DIAGNOSIS OF INTESTINAL TUBERCULOSIS BY POLYMERASE CHAIN REACTION ON ENDOSCOPIC BIOPSY SPECIMENS

It is often difficult to establish the diagnosis of intestinal tuherculosis hecause of close similarities with other conditions, in particular. Crohn's disease. In the present study, we used the polymerase chain reaction (PCR) assay on endoscopic biopsy specimens obtained from a patient with chronic diarrhea. Positive hybridization was obtained with the Mycobacterium tuberculosis prohe and the patient was treated with anti-tuberculous drugs with complete resolution of the endoscopic ahnormalities. This study demonstrates that polymerase chain reaction assay can he used on endoscopic hiopsy specimens to diagnose intestinal tuberculosis.     

克罗恩病和肠结核活检及手术标本的病理学特征分析148例

目的:探讨克罗恩病(Crohn's disease, CD)和肠结核(intestinal tuberculosis,ITB)活检及手术标本的病理学特征在二者鉴别诊断中的价值.方法:选取在湘雅二医院、湘雅医院、湘西自治州人民医院确诊的CD和ITB患者各55例,其中活检标本各55例;手术病理标本CD 29例,手术ITB 9例.统计每例标本的病理学特征并进行比较.结果:CD患者活检标本与ITB患者活检标本比较,黏膜下层增宽、裂隙状溃疡及肉芽肿差异均有统计学意义(37.5%vs14.0%,10.9%vs0%,10.9%vs43.6%,均P<0.05);手术标本比较,黏膜下层增宽、裂隙状溃疡、固有肌层增厚、鹅卵石征及肉芽肿差异均有统计学意义(51.7%vs11.1%,34.5%vs0%,62.1%vs11.1%,37.9%vs0%,20.7%vs77.8%,均P<0.05).结论:活检标本的病理学特征鉴别CD和ITB价值有限,手术标本病理学特征对他们有鉴别价值,但仍需结合临床、内镜及影像学检查综合诊断.     

内镜活检对肠结核的诊断价值

目的探讨结肠镜检查及其活检标本对肠结核的诊断价值。方法对高度怀疑肠结核的患者34例进行结肠镜、胸腹部X线、病理组织学和结核菌PCR试验检查，并比较其阳性率。结果34例患者最终确诊为肠结核的有23例、克罗崽病3例、结肠癌3例，其他疾病5例。在各疾病中的阳性率均无明显差异。腹部X线阳性率47．8％，假阳性27．3％；内镜诊断阳性率为52．2％，假阳性27．3％；活检组织病理学阳性率82．6％，假阳性9．1％；PCR阳性率73．9％，假阳性18．2％；PPD阳性率52．2％，假阳性9．1％，结论结肠镜检查诊断肠结核的阳性率不高，结肠镜活柃标本进行组织学和结核菌PCR检测可显著提高肠结核的诊断率，但要注意假阳性结果。     

Endoscopic mucosal biopsies are useful in distinguishing granulomatous colitis due to Crohn's disease from tuberculosis

BACKGROUND: Intestinal tuberculosis and Crohn's disease are chronic granulomatous disorders that are difficult to differentiate histologically. AIMS: To characterise distinctive diagnostic features of tuberculosis and Crohn's disease in mucosal biopsy specimens obtained at colonoscopy. METHODS: Selected histological parameters were evaluated retrospectively in a total of 61 biopsy sites from 20 patients with tuberculosis and 112 biopsy sites from 20 patients with Crohn's disease. The patients were chosen on the basis of clinical history, colonoscopic findings, diagnostic histology, and response to treatment. RESULTS: The histological parameters characteristic of tuberculosis were multiple (mean number of granulomas per section: 5.35), large (mean widest diameter: 193 microm), confluent granulomas often with caseating necrosis. Other features were ulcers lined by conglomerate epithelioid histiocytes and disproportionate submucosal inflammation. The features characteristic of Crohn's disease were infrequent (mean number of granulomas per section: 0.75), small (mean widest diameter: 95 microm) granulomas, microgranulomas (defined as poorly organised collections of epithelioid histiocytes), focally enhanced colitis, and a high prevalence of chronic inflammation, even in endoscopically normal appearing areas. CONCLUSIONS: The type and frequency of granulomas, presence or absence of ulcers lined by epithelioid histiocytes and microgranulomas, and the distribution of chronic inflammation have been identified as histological parameters that can be used to differentiate tuberculosis and Crohn's disease in mucosal biopsy specimens obtained at colonoscopy.     

聚合酶链反应对肠结核和克隆病的诊断价值

肠结核的诊断及其与克隆病的鉴别诊断颇为困难。在本研究中我们探讨了聚合酶链反应（ＰＣＲ）技术在这两方面的价值。３６例肠结核、２６例克隆病标本被纳入本研究。引物来自结核杆菌特异重复插入序列ＩＳ６１１０。其产物特导性通过Ｓａ１Ｉ限制性内切酶消化和地高辛标记的探针经Ｓｏｕｔｈｅｒｎ杂交证实。结果显示：在３６例肠结核中，２７例ＰＣＲ阳性１２６例克隆病中无１例阳性。从而证实了ＰＣＲ对肠结核是一种快速、敏感和特异的病原学诊断方法；并对肠结核与克隆病的鉴别诊断具有极高价值。     

克罗恩病与肠结核临床及病理特征的对比研究

目的 探讨克罗恩病(CD)与肠结核(ITB)临床与病理特征,为两者鉴别诊断提供依据.方法 对1996-2007年四川大学华西医院临床、病理资料完整的33例CD和34例ITB的临床及病理资料进行同顾性分析.结果 CD出现症状到确诊的时间明显长于ITB(P<0.05),CD多因肠梗阻或诊断不明而手术,CD的便血、肠梗阻、肠外表现明显多于ITB(P值均<0.05),而盗汗、合并肺结核、低白蛋白血症和ESR升高、血清结核抗体阳性则更常见于ITB(P值均<0.05),CD患者仅累及空、回肠的情况明显多于ITB(P<0.05);CD患者内镜下纵形溃疡及鹅卵石样外观明显多于ITB(P值均<0.05),而ITB组环形溃疡更多见(P<0.05);ITB组的肉芽肿检出率(70.6%)明显高于CD组(29.4%)(P<0.05),且肉芽肿的位置有助于两者的鉴别;CD的手术标本的固有层底部/黏膜下层淋巴细胞聚集现象明显多于内镜活检标本(P<0.05).结论 尽管CD与ITB临床表现极其相似,但各自仍有一定的特征性,诊断需结合临床及病理资料进行综合分析.肉芽肿出现的几率、位置及炎症细胞分布范围与深度可作为两者病理鉴别要点.     

Intestinal Tuberculosis: Clinicopathologic Analysis and Diagnosis by Endoscopic Biopsy

Objective: Tuberculosis is still an important cause of granulomatous colitis in developing countries. If we can diagnose tuberculosis using endoscopic biopsy material, clinicians can avoid invasive diagnostic procedures and needless operations. For this purpose, we evaluated clinical manifestations, pathological findings, and diagnostic methods in endoscopically biopsied intestinal tuberculosis patients.
Methods: From January 1991 to December 1996, 42 patients with intestinal tuberculosis were endoscopically examined and tissue culture, immunohistochemical stain, Ziehl-Neelsen stain, and polymerase chain reaction in fresh and fixed tissue were applied. The pathological findings were analyzed and compared with the results of the other diagnostic methods.
Results: In tuberculosis patients, transverse ulcers with surrounding hypertrophic mucosa and multiple erosions were usual colonoscopic findings. The granulomas were found in 74% of the cases. The positivity ranged from 30–45%. There were no significant differences in the positivity among those diagnostic methods (   p > 0.05  ). The positivity of Ziehl-Neelsen stain in fixed tissue was higher in the group having granulomas and it was reversed in PCR (   p < 0.05  ). The increasing number of biopsy particles raised the positivity of Ziehl-Neelsen stain and PCR in fixed tissue (   p < 0.05  ). Conclusions: Transverse ulcers were the most characteristic colonoscopic finding and granulomas were frequent pathological findings in intestinal tuberculosis. Higher positivity and reliable results were found in tissue culture, Ziehl-Neelsen stain, and polymerase chain reaction. To increase the diagnostic rate, the endoscopist should take enough tissue and deep biopsy material from ulcer bases and diseased mucosae.     

The usefulness of colonoscopic biopsy in the diagnosis of intestinal tuberculosis and pattern of concomitant extra-intestinal tuberculosis]

BACKGROUND/AIMS: Intestinal tuberculosis can be difficult to diagnose because it may mimic many other intestinal diseases. The aim of this study was to evaluate the diagnostic yield of colonoscopic biopsy and frequency of concomittent extra-intestinal tuberculosis in intestinal tuberculosis. METHODS: The medical records of 225 consecutive patients with intestinal tuberculosis (81 men, 144 women; mean age 40.6 yrs) were analyzed retrospectively. RESULTS: Histological examination of colonoscopic biopsy specimens revealed granulomas in 163 (72.4%) of the 225 patients. However, caseous necrosis was found in only 25 (11.1%) patients, and acid-fast bacilli (AFB) were noted in 39 (17.3%) of the 225 patients. Mycobacterium tuberculosis was isolated from the culture of biopsy specimens in 52 (29.3%) of 177 patients. Eighty-four patients (37.3%) had concomitant extra-intestinal tuberculosis and 67 (29.8%) showed active pulmonary tuberculosis. Histological examination of the biopsy specimens enabled the diagnosis of intestinal tuberculosis by the presence of either caseating granulomas or AFB in 52 (23.1%) patients. Combination of histological examination and Mycobacterium culture established the diagnosis in 87 (38.7%) patients. Before getting the result of Mycobacterium culture, the diagnosis could be made, by either histological examination or the presence of extra-intestinal tuberculosis in 107 (47.6%) patients. Combination of caseating granulomas, AFB staining, Mycobacterium culture, and the presence of extra-intestinal tuberculosis resulted in the diagnosis in 126 (56.0%) patients. CONCLUSIONS: To increase the diagnostic yield, AFB staining and Mycobacterium culture should be routinely performed on biopsy specimens in addition to routine histological examination for caseating granulomas.     

克罗恩病和肠结核的组织病理学研究

目的：明确克罗恩病和肠结核的组织病理学特征，找出异同点。方法：利用手术切除的肠结核和克罗恩病理标本，观察其组织病理学特征并比较。结果：克罗恩病的特征为裂隙性溃疡、非干酪样坏死性肉芽肿、肿膜下层增宽；肠结核的特征为干酪样坏死、粘膜下层闭锁，肉芽肿融合，组织切片有许多相似之处，如微肉芽肿，全层炎症等，结论：典型的肠结核和克罗恩病易于鉴别，但二者组织病理学的相似性，给部分病例的鉴别诊断带来困难。     

Crohn's ileocolitis with initially superimposed cytomegalovirus infection, resembling intestinal tuberculosis]

We describe a case of 41-year-old Japanese man with Crohn's ileocolitis and cytomegalovirus infection, confirmed by histology of ileal ulcers. Although his colonoscopic and radiological features resembled those of intestinal tuberculosis, granulomas of typical Crohn's disease were evident on histology of biopsy specimens taken from the duodenum and colon. The lesions remain unchanged even after 1.5 years by oral administration of salazosulphapyridine 3g daily.     

Histopathology and TB-PCR kit analysis in differentiating the diagnosis of intestinal tuberculosis and Crohn’s disease

AIM: To compare the histopathologic features of intestinal tuberculosis (ITB) and Crohn’s disease (CD) and to identify whether polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) would be helpful for differential diagnosis between ITB and CD.METHODS: We selected 97 patients with established diagnoses (55 cases of ITB and 42 cases of CD) who underwent colonoscopic biopsies.Microscopic features of ITB and CD were reviewed,and eight pathologic parameters were evaluated.Nine cases of acid fast bac...     

内镜及病理学检查在克罗恩病和肠结核鉴别诊断中的价值

目的 评价内镜及组织病理学检查在克罗恩病和肠结核的鉴别诊断中的价值。方法 回顾性复习经手术证实的克罗恩病和肠结核各30例资料，对其临床、内镜表现、手术记录等进行分析，并重新审读病理切片。结果 内镜诊断克罗恩病的灵敏度、特异度和准确性分别为80．0％、25．6％和49．3％，而在肠结核中的灵敏度、特异度和准确性分别为86．7％、46．2％和63．8％。克罗恩病的病理学特征有非干酪样肉芽肿、粘膜下层增宽、裂隙样溃疡和淋巴细胞聚集；肠结核的病理特征有肠壁或肠淋巴结干酪样坏死、粘膜下层变窄或闭缩。结论 尽管找到了克罗恩病和肠结核的临床、内镜和组织病理学特征，但手术标本的组织病理学在鉴别诊断中仍起决定作用。     

Intestinal tuberculosis: Easier overlooked than diagnosed]

Intestinal tuberculosis: Easier overlooked than diagnosed.The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted.     

Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.

BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn's disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn's disease and suggest that the range of intestinal lesions in Crohn's disease may be wider than suspected on the basis of regular endoscopic and histological examinations.     

克隆产现与副结核杆菌

分支杆菌、尤其是副结核杆菌长期被疑为克隆病的致病菌。采用聚合酶链反应技术对手术及内镜活检的７４例石蜡包埋组织中的副结核杆菌ＤＮＡ进行检测。扩增的靶ＤＮＡ为副结核杆菌染色体特异重复插入序列ＩＳ９００１上４００ｂｐ的片段。其产笺特异性通过生物素杆主民的副结核杆菌全染色体探针Ｓｏｕｔｈｅｒｎ杂交证实。     

内镜及活检病理对回盲部溃疡的鉴别诊断

目的评价内镜及活检病理对回盲部溃疡性病变病因的诊断价值。方法经内镜检查发现回盲部溃疡，结合临床表现和活检病理对证实的回盲部溃疡改变如肠结核病、克罗恩病、溃疡性结肠炎、恶性淋巴瘤、大肠癌（溃疡型）进行鉴别诊断。结果内镜检查对溃疡性结肠炎、大肠癌较易诊断；对肠结核病、克罗恩病、恶性淋巴瘤诊断率不高。内镜组织活检病理形态学研究表明：异型淋巴细胞、异型上皮、类上皮结节合并干酪样坏死分别相对于恶性淋巴瘤、溃疡型大肠癌和肠结核病均有确诊意义（P〈0．05）；单纯类上皮结节（即结节样肉芽肿）见于克罗恩病和肠结核病，若未发现肠结核干酪样坏死，两者不易鉴别；隐窝脓肿多见于溃疡性结肠炎，但该病理特征诊断意义不强，可见于多种病变。结论回盲部病变以溃疡型病变最为多见。内镜及活检组织病理学检查对回首部溃疡病变的诊断是安全有效的，综合分析其结果可进一步提高诊断准确率。     

Microaggregate of immunostained macrophages in noninflamed gastroduodenal mucosa: a new useful histological marker for differentiating Crohn's colitis from ulcerative colitis

OBJECTIVE: In 10% of cases it may be difficult to differentiate Crohn's colitis from ulcerative colitis. Distinguishing the two conditions is important because they are distinct entities with different therapeutic implications. Noncaseating granulomas are usually considered diagnostic of Crohn's disease. We previously reported that the presence of a microaggregate of immunostained macrophages within the noninflamed gastroduodenal mucosa was a characteristic finding of Crohn's disease. The aim of this study was to determine whether a microaggregate of immunostained macrophages can be a reliable marker for differentiating Crohn's colitis from ulcerative colitis. METHODS: We investigated the presence of microaggregates of immunostained macrophages and epithelioid cell granulomas in biopsy specimens taken from the noninflamed gastroduodenal mucosa of 22 known Crohn's colitis patients and 23 established ulcerative colitis patients. The incidence of microaggregates and granulomas was compared between these two groups. RESULTS: Microaggregates and granulomas were detected only in the Crohn's colitis patients. In addition, the presence of microaggregates was more frequent than that of granulomas in Crohn's colitis patients (54.5% and 18.2%, respectively, 95% confidence interval for the difference: 10.0-62.7%). CONCLUSION: Detecting a microaggregate of immunostained macrophages in a biopsy specimen taken from noninflamed gastroduodenal mucosa seems to be a useful method for differentiating Crohn's colitis from ulcerative colitis.     

如何通过黏膜活检和超声内镜提供IBD的诊断线索

炎症性肠病(IBD)包括克罗恩病和溃疡性结肠炎,与肠道结核、淋巴瘤等均以肠道溃疡为特征,诊断往往依赖病理诊断金标准。但在临床上由于病理活检取材的局限,常不能提供疾病确诊的病理学依据,因而相互间的鉴别诊断较困难,常为临床上的治疗带来困惑。本文根据作者长期的内镜活检和超声内镜检查经验,介绍如何通过黏膜活检和超声内镜提供IBD的诊断线索,为临床医生确诊该类疾病提供借鉴和帮助。     

Segmental Tuberculosis of the Colon Diagnosed By Colonoscopy

Segmental tuberculosis of the colon is a rare clinical entity. In the absence of pulmonary or ileocecal involvement, colonic tuberculosis may be difficult to differentiate from neoplasm or Crohn's disease by symptomatic and radiological means. Colonoscopy and biopsy can, however, establish the diagnosis and prevent operative intervention, as indicated in the present report. A patient with a radiologically demonstrated strictured lesion of the sigmoid colon was found at colonoscopy to have several hemorrhagic transverse ulcers ranging in diameter between 1–4.5 cm. Multiple target colonoscopic biopsies, specifically from the ulcer beds, revealed necrotizing granulomas and acid-fast bacilli. Antituberculous chemotherapy produced remarkable symptomatic, radiographic and endoscopic improvements and averted exploratory laparotomy for the establishment of the diagnosis. This case report points out the importance of colonoscopic biopsy as a useful diagnostic modality in this disease.     

Mycobacteria and inflammatory bowel disease. Results of culture

We have been able to isolate mycobacteria from intestinal specimens obtained by surgical resection or endoscopic biopsy from patients with Crohn's disease, ulcerative colitis, and noninflammatory bowel diseases. Nineteen slow-growing (Runyon groups I and III) and 17 rapid-growing (Runyon group IV) mycobacterial isolates were obtained. Slow-growing mycobacteria were recovered from approximately one-third of intestinal biopsy specimens from Crohn's disease, one-quarter of ulcerative colitis biopsies, and 40% of biopsies from noninflammatory bowel disease patients. Isolates were most commonly members of the Mycobacterium avium-complex. One isolate (from an ulcerative colitis patient) was biochemically similar to the Mycobacterium strain previously associated with Crohn's disease, and one from a Crohn's disease patient was Mycobacterium kansasii. The rapid-growing organisms were members of the Mycobacterium fortuitum-complex. In addition to conventional mycobacteria, spheroplasts (cell wall-defective forms) were isolated from 12 patients with Crohn's disease (most often from surgically resected colon) and 3 patients with ulcerative colitis; none were isolated from non-inflammatory bowel disease patients. We have been unable to identify a consistent relationship between the presence, or the species, of Mycobacterium and Crohn's disease. Our results do not support the proposed role of a specific mycobacterium in the pathogenesis of Crohn's disease. The cause of Crohn's disease remains unclear.