Duodenal wall cysts may be derived from a ductal component of ectopic pancreatic tissue

AIMS: To clarify the mechanism of origin of duodenal wall cysts in patients with chronic pancreatitis, developing into duodenal stenosis. METHODS AND RESULTS: Specimens from 12 pancreatoduodenectomized patients with chronic pancreatitis and 51 controls were studied histopathologically and immunohistochemically. Variously shaped cystic lesions, averaging about 15 mm in diameter, were found in the duodenum in six of the 12 patients with chronic pancreatitis, but were not observed in the controls. Each case had an average of two cysts, which were located mainly in the muscularis propria of the duodenum with or without submucosal or extraduodenal-peripancreatic extensions. The inner part of the cyst wall consisted of a moderate rim of granulation tissue, with both myofibroblasts and smooth muscle proliferation in the tissue surrounding the cyst and the submucosal layer of the duodenum, occasionally accompanied by an epithelial lining. A ductal structure in the muscularis propria of the duodenum, possibly a ductal component of ectopic pancreatic tissue, was found in five of the six cases. Some of these structures showed cystic changes. Three of the six patients had accompanying duodenal stenosis. CONCLUSIONS: Duodenal wall cysts occur mainly in the muscularis propria of the duodenum associated with both myofibroblasts and smooth muscle proliferation, and may result in duodenal stenosis. These cysts may be derived from a ductal component of ectopic pancreatic tissue.     

Histopathological study on mechanism and background of tumor-forming pancreatitis

Fifteen cases of tumor-forming pancreatitis, detected as tumors by diagnostic imaging or by physical examination were histologically examined. Eleven of the 15 patients were heavy drinkers. Tumorous lesions were located in the head of the pancreas in 11 cases and in the body or tail of the pancreas in four cases. Macroscopic examination revealed tumorous swelling or sclerotic appearance in the pancreatic tissue. Histologically, these lesions showed tumorous swelling with (n = 12) or without (n = 3) a background of chronic pancreatitis. In the former, the tumorous lesions consisted of extensive fibrosis, including necrosis or abscesses, stones and reparative granulation tissue, and there was a successive transition to the surrounding chronic pancreatitis pattern. The latter three tumorous lesions presented with inter- and intralobular fibrosis with lymphoid hyperplasia or lymphoplasmacytic infiltration and were adjacent to normal pancreatic tissue. Therefore, tumor-forming pancreatitis shows at least two distinct types: a reparative tumorous swelling with a background of chronic pancreatitis, which is considered to have given rise to the tumor at some stage; and a lymphoid and fibrous proliferation in normal pancreatic tissue, which is considered to represent an autoimmune-related disease process.     

Paraduodenal pancreatitis: a clinico-pathologically distinct entity unifying "cystic dystrophy of heterotopic pancreas", "para-duodenal wall cyst", and "groove pancreatitis"

A distinct form of chronic pancreatitis occurring predominantly in and around the duodenal wall (near the minor papilla) has been reported under various names, including cystic dystrophy of heterotopic pancreas, pancreatic hamartoma of duodenum, para-duodenal wall cyst, myoadenomatosis, and groove pancreatitis. Our experience with these lesions and the review of the literature show that these lesions have the following common characteristics: (1) The duodenal wall contains dilated ducts, some with inspissated secretions, and pseudocystic changes as well as adjacent stromal reactions including hypercellular granulation tissue, foreign-body type giant cell reaction engulfing mucoprotein material, and myofibroblastic proliferation. (2) Brunner's gland hyperplasia is typically present. (3) Dense myoid stromal proliferation, with intervening rounded lobules of pancreatic acinar tissue, creates a histologic picture reminiscent of "myoadenomatosis," "pancreatic hamartoma," or even leiomyoma in some cases. (4) Spillover of fibrosis into the adjacent pancreas and soft tissue occurs, especially in the "groove" area (between the pancreas, common bile duct and duodenum), including the region around the common bile duct. (5) Clinically, these lesions often mimic "pancreas cancer" or periampullary tumors, because of marked scarring as well as the ill-defined borders of the process. Patients with these findings are predominantly males, 40-50 years old, with a history of alcohol abuse. That the process is often centered in the region of minor papilla (and the adjacent pancreas) suggests that an anatomic variation of the ductal system may render this area particularly susceptible to the effects of alcoholic injury, and the myo-adenomatoid and cystic changes on the duodenal wall may in turn represent changes related to a localized recurrent pancreatitis. In conclusion, these clinicopathologic findings characterize a distinctive process that can be referred to as paraduodenal pancreatitis.     

Morphologic features of the structure of the major duodenal papilla in healthy subjects and pathology of the biliopancreatic region

The major duodenal papilla (MDP) was studied morphologically on the section material from 57 cases of diseases of the biliopancreatic area and from 60 other diseases. Two types of the structure of folds-valves of MDP mucosa were found to correspond to two main variants of fusion of the common bile duct and pancreatic duct. In the presence of a common channel of MDP (73%) the valves are arranged in 3 or 4 layers and each valve consists of 3 cusps. In cholelithiasis, chronic pancreatitis, and cholecystopancreatitis, signs of chronic inflammation in the MDP wall were found in all the cases and hyperplastic changes in half of the cases. In 7 observations of cholelithiasis, a close correlation between the development of MDP stenosis and the degree of adenomyosis and papillary outgrowths of the mucous membrane was established.     

Paraduodenal pancreatitis: a new unifying term and its morphological characteristics

Two inflammatory lesions represent the major differential diagnosis of pancreatic cancer clinically and on imaging: autoimmune (IgG4) pancreatitis and paraduodenal pancreatitis. This latter lesion has been described under various denominations, especially in most early reports by using the term “cystic dystrophy developed in heterotopic pancreas”. Most cases present in young alcoholic males as cystic and inflammatory mass forming lesions centred in the duodenum and the juxtaduodenal pancreatic tissue, predominating in the region of the minor papilla. They may be associated with chronic calcifying pancreatitis. Pathogenetically, key factors are alcohol and anatomical or functional obstruction of the papilla minor.     

IgG4-positive plasma cell infiltration in the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis typically produces an enlarged pancreas with narrowing of the pancreatic duct, and can mimic carcinoma. Autoimmune pancreatitis usually responds to corticosteroid treatment, making it important to differentiate from pancreatic ductal adenocarcinoma. Affected patients often have an elevated serum IgG4. It has been proposed that increased numbers of IgG4-positive plasma cells in tissue might be a marker for the condition. We investigated the role of IgG4 staining in the diagnosis of autoimmune pancreatitis, first in resected pancreas specimens (29 autoimmune pancreatitis, nine chronic alcoholic pancreatitis and 25 pancreatic cancer), then in pancreatic needle biopsies. Immunohistochemical stains for IgG4 were scored as none, mild, moderate or marked, according to published criteria. Moderate to marked numbers of IgG4-positive plasma cells were seen in 21/29 autoimmune pancreatitis patients, and were distributed in and around ducts, in interlobular fibrous tissue and in peripancreatic fat. In contrast, eight of nine examples of chronic alcoholic pancreatitis and 22/25 ductal adenocarcinomas had scores of none or mild. When we subdivided autoimmune pancreatitis into the histologic subtypes lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-destructive pancreatitis, 16/17 lymphoplasmacytic sclerosing pancreatitis had moderate to marked staining, compared to five to 12 idiopathic duct-destructive pancreatitis. Needle biopsies from nine patients suspected of having autoimmune pancreatitis had increased numbers of IgG4 cells. We conclude that pancreatic tissue from patients with autoimmune pancreatitis often shows moderate or marked infiltration by IgG4-positive plasma cells (>10/HPF). This is particularly so in the subtype we have designated lymphoplasmacytic sclerosing pancreatitis. We rarely see IgG4 staining in patients with chronic alcoholic pancreatitis and pancreatic ductal adenocarcinoma. IgG4-positive plasma cells are a useful marker for the tissue diagnosis of autoimmune pancreatitis.     

Histopathologic and immunohistochemical studies on the mechanism of interlobular fibrosis of the pancreas

OBJECTIVE: To elucidate the mechanism of interlobular fibrosis of the pancreas, which is categorized as chronic alcoholic pancreatitis. METHODS: Forty pancreatic tissue samples from patients with ampullary carcinomas, which cause various degrees of stricture of the main pancreatic duct, and 20 patients with chronic alcoholic pancreatitis were studied histopathologically and immunohistochemically. RESULTS: Fibrosis was observed in 23 of 40 patients with ampullary carcinomas and was classified into 3 categories: mild changes (10 cases), moderate changes (9 cases), and marked changes (4 cases). In the mild change cases, mild fibrosis was diffusely distributed in the interlobular areas, with scant immunoreactivity of anti-alpha-smooth muscle actin (alpha-SMA) and an expansive lobular appearance, whereas moderate and marked change cases showed interlobular and intralobular fibrosis with marked anti-alpha-SMA immunoreactivity and lobular atrophy. By quantitative analysis, the mild change cases showed both higher MIB1-positive and lower apoptotic acinar cell ratios than those of moderate and marked changes. Anti-alpha-SMA immunoreactivity in the patients with chronic alcoholic pancreatitis was found in interlobular fibrosis. Hence, mild changes in cases of ampullary carcinomas had histologic findings similar to chronic alcoholic pancreatitis, except for excessive fibrosis cases with patchy distribution. CONCLUSION: Incomplete obstruction of the main pancreatic duct caused the beginning of interlobular fibrosis, which is categorized as chronic alcoholic pancreatitis.     

Lack of specificity of monoclonal antibody B72.3 in distinguishing chronic pancreatitis from pancreatic adenocarcinoma.

Making the morphologic distinction between chronic pancreatitis and pancreatic adenocarcinoma is a diagnostic challenge in small biopsy specimens and fine-needle aspiration samples. It has been suggested that immunohistochemical evaluation for the tumor-associated glycoprotein-72 antigen recognized by the monoclonal antibody B72.3 may be helpful in this setting. Formalin-fixed, routinely processed, paraffin-embedded tissue from 29 known cases of chronic pancreatitis and 31 cases of pancreatic adenocarcinoma were evaluated for reactivity with monoclonal antibody B72.3 using a standard avidin-biotin complex technique. Positive staining was seen in 26 of 31 adenocarcinomas (84%) and in 6 of 29 cases (21%) of chronic pancreatitis. Although monoclonal antibody B72.3 is more commonly reactive with pancreatic adenocarcinoma than with chronic pancreatitis, too many cases of chronic pancreatitis are reactive with this antibody for it to be useful as a diagnostic adjunct.     

慢性胰腺炎CT影像解剖学分型及其临床意义

目的 根据慢性胰腺炎CT表现的不同,探讨慢性胰腺炎的CT影像解剖学分型及分型的意义.方法收集1996年1月至2009年1月入住我院经临床或手术证实的213例慢性胰腺炎患者,其中男性156例,女性57例,平均年龄为(48.0±11.5)岁;平均住院天数(18.4±9.2)d;胆系疾病68例(32%),反复发作急性胰腺炎3...     

Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis

Mesothelin, a cell surface glycoprotein present on normal mesothelial cells, has been reported to be expressed in pancreatic adenocarcinomas. We conducted this study to fully characterize mesothelin expression in surgically resected, formalin-fixed, paraffin-embedded tissue specimens of 18 pancreatic adenocarcinomas, 9 adenocarcinomas of the ampulla of Vater, 12 adenocarcinomas of the common bile duct, and 17 cases of chronic pancreatitis. Mesothelin immunostaining was performed using the antimesothelin monoclonal antibody 5B2. All 18 cases (100%) of pancreatic adenocarcinomas showed mesothelin expression, as did 8 (89%) of 9 cases of ampullar adenocarcinoma and all 12 cases (100%) of common bile duct adenocarcinoma. In all cases of pancreaticobiliary adenocarcinoma, the adjacent normal pancreas did not stain for mesothelin. Of 17 specimens of chronic pancreatitis, 16 were negative for mesothelin expression, and 1 case showed weak mesothelin staining of fewer than 5% of normal pancreatic ducts. Our results demonstrated mesothelin expression in the majority of pancreaticobiliary adenocarcinomas and no expression in normal pancreatic tissues and in chronic pancreatitis.     

Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens

Background and Aims Autoimmune pancreatitis seems to be a disease with a heterogeneous appearance. Our intention was to establish key diagnostic criteria, define grades of severity and activity, identify features of potential subtypes and evaluate the diagnostic relevance of biopsy specimens.Methods Histopathological criteria and clinical features were recorded in pancreatic resection specimens from 53 patients who were found to have chronic pancreatitis lacking pseudocysts, calculi, irregular duct dilatations, pancreas divisum and/or duodenal wall inflammation. The severity of the chronic inflammation was graded, and the activity of the acute inflammatory component and the granulocytic epithelial lesion (GEL) were determined. Additionally, pancreatic biopsy specimens from 9 patients with suspected AIP were assessed.Results Periductal lymphoplasmacytic infiltration was identified in all cases, followed in order of frequency by periductal fibrosis and venulitis. These changes were absent in 147 pancreatic specimens that showed chronic pancreatitis associated with pseudocysts, calculi, pancreas divisum and/or duodenal wall inflammation. In 90% of the cases, these chronic changes were graded as 3 or 4. In 81%, the inflammatory process resided in the head of the pancreas and involved the common bile duct. GELs were present in 42% of the patients, who had a mean age of 40.5 years, an almost equal male–female ratio and a high coincidence of ulcerative colitis or Crohns disease. Patients without GELs were older (mean age 64 years), showed a male preponderance, commonly had Sjögrens syndrome and often developed recurrent bile-duct stenosis. Diagnostically relevant lesions were present in two of five wedge biopsy specimens and three of four fine-needle specimens.Conclusions Periductal lymphoplasmacytic infiltration and fibrosis, preferential occurrence in the pancreatic head and venulitis characterize autoimmune pancreatitis. GELs predominantly occur in a subset of patients who are younger, more commonly have ulcerative colitis and Crohns disease and seem to have fewer recurrences than patients without GELs. Pancreatic biopsy material proved to be a very helpful adjunct for establishing the diagnosis.     

Pancreatic PP cell distribution and hyperplasia

Summary The endocrine pancreatic tissue from 13 patients with severe chronic pancreatitis, 5 patients with pancreatic duct carcinoma and 4 non-diseased pancreases was analysed by immunocytochemistry and morphometry. The controls revealed two distinct islet types with different regional distribution. The lower dorsal part of the pancreatic head contained islets with irregular outlines and a high number of PP cells (PP-cells 60.4±4.1%; B-cells 29.4±4.6%; A-cells 7.4±1.5%; D-cells 2.8±0.6%). The other parts of the pancreas contained compact islets with only a few PP cells (PP-cells 1.0±0.4%; B-cells 69.3±3.0%; A-cells 24.1±2.1%; D-cells 5.8±0.5%). In chronic pancreatitis the sclerotic tissue of the body and the tail region contained compact islets with altered cell inter-relationships when compared with controls. While the number of B-cells was diminished (48.5%), A and PP cells appeared to be increased in number (42.7 and 4.1%, respectively). Furthermore, ductulo-insular proliferations were conspicuous (nesidioblastosis) with budding-off of small endocrine cell clusters made up predominantly of A and PP cells. In 3 patients with pancreatic carcinoma increased numbers of PP cells and of A cells were found along the advancing edge of the carcinoma.The data emphasize the necessity of taking into consideration regional PP cell distribution in each case in which an increase of PP cells is observed. True hyperplasia is found in chronic pancreatitis and, focally, in some cases with pancreatic carcinoma.     

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma.

The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.     

Fine-needle aspiration biopsy of the pancreas: a study of 61 cases

Eighty-six fine-needle aspirates (FNAs) of pancreas from 74 patients were reviewed. Histological confirmation or clinical follow-up of the final diagnosis was available in 61 aspirates from 49 patients. Of 42 proven malignant cases, FNAs were diagnosed as positive in 21 (50%), suspicious in 4 (9.5%), negative in 12 (28.6%), and unsatisfactory in 5 (11.9%). Of 19 proven benign cases, FNAs were diagnosed as negative in 15 (78.9%) and unsatisfactory in 4 (21%). This resulted in a 50% sensitivity, a 100% specificity, a diagnostic efficiency of 59%, a predictive value of a positive test of 100%, and a predictive value of a negative test of 55.6%. Thirty-six primary pancreatic adenocarcinomas and six metastatic tumors to the pancreas were encountered. Benign cases were attributed to anatomical pancreatic variants, acute pancreatitis, abscess, chronic pancreatitis, and pseudocysts. Pancreatic FNA was safe, accurate, and relatively inexpensive, but it was relatively insensitive in the diagnosis of malignancy.     

Lymphoplasmacytic sclerosing (autoimmune) pancreatitis

Lymphoplasmacytic sclerosing pancreatitis (LPSP), also known as autoimmune pancreatitis or nonalcoholic, duct destructive chronic pancreatitis, has been increasingly recognized in the past decade as a histologically distinctive type of pancreatitis that affects middle-aged patients who lack the typical risk factors for chronic pancreatitis (alcohol abuse in particular). LPSP is sometimes associated with other autoimmune diseases or fibroinflammatory lesions, although in some patients, pancreatic and biliary involvement represent the only known disease process. Many patients present with pancreatic masses clinically and radiographically simulating pancreatic carcinoma, and associated bile duct strictures enhance the resemblance. Elevated serum IgG4 levels have been described in patients with LPSP and have been used to distinguish LPSP from pancreatic carcinoma preoperatively. Although there is some heterogeneity of pathologic findings, resected cases of LPSP typically demonstrate dense periductal lymphoplasmacytic inflammation, periductal and parenchymal fibrosis, and obliterative venulitis; neutrophilic infiltration of the ductal epithelium ("granulocytic epithelial lesions") may also occur. Large tumor-like masses of fibroinflammatory tissue ("reactive fibroinflammatory pseudotumors") may develop and extend beyond the pancreas. Following surgical resection, a few patients suffer recurrence of fibroinflammatory lesions in the pancreatobiliary tree, or they may develop other manifestations of autoimmune disease elsewhere in the body. However, the overall prognosis is excellent. Response to steroid therapy has been noted. Current studies are focusing on identifying additional preoperative diagnostic tests and on characterizing possible variants of LPSP. This review presents the defining clinical and pathologic features of LPSP and discusses the ongoing efforts to understand the pathogenesis of this disease.     

Morphofunctional characteristics of arterial bed in exacerbation of gastroduodenal ulcer disease and chronic pancreatitis

Samples of the stomach, duodenum and pancreas removed from 76 patients obtained during organ-preserving operations for ulcer and chronic pancreatitis were examined morphologically. It is found that the most frequent type of changes in the intraorgan arteries is their wall hypertrophy in combination with hyperelastosis and elastotic fibrosis. This characterizes chronic local arterial hypertension. An additional morphological symptom complex caused by a vegetative vascular crisis is formed in the arteries of the damaged organ in exacerbation of the disease. The complex includes prominent dystonic and alterative changes of small arteries leading to stasis and thrombogenesis in the microvessels. Unknown so far phenomenon of arterial invagination in 18 patients was observed. It leads to a complete block of circulation, acute ischemia followed by tissue necrosis which was most typical for ulcer exacerbation and chronic pancreatitis.     

Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray based study.

Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 + to 3 + based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2 +) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.     

Papillomatosis of the opening of the major duodenal papilla in chronic, recurrent pancreatitis (based on surgical biopsy data)]

Examinations of 55 major duodenal papillas (MDP) amputated in patients with chronic relapsing pancreatitis revealed papillomatosis of the opening zone in 20 (36%). Papillomatosis developed when the pancreating and bile ducts discharged into the duodenum separately at the top of MDP without forming an ampoule. Papillomatosis was manifested by fibrous-epithelial papillar hyperplastic outgrowths representing pathologically altered folds of the MDP mucous membrane. The features of changes in papillary outgrowths were shown to include circulatory disorders, lympho-plasmocytic infiltration of the stroma, adenomatosis, etc. The causes of papillomatosis development and its association with chronic relapsing pancreatitis are discussed.     

Fibrogenesis in alcoholic chronic pancreatitis: the role of tissue necrosis, macrophages, myofibroblasts and cytokines.

Myofibroblasts and cytokines such as transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF)-B have been found to play an important role in pancreatitis-associated fibrogenesis. It is still unclear, however, where in the inflamed pancreas and when these fibrogenic cells and cytokines can be detected. In this study we examined pancreatic tissue from patients with alcoholic chronic pancreatitis to determine the localization and distribution of myofibroblasts and the expression of cytokines in relation to the tissue damage and the activity of the inflammatory process. In tissue from pancreatic specimens from 59 patients with alcoholic chronic pancreatitis the inflammatory process was histologically staged. Myofibroblasts and the cytokines latency-associated peptide, a TGF-beta propeptide, TGF-beta receptor II, PDGF-B and the alpha-isoform of the PDGF receptor were immunohistochemically identified in 10 selected cases representing the four defined stages of alcoholic chronic pancreatitis. In stage I, the stage with overt tissue injury, myofibroblasts were numerous and especially associated with macrophages around areas of necrosis. In stage II, the stage with cellular fibrosis, myofibroblasts were the main component of the interlobular tissue. In stage III, the stage with dense fibrosis, myofibroblasts were rare, and in stage IV, when calculi were present, myofibroblasts were only detected adjacent to duct ulcerations caused by calculi. Latency-associated peptide and TGF-beta receptor II as well as PDGF-B and PDGF receptor-alpha were mainly expressed by macrophages, myofibroblasts and epithelial cells in stages I and II. The results suggest that the fibrogenic process in alcoholic chronic pancreatitis is initiated by a cytokine-based interplay of macrophages and myofibroblasts that follows tissue injury.     

Non-alcoholic duct destructive chronic pancreatitis: a histological, immunohistochemical and in-situ apoptosis study of 18 cases

AIMS: To assess retrospectively pancreatic changes in non-alcoholic duct-destructive chronic pancreatitis and to investigate the role of apoptosis in duct destruction. METHODS AND RESULTS: Eighteen patients (mean age 46 years, nine women and nine men) underwent pancreatic resection for suspected pancreatic tumour and were diagnosed as having non-alcoholic duct-destructive chronic pancreatitis. We performed a morphological study either semiquantitatively (fibrosis and inflammation) or quantitatively (CD3+ intraepithelial lymphocytes, M30 and TUNEL+ apoptotic cells). The results were compared with those obtained in 10 cases of chronic alcoholic pancreatitis and nine cases of chronic obstructive pancreatitis. Pancreatic changes were diffuse and heterogeneous in 14 cases, but segmental in four cases. The main pancreatic lesions were ductal epithelial alteration, periductal inflammation and fibrosis. There were no cysts or calcifications. We found a marked increase in mast cells in the infiltrate, a slight increase in TiA1+ lymphocytes and in intraepithelial lymphocytes compared with other types of chronic pancreatitis. No significant increase in ductal apoptosis was observed. CONCLUSION: Non-alcoholic duct-destructive chronic pancreatitis is a well-defined pathological entity, distinct from alcoholic and obstructive chronic pancreatitis. Our results indicate that apoptosis probably does not play a major role in ductal alterations.