Double-stapled esophagogastric anastomosis for resection of esophagogastric or cardia cancer: new application for an old technique.

In colorectal surgery, the double-stapled technique is used extensively, because it is a fairly safe and simple procedure and is useful in relatively inaccessible areas. For these reasons, we adapted the procedure to the upper gastrointestinal tract. The present study reports our first experiences of the surgical efficacy using an esophagogastric double-stapled end-to-end anastomosis for subtotal esophagectomy and cardia resection. We retrospectively studied 31 patients treated between January 1991 and January 1997 with respect to hospital mortality, anastomotic leakage, cancer recurrence, and benign stricture rate. No hospital mortality was seen. One nonfatal anastomotic leak occurred (3%). In three patients, esophageal resection was not radical (10%). Of the remaining 28 patients, one had an anastomotic cancer recurrence (4%). Eleven of the remaining 27 patients (41%) developed a benign anastomotic stricture. All achieved normal swallowing after a median of two endoscopic dilatation procedures using TTS balloons. In conclusion, the double-stapled end-to-end anastomosis technique after resection for esophagogastric or cardia cancer is a simple and expeditious procedure, carrying an acceptable perioperative morbidity and cancer recurrence rate. Larger staplers are recommended to lower the high stricture rate observed after the usage of a 21-mm stapler in this study.

Endoscopic palliation of inoperable cancer of the oesophagus or cardia by argon electrocoagulation.

BACKGROUND: Cancer of the oesophagus and the cardia tends to present late. Palliation of dysphagia is the prospect of most of the patients. This paper reports the use of argon electrocoagulation in 83 patients with inoperable cancer strictures in the oesophagus and cardia. METHODS: The argon electrocoagulation was done by a fibre conducting electricity and argon air to the site of coagulation. After treatment the patients were allowed to take fluids and normal food the same evening or the next morning. After recanalization the patients were treated regularly every 3-4 weeks. RESULTS: Recanalization enabling passage for normal food was achieved with 1 treatment in 48 patients (58%), whereas 22 (26%) needed more than 1 treatment. In 13 patients (16%) the ability to eat normal food was not achieved. In these patients dysphagia improved at least one grade. Perforation was seen in seven patients (8%) and in 1% of treatments. Perforations were successfully treated conservatively in six of the seven patients. Sixty-three patients (76%) died during the investigation period, on average 146 days (range, 43-397 days) after diagnosis. CONCLUSION: Argon electrocoagulation offers an easy, cheap, and safe alternative to treatment with laser photocoagulation and expandable metal stents.

Nonsurgical treatment of esophageal perforations after endoscopic palliation in advanced esophageal cancer.

BACKGROUND AND STUDY AIMS: Iatrogenic esophageal perforation during palliative endoscopic treatment in patients with incurable esophageal or cardiac cancer is a severe complication, associated with a high rate of mortality. The treatment remains controversial, since both nonsurgical and surgical treatment regimens are used. The present study describes a nonsurgical regimen. PATIENTS AND METHODS: Nine cases of perforation occurred in 142 consecutive patients referred for endoscopic palliation of dysphagia, corresponding to a perforation rate of 6%. Laser therapy was the main treatment used (argon plasma coagulation or Nd:YAG photocoagulation). RESULTS: Nonsurgical treatment was successful in six patients (75%). Two patients died (22%) as a direct result of esophageal perforation following endoscopic palliation procedures. CONCLUSION: These findings show an acceptable mortality rate using a nonsurgical treatment regimen involving broad-spectrum antibiotics, nasogastric suction, and parenteral nutrition, with pleural drainage and endoprosthesis placement in addition when indicated.

Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy.

The importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p < 0.05), increased the clearance of total alpha-amino-nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p < 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p < 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin.

Elective laparoscopic cholecystectomy nearly abolishes the postoperative hepatic catabolic stress response.

OBJECTIVE: Surgery results in a catabolic state of postoperative stress, where the efficiency of the liver to convert amino acids to urea is increased. This study measured the metabolic consequences of the less traumatic laparoscopic surgery in elective cholecystectomy compared with traditional open surgery technique. SUMMARY BACKGROUND DATA: The authors previously have shown that open cholecystectomy doubles the urea synthesis measured by the means of the functional hepatic nitrogen clearance. Glucagon and cortisol increased by 50% (p < 0.05) and 75% (p < 0.05), respectively, after open cholecystectomy. METHODS: Patients undergoing uncomplicated elective laparoscopic cholecystectomies were included. Preoperatively and on the first postoperative day, blood and urine samples were drawn every hour under basal conditions and during amino acid infusion. The urea synthesis rate was calculated from the urea excreted in urine and accumulated in total body water. Functional hepatic nitrogen clearance was quantified as the slope of the linear relation between blood amino-N concentration and the urea synthesis rate. The results were compared with an historic matched group of patients who underwent open cholecystectomies and were studied by the same protocol. RESULTS: The laparoscopic cholecystectomy increased the functional hepatic nitrogen clearance by only 25% (from 8.7 +/- 0.9 to 11.1 +/- 1.5 mL/sec [mean +/- SEM; p < 0.05]), compared with a doubling after open cholecystectomy (from 9.4 +/- 0.9 to 17.6 +/- 3.3 mL/sec [p < 0.05]). The difference between the groups was significant (p < 0.05). Neither glucagon nor cortisol increased significantly after laparoscopic cholecystectomy. CONCLUSIONS: The laparoscopic technique results in a much smaller postoperative hepatic catabolic stress response and probably reduced tissue loss of amino-N. This may be important for the more rapid convalescence and reduced postoperative fatigue.

The in vivo effect of interleukin-1 beta on urea synthesis is mediated by glucocorticoids in rats.

Interleukin-1 beta has been proposed as one mediator of parts of the catabolic response following surgery. However, it is not known whether such an effect is due to interleukin-1 beta itself or the associated changes in glucocorticoids. The effect of interleukin-1 beta on urea synthesis was investigated in rats given a high (10 micrograms kg-1) and a low dose (0.1 microgram kg-1) of recombinant interleukin-1 beta (NOVO, Denmark) 3 h prior to determination of the rate of urea synthesis in vivo. Urea synthesis increased dose-dependently after the low dose from 4.0 +/- 0.3 (control) to 6.3 +/- 0.3 (P < 0.01), and after the high dose to 7.7 +/- 0.3 mumol (min.100 gBW)-1 (P < 0.01). The blood concentration of amino acids fell during interleukin-1 beta treatment, so the effect on urea synthesis was not due solely to increased proteolysis, but was exerted predominantly in the liver. Pharmacological glucocorticoid receptor blockade (hormone analogue RU486, Roussel-Uclaf, Paris, France) given 1 h prior to the interleukin treatment, completely abolished the interleukin-1 beta induced increases in urea synthesis. The study demonstrates that interleukin-1 beta stimulates urea synthesis in vivo, and that the major part of the effect depends on glucocorticoid action.

Xylitol normalizes the accelerated hepatic capacity for conversion of amino nitrogen to urea nitrogen in diabetic rats.

In diabetes, the capacity of urea nitrogen synthesis, ie, a substrate-independent measure of the hepatic conversion of amino nitrogen to urea nitrogen, is increased. Xylitol decreases urea synthesis in normal rats. Capacity of urea nitrogen synthesis and nitrogen balance were measured during intravenous alanine loading in control rats, rats with experimental diabetes (streptozocin 75 mg/kg), and rats with experimental diabetes infused with xylitol to 1 mmol/L. In control rats, capacity of urea nitrogen synthesis was 9.4 +/- 1.1 mumol/min per 100 g of body weight, and nitrogen balance -2.7 +/- 1.2 mumol/min per 100 g of body weight. In the diabetics, these values were markedly increased to 26.6 +/- 1.9 and -16.3 +/- 2.1 mumol/min per 100 g of body weight, respectively (p < 0.01). The infusion of xylitol normalized these values to 11.2 +/- 1.0 and -3.6 +/- 2.1 mumol/min per 100 g of body weight for capacity of urea nitrogen synthesis and nitrogen balance, respectively. Xylitol did not change glucagon or insulin. Xylitol improved the nitrogen economy of uncontrolled diabetic rats by decreasing urea synthesis. The mechanism is not settled, but it does not involve insulin or glucagon.

The hepatic catabolic stress response. Hormonal regulation of urea synthesis after surgery.

Following non complicated surgical trauma in man a hepatic condition has been identified that is characterized by lower than normal plasma alpha-amino nitrogen concentration and increased plasma clearance of gluconeogenic and ureagenic amino acids. Amino acids are removed from the blood by the liver, by way of a doubling of the hepatic efficacy fo urea synthesis. At any plasma amino acid concentration twice as much amino-nitrogen is excreted as urea-nitrogen, and thus lost for protein synthesis. This hepatic stress response lasts for one week postoperatively. In rats, hysterectomy elicits a similar response, but the time of the maximum increase in urea synthesis occurs earlier. Combined neuro-hormonal blockade totally prevents the response in cholecystectomized patients. In rats, it is preventable by selective blockades of glucocorticoid action and of prostaglandins synthesis. In isolated livers catecholamines, corticosterone, and glucagon together bring about 40% of the increase in urea synthesis in vivo, but only in livers "conditioned" by hysterectomy three hours earlier. Prostaglandin E2 in itself has no effect on urea synthesis, but accelerates the effect of the hormones. The regulatory system is incompletely elucidated, although several mediators are identified. A hierarchical system is suggested and discussed, and further possible regulators indicated. The role of liver for whole body nitrogen homeostasis during stress is estimated. The increase in hepatic efficacy for urea synthesis in itself accounts for about 50% of the postoperative nitrogen loss. Identification of the pathophysiological changes following surgical trauma is probably decisive for endeavours to improve postoperative morbidity and mortality. Modification of the hepatic contribution to postoperative loss of nitrogen may be necessary.

Effect of glucagon immunoneutralization on the increase in urea synthesis after hysterectomy in rats.

To study the effect of glucagon immunoneutralization on postoperative changes of urea synthesis, hysterectomized rats were given one injection of a specific high titre antibody against pancreatic glucagon 24 h before operation raising the plasma glucagon binding capacity to values 10-20 times higher than the plasma glucagon concentration in control animals. Earlier studies have shown that the spontaneous rate of urea-N synthesis (UNSR) doubles 3 h after operation, and that the Vmax of the process, the capacity of urea-N synthesis (CUNS) is 50% higher than normal values 24 h after operation. Therefore, the effect of glucagon on UNSR and CUNS were investigated 3 and 24 h postoperatively, respectively. Control animals were given non immune rabbit serum. Glucagon immunoneutralization partly normalized the early increase in UNSR 3 h postoperatively (control: 4.7 +/- 0.3, hysterectomy+serum: 6.7 +/- 0.4, hysterectomy+Gluc-Ab: 5.5 +/- 0.4 mumol (min.100 g BW)-1), but had no effect on the increase of CUNS 24 h postoperatively (control: 7.9 +/- 0.3, hysterectomy+serum: 9.5 +/- 0.3, hysterectomy+Gluc-Ab: 9.8 +/- 0.5 mumol (min.100 g BW)-1). This shows that glucagon is important for the early postoperative increase in the efficacy of urea synthesis, whereas the late increase in capacity seems not to depend on hyperglucagonemia.

Hormonal and neural blockade prevents the postoperative increase in amino acid clearance and urea synthesis.

The combined effect of continuous blockade of glucagon and cortisol by somatostatin and etomidate and thoracic epidural analgesia on hepatic conversion of amino nitrogen was studied in eight patients who underwent elective cholecystectomy on day 1 after operation and was compared with 16 patients who underwent operation without blockade. Surgery increased the plasma clearance of total alpha-amino nitrogen from 5.2 +/- 0.3 to 6.6 +/- 0.3 ml/sec (mean +/- sem; p less than 0.05). This increase was due to increased elimination by the liver, because the hepatic effectiveness for amino nitrogen conversion measured by the functional hepatic nitrogen clearance increased from 9 +/- 2 to 16 +/- 4 ml/sec (p less than 0.05). In contrast, during the combined neural and hormonal blockade, surgery decreased the plasma clearance of amino nitrogen from 5.3 +/- 0.3 to 3.9 +/- 0.3 ml/sec (p less than 0.05), and the blockade prevented the postoperative increase in functional hepatic nitrogen clearance. The results suggest that glucagon, cortisol, and afferent neural reflexes are mediators of the hepatic contribution to catabolism after operation.

Effects of epinephrine on urea synthesis in vivo in rats.

Three hours after hysterectomy the rate of urea synthesis doubles in rats. At the same time the increase in catecholamines is at a maximum, suggesting that catecholamines might be of regulatory importance. The effect of exogenous epinephrine on the rate of urea synthesis was studied in rats receiving epinephrine at rates of 2 and 20 micrograms/kg/h. The low dose increased plasma concentration of catecholamines two-fold over control values (p less than 0.01), comparable with the increase seen after surgery, and the high dose of epinephrine increased the concentration five-fold. The high dose increased the rate of urea synthesis by 30% (p less than 0.05), whereas the low dose had no effect. Following a high dose of epinephrine, alanine decreased from 358 +/- 29 to 254 +/- 17 mmol/l (p less than 0.05), indicating that the increase in urea synthesis was due to an effect on the liver rather than on extra-hepatic tissues, in that more aminonitrogen was eliminated from plasma than released into it. In conclusion, epinephrine in physiological concentrations cannot by itself account for the increase of urea synthesis seen in vivo after surgery.

Glucagon immunoneutralization in diabetic rats normalizes urea synthesis and decreases nitrogen wasting.

To study the effect of glucagon neutralization on urea synthesis in diabetic rats, animals with newly induced (75 mg/kg streptozocin) experimental diabetes mellitus were divided into two groups. One group was given one weekly injection of nonimmune rabbit serum (n = 6), and the other group was given one weekly injection of a specific high-titer antibody against pancreatic glucagon (n = 6). Four weeks later, serum-treated diabetic rats had fasting glucagon concentrations 2-3 times higher than nondiabetic controls given one weekly injection of saline (control). Plasma glucagon binding capacity of diabetic rats given glucagon antibodies was 10-15 times higher than the glucagon concentration. A second group of nondiabetic controls were given nonimmune serum. Blood glucose concentration and urinary glucose output were identical in both groups of diabetic animals. Food intake doubled in both groups of diabetic rats. In control rats, the accumulated nitrogen balance, determined weekly for 4 wk, was positive at 81 +/- 3.1 mmol/96 h; in serum-treated diabetic rats, the accumulated nitrogen balance was negative, -8.3 +/- 2.4 mmol/96 h throughout the 4 wk, whereas it was higher at 4.7 +/- 2.3 mmol/96 h in the glucagon antibody-treated diabetic rats (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blockade of glucocorticoid receptors prevents the increase in urea synthesis after hysterectomy in rats.

The postoperative increase in hepatic conversion of amino nitrogen to urea nitrogen seems to be a primary cause of post-surgical catabolism. The importance of glucocorticosteroids for the spontaneous urea nitrogen synthesis rate (UNSR) and for the maximally amino acid-stimulated capacity of urea nitrogen synthesis (CUNS) was investigated 3 and 24 h postoperatively, respectively, in hysterectomized rats. Corticosteroid effects were neutralized by glucocorticoid receptor blockade by the pharmacological analogue RU486. Hysterectomy doubled UNSR from 3.16 +/- 0.20 to 6.12 +/- 0.27 mumol (per min per 100 g body weight) after 3 h (P less than 0.01) and increased CUNS by 40% from 7.47 +/- 0.30 to 10.29 +/- 0.41 mumol (per min per 100 g body weight) after 24 h (P less than 0.01). These changes were both normalized by the receptor blockade. Hysterectomy decreased total blood alpha-amino nitrogen concentration by 25% from 3.4 +/- 0.2 to 2.6 +/- 0.2 mmol l-1 (P less than 0.05) 3 h after surgery, which was normalized by glucocorticoid receptor blockade. Hysterectomized rats lost 10 +/- 1 g the first 24 h after surgery. The blockade reduced the weight loss to 6 +/- 1 g body weight (P less than 0.05) without changing food intake. The results indicate that glucocorticoid action plays a major role in the postoperative increase in hepatic amino nitrogen conversion.

Elective cholecystectomy increases plasma amino-acid clearance and hepatic capacity for urea synthesis for one week.

The importance of the liver in post-operative catabolism was studied in 6 cholecystectomy patients given a mixture of amino-acids as prime-continuous infusions pre-operatively and on the 1st, 3rd, 6th and 12th post-operative day. The plasma clearance of total alpha-amino-nitrogen and of single amino-acids, the urea-nitrogen synthesis rate, and the functional hepatic nitrogen clearance were calculated. Surgery decreased fasting blood amino-nitrogen concentration by 15% (p < 0.01), and increased the plasma clearance of amino-nitrogen by 30% (P < 0.05) on the 1st, 3rd and 6th post-operative day. Surgery doubled the functional hepatic nitrogen clearance (p < 0.01) on the 1st, 3rd and 6th post-operative day. This indicates that post-operative stress catabolism is partly due to a hepatic condition by which the liver eliminates more amino-nitrogen despite lower amino-acid concentration in the blood, for one week post-operatively.

Effects of hysterectomy and semi-starvation on amino-acid gradients across liver, muscle and gut in rats.

To study the effects of surgical stress and insufficient food intake on amino-acid exchange of liver, gut, and muscle, blood was sampled in random sequence from the aorta, the inferior caval vein, the portal vein, and the hepatic veins in 3 groups of 20 rats each. Control rats were fed ad libitum, hysterectomised rats were studied on the first and third post-operative day, and semi-starved rats were pair-fed to hysterectomised rats to an intake of 13% of control on the first day. Both groups lost 5-8% of body weight. Surgery increased the concentration gradient (release) of urea across liver by 60%, the glucose gradient (release) by 35%, and doubled the concentration gradients (uptake) across liver of alanine, arginine, glycine, lysine, proline, serine, and threonine, and decreased their plasma concentrations. There was no major change in hepatic amino-acid gradients in semi-starved animals, and there was no appreciable change in gradients of single amino-acids across gut or muscle in animals subjected to surgery or semi-starvation. Post-surgical increases in urea synthesis and hepatic uptake of uragenic and gluconeogenic amino-acids are due to the surgical stress and not to the post-operative semi-starvation.

Contradictory effects of uncomplicated versus complicated abdominal surgery on the hepatic capacity for urea synthesis in rats.

Female Wistar rats weighing 217 g were subjected to two types of surgical stress: uncomplicated (hysterectomy) and complicated (spleen and uterus ligated, crushed, and left in situ). Liver function as assessed by amino-N conversion was measured as the capacity for urea-N synthesis preoperatively (control animals) and on Days 1, 3, and 6 postoperatively. Uncomplicated surgery transiently increased the capacity for urea-N synthesis by 30% the first postoperative day (P less than 0.001). Complicated surgery decreased the capacity for urea-N synthesis to 55% throughout the investigation period (P less than 0.001). This was not due to a general change in liver mass since galactose elimination capacity remained constant. The increase in the capacity for urea-N synthesis after uncomplicated surgery is probably due to glucagon since plasma glucagon increased whereas plasma insulin and blood glucose remained unchanged after amino acid loading. The persistent decrease in the capacity for urea-N synthesis in complicated surgery is not due to changes in these regulators: glucagon increased, insulin decreased, and the rats were hypoglycemic. All changes are expected to increase the capacity for urea-N synthesis. The mechanism for the emergence of these two distinct metabolic patterns is not known. The phenomenon is probably important for interpretation of metabolic data on clinical stress.

Increased amino acid clearance and urea synthesis in a patient with glucagonoma.

Fasting concentrations, clearance of exogenous infused amino acids, and lean body mass were studied in a patient with glucagonoma syndrome (fasting glucagon = 380 pmol/l, normal range 15-45 pmol). The fasting concentrations of all amino acids were reduced. The clearances of alanine, arginine, glycine, isoleucine, leucine, lysine, methionine, proline, serine, threonine, and tyrosine were increased. The urea synthesis rate during amino acid infusion was 27 mumols/kg per minute (normal range 20-24 mumols/kg per minute). The lean body mass of the patients was reduced to 59% of the expected value. It is suggested that the weight loss of patients with glucagonoma syndrome is partly due to increased hepatic conversion of amino acid nitrogen to urea nitrogen, resulting in decreased blood amino acid concentration, and secondary to this, organ protein catabolism, as shown by the decreased lean body mass.

Indomethacin prevents the increase in urea synthesis capacity and the weight loss after hysterectomy in rats.

Prostaglandins have been suggested to be mediators of post-operative catabolism. Previous studies have shown that stimulation of urea synthesis contributes to post-operative nitrogen loss. The effect of prostaglandins on this hepatic function was assessed in hysterectomized rats on the first post-operative day by measurements of the Capacity of Urea-N Synthesis (CUNS) with and without indomethacin treatment. Hysterectomy increased CUNS by 1 3 and led to a weight loss of 10 g in one day. Indomethacin prevented the increase in CUNS and the post-operative weight loss in operated animals; it also decreased CUNS by 1 3 in control rats. Blood amino-nitrogen concentration of indomethacin treated hysterectomized rats was 1 3 lower than in untreated animals, indicating an even more marked effect of indomethacin on post-operative tissue amino-acid release than on CUNS. Indomethacin exerts a nitrogen sparing effect, possibly depending on normalization of both post-operative hepatic amino-nitrogen conversion and tissue proteolysis. This may be of clinical importance in controlling post-operative catabolism.

Increased hepatic amino nitrogen conversion after elective cholecystectomy in man.

1. The effect of elective, uncomplicated cholecystectomy on plasma clearances of amino acids and on amino acid-stimulated urea synthesis was investigated in 10 patients, pre-operatively and on the first post-operative day, and compared with six controls treated identically apart from the surgery. 2. A mixture of amino acids was given as a prime-continuous infusion. Steady-state concentrations 75% higher than basal were attained and were maintained for 90 min. The clearances of amino acids were calculated as the ratios between amino acid infusion rate and the concentration. The urea synthesis rate was calculated as urinary excretion corrected for accumulation and intestinal loss. 3. After surgery the fasting plasma concentrations of alanine, arginine, glutamine plus glutamate, glycine, proline, lysine and threonine decreased by 20-30%, but were unchanged in the control group. The plasma clearance of alpha-amino nitrogen increased from 5.1 +/- 1.2 ml/s before surgery (mean +/- SD) to 6.1 +/- 1.1 ml/s (P less than 0.05, paired t-test) after surgery due to increased clearances of the above-mentioned amino acids. In the control group, the clearance decreased from 6.4 +/- 1.6 to 5.9 +/- 1.1 (P less than 0.05, paired t-test). The amino acid-stimulated urea synthesis rate after surgery was 37 +/- 9 mumol of N/s vs 30 +/- 6 (P less than 0.01, paired t-test) in the controls despite a lower alpha-amino nitrogen concentration (4.5 +/- 0.5 mmol/l vs 5.1 +/- 0.5 mmol/l, P less than 0.05, paired t-test). The post-operative urea synthesis rate exceeded the amino nitrogen infusion by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)