Tsukasa Nakamura ¹, Yasuhiko Kawagoe, Takaharu Matsuda, Akiko Ueda, Yoshihiko Ueda, Yutaka Takahashi, Araki Tanaka, Hikaru Koide Blood Purif  2004;22(6):499-504. doi: 10.1159/000081896. 

Background/aim: Increases in microalbuminuria and endothelin (ET-1) are involved in the development of ulcerative colitis (UC) and in its progress. Because granulocyte and monocyte adsorption apheresis has proven to be useful in the treatment of UC, we examined whether urinary albumin excretion and plasma ET-1 concentrations are altered and whether granulocyte and monocyte adsorption apheresis affects the concentrations of these two factors in patients with active UC. Methods: Twenty patients with active UC and 20 age-matched healthy volunteers (our hospital staffs) were included in this study. UC patients were randomly divided into two treatment groups: a granulocyte and monocyte adsorption treatment group (n = 10) and a conventional treatment group (n = 10). The urine albumin/creatinine ratio, plasma ET-1 concentration and tumor necrosis factor (TNF)-alpha were determined before and after treatment and compared between 2 treatment groups. The 10 adsorption treatment patients underwent 5 consecutive weekly apheresis sessions, each of 60 min duration at a flow rate of 30 ml/min. Results: The urine albumin/creatinine ratio in UC patients (6.4 +/- 2.2 mg/mmol) were higher than that in healthy subjects (1.0 +/- 0.7 mg/mmol, p < 0.01). In addition, the plasma ET-1 level in UC patients (3.5 +/-1.5 pg/ml) was higher than that in healthy subjects (0.8 +/- 0.4 pg/ml, p < 0.01). Plasma TNF-alpha was detected in UC patients (18.8 +/- 8.4 pg/ml), but not in healthy subjects. The urine albumin/creatinine ratio was highly correlated with the plasma ET-1 level (r = 0.62; p < 0.01) and plasma TNF-a level (r = 0.66, p < 0.01). Granulocyte and monocyte adsorption apheresis reduced the urine albumin/ creatinine ratio from 6.6 +/- 2.4 to 1.8 +/- 0.6 mg/mmol (p < 0.01), reduced the plasma ET-1 level from 3.7 +/- 1.6 to 1.4 +/- 0.6 pg/ml (p < 0.05) and reduced the plasma TNF-alpha from 19.2 +/- 8.6 to 3.8 +/- 1.2 pg/ml (p < 0.01). Conventional treatment did not affect these factors. Conclusion: Our data suggest that increases in the urine albumin/creatinine ratio, ET-1 and TNF-alpha play an important role in active UC and that granulocyte and monocyte adsorption apheresis is effective in ameliorating such increases.

https://pubmed.ncbi.nlm.nih.gov/15528877/

https://www.karger.com/Article/Abstract/81896

Yukihiko Kawasaki ¹, Junzo Suzuki, Shigeo Suzuki, Hitoshi Suzuki

J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):422-5. doi: 10.1097/00005176-200410000-00021.

Generally, UC is associated with intervals of acute exacerbation and the administration of corticosteroids is effective in bringing about a clinical remission (¹). Corticosteroids are not always effective even in doses over 1 mg/kg/day. In addition, the long-term use of corticosteroids often causes serious side effects such as growth retardation, glaucoma, hormonal disturbance, peptic ulcer, liver dysfunction and psychologic problems. Alternative treatment for active UC may be necessary to avoid the clinical problems associated with corticosteroid therapy. In recent years, leukocytapheresis (LCAP) and granulocytapheresis (GCAP) using a leukocyte removal filter has been found effective in some cases of adults with inflammatory bowel disease (^2,3). However, there have been few reports concerning the efficacy of LCAP and GCAP for UC in childhood (⁴).We report two children with severe steroid-dependent UC in whom LCAP with leukocyte removal filter was used in treatment. LCAP therapy was safe and effective in two children with refractory UC and allowed discontinuation of corticosteroid therapy with an improvement in quality of life. Prospective studies of this therapy will be needed to clarify the role of LCAP in treatment of childhood UC.

https://pubmed.ncbi.nlm.nih.gov/15448435/

https://journals.lww.com/jpgn/Fulltext/2004/10000/Leukocytapheresis_with_Leukocyte_Removal_Filter.21.aspx

Purushothaman Premchand ¹, Ken Takeuchi, Ingvar Bjarnason Eur J Gastroenterol Hepatol 2004 Sep;16(9):943-5. doi: 10.1097/00042737-200409000-00023.

Refractory ulcerative colitis that fails conventional intense medical treatment often leads to colectomy. Although ciclosporin and infliximab may avert colectomy in certain cases, these treatments come with substantial toxicity and may only act as a bridge to avert emergency surgery. Granulocyte monocyte/macrophage adsorption apheresis is a new treatment and has shown efficacy for refractory colitis in up to 80% of cases in a Japanese study and is apparently only associated with negligible side effects. We report a case of severe refractory proctitis destined for colectomy effectively treated with granulocyte monocyte/macrophage adsorption apheresis. After two of five sessions the patient achieved full clinical remission, which has been sustained with the addition of azathioprine for more than 1 year.

https://pubmed.ncbi.nlm.nih.gov/15316424/

Cuenca, F & Paredes, J & Mendoza, J & Cruz, D & Herrero, A & Díaz-Rubio, M.Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva .2004,96. 501-3, 504. DOI:10.4321/S1130-01082004000700007.

Objective: To describe our experience with granulocyte apheresis to induce remission in patients with active Crohn’s disease refractory to conventional treatment. We summarize the results previously obtained with this technique.

Conclusions: Granulocyte apheresis is a safe and well tolerated therapeutic modality that can be a valid therapeutic alternative in the induction of remission in inflammatory bowel disease, although controlled clinical trials must be conducted to define long-term efficacy, as well as to establish «optimal patient» selection, re-treatment interval, and number of sessions.

https://pubmed.ncbi.nlm.nih.gov/15283632/

Yutaka Kohgo, Journal of Gastroenterology volume 39, pages1226–1227 (2004)

https://link.springer.com/article/10.1007%2Fs00535-004-1509-4

Hiroyuki Hanai ¹, Ken Takeuchi, Takayuki Iida, Nobuhito Kashiwagi, Abby R Saniabadi, Isao Matsushita, Yoshihiko Sato, Naoki Kasuga, Toshihiro Nakamura, Dig Dis Sci. 2004 Sep;49(9):1438-43.

In conclusion, GM appear to contribute to intestinal inflammation and UC activity and reduction of these cells by GMA should benefit patients with active UC. Further, the correlations among calprotectin, UC activities, and PB neutrophils should serve as the basis for preemptive actions to control this disease.

https://pubmed.ncbi.nlm.nih.gov/15481316/

Jorge Amil Dias, J Pediatr Gastroenterol Nutr. 2004 Nov;39(5):485-6.

https://pubmed.ncbi.nlm.nih.gov/15572886/

Hiroyuki Hanai ¹, Fumitoshi Watanabe, Masami Yamada, Yoshihiko Sato, Ken Takeuchi, Takayuki Iida, Kotaro Tozawa, Tatsuo Tanaka, Yasuhiko Maruyama, Isao Matsushita, Yasushi Iwaoka, Abby Saniabadi, Am J Gastroenterol. 2004 Aug;99(8):1532-8.

The sources of s-RI/RII are believed to be activated monocytes and neutrophils with further release when these leukocytes adhere to the column carriers. s-RI/RII released during GMA should contribute to the clinical efficacy of this procedure.

https://pubmed.ncbi.nlm.nih.gov/15307873/

Kanako Mori ¹, Takao Yoshihara, Takashi Ando, Satoko Tsubai, Satoshi Matsuo, Michiko Aoyama, Tohru Yamamoto, Yoshio Kawase, J Pediatr Gastroenterol Nutr. 2004 Nov;39(5):549-51

https://pubmed.ncbi.nlm.nih.gov/15572898/

Makoto Higuchi, AkihiroShinii ,NaoshiNakamura , IaijiAkamatsu, Hideo Arakura, Tbru Ichikawa , Kazuhiko Horab ,YejiKamijo ,Ybko Kanekoi, rfetuji Kakegawa and Kendo Kiyosawa, Jpn JApheresis23 (2):189-19S,2004

Fourpatients (3men and 1 woman) with intractable ulcerative colitis(UC)were treated using granulocytapheresis (GCAP) with Adacolumn. Mean age at the first GCAP was 37.5± 11years.Mean observation
period beforeGCAP was 157± 105 months. A clinical activity index (CAI,Rachmilewitzcriteria) and Matts’
endoscopic classification were used forthe estimation. GCAP was not effective intwo cases, however it,was
very effective inthe others. TheCAI score of one male patient decreased from8 to 5,and Matts’ grade from
3 to 2,after the 5thGCAR his patient could be taken off conicosteroid and the immunosuppressant.
Then he received GCAP every month. Both his CAI score and Matts’grade had decreased to 1sixteen months
after the first GCAR Four sessions of GCAP enabled us to reduce the prednisolone dose from20 to 5 mg lday,
and loweredt heCAI score (8to4) of another male patient before tota1 colectomy, Further examination is needed of the indications, times and intervals of GCAP in the treatment of intractable

https://dl.ndl.go.jp/view/download/digidepo_10555521_po_ART0003553409.pdf?contentNo=1&alternativeNo=