慢性胰腺炎的病因和发病机制

慢性胰腺炎可由多种因素所致,以胰腺组织结构的进行性、不可逆性损害和内外分泌功能不全为主要表现。胰腺纤维化为其典型的病理学改变,临床表现有反复发作的腹痛及胰腺内、外分泌功能不全等。与慢性胰腺炎相关的病因及危险因素主要包括胆石病、酗酒、遗传因素、自身免疫因素等,其发病机制仍不甚明确,临床中慢性胰腺炎的发生更是多种病因、多种发病机制共同作用的结果。进一步研究慢性胰腺炎的具体病因及发病机制,对预防和治疗慢性胰腺炎具有重要意义。     

急性胰腺炎后的晚期结局:功能损害的胃肠道并发症

急性胰腺炎发作后在胰腺的腺体内可发生功能和形态学的改变。在发作的不同时期，胰腺的内分泌和外分泌功能受到不同程度的损害。许多研究指出，急性胰腺炎后影响形态学和功能改变的因素是疾病的严重程度和病因。大多数坏死性胰腺炎病人，在发病后的第一个表现有外分泌功能不足，有些病人以后可逐步恢复正常，但有相当一部分病人不能完全恢复正常。胆源性胰腺炎所致的功能改变罕有持续一年以上者。慢性酒精性胰腺炎所致的外分泌功能障碍能持续数月，甚至不能恢复正常。形态学改变酒精性病因者也多见于胆源性病因者。急性酒精性胰腺炎可进展成…     

慢性胰腺炎的个体化外科干预

慢性胰腺炎发病机制复杂,病情进展多变,导致外科干预时机及手术方式的选择存在一定困难。慢性胰腺炎的治疗应依据个体化原则去除病灶,尽量保存正常胰腺实质,延缓胰腺内、外分泌功能损害的进程,改善患者生命质量,降低胰腺癌发生的风险。慢性胰腺炎患者早期可考虑保守和内镜治疗,胰管梗阻、狭窄合并结石、胰腺实质广泛钙化等慢性胰腺炎患者则需手术治疗。Frey术适合以胰管扩张和胰管结石为主的慢性胰腺炎患者,Beger术适合以胰头部炎性肿块或胰头部钙化为主的慢性胰腺炎患者。     

慢性胰腺炎的胰酶替代治疗

慢性胰腺炎是由于各种原因造成的胰腺组织结构和功能慢性进行性损害。在慢性胰腺炎的发生发展过程中,早期主要症状为疼痛,晚期则疼痛症状减轻,代之以胰腺外分泌功能不全所引起的进行性消化不良和营养不良,严重影响到病人的生活质量和疾病预后。目前,对于慢性胰腺炎的治疗方法包括一般治疗、胰酶替代治疗和外科治疗(包括减压术、切除术和神经阻断术)。随着对慢性胰腺炎发生发展机制的深入研究和各种不同胰酶制剂的相继问世,人们对胰酶替代治疗在慢性胰腺炎治疗中的地位有了新的认识。     

慢性胰腺炎的诊治策略

慢性胰腺炎临床并不少见,为各种病因引起的胰腺组织和功能不可逆的慢性炎症性疾病,其病理特征为胰腺腺泡萎缩、破坏和间质纤维化.其早期临床症状为反复发作的上腹部疼痛或胰腺炎,进展期可合并胰腺外、内分泌功能不全的症状.影像学上表现为胰腺实质钙化、胰管扩张、胰管结石和胰腺假性囊肿形成等.而大量流行病学研究表明,慢性胰腺炎是胰腺癌的高危因素.     

慢性胰腺炎的诊断和治疗

慢性胰腺炎为胰腺持续性炎症性疾病，以胰腺实质发生慢性持续性炎性损害和纤维化为主要病理表现，可导致胰管扩张、胰管结石或钙化等不可逆性的形态改变，常引起顽固性疼痛和永久性内、外分泌功能丧失。迄今，其发病机理、病理生理和临床过程仍不十分清楚，各种治疗也仅限于慢性胰腺炎的症状和并发症，因此，此疾病仍是严重威胁人类健康的严重问题。     

慢性胰腺炎的外科治疗

慢性胰腺炎是各种病因引起胰腺组织和功能不可逆改变的慢性炎症性疾病。主要表现为反复发作的上腹部疼痛和胰腺内、外分泌功能不全。治疗原则是去除病因,控制症状,改善胰腺内、外分泌功能不全及防治并发症发生。常用治疗方法包括药物、内镜及手术等,其中外科治疗可去除病灶、改善症状、延缓胰腺功能损伤,在慢性胰腺炎治疗中起着重要作用。由于病因及发病机制不同,临床进展程度轻、重不一,对于外科干预时机     

保留十二指肠的胰头切除对慢性胰腺炎内外分泌功能的影响

慢性胰腺炎是一种常见的引起胰腺实质进行性损害,继而影响胰内外分泌功能的严重疾病。后期的顽固性疼痛、胰胆管梗阻及胰腺假性囊肿等是常见的并发症。近10年来,国外学者探索外科治疗的价值和各种术式对胰内外分泌功能的影响。     

慢性胰腺炎时胰腺内、外分泌功能不全的发生机制及处理

目的总结慢性胰腺炎时胰腺内、外分泌功能不全的发生机制及处理方法的研究进展。方法检索近年来国内外有关慢性胰腺炎时胰腺内、外分泌功能不全研究的相关文献并对其研究进展作一综述。结果近几年对慢性胰腺炎时出现胰腺内、外分泌功能不全有了很多新的研究和发现。慢性胰腺炎时胰腺外分泌功能不全的发生机制主要是因为患者胰酶分泌减少;胰腺内分泌功能不全的发生机制主要是由于慢性胰腺炎时胰腺外分泌腺体及胰岛组织的损伤导致胰腺内分泌细胞、其他内分泌细胞的破坏以及肠-胰岛轴紊乱,继而出现各种激素(胰岛素、胰高血糖素、胰多肽等)的紊乱,最终表现出糖耐量异常或显性糖尿病。当前的治疗方法胰腺外分泌功能不全包括针对病因治疗、饮食调节及胰酶替代治疗;胰腺内分泌功能不全应提倡使用动态血糖监测系统,2型糖尿病的管理治疗方案可以用于慢性胰腺炎糖尿病,强化胰岛素治疗方案仍是慢性胰腺炎糖尿病的首选。结论目前虽然对慢性胰腺炎时胰腺内、外分泌功能不全已经有了一定程度的了解,但其有关发病机制、诊疗方案尚无突破性的进展,缺乏大样本、多中心的临床对照研究的疗效,探索更加优化的检测手段,建立完善的治疗体系,是未来的发展趋势及研究的重点。     

慢性胰腺炎的手术治疗方式

慢性胰腺炎为胰腺炎症性疾病,以胰腺实质发生慢性持续性炎性损害、纤维化及可能导致的胰管扩张、胰管结石或钙化等不可逆性的形态改变为其特征,可引起顽固性疼痛和永久性内、外分泌功能丢失.手术治疗同目前的其他治疗一样,并非能使疾病获得根本性的痊愈或完全中断疾病的进程.因此,手术治疗的目的主要有两个,一是缓解大多数患者伴随的顽固性的严重疼痛,改善生活质量;二是解除胰腺导管因炎症性增生和结石导致的狭窄、管内高压,减缓疾病进程和改善内外分泌功能.     

Clinical evidence of pathogenesis in chronic pancreatitis

Chronic pancreatitis is a continuing inflammatory disease characterized by irreversible morphological change and, typically, by pain and permanent impairment of function. The pathogenesis of pancreatitis, either acute or chronic, is still controversial. There have been no widely accepted concepts to provide a reasonable explanation linking the known etiological factors and the pathophysiological aspects of the disease. Alcohol is undoubtedly the major etiological factor in most countries, and the relative importance of alcohol as a cause of chronic pancreatitis ranges from 40% to 90% in various countries. As fewer than 10% of alcoholics develop chronic pancreatitis, other nutritional or genetic influences are likely to be involved in the pathogenesis of alcoholic pancreatitis. Accessory pancreas incidentally found in patients with chronic alcoholic pancreatitis does not always have the pathological findings seen in the main pancreas. Integrity of the pancreatic duct seems to be another important factor for chronic alcoholic pancreatitis. Gene mutations of the cystic fibrosis transmembrane conductance regulator (CFTR), cationic trypsinogen, and pancreatic secretory trypsin inhibitor have been investigated in idiopathic chronic pancreatitis. Molecular and cell biology research during the past few years has elucidated pathophysiological factors that are involved in the pathogenesis of chronic pancreatitis, but cannot demonstrate a common pathway between etiological factors and the pathogenesis or development of the disease. Received: March 20, 2002 / Accepted: April 15, 2002 Offprint requests to: T. Hayakawa     

Obesity, Pancreatitis, and Pancreatic Cancer

The only universally accepted risk factors for the development of pancreatic cancer are a positive family history or a history of smoking. Although the contribution of pancreatitis to pancreatic carcinogenesis has been debated for decades in the epidemiology literature, the actual mechanism is still unclear. With the rising epidemic of obesity, scientists have begun to focus on the contribution of chronic inflammatory state of morbidly obese patients in an effort to better understand the contribution of inflammation to the comorbidities of obesity. Notably, population studies are beginning to show that one of the most serious potential comorbidities of obesity is an increased lifetime risk of developing cancer. In this article, the current literature that exists supporting this Chronic Inflammatory Hypothesis as it pertains to obesity and pancreatic carcinogenesis is reviewed. To date, studies have focused on interleukin-6, a cytokine known to play a role in obesity, chronic pancreatitis and pancreatic cancer. The anti-inflammatory adipocytokine, adiponectin, has also shown promise as a key player in this mechanism and has recently been found to be more specific than standard tumor markers in differentiating pancreatic cancer from chronic pancreatitis. If the pathogenesis of pancreatic cancer is related to hormone levels associated with obesity, such as adipocytokines, and cytokines associated with chronic inflammation, this could potentially lead to the development of new pancreatic cancer tumor markers and ultimately new therapies and methods of prevention. The author has no conflicts of interest to disclose.     

The Frey procedure: local resection of pancreatic head combined with lateral pancreaticojejunostomy.

Management of chronic pancreatitis is mainly palliative. Most patients with chronic pancreatitis require surgical evaluation and intervention when there is suspicion of pancreatic malignancy, evidence of intractable pain, or development of pancreatitis-related local complications. The ideal operation for chronic pancreatitis, therefore, should be designed to exclude the existence of malignancy, provide long-lasting pain relief, and correct the local complications. It should be as simple and safe as possible and should preserve the remaining endocrine and exocrine functions of the pancreas.     

慢性胰腺炎诊断与治疗研究进展

慢性胰腺炎是临床上较常见的慢性消化系统疾病,发病机制尚未明确,临床主要表现为反复发作性腹痛、消化不良、脂肪泻、血糖升高等,具有症状反复、迁延难愈的特点。结合多种影像学检查和胰腺内外分泌功能检测可提高慢性胰腺炎的确诊率。但对于早期慢性胰腺炎患者,目前仍难发现、难诊断。治疗策略上着重于缓解患者症状、控制疾病进展、改善胰腺功能和防治相关并发症,强调以个体化治疗为中心的多学科综合治疗。本文就慢性胰腺炎的疾病特点和近些年来的诊治进展做简要综述。     

Chronic Pancreatitis

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal (“groove”) pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed.     

What should be the standard operation in chronic pancreatitis: Whipple or duodenum-preserving pancreatic head resection?

Surgical options in the treatment of chronic pancreatitis have undergone both development and controversial discussion in the past decades. Operations such as the classical and pylorus-preserving Whipple resections are more and more being replaced by operations such as the duodenum-preserving pancreatic head resection, which preserves extrapancreatic organs like the stomach, the duodenum and the extrapancreatic bile duct. The latter operation preserves a normal food passage and glucose metabolism after surgical intervention. In addition, the duodenum-preserving pancreatic head resection provides long-term pain relief and reduction in up to 90% of chronic pancreatitis patients, as well as a general improvement in quality of life. This article will summarize and compare the surgical options in the treatment of chronic pancreatitis and will provide arguments why the duodenum-preserving pancreatic head resection should replace the classical and the pylorus-preserving Whipple resections as the standard surgical procedure used to treat chronic pancreatitis-related complications.     

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??Etiology and pathogenesis of chronic pancreatitis WANG Xing-peng*, ZHANG Ru-ling. *Tenth People’s Hospital of Tongji University, Shanghai 200072, China
Corresponding author: WANG Xing-peng, E-mail: wangxp1965@yahoo.com.cn
Abstract Chronic pancreatitis (CP) is the progressive and permanent destruction of the pancreas resulting in exocrine and endocrine insufficiency. The typical pathological change of CP is pancreatic fibrosis, which could cause persistent or recurrent abdominal pain as well as loss of pancreatic endo- and exocrine function. The etiology and pathogenesis of CP are multifactorial, including cholelithiasis, alcoholism, genetic predisposition and autoimmune factors. However, the incidence of CP should be a result of multiple etiological factors, and the individual pathogenesis remains unclear. Further researches of individual etiology and pathogenesis of CP would be helpful to the prevention and treatment of this disease.     

Problems of pancreatitis

Pancreatitis is not one disease but several and perhaps many. Diagnosis is imperfect in all forms and the usual lack of histologic material has hampered attempts to understand the pathogenesis and possible interrelationships of the different forms of pancreatic inflammation. Acute pancreatitis does not as a rule evolve into chronic pancreatitis, even after multiple recurrences. Recurrent acute attacks can be ended by identifying and treating the factor causing the disease, including recently recognized entities such as accessory papilla stenosis associated with pancreas divisum. Attempts to improve the treatment of severe acute pancreatitis are focussing upon preventing injury to pancreatic cell structures, enhancing endogenous mechanisms for capture and disposal of activated enzymes, and upon early detection and debridement of damaged pancreatic and peripancreatic tissues. Pancreatic duct stricture or obstruction as a consequence of scarring from necrotizing pancreatitis may produce recurrent symptoms, now designated as obstructive pancreatitis. Obstructive pancreatitis has its own unique histologic characteristics and is appropriately treated by resection of the blocked segment of pancreas when the point of obstruction is distal to the papilla. Chronic pancreatitis differs from acute or obstructive pancreatitis in that it is difficult or impossible to halt its progression. The role of intraductal protein precipitates, whether of enzymes or perhaps of other unique pancreatic secretory proteins, in the pathogenesis of the disease is being evaluated. The goal of surgical treatment is not to cure, but to reduce pain, overcome associated obstruction of the bile duct or duodenum, and to treat pancreatic duct disruptions including pseudocysts and internal pancreatic fistulas. Because continuing deterioration of pancreatic function is to be expected in chronic pancreatitis, maximum conservation of pancreatic tissue by avoiding resectional procedures is advisable. This report is the gist of a paper read by A. L. W. at the 86th Annual Meeting of the Japanese Surgical Society, Tokyo, Japan, 1986     

Problems of pancreatitis

Pancreatitis is not one disease but several and perhaps many. Diagnosis is imperfect in all forms and the usual lack of histologic material has hampered attempts to understand the pathogenesis and possible interrelationships of the different forms of pancreatic inflammation. Acute pancreatitis does not as a rule evolve into chronic pancreatitis, even after multiple recurrences. Recurrent acute attacks can be ended by identifying and treating the factor causing the disease, including recently recognized entities such as accessory papilla stenosis associated with pancreas divisum. Attempts to improve the treatment of severe acute pancreatitis are focussing upon preventing injury to pancreatic cell structures, enhancing endogenous mechanisms for capture and disposal of activated enzymes, and upon early detection and debridement of damaged pancreatic and peripancreatic tissues. Pancreatic duct stricture or obstruction as a consequence of scarring from necrotizing pancreatitis may produce recurrent symptoms, now designated as obstructive pancreatitis. Obstructive pancreatitis has its own unique histologic characteristics and is appropriately treated by resection of the blocked segment of pancreas when the point of obstruction is distal to the papilla. Chronic pancreatitis differs from acute or obstructive pancreatitis in that it is difficult or impossible to halt its progression. The role of intraductal protein precipitates, whether of enzymes or perhaps of other unique pancreatic secretory proteins, in the pathogenesis of the disease is being evaluated. The goal of surgical treatment is not to cure, but to reduce pain, overcome associated obstruction of the bile duct or duodenum, and to treat pancreatic duct disruptions including pseudocysts and internal pancreatic fistulas. Because continuing deterioration of pancreatic function is to be expected in chronic pancreatitis, maximum conservation of pancreatic tissue by avoiding resectional procedures is advisable.     

Chronic Pancreatitis and Bone Disease

Patients with chronic pancreatitis (CP) may have a higher prevalence of osteoporosis than the general population thereby increasing the risk of bone fracture. The pathophysiology of bone disease in CP is multifactorial. Their risk factors for secondary osteoporosis include increasing age, low body mass index from sitophobia, maldigestion due to exocrine pancreatic insufficiency (EPI) with resulting low vitamin D, as well as smoking and alcohol abuse. An obvious association of bone disease with CP is from EPI with maldigestion of fat-soluble vitamins including vitamin-D, which has a significant role in the process of bone formation. Vitamin-D deficiency may be higher in CP patients vs controls, and it is especially so in CP patients with EPI. Screening for CP-associated osteopathy, including osteopenia and osteoporosis, should be initiated early in the course of CP, as the overall prevalence of bone disease is approximately two-thirds of CP patients. Our initial approach in the treatment of osteoporosis should include correction of maldigestion resulting from EPI with use of pancreatic enzyme replacement therapy (PERT). PERT, which is the treatment for EPI is associated with improvement in Dual energy X-ray absorptiometry (DXA) values and vitamin-D levels compared to those who are not treated. This should improve, in addition to body mass index, vitamin-D deficiency and calcium absorption as well as improve overall nutritional status. Osteopathy is common in CP patients, has significant associated morbidity, should be screened for regularly, and corrected with fat soluble vitamin supplementation and PERT to prevent clinical sequelae. In this article, we review the epidemiology, pathophysiology, and treatment of bone disease in patients with CP.