinoma. Similar to the pathogenesis of xanthogranulomatous pyelonephritis, the patient was noted to have ureteral obstruction by calculus and had urine culture positive for Klebsiella pneumoniae. To our knowledge, this is the first report of xanthogranulomatous ureteritis associated with this pathogen and the only report associated with concurrent bladder cancer. Increased pathologist and urologist awareness of xanthogranulomatous ureteritis expands the spectrum of pseudotumoral processes of the ureter.

Gastric Xanthoma Is a Predictive Marker for Early Gastric Cancer Detected after Helicobacter pylori Eradication.

Objective The detection of early gastric cancer (GC) after Helicobacter pylori eradication is expected to increase in Japan. However, the predictive markers for early GC detected after H. pylori eradication have not been extensively studied. We conducted a retrospective, single-center observational study to investigate the predictive markers for early GC detected after H. pylori eradiation. Methods A total of 421 patients underwent endoscopic submucosal dissection for early GC at NTT West Osaka Hospital between June 2006 and August 2017. Data from patients with GC (Group C; n=70) and without GC (Group NC; n=114) after H. pylori eradication were analyzed. Results The proportion of men was significantly higher in Group C than in Group NC (92.9% vs. 65.8%; p<0.0001). Complications with other malignant diseases were more prevalent in Group C than in Group NC. A significantly greater proportion of patients had gastric xanthoma (GX) in Group C than in Group NC (64.3% vs. 14.9%; p<0.0001). Regarding scores for endoscopic findings related to the risk of GC, the atrophy score, intestinal metaplasia score and total score were significantly higher in Group C than in Group NC. A multivariate logistic regression analysis identified male sex, atrophy (open type), the presence of intestinal metaplasia and GX as independent predictors for early GC detected after H. pylori eradication. An atrophy-matched control analysis also identified GX as an independent predictor. Conclusion GX is a novel predictive marker for early GC detected after H. pylori eradication.

Gastric xanthelasma and metabolic disorders: A large retrospective study among Chinese population.

AIM: To gain knowledge of xanthelasma, a large population-based study was conducted. METHODS: Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected, including blood routine, serum biochemical analysis, endoscopic findinds, histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows (IBM Inc., Chicago, IL, United States) using Student's t-test, Mann-Whitney U test, χ2 test, univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS: A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants (703 men, 667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%), abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori (H. pylori) infection rate, more of other gastric lesions including atrophy, intestinal metaplasia and dysplasia (P < 0.01). In xanthelasma patients, serum carcinoembryonic antigen, triglyceride, fasting glucose, neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high density lipoprotein-cholesterol, lymphocyte was lower (P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder polyp (P < 0.05). In logistic regression, it revealed that fasting plasma glucose (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P < 0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION: Current study described a large xanthelasma cohort in Chinese population, revealed its relationship with H. pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well.

Impact of Cyclooxygenase-2 1195 G-Carrier Genotype Associated with Intestinal Metaplasia and Endoscopic Findings Based on Kyoto Classification.

BACKGROUND/AIMS: We aimed to clarify whether cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) genotypes were associated with certain histological findings and endoscopical appearances based on Kyoto classification. METHODS: We enrolled 285 Helicobacter pylori-infected gastritis patients. Genotypes of COX-2 1195, COX-2 1290, mPGES-1, interleukin-1ß (IL-1ß) 511 and tumour necrosis factor-α (TNF-α) 308 were analyzed. Genotyping was performed by polymerase chain reaction. Endoscopic appearances and histological assessment were determined by using Kyoto classification, operative link on gastritic intestinal metaplasia assessment and the updated Sydney system. RESULTS: There was a significant (p = 0.027) relationship between the IL-1ß 511 C-carrier and histological gastric inflammation in H. pylori-infected gastritis patients. There was a significant (p = 0.009) correlation between the COX-2 1195 G-carrier genotype and histological intestinal metaplasia in the gastric antrum of H. pylori-infected gastritis patients and gastric xanthoma (p = 0.027). The COX-2 1195 G-carrier genotype was also significantly (p = 0.038) associated with the score of endoscopic intestinal metaplasia based on Kyoto classification. The mPGES-1 genotype was significantly (p = 0.002) associated with endoscopic swelling of area. CONCLUSION: Our results suggest that in Japan, there exists a significant correlation between the COX-2 1195 G-carrier genotype and intestinal metaplasia in histological and endoscopic findings based on Kyoto classification in H. pylori-infected gastric mucosa.

Xanthogranulomatous osteomyelitis of the humerus in a pediatric patient with Alagille syndrome: a case report and literature review.

Xanthogranulomatous osteomyelitis (XO) is an exceedingly rare disease characterized by infiltration of histiocytes and foamy macrophages. Both on gross examination and on radiographs, XO can mimic malignancy. We describe the case of a 5-year-old female with Alagille syndrome who presented with a pathologic fracture of the right humerus. Initial radiographs revealed multiple osteolytic lesions in the distal humerus while MRI showed a large soft tissue mass. Biopsy confirmed the diagnosis of XO, which has hitherto not been described in a patient with Alagille syndrome. The patient was admitted for IV antibiotics and taken to the operating room for an incision and debridement. Tissue cultures were obtained and grew Salmonella. Antibiotic therapy was tapered, and the patient responded to treatment. She was doing well at her 6-month follow-up visit. In the discussion section, we explore how osteopenia and immune dysregulation caused by Alagille syndrome can affect the development of XO. We summarize all previously reported cases of XO and conclude that XO presents as an osteolytic lesion that expands rapidly over the course of a few weeks. We highlight that XO can mimic sarcoma because of its mass effect but can be distinguished radiographically by the presence of surrounding sclerosis. Given the rapid onset of XO, we classify it as an acute osteomyelitis. We discuss how leukemia and Ewing sarcoma can present similarly to acute osteomyelitis. We then emphasize key features that can be used to distinguish these malignancies from acute osteomyelitis.

Xanthogranulomatous Adrenalitis: A Case Report of a Diabetic, 55-Year-Old Male.

We report a rare case of xanthogranulomatous adrenalitis in a 55-year-old man. The patient presented to the hospital with fever, nausea, and right flank pain. His medical history was significant for diabetes and an adrenal mass that was detected 6 years prior to presentation during a computed tomography (CT) scan for trauma secondary to a motor vehicle collision. The mass was thought to be a myelolipoma. Magnetic resonance imaging (MRI) revealed a 12-cm right adrenal mass that was considered suspicious for carcinoma, which was surgically excised and cultured intraoperatively. The cultures subsequently grew methicillin-resistant Staphylococcus aureus (MRSA). Grossly, the adrenal mass was an encapsulated, necrotic lesion with surrounding areas of fat necrosis. On histologic examination, the tissue showed sheets of histiocytes, lymphocytes, and plasma cells diffusely involving the adrenal gland along with bright yellow lipofuscin crystals in a background of necrosis and fibrosis.

Synovial xanthomatosis: are there clues to mechanisms for this rare disease?

We report a 64-year-old man with arthritis and nodules to describe that this picture can be caused by normo-lipidemic xanthomas. Light and electron microscopy (EM) plus polymerase chain reaction (PCR) studies were performed for diagnosis and investigation. These showed features typical of xanthomas plus PCR and EM evidence of possible infection with Chlamydia pneumoniae as a pathogenetic mechanism deserving consideration. With such rare diseases, any clues to possible mechanisms seem important to record and thus to encourage future investigations. This uncommon cause of arthritis and nodules had been confused with rheumatoid arthritis by others in this case.

Detection of spirochetal micro-organisms by focus-floating microscopy in necrobiotic xanthogranuloma.

BACKGROUND: Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disorder of unknown origin. OBJECTIVE: We conducted an investigation of skin biopsy specimens from 7 patients with NXG for the presence of Borrelia by focus-floating microscopy. METHODS: Focus-floating microscopy is a recently described, modified immunohistochemical technique in which the sections of a slide are simultaneously scanned both horizontally and vertically. Focus-floating microscopy is more sensitive for the detection of micro-organisms than polymerase chain reaction. RESULTS: Borrelia could be detected as single, paired, or clusters of spirochetes in 6 cases of NXG whereas two cases investigated with a Borrelia-specific polymerase chain reaction (23s-RNA) remained negative. LIMITATIONS: Limited biopsy material in each patient prohibited a more detailed study of the life history of cutaneous lesions in NXG. CONCLUSIONS: The detection of this micro-organism in NXG points to a specific involvement of B burgdorferi or other similar strains in the development of or as a trigger of this disease.

Involvement of Escherichia coli in pathogenesis of xanthogranulomatous cholecystitis with scavenger receptor class A and CXCL16-CXCR6 interaction.

Xanthogranulomatous cholecystitis (XGC) is characterized by the infiltration of numerous foamy macrophages. Bacterial infection is thought to be involved in the pathogenesis of XGC. Using XGC and cultured murine biliary epithelial cells (BEC), the participation of E. coli and the role of the scavenger receptor class A (SCARA), as well as chemokine(C-X-C motif) ligand 16 (CXCL16) and its receptor chemokine(C-X-C motif) receptor 6 (CXCR6), were examined in the pathogenesis of XGC. E. coli components and genes were detected in XGC on immunohistochemistry and polymerase chain reaction (PCR), respectively. SCARA-recognizing E. coli was found in foamy macrophages aggregated in xanthogranulomatous lesions. CXCL16, which functions as a membrane-bound molecule and soluble chemokine to induce adhesion and migration of CXCR6(+) cells, was detected on gallbladder epithelia, and CXCR6(+)/CD8(+) T cells and CXCR6(+)/CD68(+) macrophages were also accumulated. In cultured BEC, CXCL16 mRNA and secreted soluble CXCL16 were constantly detected and upregulated by treatment with E. coli and lipopolysaccharide through Toll-like receptor 4. These suggest that SCARA in macrophages is involved in the phagocytosis of E. coli followed by foamy changes and that bacterial infection causes the upregulation of CXCL16 in gallbladder epithelia, leading to the chemoattraction of macrophages via CXCL16-CXCR6 interaction and formation of the characteristic histology of XGC.

Three cases of xanthogranulomatous epididymitis caused by E. coli.

Xanthogranulomatous epididymitis is an uncommon but benign process, characterized by tissue destruction and the accumulation of abundant foamy macrophages mixed with lymphocytes and plasma cells. The pathogens generally found to cause xanthogranulomatous inflammation have been Proteus and E. coli. We identified such a pathogen by sequencing divergent regions of 16S rRNA, followed by pathogen-specific-PCR using alr, ipaH, ial, and iuc primer pairs in DNA microdissected from an H&E stained slide. We report here three cases of xanthogranulomatous epididymitis caused by E. coli.

Lethal outcome in xanthogranulomatous endometritis.

Xanthogranulomatous inflammation is rare, mainly involving the kidneys, while primary xanthogranulomatous endometritis (XE) is a very unusual finding, histologically characterized by partial or complete replacement of the mucosa by granulation tissue with an abundance of foamy histiocytes, siderophages and multinucleated giant cells. We present the case of a 69-year-old woman with a short history of abdominal pain and a palpable mass in the pouch of Douglas. Dilatation of the cervix drained a pyometra. Histological examination of the curettage rendered the diagnosis of XE. Microbiological studies revealed enterococcus spp. and Peptostreptococcus magnus. Despite antibiotic treatment the patient died of heart failure due to systemic inflammation. Autopsy confirmed the diagnosis of XE with transmural extension into the peritoneal cavity. Such a lethal course of XE is extraordinary. Proposed causes of XE include obstruction, infection and hemorrhage. Demonstration of enterococcus spp. and P. magnus supports the probable significance of bacteria in the development of XE. Because this condition may mimic malignant disease macroscopically and histologically, knowledge of XE is of major importance for both pathologists and gynecologists.

Xanthogranulomatous funiculitis and orchiepididymitis: report of 2 cases with immunohistochemical study and literature review.

Two patients with xanthogranulomatous inflammation are described, one with involvement of the spermatic cord and the other with 1 testicle and epididymis affected. To our knowledge, only 12 cases of xanthogranulomatous orchiepididymitis have been reported previously, one of which also presented a xanthogranulomatous funiculitis. Clinically, our patients presented with spermatic cord enlargement (case 1) and chronic orchitis that did not respond to treatment with antibiotics (case 2). Histopathologically, both cases showed extensive xanthogranulomatous inflammation with numerous foamy macrophages that were associated with colonies of microorganisms suggestive of actinomyces in case 1. Additionally, Escherichia coli was cultured from the surgical specimen of case 2. The possible underlying pathology may be diabetes in case 1 and phlebitis associated with chronic orchitis in case 2. Differential diagnoses with other lesions that are rich in macrophages, such as malakoplakia, and those testicular neoplasms without serologic tumor markers are discussed.

A close relationship between Helicobacter pylori infection and gastric xanthoma.

BACKGROUND: Although the pathogenesis of gastric xanthoma (GX) remains unclear, an association of GX with atrophic gastritis has been reported. Helicobacter pylori is closely related to atrophic gastritis. The aim of this study was to investigate the relationship among GX, H. pylori, and atrophic gastritis. METHODS: Sixty-seven patients with GX were assessed for H. pylori infection by serum anti-H. pylori IgG antibody, in addition to the rapid urease test, culture, and histologic examination using biopsy specimens of the antrum and corpus. The findings were compared with 67 age- and sex-matched control subjects without GX. The distribution of atrophic gastritis was assessed endoscopically. The severity of atrophic gastritis was determined endoscopically and histologically. Serum pepsinogen (PG) levels were also measured. Immunohistochemical staining of GX samples for H. pylori antigen was performed. H. pylori clinical isolates from patients with GX and controls were assessed for cagA by means of polymerase chain reaction. RESULTS: The prevalence of H. pylori was significantly higher in patients with GX than in controls (94% and 72%, respectively). A significantly more extensive atrophic gastritis was present in patients with GX, as determined endoscopically and histologically, than in controls. Serum PG-I levels and the PG-I/PG-II ratio were significantly lower in the GX group than in the control group. H. pylori antigens were frequently identified in the cytoplasm of xanthoma cells in H. pylori-positive specimens of GX (54 of 63 specimens, 86%), whereas no immunoreactivity for H. pylori antigens was detected in H. pylori-negative specimens of GX. There was no significant difference in the positive rate of cagA between the two groups. CONCLUSIONS: Our results identified a close relationship among H. pylori infection, GX, and atrophic gastritis. A proportion of GXs may be provoked by H. pylori infection.

Helicobacter pylori infection in gastric xanthomas: immunohistochemical analysis of 145 lesions.

A total of 145 paraffin-embedded biopsy samples of gastric xanthoma were analyzed for the localization of Helicobacter pylori (HP) antigens. By the indirect immunoperoxidase method using a polyclonal antibody, HP infection was identified on the surface of foveolar cells in 69 (48%) samples. In 38 (55%) of the 69 lesions, the HP antigens were demonstrated in the cytoplasm of xanthoma cells clustered in the actively inflamed lamina propria mucosae. Among the remaining 76 xanthoma lesions negative for HP infection on the epithelial surface, only eight (11%) showed the existence of HP antigens in the foamy histiocytes, and 39 (51%) revealed mild inflammatory change. Monoclonal antibody study using 75 specimens also gave a comparable result. Pre-embedding immuno-electron microscopy using paraffin sections revealed positively labeled rod-shaped bacteria both on the epithelial surface and in the phagosome of the xanthoma cells. These findings strongly suggest that some of the xanthoma lesions are provoked by lamina proprial invasion of surface-infected HP.

Growth temperature-dependent variation of cell envelope lipids and antibiotic susceptibility in Stenotrophomonas (Xanthomonas) maltophilia.

Clinical isolates of Stenotrophomonas (Xanthomonas) maltophilia showed growth temperature-dependent variation in susceptibility (TDVS) to aminoglycoside antibiotics between 30 degrees C and 37 degrees C, but little or no TDVS effect for polymixin B, colistin, ceftazidime, chloramphenicol and piperacillin. When phenylethanol was added at sub-inhibitory concentrations, the TDVS effect was eliminated. Gas liquid chromatography showed that 13-methyl tetradecanoate (i-15;0), was the predominant fatty acid, and was present in lower proportions in cells grown at 30 degrees C than 37 degrees C, by contrast to the unsaturated acids, which were found in increased proportions in cells grown at 30 degrees C. However, the extent of these shifts in composition did not correlate with the extent of the TDVS effect in individual strains. Membrane analysis by spin label-electron spin resonance spectroscopy showed that strains exhibiting TDVS had significantly decreased membrane fluidity compared with susceptible strains at 30 degrees C. Furthermore, analysis of the outer and cytoplasmic membranes from the strains with TDVS revealed that in organisms grown at 30 degrees C, the outer membrane remained in a more rigid conformation than the cytoplasmic membrane. We conclude that resistance of S. maltophilia to aminoglycoside antibiotics at 30 degrees C correlates with changes in the conformation of the outer membrane so that binding and/or uptake of the antibiotic is inhibited.

Verruciform xanthoma of the ear with coexisting epidermal dysplasia.

We report a case of verruciform xanthoma of the ear in a 79-year-old man. The case is unique in that it contained an area of solar keratosis. In situ hybridization using biotin-labeled probe cocktails for human papillomavirus types 6/11, 16/18, and 31/33/35 yielded negative results.