今日の臨床サポート

慢性膵炎

著者: 正宗淳 東北大学 消化器内科

監修: 下瀬川徹 みやぎ県南中核病院企業団

著者校正/監修レビュー済:2020/09/03
参考ガイドライン:
  1. 日本消化器病学会:慢性膵炎診療ガイドライン2015
患者向け説明資料

概要・推奨   

  1. 脂肪便と体重減少を伴う慢性膵炎には消化酵素薬は有効である(推奨度1)。
  1. アルコール性慢性膵炎患者には断酒が勧められる(推奨度2)。
  1. 慢性膵炎の腹痛対策として脂肪制限は必要である(推奨度2)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
正宗淳 : 講演料(マイランEPD合同会社,武田薬品工業(株),第一三共(株),大塚製薬(株)),研究費・助成金など(東レ(株)),奨学(奨励)寄付など(EAファーマ(株),旭化成ファーマ(株),アッヴィ合同会社,エーザイ(株),大塚製薬(株),武田薬品工業(株),第一三共(株),ギリアド・サイエンシズ(株))[2021年]
監修:下瀬川徹 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 日本膵臓学会により作成された慢性膵炎臨床診断基準2019に基づき、定義、診断基準、診断フローチャートなどの改訂を行った。
  1. 2016年受療患者を対象に行われた全国疫学調査に基づき、疫学に関する情報をアップデートした。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 慢性膵炎とは、遺伝的や環境要因その他の危険因子を有し、実質への傷害やストレスに対して持続的な病的反応を生じる個人に起きる、膵臓の病的線維化炎症症候群である。
  1. 膵臓の内部に不規則な線維化、細胞浸潤、実質の脱落、肉芽組織などの慢性変化が生じ、進行すると膵外分泌・内分泌機能の低下を伴う病態である。多くは非可逆性である。
  1. 診断は臨床診断基準に基づいて行う。
  1. 慢性膵炎臨床診断基準2019:表<図表>
  1. 慢性膵炎の特徴的画像所見:表<図表>
  1. 慢性膵炎の組織像:図<図表>
  1. この診断基準では、特徴的な画像所見ならびに組織所見として、確診所見と準確診所見が設けられており、いずれかが認められる場合、慢性膵炎確診または準確診の診断が下せる。
  1. 慢性膵炎診断の手順(アルゴリズム)の準確診所見のみの場合でも、③反復する上腹部痛または背部痛、④血中/尿中膵酵素値の異常、⑤膵外分泌障害、――の3項目中2項目以上が認められる場合には診断を確診に格上げできる。確診、準確診所見を認めないが、③反復する上腹部痛または背部痛、④血中/尿中膵酵素値の異常、⑤膵外分泌障害、⑥1日60g以上(純エタノール換算)の持続する飲酒歴または膵炎関連遺伝子異常、⑦急性膵炎の既往――のいずれか3項目以上と超音波内視鏡またはMRCP、ERCPにて早期慢性膵炎の画像所見が認められた場合、早期慢性膵炎と診断する。アルゴリズム
  1. 成因により、アルコール性と非アルコール性(特発性、遺伝性など)に分類される。アルコール性が成因の約2/3を占め最も多い。
  1. 自己免疫性膵炎と閉塞性膵炎は、病態の可逆性の観点から慢性膵炎として取り扱われない。
  1. まれな成因である遺伝性膵炎は、2015年より厚生労働省の指定難病となり、医療費助成の対象となっている。申請し認定されると保険料の自己負担分の一部が公費負担として助成される。([平成27年1月施行])
  1.  難病法に基づく医療費助成制度 
  1. 2016年受療患者を対象とした全国調査によると、年間推計受療患者数は56,520人である。有病率としては人口10万人あたり44.5人、新規発症(発病)率は11.6人、患者の平均年齢は約62歳であった。
  1. 男女比は4.8:1と男性に多い。特にアルコール性に限ると男女比は10:1となる。
  1. 女性は男性に比べて、より少ない累積飲酒量で、より若年でアルコール性慢性膵炎を発症するという性差もみられる。
問診・診察のポイント  
  1. 腹痛や背部痛の出現時期、性状、食事との関連を確認する。典型例では、食後、特に脂肪分の多い食事をとった後や飲酒後に症状が出現する。症状は仰臥位で悪化し、前屈位で軽減する。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

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文献 

著者: László Czakó, Tamás Takács, Peter Hegyi, László Prónai, Zsolt Tulassay, Lilla Lakner, Zoltán Döbrönte, Krisztina Boda, János Lonovics
雑誌名: Can J Gastroenterol. 2003 Oct;17(10):597-603.
Abstract/Text GOALS: To evaluate the quality of life (QoL) of patients with chronic pancreatitis before and after pancreatic enzyme replacement therapy in a prospective, multicentre, follow-up study.
STUDY: Two groups of patients were evaluated. Group 1 consisted of 31 patients with newly diagnosed chronic pancreatitis who had never been treated with pancreatic enzyme preparations. Group 2 consisted of 39 patients whose disease was diagnosed on average 3.4 years before the start of the study. The latter group of patients had undergone pancreatic enzyme replacement therapy, but during follow-up this treatment proved to be insufficient. The dose of pancreatic enzyme replacement therapy was tailored in accordance with the degree of pancreatic exocrine insufficiency measured by means of exocrine pancreatic function tests. A modified European Organizaton for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was used to assess QoL.
RESULTS: The social functioning and financial strain were significantly better, while the levels of hope and confidence were significantly reduced in group 1 compared with group 2. A significant gain in body weight and a significantly reduced defecation rate were found in both groups one month after the beginning of the pancreatic enzyme replacement therapy when compared with the pretreatment values. The prevalence of general and disease-specific symptoms and the intensity of pain were reduced in both groups after one month of enzyme substitution therapy. The working ability, the financial strain and the overall QoL scores were improved significantly in both groups, while the cognitive functioning score was found to be significantly improved during the follow-up only in group 1. The overall increase in the QoL score correlated significantly with the increase in body weight and the decrease in defecation number in both groups.
CONCLUSIONS: Pancreatic enzyme replacement therapy in patients with chronic pancreatitis not only reduced the extent of steatorrhea and pain, but also significantly improved a variety of other symptoms and the patient's QoL. Individually tailored enzyme replacement therapy improved the QoL not only in the untreated chronic pancreatitis patients, but also in the inadequately treated group. This study demonstrated that the EORTC QLQ-C30 questionnaire, with the addition of two further questions about steatorrhea, is a useful tool for the evaluation of QoL in patients with chronic pancreatitis.

PMID 14571298  Can J Gastroenterol. 2003 Oct;17(10):597-603.
著者: Daniel de la Iglesia-García, Wei Huang, Peter Szatmary, Iria Baston-Rey, Jaime Gonzalez-Lopez, Guillermo Prada-Ramallal, Rajarshi Mukherjee, Quentin M Nunes, J Enrique Domínguez-Muñoz, Robert Sutton, NIHR Pancreas Biomedical Research Unit Patient Advisory Group
雑誌名: Gut. 2017 Aug;66(8):1354-1355. doi: 10.1136/gutjnl-2016-312529. Epub 2016 Dec 9.
Abstract/Text OBJECTIVE: The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.
DESIGN: Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.
RESULTS: A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.
CONCLUSIONS: PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
PMID 27941156  Gut. 2017 Aug;66(8):1354-1355. doi: 10.1136/gutjnl-2016・・・
著者: David C Whitcomb, Glen A Lehman, Galina Vasileva, Ewa Malecka-Panas, Natalya Gubergrits, Yannan Shen, Suntje Sander-Struckmeier, Steven Caras
雑誌名: Am J Gastroenterol. 2010 Oct;105(10):2276-86. doi: 10.1038/ajg.2010.201. Epub 2010 May 25.
Abstract/Text OBJECTIVES: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). Our objective was to assess the efficacy and safety of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with EPI due to CP or PS.
METHODS: This was a double-blind, randomized, multicountry, placebo-controlled, parallel-group trial enrolling patients ≥18 years old with confirmed EPI due to CP or PS conducted in clinical research centers or hospitals. After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units per meal; 36,000 per snack) or placebo for 7 days. All patients received an individually designed diet to provide at least 100 g of fat per day. The primary efficacy measure was the change in coefficient of fat absorption (CFA) from baseline to end of the double-blind period, analyzed using non-parametric analysis of covariance. Secondary outcomes included the coefficient of nitrogen absorption (CNA), clinical symptoms, and safety parameters.
RESULTS: In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo. Th e mean ± s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 31.9 ± 18.6 vs. 8.7 ± 12.4 % ( P < 0.0001) [corrected]. Similarly, the mean ± s.d. change from baseline in CNA was greater for pancrelipase vs. placebo: 35.2 ± 29.1 vs. 8.9 ± 28.0 % ( P = 0.0005) [corrected].Greater improvements from baseline in stool frequency, stool consistency, abdominal pain, and flatulence were observed with pancrelipase vs. placebo. Treatment-emergent adverse events (TEAEs) were reported in five patients (20.0%) in the pancrelipase group and in six (20.7%) in the placebo group; the most common were gastrointestinal (GI) events and metabolism/nutrition disorders. There were no treatment discontinuations due to TEAEs.
CONCLUSIONS: Pancrelipase delayed-release 12,000-lipase unit capsules were effective in treating fat and nitrogen maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS.

PMID 20502447  Am J Gastroenterol. 2010 Oct;105(10):2276-86. doi: 10.1・・・
著者: Hariharan Ramesh, Nageshwar Reddy, Shobna Bhatia, J S Rajkumar, Amol Bapaye, Dinesh Kini, Mukesh Kalla, Vinay Thorat
雑誌名: Pancreatology. 2013 Mar-Apr;13(2):133-9. doi: 10.1016/j.pan.2013.01.009. Epub 2013 Feb 5.
Abstract/Text BACKGROUND/OBJECTIVES: To assess the efficacy and safety of pancreatin (pancrelipase) enteric-coated minimicrospheres (MMS) over a one-year period in patients with pancreatic exocrine insufficiency (PEI) due to chronic pancreatitis (CP).
METHODS: This was a 51-week, open-label extension (OLE) of a one-week, multicenter, double-blind, randomized, placebo-controlled trial in India that enrolled patients ≥18 years of age with confirmed PEI due to CP. Patients received pancreatin (Creon(®) 40000 MMS™) at a dose of 80,000 Ph. Eur. lipase units with each of three main meals/day and 40,000 with each of up to three snacks/day.
RESULTS: Of 61 patients entering the OLE, 48 completed treatment (nine were lost to follow up, two withdrew consent, one discontinued due to adverse event [acute exacerbation of CP], one protocol violation). There were significant improvements from baseline to end of OLE in mean ± SD coefficient of fat absorption (CFA: 22.7 ± 12.2%), coefficient of nitrogen absorption (CNA: 6.5 ± 7.9%), body weight (4.9 ± 4.9 kg), BMI (1.9 ± 1.9 kg/m(2)), and most nutritional laboratory parameters tested (p ≤ 0.001). Mean daily stool frequency was reduced from 2.8 to 1.6 (p < 0.001). Improvements in clinical symptoms, clinical global impression of disease symptoms, and quality of life were also observed. Treatment-emergent adverse events (TEAEs) were observed in 64% of patients overall. Only 13% of patients experienced TEAEs judged treatment related.
CONCLUSIONS: In patients with PEI due to CP, treatment with pancreatin for one year was associated with significant improvements in fat absorption, nitrogen absorption, and nutritional parameters, improvements in clinical symptoms, and a favorable safety and tolerability profile.

Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.
PMID 23561971  Pancreatology. 2013 Mar-Apr;13(2):133-9. doi: 10.1016/j・・・
著者: Timothy B Gardner, Douglas G Adler, Chris E Forsmark, Bryan G Sauer, Jason R Taylor, David C Whitcomb
雑誌名: Am J Gastroenterol. 2020 Mar;115(3):322-339. doi: 10.14309/ajg.0000000000000535.
Abstract/Text Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

PMID 32022720  Am J Gastroenterol. 2020 Mar;115(3):322-339. doi: 10.14・・・
著者: U Armbrecht, J Svanvik, Stockbrügger
雑誌名: Scand J Gastroenterol Suppl. 1986;126:55-9.
Abstract/Text Ten patients with chronic pancreatitis (with abdominal pain and/or diarrhoea) were treated in a double-blind multiple cross-over trial with Pankreon granules 20 g per day or placebo during three periods of one month each. Pain and bowel habits were recorded. Faecal fat and breath hydrogen (H2) excretion were analyzed during the last days of each treatment period. The pain score was initially low in all patients and was not affected by enzymes. The number of daily bowel movements was reduced from 3.16 to 2.32 (n.s.). Faecal fat excretion per 72 hrs was reduced from 357 +/- 158 mmol free fatty acid to 226 +/- 98 mmol (p less than 0.05). With placebo treatment H2 excretion (from 60 and 180 min after a standard breakfast) was significantly increased compared with 19 healthy volunteers (p less than 0.05). It was not significantly reduced by enzymes. In 28 comparisons the H2 output between 60 and 180 min was correlated to faecal fat. In eight patients the oro-coecal transit-time could be determined by the H2 breath test. The transit-time did not differ from that of ten healthy volunteers and remained unchanged by enzymes. Carbohydrate maldigestion occurs parallel to fat maldigestion in chronic pancreatitis, and is not sufficiently reduced by 20 g of pancreatic enzymes.

PMID 3551051  Scand J Gastroenterol Suppl. 1986;126:55-9.
著者: H Halgreen, N T Pedersen, H Worning
雑誌名: Scand J Gastroenterol. 1986 Jan;21(1):104-8.
Abstract/Text The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study. Twenty patients, 11 with and 9 without steatorrhoea, were examined. Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy (P less than 0.01). No significant pain reduction was found in either of the two groups, although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes. It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy.

PMID 3633631  Scand J Gastroenterol. 1986 Jan;21(1):104-8.
著者: C M Van Hoozen, P G Peeke, M Taubeneck, C F Frey, C H Halsted
雑誌名: Pancreas. 1997 Mar;14(2):174-80.
Abstract/Text Although surgical procedures that improve pancreatic drainage alleviate abdominal pain in the vast majority of patients with chronic pancreatitis, postoperative absorption and nutritional status are less predictable. The present study was designed to determine the efficacy of pancreatic enzyme supplementation in maintaining postoperative digestion and nutrition in patients who had received the local resection-longitudinal pancreaticojejunostomy (LR-LPJ) procedure for chronic pancreatitis. We evaluated nutritional status and intestinal absorption in 11 patients who had undergone LR-LPJ. The efficacy of postoperative pancreatic enzyme supplementation was studied by measurements of intestinal absorption and nutritional status at baseline, after 4 weeks of individualized daily dosage of pancreatin (Creon), and after an additional 4 weeks of randomization to receive another 4 weeks of pancreatin or placebo. All patients demonstrated abnormal digestion of fat, protein, and total energy at baseline 3 weeks after surgery. Pancreatin supplementation significantly improved the coefficients of absorption of dietary fat and total energy over the next 4 weeks. Between 4 and 8 weeks, pancreatin significantly improved protein absorption and nitrogen balance, whereas placebo substitution worsened the absorption of dietary fat and total energy. Nutritional status was not significantly altered over the 8-week study period, although four patients receiving pancreatin gained more than 3.6 kg body weight. The data suggest that long-term postoperative pancreatic enzyme supplementation is both efficacious and necessary in chronic pancreatitis patients after LR-LPJ.

PMID 9057190  Pancreas. 1997 Mar;14(2):174-80.
著者: J Enrique Dominguez-Munoz, Asbjørn M Drewes, Björn Lindkvist, Nils Ewald, László Czakó, Jonas Rosendahl, J Matthias Löhr, HaPanEU/UEG Working Group
雑誌名: Pancreatology. 2018 Dec;18(8):847-854. doi: 10.1016/j.pan.2018.09.016. Epub 2018 Oct 6.
Abstract/Text BACKGROUND: In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach.
METHODS: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system.
RESULTS: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life.
CONCLUSIONS: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.

Copyright © 2018. Published by Elsevier B.V.
PMID 30344091  Pancreatology. 2018 Dec;18(8):847-854. doi: 10.1016/j.p・・・
著者: Ken Kawabe, Tetsuhide Ito, Hisato Igarashi, Ryoichi Takayanagi
雑誌名: Clin J Gastroenterol. 2009 Feb;2(1):1-8. doi: 10.1007/s12328-008-0052-x. Epub 2009 Jan 7.
Abstract/Text Pancreatic diabetes is secondary diabetes followed by progressions of pancreatic exocrine diseases, such as chronic pancreatitis, pancreatic neoplasm and post-pancreatectomy. Because of destruction and reduction of the pancreatic endocrine and exocrine functional compartments, patients with pancreatic diabetes frequently show malnutrition from maldigestion and malabsorption by insufficiencies in pancreatic digestive enzymes, and show unstable glycemic control and prolonged hypoglycemia by insufficiencies in synthesis and secretion of insulin and glucagon. Epidemiological studies have suggested that the incidence and development of pancreatic diabetes in patients with chronic pancreatitis (CP) depends on several risk factors, such as alcohol intake, the presence of pancreatic calcification and the long-term duration of CP. The clinical management of pancreatic diabetes is divided into two parts: one is the supplementation of pancreatic digestive enzymes and the other is the achievement of appropriate glycemic control. The appropriate and sufficient pancreatic exocrine replacement therapy is important for the maintenance of better nutrient conditions for patients with pancreatic diabetes. Furthermore, the intensive insulin therapy combined with short- or ultra-short-acting insulin and long-acting insulin glargine can be achieved for stable glycemic control and reduction of severe frequent hypoglycemia in patients with pancreatic diabetes. These current advanced management techniques against insufficiencies of pancreatic exocrine endocrine functions are beneficial for improving and maintaining the quality of life in patients with pancreatic diabetes.

PMID 26191800  Clin J Gastroenterol. 2009 Feb;2(1):1-8. doi: 10.1007/s・・・
著者: P Díte, M Ruzicka, V Zboril, I Novotný
雑誌名: Endoscopy. 2003 Jul;35(7):553-8. doi: 10.1055/s-2003-40237.
Abstract/Text BACKGROUND AND STUDY AIMS: Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted.
PATIENTS AND METHODS: Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol.
RESULTS: Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup.
CONCLUSIONS: Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.

PMID 12822088  Endoscopy. 2003 Jul;35(7):553-8. doi: 10.1055/s-2003-40・・・
著者: Djuna L Cahen, Dirk J Gouma, Yung Nio, Erik A J Rauws, Marja A Boermeester, Olivier R Busch, Jaap Stoker, Johan S Laméris, Marcel G W Dijkgraaf, Kees Huibregtse, Marco J Bruno
雑誌名: N Engl J Med. 2007 Feb 15;356(7):676-84. doi: 10.1056/NEJMoa060610.
Abstract/Text BACKGROUND: For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct.
METHODS: All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function.
RESULTS: Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001).
CONCLUSIONS: Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-trials.com].).

Copyright 2007 Massachusetts Medical Society.
PMID 17301298  N Engl J Med. 2007 Feb 15;356(7):676-84. doi: 10.1056/N・・・
著者: Michael J Farnbacher, Steffen Mühldorfer, Markus Wehler, Bernhard Fischer, Eckhart G Hahn, H Thomas Schneider
雑誌名: Scand J Gastroenterol. 2006 Jan;41(1):111-7. doi: 10.1080/00365520510024098.
Abstract/Text OBJECTIVE: In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable.
MATERIAL AND METHODS: In 98 patients suffering from symptomatic CP (84 M, 14 F, 49+/-12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35+/-28 (8 days-111) months. All data were assessed retrospectively.
RESULTS: As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3+/-1 (1 day-11) months. Total stent treatment time was 10+/-10 (6 days-49) months. At 46+/-27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption.
CONCLUSIONS: Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.

PMID 16373284  Scand J Gastroenterol. 2006 Jan;41(1):111-7. doi: 10.10・・・
著者: K F Binmoeller, P Jue, H Seifert, W C Nam, J Izbicki, N Soehendra
雑誌名: Endoscopy. 1995 Nov;27(9):638-44. doi: 10.1055/s-2007-1005780.
Abstract/Text BACKGROUND AND STUDY AIMS: Endoscopic pancreatic stent drainage has been reported to relieve pain due to chronic pancreatitis in patients with ductal outflow obstruction. However, data regarding the long-term results, as presented here, have hitherto been lacking.
PATIENTS AND METHODS: Over a nine-year period, 93 patients (65 males, mean age 49 years) with narcotic-dependent pain due to chronic pancreatitis and with a dominant pancreatic duct stricture visualized by endoscopic retrograde cholangiopancreatography (ERCP), were treated by stent drainage. The duration of pain prior to treatment averaged 5.6 years. The stents were exchanged according to symptoms, and removed if the stricture was judged to be adequately dilated after stenting.
RESULTS: Sixty-nine patients (74%) reported complete (n = 46) or partial (n = 23) pain relief at six months. In this group of "early responders", 60 patients experienced sustained improvement during a mean follow-up of 4.9 years (nine had recurrent pain after a mean of 1.2 years). Stents were removed in 49 patients after a mean of 15.7 months; during a mean follow-up of 3.8 years, 36 patients remained pain-free, and 13 had a relapse of pain (11 were retreated by endoscopic drainage and subsequently became pain-free). Complications seen included mild pancreatitis (n = 4) and abscess formation secondary to stent clogging (n = 2). Most patients experienced a regression of the ductal dilation after stenting.
CONCLUSION: In selected patients, early responders to pancreatic stent drainage are likely to benefit over the long term. Stent removal after stricture dilation may be associated with continued pain relief.

PMID 8903975  Endoscopy. 1995 Nov;27(9):638-44. doi: 10.1055/s-2007-1・・・
著者: L Gullo, L Barbara, G Labò
雑誌名: Gastroenterology. 1988 Oct;95(4):1063-8.
Abstract/Text Exocrine pancreatic function was studied sequentially by means of the secretin-cerulein test in 32 patients with alcoholic chronic pancreatitis to elucidate the long-term course of pancreatic dysfunction, and to determine whether the cessation of alcohol use had any influence on the natural history of pancreatic functional changes caused by this disease. At initial studies, 5 patients had normal pancreatic function, and the remaining 27 had pancreatic insufficiency, which was mild to moderate in most subjects. The final studies, carried out at an average of 7.3 yr (range, 4-11 yr) after the first, showed a significant deterioration in pancreatic function, both in patients who stopped alcohol after the initial study (n = 18) and in those who did not (n = 14). The deterioration, however, was significantly less marked in patients who stopped drinking alcohol than in those who continued. These data indicate that pancreatic functional changes caused by alcoholic pancreatitis progress even after cessation of alcohol use; however, the progression is slower and less severe when alcohol intake is stopped.

PMID 3410221  Gastroenterology. 1988 Oct;95(4):1063-8.
著者: H Miyake, H Harada, K Kunichika, K Ochi, I Kimura
雑誌名: Pancreas. 1987;2(4):378-85.
Abstract/Text Course and prognosis of 125 patients with chronic pancreatitis (CP) were evaluated. Follow-up period ranged from 1-20 years with a median of 6.3 years. The following conclusions were obtained. Recent increase of CP in our clinics was ascribed to alcoholic CP and idiopathic CP in the aged. Of 106 patients with pain, 74 showed improvement or disappearance of pain. Drinking habit and observation period were the main factors determining the rate of pain relief. Serial endoscopic retrograde pancreatography (ERP) showed aggravation in 17/47 patients, cholecystokinin-pancreozymin (CCK-PZ) secretin test in 4/40 patients, and oral glucose tolerance test (OGTT) in 7/25 patients. Exocrine function showed improvement in five patients, whereas endocrine function showed none. Improvement or aggravation of exocrine function was closely related to drinking habit. Main complications included 15 cases of peptic ulcer, 19 of pancreatic pseudocyst, and 15 of bile duct stenosis. Twenty-six patients died, often due to malignant neoplasms and diabetic complications. Those who continued drinking as much showed a lower survival rate than those who discontinued or decreased alcohol intake. The socioeconomic status deteriorated often due to pain or alcoholism. Three patients had to degrade jobs and six fell into inactive social life.

PMID 3628235  Pancreas. 1987;2(4):378-85.
著者: T Hayakawa, T Kondo, T Shibata, Y Sugimoto, M Kitagawa
雑誌名: Dig Dis Sci. 1989 Jan;34(1):33-8.
Abstract/Text To evaluate the influence of chronic alcoholism on clinical features of chronic pancreatitis in Japan, pain evolution, pancreatic insufficiency, and long-term prognosis were studied by comparing chronic alcoholic pancreatitis (N = 88) with idiopathic pancreatitis (N = 67). The 155 patients with known course of the disease over three years were followed-up further for five more years, and pain evolution was evaluated once at the start and once at the end of the follow-up period. At the time of diagnosis, severe pain (59 vs 33%, P less than 0.001), pancreatic calcification (63 vs 31%, P less than 0.001), advanced exocrine pancreatic insufficiency (72 vs 60%, NS), and overt diabetes (48 vs 17%, P less than 0.001) were more common in alcoholic than in idiopathic pancreatitis, respectively. Pain evolution was similar in both pancreatitis, and the pain decreased with time. The rate of abstinence was higher in groups with pain relief than without in alcoholic pancreatitis. Cumulative mortality rate during the five years was higher in alcoholic than idiopathic pancreatitis (26 vs 10%, P less than 0.01). These results suggest more favorable evolution of the disease can be expected by abstinence from alcohol.

PMID 2910680  Dig Dis Sci. 1989 Jan;34(1):33-8.
著者: P G Lankisch, A Löhr-Happe, J Otto, W Creutzfeldt
雑誌名: Digestion. 1993;54(3):148-55.
Abstract/Text The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

PMID 8359556  Digestion. 1993;54(3):148-55.
著者: W B Strum
雑誌名: J Clin Gastroenterol. 1995 Jan;20(1):37-41.
Abstract/Text The role of alcohol in causing chronic pancreatitis is well-known, but the role of abstinence remains controversial and not well-understood. In this article, I examine the literature dealing with the effect of abstinence on chronic pain and the long-term outcome of chronic pancreatitis. A series of 50 patients with alcoholic chronic pancreatitis from my practice supplements the data. Alcohol consumption > 70 g/day for 7 or more years is characteristic. Moderate to severe abdominal pain is the dominant symptom. When patients stop drinking, abdominal pain disappears in the majority, pancreatic function deteriorates more slowly, the death rate diminishes, and a normal life is often possible. If abdominal pain continues after abstinence and the pancreatic duct remains dilated, a lateral pancreatojejunostomy helps most patients. In many patients not suitable for surgery, pain resolves with time.

PMID 7884175  J Clin Gastroenterol. 1995 Jan;20(1):37-41.
著者: G de las Heras, J de la Peña, M J López Arias, A C Gonzalez-Bernal, L Martín-Ramos, F Pons-Romero
雑誌名: J Clin Gastroenterol. 1995 Jan;20(1):33-6.
Abstract/Text To study the role that continuous drinking plays in the pain of chronic pancreatitis, we have examined 67 patients with alcoholic chronic pancreatitis with pain and 29 patients without pain, and we report on their alcoholic habits. Drinking habits played a part 92 (67.6%) of 136 times in patients with pain; in 185 without pain, 86 (46.5%) had continued their drinking habit (p < 0.001). Advanced pancreatic exocrine insufficiency was seen in 27 patients; 11 of them had pain during follow-up, whereas 16 did not. The nondrinker rate was similar in patients with and without pain, whereas among 69 patients with better pancreatic exocrine function, 56 had pain episodes and 13 did not. Alcoholic consumers were significantly more in number in the pain group: 70.4% versus 35% of the no pain group (p < 0.002). Our study shows that drinking alcohol in patients with chronic pancreatitis increased the frequency of painful episodes when there was relatively good pancreatic function, whereas in severe pancreatic insufficiency drinking had less influence on the development of pain.

PMID 7884174  J Clin Gastroenterol. 1995 Jan;20(1):33-6.
著者: Rémy F Meier, Christoph Beglinger
雑誌名: Best Pract Res Clin Gastroenterol. 2006;20(3):507-29. doi: 10.1016/j.bpg.2006.01.004.
Abstract/Text The pancreas plays a major role in nutrient digestion. Therefore, in both acute and chronic pancreatitis, exocrine and endocrine pancreatic insufficiency can develop, impairing digestive and absorptive processes. These changes can lead to malnutrition over time. In parallel to these changes, decreased caloric intake and increased metabolic activity are often present. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. In severe acute pancreatitis, enteral nutrition with a naso-jejunal feeding tube and a low molecular diet displays clear advantages compared to parenteral nutrition. Infectious complications, length of hospital stay and the need for surgery are reduced. Furthermore, enteral nutrition is less costly than parenteral nutrition. Parenteral nutrition is reserved for patients who do not tolerate enteral nutrition. Abstinence from alcohol, dietary modifications and pancreatic enzyme supplementation is sufficient in over 80% of patients with chronic pancreatitis. In addition, oral supplements are helpful. Enteral nutrition can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis.

PMID 16782526  Best Pract Res Clin Gastroenterol. 2006;20(3):507-29. d・・・
著者: Roland H Pfutzer, Alexander Schneider
雑誌名: Dig Dis. 2005;23(3-4):241-6. doi: 10.1159/000090171.
Abstract/Text Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. The majority of cases in the Western world are related to alcohol consumption. Treatment of alcoholic chronic pancreatitis has been difficult, since the mechanisms of disease progression and the causes of pain are poorly understood. The conservative management of chronic pancreatitis focuses on (a) avoidance of precipitating factors such as alcohol and smoking; (b) treatment of pain, and (c) replacement of exocrine and endocrine function. There is a lack of good controlled, randomized treatment trials in alcoholic pancreatitis. However, there is good evidence that lifestyle changes, such as alcohol cessation, hamper progression of the disease. Conservative treatment of pain should be based on a stepwise approach; however, underlying causes such as pseudocysts may require endoscopic or surgical therapy. Treatment of exocrine insufficiency requires pancreatic enzyme supplementation and adjustment to several smaller meals per day, while treatment of endocrine insufficiency requires insulin treatment.

Copyright 2005 S. Karger AG, Basel.
PMID 16508288  Dig Dis. 2005;23(3-4):241-6. doi: 10.1159/000090171.
著者: Julie C Shea, Michele D Bishop, Eliza M Parker, Andres Gelrud, Steven D Freedman
雑誌名: Pancreatology. 2003;3(1):36-40. doi: 10.1159/000069144.
Abstract/Text BACKGROUND/AIM: Pain in patients with chronic pancreatitis is difficult to manage. We examined if an enteral formulation containing medium-chain triglycerides (MCT) and hydrolyzed peptides would (1) minimally stimulate the exocrine pancreas by blunting cholecystokinin release and (2) decrease pain in patients with chronic pancreatitis.
METHODS: In the first part of the study, on separate days, 6 healthy controls consumed a standard enteral formulation, an enteral formulation containing MCT and hydrolyzed peptides, and a high-fat meal. Baseline and postprandial plasma cholecystokinin (CCK) concentrations were analyzed. Subsequently, 8 patients with chronic pancreatitis were enrolled and instructed to complete a visual analog pain assessment for a baseline period of 2 weeks followed by three cans per day of the enteral formulation containing MCT and hydrolyzed peptides for 10 weeks.
RESULTS: Mean CCK levels for our control subjects were 0.46 +/- 0.29 pM at baseline, 10.75 +/- 0.45 pM in response to the high-fat meal, and 7.9 +/- 1.25 pM in response to the standard enteral formulation. Of note, CCK levels were 1.43 +/- 0.72 pM in response to the enteral supplement containing MCT and hydrolyzed peptides. In patients with chronic pancreatitis, the average improvement in pain scores from baseline to the conclusion of the study was 61.8% (p = 0.01). This corresponded to a clinical improvement in 6 of the 8 patients.
CONCLUSIONS: A complete enteral supplement containing MCT and hydrolyzed peptides minimally increases plasma CCK levels. This therapy may be effective in reducing postprandial pain associated with chronic pancreatitis.

Copyright 2003 S. Karger AG, Basel and IAP
PMID 12649562  Pancreatology. 2003;3(1):36-40. doi: 10.1159/000069144.・・・
著者: Nobuo Ashizawa, Tomoyuki Hashimoto, Tatsuya Miyake, Toshihiro Shizuku, Tomonori Imaoka, Yoshikazu Kinoshita
雑誌名: J Gastroenterol Hepatol. 2006 Apr;21(4):767-71. doi: 10.1111/j.1440-1746.2005.04041.x.
Abstract/Text BACKGROUND: Differentiation between functional dyspepsia and early chronic pancreatitis is difficult because these diseases do not produce specific abnormalities in laboratory testing. The aim of this study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against functional dyspepsia and to characterize patients with favorable responses.
METHODS: Dyspeptic patients who exhibited no abnormalities on laboratory blood and urine testing, abdominal ultrasonography and upper gastrointestinal endoscopy were randomized to receive camostat mesilate 200 mg three times daily or famotidine 20 mg twice daily for 4 weeks. Symptoms severity was recorded before and at 2 and 4 weeks after starting treatment using a visual analog scale.
RESULTS: Epigastralgia was significantly improved after 2 and 4 weeks of treatment in both groups (P < 0.01); this improvement tended to be more marked in the camostat mesilate group (P < 0.05 at 2 weeks). The beneficial effect of camostat mesilate on epigastralgia was more prominent in chronic alcohol drinkers at 2 weeks (P < 0.05) and 4 weeks (P < 0.01).
CONCLUSIONS: Camostat mesilate is superior to famotidine for relieving epigastralgia in patients with functional dyspepsia. Its pain-relieving effect is greater in patients who habitually drink alcohol.

PMID 16677167  J Gastroenterol Hepatol. 2006 Apr;21(4):767-71. doi: 10・・・
著者: A Brown, M Hughes, S Tenner, P A Banks
雑誌名: Am J Gastroenterol. 1997 Nov;92(11):2032-5.
Abstract/Text OBJECTIVE: Pancreatic enzyme therapy is widely used in the treatment of pain in chronic pancreatitis. The aim of our study was to perform a meta-analysis to determine whether pancreatic enzyme supplementation significantly decreases abdominal pain in patients with chronic pancreatitis.
METHODS: From a MEDLINE search, we identified, evaluated, and subjected to a meta-analysis, six randomized, double-blind, placebo-controlled trials. Important features of data extraction included the method of subject inclusion, definition of disease, enzyme preparation, response to pancreatic enzyme therapy versus placebo, and modality for measuring response.
RESULTS: In the meta-analysis, the pooled estimate of the percentage of patients per study who preferred enzymes relative to placebo was 52% (95% confidence interval, 45-60%). A test of homogeneity indicated that there was no statistically significant heterogeneity across studies in the percentage of patients preferring enzymes.
CONCLUSION: Statistical analysis demonstrates no significant benefit of supplemental pancreatic enzyme therapy to relieve pain associated with chronic pancreatitis.

PMID 9362186  Am J Gastroenterol. 1997 Nov;92(11):2032-5.
著者: J Slaff, D Jacobson, C R Tillman, C Curington, P Toskes
雑誌名: Gastroenterology. 1984 Jul;87(1):44-52.
Abstract/Text The purposes of this study were to (a) evaluate the effect of pancreatic extract administered to patients with chronic pancreatitis and recurrent abdominal pain in a placebo-controlled, double-blind crossover study, (b) investigate the effects of acute intraduodenal pancreatic enzyme perfusion on pancreatic secretion, and (c) assess the effect of chronic, noninterrupted pancreatic extract administration on basal and stimulated pancreatic secretion. These studies demonstrated that pancreatic extract decreases abdominal pain and that intraduodenal perfusion with proteases but not with amylase or lipase suppresses pancreatic exocrine secretion in patients with chronic pancreatitis. Chronic administration of pancreatic extract to patients with chronic pancreatitis decreased both basal and stimulated pancreatic exocrine secretion.

PMID 6202586  Gastroenterology. 1984 Jul;87(1):44-52.
著者: G Isaksson, I Ihse
雑誌名: Dig Dis Sci. 1983 Feb;28(2):97-102.
Abstract/Text In a double-blind study on 19 patients with the diagnosis of chronic pancreatitis, the effects of treatment with a granulated pancreatic enzyme preparation (Pankreon) were compared with those of placebo administration. One week of treatment with each preparation was preceded by one week without any medication. The patients kept daily records of their symptoms, plotting the severity of pain on an analog scale. Weekly assessments of the mean pain level were also made by an examiner questioning the patients. Recordings of body weights and pancreas and liver laboratory tests were done weekly. Fifteen of 19 patients noted less pain during the week of treatment with pancreatic enzymes as compared to that of placebo treatment (P less than 0.05). The average reduction of pain, as calculated for all patients, was 30% as evaluated by both patients (P less than 0.01) and the examiner (P less than 0.05). No differences were found in other parameters examined. A possible explanation of the findings could be an effect on the intraductal pressure by intraluminal trypsin.

PMID 6825540  Dig Dis Sci. 1983 Feb;28(2):97-102.
著者: J Mössner, R Secknus, J Meyer, C Niederau, G Adler
雑誌名: Digestion. 1992;53(1-2):54-66.
Abstract/Text According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain.

PMID 1289173  Digestion. 1992;53(1-2):54-66.
著者: A Malesci, E Gaia, A Fioretta, P Bocchia, G Ciravegna, P Cantor, I Vantini
雑誌名: Scand J Gastroenterol. 1995 Apr;30(4):392-8.
Abstract/Text BACKGROUND: This study was aimed to investigate the effect of long-term treatment with high-protease pancreatic extract on the recurrent abdominal pain of patients with chronic pancreatitis.
METHODS: Twenty-six patients with a firm diagnosis of chronic pancreatitis and a pattern of recurrent pain were recruited and randomly assigned to treatment with pancreatic extract (Pancrex-Duo capsules, each containing 34,375 USP units of protease in enteric-coated microspheres) or placebo, at a dose of four capsules four times daily, for 4 months. At the end of the first period patients were switched to the other medication for the next 4 months. Four patients did not complete the study because of unbearable recurring pain or inadequate compliance with treatment. The other 22 patients daily recorded the presence, intensity, and duration of pain and the consumption of analgesics, for 8 months.
RESULTS: No difference was found when intraindividual records during placebo and extract treatment periods were compared. Conversely, in the second 4 months of follow-up, regardless of the treatment given in the first period, there was a significant reduction in the cumulative pain score (median, 95; range, 0-1005, versus 134; 0-972; p < 0.05), in the number of days (8; 0-132, versus 13; 0-126; p < 0.02) and hours (54; 0-680, versus 80; 0-602; p < 0.05) of pain, and in the analgesic consumption score (0; 0-22, versus 12; 0-44; p = 0.02).
CONCLUSIONS: Chronic supplementation with pancreatic extract is not beneficial in the management of recurrent pain in patients with chronic pancreatitis.

PMID 7610357  Scand J Gastroenterol. 1995 Apr;30(4):392-8.
著者: O J Rämö, P A Puolakkainen, K Seppälä, T M Schröder
雑誌名: Scand J Gastroenterol. 1989 Aug;24(6):688-92.
Abstract/Text The effect of self-administration (ad lib) of pancreatic enzyme substitution (Pancrease) in comparison with the dosage recommended by the manufacturer on abdominal symptoms and nutritional variables was studied in 10 patients with chronic pancreatitis. Both dosages were started in randomized order and they were continued for 4 weeks. Before and after each period of administration the patients were studied physically and weighed, and laboratory tests were performed. In addition, the patients kept daily records of pain (score, 0-3), bowel movements, amount of medication needed for maximum relief of symptoms and other remarks, if any. During self-administration, the number of capsules taken increased (5 +/- 1.3 to 11.4 +/- 2.4; p less than 0.001), the frequency of bowel movements decreased (3.6 +/- 1.4 to 1.6 +/- 0.7; p less than 0.05), and the pain was also relieved significantly (2.2 +/- 0.7 to 1.1 +/- 0.7; p less than 0.05) when compared with the regular dosage. Self-administration of the preparation did not have any significant effects on nutritional variables. Dryness of the mouth was the only complaint during self-administration of the drug in 4 of 10 patients. In conclusion, this study in selected patients with chronic pancreatitis indirectly supports the presence of a negative feedback regulation of exocrine pancreatic secretion in man. Thus, it may be beneficial to try self-administration of pancreatic enzyme substitution in selected patients to achieve maximum relief of symptoms in chronic pancreatitis.

PMID 2479083  Scand J Gastroenterol. 1989 Aug;24(6):688-92.
著者:
雑誌名: Gastroenterology. 1998 Sep;115(3):763-4.
Abstract/Text
PMID 9721174  Gastroenterology. 1998 Sep;115(3):763-4.
著者: J Mössner, V Keim, C Niederau, M Büchler, M V Singer, P G Lankisch, B Göke
雑誌名: Z Gastroenterol. 1998 May;36(5):359-67.
Abstract/Text
PMID 9654702  Z Gastroenterol. 1998 May;36(5):359-67.
著者: T Sauerbruch, J Holl, M Sackmann, G Paumgartner
雑誌名: Gut. 1992 Jul;33(7):969-72.
Abstract/Text Extracorporeal shock wave lithotripsy of pancreatic duct stones (largest stone 12 (SD) 6 mm) was performed in 24 patients with abdominal pain and a dilated duct system (main pancreatic duct 10 (3) mm). The procedure was well tolerated in all but two patients, who had a mild pancreatitic attack immediately after lithotripsy. Disintegration of the stones was achieved in 21 patients. This allowed complete clearance of the duct system by an endoscopic approach in 10 (42%) patients and partial clearance in 7 (29%) patients. Within a mean follow up period of 24 (14) months half of the patients showed complete or considerable relief of pain and alleviation of symptoms was achieved in seven patients. Relief of pain occurred more often after complete ductal clearance. There were no fatalities within the follow up period. These findings underline the value of a combined non-surgical approach, using endoscopy and adjuvant shock wave lithotripsy to patients with large pancreatic calculi and pain attacks.

PMID 1644340  Gut. 1992 Jul;33(7):969-72.
著者: M Delhaye, A Vandermeeren, M Baize, M Cremer
雑誌名: Gastroenterology. 1992 Feb;102(2):610-20.
Abstract/Text Extracorporeal shock-wave lithotripsy (ESWL) has been used to disintegrate pancreatic stones located in the main pancreatic duct for 123 patients with severe chronic pancreatitis. Endoscopic management following ESWL is aimed at restoring the pancreatic flow to the duodenum. Stone disintegration was achieved in 122 patients, whereas a decrease in the main pancreatic duct diameter resulted in 111, and complete clearance of the main pancreatic duct was obtained in 72. Pain relief, complete (40/88) or partial (35/88), correlated significantly with the results of the endoscopic drainage of the main pancreatic duct (e.g., decrease in main pancreatic duct diameter). Relapsing pain was most often related to recurrent pancreatic duct obstruction. Of 76 patients whose body weight had decreased before ESWL, 54 gained weight. Improvement of the exocrine function, evaluated by the [14C]triolein breath test before and 11 months, on the average, after ESWL, was observed in 12 patients among 22 for whom this test was performed before and after treatment. Improvement of the endocrine function after relief of obstruction of the main pancreatic duct was less frequently recorded (4/41). ESWL of pancreatic stones is a new, safe, and highly effective method of facilitating the endoscopic procedures for relief of pancreatic duct obstruction in severe chronic pancreatitis.

PMID 1732129  Gastroenterology. 1992 Feb;102(2):610-20.
著者: Richard A Kozarek, John J Brandabur, Terrence J Ball, Michael Gluck, David J Patterson, Fouad Attia, Renee France, L William Traverso, Paul Koslowski, Robert P Gibbons
雑誌名: Gastrointest Endosc. 2002 Oct;56(4):496-500. doi: 10.1067/mge.2002.128105.
Abstract/Text BACKGROUND: There is controversy as to whether extracorporeal shock wave lithotripsy fragmentation and ERCP retrieval of pancreatic stones are associated with relief of chronic pain or relapsing attacks of pancreatitis. Our most recent experience with this technology is reviewed.
METHODS: Forty patients with chronic calcific pancreatitis who required extracorporeal shock wave lithotripsy between 1995 and 2000 to facilitate pancreatic duct stone removal were retrospectively reviewed. Data collected included patient presentation, number of lithotripsy and ERCP sessions required, complications, and outcomes measures to include pre- and post-ESWL pain scale, monthly oxycodone (5 mg)-equivalent pills ingested, yearly hospitalizations, and need for subsequent surgery.
RESULTS: A single extracorporeal shock wave lithotripsy session was required for 35 patients who underwent a total of 86 ERCPs to achieve complete stone extraction from the main pancreatic duct. Minor complications occurred in 20%. There was one episode of pancreatic sepsis that was treated with antibiotics and removal of an occluded pancreatic prosthesis. At a mean [SD] follow-up of 2.4 (0.6) years, 80% of patients had avoided surgery and there was a statistically significant decrease in pain scores (6.9 [1.3] vs. 2.9 [1.1]; p = 0.001), yearly hospitalizations for pancreatitis (3.9 [1.9] vs. 0.9 [0.9]; p = 0.001), and oxycodone-equivalent narcotic medication ingested monthly (125 [83] vs. 81 [80]; p = 0.03).
CONCLUSIONS: Extracorporeal shock wave lithotripsy fragmentation of pancreatic duct calculi in conjunction with endoscopic clearance of the main pancreatic duct is associated with significant improvement in clinical outcomes in most patients with chronic pancreatitis.

PMID 12297763  Gastrointest Endosc. 2002 Oct;56(4):496-500. doi: 10.10・・・
著者: Nalini M Guda, Susan Partington, Martin L Freeman
雑誌名: JOP. 2005 Jan 13;6(1):6-12. Epub 2005 Jan 13.
Abstract/Text CONTEXT: Main pancreatic duct stones may contribute to pain in chronic pancreatitis. Extracorporeal shock wave lithotripsy (ESWL) has been used alone or in combination with endoscopic therapy for fragmentation of stones. Published studies have shown mixed efficacy due to small sample size.
OBJECTIVE: Systematic analysis of all published data evaluating ESWL with or without endoscopic therapy in pancreatic duct clearance and symptom relief.
METHODS: Two investigators independently reviewed the computer databases. 31 potential studies were identified. Only studies using ESWL with or without endoscopic therapy were included. Completeness of the search was confirmed by an expert. Studies were independently coded by two investigators and differences rectified by mutual consent.
MAIN OUTCOME MEASURES: Pain at follow-up and duct clearance.
RESULTS: Seventeen studies published between 1989 and 2002 were included. Sixteen had a measure of pain at follow-up and duct clearance. All studies were case series with a total of 588 subjects, and included varying number of subjects undergoing endoscopic pancreatic sphincterotomy and stone extraction. The mean effect size (weighted correlation coefficient) for pain was 0.6215 and for duct clearance was 0.7432; thus indicating a large effect. All studies showed homogeneity suggesting similar effect size irrespective of the combinations of therapy.
CONCLUSIONS: ESWL is effective in clearance of stones from the pancreatic duct and in relief of pain. Published studies showed homogeneity of the effect size of ESWL both in pancreatic duct clearance and relief of pain.

PMID 15650279  JOP. 2005 Jan 13;6(1):6-12. Epub 2005 Jan 13.
著者: H E Adamek, R Jakobs, A Buttmann, M U Adamek, A R Schneider, J F Riemann
雑誌名: Gut. 1999 Sep;45(3):402-5.
Abstract/Text BACKGROUND: There have been conflicting reports as to whether pancreatic ductal drainage achieved by endoscopy and lithotripsy improves the clinical outcome of patients with chronic pancreatitis.
AIMS: To determine the clinical outcome in patients with chronic pancreatitis who received extracorporeal shock wave lithotripsy (ESWL), and were followed up for two to eight years.
METHODS: Eighty patients with severe chronic pancreatitis and endoscopically unretrievable obstructive stones underwent ESWL with a piezoelectric lithotripter between 1989 and 1996. Clinical status, relief of symptoms, further endoscopic or surgical interventions, and mortality were defined.
RESULTS: Forty three (54%) patients were treated successfully with ESWL. The only feature associated with treatment success was the presence of a single stone rather than multiple stones. Successfully treated patients tended to experience less pain, although this did not reach statistical significance. A slight increase in weight was noted in our patients; however, there was no notable improvement in anomalous stools and diabetes mellitus. Five patients died due to extrapancreatic reasons. No pancreatic carcinomas developed.
CONCLUSIONS: ESWL associated with endoscopic drainage is a safe technique that is particularly successful in patients with a single stone. However, pancreatic drainage by endoscopy and ESWL has almost no effect on pain in chronic pancreatitis. Furthermore, endoscopic management and ESWL does not prevent or postpone the development of glandular insufficiency.

PMID 10446109  Gut. 1999 Sep;45(3):402-5.
著者: Kazuo Inui, Susumu Tazuma, Taketo Yamaguchi, Hirotaka Ohara, Tadao Tsuji, Hiroyuki Miyagawa, Yoshinori Igarashi, Yuta Nakamura, Yutaka Atomi
雑誌名: Pancreas. 2005 Jan;30(1):26-30.
Abstract/Text OBJECTIVES: A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones.
METHODS: A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic.
RESULTS: Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%).
CONCLUSION: ESWL is the treatment of choice for clearing pancreatic stones.

PMID 15632696  Pancreas. 2005 Jan;30(1):26-30.
著者: T Rösch, S Daniel, M Scholz, K Huibregtse, M Smits, T Schneider, C Ell, G Haber, J-F Riemann, R Jakobs, R Hintze, A Adler, H Neuhaus, M Zavoral, F Zavada, V Schusdziarra, N Soehendra, European Society of Gastrointestinal Endoscopy Research Group
雑誌名: Endoscopy. 2002 Oct;34(10):765-71. doi: 10.1055/s-2002-34256.
Abstract/Text BACKGROUND AND STUDY AIMS: Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort.
PATIENTS AND METHODS: Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain).
RESULTS: Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy.
CONCLUSIONS: Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.

PMID 12244496  Endoscopy. 2002 Oct;34(10):765-71. doi: 10.1055/s-2002-・・・
著者: Myriam Delhaye, Marianna Arvanitakis, Gontran Verset, Michel Cremer, Jacques Devière
雑誌名: Clin Gastroenterol Hepatol. 2004 Dec;2(12):1096-106.
Abstract/Text BACKGROUND & AIMS: Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions.
METHODS: Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality.
RESULTS: Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success.
CONCLUSIONS: Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.

PMID 15625655  Clin Gastroenterol Hepatol. 2004 Dec;2(12):1096-106.

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