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Gastric Acid Secretion and Gastroduodenal pH after Pancreaticogastrostomy in Dogs
JOURNAL OF SURGICAL RESEARCH ARTICLE NO.
61, 152–158 (1996)
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Gastric Acid Secretion and Gastroduodenal pH after Pancreaticogastrostomy in Dogs HIROYUKI SHINCHI, M.D.,*,1 SONSHIN TAKAO, M.D., PH.D.,*,† KIYOTAKA FUKURA, M.D.,* AND TAKASHI AIKOU, M.D., PH.D.* *First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890, Japan; and †Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218 Submitted for publication October 7, 1994
Pancreaticogastrostomy has been reintroduced as a useful alternative procedure to pancreaticojejunostomy after Whipple resection or pylorus-preserving pancreaticoduodenectomy because of the very low incidence of leakage and disruption. In this study, gastric acid secretion, serum gastrin level, and 24-hr dual gastroduodenal pH after pancreaticogastrostomy were examined on the assumption that a canine model was a pylorus-preserving pancreaticoduodenectomy. Basal acid output (BAO), maximal acid output (MAO), and dual gastroduodenal pH were measured in eight dogs with gastric fistula. After pancreaticogastrostomy, BAO levels showed a slight increase significantly, but MAO levels showed no change. Serum gastrin levels in the fasting and postprandial states showed the similar patterns between before and after surgery. In the 24-hr dual gastroduodenal pH monitoring, gastric pH and duodenal pH also did not change in the fasting and postprandial states. These results suggested that the maintenance of the normal gastric pH after pancreaticogastrostomy was caused by a little increase of BAO, and the neurohumoral relationship between the stomach, duodenum, and pancreas was preserved even after pancreaticogastrostomy. Therefore, the pancreaticogastrostomy is a recommendable reconstructive procedure physiologically after pylorus-preserving pancreaticoduodenectomy. q 1996 Academic Press, Inc.
INTRODUCTION
In general, pancreaticojejunostomy has been used to reconstruct the digestive tract and remnant pancreas after Whipple resection. However, this anastomosis continues to be a source of major morbidity due to the high incidence of anastomotic leakage and disruption [1, 2]. Since the 1970s, the pancreaticogastrostomy has 1 To whom correspondence should be addressed at First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890, Japan. Fax: 0992-65-7426.
0022-4804/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
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been reintroduced and used occasionally as a useful alternative procedure to pancreaticojejunostomy after Whipple resection or pylorus-preserving pancreaticoduodenectomy (PPPD). The pancreaticogastrostomy offers several advantages over the pancreaticojejunostomy. First, the anastomosis can be created easily without tension because of the proximity between the stomach and the pancreas. Second, the incomplete activation of the pancreatic enzymes in the acid milieu of the stomach may lead to result in a low incidence of remnant pancreatitis and anastomotic fistula. Third, the alkaline pancreatic secretion may prevent stomal ulceration of the gastrojejunostomy [3–10]. However, the physiological alterations after pancreaticogastrostomy in PPPD has been controversial, and gastric acid secretion, serum gastrin level, and the actual intraluminal pH profile have not yet been reported. Therefore, this study was designed to examine simultaneously gastric acid secretion, serum gastrin level, and gastricduodenal pH before or after pancreaticogastrostomy on the assumption that a canine model was a PPPD. MATERIALS AND METHODS
Preparation Eight male mongrel dogs, varying in weight from 10 to 15 kg, were subjected to laparotomy with creation of a gastric fistula placed near the greater curvature of the corpus and drained by a Thomas cannula (Natsume Co., Tokyo, Japan). We used these dogs with Thomas cannula for our experimental series after 4 weeks. The experiments were conducted with conscious dogs that had been deprived of food, but not water, for 18 hr.
Pancreaticogastrostomy Pancreaticogastrostomy was performed as follows. The accessory (ventral) pancreatic duct was divided and ligated, and then a 2-cm length of the pancreatic head was dissected to separate from the duodenum. The main (dorsal) pancreatic duct was divided, and then the distal stump was ligated to stop the pancreatic juice flowing into the duodenum. A 2-cm tube of 4 Fr Atom multipurpose catheter (Atom Co., Tokyo, Japan) was introduced into the proximal stump of the main pancreatic duct, and was secured with a single 4-O absorbable suture to ensure patency of the duct during the creation of
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FIG. 1. A canine experimental model of pancreaticogastrostomy. (A) Placement of sutures between the posterior wall of the stomach and the pancreas. A tube is inserted into the main (dorsal) pancreatic duct, and then the pancreas and the posterior wall of the stomach were sutured. The insert figure shows the cephalad portion of the pancreaticogastric anastomosis. (B) Completion of pancreaticogastrostomy. The asterisk shows the accessory (ventral) pancreatic duct, which was divided and ligated. Gastrostomy cannula is placed in the greater curvature of the stomach. the anastomosis. Then, a 2-cm seromuscular incision was made on the posterior wall of the stomach, followed by a 2–3-mm stab incision in the gastric mucosa. The anterior surface of the pancreas was sutured to the seromuscular portion of the posterior wall of the stomach using a single layer of interrupted 3-O silk sutures (Fig. 1A). The pancreatic duct was anastomosed to the gastric mucosa with an absorbable 4-O purse-string suture like as the cephalad portion of the pancreaticogastric anastomosis (Fig. 1A, insert). The caudal portion of the pancreaticogastric anastomosis was then completed with interrupted 3-O silk sutures (Fig. 1B). Neither vagotomy nor resection of the stomach, duodenum, or pancreas was performed. There was no postoperative complication related to pancreaticogastrostomy.
taining 2 mg/ml of ethylene diaminetetraacetic acid (EDTA) and a 400 KIU/ml of aprotinin. Samples were centrifuged at 3000 rpm for 10 min, and the serum was kept at 0207C until measurements were conducted. Serum gastrin concentrations were determined by radioimmunoassay (GASTRIN RIAKIT II, Dinabot Co., Tokyo, Japan).
Twenty-Four-Hour Gastric and Duodenal pH Monitoring Intragastric and duodenal pH monitorings were simultaneously performed before and after pancreaticogastrostomy. Antimony pH
Patency of Pancreaticogastrostomy To verify the patency of the pancreatic anastomosis, a fasting secretin stimulation test was performed after 4 weeks of pancreaticogastrostomy. Basal gastric secretions were collected for 60 min, and then a 3 U/kg secretin (Secrepan; Eisai, Tokyo, Japan) was administered intravenously. Gastric contents were collected at 15-min intervals for 60 min. The pH was measured with a glass electrode, and pancreatic amylase activity was determined using a commercially available kit (Alpha Amylase PNP; Boehringer, Mannheim, Germany). Moreover, autopsy examination was performed on each dog when all testing was completed.
Measurement of Gastric Acid Secretion Gastric secretions were collected by gravity drainage through the gastrocutaneous fistula. Basal acid output (BAO) and maximal acid output (MAO) in response to a 6-mg/kg tetragastrin (im) were measured. They were calculated after 15-min intervals to the nearest 0.1 ml, and titrated with sodium hydroxide (NaOH) to pH 7.0. BAO was defined as the sum of the four interval outputs, and MAO was defined as the sum of the four highest consecutive interval outputs following the stimulation. These values were expressed as millimole of acid per hour. Postoperative tests were repeated in duplicate for 6 weeks after pancreaticogastrostomy.
Measurement of Serum Gastrin Level The serum gastrin levels were examined in the fasting and postprandial states. Blood samples were collected into chilled tubes con-
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FIG. 2. Placement of the pH sensors passing through the gastric cannula during the 24-hr monitoring. Note that the proximal sensor is in the antrum of the stomach (A), while the distal sensor is in the descending portion of the duodenum (B).
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FIG. 3. Changes of gastric pH and amylase activity in the gastric juice after intravenous administration of a 3 U/kg secretin following pancreaticogastrostomy. Asterisks show the significant increase over a basal secretion (P õ 0.05), indicating a patent pancreaticogastric anastomosis.
electrodes, which were calibrated in standard buffer solutions at pH 7 and pH 1, were passed through the gastrocutaneous fistula and placed in the second portion of the duodenum and the antrum of the stomach under fluoroscopic guidance (Fig. 2). A digitrapper (Mark II Gold, Synectics Medical) was used to record the pH from each electrode every 4 sec. The data were stored and analyzed by the computer software (Esophagram, Synectics Medical) [11–14]. After an equilibration period of 30 min, the baseline fasting pH was recorded for a period of 90 min. Then, a standardized liquid meal of 40 g/kg minced meat in a 20 ml/kg water, adjusted to pH 6.4, was given. After this meal, gastric and duodenal pH measurements were recorded for 22 hr. During pH measurements, the dogs were allowed to pursue normal activity, and to get only water.
FIG. 5. Serum gastrin levels in the fasting and postprandial states (up to 6 hr after meal) before or after pancreaticogastrostomy.
RESULTS
Patency of Pancreaticogastric Anastomosis The secretin stimulation test showed a marked increase in both the pH level and amylase activity in
Analysis of pH Recordings The gastric and duodenal pH data were analyzed separately for the 24-hr period. The means of fasting gastric and duodenal pH were calculated from the data of an initial 90-min period. The postprandial 22-hr pH recording was divided into three periods that were the fed period (FED; postprandial 0–3 hr), the postprandial steady acid pH period (STEAD; postprandial 3–10 hr) and the remaining fasted period (FAST; postprandial 10–22 hr). For each of three periods, the following values were calculated: (1) the number of alkaline spikes (ú pH 6) in the gastric pH, and the number of acid spikes (õ pH 4) in the duodenal pH; (2) the number of these consecutive episodes for over 5 min; (3) the percentage of a time (%time) with õ pH 4 or ú pH 6; and (4) the cumulative percentage of the total pH data. All procedures were approved by institutional Animal Care and Use Committee at Kagoshima University School of Medicine.
Statistical Analysis Results were expressed as mean { SE. Differences of data between before and after pancreaticogastrostomy were tested for significance at the 0.05 level by the Wilcoxon matched pairs test.
FIG. 4. Changes in basal and maximal acid output before or after pancreaticogastrostomy. The asterisk shows the significant elevation in BAO (P õ 0.05). BAO Å basal acid output, MAO Å maximal acid output
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FIG. 6. (A) Postprandial 22-hr gastric pH distribution by %time at each pH interval. No significant differences between before and after pancreaticogastrostomy were noted at any pH interval. (B) %time in the gastric contents with a pH of less than 4 or greater than 6 in FED, STEAD, and FAST periods. No significant differences were noted.
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FIG. 7. Twenty-four-hour gastric pH tracing from two dogs before or after pancreaticogastrostomy. The gastric pH patterns in the fasting (FAST) period were divided into two types. Type A, the steady acid pH is observed throughout FAST period. Type B, the gastric content exhibited the cyclic variations between acidic and alkaline pH during FAST period. The gastric pH patterns of both type A and type B remained constant before or after pancreaticogastrostomy. FED Å feeding period, STEAD Å postprandial steady state, FAST Å fasting period.
the gastric contents (Fig. 3), autopsy examination also revealed the patency of pancreaticogastrostomy in all dogs. These results indicated that the pancreaticogastric anastomoses were patent. Gastric Acid Secretion
Serum Gastrin Levels Serum gastrin levels before or after pancreaticogastrostomy showed a similar pattern in fasting and postprandial states up to 6 hr after meal (Fig. 5). The differences between these patterns were not shown significantly.
BAO and MAO levels before or after pancreaticogastrostomy are shown in Fig. 4. BAO levels showed a slight increase (P õ 0.05) after pancreaticogastrostomy, but MAO levels did not show any change.
Twenty-Four-Hour Dual Gastroduodenal pH Monitoring Baseline fasting gastric and duodenal pH. Gastric pH was 3.2 { 0.3 or 2.7 { 0.6, and duodenal pH was
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6.6 { 0.2 or 7.4 { 0.3 before or after pancreaticogastrostomy, respectively. They were not statistically significant differences. Postprandial 22-hr gastric pH. The relationship of %time at any pH interval between before and after pancreaticogastrostomy was no significant difference (Fig. 6A). Furthermore, the relationship of % time in the gastric contents between before and after pancreaticogastrostomy was no significant difference in any of the three postprandial periods (Fig. 6B). Gastric pH was observed to follow two distinct patterns during FAST period; type A exhibited a persistent acid pH, while type B was characterized by cyclic variation between an acid and an alkaline pH. Five dogs were noted to have type A tracings, while the remaining three exhibited the type B pattern. These patterns were not correlated with BAO or MAO. Following pancreaticogastrostomy, type A dogs displayed a similar fasting pH pattern. The sporadic alkaline spikes were observed in one of these dogs. The type B dogs also showed similar patterns of gastric pH before and after surgery (Fig. 7). Postprandial 22-hr duodenal pH. The relationship of %time between before and after pancreaticogastrostomy was no significant difference at any pH interval (Fig. 8). Furthermore, %time in the duodenal contents was similarly unchanged in any of the three postprandial periods (Fig. 9). The relationship between BAO and gastric or duodenal pH was no significant differences before and after pancreaticogastrostomy. MAO was also not correlated with gastric or duodenal pH. Autopsy Results Autopsy examination revealed several small erosions in the antrum of the stomach in two dogs. In the remaining six dogs, no morphological changes were observed in the stomach, duodenum, pancreas, and liver. The pancreaticogastric anastomosis was patent in all dogs. DISCUSSION
Pancreaticojejunostomy has been used to reconstruct the digestive tract and the remnant pancreas after Whipple resection or PPPD. However, the propensity for getting leakage or disruption at the site of the pancreaticojejunostomy is a major reason for morbidity and mortality [1, 2]. Because of the very low incidence of leakage and disruption, pancreaticogastrostomy has gained widespread clinical use as a possible alternative to pancreaticojejunostomy since the 1970s [3–10]. Experimental implantation of the pancreas into the stomach was first performed in dogs by Tripodi and Sherwin in 1934 [15]. Their observations have subsequently been confirmed by several researchers [16–18]. These studies using the canine model have demonstrated long-term pancreatic secretion after pancreaticogas-
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FIG. 8. Cumulative %time of each interval of the gastric pH in FED (A), STEAD (B), and FAST (C) periods before or after pancreaticogastrostomy. No significant differences were noted.
trostomy. Waugh and Clagett in 1946 [19] performed the first human pancreaticogastrostomy. This method was reintroduced by Mackie et al. [4] in 1975 and by Reding [5] in 1978. Since the first clinical application of pancreaticogastrostomy, 188 cases have been reported in the literature, which postoperative complications occurred in 10% of patients and the cumulative mortality rate was 3.7% [10]. In our experience with 46 consecutive pancreaticogastrostomies from 1987 to 1991, the postoperative complications that related to the technique were observed in one patient (2%), and the operative mortality was 4% that were unrelated to the pancreaticogastrostomy [20]. Numerous theoretic and technical advantages of pancreaticogastrostomy have been summarized as follows. (1) Incomplete activation of pancreatic enzymes in the acid milieu of the stomach may lead to the very low incidence of pancreatitis and pancreatic fistula, while the alkaline pancreatic secretions in turn may protect the gastrojejunostomy against marginal ulceration. (2) Pancreaticogastric anastomosis is easy to accomplish technically
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FIG. 9. (A) Postprandial 22-hr duodenal pH distribution by %time at each pH interval. No significant differences were noted at any pH interval before and after pancreaticogastrostomy. (B) %time in the duodenal contents with a pH of less than 4 or greater than 6 in FED, STEAD, and FAST periods. No significant differences were noted.
without tension since the pancreas lies in natural apposition to the posterior wall of the stomach. (3) It is less prone to develop ischemic complications than a jejunal loop because of the thick gastric wall with its excellent blood supply. (4) Other contributing factors are the possibility of gastric decompression on contact with the anastomosis, and the absence of a long jejunal loop where pancreaticobiliary secretion can pool and increase both intraluminal pressure and loop weight. As stated previously, pancreaticogastrostomy has been established as a secure procedure. There is, however, little information on the physiological standpoint, especially about the actual intraluminal pH profile of the gastrointestinal tract after pancreaticogastrostomy. Therefore, the physiological changes in gastric acid secretion, serum gastrin level, and gastricduodenal pH after pancreaticogastrostomy were investigated in this study. Following pancreaticogastrostomy, BAO levels slightly elevated, indicating a small influence on acid
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secretion. However, MAO levels after tetragastrin stimulation showed no change. The reflux of duodenal contents has been known to cause an increase in basal acid secretion. Thomas [21] has reported an increase of MAO of 68% in dogs with chronic diversion of duodenal contents into the stomach. However, this increase of acid secretion did not occur when the bile alone was diverted into the stomach, and was abolished by vagotomy. Wickbom et al. [22] have demonstrated that the pancreaticogastrostomy produced a significant increase in Heidenhain pouch secretion, while a cholecystogastrostomy did not. These results suggested that the acid hypersecretion might be due to some pancreatic enzyme or its fragment, or an alkaline pH. Our results in the present study were similar to their findings on BAO levels, but not MAO levels, and suggest that a little elevation of BAO seemed to neutralize the alkaline pancreatic contents, and maintained the normal gastric pH. Similar patterns of serum gastrin levels before and after pancreaticogastrostomy indicated that the antral alkalization did not occur after pancreaticogastrostomy. Pancreaticogastrostomy had little influence on the gastric pH as assessed by 24-hr pH monitoring. In the FED period, the acidity slightly increased after pancreaticogastrostomy, but not significantly. A similar pH pattern was seen in the STEAD period, but the brief alkaline spikes of over pH 6, which indicate the pancreatic juice flowing into the stomach through the pancreaticogastric anastomosis, were sporadically found in four dogs after surgery. Therefore, the gastric pH patterns suggest that the relationship between gastric and exocrine pancreatic secretion was preserved after pancreaticogastrostomy. In the duodenum, the mean pH and %time in any periods after pancreaticogastrostomy did not show any change compared to those before surgery. These results suggest that the intraduodenal pH environment remained normal following pancreaticogastrostomy and the duodenal neutralization seemed to be sufficient. A number of studies have been reported on gastroduodenal pH profile in healthy controls and patients with duodenal ulcer [21–28]. These studies have shown that the considerable pH gradients were steeper in the duodenal bulb taking the frequent wide and rapid pH fluctuation, and gradually reduced in the duodenum as a consequence of the neutralizing processes. The highly acidic gastric content in the duodenum is supposed to be neutralized by bicarbonate from the pancreas, liver, and duodenal mucosa. In this study, the duodenal pH electrode was positioned in the second part of the duodenum, so the duodenal pH did not change significantly after pancreaticogastrostomy. This result suggests that pancreatic bicarbonate in the stomach may keep an ability to neutralize gastric acid in the duodenum, or pancreatic bicarbonate may not be essential for the neutralization of gastric acid. The most likely additional source of bicarbonate may be the duodenal mucosa, as shown recently [31].
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In summary, our experimental model was available to evaluate the relationship between gastric and exocrine pancreatic secretion. The results of gastric acid secretion, serum gastrin level, and gastroduodenal pH suggest that the neurohumoral relationship between the stomach, duodenum, and pancreas was preserved after pancreaticogastrostomy. Therefore, the pancreaticogastrostomy is a recommendable reconstructive procedure technically and physiologically after PPPD.
14.
15. 16.
17. 18.
REFERENCES 1. Hayes, D. H., Bolton, J. S., Willis, G. W., and Bowen, J. C. Carcinoma of the ampulla of Vater. Ann. Surg. 206: 572, 1987.
19. 20.
2. Trede, M., Chir, B., and Schwall, G. The complications of pancreatectomy. Ann. Surg. 207: 39, 1988. 3. Park, C. D., Mackie, J. A., and Rhoads, J. E. Pancreaticogastrostomy. Am. J. Surg. 113: 85, 1967.
21.
4. Mackie, J. A., Rhoads, J. E., and Park, C. D. Pancreaticogastrostomy: A further evaluation. Ann. Surg. 182: 541, 1975.
22.
5. Reding, R. Die pancreato-gastrostomie als modifikation der whippleschen operation. Zentralbl. Chir. 103: 943, 1978.
23.
6. Telford, G. L., and Mason, G. R. Pancreaticogastrostomy: clinical experience with direct pancreatic-duct-to-gastric-mucosa anastomosis. Am. J. Surg. 147: 832, 1984.
24.
7. Flautner, L., Tihanyl, T., and Szecseny, A. Pancreatogastrostomy: An ideal complement to pancreatic head resection with preservation of the pylorus in the treatment of chronic pancreatitis. Am. J. Surg. 150: 608, 1985. 8. Kapur, B. M. Pancreaticogastrostomy in pancreaticoduodenal resection for ampullary carcinoma: Experience in thirty-one cases. Surgery 100: 489, 1986.
25. 26.
27.
9. Icard, P., and Dubois, F. Pancreaticogastrostomy following pancreaticoduodenectomy. Ann. Surg. 207: 253, 1988. 10. Delcore, R., Thomas, J. H., Pierce, G. E., and Hermreck, A. S. Pancreaticogastrostomy: A safe drainage procedure after pancreatoduodenectomy. Surgery 108: 641, 1990. 11. Fuchs, K. H., DeMeester, T. R., Hinder, R. A., Stein, H. J., Barlow, A. P., and Gupta, N. C. Computerized identification of pathologic duodenogastric reflux using 24-hour gastric pH monitoring. Ann. Surg. 213: 13, 1991. 12. Walt, R. Twenty four hour intragastric acidity analysis for the future. Gut 27: 1, 1986. 13. Fimmel, C. J., Etienne, A., Ciluffo, T., von Ritter, C., Gasser, T., Rey, J. P., Caradonna-Moscatelli, P., Sabbatini, F., Pace, F., Buhler, H. W., Bauerfeind, P., and Blum, A. L. Long term
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28.
29.
30. 31.
ambulatory gastric pH monitoring: Validation of a new method and effect of H2-antagonist. Gastroenterology 88: 1842, 1985. Emde, C., Garner, A., and Blum, A. L. Technical aspects of intraluminal pH-metry in man: Current status and recommendations. Gut 28: 1177, 1987. Tripodi, A. M., and Sherwin, C. F. Experimental transplantation of the pancreas into the stomach. Arch. Surg. 28: 345, 1934. Person, E. C., and Glenn, F. Pancreaticogastrostomy: Experimental transplantation of the pancreas into the stomach. Arch. Surg. 39: 530, 1939. Wells, C. A., and Annis, D. Experimental pancreaticogastrostomy. Lancet 1: 97, 1949. Ferguson, D. J., and Wangensteen, O. H. Experimental anastomoses of the pancreatic duct. Ann. Surg. 132: 1066, 1950. Waugh, J. M., and Clagett, O. T. Resection of the duodenum and head of the pancreas for carcinoma. Surgery 20: 224, 1946. Takao, S., Shimazu, H., Maenohara, S., Shinchi, H., and Aikou, T. A modified pancreaticogastrostomy following pancreatico-duodenectomy. Am. J. Surg. 165: 317, 1993. Thomas, W. E. G. Functional changes in acid secretion produced by duodeno-gastric reflux. Gut 21: 413, 1980. Wickbom, G., Faith, M., Woodward, E. R., and Dragstedt, L. R. The effect of duodenal regurgitation into the canine stomach on gastric secretion. J. Surg. Res. 14: 497, 1973. Rhodes, J., and Prestwich, C. J. Acidity at different sites in the proximal duodenum of normal subjects and patients with duodenal ulcer. Gut 7: 509, 1966. Rune, S. J., and Viskum, K. Duodenal pH values in normal controls and in patients with duodenal ulcer. Gut 10: 569, 1969. Rune, S. J. pH in the human duodenum. Its physiological and pathophysiological significance. Digestion 8: 261, 1973. McCloy, R. F., Greenberg, G. R., and Baron, J. H. Duodenal pH in health and duodenal ulcer disease: Effect of a meal, CocaCola, smoking, and cimetidine. Gut 25: 386, 1984. Ovesen, L., Bendtsen, F., Tage-Jensen, U., Pedersen, N. T., Gram, B. R., and Rune, S. J. Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency. Gastroenterology 90: 958, 1986. Namamoto, K. Effects of duodenal pH levels on secretin-secretion in the fasting phase of dogs. Arch. Jpn. Chir. 52: 747, 1983 (in Japanese). Eriksen, C. A., Sadek, S. A., and Cuschieri, A. 24-hour ambulatory dual gastroduodenal pH monitoring. Ann. Surg. 208: 702, 1988. Ito, Z. Endocrinology of the Gut. Tokyo: Nanzando, 1979. Pp. 266–275. Flemstro¨m, G., and Kivilaakso, E. Demonstration of a pH gradient at the luminal surface of the rat duodenum in vitro and its dependence on mucosal alkaline secretion. Gastroenterology 84: 787, 1983.
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Gastric Acid Secretion and Gastroduodenal pH after Pancreaticogastrostomy in Dogs HIROYUKI SHINCHI, M.D.,*,1 SONSHIN TAKAO, M.D., PH.D.,*,† KIYOTAKA FUKURA, M.D.,* AND TAKASHI AIKOU, M.D., PH.D.* *First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890, Japan; and †Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218 Submitted for publication October 7, 1994
Pancreaticogastrostomy has been reintroduced as a useful alternative procedure to pancreaticojejunostomy after Whipple resection or pylorus-preserving pancreaticoduodenectomy because of the very low incidence of leakage and disruption. In this study, gastric acid secretion, serum gastrin level, and 24-hr dual gastroduodenal pH after pancreaticogastrostomy were examined on the assumption that a canine model was a pylorus-preserving pancreaticoduodenectomy. Basal acid output (BAO), maximal acid output (MAO), and dual gastroduodenal pH were measured in eight dogs with gastric fistula. After pancreaticogastrostomy, BAO levels showed a slight increase significantly, but MAO levels showed no change. Serum gastrin levels in the fasting and postprandial states showed the similar patterns between before and after surgery. In the 24-hr dual gastroduodenal pH monitoring, gastric pH and duodenal pH also did not change in the fasting and postprandial states. These results suggested that the maintenance of the normal gastric pH after pancreaticogastrostomy was caused by a little increase of BAO, and the neurohumoral relationship between the stomach, duodenum, and pancreas was preserved even after pancreaticogastrostomy. Therefore, the pancreaticogastrostomy is a recommendable reconstructive procedure physiologically after pylorus-preserving pancreaticoduodenectomy. q 1996 Academic Press, Inc.
INTRODUCTION
In general, pancreaticojejunostomy has been used to reconstruct the digestive tract and remnant pancreas after Whipple resection. However, this anastomosis continues to be a source of major morbidity due to the high incidence of anastomotic leakage and disruption [1, 2]. Since the 1970s, the pancreaticogastrostomy has 1 To whom correspondence should be addressed at First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890, Japan. Fax: 0992-65-7426.
0022-4804/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
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m4784$$$53
been reintroduced and used occasionally as a useful alternative procedure to pancreaticojejunostomy after Whipple resection or pylorus-preserving pancreaticoduodenectomy (PPPD). The pancreaticogastrostomy offers several advantages over the pancreaticojejunostomy. First, the anastomosis can be created easily without tension because of the proximity between the stomach and the pancreas. Second, the incomplete activation of the pancreatic enzymes in the acid milieu of the stomach may lead to result in a low incidence of remnant pancreatitis and anastomotic fistula. Third, the alkaline pancreatic secretion may prevent stomal ulceration of the gastrojejunostomy [3–10]. However, the physiological alterations after pancreaticogastrostomy in PPPD has been controversial, and gastric acid secretion, serum gastrin level, and the actual intraluminal pH profile have not yet been reported. Therefore, this study was designed to examine simultaneously gastric acid secretion, serum gastrin level, and gastricduodenal pH before or after pancreaticogastrostomy on the assumption that a canine model was a PPPD. MATERIALS AND METHODS
Preparation Eight male mongrel dogs, varying in weight from 10 to 15 kg, were subjected to laparotomy with creation of a gastric fistula placed near the greater curvature of the corpus and drained by a Thomas cannula (Natsume Co., Tokyo, Japan). We used these dogs with Thomas cannula for our experimental series after 4 weeks. The experiments were conducted with conscious dogs that had been deprived of food, but not water, for 18 hr.
Pancreaticogastrostomy Pancreaticogastrostomy was performed as follows. The accessory (ventral) pancreatic duct was divided and ligated, and then a 2-cm length of the pancreatic head was dissected to separate from the duodenum. The main (dorsal) pancreatic duct was divided, and then the distal stump was ligated to stop the pancreatic juice flowing into the duodenum. A 2-cm tube of 4 Fr Atom multipurpose catheter (Atom Co., Tokyo, Japan) was introduced into the proximal stump of the main pancreatic duct, and was secured with a single 4-O absorbable suture to ensure patency of the duct during the creation of
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FIG. 1. A canine experimental model of pancreaticogastrostomy. (A) Placement of sutures between the posterior wall of the stomach and the pancreas. A tube is inserted into the main (dorsal) pancreatic duct, and then the pancreas and the posterior wall of the stomach were sutured. The insert figure shows the cephalad portion of the pancreaticogastric anastomosis. (B) Completion of pancreaticogastrostomy. The asterisk shows the accessory (ventral) pancreatic duct, which was divided and ligated. Gastrostomy cannula is placed in the greater curvature of the stomach. the anastomosis. Then, a 2-cm seromuscular incision was made on the posterior wall of the stomach, followed by a 2–3-mm stab incision in the gastric mucosa. The anterior surface of the pancreas was sutured to the seromuscular portion of the posterior wall of the stomach using a single layer of interrupted 3-O silk sutures (Fig. 1A). The pancreatic duct was anastomosed to the gastric mucosa with an absorbable 4-O purse-string suture like as the cephalad portion of the pancreaticogastric anastomosis (Fig. 1A, insert). The caudal portion of the pancreaticogastric anastomosis was then completed with interrupted 3-O silk sutures (Fig. 1B). Neither vagotomy nor resection of the stomach, duodenum, or pancreas was performed. There was no postoperative complication related to pancreaticogastrostomy.
taining 2 mg/ml of ethylene diaminetetraacetic acid (EDTA) and a 400 KIU/ml of aprotinin. Samples were centrifuged at 3000 rpm for 10 min, and the serum was kept at 0207C until measurements were conducted. Serum gastrin concentrations were determined by radioimmunoassay (GASTRIN RIAKIT II, Dinabot Co., Tokyo, Japan).
Twenty-Four-Hour Gastric and Duodenal pH Monitoring Intragastric and duodenal pH monitorings were simultaneously performed before and after pancreaticogastrostomy. Antimony pH
Patency of Pancreaticogastrostomy To verify the patency of the pancreatic anastomosis, a fasting secretin stimulation test was performed after 4 weeks of pancreaticogastrostomy. Basal gastric secretions were collected for 60 min, and then a 3 U/kg secretin (Secrepan; Eisai, Tokyo, Japan) was administered intravenously. Gastric contents were collected at 15-min intervals for 60 min. The pH was measured with a glass electrode, and pancreatic amylase activity was determined using a commercially available kit (Alpha Amylase PNP; Boehringer, Mannheim, Germany). Moreover, autopsy examination was performed on each dog when all testing was completed.
Measurement of Gastric Acid Secretion Gastric secretions were collected by gravity drainage through the gastrocutaneous fistula. Basal acid output (BAO) and maximal acid output (MAO) in response to a 6-mg/kg tetragastrin (im) were measured. They were calculated after 15-min intervals to the nearest 0.1 ml, and titrated with sodium hydroxide (NaOH) to pH 7.0. BAO was defined as the sum of the four interval outputs, and MAO was defined as the sum of the four highest consecutive interval outputs following the stimulation. These values were expressed as millimole of acid per hour. Postoperative tests were repeated in duplicate for 6 weeks after pancreaticogastrostomy.
Measurement of Serum Gastrin Level The serum gastrin levels were examined in the fasting and postprandial states. Blood samples were collected into chilled tubes con-
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FIG. 2. Placement of the pH sensors passing through the gastric cannula during the 24-hr monitoring. Note that the proximal sensor is in the antrum of the stomach (A), while the distal sensor is in the descending portion of the duodenum (B).
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FIG. 3. Changes of gastric pH and amylase activity in the gastric juice after intravenous administration of a 3 U/kg secretin following pancreaticogastrostomy. Asterisks show the significant increase over a basal secretion (P õ 0.05), indicating a patent pancreaticogastric anastomosis.
electrodes, which were calibrated in standard buffer solutions at pH 7 and pH 1, were passed through the gastrocutaneous fistula and placed in the second portion of the duodenum and the antrum of the stomach under fluoroscopic guidance (Fig. 2). A digitrapper (Mark II Gold, Synectics Medical) was used to record the pH from each electrode every 4 sec. The data were stored and analyzed by the computer software (Esophagram, Synectics Medical) [11–14]. After an equilibration period of 30 min, the baseline fasting pH was recorded for a period of 90 min. Then, a standardized liquid meal of 40 g/kg minced meat in a 20 ml/kg water, adjusted to pH 6.4, was given. After this meal, gastric and duodenal pH measurements were recorded for 22 hr. During pH measurements, the dogs were allowed to pursue normal activity, and to get only water.
FIG. 5. Serum gastrin levels in the fasting and postprandial states (up to 6 hr after meal) before or after pancreaticogastrostomy.
RESULTS
Patency of Pancreaticogastric Anastomosis The secretin stimulation test showed a marked increase in both the pH level and amylase activity in
Analysis of pH Recordings The gastric and duodenal pH data were analyzed separately for the 24-hr period. The means of fasting gastric and duodenal pH were calculated from the data of an initial 90-min period. The postprandial 22-hr pH recording was divided into three periods that were the fed period (FED; postprandial 0–3 hr), the postprandial steady acid pH period (STEAD; postprandial 3–10 hr) and the remaining fasted period (FAST; postprandial 10–22 hr). For each of three periods, the following values were calculated: (1) the number of alkaline spikes (ú pH 6) in the gastric pH, and the number of acid spikes (õ pH 4) in the duodenal pH; (2) the number of these consecutive episodes for over 5 min; (3) the percentage of a time (%time) with õ pH 4 or ú pH 6; and (4) the cumulative percentage of the total pH data. All procedures were approved by institutional Animal Care and Use Committee at Kagoshima University School of Medicine.
Statistical Analysis Results were expressed as mean { SE. Differences of data between before and after pancreaticogastrostomy were tested for significance at the 0.05 level by the Wilcoxon matched pairs test.
FIG. 4. Changes in basal and maximal acid output before or after pancreaticogastrostomy. The asterisk shows the significant elevation in BAO (P õ 0.05). BAO Å basal acid output, MAO Å maximal acid output
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FIG. 6. (A) Postprandial 22-hr gastric pH distribution by %time at each pH interval. No significant differences between before and after pancreaticogastrostomy were noted at any pH interval. (B) %time in the gastric contents with a pH of less than 4 or greater than 6 in FED, STEAD, and FAST periods. No significant differences were noted.
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FIG. 7. Twenty-four-hour gastric pH tracing from two dogs before or after pancreaticogastrostomy. The gastric pH patterns in the fasting (FAST) period were divided into two types. Type A, the steady acid pH is observed throughout FAST period. Type B, the gastric content exhibited the cyclic variations between acidic and alkaline pH during FAST period. The gastric pH patterns of both type A and type B remained constant before or after pancreaticogastrostomy. FED Å feeding period, STEAD Å postprandial steady state, FAST Å fasting period.
the gastric contents (Fig. 3), autopsy examination also revealed the patency of pancreaticogastrostomy in all dogs. These results indicated that the pancreaticogastric anastomoses were patent. Gastric Acid Secretion
Serum Gastrin Levels Serum gastrin levels before or after pancreaticogastrostomy showed a similar pattern in fasting and postprandial states up to 6 hr after meal (Fig. 5). The differences between these patterns were not shown significantly.
BAO and MAO levels before or after pancreaticogastrostomy are shown in Fig. 4. BAO levels showed a slight increase (P õ 0.05) after pancreaticogastrostomy, but MAO levels did not show any change.
Twenty-Four-Hour Dual Gastroduodenal pH Monitoring Baseline fasting gastric and duodenal pH. Gastric pH was 3.2 { 0.3 or 2.7 { 0.6, and duodenal pH was
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6.6 { 0.2 or 7.4 { 0.3 before or after pancreaticogastrostomy, respectively. They were not statistically significant differences. Postprandial 22-hr gastric pH. The relationship of %time at any pH interval between before and after pancreaticogastrostomy was no significant difference (Fig. 6A). Furthermore, the relationship of % time in the gastric contents between before and after pancreaticogastrostomy was no significant difference in any of the three postprandial periods (Fig. 6B). Gastric pH was observed to follow two distinct patterns during FAST period; type A exhibited a persistent acid pH, while type B was characterized by cyclic variation between an acid and an alkaline pH. Five dogs were noted to have type A tracings, while the remaining three exhibited the type B pattern. These patterns were not correlated with BAO or MAO. Following pancreaticogastrostomy, type A dogs displayed a similar fasting pH pattern. The sporadic alkaline spikes were observed in one of these dogs. The type B dogs also showed similar patterns of gastric pH before and after surgery (Fig. 7). Postprandial 22-hr duodenal pH. The relationship of %time between before and after pancreaticogastrostomy was no significant difference at any pH interval (Fig. 8). Furthermore, %time in the duodenal contents was similarly unchanged in any of the three postprandial periods (Fig. 9). The relationship between BAO and gastric or duodenal pH was no significant differences before and after pancreaticogastrostomy. MAO was also not correlated with gastric or duodenal pH. Autopsy Results Autopsy examination revealed several small erosions in the antrum of the stomach in two dogs. In the remaining six dogs, no morphological changes were observed in the stomach, duodenum, pancreas, and liver. The pancreaticogastric anastomosis was patent in all dogs. DISCUSSION
Pancreaticojejunostomy has been used to reconstruct the digestive tract and the remnant pancreas after Whipple resection or PPPD. However, the propensity for getting leakage or disruption at the site of the pancreaticojejunostomy is a major reason for morbidity and mortality [1, 2]. Because of the very low incidence of leakage and disruption, pancreaticogastrostomy has gained widespread clinical use as a possible alternative to pancreaticojejunostomy since the 1970s [3–10]. Experimental implantation of the pancreas into the stomach was first performed in dogs by Tripodi and Sherwin in 1934 [15]. Their observations have subsequently been confirmed by several researchers [16–18]. These studies using the canine model have demonstrated long-term pancreatic secretion after pancreaticogas-
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FIG. 8. Cumulative %time of each interval of the gastric pH in FED (A), STEAD (B), and FAST (C) periods before or after pancreaticogastrostomy. No significant differences were noted.
trostomy. Waugh and Clagett in 1946 [19] performed the first human pancreaticogastrostomy. This method was reintroduced by Mackie et al. [4] in 1975 and by Reding [5] in 1978. Since the first clinical application of pancreaticogastrostomy, 188 cases have been reported in the literature, which postoperative complications occurred in 10% of patients and the cumulative mortality rate was 3.7% [10]. In our experience with 46 consecutive pancreaticogastrostomies from 1987 to 1991, the postoperative complications that related to the technique were observed in one patient (2%), and the operative mortality was 4% that were unrelated to the pancreaticogastrostomy [20]. Numerous theoretic and technical advantages of pancreaticogastrostomy have been summarized as follows. (1) Incomplete activation of pancreatic enzymes in the acid milieu of the stomach may lead to the very low incidence of pancreatitis and pancreatic fistula, while the alkaline pancreatic secretions in turn may protect the gastrojejunostomy against marginal ulceration. (2) Pancreaticogastric anastomosis is easy to accomplish technically
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FIG. 9. (A) Postprandial 22-hr duodenal pH distribution by %time at each pH interval. No significant differences were noted at any pH interval before and after pancreaticogastrostomy. (B) %time in the duodenal contents with a pH of less than 4 or greater than 6 in FED, STEAD, and FAST periods. No significant differences were noted.
without tension since the pancreas lies in natural apposition to the posterior wall of the stomach. (3) It is less prone to develop ischemic complications than a jejunal loop because of the thick gastric wall with its excellent blood supply. (4) Other contributing factors are the possibility of gastric decompression on contact with the anastomosis, and the absence of a long jejunal loop where pancreaticobiliary secretion can pool and increase both intraluminal pressure and loop weight. As stated previously, pancreaticogastrostomy has been established as a secure procedure. There is, however, little information on the physiological standpoint, especially about the actual intraluminal pH profile of the gastrointestinal tract after pancreaticogastrostomy. Therefore, the physiological changes in gastric acid secretion, serum gastrin level, and gastricduodenal pH after pancreaticogastrostomy were investigated in this study. Following pancreaticogastrostomy, BAO levels slightly elevated, indicating a small influence on acid
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secretion. However, MAO levels after tetragastrin stimulation showed no change. The reflux of duodenal contents has been known to cause an increase in basal acid secretion. Thomas [21] has reported an increase of MAO of 68% in dogs with chronic diversion of duodenal contents into the stomach. However, this increase of acid secretion did not occur when the bile alone was diverted into the stomach, and was abolished by vagotomy. Wickbom et al. [22] have demonstrated that the pancreaticogastrostomy produced a significant increase in Heidenhain pouch secretion, while a cholecystogastrostomy did not. These results suggested that the acid hypersecretion might be due to some pancreatic enzyme or its fragment, or an alkaline pH. Our results in the present study were similar to their findings on BAO levels, but not MAO levels, and suggest that a little elevation of BAO seemed to neutralize the alkaline pancreatic contents, and maintained the normal gastric pH. Similar patterns of serum gastrin levels before and after pancreaticogastrostomy indicated that the antral alkalization did not occur after pancreaticogastrostomy. Pancreaticogastrostomy had little influence on the gastric pH as assessed by 24-hr pH monitoring. In the FED period, the acidity slightly increased after pancreaticogastrostomy, but not significantly. A similar pH pattern was seen in the STEAD period, but the brief alkaline spikes of over pH 6, which indicate the pancreatic juice flowing into the stomach through the pancreaticogastric anastomosis, were sporadically found in four dogs after surgery. Therefore, the gastric pH patterns suggest that the relationship between gastric and exocrine pancreatic secretion was preserved after pancreaticogastrostomy. In the duodenum, the mean pH and %time in any periods after pancreaticogastrostomy did not show any change compared to those before surgery. These results suggest that the intraduodenal pH environment remained normal following pancreaticogastrostomy and the duodenal neutralization seemed to be sufficient. A number of studies have been reported on gastroduodenal pH profile in healthy controls and patients with duodenal ulcer [21–28]. These studies have shown that the considerable pH gradients were steeper in the duodenal bulb taking the frequent wide and rapid pH fluctuation, and gradually reduced in the duodenum as a consequence of the neutralizing processes. The highly acidic gastric content in the duodenum is supposed to be neutralized by bicarbonate from the pancreas, liver, and duodenal mucosa. In this study, the duodenal pH electrode was positioned in the second part of the duodenum, so the duodenal pH did not change significantly after pancreaticogastrostomy. This result suggests that pancreatic bicarbonate in the stomach may keep an ability to neutralize gastric acid in the duodenum, or pancreatic bicarbonate may not be essential for the neutralization of gastric acid. The most likely additional source of bicarbonate may be the duodenal mucosa, as shown recently [31].
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In summary, our experimental model was available to evaluate the relationship between gastric and exocrine pancreatic secretion. The results of gastric acid secretion, serum gastrin level, and gastroduodenal pH suggest that the neurohumoral relationship between the stomach, duodenum, and pancreas was preserved after pancreaticogastrostomy. Therefore, the pancreaticogastrostomy is a recommendable reconstructive procedure technically and physiologically after PPPD.
14.
15. 16.
17. 18.
REFERENCES 1. Hayes, D. H., Bolton, J. S., Willis, G. W., and Bowen, J. C. Carcinoma of the ampulla of Vater. Ann. Surg. 206: 572, 1987.
19. 20.
2. Trede, M., Chir, B., and Schwall, G. The complications of pancreatectomy. Ann. Surg. 207: 39, 1988. 3. Park, C. D., Mackie, J. A., and Rhoads, J. E. Pancreaticogastrostomy. Am. J. Surg. 113: 85, 1967.
21.
4. Mackie, J. A., Rhoads, J. E., and Park, C. D. Pancreaticogastrostomy: A further evaluation. Ann. Surg. 182: 541, 1975.
22.
5. Reding, R. Die pancreato-gastrostomie als modifikation der whippleschen operation. Zentralbl. Chir. 103: 943, 1978.
23.
6. Telford, G. L., and Mason, G. R. Pancreaticogastrostomy: clinical experience with direct pancreatic-duct-to-gastric-mucosa anastomosis. Am. J. Surg. 147: 832, 1984.
24.
7. Flautner, L., Tihanyl, T., and Szecseny, A. Pancreatogastrostomy: An ideal complement to pancreatic head resection with preservation of the pylorus in the treatment of chronic pancreatitis. Am. J. Surg. 150: 608, 1985. 8. Kapur, B. M. Pancreaticogastrostomy in pancreaticoduodenal resection for ampullary carcinoma: Experience in thirty-one cases. Surgery 100: 489, 1986.
25. 26.
27.
9. Icard, P., and Dubois, F. Pancreaticogastrostomy following pancreaticoduodenectomy. Ann. Surg. 207: 253, 1988. 10. Delcore, R., Thomas, J. H., Pierce, G. E., and Hermreck, A. S. Pancreaticogastrostomy: A safe drainage procedure after pancreatoduodenectomy. Surgery 108: 641, 1990. 11. Fuchs, K. H., DeMeester, T. R., Hinder, R. A., Stein, H. J., Barlow, A. P., and Gupta, N. C. Computerized identification of pathologic duodenogastric reflux using 24-hour gastric pH monitoring. Ann. Surg. 213: 13, 1991. 12. Walt, R. Twenty four hour intragastric acidity analysis for the future. Gut 27: 1, 1986. 13. Fimmel, C. J., Etienne, A., Ciluffo, T., von Ritter, C., Gasser, T., Rey, J. P., Caradonna-Moscatelli, P., Sabbatini, F., Pace, F., Buhler, H. W., Bauerfeind, P., and Blum, A. L. Long term
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28.
29.
30. 31.
ambulatory gastric pH monitoring: Validation of a new method and effect of H2-antagonist. Gastroenterology 88: 1842, 1985. Emde, C., Garner, A., and Blum, A. L. Technical aspects of intraluminal pH-metry in man: Current status and recommendations. Gut 28: 1177, 1987. Tripodi, A. M., and Sherwin, C. F. Experimental transplantation of the pancreas into the stomach. Arch. Surg. 28: 345, 1934. Person, E. C., and Glenn, F. Pancreaticogastrostomy: Experimental transplantation of the pancreas into the stomach. Arch. Surg. 39: 530, 1939. Wells, C. A., and Annis, D. Experimental pancreaticogastrostomy. Lancet 1: 97, 1949. Ferguson, D. J., and Wangensteen, O. H. Experimental anastomoses of the pancreatic duct. Ann. Surg. 132: 1066, 1950. Waugh, J. M., and Clagett, O. T. Resection of the duodenum and head of the pancreas for carcinoma. Surgery 20: 224, 1946. Takao, S., Shimazu, H., Maenohara, S., Shinchi, H., and Aikou, T. A modified pancreaticogastrostomy following pancreatico-duodenectomy. Am. J. Surg. 165: 317, 1993. Thomas, W. E. G. Functional changes in acid secretion produced by duodeno-gastric reflux. Gut 21: 413, 1980. Wickbom, G., Faith, M., Woodward, E. R., and Dragstedt, L. R. The effect of duodenal regurgitation into the canine stomach on gastric secretion. J. Surg. Res. 14: 497, 1973. Rhodes, J., and Prestwich, C. J. Acidity at different sites in the proximal duodenum of normal subjects and patients with duodenal ulcer. Gut 7: 509, 1966. Rune, S. J., and Viskum, K. Duodenal pH values in normal controls and in patients with duodenal ulcer. Gut 10: 569, 1969. Rune, S. J. pH in the human duodenum. Its physiological and pathophysiological significance. Digestion 8: 261, 1973. McCloy, R. F., Greenberg, G. R., and Baron, J. H. Duodenal pH in health and duodenal ulcer disease: Effect of a meal, CocaCola, smoking, and cimetidine. Gut 25: 386, 1984. Ovesen, L., Bendtsen, F., Tage-Jensen, U., Pedersen, N. T., Gram, B. R., and Rune, S. J. Intraluminal pH in the stomach, duodenum, and proximal jejunum in normal subjects and patients with exocrine pancreatic insufficiency. Gastroenterology 90: 958, 1986. Namamoto, K. Effects of duodenal pH levels on secretin-secretion in the fasting phase of dogs. Arch. Jpn. Chir. 52: 747, 1983 (in Japanese). Eriksen, C. A., Sadek, S. A., and Cuschieri, A. 24-hour ambulatory dual gastroduodenal pH monitoring. Ann. Surg. 208: 702, 1988. Ito, Z. Endocrinology of the Gut. Tokyo: Nanzando, 1979. Pp. 266–275. Flemstro¨m, G., and Kivilaakso, E. Demonstration of a pH gradient at the luminal surface of the rat duodenum in vitro and its dependence on mucosal alkaline secretion. Gastroenterology 84: 787, 1983.
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