今日の臨床サポート

膵臓の石灰化

著者: 廣田衛久 東北医科薬科大学 内科学第二(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:2021/02/03
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 第2版
  1. 国際膵臓学会(IAP)/ 米国膵臓学会(APA),日本膵臓学会/ 欧州膵臓クラブ(EPC):International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.
  1. 国際膵臓学会(IAP)/ 米国膵臓学会(APA), 日本膵臓学会 / 欧州膵臓クラブ(EPC):International consensus guidelines on interventional endoscopy in chronic pancreatitis.
  1. 欧州消化器内視鏡学会(ESGE):Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Updated August 2018
患者向け説明資料

概要・推奨   

  1. 膵管内の結石(膵石)を認めた場合と、膵全体に分布する複数かつびまん性の石灰化を認めた場合は慢性膵炎と診断できる(推奨度1)
  1. 加齢現象に伴い膵石が観察される場合がある。
  1. 石灰化を伴った膵腫瘍がまれに存在する。
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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:
廣田衛久 : 特に申告事項無し[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. 慢性膵炎の臨床診断基準が改訂され、全国調査もアップデートされたため、最新の情報を掲載した。
  1. 最新の国際ガイドラインより、慢性膵炎の疼痛に対する早期手術の記載を追加した。

病態・疫学・診察

疫学情報・病態・注意事項  
  1. 膵臓の石灰化は以下の2つに大別される。1)膵管内結石(膵石)、2)膵実質の石灰化。
  1. 1)膵管内結石は慢性膵炎の確診所見であり、CT、US、超音波内視鏡(EUS)により膵管内結石を認めた場合、慢性膵炎と確定診断できる[1][2]。剖検例の観察から、高齢者では慢性膵炎の臨床所見に乏しい加齢性変化と思われる膵石を70歳代の約4%、80歳代の約8%、90歳代では約17%に認めるという報告がある[3]
 
膵管内結石(膵石)の単純CT画像

膵体部に膵石(矢印)を認める。それより尾側の主膵管が拡張している。膵尾部の膵実質内にも小石灰化を認める。慢性膵炎確診の画像所見である。

出典

img1:  著者提供
 
 
 
膵石の超音波内視鏡(EUS)像

拡張した主膵管(矢頭)内に音響陰影を伴う高エコー(膵石;矢印)を2個認める。慢性膵炎確診の画像所見である。

出典

img1:  著者提供
 
 
 
  1. 2)膵実質の石灰化も多くは慢性膵炎を診断する所見である。CT、US、EUSにて膵全体に分布する複数ないしびまん性の石灰化を認めた場合、慢性膵炎と確定診断できる[1][2]
 
膵実質石灰化の単純CT画像

膵体尾部の膵実質に複数の石灰化を認める。慢性膵炎確診の画像所見である。

出典

img1:  著者提供
 
 
 
  1. 加齢現象に伴い膵石が観察される場合があるO
  1. 剖検例の検討から、70歳以上の高齢者では高率に膵石を認めたと報告されている。
  1. 膵石は69歳以下では0%であったが、70歳代では4.2%、80歳代では7.7%、90歳代では16.7%に認められ、高齢者の膵石は多くが末梢の膵管内に存在し、腹痛やアルコール依存症などとは関係しないことが特徴である[3]
 
  1. わが国の全国疫学調査によると、2019年1年間に慢性膵炎で医療機関を受療した患者数は推定5万6,520人、人口10万人あたり44.5人であった。慢性膵炎患者の約67%に膵石または膵石灰化を認めた[4]
 
  1. 最近の全国調査では2019年1年間で受療した慢性膵炎の患者数は推定約56,520人であり、人口10万人あたり44.5人である。慢性膵炎患者のうち約67%に膵石灰化を認めたため、慢性石灰化膵炎患者は推定3万7,900人であるO
  1. これまで、膵石灰化を対象とした疫学調査研究はない。膵石灰化の95%は慢性膵炎と診断されることから、慢性膵炎の疫学調査結果を示す。
  1. わが国では厚労省難治性膵疾患研究班により、定期的に慢性膵炎患者の疫学調査が行われている。最新の調査結果では、2019年1年間に日本全国の医療機関を受療した慢性膵炎患者数は推定5万6,520人であり、人口10万人あたり44.5人と、緩やかに増加傾向にある[4]
  1. 慢性膵炎患者のうち、膵石灰化を認めたのは全体で約67%であった。膵石灰化率は成因により異なり、アルコール性では70.3%、特発性では59.7%であった[4]
 
  1. 膵臓の石灰化と鑑別を要するものとして、膵腫瘍の石灰化がある。solid-pseudopapillary neoplasm (SPN)、膵内分泌腫瘍、漿液性嚢胞腫瘍(serous cystic neoplasm、SCN)などで石灰化を認めることがある[5][6]
 
Solid and pseudopapillary neolasm(SPN)の卵殻状石灰化

膵頭部に卵殻状石灰化を認める(矢印)。切除を行い、SPNの診断であった。

出典

img1:  著者提供
 
 
問診・診察のポイント  
問診:
  1. 膵に石灰化を認める場合は、慢性膵炎を念頭に以下の問診を行う。

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文献 

著者: Tooru Shimosegawa, Keisho Kataoka, Terumi Kamisawa, Hiroyuki Miyakawa, Hirotaka Ohara, Tetsuhide Ito, Satoru Naruse, Naohiro Sata, Koichi Suda, Morihisa Hirota, Yoshifumi Takeyama, Keiko Shiratori, Takashi Hatori, Makoto Otsuki, Yutaka Atomi, Kentaro Sugano, Masao Tanaka
雑誌名: J Gastroenterol. 2010 Jun;45(6):584-91. doi: 10.1007/s00535-010-0242-4. Epub 2010 Apr 28.
Abstract/Text In Japan, we are now using the clinical diagnostic criteria for chronic pancreatitis (CP) that were revised in 2001 to add the findings of magnetic resonance cholangiopancreatography to the criteria compiled by the Japan Pancreas Society (JPS) in 1995. Because the current criteria are set for diagnosing advanced CP, they are unlikely to improve patients' prognoses. In addition, they seem unsuitable for current clinical practice because exocrine pancreatic function tests, which have become obsolete in Japan, are included in the diagnostic factors. For these reasons, the Research Committee on Intractable Pancreatic Diseases supported by the Ministry of Health, Labour and Welfare of Japan, the JPS and the Japanese Society of Gastroenterology have revised the criteria. The revised criteria are unique in that they contain an introduction to the concept of early CP. It is a challenge aimed at improvement of the long-term prognosis of CP patients by early diagnosis and therapeutic intervention in this disease. We need to determine and clarify the clinico-pathological outcome of early CP by a prospective long-term follow-up of the patients in this category.

PMID 20422433  J Gastroenterol. 2010 Jun;45(6):584-91. doi: 10.1007/s0・・・
著者: H Nagai, K Ohtsubo
雑誌名: Gastroenterology. 1984 Feb;86(2):331-8.
Abstract/Text The incidence of pancreatic calculi in autopsy material was found to increase in proportion to age after 70 yr: 0% under 69 yr of age (0 of 134), 4.2% in the 70s (5 of 119), 7.7% in the 80s (9 of 117), and 16.7% in the 90s (8 of 48). Most of the stones were found scattered throughout the peripheral ducts. Pancreatic lithiasis in the aged was clinically characterized by lack of signs and symptoms, absence of alcoholism, and was unassociated with hypercalcemia. Extensive parenchymal atrophy and fibrosis were limited to the areas upstream from the calculi. The stones were found in the ducts just above the sites of obstruction where squamous metaplasia was invariably present. Immunohistologic study showed intense staining for lactoferrin in the protein plugs and in the cytoplasm of cuboidal or squamous cells of ducts containing the plugs. Ductal stenosis, either primarily caused or secondarily exacerbated by squamous metaplasia, and lactoferrin-positive cells appeared to play a role in the pathogenesis of pancreatic lithiasis in the aged.

PMID 6690361  Gastroenterology. 1984 Feb;86(2):331-8.
著者: Atsushi Masamune, Kazuhiro Kikuta, Kiyoshi Kume, Shin Hamada, Ichiro Tsuji, Yoshifumi Takeyama, Tooru Shimosegawa, Kazuichi Okazaki, Japan Pancreas Society
雑誌名: J Gastroenterol. 2020 Nov;55(11):1062-1071. doi: 10.1007/s00535-020-01704-9. Epub 2020 Jul 16.
Abstract/Text OBJECTIVES: To provide updated clinico-epidemiological information on chronic pancreatitis (CP) in Japan.
METHODS: We conducted a two-stage nationwide epidemiological survey; the number of CP patients was estimated in the first-stage survey, and their clinical features were examined in the second-stage survey. We surveyed patients with CP who had visited hospitals in 2016 and were diagnosed according to the Japanese diagnostic criteria 2009 (DC2009). Furthermore, we validated the new Japanese diagnostic criteria (DC2019) in patients with early CP diagnosed according to DC2009.
RESULTS: The number of patients with definite/probable CP in 2016 was 56,520 (prevalence, 44.5 per 100,000 persons), and that of early CP was 4470 (prevalence, 3.5 per 100,000 persons). We obtained detailed clinical information of 2150 patients with definite/probable CP and 249 patients with early CP. Compared with the early CP cases, the definite/probable CP cases had higher proportions of male (4.8 vs. 1.3), alcohol-related etiology (72.0% vs. 45.8%), smoking history (69.6% vs. 41.0%), diabetes mellitus (42.3% vs. 19.3%), and past history of acute pancreatitis (AP) (50.4% vs. 22.1%). Among the patients with early CP diagnosed according to DC2009, 93 (37.3%) were diagnosed with early CP according to DC2019, but the diagnosis of the remaining 156 (62.7%) patients was downgraded. Alcohol-related etiology, smoking history, early disease onset, and past history of AP were associated with the maintenance of early CP diagnosis in DC2019.
CONCLUSION: We clarified the current status of CP in Japan. Further validation studies are warranted to clarify the diagnostic utility of DC2019.

PMID 32676800  J Gastroenterol. 2020 Nov;55(11):1062-1071. doi: 10.100・・・
著者: Catherine E Dewhurst, Koenraad J Mortele
雑誌名: Radiol Clin North Am. 2012 May;50(3):467-86. doi: 10.1016/j.rcl.2012.03.001. Epub 2012 Mar 28.
Abstract/Text Cystic tumors of the pancreas are a subset of rare pancreatic tumors that vary from benign to malignant. Many have specific imaging findings that allow them to be differentiated from each other. This article (1) reviews the imaging features of the common cystic pancreatic lesions, including serous microcystic adenoma, mucinous cystic tumor, intraductal papillary mucinous tumor, and solid pseudopapillary tumor, and including the less common lesions such as cystic endocrine tumors, cystic metastases, cystic teratomas, and lymphangiomas; and (2) provides comprehensive algorithms on how to manage the individual lesions, with recommendations on when to reimage patients.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 22560692  Radiol Clin North Am. 2012 May;50(3):467-86. doi: 10.10・・・
著者: Nancy A Hammond, Frank H Miller, Kevin Day, Paul Nikolaidis
雑誌名: Abdom Imaging. 2013 Jun;38(3):561-72. doi: 10.1007/s00261-012-9922-2.
Abstract/Text Contrast-enhanced multiphase CT and dynamic gadolinium-enhanced MR have been validated in the literature as outstanding modalities for the evaluation of pancreatic pathology. In addition to the more frequently seen pancreatic adenocarcinoma, neuroendocrine tumors of the pancreas and cystic lesions such as serous and mucinous cystadenomas and IPMNs, a variety of benign and malignant lesions may occur in the pancreas. The purpose of this pictorial essay is to review the imaging findings of a variety of uncommon, benign and malignant, pancreatic neoplasms.

PMID 22711184  Abdom Imaging. 2013 Jun;38(3):561-72. doi: 10.1007/s002・・・
著者: P Layer, H Yamamoto, L Kalthoff, J E Clain, L J Bakken, E P DiMagno
雑誌名: Gastroenterology. 1994 Nov;107(5):1481-7.
Abstract/Text BACKGROUND/AIMS: Compared with alcoholic pancreatitis, little is known about the natural history of idiopathic pancreatitis. Two hundred forty-nine patients with alcoholic pancreatitis and 66 patients with idiopathic chronic pancreatitis seen at our institution between 1976 and 1982 were investigated.
METHODS: Records were analyzed retrospectively from the onset of symptomatic disease, and patients were followed up prospectively until 1985. Patients with early-onset (n = 25) and late-onset (n = 41) idiopathic chronic pancreatitis had a median age at onset of symptoms of 19 and 56 years, respectively.
RESULTS: The gender distribution was nearly equal in idiopathic chronic pancreatitis, but 72% of patients with alcoholic pancreatitis were men (P = 0.001 vs. idiopathic). In early-onset idiopathic pancreatitis, calcification and exocrine and endocrine insufficiency developed more slowly than in late-onset idiopathic and alcoholic pancreatitis (P = 0.03). However, in early idiopathic chronic pancreatitis, pain frequently occurred initially (P = 0.003 vs. late and alcoholic) and was more severe (P = 0.04 vs. late and alcoholic). In late-onset idiopathic pancreatitis, pain was absent in nearly 50% of patients.
CONCLUSIONS: There are two distinct forms of idiopathic chronic pancreatitis. Patients with early-onset pancreatitis have initially and thereafter a long course of severe pain but slowly develop morphological and functional pancreatic damage, whereas patients with late-onset pancreatitis have a mild and often a painless course. Both forms differ from alcoholic pancreatitis in their equal gender distribution and a much slower rate of calcification.

PMID 7926511  Gastroenterology. 1994 Nov;107(5):1481-7.
著者: Rudolf W Ammann, Beat Mullhaupt
雑誌名: J Gastroenterol. 2007 Jan;42 Suppl 17:118-26. doi: 10.1007/s00535-006-1940-9.
Abstract/Text
PMID 17238040  J Gastroenterol. 2007 Jan;42 Suppl 17:118-26. doi: 10.1・・・
著者: M Imoto, E P DiMagno
雑誌名: Pancreas. 2000 Aug;21(2):115-9.
Abstract/Text An association exists between cigarette smoking and pancreatitis owing to alcohol. We determined whether cigarette smoking affected the course of pancreatic calcification and insufficiency in idiopathic chronic pancreatitis. Medical records were analyzed of 24 persons with early- and 42 with late-onset idiopathic chronic pancreatitis who were diagnosed between 1976 and 1982 and then followed prospectively until 1985. Smoking equaled >5 pack-years before calcification or insufficiency or last follow-up. Mean follow-up after onset of chronic pancreatitis was 27 and 13 years in early- and late-onset idiopathic chronic pancreatitis, respectively. Incidence of calcification in the two groups was 58 and 43%, respectively. In early-onset idiopathic chronic pancreatitis, smokers and nonsmokers developed calcification at a similar rate and frequency (58%). In late-onset idiopathic chronic pancreatitis, smokers developed pancreatic calcifications faster (p < 0.001) and more frequently (83 vs. 13%, p < 0.001) than nonsmokers. The association between smoking and pancreatic calcification was independent of gender, body mass index, and exocrine or endocrine insufficiency. Smoking did not affect development of exocrine or endocrine insufficiency. Cigarette smoking increases the risk of pancreatic calcification of late- but not of early-onset idiopathic chronic pancreatitis. These data support encouraging cessation of smoking in chronic pancreatitis.

PMID 10975703  Pancreas. 2000 Aug;21(2):115-9.
著者: P Maisonneuve, A B Lowenfels, B Müllhaupt, G Cavallini, P G Lankisch, J R Andersen, E P Dimagno, A Andrén-Sandberg, L Domellöf, L Frulloni, R W Ammann
雑誌名: Gut. 2005 Apr;54(4):510-4. doi: 10.1136/gut.2004.039263.
Abstract/Text BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes.
AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes.
PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries.
METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption.
RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis.
CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.

PMID 15753536  Gut. 2005 Apr;54(4):510-4. doi: 10.1136/gut.2004.039263・・・
著者: Patrick Maisonneuve, Luca Frulloni, Beat Müllhaupt, Katia Faitini, Giorgio Cavallini, Albert B Lowenfels, Rudolf W Ammann
雑誌名: Pancreas. 2006 Aug;33(2):163-8. doi: 10.1097/01.mpa.0000227916.94073.fc.
Abstract/Text OBJECTIVES: Chronic pancreatitis is usually caused by heavy alcohol intake and, in many studies, also smoking. Because heavy drinkers usually smoke, making it difficult to separate the effects of these 2 factors, we thought to study the impact of smoking on the progression of nonalcoholic idiopathic chronic pancreatitis (ICP) METHODS: We used data from 83 patients with ICP in Switzerland and from 83 patients in Italy. We studied the impact of smoking on progression of disease as measured by the appearance of calcification and diabetes using Cox regression models.
RESULTS: In both centers, the prevalence of smoking was significantly higher in patients with ICP than in the background population. In Italian patients, smoking increased the risk of pancreatic calcifications (hazard ratio = 2.09; 95% confidence interval, 1.07-4.10). Smoking also shortened the time to appearance of calcification. Heavy smoking (>20 cigarettes per day) was associated with the appearance of diabetes (hazard ratio = 3.94; 95% confidence interval, 1.14-13.6). For those patients who never reported consuming alcohol, smoking remains a significant risk factor.
CONCLUSIONS: In nonalcoholic ICP, smoking is associated with disease progression as measured by the appearance of pancreatic calcification and, to a lower extent, of diabetes. These findings were chiefly observed in patients who were older than 35 years at the time of onset of disease.

PMID 16868482  Pancreas. 2006 Aug;33(2):163-8. doi: 10.1097/01.mpa.000・・・
著者: Angelo Andriulli, Edoardo Botteri, Piero L Almasio, Italo Vantini, Generoso Uomo, Patrick Maisonneuve, ad hoc Committee of the Italian Association for the Study of the Pancreas
雑誌名: Pancreas. 2010 Nov;39(8):1205-10. doi: 10.1097/MPA.0b013e3181df27c0.
Abstract/Text OBJECTIVES: To assess the evidence for tobacco smoking as a risk factor for the causation of chronic pancreatitis.
METHODS: We performed a meta-analysis with random-effects models to estimate pooled relative risks (RRs) of chronic pancreatitis for current, former, and ever smokers, in comparison to never smokers. We also performed dose-response, heterogeneity, publication bias, and sensitivity analyses.
RESULTS: Ten case-control studies and 2 cohort studies that evaluated, overall, 1705 patients with chronic pancreatitis satisfied the inclusion criteria. When contrasted to never smokers, the pooled risk estimates for current smokers was 2.8 (95% confidence interval [CI], 1.8-4.2) overall and 2.5 (95% CI, 1.3-4.6) when data were adjusted for alcohol consumption. A dose-response effect of tobacco use on the risk was ascertained: the RR for subjects smoking less than 1 pack per day was 2.4 (95% CI, 0.9-6.6) and increased to 3.3 (95% CI, 1.4-7.9) in those smoking 1 or more packs per day. The risk diminished significantly after smoking cessation, as the RR estimate for former smokers dropped to a value of 1.4 (95% CI, 1.1-1.9).
CONCLUSIONS: Tobacco smoking may enhance the risk of developing chronic pancreatitis. Recommendation for smoking cessation, besides alcohol abstinence, should be incorporated in the management of patients with chronic pancreatitis.

PMID 20622705  Pancreas. 2010 Nov;39(8):1205-10. doi: 10.1097/MPA.0b01・・・
著者: Morihisa Hirota, Tooru Shimosegawa, Atsushi Masamune, Kazuhiro Kikuta, Kiyoshi Kume, Shin Hamada, Atsushi Kanno, Kenji Kimura, Ichiro Tsuji, Shinichi Kuriyama, Research Committee of Intractable Pancreatic Diseases
雑誌名: Pancreatology. 2014 Nov-Dec;14(6):490-6. doi: 10.1016/j.pan.2014.08.008. Epub 2014 Sep 3.
Abstract/Text OBJECTIVES: A nationwide survey was conducted to clarify the epidemiological features of patients with chronic pancreatitis (CP) in Japan.
METHODS: In the first survey, both the prevalence and the incidence of CP in 2011 were estimated. In the second survey, the clinicoepidemiological features of the patients were clarified by mailed questionnaires. Patients were diagnosed by the Japanese diagnostic criteria for chronic pancreatitis 2009.
RESULTS: The estimated annual prevalence and incidence of CP in 2011 were 52.4/100,000 and 14.0/100,000, respectively. The sex ratio (male/female) of patients was 4.6, with a mean age of 62.3 years. Alcoholic (67.5%) was the most common and idiopathic (20.0%) was the second most common cause of CP. Comorbidity with diabetes mellitus (DM) and pancreatic calcifications (PC) occurred more frequent in ever smokers independently of their drinking status. Among patients without drinking habit, the incidences of DM and PC were significantly higher in ever smokers than in never smokers. The multiple logistic regression analysis revealed smoking was an independent factor of DM and PC in CP patients: DM, Odds ratio (OR) 1.644, 95% confidence interval (CI) 1.202 to 2.247 (P = 0.002): PC, OR 2.010, 95% CI 1.458 to 2.773 (P < 0.001). On the other hand, smoking was not identified as an independent factor for the appearance of abdominal pain by this analysis.
CONCLUSION: The prevalence of Japanese patients with CP has been increasing. Smoking was identified as an independent factor related to DM and PC in Japanese CP patients.

Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.
PMID 25224249  Pancreatology. 2014 Nov-Dec;14(6):490-6. doi: 10.1016/j・・・
著者: K Mergener, J Baillie
雑誌名: Lancet. 1997 Nov 8;350(9088):1379-85. doi: 10.1016/S0140-6736(97)07332-7.
Abstract/Text
PMID 9365465  Lancet. 1997 Nov 8;350(9088):1379-85. doi: 10.1016/S014・・・
著者: Morihisa Hirota, Tooru Shimosegawa, Atsushi Masamune, Kazuhiro Kikuta, Kiyoshi Kume, Shin Hamada, Yasuyuki Kihara, Akihiko Satoh, Kenji Kimura, Ichiro Tsuji, Shinichi Kuriyama, Research Committee of Intractable Pancreatic Diseases
雑誌名: Pancreatology. 2012 Mar-Apr;12(2):79-84. doi: 10.1016/j.pan.2012.02.005. Epub 2012 Feb 16.
Abstract/Text OBJECTIVES: A nationwide survey was conducted to clarify the epidemiological features of patients with chronic pancreatitis (CP) in Japan.
METHODS: Two sequential surveys were conducted. In the first survey, both the prevalence and incidence of CP in Japan in 2007 were estimated by a questionnaire, which was mailed to 3027 randomly chosen Japanese facilities. In the second survey, the second questionnaire was then mailed to 1110 facilities selected by the first survey to clarify the clinicoepidemiological features of the patients.
RESULTS: The estimated annual prevalence of CP was 36.9 per 100,000; 53.2 in males and 21.2 in females. The estimated annual incidence was 11.9 per 100,000. The prevalence and the incidence of CP gradually increased in Japan as compared to former surveys. The sex ratio (male/female) of definitive and probable CP patients was 4.5, with a mean age of 59.4 years; 59.2 years in males and 60.2 years in females. Alcoholic (69.7%) was most the common and idiopathic (21.0%) was the second most common cause of CP. The proportion of alcoholic CP increased as compared to the 55.5% found in 1994. The clinical features of overall Japanese patients with CP were: abdominal pain (60.6%), malabsorbtion (12.2%), diabetes mellitus (39.7%) and pancreatolithiasis (75.7%). Alcoholic patients were characterized by high morbidity as compared to nonalcoholic patients: abdominal pain (alcoholic 65.0% vs nonalcoholic 53.0%, p < 0.0001), diabetes mellitus (44.8% vs 31.4%, p < 0.0001) and pancreatolithiasis (84.0% vs 60.8%, p < 0.0001).
CONCLUSION: The prevalence and the incidence of CP, especially alcoholic CP, have been increasing in Japan.

Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.
PMID 22487515  Pancreatology. 2012 Mar-Apr;12(2):79-84. doi: 10.1016/j・・・
著者: A B Lowenfels, P Maisonneuve, G Cavallini, R W Ammann, P G Lankisch, J R Andersen, E P Dimagno, A Andrén-Sandberg, L Domellöf
雑誌名: N Engl J Med. 1993 May 20;328(20):1433-7. doi: 10.1056/NEJM199305203282001.
Abstract/Text BACKGROUND: The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases.
METHODS AND RESULTS: We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively.
CONCLUSIONS: The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis.

PMID 8479461  N Engl J Med. 1993 May 20;328(20):1433-7. doi: 10.1056/・・・
著者: Makoto Otsuki
雑誌名: J Gastroenterol. 2003;38(4):315-26. doi: 10.1007/s005350300058.
Abstract/Text Chronic pancreatitis is a chronic clinical disorder characterized by irreversible damage to the pancreas and the development of histologic evidence of inflammation and fibrosis, and eventually the destruction and permanent loss of exocrine and endocrine tissue. A nationwide survey in Japan revealed an increase in the total number of patients treated for chronic pancreatitis from 32 000 in 1994 to 42 000 in 1999. The overall prevalence and the incidence rate of chronic pancreatitis also increased, from 28.5 and 5.4, respectively, in 1994 to 32.91 and 5.77 per 100 000 population, respectively, in 1999. Diagnostic criteria for chronic pancreatitis in Japan were proposed by the Japan Pancreas Society in 1995 and revised in 2001. The criteria were established to rule out false-positive cases and to confidently diagnose definite and probable cases of chronic pancreatitis, and thus easily detect advanced chronic pancreatitis, but the criteria are unable to lead to the early diagnosis of chronic pancreatitis. Cancer is the major cause of death in patients with chronic pancreatitis in Japan (49.6% of all deaths in patients with chronic pancreatitis). Clarification of the mechanisms by which possible chronic pancreatitis progresses to probable or definite chronic pancreatitis, and to pancreatic cancer, is an important research goal. Because even chronic pancreatitis defined as irreversible appears to be reversible for some time in its clinical course, there is an urgent need to develop methods for diagnosing reversible chronic pancreatitis, and to prevent the transition from chronic pancreatitis to pancreatic cancer.

PMID 12743770  J Gastroenterol. 2003;38(4):315-26. doi: 10.1007/s00535・・・
著者: B Etemad, D C Whitcomb
雑誌名: Gastroenterology. 2001 Feb;120(3):682-707.
Abstract/Text The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.

PMID 11179244  Gastroenterology. 2001 Feb;120(3):682-707.
著者: Y Issa, M A Kempeneers, H C van Santvoort, T L Bollen, S Bipat, M A Boermeester
雑誌名: Eur Radiol. 2017 Sep;27(9):3820-3844. doi: 10.1007/s00330-016-4720-9. Epub 2017 Jan 27.
Abstract/Text OBJECTIVES: Obtain summary estimates of sensitivity and specificity for imaging modalities for chronic pancreatitis (CP) assessment.
METHODS: A systematic search was performed in Cochrane Library, MEDLINE, Embase and CINAHL databases for studies evaluating imaging modalities for the diagnosis of CP up to September 2016. A bivariate random-effects modeling was used to obtain summary estimates of sensitivity and specificity.
RESULTS: We included 43 studies evaluating 3460 patients. Sensitivity of endoscopic retrograde cholangiopancreatography (ERCP) (82%; 95%CI: 76%-87%) was significant higher than that of abdominal ultrasonography (US) (67%; 95%CI: 53%-78%; P=0.018). The sensitivity estimates of endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and computed tomography (CT) were 81% (95%CI: 70%-89%), 78% (95%CI: 69%-85%), and 75% (95%CI: 66%-83%), respectively, and did not differ significantly from each other. Estimates of specificity were comparable for EUS (90%; 95%CI: 82%-95%), ERCP (94%; 95%CI: 87%-98%), CT (91%; 95% CI: 81%-96%), MRI (96%; 95%CI: 90%-98%), and US (98%; 95%CI: 89%-100%).
CONCLUSIONS: EUS, ERCP, MRI and CT all have comparable high diagnostic accuracy in the initial diagnosis of CP. EUS and ERCP are outperformers and US has the lowest accuracy. The choice of imaging modality can therefore be made based on invasiveness, local availability, experience and costs.
KEY POINTS: • EUS, ERCP, MRI and CT have high diagnostic sensitivity for chronic pancreatitis • Diagnostic specificity is comparable for all imaging modalities • EUS and ERCP are outperformers and US has the lowest accuracy • The choice of imaging can be made based on clinical considerations.

PMID 28130609  Eur Radiol. 2017 Sep;27(9):3820-3844. doi: 10.1007/s003・・・
著者: Heiko Witt, Minoti V Apte, Volker Keim, Jeremy S Wilson
雑誌名: Gastroenterology. 2007 Apr;132(4):1557-73. doi: 10.1053/j.gastro.2007.03.001.
Abstract/Text Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential 'disease modifier' role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usually conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient's quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.

PMID 17466744  Gastroenterology. 2007 Apr;132(4):1557-73. doi: 10.1053・・・
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: Keisho Kataoka, Junichi Sakagami, Morihisa Hirota, Atsushi Masamune, Tooru Shimosegawa
雑誌名: Pancreas. 2014 Apr;43(3):451-7. doi: 10.1097/MPA.0000000000000038.
Abstract/Text OBJECTIVE: Most patients with chronic pancreatitis develop intractable abdominal pain and malnutrition. A low-fat diet is one of the options used to manage intractable abdominal pain and malnutrition. However, few reports have examined the pain-suppression effect. To investigate the effects of oral ingestion of a low-fat elemental diet composed of purified amino acids on pain and nutritional status in patients with chronic pancreatitis, a multicenter prospective study was conducted.
METHODS: Patients with chronic pancreatitis with symptoms of abdominal pain were enrolled. In addition to meals, patients ingested a low-fat elemental diet composed of purified amino acids for 12 weeks. Before and after treatment, patients were asked to indicate their pain grade using a 100-mm horizontal visual analog scale, and nutritional indices, including body mass index and blood levels of pancreatic enzymes, were measured.
RESULTS: A total of 596 patients were eligible for analysis. Marked pain reduction was observed with a significant decrease of the mean visual analog scale score by 32.9 mm from 52.9 mm after 12 weeks (P < 0.001). There were also significant improvements in nutritional indices.
CONCLUSIONS: An oral low-fat elemental diet composed of purified amino acids, which requires no special treatment procedures, may improve patients' quality of life.

PMID 24622078  Pancreas. 2014 Apr;43(3):451-7. doi: 10.1097/MPA.000000・・・
著者: J E Clain, R K Pearson
雑誌名: Surg Clin North Am. 1999 Aug;79(4):829-45.
Abstract/Text The question that serves as this article's title is rhetorical. Clinicians have diagnosed and managed chronic pancreatitis without a gold standard for decades and must continue to do so in the foreseeable future. Although clinicians have a much wider array of diagnostic tools available for the diagnosis of chronic pancreatitis, a single readily applied gold standard remains elusive. Diagnostic studies are rarely compared with a true gold standard--histopathology. Furthermore, even if a safe biopsy technique were available, it might fall short of a gold standard, given the patchy nature of early-stage chronic pancreatitis. Indeed, different stages of chronic pancreatitis require not only recognition of the different clinical presentations but also different levels of intensity of diagnostic testing to establish the diagnosis confidently. The diagnosis in most patients with chronic pancreatitis can be made confidently with a good clinical history and a limited number of currently available structural and functional tests. No single diagnostic study, functional or structural, suffices for all patients. It is also axiomatic that patients with intractable abdominal pain in whom early-stage chronic pancreatitis is suspected represent a challenge for clinicians partly because of this lack of a single, dependable gold standard. Perhaps we have reached the point at which further refinements of current tests of structure or function are not beneficial because increased sensitivity is countered by loss of specificity. We suggest that a new approach to developing a gold standard for the diagnosis of chronic pancreatitis is necessary. With advances in the understanding of the mediators of the inflammatory process, it may be possible to devise a test to assess the earliest events in this disease.

PMID 10470330  Surg Clin North Am. 1999 Aug;79(4):829-45.
著者: Marc F Catalano, Anand Sahai, Michael Levy, Joseph Romagnuolo, Maurits Wiersema, William Brugge, Martin Freeman, Kenji Yamao, Marcia Canto, Lyndon V Hernandez
雑誌名: Gastrointest Endosc. 2009 Jun;69(7):1251-61. doi: 10.1016/j.gie.2008.07.043. Epub 2009 Feb 24.
Abstract/Text BACKGROUND: EUS is increasingly used in the diagnosis of chronic pancreatitis (CP). A number of publications in this field have used different EUS terminology, features, and criteria for CP, making it difficult to reproduce their findings and apply them in clinical practice. Moreover, traditional criteria such as the Cambridge classification for CP are arguably outdated and have lost their relevance.
OBJECTIVE: Our purpose was to establish consensus-based criteria for EUS features of CP.
DESIGN: Consensus study.
MAIN OUTCOME MEASUREMENTS: Thirty-two internationally recognized endosonographers anonymously voted on terminology of EUS features, rank order, and category (major vs minor criteria). Consensus was defined as greater than two thirds agreement among participants.
RESULTS: Major criteria for CP were (1) hyperechoic foci with shadowing and main pancreatic duct (PD) calculi and (2) lobularity with honeycombing. Minor criteria for CP were cysts, dilated ducts > or =3.5 mm, irregular PD contour, dilated side branches > or =1 mm, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules.
LIMITATION: Lack of broadly accepted reference standard.
CONCLUSION: In a complex disease such as CP that has no universally accepted reference standard, an EUS-based criterion for diagnosis can be determined by expert consensus opinion and the existing body of evidence. Here we present the new "Rosemont criteria" for the EUS diagnosis of CP.

PMID 19243769  Gastrointest Endosc. 2009 Jun;69(7):1251-61. doi: 10.10・・・
著者: Morihisa Hirota, Tooru Asakura, Atsushi Kanno, Tooru Shimosegawa
雑誌名: J Hepatobiliary Pancreat Sci. 2010 Nov;17(6):770-5. doi: 10.1007/s00534-009-0182-7. Epub 2009 Oct 14.
Abstract/Text Endoscopic treatment associated with or without extracorporeal shock wave lithotripsy (ESWL) for chronic pancreatitis has been employed for about 20 years. Although two randomized control trials have revealed the greater effectiveness of surgery as compared to endoscopic treatment for chronic pancreatitis, a considerable number of patients have successfully obtained complete and long-term relief from pain by the less invasive endoscopic treatment. In this review, we discuss the indications, techniques and results of endoscopic treatment and ESWL for painful chronic pancreatitis. We also discuss the characteristic clinical features that are predictive of a good response to endoscopic treatment and ESWL.

PMID 19826752  J Hepatobiliary Pancreat Sci. 2010 Nov;17(6):770-5. doi・・・
著者: A Maydeo, N Soehendra, N Reddy, S Bhandari
雑誌名: Endoscopy. 2007 Jul;39(7):653-8. doi: 10.1055/s-2007-966447. Epub 2007 May 21.
Abstract/Text Endotherapy for pancreatic stone is an emerging specialty. The judicious application of extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) in selected groups of patients has increased the success rates of endotherapy, with excellent long-term results. In this review the authors share their vast experience of treating patients with pancreatic stones. The article will focus on the basic principles of pancreatic endotherapy, the instrumentation required, details of the ESWL technique and its applications, as well as the limitations, success rate, and complications of endotherapy in selected patients.

PMID 17516288  Endoscopy. 2007 Jul;39(7):653-8. doi: 10.1055/s-2007-96・・・
著者: Jean-Marc Dumonceau, Myriam Delhaye, Andrea Tringali, Marianna Arvanitakis, Andres Sanchez-Yague, Thierry Vaysse, Guruprasad P Aithal, Andrea Anderloni, Marco Bruno, Paolo Cantú, Jacques Devière, Juan Enrique Domínguez-Muñoz, Selma Lekkerkerker, Jan-Werner Poley, Mohan Ramchandani, Nageshwar Reddy, Jeanin E van Hooft
雑誌名: Endoscopy. 2019 Feb;51(2):179-193. doi: 10.1055/a-0822-0832. Epub 2019 Jan 17.
Abstract/Text ESGE suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team and surgical options should be considered.Weak recommendation, low quality evidence.ESGE suggests, for the selection of patients for initial or continued endoscopic therapy and/or ESWL, taking into consideration predictive factors associated with a good long-term outcome. These include, at initial work-up, absence of MPD stricture, a short disease duration, non-severe pain, absence or cessation of cigarette smoking and of alcohol intake, and, after initial treatment, complete removal of obstructive pancreatic stones and resolution of pancreatic duct stricture with stenting.Weak recommendation, low quality evidence.ESGE recommends ESWL for the clearance of radiopaque obstructive MPD stones larger than 5 mm located in the head/body of the pancreas and endoscopic retrograde cholangiopancreatography (ERCP) for MPD stones that are radiolucent or smaller than 5 mm. Strong recommendation, moderate quality evidence.ESGE suggests restricting the use of endoscopic therapy after ESWL to patients with no spontaneous clearance of pancreatic stones after adequate fragmentation by ESWL.Weak recommendation, moderate quality evidence.ESGE suggests treating painful dominant MPD strictures with a single 10-Fr plastic stent for one uninterrupted year if symptoms improve after initial successful MPD drainage. The stent should be exchanged if necessary, based on symptoms or signs of stent dysfunction at regular pancreas imaging at least every 6 months. ESGE suggests consideration of surgery or multiple side-by-side plastic stents for symptomatic MPD strictures persisting beyond 1 year after the initial single plastic stenting, following multidisciplinary discussion. Weak recommendation, low quality evidence.ESGE recommends endoscopic drainage over percutaneous or surgical treatment for uncomplicated chronic pancreatitis (CP)-related pseudocysts that are within endoscopic reach.Strong recommendation, moderate quality evidence.ESGE recommends retrieval of transmural plastic stents at least 6 weeks after pancreatic pseudocyst regression if MPD disruption has been excluded, and long-term indwelling of transmural double-pigtail plastic stents in patients with disconnected pancreatic duct syndrome.Strong recommendation, low quality evidence.ESGE suggests the temporary insertion of multiple side-by-side plastic stents or of a fully covered self-expandable metal stent (FCSEMS) for treating CP-related benign biliary strictures.Weak recommendation, moderate quality evidence.ESGE recommends maintaining a registry of patients with biliary stents and recalling them for stent removal or exchange.Strong recommendation, low quality evidence.

© Georg Thieme Verlag KG Stuttgart · New York.
PMID 30654394  Endoscopy. 2019 Feb;51(2):179-193. doi: 10.1055/a-0822-・・・
著者: Masayuki Kitano, Thomas M Gress, Pramod K Garg, Takao Itoi, Atsushi Irisawa, Hiroyuki Isayama, Atsushi Kanno, Kei Takase, Michael Levy, Ichiro Yasuda, Phillipe Lévy, Shuiji Isaji, Carlos Fernandez-Del Castillo, Asbjørn M Drewes, Andrea R G Sheel, John P Neoptolemos, Tooru Shimosegawa, Marja Boermeester, C Mel Wilcox, David C Whitcomb
雑誌名: Pancreatology. 2020 Sep;20(6):1045-1055. doi: 10.1016/j.pan.2020.05.022. Epub 2020 Jul 10.
Abstract/Text BACKGROUND/OBJECTIVES: This paper is part of the international consensus guidelines on chronic pancreatitis, presenting for interventional endoscopy.
METHODS: An international working group with experts on interventional endoscopy evaluated 26 statements generated from evidence on 9 clinically relevant questions. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to evaluate the level of evidence. To determine the level of agreement, a nine-point Likert scale was used for voting on the statements.
RESULTS: Strong consensus was obtained for 15 statements relating to nine questions including the recommendation that endoscopic intervention should be offered to patients with persistent severe pain but not to those without pain. Endoscopic decompression of the pancreatic duct could be used for immediate pain relief, and then offered surgery if this fails or needs repeated endoscopy. Endoscopic drainage is preferred for portal-splenic vein thrombosis and pancreatic fistula. A plastic stent should be placed and replaced 2-3 months later after insertion. Endoscopic extraction is indicated for stone fragments remaining after ESWL. Interventional treatment should be performed for symptomatic/complicated pancreatic pseudocysts. Endoscopic treatment is recommended for bile duct obstruction and afterwards surgery if this fails or needs repeated endoscopy. Surgery may be offered if there is significant calcification and/or mass of the pancreatic head. Percutaneous endovascular treatment is preferred for hemosuccus pancreaticus. Surgical treatment is recommended for duodenal stenosis due to chronic pancreatitis.
CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning indications and key aspects for interventional endoscopy in the management of patients with chronic pancreatitis.

Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.
PMID 32792253  Pancreatology. 2020 Sep;20(6):1045-1055. doi: 10.1016/j・・・
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: Djuna L Cahen, Dirk J Gouma, Philippe Laramée, Yung Nio, Erik A J Rauws, Marja A Boermeester, Olivier R Busch, Paul Fockens, Ernst J Kuipers, Stephen P Pereira, David Wonderling, Marcel G W Dijkgraaf, Marco J Bruno
雑誌名: Gastroenterology. 2011 Nov;141(5):1690-5. doi: 10.1053/j.gastro.2011.07.049. Epub 2011 Aug 16.
Abstract/Text BACKGROUND & AIMS: A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years.
METHODS: Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle.
RESULTS: During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable.
CONCLUSIONS: In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 21843494  Gastroenterology. 2011 Nov;141(5):1690-5. doi: 10.1053/・・・
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: Morihisa Hirota, Tohru Asakura, Atsushi Kanno, Kazuhiro Kikuta, Kiyoshi Kume, Shin Hamada, Jun Unno, Hiromichi Ito, Hiroyuki Ariga, Atsushi Masamune, Kennichi Satoh, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Tooru Shimosegawa
雑誌名: Pancreas. 2011 Aug;40(6):946-50. doi: 10.1097/MPA.0b013e31821a9215.
Abstract/Text OBJECTIVES: The aim of this study was to compare the benefits between endoscopic drainage and surgical drainage of the pancreatic duct for patients with chronic calcified pancreatitis.
METHODS: A total of 68 patients were classified into endoscopic (n = 34) or surgical (n = 34) treatment groups. Patients receiving endoscopic treatment were further divided into 2 subgroups: a short-period group, patients who could discontinue serial pancreatic stenting within 1 year (n = 19); and a long-period group, patients who needed pancreatic drainage by serial endoscopic stenting for more than 1 year (n = 15). The medical records of these patients were retrospectively analyzed.
RESULTS: Hospital stays, frequency of hospitalizations, and medical expense were similar between the short-period endoscopic treatment group and surgery group. On the other hand, patients in the long-period endoscopic treatment group required significantly longer hospital stays, more frequent hospitalizations, and had higher medical expenses than the short-period endoscopic treatment group as well as than the surgery group.
CONCLUSIONS: Patients who underwent serial endoscopic stenting for more than 1 year showed no benefit compared with surgical treatment in terms of the frequency of hospital stays and medical costs.

PMID 21747315  Pancreas. 2011 Aug;40(6):946-50. doi: 10.1097/MPA.0b013・・・
著者: Usama Ahmed Ali, Vincent B Nieuwenhuijs, Casper H van Eijck, Hein G Gooszen, Ronald M van Dam, Olivier R Busch, Marcel G W Dijkgraaf, Femke A Mauritz, Sjoerd Jens, Jay Mast, Harry van Goor, Marja A Boermeester, Dutch Pancreatitis Study Group
雑誌名: Arch Surg. 2012 Oct;147(10):925-32. doi: 10.1001/archsurg.2012.1094.
Abstract/Text OBJECTIVE: To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP).
DESIGN: Cohort study with long-term follow-up.
SETTING: Five specialized academic centers.
PATIENTS: Patients with CP treated surgically for pain.
INTERVENTIONS: Pancreatic resection and drainage procedures for pain relief.
MAIN OUTCOME MEASURES: Pain relief (pain visual analogue score ≤4), pancreatic function, and quality of life.
RESULTS: We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors.
CONCLUSIONS: The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.

PMID 23117832  Arch Surg. 2012 Oct;147(10):925-32. doi: 10.1001/archsu・・・
著者: M A Kempeneers, Y Issa, U Ahmed Ali, R D Baron, M G Besselink, M Büchler, M Erkan, C Fernandez-Del Castillo, S Isaji, J Izbicki, J Kleeff, J Laukkarinen, A R G Sheel, T Shimosegawa, D C Whitcomb, J Windsor, Y Miao, J Neoptolemos, M A Boermeester, Working group for the International (IAP – APA – JPS – EPC) Consensus Guidelines for Chronic Pancreatitis
雑誌名: Pancreatology. 2020 Mar;20(2):149-157. doi: 10.1016/j.pan.2019.12.005. Epub 2019 Dec 17.
Abstract/Text BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP.
METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient.
RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients.
CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.
PMID 31870802  Pancreatology. 2020 Mar;20(2):149-157. doi: 10.1016/j.p・・・
著者: Yama Issa, Marinus A Kempeneers, Marco J Bruno, Paul Fockens, Jan-Werner Poley, Usama Ahmed Ali, Thomas L Bollen, Olivier R Busch, Cees H Dejong, Peter van Duijvendijk, Hendrik M van Dullemen, Casper H van Eijck, Harry van Goor, Muhammed Hadithi, Jan-Willem Haveman, Yolande Keulemans, Vincent B Nieuwenhuijs, Alexander C Poen, Erik A Rauws, Adriaan C Tan, Willem Thijs, Robin Timmer, Ben J Witteman, Marc G Besselink, Jeanin E van Hooft, Hjalmar C van Santvoort, Marcel G Dijkgraaf, Marja A Boermeester, Dutch Pancreatitis Study Group
雑誌名: JAMA. 2020 Jan 21;323(3):237-247. doi: 10.1001/jama.2019.20967.
Abstract/Text Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function.
Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.
Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018.
Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed.
Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality.
Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach.
Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings.
Trial Registration: ISRCTN Identifier: ISRCTN45877994.

PMID 31961419  JAMA. 2020 Jan 21;323(3):237-247. doi: 10.1001/jama.201・・・
著者: Matthew J DiMagno, Eugene P Dimagno
雑誌名: Curr Opin Gastroenterol. 2006 Sep;22(5):487-97. doi: 10.1097/01.mog.0000239862.96833.89.
Abstract/Text PURPOSE OF REVIEW: As in our previous reviews, we endeavor to review important new observations in chronic pancreatitis made in the past year. Topics recently reviewed were truncated to accommodate a surge in publications on clinical aspects of chronic pancreatitis, which contained new observations or insights into new or old concepts.
RECENT FINDINGS: Cystic fibrosis carriers have been found to be at increased risk of pancreatitis. Autoimmune pancreatitis may belong to a multiorgan immunoglobulin G4-related autoimmune disease, and the natural history of chronic pancreatitis differs among the etiologies. Diffusion-weighted magnetic resonance imaging improves upon previous methodologies for diagnosing reduced pancreatic exocrine secretion, and fecal elastase-1 has been found to be a poor test for diagnosing pancreatic malabsorption. Visceral hyperalgesia or heightened central pain perception may contribute to pain in chronic pancreatitis. Instruments are evolving to assess quality of life in chronic pancreatitis, and fibrolytic agents have been found to have therapeutic promise.
SUMMARY: Researchers this past year have further characterized genetic, molecular and clinical aspects of chronic pancreatitis. Advancing the understanding of fibrogenesis, mechanisms of exocrine insufficiency, calcification, and pain and continuing development/modification of diagnostic tests should lead to improved prevention, detection and treatment of the condition. More accurate quantification of outcomes is critical for translating potential therapies from bench to bedside.

PMID 16891879  Curr Opin Gastroenterol. 2006 Sep;22(5):487-97. doi: 10・・・
著者: Tetsuya Ito, Shigeyuki Kawa, Akihiro Matsumoto, Kensuke Kubota, Terumi Kamisawa, Kazuichi Okazaki, Kenji Hirano, Yoshiki Hirooka, Kazushige Uchida, Atsuhiro Masuda, Hirotaka Ohara, Kyoko Shimizu, Norikazu Arakura, Atsushi Masamune, Atsushi Kanno, Junichi Sakagami, Takao Itoi, Tetsuhide Ito, Toshiharu Ueki, Takayoshi Nishino, Kazuo Inui, Nobumasa Mizuno, Hitoshi Yoshida, Masanori Sugiyama, Eisuke Iwasaki, Atsushi Irisawa, Tooru Shimosegawa, Tsutomu Chiba
雑誌名: Pancreas. 2019 Jan;48(1):49-54. doi: 10.1097/MPA.0000000000001210.
Abstract/Text OBJECTIVE: Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP.
METHODS: Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation.
RESULTS: Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones.
CONCLUSIONS: The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.

PMID 30540679  Pancreas. 2019 Jan;48(1):49-54. doi: 10.1097/MPA.000000・・・

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