©1991 S. Kargcr AG. Basel 0014-312X/9I /0234-0214S2.75/0
Eur Surg Res 1991;23:214-221
Prophylactic Administration of Urinary Trypsin Inhibitor Prevents Postoperative Hyperamylasemia after R2 Gastrectomy in Patients with Gastric Cancer A Prospective Randomized Trial D. Korenaga, H. Orita, Y. Kakeji, M. Haraguchi, Y. Maehara, K. Sugimachi Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Key Words. Gastric cancer • Surgery • Hyperamylasemia
Introduction In the last 2 decades, there has been strik ing improvement in Japan in the prognosis of gastric cancer [1]. Although much of the
improvement is attributed to the better de tection of early gastric cancer, the standard ization of extensive lymphadenectomy (i.e. complete removal of extragastric nodes as well as perigastric nodes), regardless of the
Downloaded by: UCSF Library & CKM 132.174.255.215 - 9/4/2017 9:44:46 AM
Abstract. The purpose of this prospective randomized study was to determine whether prophylactic administration of urinary trypsin inhibitor prevents postoperative damage to the pancreas caused by R2 gastrectomy in patients with gastric cancer, by analyzing related enzyme activities. Among the 22 patients who underwent distal partial gastrectomy together with R2 lymphadenectomy, 12 were given the drug for 3 days postoperatively, and 10 no therapeutic agent. These groups were otherwise comparable. Postoperatively, the control patients had significantly higher levels of total amylase activity in the serum and P-type amylase when compared to the preoperative data. These amylase activities almost remained at the preoperative level in those given the drug. When the ratio of increase in enzyme activities (postoperative value divided by preoperative value) were compared, on the 7th postoperative day, total amylase activity in the serum and P-type amylase were significantly different between the two groups (p < 0.05). This difference was also evident when compar ing total amylase activity in the urine (p < 0.05). These findings indicate that prophylactic administration of urinary trypsin inhibitor would aid in preventing postoperative hyperamy lasemia caused by R2 gastrectomy in patients with gastric cancer.
Treatment of Hyperamylasemia after Gastric Cancer Surgery
ized trial, we investigated whether or not prophylactic administration of urinary tryp sin inhibitor would prevent postoperative damage to the pancreas caused by R2 gas trectomy in patients with gastric cancer.
Materials and Methods Patients Twenty-five Japanese patients with gastric cancer, who had been treated surgically in the Second Depart ment ofSurgey, Faculty of Medicine. Kyushu Univer sity, between 1987 and 1988 were enrolled in this pro spective randomized study. The criteria for patient selection were: ( 1) age less than 80 years; (2) no pre vious administration of specific inhibitors of pan creatic enzymes either before or during surgery for treatment of possible postoperative pancreatitis; (3) scheduled to undergo a standard operation such as distal partial gastrectomy with R2 lymphadenectomy, and (4) adequate organ system function on preopera tive evaluation: serum GOT and GPT levels < 4 0 IU/1, serum creatinine level < 1.0 mg/dl. leukocytes > 4 ,0 0 0 /m m \ platelets > lOO-OGO/mm’. Type o f Surgery Surgery was performed by the same surgical team. The R2 gastrectomy was performed according to the procedure described by the Japanese Research Soci ety for Gastric Cancer [1, 14]. The entire greater omentum, superior leaf of the mesocolon, pancreatic capsule and lesser omentum were removed en bloc with the stomach. In this series, all the tumors were located in the lower two thirds of the stomach. Hence, a distal partial gastrectomy was performed together with dissection of the perigastric nodes along the lesser and greater curvatures and those in the right paracardial, suprapyloric and infrapyloric regions. Extragastric nodes, such as those along the left gastric, splenic, celiac and common hepatic arteries, were also dissected. The left gastric artery was ligated and divided at its origin. Treatment With informed consent, these 25 patients were randomized immediately after surgery by flipping a coin. Thus, two groups were designated: those who received urinary trypsin inhibitor (Ulinastatin; Mo-
Downloaded by: UCSF Library & CKM 132.174.255.215 - 9/4/2017 9:44:46 AM
presence or absence of metastasis, appears to improve prognosis [1, 2], Since the 1960s, we have introduced radical gastrectomy and extensive lymphadenectomy as standard procedure. Because perioperative manage ment, surgical techniques and anesthesia have improved greatly, extensive lymphad enectomy is now feasible with a greater mar gin of safety [1-3]. The operative procedure has also been applied to clinical trials per formed by Western surgeons [4-6]. How ever, postoperative care remains very impor tant in the elderly or other poor-risk pa tients. Acute pancreatitis is a severe complica tion of upper abdominal surgery. The inci dence is reported to be between 0.6 and 10% [7-9]. Direct pancreatic injury is a relatively common complication after radical gastric surgery. Anastomotic leakage also predis poses such patients to a worsening of con comitant pancreatic disorders. An earlier study on enzymatic evidence for pancreatitis after gastric surgery revealed that patients undergoing en bloc lymph node dissection are vulnerable to damage to the pancreas, compared with events in the non-lymphadenectomized [10]. Although elevated levels of P-type amylase do not always correlate with pancreatitis, determination of total amylase activity and the amylase isozyme pattern help to determine correctly the degree of pancreatic damage caused by lymphadenec tomy [10]. Specific inhibitiors of pancreatic en zymes, such as aprotinin [11], gabexate me sylate [ 12] and urinary trypsin inhibitor [ 13], have been used to treat acute pancreatitis; however, studies on the efficacy of these drugs in preventing pancreatic damage after radical gastric surgery apparently have not been reported. In this prospective random
215
Korcnaga/Orita/Kakeji/Haraguchi/Maehara/Sugimachi
216
study. Two lacked preoperative data on related en zyme activities, and I had a salivary gland removed because of malignancy.
Ulinastatin (i.v) 0.5—1 xlO’ U/day
Op
1
2
3
4
5
6
7
Eur Surg Res 1991;23:214-221
Prophylactic Administration of Urinary Trypsin Inhibitor Prevents Postoperative Hyperamylasemia after R2 Gastrectomy in Patients with Gastric Cancer A Prospective Randomized Trial D. Korenaga, H. Orita, Y. Kakeji, M. Haraguchi, Y. Maehara, K. Sugimachi Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Key Words. Gastric cancer • Surgery • Hyperamylasemia
Introduction In the last 2 decades, there has been strik ing improvement in Japan in the prognosis of gastric cancer [1]. Although much of the
improvement is attributed to the better de tection of early gastric cancer, the standard ization of extensive lymphadenectomy (i.e. complete removal of extragastric nodes as well as perigastric nodes), regardless of the
Downloaded by: UCSF Library & CKM 132.174.255.215 - 9/4/2017 9:44:46 AM
Abstract. The purpose of this prospective randomized study was to determine whether prophylactic administration of urinary trypsin inhibitor prevents postoperative damage to the pancreas caused by R2 gastrectomy in patients with gastric cancer, by analyzing related enzyme activities. Among the 22 patients who underwent distal partial gastrectomy together with R2 lymphadenectomy, 12 were given the drug for 3 days postoperatively, and 10 no therapeutic agent. These groups were otherwise comparable. Postoperatively, the control patients had significantly higher levels of total amylase activity in the serum and P-type amylase when compared to the preoperative data. These amylase activities almost remained at the preoperative level in those given the drug. When the ratio of increase in enzyme activities (postoperative value divided by preoperative value) were compared, on the 7th postoperative day, total amylase activity in the serum and P-type amylase were significantly different between the two groups (p < 0.05). This difference was also evident when compar ing total amylase activity in the urine (p < 0.05). These findings indicate that prophylactic administration of urinary trypsin inhibitor would aid in preventing postoperative hyperamy lasemia caused by R2 gastrectomy in patients with gastric cancer.
Treatment of Hyperamylasemia after Gastric Cancer Surgery
ized trial, we investigated whether or not prophylactic administration of urinary tryp sin inhibitor would prevent postoperative damage to the pancreas caused by R2 gas trectomy in patients with gastric cancer.
Materials and Methods Patients Twenty-five Japanese patients with gastric cancer, who had been treated surgically in the Second Depart ment ofSurgey, Faculty of Medicine. Kyushu Univer sity, between 1987 and 1988 were enrolled in this pro spective randomized study. The criteria for patient selection were: ( 1) age less than 80 years; (2) no pre vious administration of specific inhibitors of pan creatic enzymes either before or during surgery for treatment of possible postoperative pancreatitis; (3) scheduled to undergo a standard operation such as distal partial gastrectomy with R2 lymphadenectomy, and (4) adequate organ system function on preopera tive evaluation: serum GOT and GPT levels < 4 0 IU/1, serum creatinine level < 1.0 mg/dl. leukocytes > 4 ,0 0 0 /m m \ platelets > lOO-OGO/mm’. Type o f Surgery Surgery was performed by the same surgical team. The R2 gastrectomy was performed according to the procedure described by the Japanese Research Soci ety for Gastric Cancer [1, 14]. The entire greater omentum, superior leaf of the mesocolon, pancreatic capsule and lesser omentum were removed en bloc with the stomach. In this series, all the tumors were located in the lower two thirds of the stomach. Hence, a distal partial gastrectomy was performed together with dissection of the perigastric nodes along the lesser and greater curvatures and those in the right paracardial, suprapyloric and infrapyloric regions. Extragastric nodes, such as those along the left gastric, splenic, celiac and common hepatic arteries, were also dissected. The left gastric artery was ligated and divided at its origin. Treatment With informed consent, these 25 patients were randomized immediately after surgery by flipping a coin. Thus, two groups were designated: those who received urinary trypsin inhibitor (Ulinastatin; Mo-
Downloaded by: UCSF Library & CKM 132.174.255.215 - 9/4/2017 9:44:46 AM
presence or absence of metastasis, appears to improve prognosis [1, 2], Since the 1960s, we have introduced radical gastrectomy and extensive lymphadenectomy as standard procedure. Because perioperative manage ment, surgical techniques and anesthesia have improved greatly, extensive lymphad enectomy is now feasible with a greater mar gin of safety [1-3]. The operative procedure has also been applied to clinical trials per formed by Western surgeons [4-6]. How ever, postoperative care remains very impor tant in the elderly or other poor-risk pa tients. Acute pancreatitis is a severe complica tion of upper abdominal surgery. The inci dence is reported to be between 0.6 and 10% [7-9]. Direct pancreatic injury is a relatively common complication after radical gastric surgery. Anastomotic leakage also predis poses such patients to a worsening of con comitant pancreatic disorders. An earlier study on enzymatic evidence for pancreatitis after gastric surgery revealed that patients undergoing en bloc lymph node dissection are vulnerable to damage to the pancreas, compared with events in the non-lymphadenectomized [10]. Although elevated levels of P-type amylase do not always correlate with pancreatitis, determination of total amylase activity and the amylase isozyme pattern help to determine correctly the degree of pancreatic damage caused by lymphadenec tomy [10]. Specific inhibitiors of pancreatic en zymes, such as aprotinin [11], gabexate me sylate [ 12] and urinary trypsin inhibitor [ 13], have been used to treat acute pancreatitis; however, studies on the efficacy of these drugs in preventing pancreatic damage after radical gastric surgery apparently have not been reported. In this prospective random
215
Korcnaga/Orita/Kakeji/Haraguchi/Maehara/Sugimachi
216
study. Two lacked preoperative data on related en zyme activities, and I had a salivary gland removed because of malignancy.
Ulinastatin (i.v) 0.5—1 xlO’ U/day
Op
1
2
3
4
5
6
7
