Tropical calcific pancreatitis.........An overview

Tropical calcific pancreatitis is a nonalcoholic type of chronic pancreatitis affecting the childrens and young adults characterized clinically by recurrent abdominal pain in childhood, diabetes in adolescent and death in early childhood. Although the exact etiology is not known, malnutrition and chronic cassava toxicity either singly or in combination are presumed to be the prime factor in pancreatic injury unopposed by detoxification of free radical. Moreover micronutrients deficiency, oxidant stress and antioxidant deficiency might play substantial role. Diabetes secondary to tropical calcific pancreatitis is a distinctive and frequent problem, being named by W.H.O. study group as 'fibrocalculous pancreatic diabetes (FCPD) and classified as one of the variant of the so-called malnutrition related diabetes mellitus (MRDM).熱帯地方の貧困層の小児や若干成人にみられる非アルコール性の慢性膵炎で,小児期に反復する腹痛で発症し,10～20歳で膵性糖尿病になり,20～ 30歳で死亡する類似の病像を示す症例をTropical calcific pancreatitis(熱帯性石灰化慢性膵炎)という｡高率に膵石を伴う｡成因は乳幼児期からの熱量,蛋白貰,micronutrients(亜鉛,銅,セレニウム)の摂取不足に加えて食事中シアン産生物質や環境中oxidantsなど複合因子によると推測されている｡病理像は世界各国にみられる慢性膵炎典型例に類似する｡最近は,生活環境や医療事情の改善により,全身栄養障害の減少や生存期間 の延長など病像が変貌しっつある｡糖尿病を重視する立場からはFibrocalculous pancreatic diabetesと呼ばれ,同一地域にみられるProtein-deficient pancreatic diabetesと合わせてMalnutrition-related diabetes mellitus(MRDM)と総称し,糖尿病の一亜型に分類されている

Alcohol-induced pancreatitis

膵炎のうちもっとも頻度が高いアルコール性膵炎（AIP）の疫学，臨床像および発生機序に関する従来の知見を総括した。AIPの大多数は慢性膵炎である。通常は長期にわたる多量の飲酒を背景に発症するが，遺伝的素因および食事因子も重要な役割を演じる。発症初期には血中膵酵素の上昇をともなう腹痛が病像を支配するが，進展すると膵外分泌不全による消化吸収障害と膵内分泌不全による糖尿病が病像を支配するようになる。アルコール性慢性膵炎は非アルコール性慢性膵炎にくらべて確診時にすでに進展した症例が多く，合併症が多く，進行が早く，予後が悪い。死亡の主たる原因は癌の併発と糖尿病の合併症で，膵炎の急性増悪発作がこれにつぐ。併発する癌のなかでは膵癌よりもむしろ上部気道および上部消化管の癌が多い。発生機序としてはDuctal－Plug説とToxic－Metabolic説が有力であるが，最近は細 胞内膵酵素活性化説とFree　Radical説も注目をあびている。This paper is to review the literature on the epidemiology, clinical pictures and etiopathogenesis of alcohol-induced pancreatitis (AIP). The incidence of AIP has been increasing worldwide, paralleling the increase in alcohol consumption. AIP manifests itself following a longterm consumption of large amounts of alcohol. There is no known threshold value of alcohol consumption in terms of the risk of developing AIP, although the logarithm of the risk of developing AIP is lineally correlated with the amount of alcohol intake. Why some alcoholics develop pancreatitis whereas others with equal consumption of ethanol are spared remains to be explained. Therefore, two additional factors are considered to play important roles in developing AIP : genetic predisposition and diet. The majority of AIP IS chronic pancreatitis (AICP), although a minority can be acute pancreatitis (AIAP). AIAP shows somewhat higher morbidity and mortality than the common variety of acute pancreatitis. If recovered from an attack, AIAP shows morphological and functional restoration. AICP manifests itself with an acute attack of abdominal pain, insidious onset of abdominal pam, or a pain-free variety. An acute attack in AICP resemble that m AIAP ; often these two can be differentiated only by follow-up studies. AICP shows no morphological and functional restoration, and often shows progressive deterioration. Abdominal pain with elevated serum pancreatic enzymes is a predominant clinical picture m the early stage of AICP, whereas in the late stage symptoms and signs deriving from exocrine insufficiency (maldigestion) and endocrine insufficiency (pancreatic diabetes) begin to dominate the clinical pictures. AICP is in the more advanced stage and shows more complications than nonalcoholic chronic pancreatitis at the time of diagnosis. In addition, AICP shows more rapid progress and higher morbidity and mortality. The incidence of microangiopathy in pancreatic diabetes resemble that in primary diabetes, being higher in patients with a longer history of diabetes, those on insulin treatment and those under poorer control. Main causes of death are development of cancer in the upper respiratory and gastrointestinal tract and diabetic complications (hypoglycemic shock, renal failure, and intractable pneumonia), and acute attack of pancreatitis leads to death less frequently. Ductal-Plug theory and classical Toxic-Metabolic theory are most popular to explain the pathogenesis of AIP ; however, increasing evidence has been reported that oxygen free radicals and intracellular activation of zymogens by lysosomal enzymes may be involved in the pathogenesis

Clinical study on polypoid lesions of the colon

1986年4月から1990年2月末までの間に岡山大学医学部附属病院三朝分院で経験した早期大腸癌を含む大腸ポリープ90例（107病変）を対象に，年齢，臨床症状，便潜血反応，病変存在部位について検討を行い，以下の成績を得た。(1)大腸検査総数の22.4％にポリープが発見された。ポリープの77％は腺腫，5％は腺癌（早期癌）であった。(2)便潜血反応はポリープ例の75.9％に陽性であり，右側大腸ポリープでの陽性率は高かったが，S状結腸および直腸ポリープでは70％程度であった。(3)若年者では右側結腸にポリープが発見されることは稀であるが，50才以上では18％程度に認められた。高齢者では右側結腸も内視鏡で検査することが重要である。(4)免疫学的便潜血検査法の導入により大腸ポリープの発見効率が改善するものと考え られた。This report is concerned with clinical study on 90 patients with polypoid lesions (107 lesions) which we have encountered in Misasa Hospital, Okayama University in the past 4 years. Following results were obtained : (1) Polypoid lesions were detected in 90 (22.4%) and advanced adenocarcinoma (mostly resectable) in 22 (5.5%) of 402 patients who were examined by sigmoidoscopy and barium enema ; (2) Histological examination of the polypoid lesions showed adenoma in 77.2%, hyperplastic polyp in 8.7%, inflammatory polyp in 7.6%, neurinoma in 0.3% and early cancer (adenocarcinoma) in 5.4% ; (3) It was impossible to differentiate benign and malignant polypoid lesions on the basis of endoscopic and X-ray findings alone ; (4) Forty-two percent of the polypoid lesions was detected in the sigmoid colon, 30% in the rectum, 16.8% in the descending colon, 9.3% in the ascending colon, 0.9% in the caecum ; (4) Patients younger than 50 years of age showed only one polypoid lesion in the right hemicolon, whereas elder patients showed as many as 17 polypoid lesions ; (5) Among the 90 patients with polypoid lesions, 40 presented with abdominal pain, 20 with no symptoms (annual health check-up), 17 with irregular bowel habits, and 10 with melena ; (6) Among the 90 patients, occult blood in stool was positive in 75.8% with a lower positive rate in the lesions of the sigmoid and rectum ; (7) Among 5 asymptomatic patients with lesions and with a negative hemoccult test, 3 patients with a polypoid lesion were examined because of the patients' request, 1 patient with a polypoid lesion because of a positive family history, and the remaining 1 patient in a search for the primary lesion of the metastatic liver cancer ; (8) Among patients with a positive hemoccult test, the detection rate of polypoid lesions was 41.9% with use of an immunological method, whereas it was 19.7% with use of a chemical method. In conclusion, (1) detection of colonic polypoid lesions can lead to the detection of early cancer, although only histological examination can confirm the accurate diagnosis ; (2) a hemoccult test in stool with an immunological method is an effective method for screening asymptomatic colonic polypoid lesions, although it must be admitted that negative results may occasionally occur ; (3) macroscopic observation of the stool mass is important before sampling, because lesions of the sigmoid colon or the rectum may show scanty blood only on the limited area of the surface of the stool ; (4) patients elder than 50 years of age should be examined more carefully for the whole colon preferably with an endoscope, because they show a high incidence of small polypoid lesions in the right hemicolon

Re-evaluation of spa-drink therapy for digestive diseases

従来飲泉などの温泉治療は経験的知識にもとづいて行われる部分が多かったが，今後は科学的検査法を用いて有用性，適応疾患，適応病態，などを決定する必要がある。筆者らは，最近紹介された簡便な消化器検査法を用いて消化器疾患に対する飲泉療法の適応を再吟味しているので，これまでに得られた成績を中心に概説した。すなわち，(1)飲泉は1回でも連日の飲用でも，胃粘膜血流を改善する作用がある。(2)胃排出機能に対しては調整的効果を有する。(3)連日の飲泉は膵外分泌機能を改善する。したがって慢性の胃，膵疾患において粘膜血流障害，胃運動機能異常あるいは膵外分泌機能低下に起因する病気・病態に対しては積極的に飲泉療法を試みるべきである。温泉水の温度は40℃前後，飲泉の量は150～200ml，タイミングは食間空腹時がよい。With the advent of new instruments for examining the digestive organs, we have attempted to re-evaluate the efficacy and indications of spa-drink therapy for digestive diseases. This report deals with an overview of the results we have obtained so far. Effect of oral intake of thermal water (Misasa thermal water, 38-42℃, 150-200 ml) on gastric mucosal blood flow was evaluated, using an endoscopic organ reflex spectrophotometry together along with an Olympus XQ - 10 forward viewing gastrofiberscope. Single intake of thermal water as well as long-term spa-drink therapy (two times a day between meals for more than two weeks) brought about an improvement of gastric mucosal blood flow. Gastric emptying function was evaluated with an acetaminophen method. Single intake of thermal water brought about disordered gastric emptying (excessively accelerated or suppressed). However, long-term spa-drink therapy brought about an improvement (normalization) of gastric emptying function. Exocrine pancreatic function was evaluated with a synthetic peptide, N-BT-PABA, and also by measuring fecal chymotrypsin actIvIty. Longterm spa-drink therapy brought about an improvement of exocrine pancreatic function. Motility of the gall-bladder was evaluated by abdominal ultra-sonography. Long-term spa-drink therapy gave no effect on the motility of the gallbladder. In conclusion, our recent study indicate that : (1) single oral intake of thermal water as well as longterm spa-drink therapy is effective for gastric diseases related to decreased gastric mucosal blood flow (treatment of intractable peptic ulcer and chronic gastritis, and prevention of recurrence of peptic ulcer) ; (2) long-term spa-drink therapy is effective for dyspepsia syndrome; (3) long-term spa-drink therapy is effective as a supplemental method in the treatment of exocrine pancreatic dysfunction (chronic pancreatitis) ; (4) thermal water should be taken between meals

Trial of a mass screening survery for detecting early pancreatic cancer

早期膵癌を発見するためのスクリーニング法を確立するため，1986年6月1日から1990年6月30日までの期間のprospective studyを行った。対象は，人間ドックを目的として来院した患者を主とする三朝分院の外来患者1,748名である。一次スクリーニング検査として，血清アミラーゼ，エラスターゼI，腹部超音波検査（US）を施行し155名の要精検者が得られ，要精検率は8.9％であった。155名の要精検者に，二次検査として，USの再精査，ERCP，腹部CTを施行した。その結果，早期膵癌患者1名，進行膵癌患者4名を発見し，膵癌発見率は0．29％と良好な成績であった。加えて，一次スクリーニングの検査項目を限定することによりcost－benifitを改善することができた。発見された膵癌患者の3名は60歳代であった。また，年代別要精検率は加齢とともに上昇した。1年以後にfollow-up検査を受けた患者の数は641名でfoilow－up率は36．7％であり，そのなかから膵癌は発見されなかった。60歳代のfollow－up率は40歳以上60歳未満のそれにくらべて有意の低値をとった。早期膵癌の見逃しを少なくするためには，今後，60歳代を中心とする患者のfollow－up率をさらに高めることが必要である。To find an effective mass screening method for detecting early pancreatic cancer among asymptomatic populations and patients with vague abdominal symptoms, a prospective study was attempted on 1748 patients who came to Medical Clinic of Misasa Branch Hospital, Okayama University Medical School mostly for a routine annual chek-up from June 1, 1986 through June 30, 1990. These patients underwent first-step screeing tests including serum amylase, elastase I and routine abdominal ultrasonography (US). Consequently 155 patients (8.9% of the total 1748 patients) showed abnormal findings and underwent secondstep tests including US, ERCP and computed tomography. Final diagnosis was early pancreatic cancer in one patient and advanced pancreatic cancer in four. Three of the 5 patients with pancreatic cancer were in their sixties. Detection rate of pancreatic cancer (0.29%) in this series was satisfactory as compared with the results of previous reports with US alone. The rate of second-step examination increased with age. Six hundred and forty-one patients (36.7% of the 1748 patients) underwent follow-up examinations more than one year after the previous test. No pancreatic cancer was detected in the 641 patients. The rate of follow-up examination in patients in their sixties was significantly lower than in those in their forties or fifties. It is important to improve the follow-up rate in patients in their sixties, because they are at a high risk for pancreatic cancer as suggested by the present study

Diabetic complications in the advanced stage of chronic pancreatitis.

慢性膵炎が進行すると膵内外分泌不全に対する治療が主体となる。かつては膵疾患に由来する糖尿病（膵性糖尿病）においては糖尿病性合併症の発症が少ないとされていたが，慢性膵炎の長期経過観察例の増加とともにその頻度が一次性糖尿病にくらべて必ずしも低くないことが指摘されるようになった。そこで今回，厚生省難治性膵疾患調査研究班「慢性膵炎の新しい治療法の開発」小委員会の研究活動の一環として膵性糖尿病の治療法を再検討することになったのを機会に，その手始めに野性糖尿病の合併症に関する従来の報告を整理した。その結果，一次性糖尿病の場合にくらべて，細小血管症（網膜症，腎症，神経障害）はほぼ同程度であるが軽症例が多いこと，大血管症（心筋梗塞，脳硬塞，動脈硬化症）は少ないことが示唆された。そのほか，膵性糖尿病の合併症の発症に関与すると考えられる諸因子についても概説した。Exocrine dysfunction (maldigestion) and endocrine dysfunction (diabetes) are malll clinical features in the advanced stage of chronic pancreatitis. Diabetic complications were previously considered to be infrequent in diabetes secondary to chronic pancreatitis (pancreatic diabetes). However, the recent improvement in life expectancy and closer observation of the clinical course of patients with chronic pancreatitis have revealed that diabetic complications are not infrequent in pancreatic diabetes as compared with primary diabetes mellitus and that diabetes is one of the most important prognostic factors in chronic pancreatitis. We, therefore, reviewed recent articles on the topics before beginning a national survey of diabetic complications in patients with pancreatic diabetes. It has been suggested that : (1) diabetic microangiopathy (retinopathy, nephropathy and peripheral neuropathy) is almost as frequent in secondary diabetes as in primary diabetes, although the severity is less in secodary diabetes : (2) peripheral neuropathy is frequent in alcoholic chronic pancreatitis : (3)macroangiopathy (myocardial infarction, cerebral thrombosis, atherosclerosis) is less frequent in pancreatic diabetes. We also discussed various factors which may precipitate the diabetic complications

Experimental model of chronic pancreatitis, a review - Does it really exist?

Experimental model of pancreatitis is mandatory for elucidating the pathobiology of the disease and also to see the response of a novel treatment. In addition, the need for an animal model of chronic pancreatitis is further strengthened by the relative inaccessibility and paucity of the human pancreatitis tissue. Whereas various models of acute pancreatitis and also of exocrine pancreatic tumor have been described, chronic pancr-eatitis has not been consistently reproduced in experimental animals. Many researchers attempted to establish an experimental model of chronic pancreatitis either by partially obstructing the drainage of pancreatic secretion in dogs and cats or by feeding alcohol to dogs and rats with and without temporary occlusion of the biliopancreatic duct or by surgically inducing ischaemia in the pancreas of the dogs. But, none of these models is identical with human disease. A consistently reproducible model of human chronic pancr-eatitis probably does not exist. In this expanding era of molecular biology which promises us to enhance greatly our understanding of this disease, a right experimental model of chronic pancreatitis is still in progress.疾患の実験モデルの作成は,その疾患の病因,病態の解明,さらに治療法の開発のために重要である｡筆者らの一人は厚生省難治性膵疾患調査研究班の班員として,慢性膵炎の病態の解明や治療法の開発に関する研究を行っており,その研究の一環として,慢性膵炎の実験モデルの作成を現在行っている｡そこで,これまで報告されている慢性膵炎の実験モデルについて概要を報告した｡種々の動物や方法でヒト慢性膵炎に病因,病態,組織像が類似するモデルの作成が試みられてきたが,そのすべてが合致するような慢性膵炎モデルは確 立されてはいない｡近年の分子生物学的研究の進歩は著しく,実験モデルへの応用が種々なされている現在,より簡便で再現性のある慢性膵炎モデルの作成が望まれるところである

Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells

The cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+)CD41(+)CD45(−) phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner