The pancreas in cystic fibrosis: chemical composition and comparative morphology

Sections of pancreas from 16 individuals who died with cystic fibrosis (CF) were classified by morphometric criteria into four categories in increasing order of pancreatic involvement. The concentration of acini, islets, main ducts, lobular ducts, connective tissue, and fat was compared with control levels. The results show that in the least involved pancreases, from neonates who died under 5 months of age, acini were reduced to 33% of control levels and the following were increased: islets, to 410%, lobular ducts, to 250%; and main ducts, to 1700% of controls. With increasing severity of the pancreatic disease the acini were further reduced to 5% and lobular ducts to 37% of control levels, respectively. Main ducts increased by 19-fold, and fatty infiltration accounted for more than 25% of the fresh weight of the pancreas in 9 of the 16 specimens. Comparative biochemical studies of 35 fibrocystic pancreases were quantitatively related to the severity of the pancreatic involvement as follows. Water and volatile matter, normally accounting for 80 +/-% of the weight of the fresh pancreas, was reduced to less than 30% in the most affected organs. The concentration of zinc diminished from near normal mean levels of 193 mugZn/g dry pancreas to 10% of this amount in the severely involved pancreas. Elevated concentrations of calcium, amounting to over 10 times control level, were found in obstructed ductal structures. Calcium was depleted from pancreatic sections adjacent to the obstructions. The following biochemical indicators were significantly different in their mean levels in the 35 fibrocystic pancreases when compared with the 17 controls: (P less than or equal to 0.001) fat, water, zinc, calcium, copper, magnesium, potassium, and sodium (P less than or equal to 0.01).     

Intraperitoneal transplantation of isolated hepatocytes of the pig: the implantable bioartificial liver]

To elucidate the histopathological features of pancreatic ischemia, we examined postmortem pancreases in which cholesterol emboli were present. Cholesterol emboli were detected in 17 pancreases (6 of 36 cases of aortic aneurysm and 11 of 223 control cases). Two of the 17 pancreases had well-demarcated patchy lesions composed of degenerating acinar cells showing deeply eosinophilic cytoplasm and pyknotic nuclei, indicating fresh ischemia. In the marginal zone of the larger lesions and in the small lesions, the intralobular ductules had avoided the ischemic changes. Five of the 17 pancreases had patchy fibrotic foci containing small ductules with slightly retraction features. These ductules are considered to be the remnant intralobular ductules that have avoided the previous ischemic damage. We conclude that these patchy fibrotic foci are the healed ischemic lesions. The current findings suggest that the healed ischemic lesions can be differentiated from common pancreatic fibrosis. The existence of remnant intralobular ductules and the patchy retraction features may be useful histological markers for the determination of healed ischemic lesions.     

An outbreak of Candida parapsilosis prosthetic valve endocarditis

The histologic features of normal and hyperplastic epithelia of the extra-glandular excretory ducts of human minor salivary glands were studied, and their pathologic significance evaluated. Normal duct epithelium consisted of two layers: inner columnar cells, and basal cubical or squamous cells. A few goblet cells were present among the inner cells. Hyperplasia of the duct epithelia occurred focally or entirely, and was classified into the following histologic types: (1) simple hyperplasia, and (2) metaplastic hyperplasia, which were divided into (a) mucous cell hyperplasia, (b) oncocytic hyperplasia and (c) squamous cell hyperplasia. Squamous cell hyperplasia was subdivided into (i) acanthotic type and (ii) reserve cell-like type with or without dysplasia. Simple or metaplastic epithelial hyperplasia of the extra-glandular excretory ducts of minor salivary glands may be induced by chronic inflammation or other types of irritation, and proliferating cells of such regenerating tissue sometimes exhibit features reminiscent of a neoplastic process. Furthermore, it is suggested that metaplastic epithelial hyperplasia of the excretory minor salivary gland ducts could be the site of origin of tumor development, i.e., some oral squamous cell carcinomas may arise from primary lesions in the hyperplastic epithelium of the extraglandular excretory minor salivary gland ducts.     

Occlusion of the pancreatic ducts with "Ethibloc" injections. Experimental study in the dog

"Ethibloc" is a zeine-alcohol suspension which polymerizes in an aqueous medium after approximately 15 minutes. The product was injected in the pancreatic duct of 20 dogs. The procedure was free from complications, apart from the development of edematous pancreatitis without clinical manifestations. Healthy pancreases were transformed into fibrous organs within ten days or so, as is found in advanced stages of chronic pancreatitis. No effect occurred on the islets of Langerhans and a diabetes of the experimental type did'nt develop. "Ethibloc" would therefore appear to be of value in humans for the treatment of chronic pancreatitis, in order to reduce the period for transformation of the lesions without increasing the incidence of complications, and also for pancreatic fistulae of various origins, as a result of the rapid sclerosis of exocrine tissue that it provokes.     

Effect of granulocyte colony-stimulating factor on the course of infection with gram-positive bacteria in mice during granulocytopenia induced by sublethal irradiation or cyclophosphamide

Ligation of the common bile-pancreatic duct induces hyperamylasemia and acute pancreatitis in rats. Pancreatic morphologic changes include edema, acinar cell damage, and mild inflammation. The pathogenesis of acute pancreatitis in this model is not understood, but may involve altered secretion and intrapancreatic activation of acinar proteases. We hypothesized that trypsinogen activation, measured by the production of plasma and pancreatic trypsinogen activation peptides (TAP), occurs early in this model. We performed the following experiments: rats were prepared with (1) bile-pancreatic ducts ligated and (2) ducts dissected but not ligated (sham). Rats were killed after 6, 24, and 48 hr. Serum amylase was measured and histologic sections were analyzed for morphologic changes. TAP was measured in both serum and pancreatic tissue homogenates using a specific polyclonal. anti-TAP antibody in an enzyme-linked immunosorbant assay. After 6, 24, and 48 hr of bile-pancreatic duct ligation, hyperamylasemia and acute morphologic changes of acute pancreatitis were observed. Evidence of acinar cell destruction was not evident until 48 hr after ligation. Levels of serum and pancreatic tissue TAP were significantly elevated at both 24 and 48 hr after ligation compared to those of sham. We conclude that increased intrapancreatic trypsinogen activation occurs early in this form of experimental acute pancreatitis and that it occurs prior to evidence of acinar cell destruction. These data and observations support the possibility that intrapancreatic protease activation contributes to the pathogenesis of ligation-induced acute pancreatitis.     

Fatal chronic oxalosis after sublethal ethylene glycol poisoning

Aberrant crypt foci (ACF) have been identified in the methylene-blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty-four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5-10 min. The strips were measured, put on a glass slide and observed under a light microscope at x25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty-four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.     

Compliance with supportive periodontal therapy

CONCLUSIONS: Bronchobiliary fistula is an in frequent manifestation of common bile duct obstruction. The slowly progressive narrowing of the common duct by the fibrosis of chronic pancreatitis is an even more rare mechanism of such fistula formation with only two cases having been reported previously. A third case of bronchobiliary fistula caused by chronic pancreatitis is presented and its successful management is discussed. BACKGROUND: A 54-yr-old male with known chronic pancreatitis presented with a cough productive of copious amounts of bile and with pulmonary infiltrates. METHODS: Diagnosis of bronchobiliary fistula was made based on HIDA scan and confirmed by operative cholangiogram. RESULTS: Successful correction of this fistula was accomplished by operative closure of the fistulous tract and diversion of the narrowed bile duct by hepaticojejunal bypass.     

Two-color analysis of peripheral lymphocyte surface antigens in inherently healthy adults

We examined the efficacy of relatively low temperature collagenase digestion at 20 degrees C on the yield and viability of islets after long-term cold preservation. Wistar rat pancreases were distended with University of Wisconsin solution via a pancreatic duct at the time of harvesting to which collagenase and 2.5 mM calcium chloride were added. The pancreases were cold-preserved at 4 degrees C for 24 or 48 hr. After storage, they were incubated for collagenase digestion at 37 degrees C or 20 degrees C for various incubation periods to obtain the peak yield. At 20 degrees C, in vitro collagenase activity measured by the FALGPA method was one fourth of that at 37 degrees C, and pancreases were well digested with a prolonged digestion period (60-90 min vs. 15-20 min for the 37 degrees C group). In vitro insulin secretion of islets isolated from freshly removed pancreases was maintained at 20 degrees C for 120 min in University of Wisconsin solution as compared with 30 min at 37 degrees C. Therefore, the preserved pancreases used in this study were incubated either at 37 degrees C or 20 degrees C at various times in order to obtain peak islet yields. The islet yields from 24-hr cold-preserved pancreases at 37 degrees C and 20 degrees C digestion were 573 +/- 59/rat (n = 6) and 497 +/- 84/rat (n = 11), respectively, and those from 48-hr cold-preserved pancreases were 395 +/- 113/rat (n = 6) and 414 +/- 75/rat (n = 6), respectively. The yields from 24- and 48-hr cold-preserved pancreases were significantly low compared with 635 +/- 52/rat for fresh pancreases (n = 15), but there was no significant difference between the 2 methods. The viability of the isolated islets, which was examined by transplantation to streptozotocin-induced diabetic C57BL/6 mice, showed a significant difference in the capacity to ameliorate diabetes. The functional success rate of islet transplantation after 24-hr cold preservation was equally good (8/8 for 37 degrees C group vs. 9/10 for 20 degrees C group), but the rate for those from 48-hr cold-preserved pancreases was significantly better with digestion at 20 degrees C than at 37 degrees C (1/8 for 37 degrees C group vs. 7/8 for 20 degrees C group, P < 0.05). We concluded that viable islets can be isolated from 48-hr cold-preserved pancreases with the low temperature collagenase digestion method, which shows promise as a modality for successful clinical islet transplantation.     

Characterization of apomucin expression in intrahepatic cholangiocarcinomas and their precursor lesions: an immunohistochemical study

To date, seven apomucins have been characterized and their expression in malignant and premalignant lesions is under evaluation. In this study, we examined the expression of MUC1, MUC2, MUC3, and MUC5/6 apomucins in cholangiocarcinoma (CC) and biliary epithelial dysplasia. We used 14 liver samples from patients with hepatolithiasis and CC, 11 with hepatolithiasis showing biliary epithelial dysplasia, 31 with CC alone (19 hilar, 10 peripheral, and 2 unclassifiable), and 14 with combined hepatocellular-cholangiocellular carcinoma (HC-CC) and immunohistochemically characterized the expression profiles of apomucins. Nondysplastic biliary epithelial cells in the intrahepatic large bile ducts constantly expressed MUC3 apomucin. MUC5/6 and MUC3 apomucin expression was widespread in dysplastic biliary epithelial cells in hepatolithiasis, although the latter was reduced or absent in dysplastic foci. CC extensively expressed MUC1 apomucin and focally expressed MUC2 apomucin. In addition, CC of the hilar type, including those with hepatolithiasis, frequently expressed MUC3 apomucin (68% and 57%, respectively), whereas those of the peripheral type infrequently expressed MUC3 apomucin (10%) (P < .01). MUC5/6 apomucin was more frequently expressed in well-differentiated (89%), compared with poorly differentiated CC (42%) (P < .01). Cholangiocellular elements of combined HC-CC frequently expressed MUC1 apomucin, although they rarely expressed MUC2 and MUC3 apomucin and infrequently expressed MUC5/6 apomucin. The frequent and aberrant expression of "gastric type" MUC5/6 apomucin in biliary epithelial dysplasia, as well as in CC, suggests that biliary epithelial cells gain a gastric apomucin phenotype during carcinogenesis. MUC3 apomucin expression in CC is a marker that suggests that CC arises in the intrahepatic large bile ducts.     

Basic principles of surgical policy in complicated chronic pancreatitis

The paper presents some experience with surgical treatment of 183 patients with complicated forms of chronic pancreatitis. The type of a surgical intervention depended on the pattern of pancreatic morphological changes. Operations of internal drainage of the pancreas in 103 patients with ductal hypertension provide the largest percentage (92.4%) of good and satisfactory results. Resectional methods of surgical treatment for chronic pancreatitis (n = 36) without signs of intraductal hypertension and with the prevalence of predominant lesions in some portions of the gland yield 80% good and satisfactory results. The incidence of postoperative complications following pancreatic resections is higher than those after drainages (16.2 versus 11.6%). The paper gives a concept of combined operations on the pancreas and bile ducts in chronic pancreatitis complicated by stricture of the distal common bile duct, revealed in 24.4% of cases.     

Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma

To understand the molecular pathways involved in the pathogenesis of squamous cell lung carcinoma, we obtained DNA from 94 microdissected foci from 12 archival surgically resected tumors including histologically normal epithelium (n=13), preneoplastic lesions (n=54), carcinoma is situ (CIS) (n=15) and invasive tumors (n=12). We determined loss of heterozygosity (LOH) at 10 chromosomal regions (3p12, 3p14.2, 3p14.1-21.3, 3p21, 3p22-24, 3p25, 5q22, 9p21, 13q14 RB, and 17p13 TP53) frequently deleted in lung cancer, using 31 polymorphic microsatellite markers, including 24 that spanned the entire 3p arm. Our major findings are as follows: (1) Thirty one percent of histologically normal epithelium and 42% of mildly abnormal (hyperplasia/metaplasia) specimens had clones of cells with allelic loss at one or more regions; (2) There was a progressive increase of the overall LOH frequency within clones with increasing severity of histopathological changes; (3) The earliest and most frequent regions of allelic loss occurred at 3p21, 3p22-24, 3p25 and 9p21; (4) The size of the 3p deletions increased with progressive histologic changes; (5) TP53 allelic loss was present in many histologically advanced lesions (dysplasia and CIS); (6) Analyses of 58 normal and non-invasive foci having any molecular abnormality, indicated that 30 probably arose as independent clonal events, while 28 were potentially of the same clonal origin as the corresponding tumor; (7) Nevertheless, when the allelic losses in the 30 clonally independent lesions and their clonally unrelated tumors were compared the same parental allele was lost in 113 of 125 (90%) of comparisons. The mechanism by which this phenomenon (known as allele specific mutations) occurs is unknown; (8) Four patterns of allelic loss in clones were found. Histologically normal or mildly abnormal foci had a negative pattern (no allelic loss) or early pattern of loss while all foci of CIS and invasive tumor had an advanced pattern. However dysplasias demonstrated the entire spectrum of allelic loss patterns, and were the only histologic category having the intermediate pattern. Our findings indicate that multiple, sequentially occurring allele specific molecular changes commence in widely dispersed, apparently clonally independent foci, early in the multistage pathogenesis of squamous cell carcinomas of the lung.     

Intrahepatic bile duct injury and nodular regenerative hyperplasia of the liver in a patient with polyarteritis nodosa

Although involvement of the hepatic vasculature in patients with polyarteritis nodosa is not unusual, biliary manifestations are very rare. We describe a patient with polyarteritis nodosa presenting with a febrile cholestatic anicteric syndrome. Histological examination of the liver revealed necrotizing arteritis of small hepatic arteries associated with significant lesions of intrahepatic bile ducts of the sclerosing cholangitis type, i.e. fibrous collar around the ducts, periductal inflammation and ductal proliferation. Concomitant nodular regenerative hyperplasia was found, a condition which has rarely been described in association with polyarteritis nodosa. We think that hepatic arteritis compromising arterial blood flow to the liver was responsible for the most likely ischemic nature of the bile duct injury and the nodular regenerative hyperplasia seen in our patient.     

Transduodenal sphincteroplasty and transampullary septectomy for papillary stenosis

Twenty patients received transduodenal sphincteroplasty and transampullary septectomy between 1987 and 1993. Seven patients had post-cholecystectomy pain which was much improved or abolished in 5 of 7 patients at a mean follow-up of 4 years and 5 months. Four of five patients with chronic pancreatitis were improved at 3 years and 2 months. Three of five patients with recurrent acute pancreatitis were improved at 4 years and 5 months. One of three patients with chronic abdominal pain of hepatobiliary origin was improved at 3 years. Transduodenal sphincteroplasty and transampullary septectomy can relieve pain in patients with post-cholecystectomy pain, recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain of hepatobiliary origin, presumably by improving drainage of the obstructed ducts.     

Chronic pancreatitis: a cause of cholestasis

The bile ducts were visualised using endoscopic retrograde cholangiopancreatography (ERCP), percutaneous or intravenous cholangiography in 38 patients with non-gallstone chronic pancreatitis. Stenosis of the intrapancreatic portion of the distal common bile duct was demonstrated in 11 patients. Ten of the 11 developed transient cholestasis during exacerbations of their chronic pancreatitis. In six cholestasis eventually persisted requiring surgical relief. Secondary biliary cirrhosis was present in one patient. No evidence of pancreatic carcinoma was found in the patients explored surgically. Ten of the patients are alive more than one year after diagnosis. Chronic pancreatitis was of alcoholic aetiology in 10 of the patients with biliary stenosis. Cholestasis and biliary stricture are common but poorly recognised complications of non-gallstone chronic pancreatitis, especially when pancreatitis is severe and due to alcohol.     

Evaluation of axis alignment system for correction of myopic astigmatism with the excimer laser

BACKGROUND: Anomalous pancreaticobiliary junction (APBJ) without congenital choledochal cyst (CCC) carries a high risk of gallbladder carcinoma development. The aim of this study was to obtain information allowing early diagnosis and appropriate management. METHODS: The clinical features, imaging findings and surgical outcome of 18 patients with APBJ without CCC were analysed retrospectively. RESULTS: Fourteen patients had symptoms, including those of acute pancreatitis (five patients). In 16 patients the gallbladder showed abnormalities, including carcinoma (eight) and mucosal hyperplasia (11). Ultrasonography detected gallbladder carcinoma with 100 per cent sensitivity and mucosal hyperplasia with 91 per cent sensitivity. A long common channel was demonstrated by endoscopic retrograde cholangiopancreatography (ERCP) in all patients, endoscopic ultrasonography in nine of ten, and magnetic resonance cholangiopancreatography (MRCP) in five of five. Five of eight patients with gallbladder carcinoma underwent extended cholecystectomy with bile duct excision. Three patients with cancer and eight with no cancer had cholecystectomy alone. None developed bile duct carcinoma or acute pancreatitis after operation. All patients without malignancy remained asymptomatic for a mean follow-up period of 4.7 years. CONCLUSION: Prophylactic cholecystectomy is recommended for patients with APBJ without CCC. For early diagnosis of APBJ, gallbladder abnormalities on ultrasonography or acute pancreatitis of unknown aetiology should prompt further investigation with ERCP or less invasive imaging modalities such as endoscopic ultrasonography and MRCP.     

Diagnosis of mucin-producing tumor of the pancreas by balloon-catheter endoscopic retrograde pancreatography--compression study

The procedure of choice for the treatment of mucin-producing pancreatic tumor (MPPT) remains controversial, since it includes not only malignant but also benign lesions. The purpose of the present study was to characterize 53 consecutive cases of MPPT and to elucidate the characteristics of benign or malignant MPPT according to the findings of an improved method of endoscopic retrograde pancreatography (ERP), namely balloon-catheter ERP-compression study (balloon ERP-CS), as well as endoscopic ultrasonography (EUS), in comparison with a histological examination. There were 37 male and 16 female cases with a median age of 63+/-11 (mean+/-SD). The balloon ERP-CS was performed in all cases, and the obtained pancreatograms were classified into two types: Main Duct type and Branch Duct type. The latter was further divided into subtypes A and B. The Branch Duct A type showed only cystic dilatation of the branch duct. If the main pancreatic duct downstream to a cyst showed more than a 5 mm dilatation, this was classified as a Branch Duct B type. Seventeen out of 19 Main duct types (89%) were histologically diagnosed as neoplasms including 13 lesions of cancer and 4 of adenoma. All the Branch Duct A type cases were diagnosed as hyperplasias. 23 Branch Duct B type cases contained 7 cancers, 8 adenomas, and 8 hyperplasias. In the Main Duct type, benign or malignant, the diagnostic ability of balloon ERP-CS was calculated as sensitivity 100%, specificity 40%, and accuracy 84%; in the Branch Duct type, sensitivity 73%, specificity 86%, and accuracy 82%. On EUS, it was found that the size of the tumor in the cyst, with respect to the maximum diameter as well as height, correlated well with the grade of malignancy. All tumors (n=35) greater than 20 mm in diameter were found to be cancerous. These findings indicate that the MPPT is highly suggestive of neoplasms when the dilatation of the main pancreatic duct is detected by balloon ERP-CS and when, in a case without dilatation of the main pancreatic duct, a nodular lesion greater than 10 mm in diameter is identified in the cyst by balloon ERP-CS as well as EUS. Our current patient management strategy for operations is as follows: Main Duct type patients and Branch Duct type patients with a nodular defect detected by balloon ERP-CS and with an elevation of more than 10 mm in EUS should have an operation. Other Branch Duct type patients without main pancreatic duct dilatation are followed up by balloon ERP-CS.     

Expression of intermediate filaments in normal and neoplastic exocrine pancreas

The intermediate filament (IF) proteins present in the normal and pathological exocrine human pancreas were studied by immunolocalization using antibodies to cytokeratins (CKs) and vimentin. Acinar cells of normal pancreas showed a presence of simple CKs 8 and 18. Duct epithelium consistently expressed CKs 7, 8, 18 and 19 whereas centroacinar cells were rather low in CK 7. A subpopulation of CK 4 cells was detected in inter-intralobular ducts. In addition, some ducts contained individual cells or groups of cells that were positive for the stratification-related CKs (CKs 4, 5, 13, 15, 16). All pancreatic ductal adenocarcinomas regularly expressed CKs 7, 8, 18, 19 and were also positive for the 34 beta E12 antibody. Cytokeratin 4 was detected in a minor population of tumor cells. Pancreatic carcinoma also contained minor amounts of stratification-related CKs in variable combinations. Mucinous cystoadenocarcinoma showed the presence of CKs 7, 8, 18, 19 and was also positive for 34 beta E12, whereas the serous microcystic tumor presented CKs 8, 18, 19 and a variable amount of CKs 4 and 7. The duct-ductular alterations of the exocrine pancreas contained a different combination and distribution of CK isoforms similar to normal pancreatic ductal system. Mucinous hypertrophy and pyloric gland metaplasia reacted with antibodies to CKs 7, 8, 18 and 19. Vimentin was focally present both in normal and neoplastic tissue. Our results indicate that pancreatic ducts are characterized by an intrinsic "biliary-pancreatic duct type" immunoprofile (CKs 7, 8, 18 and 19), in contrast to acinar cells expressing exclusively CKs 8 and 18. We also detected a subpopulation of ducts regularly expressing CK 4. Surprisingly, several stratification-related CKs were detected both in normal and neoplastic exocrine pancreas. Moreover, the differentiation phenotypes of pancreatic tumors were reminiscent of normal cellular compartments.     

Laparoscopic intracorporeal ultrasound. An alternative to cholangiography?

The purpose of this study was to compare laparoscopic intracorporeal ultrasound (LICU) examination of the biliary duct system with cholangiography for delineation of duct anatomy and determination of presence or absence of ductal calculi. Thirty-one patients had LICU examination of the extrahepatic bile ducts after exposure of the gallbladder but prior to dissection of the cystic duct. After LICU examination, cystic duct dissection and cholangiography were done. Evaluation of duct anatomy and decision for duct exploration were based on findings of both tests. All patients had successful LICU examination and 30 had successful cholangiography. Duct size as determined by LICU corresponded precisely with cholangiography. LICU provided useful anatomical information in two patients with aberrant anatomy and detected cholangiogram. LICU aids in delineation of biliary duct anatomy and accurately determines presence or absence of duct calculi.     

Histologic studies on pancreas changes, caused by experimental fractionated local roentgen irradiation

After exposition to a total dose of 8000 R delivered with 16 fractions, the pancreatic parenchymal changes in rats were investigated by the author using histological and histochemical techniques. The observations were performed from the first to the 150th day following the last fraction. During the period of acute changes (1st to 15th day), the most part of the acini is morphologically intact, many smaller or greater necrotic foci, however, are to be seen. This is partly due to the enzymes with cytolytic effects coming from the damaged smaller ducts and from glandular acini. The formation of the other part of the necrobiotic foci originates not only from direct radiation injury, but also from the capillary lesion by radiation. The injury to the wall of greater ducts induces edema, inflammations, dilatation of efferent ductules and stasis, all this leading consequently to an atrophy of the acini associated with the efferent ducts. During the period of chronical changes (50th to 150th day), the number of capillaries diminishes, the necrobiotic foci are multiplied especially in places where no capillaries are visible. This clearly emphasizes the role of the pathological reasons for capillary lesions. The regenerative phenomena occur only to a lesser extent, being confirmed to the efferent ducts. The extension of the necrotic zones together with the insignificant regeneration leads to a gradual destruction of the tissular substance. All this draws attention to the fact, that the radiation sensitivity of the organ can only be determined, if its acute and chronical changes are known.     

Diagnosis of a "hereditary pancreatitis" by the detection of a mutation in the cationic trypsinogen gene

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman was admitted with the suspected diagnosis of pancreatic carcinoma. As a child she had had repeated attacks of abdominal pain of undetermined cause. When aged 48 years she had developed diabetes mellitus. Her now 42-year-old daughter had from the age of 9 years suffered from repeated attacks of acute pancreatitis that had finally led to chronic pancreatitis. The patient's 15-year-old grandchild was having recurrent bouts of abdominal pain. INVESTIGATIONS: Imaging procedures revealed calcifications in the pancreas and an infiltrating space-occupying lesion, about 3 cm in diameter, in the head of the pancreas with lymph node and liver metastases. Cytological analysis of material aspirated from the space-occupying mass showed typical findings of ductal pancreatic carcinoma. FURTHER TESTS, TREATMENT AND COURSE: At first the patient's course was not typical for a genetically-determined disease, but the family history raised the suspicion of hereditary pancreatitis. A genetic test (Afl-III-RFLP test) demonstrated the mutation Arg 117 His in the cationic trypsinogen gene in all diseased or symptomatic family members. The patient died of the complications of the pancreatic cancer. CONCLUSION: Genetic tests are valuable in the diagnosis of hereditary pancreatitis, because the increased cancer risk can be met by frequent examinations in affected family members.