J Gastroenterol 2006; 41:848854DOI 10.1007/s00535-006-1875-1
Leukocyte removal therapy for ulcerative colitis does not affectpostoperative complications
Hiroki Ikeuchi1, Takehira Yamamura1, Masato Kusunoki2, Hiroki Nakano1, Motoi Uchino1,Mitsuhiro Nakamura1, Masafumi Noda1, Hidenori Yanagi1, and Takayuki Matsumoto3
1 Second Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan2 Second Department of Surgery, Mie University School of Medicine, Tsu, Japan3 Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
The etiology of ulcerative colitis (UC) remains un-known, and a fundamental therapy has not been estab-lished. The disease is generally treated medically withdrugs such as mesalazine and corticosteroids, and occa-sionally with immunosuppressive agents. However, theside effects of drug therapy can present problems, par-ticularly with long-term use. Thus, alternative therapiesare considered to be necessary and desirable.
Leukocyte removal therapy (LRT) has been reportedto be effective for various disorders related to autoim-mune responses, especially UC.1,2 Further, apheresis,which removes plasma components, is considered to bean effective nondrug strategy for the management ofimmune disorders. The Japan Ministry of Health hasapproved leukocyte apheresis (LCAP) with a leukocyteremoval filter (Cellsorba; Asahi Medical, Tokyo,Japan), granulocytemonocyte adsorptive apheresis(GCAP) using an Adacolumn (Japan ImmunoresearchLaboratories, Takasaki Japan), and centrifugal leuko-cyte apheresis using a centrifugal cell separator (Com-ponent Collection System; Haemonetics, Braintree,MA, USA) for treatment of active UC. Recently, LRThas been shown by our hospital and others to reduce theneed for surgery in patients with steroid-resistant dis-ease, though an operation may eventually be requiredfor those who are not helped by that treatment.3,4
The aim of this study was to compare the postopera-tive complication rates between patients who receivedand those that did not receive preoperative LRT. This isthe first known report of the relationship between pre-operative LRT and postoperative complications in UCpatients. We considered that if LRT did not have aneffect on postoperative complications, then physicianswould be able to treat acute UC patients confidentlywith the procedure.
Received: April 6, 2006 / Accepted: July 23, 2006Reprint requests to: H. Ikeuchi
Background. We investigated the incidence of postop-erative complications in patients treated with or withoutpreoperative leukocyte removal therapy (LRT). Meth-ods. The case notes of 387 patients with ulcerative coli-tis (UC) who underwent surgical intervention wereretrospectively reviewed. One hundred nine patientswere treated with LRT within 8 weeks before surgery(LRT group), and 278 had not received LRT since atleast 8 weeks before surgery (without LRT group). Wereviewed the postoperative complications according totype of initial operation. Results. Of the patients whounderwent an ileal J-pouch anal anastomosis (IPAA)without an ileostomy, 3 (6.5%) in the LRT group devel-oped pouch-related complications (PRC), while 11(7.5%) in the without LRT group developed PRC. Theoverall postoperative complication rates were 28.3% inthe LRT group and 21.8% in the without LRT group.For patients who underwent an IPAA with an ileo-stomy, the overall rates of postoperative complicationswere 39.1% in the LRT group and 31.8% in the withoutLRT group. Among those undergoing a total colec-tomy, 33.3% in the LRT group and 18.2% in the with-out LRT group had postoperative complications. Nostatistically significant differences were demonstratedbetween the two groups with respect to postoperativecomplications. Conclusions. Our results suggest thatpreoperative LRT does not influence the rate of postop-erative complications in UC patients.
Key words: leukocyte removal therapy, ulcerative coli-tis, complications
Editorial on page 923
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H. Ikeuchi et al.: Leukocyte removal therapy and postoperative complications 849
Patients and methods
We reviewed the records of 387 patients who underwenta restorative proctocolectomy with an ileal J-pouch analanastomosis (IPAA) for UC at our institution betweenJanuary 2000 and December 2004. Each satisfied thediagnostic criteria for UC established by the ExpertCommittee on Inflammatory Bowel Disease appointedby the Japan Ministry of Health.3 Preoperative condi-tions were determined using a clinical activity index(CAI score) for evaluation of patients with ulcerativecolitis.4
This study was a retrospective analysis of outcomes in aseries of consecutive patients who underwent opera-tions performed by a single surgical team. We reviewedpostoperative complications, including infectiouscomplications, pouch-related complications, intestinalobstructions, urinary complications, and stoma-relatedcomplications, according to type of initial operation at 3weeks after the initial operation.
Definitions of groups
The patients were divided into two groups, those whoreceived LRT no more than 8 weeks before surgery(LRT group) and those who did not undergo LRTwithin 8 weeks before surgery (without LRT group).
All of the ileal pouches were created with a J-shapedreservoir, 15 to 20 cm in axial length. In 324 (83.7%) ofthe patients, an IPAA with or without an ileostomy wasperformed as the initial operation. In 318 (98.1%) ofthose, the pouch was anastomosed to the dentate linewith a mucosectomy using a hand-sewn suture. The pro-cedure used for complete transanal mucosectomy withan ultrasonically activated scalpel (harmonic scalpel)has been described previously.5 In the remaining sixcases (1.9%), the pouch was anastomosed to the uppermargin of the anal canal by a double stapling method.
LCAP and GCAP
LCAP was performed using a Plasauto 1000 apheresisunit (Asahi Medical, Tokyo, Japan) equipped with aCellsorba leukocyte removal filter, because leukocyteremoval in LCAP is accomplished by adherence of leu-kocytes to fibers in the filter. Leukocyte adsorptiveapheresis was performed using an Adacolumn filled
with cellulose acetate beads, each 2 mm in diameter. Inthat system, the beads selectively absorb granulocytesand monocytes/macrophages, whereas lymphocytes arenot removed in significant numbers. This system isa direct blood perfusion device, in which blood isaccessed from the antecubital vein of one arm andreturned via the antecubital vein of the contralateralarm. Nafamostat mesylate was commonly used as theanticoagulant.
Grouped data are described by median and range. Theresults were compared using Mann-Whitney U and -squared tests, with probability values less than 0.05 con-sidered to be significant.
Characteristics of the 387 patients are shown in Table 1.There were 109 in the LRT group and 278 in the withoutLRT group. Sex and age were not significantly differentbetween the groups, whereas the duration of disease inthe without LRT group was significantly longer. Fur-ther, the incidence of total colitis type, severe or fulmi-nant, and the CAI score were significantly greater in theLRT group than in the without LRT group.
Preoperative medical treatments
The preoperative medical treatments utilized are shownin Table 2. Daily doses of steroids in the LRT groupwere significantly higher than those in the without LRTgroup.
Type of LRT procedure
In the LRT group, 56 (51.4%) of 109 patients weretreated with LCAP and 47 (43.1%) were treated withGCAP. The remaining six patients were treated pre-operatively with both LCAP and GCAP. None ofthe patients were treated with centrifugal leukocyteapheresis.
Number of LRT procedures
The numbers of preoperative LRT procedures for eachpatient are shown in Table 3. Four of 9 patients whowere treated as emergency cases after being transferredfrom another hospital for treatment of fulminant colitisunderwent a single LRT procedure immediately priorto the operation. Further, 14 (17.3%) of 81 (17.3%) who
850 H. Ikeuchi et al.: Leukocyte removal therapy and postoperative complications
underwent elective surgery were originally indicated foremergency surgery at the time of hospitalization. How-ever, LRT was effective for those patients, and theywere able to avoid an emergency operation.
Surgical indications are shown in Table 4. The incidenceof emergency operations in the LRT group (25.7%) wassignificantly greater than that in the without LRT group(14.7%). Four patients in the LRT group were origi-nally transferred from other hospitals because of fulmi-nant colitis and underwent a single LRT procedureprior to emergency surgery. Of these, three underwentan IPAA with an ileostomy and one a total colectomy.
Details regarding the initial operations are shown inTable 5. In the LRT group, 46 patients (42.2%) under-went an IPAA without an ileostomy, 46 (42.2%) anIPAA with an ileostomy, and 15 (13.8%) a total colec-tomy. In the without LRT group, the respective num-bers were 147 (52.9%), 85 (30.6%), and 33 (11.9%)patients.
Among all 387 patients, 193 (49.9%) underwent anIPAA without a diverting ileostomy (Table 6). Of those,the mean CAI score for the LRT group (8; range, 317)was significantly greater than that for the without LRTgroup (7.5; range, 216). We found infectious complica-tions in 6 (13.0%) of 46 patients in the LRT groupand 10 (6.8%) of 147 in the without LRT group, adifference that was not significant. In the LRT group,three (6.5%) patients developed pouch-related compli-cations (PRC), though only one (2.2%) underwent asecondary ileostomy. Further, 11 (7.5%) patients in thewithout LRT group developed PRC, of whom 4 (2.7%)underwent a reoperation. Intestinal obstructions oc-curred in three (6.5%) patients in the LRT group andseven (7.5%) in the without LRT group. Two of threepatients in the LRT group and one of seven patients inthe without LRT group required a laparotomy withdivision of adhesions, while the remaining patients re-sponded to conservative treatment. Thus, a total of13 (28.3%) patients in the LRT group and 32 (21.8%)in the without LRT group experienced postoperativecomplications.
Of all 387 patients, 131 (33.9%) underwent an IPAAwith an ileostomy (Table 7). The mean CAI score forthose in the LRT group (8; range, 419) was signifi-cantly greater than that of those in the wi...