改良腹腔器官簇移植在自身免疫性肠平滑肌炎继发性慢性假性肠梗阻中的应用价值

Application value of modified multivisceral transplantation in chronic intestinal pseudo-obstruction secondary to autoimmune leiomyositis

目的探讨改良腹腔器官簇移植(MMT)在自身免疫性肠平滑肌炎(AEL)继发性慢性假性肠梗阻(CIPO)中的应用价值。方法采用回顾性描述性研究方法。收集2022年2月清华大学附属北京清华长庚医院收治的1例29岁行MMT治疗AEL继发性CIPO男性受者的临床病理资料。受者术前活组织病理学检查结果示直肠、乙状结肠、升结肠、回肠固有肌层及少许黏膜下层可见肌间神经丛及神经节细胞,肌间见少许慢性炎细胞浸润,诊断为神经型CIPO可能性大。结果(1)手术情况受者手术时间为870min,冷缺血时间为570min,术中血制品用量包括红细胞14U、新鲜冰冻血浆1400mL、血小板2个治疗量。(2)术后组织病理学检查结果。受者术后组织病理学检查结果示小肠、十二指肠黏膜慢性炎症、局部糜烂,局灶黏膜肌层散乱消失;固有层尤其是固有肌层内大量CD3^(+)和CD8^(+)淋巴细胞浸润,病变严重处浆膜下层及肌层带状淋巴细胞浸润;肌纤维变性、减少、纤维化;平滑肌细胞胞质内色素颗粒沉着;肌间、黏膜下神经节及Cajal细胞未见异常;浆膜层纤维化,局部纤维素渗出;结肠黏膜慢性炎症,局部肌层散在及灶性淋巴细胞浸润,肌炎性改变。病理学诊断:AEL继发性CIPO。(3)术后免疫排斥反应和复发及治疗情况。受者术后8d肠镜活组织病理学检查诊断为急性细胞性排斥反应,B淋巴细胞、CD3^(+)淋巴细胞、CD4淋巴细胞、CD8^(+)淋巴细胞分别为27.00×10^(3)、373.00×10^(3)、179.00×10^(3)、142.00×10^(3)个细胞/mL,采用他克莫司、免抗人胸腺细胞免疫球蛋白、甲强龙、吗替麦考酚酯、巴利息单克隆抗体行抗免疫排斥反应治疗;术后57dB淋巴细胞、CD3^(+)淋巴细胞、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞分别为0.72×10^(3)、239.59×10^(3)、89.28×10^(3)、91.53×10^(3)个细胞/mL;术后79d肠镜活组织病理学检查诊断为AEL复发,B淋巴细胞、CD3^(+)淋巴细胞、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞分别为0.32×10^(3)、264.92×10^(3)、46.95×10^(3)、169.54×10^(3)个细胞/mL,采用他克莫司、甲强龙治疗;术后89d肠镜活组织病理学检查诊断为AEL复发未缓解,B淋巴细胞、CD3^(+)淋巴细胞、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞分别为0.28×10^(3)、187.00×10^(3)、55.52×10^(3)、92.45×10^(3)个细胞/mL,采用他克莫司、甲强龙治疗;术后92d肠镜活组织病理学检查诊断为肠黏膜恢复正常状态。(4)术后经口进食和停止肠外营养时间。受者术后28d开始经口进食,术后35d停止肠外营养。(5)随访情况。受者术后114d出院,至随访截止时间,移植物功能良好。受者保持低脂、高糖、高蛋白饮食原则,完全经口进食,体质量指数为22kg/m^(2),恢复正常工作。结论MMT治疗AEL继发性CIPO可行。

Objective To investigate the application value of modified multivisceral transplantation(MMT)in chronic intestinal pseudo-obstruction(CIPO)secondary to autoimmune enteril leiomyositis(AEL).Methods The retrospective and descriptive study was conducted.The clinicopathological data of a recipient who was admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University on February 2022 and underwent MTT for CIPO secondary to AEL were collected.The recipient was a male,aged 29 years old.Results of preoperative histopathological examination showed that there were muscle plexus and ganglion cells in the rectum,sigmoid colon,ascending colon,intrinsic muscle layer of ileum,and a small amount of submucosal layer.There was also a small amount of chronic inflammatory cell infiltration in the muscle,indicating a high possibility of diagnosis of neurogenic CIPo.Results(1)Surgical situations.The operation time was 14 hours and 30 minutes,and the cold ischemia time was 9 hours and 30 minutes.The intraoperative blood product dosage included 14 U of red blood cells,1400 mL of fresh frozen plasma,and two therapeutic doses of platelets.(2)Postoperative histopathological examination.Results of postoperative histopathological examination showed chronic inflammation and local erosion of the small intestine and duodenal mucosa,with scattered disappearance of the focal mucosal muscle layer;There is a large infiltration of CD3 and CD8'lymphocytes in the lamina propria,especially in the muscularis propria.In severe lesions,there is infiltration of ribbon lymphocytes in the subserosal and muscular layers;Muscle fiber degeneration,reduction,and fibrosis.Deposition of pigment granules in the cytoplasm of smooth muscle cells;No abnormalities were found in the intermuscular,submucosal ganglia,and Cajal cells;Fibrosis of the serosal layer with local cellulose exudation;Chronic inflammation of the colonic mucosa,scattered and focal lymphocyte infiltration in the local muscle layer,and myositis related changes.Pathological diagnosis was secondary CIPO induced by AEL.(3)Postoperative immune rejection,recurrence and treatment.Results of colonoscopy and histopathological examination at postoperative 8 days showed acute cellular rejection.The cell count of recipient's B lymphocytes,CD3^(+)lymphocytes,CD4 lymphocytes,and CD8^(+)lymphocytes were 27.00x10,373.00×10^(3),179.00×10^(3)and 142.00×10^(3)cell/mL,respectively.Anti-immune rejection treatment was performed using tacrolimus,rabbit anti-human thymocyte immunoglobulin,methylprednisolone mycophenolate mofetil,and monoclonal antibodies against basil.The cell count of recipient's B lymphocytes,CD3^(+)lymphocytes,CD4^(+)lymphocytes,and CD8^(+)lymphocytes at postoperative 57 days were 0.72×10°,239.59x10′,89.28x10'and 91.53x103 cell/mL,respectively.Results of colonoscopy and histopathological examination at postoperative 79 days showed the recurrence of AEL.The cell count of recipient's B lymphocytes,CD3^(+)lymphocytes,CD4^(+)lymphocytes,and CD8^(+)lymphocytes were 0.32×10^(3),264.92×10^(3),46.95×10^(3)and 169.54×10^(3) cell/mL,respectively.The tacrolimus and methylprednisolone were used for treatment.Results of colonoscopy and histopathological examination at postoperative 89 days showed AEL recurrence without remission.The cell count of recipient's B lymphocytes,CD3^(+)lymphocytes,CD4^(+)lympho-cytes,and CD8^(+)lymphocytes were 0.28×10^(3),187.00×10^(3),55.52×10^(3) and 92.45×10^(3) cell/mL,respec-tively.The tacrolimus and methylprednisolone were used for treatment.Results of colonoscopy and histopathological examination at postoperative 92 days showed the intestinal mucosa had returned to a normal state.(4)Postoperative oral feeding time and time to get rid of parenteral nutrition.The recipient began oral feeding at postoperative 28 days and eliminated parenteral nutrition at postoperative 35 days.(5)Follow-up.The recipient was discharged 114 days after surgery and as of the follow-up deadline,the graft function was good.The recipient maintained a low-fat,high sugar,and high protein diet,completely consumed orally,with a body mass index of 22 kg/m^(2),and has returned to normal work.ConclusioMn MTcanbe used for the treatment of CIPO secondary to AEL.