Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

全结直肠切除、回肠J形贮袋肛管吻合术后肛管压力的变化

目的探讨全结直肠切除回肠贮袋肛管吻合术(ileal pouch-anal anastomosis,IPAA)后患者控便能力与肛管压力的关系。方法对16例患者行IPAA术,术后1个月、6个月、1年时随访控便能力,并检测肛管压力。结果12例获得随访,平均2.3(1.0~4.5)年,患者排便次数在术后1年时明显少于术前和术后1个月(P<0.05);肛管静息压和最大缩柞压在术后1个月、6个月时明显低于术前(P<0.05),但在术后1年时已有明显改善,与术前相似(P>0.05)。结论IPAA术后肛管压力的改变可能与患者的控便能力有关。     

Lymphoid follicular hyperplasia–a distinctive feature of diversion colitis

Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intesting following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Behcet's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease. with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined.     

不同方案缺血预处理对大鼠横形腹直肌肌皮瓣再灌注损伤的影响

目的 探讨不同方案缺血预处理（ischemic preconditioning，IPC）对大鼠横形腹直肌肌皮瓣（transverse rectus abdominis musculocutaneous flap，TRAM）移植后再灌注损伤的影响。方法选取雄性Wistar大鼠90只，建立TRAM模型，随机分为对照组和实验组，对照组10只，无需预处理过程，持续缺血4h后，恢复肌皮瓣血供；实验组分为8个亚组，每组10只，以微血管夹阻断腹壁下血管5min，再恢复血流5min，处理1次为sIPC5／5组，处理2次为bIPC5／5组，依次为sIPC5／10组（缺血5min／再灌注10min1次）、bIPC5／10组（缺血5min／再灌注10min2次）、sIPC10／5组（缺血10min／再灌注5min 1次）、bIPC 10／5组（缺血10min／再灌注5min2次）、sIPC10／10组（缺血10min／再灌注10min1次）、bIPC10／10组（缺血10min／再灌注10min2次），其余实验步骤与对照组相同；每组肌皮瓣恢复血供4h后，取3只处死取材，测定肌组织含水量及HE染色镜检观察骨骼肌组织结构，其余动物于术后第7天判断皮瓣成活情况，计算成活面积百分比。结果恢复血供12h后，各实验组肌皮瓣两侧边缘部分肿胀，色泽黯淡，较对照组肿胀范围小，程度轻；光镜下见各实验组肌纤维轻度肿胀，染色均一，肌纤维结构尚完整，胞核呈梭形，无明显肿胀。对照组肿胀明显，部分肌纤维断裂。各实验组与对照组相比肌组织水含量明显减少（P〈0．001），皮瓣成活面积提高了2～3倍（P〈0.001）。两次预处理对肌皮瓣成活面积的影响与相应的单次预处理比较，差异有统计学意义（P〈0．05）。结论IPC可明显减轻大鼠TRAM再灌注损伤程度，其保护效应受缺血／再灌注时间、处理次数等因素的影响。     

Atypical Allergic Colitis in Preterm Infants

ABSTRACT. Two atypical cases of colitis due to cow's milk protein intolerance (CMPI) are reported, affecting preterm infants. One developed a toxic dilatation of the colon and responded well to a casein hydrolysate based feed. The second presented insidiously and failed to tolerate a casein hydrolysate, but responded well to a chicken-based modular feed.     

Leukocyte Apheresis Using a Centrifugal Cell Separator in Refractory Ulcerative Colitis: A Multicenter Open Label Trial

Abstract: Recently, successful results of ulcerative colitis (UC) treatments with leukocyte apheresis have been reported by several institutes. To certify the efficacy of leukocyte apheresis in refractory UC patients, a multicenter open label trial was conducted, and results were analyzed. Fifty patients diagnosed with active steroid‐resistant UC were enrolled in this study from 14 medical centers. Using a centrifugal cell separator (Component Collection System, Haemonetics), leukocyte apheresis was performed once a week for 5 weeks. General conditions and abdominal symptoms were recorded daily, and laboratory tests were followed weekly. Changes of colonoscopic and histological manifestations of luminal activity through the study period were evaluated. At the end of the study period, stool frequency was decreased to less than 4 times a day in 68.4% (26 of 38) and serum C‐reactive protein (CRP) concentration was normalized in 56.7% (17 of 30) of the patients. Colonoscopic remission was achieved in 57.7% (26 of 45), and histological improvement was noted in 54.1% (20 of 37) of the patients tested. Improved disease activity was demonstrated in 74% (37 of 50) of the patients by general assessment criteria. Analysis of the trial data confirmed the valid clinical efficacy of leukocyte apheresis by centrifugal cell separator in refractory UC patients.     

Outcome of a conservative approach in severe ulcerative colitis.

BACKGROUND: Severe ulcerative colitis is potentially life threatening even though a policy of intensive medical management and early colectomy in recent years reduced mortality to almost zero. However, colectomy, with or without ileal-anal anastomosis, has its own problems (morbidity, pouchitis, cuffitis) and no reliable prognostic index of surgical outcome has been developed. Intravenous steroids are still the mainstay of medical therapy but their maximal duration before stating a 'treatment failure' has not been defined. AIM OF THE STUDY: To evaluate the effectiveness, safety and outcome of an intensive medical approach in a series of patients with severe ulcerative colitis. PATIENTS AND METHODS: One hundred and forty-nine episodes of severe ulcerative colitis in 115 patients admitted to a Gastroenterology Unit in a 7-year period were retrospectively evaluated. Intravenous glucocorticosteroids--methylprednisolone 1 mg/kg/day--and topical steroids were administered, and supportive treatments with intensive monitoring were extended to all the patients. Second-line strategies for steroid-refractoriness were prolonged glucocorticosteroids treatment, oral ciclosporin, infliximab or surgery. RESULTS: The median number of Truelove criteria at admission was 3 (range 2-5), median CRP 34 mg/l (range 10-196). Median follow-up after discharge was 49 months. In 84 (57%) episodes an early response was noted, while 65 (43%) did not respond within 10 days to the standard steroid treatment. In the non-responders group, 28 patients went into remission with a prolonged steroid treatment (slow responders); 15 patients were treated with ciclosporin (eight responders) and 6 with infliximab (four responders). A total of 24 colectomies was performed in this group of patients (in 21 cases within 30 days from admission). Slow responders showed lower albumin levels (P = 0.02), higher cumulative dose of glucocorticosteroids in the year prior to admission (P = 0.02) and higher age (P = 0.03), in comparison with early responders. Major complications were noted in four episodes which responded to medical treatment. Disease-related mortality was zero. CONCLUSIONS: Medical treatment and use of second-line therapies were effective in the present series of patients. A group of slow responders has been identified and, if an intensive medical monitoring is guaranteed, steroids can be safely prolonged after the first 10 days of treatment. Cumulatively, about 80% of the patients responded to short-term medical treatment, only 5% of the patients underwent colectomy in the follow-up period. Major adverse events were recorded in four patients, who had recovered completely after adequate medical treatment.     

Prostaglandin E1‐effective,transient‐type ischemic colitis developed after surgical resection of sigmoid colon cancer. A case report

A 55‐year‐old‐man had a laparoscopic resection of the sigmoid colon due to colon cancer with submucosal invasion. After the surgery he suffered ileus and had a laparotomy. Six months later he complained of frequent defecation. Colonoscopy confirmed a circular ulcer extending from the anal side of the anastomosis in the sigmoid colon to the mid rectum. Endoscopic ultrasound demonstrated thickening of all layers of the diseased colon and rectum. We diagnosed ischemic colitis. After intravenous drip infusion of prostaglandin, symptoms and colonic stricture gradually improved. Although abdominal angiography revealed a narrowing of the peripheral sigmoid branch of the inferior mesenteric artery, blood flow was unrestricted. Colonoscopy performed 84 days after discharge revealed an ulcer scar.     

‘Ischemic tolerance’ phenomenon detected in various brain regions

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the ‘ischemic tolerance’ phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of ‘ischemic tolerance’.     

Radiology of the continent ileostomy reservoir: I. Method of examination and normal findings

The aim of the present study is to describe the radiologic methods used to study continent ileostomy reservoirs and to depict the normal radiologic features and variations identified by these procedures. During an 8-year period, 408 double-contrast studies were performed in 261 patients. The present study comprises 170 examinations in 99 patients with normal findings. A high-density barium contrast medium and air were used. Modest variation in the size and shape of the reservoirs was observed. The mucosal pattern of the reservoirs resembled that of the ileum but the folds were slightly wider. The continence-providing valves were 3–5 cm long and had a diameter of 2.5–4.0 cm. The diameter of the afferent ileal segments was usually slightly larger than that of more proximal ileal segments, with an upper limit of approximately 4 cm. The efferent ileal segments generally had a straight course without widening or outpouches. Retrograde barium double-contrast examination is a satisfactory method for the evaluation of continent ileostomy reservoirs. Here we define the range of normal variations of such reservoirs as seen on retrograde double-contrast radiologic examinations.