A fresh approach to the pathogenesis of pancreatitis.

McCutcheon, A. D.

doi:10.1136/gut.9.3.296

Cited by 129 publications

(31 citation statements)

References 126 publications

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“…The role of duodenal reflux in initiating acute pancreatitis has been most strongly advocated by McCutcheon (1968), and further support for this viewpoint conies from the experimental work on monkeys by Johnson and Doppman (1967). While the patients with previously constructed blind loops and with duodenal ulceration reported in this study may support such a theory it should be noted that there was also a high incidence of biliary pathology in these patients.…”

Section: Discussionmentioning

confidence: 95%

Observations on acute pancreatitis

Imrie

1974

British Journal of Surgery

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Section: Discussionmentioning

confidence: 95%

Observations on acute pancreatitis

Imrie

1974

British Journal of Surgery

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“…At least three possible mechanisms can be postulated. These include autoactivation (Colomb et al, 1979), activation by cathepsin B (Greenbaum et al, 1959) and activation by duodenal enterokinase or enteropeptidase refluxed into the pancreatic duct (McCutcheon, 1968;Hadorn et al, 1974) or absorbed into the portal circulation (Talbot et al, 1984). In addition, human pancreatic trypsinogen occurs as two variants differing slightly from one another in biochemical properties such as isoelectric point, susceptibility to inhibitors and substrate specificity (Rinderknecht & Geokas, 1973).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions

Ohta

Terada²,

Nagakawa³

et al. 1994

Br J Cancer

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Summary Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. Fifteen of 20 invasive tubular adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular pattern located in the supranuclear cytoplasm of the carcinoma cells. In addition, metastatic lesions, including those in peripancreatic lymph nodes and neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal (noninvasive) papillary adenocarcinomas did not express pancreatic trypsinogen. Cathepsin B expression was recognised in 14 of 20 invasive tubular adenocarcinomas (70%) in a fine granular pattern located diffusely in the cytoplasm of the carcinoma cells, while none of the three intraductal papillary adenocarcinomas had detectable cathepsin B. These findings suggest that pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and cathepsin B immunoreactive peptides, raising the possibility that pancreatic trypsinogen and cathepsin B may act independently of each other in the process of carcinoma invasion and metastasis, like other different classes of proteases involved in the proteolytic modification of the matrix barrier.Pancreatic trypsinogen is one of the proteolytic enzymes produced by pancreatic acinar cells. A recent study (Miszczuk-Jamska et al., 1991) has shown that a new human pancreatic adenocarcinoma cell line (CFPAC-1) and a previously established human pancreatic carcinoma cell line (CAPAN-1) produce human pancreatic trypsinogen. This enzyme is a target protease for pancreatic secretory trypsin inhibitor (PSTI). Tumour-associated trypsinogen is also known to be a serine protease produced by malignant tumour cells, and is believed to play an essential role in cancer invasion and metastasis by degrading trypsin-sensitive extracellular matrix components (Tryggvason et al., 1987;Koivunen et al., 1991a). Tumour-associated trypsinogen has been identified as a target protease for a tumour-associated trypsin inhibitor (TATI), also referred to as PSTI (Huhtala et al., 1982;Halila et al., 1988;Stenman et al., 1988). A recent study (Koivunen et al., 1989) has shown that tumourassociated trypsinogen and pancreatic trypsinogen are similar with respect to amino-terminal sequence, molecular weight and immunoreactivity, but that significant differences exist with respect to isoelectrophoretic mobility and stability. Therefore, it is possible that pancreatic trypsinogen may also take part in the protease cascade associated with tumour invasion and metastasis. It is currently not known whether the differences between tumour-associated trypsinogen and pancreatic trypsinogen are a result of tissue-specific trypsinogen modification or distinct genes.We have therefore evaluated the presence or absence of pancreatic trypsinogen immunohistochemically in 23 surgically resected pancreatic ductal adeno...

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“…This situation arose in 4 of our patients, and since the dilatation extended below the cystic duct one must postulate that a gallstone has caused obstruction and then passed through the papilla before surgery. Certainly there is strong evidence that stones passed in this way are a frequent cause of acute pancreatitis (McCutcheon, 1968). Secondly, gallstones may be present yet not be responsible for the jaundice; 4 of our patients had such a 'double pathology'.…”

Section: Discussionmentioning

confidence: 96%

The role of grey scale ultrasonography in the investigation of jaundice

McKay

Duncan

Lam

et al. 1979

British Journal of Surgery

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Sixty-seven patients were prospectively studied using grey scale ultrasound (GSU) to assess its possible role as part of a jaundice investigation programme. All scans were performed by one radiologist, without clinical information. When intrahepatic ductal dilatation was found an attempt was made to establish the level and cause of obstruction. The calibre of the intrahepatic bile ducts was correctly reported in 66 patients (98 per cent). Forty-three proved to have extrahepatic cholestasis, 24 had intrahepatic cholestasis. No patient with intrahepatic cholestasis had dilated ducts seen on ultrasound. In 43 patients with obstructive jaundice, GSU accurately detected the level of obstruction in 28. This accuracy varied with the cause of obstruction. A direct indication of diagnosis was possible in 45 of the 67 patients. In a unit specializing in the management of complicated hepatobiliary problems, GSU has been shown to be accurate in differentiating extra- from intrahepatic jaundice. Being non-invasive, it appears ideally suited for use as a screening procedure, permitting selection of appropriate invasive investigations to provide complete preoperative imaging of the biliary tree. In patients with jaundice due to gallstones, GSU may be the only imaging technique required before surgery provided good operative cholangiography is available.

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A fresh approach to the pathogenesis of pancreatitis.

Cited by 129 publications

References 126 publications

Observations on acute pancreatitis

Observations on acute pancreatitis

Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions

The role of grey scale ultrasonography in the investigation of jaundice

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