Autoimmune pancreatitis: unveiling a hidden entity

HYPOTHESIS: After alcohol-induced and hereditary disease, idiopathic chronic pancreatitis is the most common cause of calcifying pancreatitis. This designation is used when no associated cause of chronic pancreatitis is found. We present 6 cases of idiopathic pancreatitis in which the postoperative pathological examination results demonstrated lymphoplasmacytic sclerosing pancreatitis or autoimmune pancreatitis. DESIGN: Retrospective case series. The medical records of 6 patients referred and treated for autoimmune pancreatitis were reviewed. The duration of follow-up varies, the longest being 5 years. The disease and a literature review are reported. SETTING: A 200-bed community hospital located in a large city. The patients were referred after being treated elsewhere for recurrent pancreatitis. PATIENTS AND METHODS: Six patients with chronic recurrent pancreatitis were evaluated. They were selected because pathological review indicated that they all had autoimmune pancreatitis. RESULTS: Six cases of lymphoplasmacytic sclerosing pancreatitis are presented and suggest that lymphoplasmacytic sclerosing pancreatitis should be thought of more often in chronic autoimmune pancreatitis. CONCLUSION: Lymphoplasmacytic sclerosing pancreatitis is an increasingly recognized cause of chronic pancreatitis and should be considered in the evaluation of patients with chronic pancreatitis and no discernible cause.     

Eosinophilic pancreatitis and increased eosinophils in the pancreas

Prominent eosinophilic infiltrates are an unusual finding in the pancreas. Eosinophilic pancreatitis is one rare etiology of pancreatic eosinophilia, but other described causes of eosinophilic infiltrates have also included pancreatic allograft rejection, pancreatic pseudocyst, lymphoplasmacytic sclerosing pancreatitis (LPSP), inflammatory myofibroblastic tumor, and histiocytosis X. In this study we describe the clinicopathologic features of three new cases of eosinophilic pancreatitis and conduct a retrospective 18-year institutional review of the myriad disease processes associated with pancreatic eosinophilia. In the files of the Johns Hopkins Hospital, <1% of all pancreatic specimens had been noted to show increased numbers of eosinophils. Eosinophilic pancreatitis itself was a rare etiology for pancreatic eosinophilia, with only one in-house case over the 18-year study period and two additional referral cases. Other disease processes associated with prominent eosinophilic infiltrates were more common and included pancreatic allograft rejection (14 cases), LPSP (5 of 24 total LPSP cases evaluated), inflammatory myofibroblastic tumor (4 cases), and systemic mastocytosis (1 case). Patients with eosinophilic pancreatitis showed two distinct histologic patterns: 1) a diffuse periductal, acinar, and septal eosinophilic infiltrate with eosinophilic phlebitis and arteritis; and 2) localized intense eosinophilic infiltrates associated with pseudocyst formation. All three patients with eosinophilic pancreatitis had peripheral eosinophilia, and all had multiorgan involvement. One patient with LPSP also had marked peripheral eosinophilia, and 5 of 24 LPSP cases demonstrated prominent eosinophilic infiltrates in the gallbladder, biliary tree, and/or duodenum. Notably, not all of these patients with LPSP with prominent eosinophils in other organs had increased eosinophils in the pancreas itself. These results emphasize the infrequent nature of pancreatic eosinophilia and its multiple potential disease associations. True eosinophilic pancreatitis, although a fascinating clinicopathologic entity, is one of the rarest causes of pancreatic eosinophilia.     

Evaluation of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose for the differentiation of chronic pancreatitis and pancreatic cancer

BACKGROUND: The clinical presentation of patients with pancreatic cancer may resemble the clinical picture of chronic pancreatitis. A definitive preoperative diagnosis is not always obtained in patients with a history of chronic pancreatitis despite the use of modern imaging techniques. Operative strategy therefore remains unclear before operation in these patients. METHODS: Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was introduced recently into clinical oncology because of its ability to demonstrate metabolic changes associated with various disease processes. The impact of FDG-PET on the differentiation of chronic pancreatitis and pancreatic cancer was investigated. FDG-PET was performed in 48 patients with chronic pancreatitis (n = 12), acute pancreatitis (n = 3) and pancreatic cancer (n = 27), and in controls (n = 6). Histological examination was undertaken in all cases except controls. The FDG-PET results were obtained without knowledge of results of other imaging procedures. The results were then compared with those of computed tomography, ultrasonography, endoscopic retrograde cholangiopancreaticography, operative findings and histology. PET images were analysed semiquantitatively by calculating a standard uptake value (SUV) 90-120 min after application of the tracer. RESULTS: Cut-off values were validated as follows: SUV greater than 4.0 for pancreatic cancer, SUV of 3.0-4.0 for chronic pancreatitis, and SUV of less than 3.0 for controls. Sensitivity and specificity of PET imaging were 0.96 and 1.0 for pancreatic cancer, and 1.0 and 0.97 for chronic pancreatitis. In five cases only FDG-PET led to the correct preoperative diagnosis. CONCLUSION: The results give further evidence that FDG-PET is an important non-invasive method for the differentiation of chronic pancreatitis and pancreatic cancer. Delayed image acquisition in the glycolysis plateau phase permits improved diagnostic performance. This imaging technique is extremely helpful before operation in patients with an otherwise unclear pancreatic mass, despite its costs.     

Duodenum-preserving head resection for chronic pancreatitis: an institutional experience and national survey of usage

BACKGROUND: Duodenum-preserving pancreatic head resections (DPPHRs) have been shown in European randomized clinical trials to be superior to pancreaticoduodenectomy for chronic pancreatitis, but DPPHR procedures have been slow to be adopted in the United States. METHODS: To assess national attitudes of surgeons toward DPPHR, a web-based survey was administered to the U.S. members of the Pancreas Club, which is a national organization of pancreatic surgeons. We also performed a retrospective review of 21 DPPHRs, performed by the senior author, for chronic pancreatitis between January 2000 and March 2005. RESULTS: The web-based national survey was completed by 64 of 118 members of the Pancreas Club (54.24%). Of the 59 surgeons who perform operations for chronic pancreatitis, 34 had performed a DPPHR at least once. Only 23 U.S. surgeons continue to perform these procedures. Most surgeons who are not performing DPPHRs responded that, despite the published literature, existing procedures such as the Whipple and Puestow were better procedures. In our clinical series, 12 men and 9 women with a mean age of 48.2 +/- 9.6 years underwent DPPHR. The median length of stay was 9 days with 6 patients (28%) who had complications in the postoperative period. Ten of 20 potentially evaluable patients completed a visual analog pain scale and EORTC C-30 quality-of-life questionnaire. Pancreatic functioning approached the normal range in all domains. As compared with a general population of patients with chronic pancreatitis, significant improvement occurred in pancreatic-related pain and digestive function. Self-reported pain was significantly better after operation than before operation. CONCLUSIONS: DPPHR provides excellent functional results with relatively low postoperative morbidity and duration of stay. These procedures are underused in the United States, with very few surgeons who use, teach them, or report their results.     

Intraluminal duodenal diverticulum causing acute pancreatitis: CT scan diagnosis and review of the literature

BACKGROUND: Intraluminal duodenal diverticulum is a rare congenital anomaly. First described by Boyd in 1845, no more than 100 cases have been reported up to now: only 17 are associated with acute pancreatitis. METHODS: A new case of intraluminal duodenal diverticulum with acute pancreatitis is reported and the literature about this association reviewed. RESULTS: The diagnosis was made by helical CT scan. The pathogenesis of pancreatitis was possibly due to a pure duodenal content reflux through the papilla of Vater. The patient was successfully treated by surgery. CONCLUSIONS: Intraluminal duodenal diverticulum is a rare but curable cause of pancreatitis, usually affecting young people. We describe, for the first time, its unusual helical CT imaging with two-dimensional reformations.     

Subacute cytosteatonecrosis of pancreatic origin. Surgical problem in 5 cases (author's transl)

The authors report 5 cases of subcutaneous cytosteatonecrosis (Weber-Christian syndrome of pancreatic origin) and review 68 cases in the world literature. The skin, bone joint and general manifestations may appear without any clinical or radiological sign of pancreatitis. The rise in blood and urinary amylase and lipase, the skin lesions, the joint pleural and peritoneal effusions, orient the diagnosis towards the pancreas and suggest a full radiological arteriographic and echotomographic investigation. The pancreatic disease was pancreatitis in 50 cases, cancer in 18 cases. Too long a delay between the initial signs and the diagnosis may lead to early operation even in the absence of pancreatic signs. The cancer may still be limited and removable. The pancreatitis was in 18 cases a false cyst of the head in 2/3rds, whether obvious clinically or not. Operation led to its discovery usually but may miss the lesion which is then only discovered on autopsy. Removal or early by pass operations transform the prognosis which is otherwise fatal. Analysis of these cases illustrates well the problems of indication operative management and efficacy of surgery in a disease still relatively unfamiliar both to physicians and surgeons.     

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.     

胰管结石的分型及手术治疗

目的：探讨胰管结石的分型及手术方法。方法对8例行手术治疗的胰管结石合并慢性胰腺炎或胰腺癌患者病历资料进行分析。8例患者术前均行腹部B超、上腹部CT平扫＋增强或磁共振胆胰管水成像（MRCP）检查以明确诊断。其中Ⅰ型2例,采用胰头十二指肠切除术;Ⅱ型1例,采用胰尾切除＋脾切除＋胰管空肠吻合术;Ⅲ型5例,采用胰管切开取石并胰管空肠吻合术。结果8例均成功手术,1例术后并发胰漏,经非手术治疗后好转;5例糖尿病患者术后3例血糖恢复正常。结论胰管结石发病率虽然不高,但常合并胰腺炎、糖尿病甚至胰腺癌,后果严重,依胰管结石部位分型并选择合理的手术方法极为重要。     

Enteric Duplication Cyst of the Pancreas Associated with Chronic Pancreatitis and Pancreatic Cancer

Pancreas-associated enteric duplication cysts are rare developmental anomalies that communicate with the main pancreatic duct and may be associated with recurrent acute and chronic abdominal pain in children. In adults, these lesions may masquerade as pancreatic pseudocysts or pancreatic cystic neoplasms. An adult patient with a pancreas-associated enteric duplication is described which represents the first reported instance of association with both chronic calcific pancreatitis and pancreatic cancer. The clinical spectrum of pancreas-associated enteric duplication cyst, including diagnostic and therapeutic options, is reviewed.     

INTERNAL PANCREATIC FISTULAE WITH SEROUS EFFUSIONS IN CHRONIC PANCREATITIS

Background: Serous effusions in chronic pancreatitis are infrequent but persistent. These occur usually as a consequence of internal pancreatic fistulae and commonly involve the pleural cavity or peritoneum. Methods: To assess strategies in operative management, the records of 12 patients who underwent surgery for internal pancreatic fistula with underlying chronic pancreatitis were reviewed retrospectively. Seven patients had pancreatic ductal calculi. Three cases underwent external drainage. Three cases with leaking pseudocysts underwent cystojejunostomy-en-Y. Three cases with ductal dilatation or calculi underwent lateral pancreaticojejunostomy and three patients had caudal pancreatectomy for distal disease. Results: Eight patients were completely controlled of all symptoms, with no sequelae. One case each had recurrent pancreatitis and ascites but did not require re-operation. There were two deaths: one with massive haematemesis and one with pre-existent multi-organ failure and sepsis. Conclusions: Pancreatic duct stones may be causally associated with internal pancreatic fistulae. Delineation of ductal anatomy and pathological aberrations of the pancreas, including determination of the leak site, was of paramount importance in planning surgery. Peroperative ductography proved the most useful in this regard.     

自身免疫性胰腺炎

The purpose of this review is to provide a concise view of the existing knowledge of autoimmune pancreatitis (AIP) for practicing clinicians.AIP is a rare disease whose recognition and understanding are evolving.It is a type of chronic pancreatitis which often presents as obstructive jaundice,has a distinctive histology and is exquisitely sensitive to steroid therapy.This form of chronic pancreatitis has a unique clinical,biochemical,and radiological profile.The term “AIP” encompasses two subtypes:type 1 and type 2.Type 1 AIP is the pancreatic manifestation of a systemic fibro-inflammatory disease called IgG4 associated systemic diseases; type 2 AIP has been shown to be associated with inflammatory bowel disease.Existing criteria are geared towards the diagnosis of type 1 AIP.At present,pancreatic histology is a requirement for the definitive diagnosis of type 2 AIP.AIP can mimic most other pancreatic diseases in its presentation,but in clinical practice it often has to be differentiated from pancreatic cancer.There are established criteria and algorithms not only to diagnose AIP but also differentiate it from pancreatic cancer.The utility of these algorithms and the approach to management are discussed here.     

A case of intraductal papillary adenocarcinoma of the pancreas associated with mass forming chronic pancreatitis

A case of intraductal papillary adenocarcinoma of the pancreas associated with mass forming chronic pancreatitis without calcifications is described. Pancreatolithiasis, or calcified pancreas, is recognized as a high risk factor for pancreatic cancer. However, epidemiologic studies have found that carcinoma of the pancreas associated with chronic pancreatits was rare. The question is whether chronic pancreatitis without calcifications is actually a precancerous background lesion or not. This case suggests that hyperplasia of the pancreatic ductal epithelium may be a precancerous lesion for pancreatic cancer in some patients with chronic pancreatitis.     

Pancreas divisum, chronic pancreatitis and diabetes mellitus. Improvement by pancreaticojejunostomy]

The relationship between pancreas divisum and chronic pancreatitis is controversial. We report the cases of two patients aged 40 and 53 years suffering from recurrent pancreatitis and known to have histologically proven idiopathic chronic pancreatitis. One patient had insulin dependent diabetes. Pancreatography demonstrated in these two cases a pancreas divisum with a dilated dorsal pancreatic duct. A pancreatico-jejunostomy was performed, associated in one case with splenopancreatectomy for pseudo-cyst. With a follow-up of 32 and 78 months, both patients were free of symptoms and the diabetic patient had normal blood glucose levels with diet alone. The clinical history of the patients suggests a relationship between pancreas divisum and chronic pancreatitis and that pancreatico-jejunostomy may improve pancreatic pain and pancreatic function.     

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.     

Pathological study of hepatolithiasis with special reference to unusual cases

Morphological survey was performed in 140 liver specimens of hepatolithiasis which were collected from several pathological and surgical Departments in Japan. Among them there were 19 cases with unusual features suggestive of presumed lithogenic processes. They consisted of association of congenital dilatation of biliary tree (5 cases), association of stenosis or obstruction of biliary tree occurring prior to lithiasis (4 cases), association of anomalous communication between biliary tree (1 case), presence of serous glands simulating to pancreatic exocrine glands in biliary tree (1 case), association of non-biliary hepatic cirrhosis (4 cases), association of chronic ulcerative colitis (1 case), intrahepatic cholesterol stone (2 cases) and association of granulomatous cholangitis (1 case). Chronic proliferative cholangitis which is consistently seen in a common type of hepatolithiasis was found in about a half of these unusual cases and not in the remaining cases. Based on the observations of these unusual cases, the following suggestions were obtained: dilatation, bile stasis or cholangitis may be a lithogenic factor of hepatolithiasis, and chronic proliferative cholangitis associated with a numerous amount of mucinous glands is not always a prerequisite lesion and exerts a promoting and accelerating effect in hepatolithiasis.     

Acute Pancreatitis in Chronic Kidney Disease—A Common but Often Misunderstood Combination

The occurrence of pancreatitis has been reported among chronic kidney disease (CKD) patients, especially those who are on peritoneal dialysis. It contributes to an increased morbidity and mortality in patients who are already suffering from renal failure. The diagnosis of acute pancreatitis is also modified by the loss of renal function with altered levels of pancreatic enzyme estimation and the contribution of pancreatic damage due to uremia and dialysis. We describe two cases of CKD who presented with acute pancreatitis and also briefly review the literature.     

Chronic familial pancreatitis (6 cases, 3 families)]

The authors report 6 cases of chronic familial pancreatitis. They review the literature on this disease which is still little recognised and seek the specific characteristics, early onset, transmission as an autosomic dominant with incomplete penetrance, relatively favourable prognosis, together with the suggestive signs, pancreatic lithiasis and certain complications. Apart from these signs, chronic familial pancreatitis differs very little from common chronic pancreatitis. The only cause is apparently genetic. Etiopathogenesis is thus still obscure. Treatment should be started early, but surgical methods are the same as in primary chronic pancreatitis.     

Total pancreatectomy with islet cell autotransplantation in a 2-year-old child with hereditary pancreatitis due to a PRSS1 mutation

Acute recurrent and chronic pancreatitis in children carries high morbidity and burden. Compared to adults, ~75% of the cases of chronic pancreatitis in children are associated with underlying genetic mutations. The decision to intervene and the optimal timing poses unique challenges. Total pancreatectomy and islet cell autotransplantation (TPIAT) provides definitive therapy to relieve pain and improve quality of life while minimizing the risk of pancreatogenic diabetes. Substantial clinical data are available for adults; however, information on clinical outcomes in children remains scarce, particularly for very young children. Herein, we present an unusual, complex case of a 2-year-old child that underwent a successful TPIAT due to hereditary pancreatitis with an underlying mutation in PRSS1 gene, complicated by unremitting pancreatic ascites, hemorrhage, and sepsis. This is the youngest case to be reported in the literature. We provide a comprehensive report of the course and procedures implemented in this patient to guide other teams when considering these extraordinary measures in similar cases.     

Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis

Lymphoplasmacytic sclerosing pancreatitis (LPSP) represents a distinctive form of chronic pancreatitis characterized by diffuse fibroinflammatory infiltrates that can involve both the pancreatic ducts and acinar parenchyma. Several cases of inflammatory infiltrates within the gallbladder have been reported in association with LPSP, but the spectrum of gallbladder pathology in patients with LPSP has not been systematically reviewed. Many patients with LPSP have distal CBD fibrosis, strictures, and inflammation, features that overlap somewhat with primary sclerosing cholangitis (PSC). In PSC, a pattern of gallbladder pathology termed "diffuse acalculous lymphoplasmacytic chronic cholecystitis" has been previously described as showing a triad of diffuse, mucosal-based, plasma cell-rich inflammatory infiltrates. We studied 20 gallbladders from patients with LPSP and compared them with 20 gallbladders in PSC, 20 gallbladders with chronic cholelithiasis, and 10 gallbladders from patients with benign (non-LPSP) pancreatic disease. The following features were evaluated: degree and composition of mucosal inflammation and deep (mural) inflammation, lymphoid nodules, metaplasia, dysplasia/neoplasia, fibrosis, muscular hypertrophy, Rokitansky-Aschoff sinuses, and cholesterolosis. The majority (60%) of gallbladders in LPSP contained moderate or marked inflammatory infiltrates and lymphoid nodules, frequencies similar to PSC but significantly higher than in chronic cholelithiasis and benign non-LPSP pancreatic disease. LPSP gallbladders received the highest scores for deep inflammation of all groups, and 35% of LPSP gallbladders showed transmural chronic cholecystitis. Overall, "diffuse lymphoplasmacytic chronic cholecystitis" was present in 50% of PSC cases and 25% of LPSP cases, but in only 5% of chronic cholelithiasis and none of non-LPSP benign pancreatic disease. Mucosal inflammation in LPSP gallbladders correlated significantly with the presence of inflammation in the extrapancreatic portion of the CBD. These findings suggest that inflammatory pathology of the gallbladder is frequently associated with LPSP and that it is part of the spectrum of biliary tract disease in these patients, rather than a simple reflection of the pancreatitis itself.     

Role of total pancreatectomy in the treatment of paraduodenal pancreatitis:A case report

BACKGROUND Paraduodenal pancreatitis(PP) is a rare form of chronic pancreatitis presenting with symptoms of duodenal obstruction. Conservative treatment is often unsuccessful and pancreaticoduodenectomy is the preferred surgical approach. A mini review of the outcomes of surgical therapy for PP shows that the results of pancreaticoduodenectomy are predominantly favorable.CASE SUMMARY In our case report of PP, we describe an unusual course first presenting with the symptoms of chronic pancreatitis and a pseudocyst of the pancreatic tail. A pseudocystojejunostomy was performed and the late postoperative course was complicated with the symptoms of duodenal obstruction. At laparotomy, PP was found and the patient was treated with a total pancreatectomy. The postoperative course was uneventful and good weight gain with resolution of pain was demonstrated at follow up visits.CONCLUSION Surgery is currently the optimal treatment option for PP. It is also the best diagnostic tool in distinguishing between pancreatitis and pancreatic adenocarcinoma.