Concomitant cholecystectomy for asymptomatic cholelithiasis.

The outcome of 68 patients with asymptomatic cholelithiasis undergoing laparotomy for other conditions was reviewed to determine those most likely to become symptomatic postoperatively. Thirty-seven patients (54%) became symptomatic postoperatively. Eight patients (22%) required cholecystectomy within 30 days of operation or within the same hospitalization. These patients fasted for a longer period of time postoperatively (15 +/- 21 vs 4 +/- 3 days) than those undergoing later cholecystectomy. Significantly more of these patients required transfusion (38% vs 7%), mechanical ventilation (50% vs 11%), and total parenteral nutrition (50% vs 18%). Cholelithiasis frequently becomes symptomatic after laparotomy for other intra-abdominal conditions. Patients who require mechanical ventilation, transfusions, and parenteral nutrition and who are slow to resume enteral nutrition are more likely to require early cholecystectomy. Concomitant cholecystectomy adds minimal morbidity to other procedures and should be undertaken unless specific contraindications exist, particularly in this high-risk group.

The effect of intestinal resection and urogastrone on intestinal regeneration.

Intestinal regeneration in patched intestinal defects is enhanced by both intestinal resection and urogastrone. Our aim was to determine if these two stimuli have synergistic effects. Ileal defects were patched with colon serosa in 45 rabbits. Group 1 (n = 11) were control subjects; group 2 (n = 12) underwent 50% intestinal resection; group 3 (n = 11) received urogastrone (1.5 micrograms/kg per hour subcutaneously); and group 4 (n = 11) underwent intestinal resection and received urogastrone. Animals were killed at 7 and 14 days. Intestinal resection had the greater effect on epithelialization. Urogastrone inhibited contraction and intestinal resection did not. Both intestinal resection and urogastrone increased proliferative activity. Combining intestinal resection and urogastrone did not have a synergistic effect on epithelialization and diminished the effect of urogastrone on proliferation and contraction. These findings suggest that intestinal resection and urogastrone stimulate epithelialization via similar mechanisms and that urogastrone would not enhance regeneration during intestinal adaptation.

Should intestinal continuity be restored after massive intestinal resection?

We reviewed our experience with 32 patients who underwent massive intestinal resection to determine when intestinal continuity should be maintained. An enterostomy was created in 21 patients (66 percent) at the initial resection because of questionable bowel viability and an unstable condition or the need for colonic anastomosis. Intestinal continuity was restored in only 20 percent of these patients. In 11 patients (34 percent), intestinal continuity was maintained at the time of resection. Only four of these patients (36 percent) had a satisfactory long-term outcome. Overall, intestinal continuity was maintained in 10 of the 22 patients (45 percent) followed over the long-term. Three quarters of patients with intestinal remnants shorter than 3 feet had an enterostomy. We believe intestinal continuity should be restored at the time of massive resection only in carefully selected patients when bowel viability is ensured, remnant length is greater than 3 feet, and a colonic anastomosis is not required. Maintaining intestinal continuity eliminates the inconvenience of the stoma but may cause dietary restriction and perianal discomfort.

Influence of the etiology of pancreatitis on the natural history of pancreatic pseudocysts.

We reviewed our experience with 90 patients with pancreatic pseudocysts to determine if the cause of pancreatitis influenced the patients' outcome. Acute pancreatitis (AP) occurred in 57 (63%) patients due to alcoholic (n = 15), postoperative (n = 14), biliary (n = 12), and other etiologies (n = 16). Thirty-three (37%) patients had chronic pancreatitis (CP) secondary to alcohol use (n = 27) or other causes (n = 6). Multiple pseudocysts were significantly more frequent in patients with acute alcoholic pancreatitis than in patients with chronic pancreatitis (47% versus 19%, p < 0.05). Spontaneous resolution occurred within 8 weeks in 10 (11%) patients with pseudocysts (AP = 9%, CP = 15%, p = NS). However, no patient with pseudocyst associated with biliary or postoperative pancreatitis underwent spontaneous resolution. Although pseudocysts associated with chronic pancreatitis were smaller in size (8.0 +/- 4.7 versus 5.7 +/- 3.8 cm, p < 0.05), a similar proportion of them required operation compared with AP pseudocysts (56% versus 58%). There were significantly more deaths in patients with postoperative pancreatitis compared with all other groups (29% versus 7%, p < 0.05). The outcome of pseudocysts was similar regardless of size (greater than 6 cm versus less than 6 cm) and presentation (acute versus delayed). Thus, the etiology of pancreatitis was a more important determinant of pseudocyst outcome than pseudocyst size or presentation.

Increased incidence of pancreas-related complications in patients with postoperative pancreatitis.

The incidence and significance of pancreas-related complications (pseudocysts, abscesses, and fistulas) were evaluated in 100 patients with acute pancreatitis. Alcoholic (40 percent), biliary (20 percent), and postoperative (15 percent) pancreatitis were seen most frequently. Eighteen patients had severe pancreatitis (3 or more Ranson's criteria). The overall mortality rate was 8 percent, and there were 16 pancreas-related complications. Pancreas-related complications developed in eight patients (53 percent), including two pseudocysts, four abscesses, and two fistulas. The incidence of pancreas-related complications was significantly greater in the postoperative group than in the overall 9 percent incidence in the other groups (p less than 0.005). Half of these patients required operation for their complications. Patients with postoperative pancreatitis are at a markedly increased risk of pancreas-related complications. Since these complications occur even in apparently mild cases of pancreatitis, these patients should be followed closely to detect pancreas-related complications.

Influence of nutrient delivery on gut structure and function.

Food is an important stimulus for the growth of gastrointestinal mucosa. Gut structure is influenced by the route of nutrient administration, dietary composition and the availability of specific nutrients. The alterations in intestinal structure and function that occur when enteral nutrition is withheld suggests that the ingestion of food results in physiologic responses that are responsible for the maintenance of gut mass during the fed state. The mechanism of mucosal suppression that occurs during starvation, stress, and total parenteral nutrition is not completely understood but may involve the absence of luminal substrates, decreased pancreaticobiliary secretions and alterations in the endocrine or paracrine events that normally accompany eating, digestion, and absorption. Enterocytes prefer glutamine and ketone bodies as oxidative fuels, whereas colonocytes utilize short chain fatty acids. Although enteral delivery of nutrients is the preferred route for maintenance of intestinal mass, provision of specific nutrients and hormonal stimulation during parenteral alimentation has been shown to be important in maintaining mucosal structure and function. If not adequately maintained, the intestine becomes susceptible to a variety of injuries which may result in impaired ability to digest and absorb nutrients and loss of mucosal barrier function.

Urogastrone reduces gut atrophy during parenteral alimentation.

Urogastrone (UG) exerts trophic effects on the intestine and may play a role in maintaining normal intestinal structure and function. Since administration of nutrients parenterally results in intestinal hypoplasia and hypofunction, the aim of this study was to determine the effects of UG on intestinal structure and function in parenterally fed rats. Central venous catheters were placed into 28 Sprague-Dawley rats. Group I (n = 10) received TPN alone. Group II (n = 8) received TPN and 15 micrograms/day of UG and group III (n = 10) received rat chow ad libitum. The animals that received urogastrone had significantly greater (p less than 0.05) intestinal weight (25.6 +/- 2.5 mg/cm vs 22.6 +/- 3.0 mg/cm), mucosal weight (8.4 +/- 1.4 mg/cm vs 6.2 +/- 0.9 mg/cm), mucosal protein content (6.2 +/- 1.7 mg/cm vs 2.7 +/- 0.6 mg/cm), villous height (427 +/- 27 microns vs 293 +/- 75 microns), crypt cell production rate (14.5 +/- 1.4 metaphases/hr vs 12.3 +/- 0.7 metaphases/hr) and sucrase specific activity (6.5 +/- 2.6 vs 3.7 +/- 2.0) than animals receiving only TPN. However, these parameters remained less than in chow-fed animals. Thus, simultaneous infusion of UG prevents, in part, intestinal hypofunction and hypoplasia which occurs during TPN. This may be due to maintenance of mucosal proliferative activity and brush border enzyme activity.

The influence of serosal patch size on the growth of small intestinal neomucosa.

Several factors might affect the growth of neomucosa after serosal patching of small intestinal defects. Often only short segments of small intestine can be patched because of limited serosal surface and anatomic factors. The purpose of this study was to determine the influence of patch size on neomucosal growth. Twenty male New Zealand white rabbits underwent patching with colon serosa of either a 2 X 15-cm distal ileal defect (n = 10) or three 2 X 5-cm ileal defects (n = 10). There was significantly greater coverage of the patched defect by neomucosa in the triple patch group (99.4% vs 93.1% P less than 0.005) and significantly more of the smaller defects were completely covered by neomucosa than the larger defects (12 of 15 vs 0 of 5, P less than 0.05) at 8 weeks. The final area of the defect was 27.5 and 32.8% of the initial patched area respectively for the single and triple patches. Microscopically there was no difference in villous height or crypt depth, but crypt density was significantly greater in the triple group (207 +/- 11 vs 186 +/- 17 crypts/mm, P less than 0.05). In vitro glucose uptake and disaccharidase activity were similar in both groups. Patching multiple small intestinal defects results in more rapid neomucosal growth than a single large defect of the same surface area. This might be due to a greater circumference exposed to surrounding normal mucosa with a resultant increase in crypt density. Since function and villous development of the neomucosa are similar, multiple patches should result in a greater increase in absorptive capacity.

Serosal patching impairs intestinal adaptation following enterectomy.

Increasing intestinal absorptive surface by mucosal regeneration on serosal patched intestinal defects is a potential surgical treatment for the short bowel syndrome. We previously found in long-term studies that serosal patching in dogs undergoing 75% enterectomy was deleterious to intestinal adaptation and absorption. Our aim was to evaluate the effect of serosal patching on the early morphologic and functional changes in postresectional adaptation and to examine the role of polyamine metabolic pathways in this process. Five unoperated New Zealand white rabbits (GP I) served as controls. Twelve other rabbits underwent either 50% distal enterectomy alone (GP II) or simultaneously had two 2 x 5-cm full-thickness ileal defects patched with adjacent cecal serosa (GP III). Animals in GP II gained an average of 7.2 +/- 5.3% body weight, whereas GP III animals lost 5.6 +/- 9.0% body weight (P less than 0.05). Intestinal remnant length was significantly less in GP III 3 weeks postoperatively (66 +/- 11 vs 85 +/- 8 cm, P less than 0.05) as was mucosal protein content (4.1 +/- 1.8% vs 6.2 +/- 1.9%) but villus height was similar in GPs II and III (505 +/- 131 vs 508 +/- 110 microns). In vitro mucosal function was similar in all three groups. Crypt cell production rate was significantly lower while ornithine decarboxylase and diamine oxidase activity were higher in GP III compared to GP II. However, polyamine levels were similar in all three groups. Serosal patching impairs intestinal adaptation following massive enterectomy. This is due in part to a decrease in proliferative activity which is not directly related to altered polyamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of intestinal resection on the growth of intestinal neomucosa.

Intestinal resection stimulates proliferative activity in the intestinal remnant. The aim of this study was to determine the influence of intestinal resection on the growth of intestinal neomucosa. Forty-eight New Zealand white rabbits had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. Group I (n = 24) served as controls. Group II (n = 24) underwent simultaneous 50% enterectomy. Neomucosal coverage was significantly greater in Group II at 1 week (36 +/- 11% vs 67 +/- 9%, P less than 0.05) and 2 weeks (94 +/- 2% vs 99 +/- 1%, P less than 0.05), but was similar at 3 and 4 weeks. There was significantly more neomucosa at 1 week in the animals that underwent resection (134 +/- 55 mm2 vs 199 +/- 54 mm2, P less than 0.05). Degree of patch contraction, glucose uptake, and disaccharidase activities were similar in each group. Ornithine decarboxylase activity and crypt cell production rate were significantly greater at 1 week in the animals that underwent resection. Intestinal resection results in an early increase in neomucosal growth and increased proliferative activity. Since contraction of the patches occurs to a similar extent in both groups, the total amount of neomucosa was not increased. Thus, performing patching at the time of resection is not necessary for optimal growth.

Intestinal diamine oxidase levels reflect ischemic injury.

Mucosal diamine oxidase (DAO) decreases during intestinal ischemia and may be a useful marker of intestinal ischemic injury. Tissue DAO activity and histologic changes were studied in intestinal segments taken from the midpoint of the small intestine before and 2, 4, and 24 hr after manipulation of the intestinal blood supply in 24 mongrel dogs. Intestinal DAO activity decreased significantly (17 +/- 21% of control value) 24 hr after SMA ligation and was associated with abnormal histology (histology score 7.8 +/- 2.9 at 24 hr vs 0.3 +/- 0.5 at 0 hr). SMA occlusion for 2 hr resulted in a significant decrease in DAO activity (45 +/- 36% of control value) 4 hr after manipulation which returned to normal at 24 hr, as did the histologic injury. Ligation of both the mesenteric arteries and veins resulted in a more rapid decrease in DAO activity. Decreased DAO activity correlated with the extent of histologic injury. Intestinal ischemia is associated with decreased intestinal DAO activity, which is influenced by the mechanism and duration of intestinal ischemia.

Serum enzyme levels during intestinal ischemia.

Because the intestinal mucosa is most sensitive to ischemia, serum levels of mucosal enzymes, such as diamine oxidase, may be most likely to indicate intestinal ischemia. Our aim was to compare serum levels of mucosal (diamine oxidase, alkaline phosphatase) and seromuscular (creatinine phosphokinase, lactic dehydrogenase, serum glutamic oxaloacetic transminase) enzymes during intestinal ischemia of varying extent and duration in dogs. Group 1 (n = 6) underwent sham laparotomy. Group 2 (n = 8) had 50% of the small intestine devascularized. Group 3 (n = 8) had the superior mesenteric artery occluded for 2 hours and released. Group 4 (n = 8) had the superior mesenteric artery ligated. Serum samples were obtained before and 2, 4, 8, and 24 hours after operation, and histologic specimens were examined at 4 hours. Creatinine phosphokinase levels became elevated within 4 hours of ischemic injury in group 2 (223 +/- 197 vs. 68 +/- 26, p less than 0.05) and group 4 (212 +/- 136 vs. 76 +/- 29, p less than 0.05). Significant elevation of serum enzymes levels, except diamine oxidase, occurred in groups 2, 3, and 4 at 24 hours, including those with normal histology after temporary superior mesenteric artery occlusion. Thus seromuscular enzymes, particularly creatinine phosphokinase, were more likely to be elevated during intestinal ischemia. Enzyme levels were not influenced by the extent and reversibility of the ischemic injury.

Postoperative pancreatitis.

Our experience with 52 patients who had postoperative pancreatitis develop during a nine year period was reviewed to characterize this group, to determine the incidence of complications and to identify variables predictive of complications. Biliary tract procedures (n = 10), colectomy (n = 9) and intestinal resection (n = 9) were the most frequently performed operations preceding pancreatitis. Thirty of the procedures were near the pancreas. Pancreatitis was detected within seven days of the operation in 26 of the patients. Sixteen patients had complications related to the pancreas, 12 had other nonlethal complications and nine died. Fourteen patients had severe pancreatitis (greater than or equal to 3 Ranson's criteria) and were more likely to have a complicated course (p less than 0.05). Complications related to the pancreas included pancreatic pseudocyst (n = 9), abscess (n = 4), fistula (n = 2) and arterial hemorrhage (n = 1). Age, operation performed, serum amylase level and frequency of hypotension, renal failure and other complications were similar in patients with and without complications related to the pancreas. A high index of suspicion must remain throughout the postoperative period to recognize inflammation of the pancreas and its complications so that prompt diagnosis and management can be undertaken.

Blood levels of caffeine and results of fetal examination after oral administration of caffeine to pregnant rats.

Pregnant FDA-strain Osborne-Mendel rats were administered repeated doses of caffeine by oral intubation (gavage) and by administration in the drinking water (ad libitum sipping). When [1-methyl-14C]caffeine was administered at a dosage of 80 mg per kg per day by ad libitum sipping on days 12 to 15 of gestation, the amounts of radioactivity in blood were variable; the highest level on day 12 was 0.2% of the dose per ml of blood. The highest blood level of caffeine observed during a 24-h sampling period averaged 5.7 micrograms ml-1. When [14C]caffeine was administered by gavage at a dosage of 80 mg kg-1 on day 12, the blood level of radioactivity reached a peak of 0.4% of the dose per ml of blood and declined rapidly thereafter. The highest amount of caffeine observed in blood averaged 63.1 micrograms ml-1, 1 h after gavage. The overall blood elimination half-life of radioactivity in pregnant rats treated by gavage was 2.6 h, and the half-life of caffeine in blood was 1.7 h. The levels of radioactivity in the fetus and maternal muscle per unit weight were comparable after each method of administration. A comparison of autopsy results from both groups indicated that resorptions were increased when compared with rats that did not receive caffeine; this effect was more marked in the gavage group than in the ad libitum sipping group. Ectrodactyly was observed only in offspring of the gavage group. The incidences of ectrodactyly or resorptions did not appear to be directly related to nutrition or fluid intake.