Mikio Imamura

Morphological and immunohistochemical changes in intestinal mucosa and PYY release following total colectomy with ileal pouch-anal anastomosis in dogs.

Other studies have shown that both morphologicaland functional adaptation occur in the ileal mucosaafter total colectomy and may be mediated by humoralfactors. To elucidate the participation of peptide YY (PYY) in intestinal adaptation after totalproctocolectomy with ileal pouch-anal anastomosis(IPAA), changes in the number of PYY-containing cellsand in histological appearance in the intestinal mucosa, especially in the mucosa of ileal pouch, wereinvestigated in dogs. We further examined changes inpostprandial PYY release in relation to those inPYY-containing cells. Ten adult beagle dogs underwent IPAA. Before and 2, 6, and 12 months aftersurgery, a test meal was given, and blood samples weretaken from a foreleg vein at intervals for 3 hr formeasurements of plasma PYY concentration byradioimmunoassay. Before and one year after surgery,morphological studies of the intestinal mucosa wereperformed using parameters such as villous height (VH),mucosal thickness (MT), and villous index (VI).Immunohistochemical studies of PYY were also done in the intestinalmucosa. Both fasting and postprandial plasma PYY levelswere reduced to half of the preoperative levels at twomonths after surgery. Thereafter, postprandial levels approached preoperative concentrations,while fasting levels remained unchanged. VH, MT, and VIwere significantly smaller in the ileal pouch than inthe ileal end of the controls. The MT of the ileal pouch was similar to that of the colon.PYY-containing cells in the mucosa of the ileal pouchwere distributed more densely than those in the ilealend, similar to those in the colon of the controls. It was concluded that after IPAA, the pouchmucosa gradually changed to resemble the colonic mucosanot only in histological appearance but also in thepopulation of PYY-containing cells. It is therefore considered that colonic transformation of theilealpouch mucosa is closely related to the increase inthe number of PYY-containing cells and the steadyrecovery of postprandial PYY secretion.

Pancreatic function and rehabilitation after pancreaticoduodenectomy

Postoperative pancreatic function and rehabilitation were monitored in 149 patients who had had reconstruction of the digestive tract by Childs method, out of a total 151 patients who had undergone pancreaticoduodenectomy. The occurrence of peptic ulcer following Childs method may be prevented by the resection of a wider area of the stomach. Because the source of gut hormone secretion is removed by the pancreaticoduodenectomy, the secretion of this hormone is subsequently reduced and thus metabolic abnormalities also occur. If careful attention however, is paid to the maintenance of residual pancreatic function most patients who undergo pancreaticoduodenectomy can be expected to lead reasonably normal lives.

Effect of biliary reconstruction procedures on gastric acid secretion

In 26 patients with Roux-Y choledochojejunostomy and 10 with jejunal interposition choledochoduodenostomy, gastrin-stimulated gastric acid secretion and serum levels of gastrin and secretin after feeding were examined before operation and at the time of follow-up. The follow-up levels of maximum acid output were higher than those before operation in each group, and they tended to be higher in patients with Roux-Y choledochojejunostomy (Group I) than in those with jejunal interposition choledochoduodenostomy (Group II), but the difference was not significant. There was no instance of postoperative peptic ulcer in either group. The levels of serum gastrin after feeding tended to be higher in Group II, whereas serum secretin levels were contrarily higher in Group I. The changes in these hormones could be considered not as the cause but rather as the outcome of the changes in postoperative gastric acid secretion.

Exacerbation of acute pancreatitis in the presence of chronic liver injury in rats, with special reference to therapeutic efficacy of prostaglandin E1.

The pathophysiology of acute pancreatitis accompanied by chronic liver injury, and the therapeutic efficacy of prostaglandin (PG)E1 were studied experimentally in rats. Chronic liver injury was produced by subcutaneous administration of CCl4. Acute pancreatitis was induced by the closed duodenal loop (CDL) method, immediately after which PGE1 (60 ng/kg/min) was infused intravenously via the jugular vein. Serum levels of amylase, alpha2-macroglobulin-trypsin complex (alpha2M-TRY), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were determined before and at 3 and 6 h after the onset of acute pancreatitis. Rats without administration of CCl4 served as controls. Serum amylase levels were lower in the liver injury (LI) group than in the normal liver (NL) group at 3 and 6 h. PGE1 had no effect on amylase levels in either group. Serum alpha2M-TRY levels were similar in the two groups at 3 h, but significantly higher in LI than in NL at 6 h. PGE1 tended to decrease alpha2M-TRY levels only in LI. Serum CRP levels were significantly more elevated in LI than in NL at 0, 3, and 6 h. PGE1 decreased CRP levels only in LI. Serum TNF-alpha concentrations were higher in LI, especially at 6 h. PGE1 reduced TNF-alpha levels in LI. Pancreatitis severity scores were significantly higher in LI. PGE1 significantly decreased the severity scores only in LI. Fat necrosis scores were significantly lower in LI. Histologically, interstitial edema was much more prominent in NL than in LI, whereas interstitial hemorrhage was more severe in LI at 3 and 6 h. PGE1 lessened the hemorrhage in LI. The extent of both vacuolization and necrosis of acinar cells was similar for both groups and tended to be improved by PGE1. It is concluded that acute pancreatitis becomes much more serious in the presence of chronic liver injury, and that PGE1 can ameliorate the exacerbated lesions, probably by improvements in blood flow through the pancreatic tissue.

Malignant insulinoma with metastasis to gallbladder and bone, accompanied by past history of peptic ulcer and hyperthyroidism

SummaryA case of a malignant insulinoma in a 53-year-old female is presented. In 1973, the patient underwent caudal pancreatectomy for a malignant insulinoma. Ten years later, it was discovered that the insulinoma had spread to the bones. On admission for cholecystectomy because of a gallbladder polyp and gallstones, she often experienced hypoglycemic attacks, and both calcium and glucagon provocation tests elicited marked release of insulin. Selective angiography of the common hepatic artery showed a tumor blush near the hilum of the liver. Immunohistochemical staining of the gallbladder polyp and the bone tumors proved positive for insulin. Plasma levels of insulin and prolactin were abnormally high. The patient had also been treated for a perforated duodenal ulcer and hyperthyroidism. It is concluded that this may have been a case of a multiple endocrine neoplasia.

Gastric acid secretion and gastrointestinal hormone release after biliary reconstruction procedures.

The changes in gastric acid secretion and gastrointestinal hormone release were studied after biliary tract reconstruction to investigate the mechanism of gastric acid hypersecretion after a biliary diversion procedure. At follow-up, gastric acid output in patients with Roux-Y choledochojejunostomy was significantly higher than before the operation. In contrast, in patients with jejunal interposition choledochoduodenostomy, which does not bring about biliary diversion, acid output increased slightly after the operation. Moreover, at follow-up, acid output in the Roux- Y group was slightly higher than it was in the interposition group. Although the fasting levels of plasma gastric inhibitory polypeptide were almost the same in both groups, the loading of a test meal elicited a lower response of plasma gastric inhibitory polypeptide in patients with the Roux- Y procedure than in those with the interposition procedure. Therefore, it is assumed that gastric inhibitory polypeptide, as an enterogastrone after a biliary reconstruction procedure, might have some influence on gastric acid secretion.

Gastric acid secretion and serum gastrin levels in chronic pancreatitis

SummaryOf 114 patients with chronic pancreatitis, 19 (16.7%) has gastric or duodenal ulcers. Patients with moderate pancreatic exocrine dysfunction tended to show high acid output and low serum gastrin levels, while those with severe dysfunction had slightly lower acid output and higher serum gastrin levels. The higher the degree of pancreatic fib rosis, the higher tended to be the acid output and serum gastrin levels. Not all patients with ulcers developed hypergastrinemia. The mechanism of acid hypersecretion and ulcer formation in patients with chronic pancreatitis cannot be explained solely by pancreatic deterioration, fibrosis or gastrin release; a decrease in the production and release of gastric inhibitory hormone should be taken into consideration.

Resected case of carcinoid tumor of the liver metastatic from the breast

Carcinoid tumor metastatic to the liver from the breast is very unusual. We report a rare case in which the patient underwent curative resection for metastatic lesions to the liver. She had undergone a modified radical mastectomy more than 1 year previously for breast cancer. Recently, it was found that plasma levels of carcinoembryonic antigen (CEA) was elevated, and abdominal ultrasonography detected a liver tumor. The patient underwent a lateral segmentectomy of the liver, resulting in normalization of plasma CEA levels. The resected specimen was diagnosed as carcinoid tumor by histological, immunohistochemical, and ultrastructural microscopic studies. Re-examination of the breast tumor proved it to be the primary carcinoid.

Effect of a specific synthetic inhibitor of neutrophil elastase(ONO-5046) on the course of acute hemorrhagic pancreatitis in dogs

In acute pancreatitis, particularly in severe cases, polymorphonuclear neutrophil (PMN) elastase induces tissue damage in remote organs such as the lung, as well in the pancreas itself. Therefore, we examined the therapeutic effect of a specific synthetic inhibitor of PMN elastase (ONO-5046: Ono Pharmaceuticals, Osaka, Japan) on the lung, liver, and kidney, as well as pancreas, in severe hemorrhagic pancreatitis in dogs. Acute hemorrhagic pancreatitis was induced by the injection of a mixture of autologous bile and porcine trypsin into the main pancreatic duct. Lipopolysaccharide (LPS) was administered intravenously as a septic challenge. Two animal groups were used. In one group, continuous infusion of ONO-5046 was started prior to the injection of LPS (ONO group). In the other group (control), saline was infused instead. At the end of the experiment (330 min after the injection of bile and trypsin), the pancreas revealed severe hemorrhagic pancreatitis, and a large amount of bloody ascites had accumulated in the peritoneal cavity. The white blood cell count was markedly reduced in response to the induction of pancreatitis, and was decreased further by the septic attack, irrespective of the administration of ONO-5046, although the count increased again in the ONO group. Serum levels of amylase and alpha2-macroglobulin-trypsin complex increased similarly in both groups following administration of bile and trypsin. Serum Ca levels decreased in both groups. At the end of the experiment, the wet weight of the lung was slightly higher in the control group (without ONO-5046). Microscopically, the pancreas showed severe hemorrhage accompanied by extensive interstitial edema in both groups. The lung and liver demonstrated mild infiltration of inflammatory cells in the interstitium in both groups, although the inflammatory change in the liver was slightly milder in the ONO group. These findings indicate that severe hemorrhagic pancreatitis cannot be alleviated by the administration of a specific inhibitor of PMN elastase alone, although this may lessen damage to remote organs such as the liver and lung. The white blood cell count decreased markedly after the induction of acute pancreatitis, and much more after a septic challenge. This seems to be closely related to the accumulation of bloody ascites in the peritoneal cavity.

Pylorus-Preserving Pancreatoduodenectomy with a Newly Devised Reconstruction of the Alimentary Tract

Experiences with pancreatoduodenectomy (PD) with Child’s reconstruction method have led us to devise a new method of alimentary tract reconstruction: the remaining stomach is anastomosed to the oral stump of the jejunum, and a short segment of the midportion of the small intestine is interposed between the pancreatic and bile ducts and the upper jejunum. Based on satisfactory results in experiments using dogs, we first applied the reconstruction method to 4 patients undergoing PD, then to 13 patients undergoing pylorus-preserving pancreatoduodenectomy (PPPD). In PPPD, the pyloric branch of the anterior vagal nerve was preserved in most cases. It took longer for patients undergoing PPPD to take a liquid meal compared to those undergoing PD (mean, 9.9 vs. 5.6 days, P <.01). Body weight increased gradually after discharge, and returned to or exceeded preoperative values at time of follow-up in most patients undergoing PPPD. Gastric acid output showed normoacidity both before and after surgery except in 2 cases suffering from bleeding gastric ulcers. Pancreatic exocrine function maintained above 75% in the pancreatic function diagnostant (PFD) test after PPPD. At follow-up, an upper gastrointestinal barium study showed a good coordination of the movement of the upper gastrointestinal tract, and only slight reflux of barium into the interposed intestine was observed. Three patients died, 2 of recurrence of cancer and 1 of lung sarcoma. The remaining 10 patients have been in good condition for a follow-up period from 6 months to more than 5 years. In conclusion, it is considered that our method of reconstruction of the alimentary tract after PPPD (or PD) brings about a good nutritional state because the upper jejunum is used efficiently and both pancreatic juice and bile are mixed with ingested food at a location close to the stomach.