Several pancreatic ductal variants have been reported. Though some of them have been suggested to be associated with pancreatitis, most of them were controversial probably due to biased sample populations based on endoscopic studies and the rarity of the variants. In the present study series, we aimed to elucidate the relevance of pancreatic ductal anatomical variation, especially of pancreas divisum, meandering main pancreatic duct, and Santorinicele without pancreas divisum, to the onset of pancreatitis based on less-biased population using non-invasive magnetic resonance cholangiopancreatography (MRCP). Thus our paper consists of three main studies: (1) pancreas divisum (PD) as a predisposing factor for idiopathic chronic and recurrent acute pancreatitis; (2) meandering main pancreatic duct (MMPD) as a relevant factor for idiopathic recurrent acute pancreatitis; (3) Santorinicele without pancreas divisum (SWOP) might be relevant to a history of pancreatitis.

First, we investigated the relation of PD and idiopathic pancreatitis. We enrolled 504 subjects from the community and 46 patients with idiopathic pancreatitis (8 acute, 23 chronic, and 15 recurrent acute types of onset). All subjects underwent MR scanning to detect the presence or absence of PD (classified into classical PD, PD with absent ventral duct, and incomplete PD) and medical examination. The rate of PD was found significantly higher for all idiopathic/idiopathic chronic/idiopathic recurrent acute pancreatitis (33 - 43%) than in the community group (2.6%), but was not higher for idiopathic acute pancreatitis (13%). All the three PD subtypes (classical PD, PD with absent ventral duct, and incomplete PD) were indicated to induce idiopathic pancreatitis. We concluded that PD should be considered a predisposing factor for chronic and recurrent acute pancreatitis when no other established cause of pancreatitis was found.

Second, we investigated the relation of MMPD and idiopathic pancreatitis. We enrolled 504 subjects from the community and 30 patients with idiopathic pancreatitis (7 acute, 13 chronic, and 10 recurrent acute types of onset). All subjects underwent MR scanning to detect the presence or absence of MMPD (classified into loop type and reversed-Z type) and medical examination. The rate of MMPD was 40% in the patient with idiopathic recurrent acute pancreatitis (RAP), which was much higher than that in the community (2.2%). Statistical analyses revealed MMPD (odds ratio, 29.0) and its loop/reverse-Z subtypes (odds ratio 20.2/24.2) to be a relevant factor to the onset of RAP. We concluded that MMPD should be considered a predisposing factor for RAP when no other established cause of pancreatitis was found.

Third, we investigated the gross rate of SWOP and its clinical and radiographic features. We enrolled 2905 subjects from the community and 2035 patients in our hospital who underwent abdominal MRCP studies. As result, Nine SWOP was found only from patient group and ten out of 12 cases aged 65 and over. Seven out of 12 cases were associated with pancreatitis including the two younger cases. We concluded that SWOP to be an rare variant and probably associated with aging and a history of pancreatitis.

In summary, we showed a new and strong evidence of pancreas divisum being a predisposing factor for idiopathic chronic pancreatitis or idiopathic recurrent acute pancreatitis and that of meandering main pancreatic duct (MMPD) being a relevant factor for idiopathic recurrent acute pancreatitis. We also showed a new but relatively weak evidence of SWOP being associated with pancreatitis.

本研究は、複数の膵管の破格について、その臨床的意義(頻度や背景因子など)、特に膵炎発症への影響の有無を明らかにするため、一般人口を代表する健診群と、大学病院の患者群を、非侵襲的に膵胆管を描出する核磁気共鳴画像法を用いて比較した横断的研究であり、下記の成果を得ている。

1.膵管癒合不全

膵管癒合不全の一般人口における頻度を、生体下に初めて調べ、2.6%との結果を得た。特発性膵炎群における膵管癒合不全の頻度は、33-43%と極めて高値であった。膵炎発症のリスク因子分析においては、膵管癒合不全の有無のみが有意となり、オッズ比は23.4倍であった。過去35年間の膵管癒合不全と膵炎の関係を裏付ける報告の中で、本報告は最もエビデンスレベルの高い報告となった。

2.蛇行主膵管

蛇行主膵管という概念を定義し、ループ型と逆Z型の2亜型を定めた。この一般人口下における頻度を、生体下に初めて調べ、2.2%(ループ型1.2%、逆Z型1.0%)との結果を得た。膵管癒合不全を除く特発性膵炎群における蛇行主膵管の頻度は、20%と高値であり、特に特発性再発性急性膵炎における蛇行主膵管の頻度は、40%と極めて高値であった。再発性急性膵炎発症のリスク因子分析においては、蛇行主膵管の有無のみが有意となり、オッズ比は26.2倍であった。ループ型も逆Z型も同様の傾向を示した。本報告は、初めての蛇行主膵管の臨床的意義を取り上げた報告であり、膵管癒合不全についで、新しい症候群の存在を示唆するものである。

3.膵管癒合不全を伴わないSantorinicele

過去に3例しか報告がない「膵管癒合不全を伴わないSantorinicele」について、初めて臨床的意義を観察した研究である。一般人口下の頻度は、0.00―0.10%の間と計算され、患者群でも0.34%と低値であった。多くの患者が、膵炎の既往を有し、比較的高齢であった。これまで先天奇形と想像されてきたが、膵炎に伴う後天的変化である可能性も示唆された。

以上、本論文は、膵管癒合不全と特発性膵炎の強い関係、蛇行主膵管と特発性膵炎、特に特発性再発性急性膵炎の強い関係、膵管癒合不全を伴わないSantoriniceleと膵炎の既往の関係を明らかにした。いずれの研究成果もこれまで結論が不定であったり、未知であったものであり、今後消化器分野の臨床に大きな影響を及ぼすと考えられる。上記理由により、本論文は、学位の授与に値するものと考えられる。