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Biomedical subjects

R C Williamson

Publications and source records attributed to R C Williamson.

At least 73 records · Page 4Linked to original sources

Effect of luminal growth factor preservation on intestinal growth.

Intestinal atrophy contributes to the clinical difficulties of patients who cannot eat normally. Atrophy is prevented by luminal food proteins but not by the equivalent aminoacids. This observation is not explained by current theories of intestinal physiology. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are secreted into the gut lumen. We speculated that these are digested by pancreatic enzymes in fasting juice, but preserved when food proteins block the active sites of these enzymes. Studies based on molecular size and bioactivity confirmed that fasting human jejunal juice destroys EGF and TGF alpha. EGF, but not TGF alpha, was preserved when the milk protein casein or an enzyme inhibitor were present; elemental diets were ineffective. Diversion of pancreatic juice to the mid point of the small intestine in rats significantly increased luminal EGF-like bioactivity and all variables of growth in the proximal enzyme-free segment. Our findings support a novel mechanism of control of intestinal growth, which has important clinical implications. The addition of enzyme-inhibiting proteins such as casein to elemental diets may preserve intestinal integrity and function.

Animals↗

Single-loop biliary and gastric bypass for irresectable pancreatic carcinoma.

Twenty-five patients with irresectable carcinoma of the pancreatic head received a modified type of palliative bypass in which the transected bile duct and the gastric antrum were anastomosed to the same Roux loop of jejunum. There were 13 women and 12 men with a median age of 54 (range 35-74) years. All but three patients were jaundiced and 11 underwent preoperative biliary decompression. In 18 patients jaundiced at the time of operation, the median preoperative serum bilirubin level was 287 (range 57-804) mumol/l. The median operative time was 4.0 (range 2.5-6.0) h. There were no hospital deaths. Minor postoperative complications occurred in nine patients and the median hospital stay after operation was 13 (range 7-49) days. The median postoperative survival was 4.8 (range 1.5-11.5) months. This operation provides good palliation safely in selected patients with irresectable pancreatic carcinoma.

Adult↗

Oral calcium inhibits rectal epithelial proliferation in familial adenomatous polyposis.

Calcium reduces colorectal cell turnover and might therefore protect against neoplasia. The inhibitory effects of dietary calcium were tested in a double-blind controlled trial in patients with familial adenomatous polyposis who had undergone previous abdominal colectomy and ileorectal anastomosis. Patients received supplemental calcium carbonate (1500 mg/day) or placebo tablets for 6 months; sigmoidoscopy was performed before and after treatment. Rectal biopsies were maintained in short-term organ culture, and crypt cell production rate (CCPR) was measured stathmokinetically. A total of 25 patients completed the trial; polyp counts were obtained before and after treatment in all and CCPR values in 16. Calcium treatment reduced the mean (s.e.m.) CCPR from 4.72 (0.48) to 2.42 (0.48) cells per crypt per h (P < 0.05), while values for placebo were unchanged (5.46 (1.21) versus 5.08 (1.17) cells per crypt per h). Calcium had no demonstrable effect on the number, size or distribution of rectal polyps. The ability of oral calcium supplementation to suppress rectal epithelial proliferation supports its potential to prevent development of colorectal carcinoma in high-risk individuals.

Adenomatous Polyposis Coli↗

Modern management of pancreatic pseudocysts.

Pseudocysts may develop as a complication of acute pancreatitis, chronic pancreatitis or pancreatic trauma. As new methods of imaging provide fuller information on their incidence and natural history, important differences are emerging between the pseudocysts of acute and chronic pancreatitis. Traditional surgical approaches to the management of pseudocyst are now being challenged by endoscopic techniques and interventional radiology. In the light of these developments the options available are reviewed and strategies for the modern management of pancreatic pseudocysts are suggested.

Adolescent↗

Management of non-functioning neuroendocrine tumours of the pancreas.

Between 1982 and 1991, 20 patients of median age 44 (range 22-76) years were treated for non-functioning neuroendocrine tumours of the pancreas. Presenting features were obstructive jaundice (seven patients), abdominal pain (seven), weight loss (six), abdominal mass (eight) and severe haemorrhage (four). Gut hormone profiles were normal except for one patient who had a raised pancreatic polypeptide level. Contrast-enhanced computed tomography localized the tumour in 17 patients and visceral angiography in 14 of 15; all but three tumours were highly vascular. Ten patients underwent curative resection, and the remainder were managed palliatively by resection (four), bypass procedures (three) or biopsy alone (three). There were two postoperative deaths and seven early complications. Seven of the remaining 18 patients have died from disease a median of 16 (range 4-30) months after presentation. The 11 survivors, eight of whom had curative resections, have been followed for a median of 42 (range 7-72) months. Ten patients are asymptomatic but only five are free from disease. These tumours are seldom curable by radical surgery, but patients may remain free from symptoms for many years.

Adenoma, Islet Cell↗

Non-Hodgkin's lymphoma presenting with jaundice and hypercalcaemia.

A patient is reported with B-cell lymphoma (centroblastic high grade non-Hodgkin's) with pancreatic involvement, who presented with jaundice and hypercalcaemia. Particularly unusual features include the presentation with a pancreatic mass and the association of hypercalcaemia with centroblastic lymphoma.

Adult↗

Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion.

The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male Wistar rats (n = 80) weighing 70-100 g were given weekly i.p. injections of azaserine (30 mg kg-1 week-1) for 3 consecutive weeks. One week later animals were randomised to receive either PBD or sham PBD and thereafter to receive s.c. injections of either saline or CR-1409 (10 mg kg-1 day-1, 5 days a week). Six months after operation surviving rats were killed as follows: sham + saline 20, PBD + saline 19, sham + CR-1409 14, PBD + CR-1409 11. Cardiac blood was taken for CCK assay and the pancreas was excised for wet weight measurement and quantitative estimation of atypical acinar cell foci (AACF), the precursor of carcinoma. PBD reduced median body weight (3-20% less than shams) but trebled the absolute and relative pancreatic weights (P < 0.001). CR-1409 blunted this adaptive response to PBD, reducing absolute pancreatic weight by 35% (P < 0.005). PBD quadrupled circulating CCK concentrations, regardless of the antagonist treatment. Acidophilic AACF occurred only in rats with PBD. CR-1409 markedly reduced the number of observed acidophilic AACF by 90% (P < 0.001) and the number of foci per pancreas by 93% (P < 0.001). Moreover, CR-1409 reduced the mean focal diameter of each lesion by 18% (P < 0.005), the mean focal volume by 58% (P < 0.05) and the percentage of pancreas occupied by acidophilic foci by 95% (P < 0.001). PBD enhances pancreatic carcinogenesis by causing hypercholecystokininaemia, and CR-1409 largely inhibits this enhancement.

Animals↗

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia.

Animals↗

Dissemination of pancreatic carcinoma following endoscopic sphincterotomy.

Endoscopic sphincterotomy (ES) is sometimes advocated for the temporary decompression of an obstructed bile duct by a periampullary tumor. We report a 27-year-old woman with a small carcinoma of the pancreatic head who developed acute pancreatitis and a pseudocyst following ES. At operation, malignant spread was virtually confined to the walls of the resolving pseudocyst cavity. Despite radical resection, she died from recurrent carcinoma 7 months postoperatively.

Acute Disease↗

Severe subcellular damage in the rat exocrine pancreas after pancreatobiliary diversion.

Cholecystokinin (CCK) may contribute to the genesis of both pancreatic carcinoma and acute pancreatitis. By transposing a long segment of jejunum to lie between the pylorus and the duodenal papilla, pancreatobiliary diversion (PBD) causes a persistent increase in circulating CCK levels, as the normal feedback inhibition of jejunal CCK release by pancreatic juice is evaded. A number of morphological, physiological, and acinar cytokinetic changes ensue. This investigation has examined the ultrastructural changes in pancreatic acinar cells after PBD in the presence and absence of CR1409 (lorglumide), a CCK receptor antagonist. After 14 days there was degranulation and vacuolation of acinar cells with involvement of the enzyme acid phosphatase. The presence of morphologically distinct extracisternal acid phosphatase indisputably predisposed acinar cells to severe damage. Treatment with CR1409 largely prevented degranulation after PBD, but vacuolation of acinar cells still occurred, indicating a possible toxic effect of the receptor antagonist. This is the first report of CCK itself, rather than one of its analogues, causing in vivo pancreatic damage that is generally considered as a forerunner to acute pancreatitis. This is of fundamental importance to the understanding of the earliest stages of the disease.

Acid Phosphatase↗

Expression of major histocompatibility antigens in human chronic pancreatitis.

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.

Adult↗

Annular pancreatitis and gastric cancer.

Annular pancreas can present in adult life, usually when inflammation of the pancreatic ring causes duodenal stenosis. Although peptic ulcer is often associated with annular pancreas, an association with gastric carcinoma has not been previously described. Here we report a patient with annular pancreas, chronic alcoholic pancreatitis and gastric carcinoma, who was successfully treated by radical proximal pancreatoduodenectomy.

Adenocarcinoma↗

Gastric emptying and enterogastric reflux after conservative and conventional pancreatoduodenectomy.

BACKGROUND: Retention of the entire stomach during pancreatoduodenectomy should theoretically improve postoperative nutrition, but some studies have reported a high incidence of delayed gastric emptying (GE). An intact pylorus should also prevent enterogastric reflux and its attendant problems, provided that the operation does not impair sphincteric competence. METHODS: We studied pyloric function in 24 patients who underwent pylorus-preserving pancreatoduodenectomy (PPP) and 12 who underwent a conventional Whipple resection including distal hemigastrectomy. Resection had been performed for benign (n = 19) or malignant (n = 17) disease. A double isotope technique was used to measure liquid and solid GE, and enterogastric reflux was measured by means of cholescintigraphy. RESULTS: Only two patients who underwent PPP required nasogastric intubation beyond 8 days. At follow-up (median, 5 months; range, 2 to 42 months) one patient with persistent vomiting required remedial surgery after PPP (apart from two with recurrent carcinoma affecting the anastomosis); after Whipple resection there were three patients with intermittent vomiting and one with dumping. Median half-time for liquid GE was not significantly different (65 minutes for PPP vs 103 minutes for Whipple resection; n < 70 minutes); likewise, the median half-time for solid GE was not significantly different (140 minutes for PPP vs 180 minutes for the Whipple procedure; n < 110 minutes). Persistent enterogastric reflux was seen in three of 20 patients who underwent PPP and three of eight who underwent Whipple resection. CONCLUSIONS: Isotopic test results of GE are frequently abnormal after either type of pancreatoduodenectomy, but symptoms are uncommon. The retained pylorus is competent to prevent enterogastric reflux and does not itself impair emptying of the stomach.

Adult↗

Surgical palliation for pancreatic cancer: developments during the past two decades.

Improvements in pancreatic imaging over the past 20 years have revolutionized the preoperative diagnosis and assessment of resectability in patients with suspected pancreatic cancer. This review highlights the resultant trends in the surgical treatment of ductal carcinoma of the pancreas, comparing series reported between 1981 and 1990 with those from the previous decade. Small but worthwhile gains have been achieved both in overall resection rate and in the survival rate from such resections. Nevertheless, 80 per cent or more of affected patients are still unsuitable for resection because of the extent of their disease. Laparotomy retains a crucial role in the management of carcinoma of the pancreatic head, although percutaneous and endoscopic stents provide a useful alternative for palliation of malignant obstructive jaundice in elderly patients or those with carcinomatosis. Operation provides the chance to confirm the nature and full extent of the tumour, to circumvent duodenal obstruction and to abolish pain, besides relieving jaundice without the need for tubes (with their potential to block). By contrast, operative treatment generally has much less to offer in patients with carcinoma of the pancreatic body, unless diagnosis and irresectability remain in doubt. In combination, radiotherapy and 5-fluorouracil may achieve more as adjuncts to palliative surgery than either agent alone. The increasing safety of pancreaticoduodenectomy raises the possibility of palliative resection in younger patients with limited but incurable disease.

Cholestasis, Extrahepatic↗