Chronic intestinal graft-versus-host disease: clinical, histological and immunohistochemical analysis of 17 children

Graft-versus-host disease (GVHD) can be acute or chronic. The pathogenesis of chronic GVHD is unclear. Chronic GVHD affects mainly skin, liver and digestive tract. Intestinal involvement is uncommon and histological features are poorly described. We report here the clinical, histological and immunohistochemical features of chronic GVHD with intestinal involvement. Intestinal biopsies from children with chronic GVHD (n=17) were compared to control children (n=21: 10 non-transplant cases, four non-GVHD transplant cases, seven acute GVHD). We evaluated clinical outcome, histological features and characterized immunohistochemically the immune cells involved locally. Chronic GVHD with intestinal involvement was usually multisystemic (88.2%) and preceded by acute GVHD in 88.2% of cases. The outcome was severe with complete recovery in only 58.8% of cases, and death related to chronic GVHD in 17.6% of cases. Histological features were characterized by (1) villous atrophy and (2) glandular lesions, mainly apoptotic with variable intensity and (3) lamina propria infiltrate with cytotoxic T lymphocytes (CD3+, CD8+, TiA1+, granzyme B-) which were significantly (P<0.001) increased compared to non-GVHD transplant and non-transplant controls. Therefore in chronic intestinal GVHD, the apoptotic process could be related to cytotoxic T lymphocytes.     

Experimental reevaluation of myocardial ondulations in the early histological diagnosis of myocardial infarct

This investigation was undertaken in order to experimentally reassess the value of myocardial waviness and stretching as early histological indicators of acute myocardial infarction. Twenty three dogs were subjected to periods of ischemia, from 30 minutes to 4 hours; wavy fibers were present in 87% and 91% of the ischemic and non-ischemic samples respectively. It is concluded that myocardial fiber waviness lacks significance as an indicator or early myocardial infarction, whose diagnosis remains a major challenge.     

c-MET immunohistochemical expression in sporadic and inflammatory bowel disease associated lesions

BACKGROUNDPost-colonoscopy colorectal cancer (CRC) rates for patients with inflammatory bowel disease (IBD) are unacceptably high. During colonoscopy, an intravenous fluorescent anti-c-MET probe may improve endoscopic detection of lesions. However, c-MET expression in IBD lesions is poorly defined, limiting translational studies. AIMTo comprehensively define c-MET expression in sporadic and IBD-associated colorectal carcinogenesis. METHODSc-MET expression was immunohistochemically assessed in 319 formalin-fixed paraffin-embedded tissue specimens, colonoscopically or surgically retrieved between 1994-2017. Tissue included: 30 normal colorectal biopsies, 30 hyperplastic polyps (HP), 31 sessile serrated lesions (SSL), 55 tubular/tubulovillous adenomas with low (TA-LGD, n = 32) or high grade dysplasia (TA-HGD, n = 23), 26 sporadic (s)-CRCs, 16 quiescent IBD biopsies, 11 active/inflamed IBD biopsies, 18 IBD-associated dysplastic lesions (IBD-dys), and 102 IBD-CRCs. Expression was scored by two independent observers as: 0 = absent, 1 = weak, 2 = moderate or 3 = strong. Mann-Whitney U and Kruskal-Wallis tests were used to assess significance. RESULTSPositive epithelial cytoplasmic and membranous c-MET expression was observed in all tissues, indicating there is ubiquitous expression in the colorectum. c-MET expression was weak in normal colonic epithelium compared with each of the sporadic colonic lesions, including TA-LGD (P < 0.001), TA-HGD (P = 0.004), HP (P < 0.001), SSL (P < 0.001), and s-CRC (P < 0.001). Specifically, in sporadic (non-IBD) lesions, expression was stronger in TA-LGD compared with normal mucosa (P < 0.001), and stronger in s-CRC compared with TA-HGD (P = 0.004). However, there was no significant difference between TA-LGD and TA-HGD (P = 0.852). Further, there was no difference in c-MET expression between HP and SSL (P = 0.065). In IBD, expression was weaker in quiescent colonic mucosa compared with inflamed colonic mucosa (P < 0.001). There was no difference between inflamed colonic mucosa and IBD-dys (P = 0.512) or IBD-CRC (P = 0.296). However, expression was stronger in IBD-dys (P < 0.001) and IBD-CRC (P < 0.001) compared with quiescent IBD colonic mucosa. CONCLUSIONThe characterisation of c-MET expression suggest that an intravenous probe may improve the endoscopic detection of lesions in both non-IBD patients and IBD patients with quiescent disease.     

A quantitative immunohistochemical evaluation of inflammatory cells at the affected and unaffected sites of inflammatory bowel disease

Levels of T lymphocytes, histiocytes and mast cells have been reported to be increased in the affected mucosa of Crohn's disease (CD) and ulcerative colitis (UC), but the colorectal distribution of these cells is not fully understood. We hypothesized that differences in cell densities between CD and UC would be characteristic, not only in the affected, but also in the unaffected mucosa. The aims of the present study were to clarify whether there were any differences in cell densities in CD, UC and infectious colitis (IC) in the affected mucosa and between CD and UC in the unaffected mucosa. Using mouse monoclonal antibodies recognizing memory T cells (OPD4), cytotoxic/suppressor T cells (C8/144B), histiocytes (PG-M1) and mast cells (AA1), we evaluated mucosal cell densities in biopsy specimens from both endoscopically affected and unaffected sites of CD (n= 12) and UC (n= 15) and from affected sites of IC (n= 10). Ten normal controls were also examined. At affected sites, all cells were significantly more abundant in UC than in the other conditions, except that the density of PG-M1⁺ in CD was similar to that seen in UC. Although the densities of OPD4⁺ and C8/144B⁺ cells at unaffected sites were slightly higher in both CD and UC and in UC, respectively, there was no significant difference in cell densities between CD and UC. The ratio of OPD4⁺ cell density at affected sites to that at unaffected sites was appreciably higher in UC than in CD. The results suggest that a common feature of UC and CD is an increase in PG-M1⁺ cells at the affected mucosa but that the other inflammatory cells studied are more abundant, particularly in UC, and that the difference between UC and CD is conspicuous when comparing the OPD4⁺ cell density of the affected mucosa with that of the unaffected mucosa.     

重视炎症性肠病的规范化诊断与治疗

近年来,我国炎症性肠病（IBD）[包括溃疡性结肠炎（UC）和克罗恩病（CD）]报告病例数急增,3年前,基于多家医院病例统计推测,其患病率分别为11．6／10万和1．4／10万,且可能有被低估之虞。使该病成为我国消化系统常见疾病和慢性腹泻的主要病因。IBD临床诊断治疗相关问题纷繁复杂,难治性病例增多,已引起同行的高度重视。2005年全国IBD协作组成立以来,我们深感需要更加完善、与时俱进的诊治规范,并强调诊治规范应具有先进性、科学性、实用性和普及性。     

Polycystic liver disease: Classification,diagnosis, treatment process,and clinical management

Polycystic liver disease(PLD) is a rare hereditary disease that independently exists in isolated PLD, or as an accompanying symptom of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease with complicated mechanisms. PLD currently lacks a unified diagnostic standard. The diagnosis of PLD is usually made when the number of hepatic cysts is more than 20. Gigot classification and Schnelldorfer classification are now commonly used to define severity in PLD. Most PLD patients have no clinical symptoms, and minority with severe complications need treatments. Somatostatin analogues,mammalian target of rapamycin inhibitor, ursodeoxycholic acid and vasopressin-2 receptor antagonist are the potentially effective medical therapies, while cyst aspiration and sclerosis, transcatheter arterial embolization, fenestration, hepatic resection and liver transplantation are the options of invasion therapies.However, the effectiveness of these therapies except liver transplantation are still uncertain. Furthermore, there is no unified strategy to treat PLD between medical centers at present. In order to better understand recent study progresses on PLD for clinical practice and obtain potential directions for future researches, this review mainly focuses on the recent progress in PLD classification, clinical manifestation, diagnosis and treatment. For information, we also provided medical treatment processes of PLD in our medical center.     

Diabetic myocardial disease: pathophysiology, early diagnosis and therapeutic options

Diabetes mellitus is a powerful risk factor for cardiovascular disease associated with high morbidity and mortality rates. Diabetic patients also have an increased incidence of heart failure which has been traditionally attributed to the concurrent presence of ischemic or hypertensive heart disease. Yet, nowadays, according to recent scientific evidence, diabetic myocardial disease (DMD) is more and more being considered as a distinct nosologic entity, independent of the co-existence of coronary artery disease, arterial hypertension or other risk factors, with the potential to lead to a self-existent progressive development of heart failure.In this article, we review the possible pathophysiologic mechanisms involved in the development of DMD as well as the structural and functional changes in the diabetic heart. We emphasize the importance of early detection of the syndrome, especially by novel echocardiographic techniques. Finally, we refer to the various therapeutic options for the optimal management of DMD according to the recent literature.     

Campylobacter pylori in gastro-duodenal diseases, with special reference to endoscopic diagnosis, histological inflammatory grading, and intestinal metaplasia

To investigate the prevalence of Campylobacter pylori (CP) and its association with histological inflammatory grading and intestinal metaplasia, biopsies were carried out in 388 patients with gastro-duodenal diseases from 2 sites in the stomach (body and antrum). In each case, 3 biopsy specimens were taken from each site for culture, acridine orange stain and urease test. CP was detected in 55% of 22 endoscopically normal patients, in 47% of 17 gastric cancer patients, in 73% of 205 gastritis patients in 91% of 99 gastric ulcer patients and in 100% of 45 duodenal ulcer patients. In gastric ulcer and duodenal ulcer patients, CP detection rate was significantly higher than in endoscopically normal patients (p less than 0.01). There was no difference in CP detection rate irrespective of ulcer stage (active, healing or scar). According to the histological gradings of inflammation (Warren's criteria), CP was detected in only 3% in grade 0-I, 20% in grade II and 83% in grade III. It was found that a close association between CP and histological gastritis with polymorphonuclear leukocytes infiltration exists (p less than 0.001). In a few cases, CP was found even in the areas of intestinal metaplasia. But the number of CP in the areas of intestinal metaplasia were fewer than in the areas of surrounding inflamed gastric mucosa. In most cases, CP was not seen in the areas of intestinal metaplasia, but was found in the areas of surrounding inflamed gastric mucosa in the same biopsy specimen.     

Clinical molecular diagnosis of Wilson disease

Wilson disease is an autosomal recessive disorder of copper transport characterized by toxic accumulation of copper in the liver, brain, and other organs. It is lethal if untreated, but effective treatment is available. The broad spectrum of clinical manifestations, including hepatic and neuropsychiatric symptoms, can present over a large age range, contributing to difficulty in recognition of this disease. The diagnosis has traditionally rested on measurements of ceruloplasmin and copper in urine and liver, but it remains a challenge due to ambiguous biochemical results that can overlap with healthy carriers. Although hepatic copper concentration has been the gold standard for diagnosis, direct sequencing of the ATP7B gene is sensitive, specific, and can obviate the need for invasive liver biopsy. In this article, the authors review the sensitivity, limitations, and pitfalls of ATP7B sequencing in the diagnosis of Wilson disease. ATP7B sequencing should be standard practice in the diagnosis of Wilson disease.     

Pediatric inflammatory bowel disease: clinical and molecular genetics

Pediatric-onset inflammatory bowel disease (IBD) is characterized by distinct phenotypic differences compared to adult-onset IBD. This raises the question whether early (pediatric) onset IBD represents the same disease process occurring in adults but merely at an earlier age or does IBD in children have a very different etiology and pathogenesis but with the same clinical presentation as adults. The use of techniques such as whole genome association studies to perform broad, unbiased screening for the contributions of common genetic variations to complex disease has rapidly assisted in the identification of several novel susceptibility loci associated with pediatric-onset Crohn's disease such as IL23R and ATG16L1. These genes join the already confirmed IBD susceptibility genes such as NOD2/CARD15, IBD5, and DLG5. Therefore, there is hope that advances in the field of clinical and molecular genetics will assist in answering the fundamental question of whether pediatric IBD has a different etiology and pathogenesis compared to adult IBD. This review examines the current status of clinical and molecular genetics of pediatric IBD, and highlights the differences between pediatric and adult IBD in disease phenotypes and genotypes. Finally, the future directions of genetic investigations in pediatric IBD are discussed.     

Endoscopy in inflammatory bowel disease: Role in diagnosis,management, and treatment

Endoscopy plays a fundamental role in the diagnosis, management, and treatment of inflammatory bowel dis-ease(IBD). Colonoscopy, flexible sigmoidoscopy, and esophagogastroduodenoscopy have long been used in the care of patients with IBD. As endoscopic technologies have progressed, tools such as endoscopic ultrasound, capsule endoscopy, and balloon-assisted enteroscopy have expanded the role of endoscopy in IBD. Furthermore, chromoendoscopy has enhanced our ability to detect dys-plasia in IBD. In this review article, we will focus on the roles, indications, and limitations of these tools in IBD. We will also discuss the most commonly used endoscopic scoring systems, as well as special considerations in post-surgical patients. Lastly, we will discuss the role of endoscopy in the diagnosis and management of fistulae and strictures.     

Hyperplastic colorectal polyp: histological, histochemical and immunohistochemical study of 43 cases

Forty-three solitary hyperplastic polyps removed from the colon or the rectum (HPC) were examined under light microscopy. A histochemical and immunohistochemical study was undertaken in order to evaluate semiquantitatively the nature and the distribution of epithelial mucins and the secretion of carcinoembryonic antigen (CEA). Ten HPC had a peculiar morphologic pattern (four with regenerative dysplasia and six with adenomatous foci). CEA secretion was always increased (37 per cent of cases) or highly increased (63 per cent of cases) with respect to the normal colonic mucosa. The nature and distribution of the secreted acid mucins were modified: sulfomucin was equal (25 per cent of cases) or higher (75 per cent of cases) than that in normal rectal or sigmoid colonic mucosae; sialomucin was strongly decreased in 91 per cent of cases. Some of these functional changes (CEA) are also observed in neoplastic lesions. These findings are not in accord with the hypothesis that hyperplastic polyp is a simple hyperplasia of the mucosal epithelium and suggest a disorder in cellular differentiation, particularly for the larger polyps.