A change in clinical practice: a partially stapled cervical esophagogastric anastomosis reduces morbidity and improves functional outcome after esophagectomy for cancer.

Cervical esophagogastric anastomoses are commonly used for reconstruction after esophagectomy because of the lower mortality rate associated with an anastomotic leak compared to intrathoracic anastomoses. However, cervical esophagogastric anastomoses have been criticized for their higher leak rates, stricture formation and greater need for later dilatations when compared with intrathoracic anastomoses. Multiple studies have looked at varying techniques to improve the outcome of the cervical esophagogastric anastomosis. This study was performed to determine whether a partially stapled (posterior stapled wall and anterior hand-sewn wall) anastomosis reliably reduced leaks and the need for later dilatation. From January 2001 to March 2006, 168 patients who underwent cervical esophagogastric anastomosis following esophagectomy (transhiatal or three-hole) for cancer were identified. Beginning in September 2003, the partially stapled technique was introduced and used in 79 patients. Clinical outcomes were compared to patients in whom hand-sewn technique was used (n = 89). Outcomes related to anastomotic leak, other hospital complications, length of stay, postoperative dilatations and survival were compared using Student's t-tests and chi-square tests (P < 0.05), as well as multiple regression analyses. An anastomotic leak occurred in 10 (12.7%) patients who received a partially stapled anastomosis. A hand-sewn anastomosis was complicated by an anastomotic leak in 24 patients (27.0%). This difference was statistically significant (P = 0.021). This lowered incidence of leak was associated with an earlier initiation of oral feeds (median 7 vs. 9.5 days, P < 0.001) and a reduction in hospital stay (median 10 vs. 15 days, P < 0.001). Furthermore, dysphagia associated with stricture requiring postoperative dilatations was markedly diminished in the stapled anastomosis [23 (31.3%) vs. 49 (55.1%), P = 0.001]. The partially stapled cervical esophagogastric anastomosis significantly decreased the incidence of postoperative anastomotic leaks and the need for postoperative dilatation to treat strictures compared to the hand-sewn anastomosis.

Anterior fundoplication decreases esophageal clearance in patients undergoing Heller myotomy for achalasia.

BACKGROUND: Anterior fundoplication (AF) following laparoscopic Heller myotomy (LHM) for achalasia may prevent esophageal leaks and gastroesophageal reflux but cause dysphagia. Our study attempts to determine the effect of AF on esophageal leaks, nuclear medicine esophageal clearance (EC), symptom frequency (SF), and Van Trappen symptom scores (SS) for dysphagia, regurgitation, and heartburn. METHODS: Between 1995 and 2004, pre- and postoperative (2-12 months) EC, SF, and SS scores were compared in 95 patients undergoing LHM for achalasia with AF (n = 71) and without (n = 24) AF. RESULTS: There were no leaks or deaths. Laparoscopic Heller myotomy decreased the frequency of postoperative dysphagia, regurgitation, and heartburn with AF (96% preoperation versus 6% postoperation, 94% versus 3%, 58% versus 6%) (p = 0.001) and without AF (100% versus 0%, 83% versus 0%, 50% versus 4%) (p = 0.001). Laparoscopic Heller myotomy improved all SS in both groups. There was no difference between postoperative dysphagia (1.38 +/- 0.64 versus 1.17 +/- 38) p = 0.06, regurgitation (1.17 +/- 51 versus 1.04 +/- 0.20) p = 0.08, and heartburn (1.29 +/- 62 versus 1.53 +/- 0.80) p = 0.185 scores between the AF and no-AF group, respectively. There is a trend toward improvement in dysphagia and regurgitation in the no-AF group. Laparoscopic Heller myotomy improved EC in the supine and upright positions in both groups of patients (p = 0.001). There was an improved mean change in EC (10 min upright) in the no-AF group versus the AF group (50.7% +/- 30.8 versus 29.7% +/- 30.2) p = 0.004. CONCLUSIONS: Laparoscopic Heller myotomy improves esophageal transit and the frequency and severity of dysphagia, heartburn, and regurgitation in a safe manner. Patients without AF show a statistically better upright EC with a trend toward improved dysphagia and regurgitation.

Effect of cancer on the in vivo energy state of rat liver and skeletal muscle.

The effect of increasing tumor burden on host liver and skeletal muscle energy status was studied using P-31 nuclear magnetic resonance spectroscopy (NMR), in rats inoculated with a nonmetastasizing methylcholanthrene-induced sarcoma (TB), and compared to nontumor bearing (NTB) and pair-fed (PF) rats. During the 28-day study, serial measurements of body weight, food intake, and tumor volume were obtained. Using a 0.9-cm double-turn surface coil, weekly NMR measurements were obtained from liver and skeletal muscle. An increasing ratio of [Pi]/[ATP] was used as one measure of intracellular energy depletion. [Pi]/[ATP] in NTB rats remained constant over time at 0.78 +/- 0.10 in liver, and 0.30 +/- 0.10 in skeletal muscle. In TB rats, the [Pi]/[ATP] ratio increased significantly in liver (P = 0.00002) and skeletal muscle (P = 0.04) with increasing tumor burden. In PF rats, no significant change occurred in [Pi]/[ATP] in liver or skeletal muscle, indicating that declining food intake was not responsible for the change in [Pi]/[ATP] seen in TB rats. Surface-coil spectroscopy of liver and skeletal muscle permits serial measurement of visceral energy stores. Increasing tumor burden results in early, ongoing depletion of energy stores as reflected by increasing [Pi]/[ATP] in these organs.

The redox state and regulation of amino acid metabolism in man.

Traditionally, regulation of amino acid metabolism in both postabsorptive and prolonged-fasted man has been generally regarded as being hormonal in nature. In particular, insulin, and to a lesser extent glucagon, have been nominated for key roles in this process. More recently, however, reconsideration of previous studies involving insulin, glucagon, and protein meals as well as previously unreported studies (cortisol and tri-iodothyronine) from this laboratory, have suggested another means of regulating amino acid metabolism in fasting man. This new hypothesis is centered on the redox state of muscle of fasting man, which is remarkably reduced in both cytosolic and mitochondrial compartments. It was found that insulin, and to a lesser extent glucagon, when infused into fasting subjects (1) rendered muscle significantly more reduced, and (2) resulted in a diminution in urinary nitrogen excretion. In contrast, when either tri-iodothyronine or cortisol were administered to fasting individuals (1) muscle was found to become more oxidized when compared with the control period, and (2) increased urinary nitrogen excretion was observed in both cases. It was noteworthy that the ingestion of a protein meal by a nitrogen-depleted individual was followed by a dramatic change in muscle redox state (the muscle became more reduced), together with marked uptakes of a variety of amino acids. It is therefore proposed that the protein conservation evidenced by fasting man may be dependent on the reduced state of muslce tissue.

Detachable balloon occlusion of bronchopleural fistulae in dogs.

The use of detachable balloon occlusion in closure of bronchopleural fistulae was investigated in eight dogs. Fistula occlusion could not be achieved in one dog, and the balloon was not large enough to occlude a fistula in a second dog. Satisfactory fistula occlusion was achieved in the remaining six dogs. All fistulae occluded were shown to be satisfactorily healed at ten days. There were no significant sequelae to bronchial occlusion during this period. Detachable balloon occlusion of bronchopleural fistulae has the potential for satisfactory fistula control prior to more definitive surgery.

Capillary muscle blood flow in human sepsis.

Tissue perfusion was determined by cardiac index (Cl) and skeletal muscle capillary blood flow (MBF), and arteriovenous oxygen difference (AVD) and oxygen uptake were compared in seven patients with severe spesis and eight nonseptic patients. Skeletal capillary muscle blood flow also was measured before and after a 2 day fast in 14 normal volunteers. In both septic and nonseptic patients, MBF varied directly with Cl. The average muscle blood flow was greater in septic than in nonseptic patients and, in addition, was greater per unit Cl. AVD in septic patients was narrower than in nonseptic patients. Septic patients with an AVD of less than 4 ml. of O2 had markedly higher MBF and Cl than did septic patients with an AVD greater than 4 ml. of O2. Fasting normal volunteers who, like the septic patients, would be catabolic had a significant increase in MBF during the fast. Although peripheral shunts are not ruled out ans an explanation of the hyperdynamic circulation in sepsis, the evidence is against their existence, at least in skeletal muscle, since capillary flow increases in direct proportion to cardiac output. If capillary flow is increased in fact in sepsis, then flow like blood pressure becomes less of a critical factor in explaining the demise of the septic patient. It might be postulated that the increased capillary flow seen in sepsis is secondary to the mobilization of amino acids from the body cell mass for gluconeogenesis and energy.

Metabolism of branched-chain amino acids in dogs with Escherichia coli endotoxin shock.

The arterial-femoral venous difference of phenylalanine concentration is proportional to net proteolysis in the leg. In ten fasting dogs receiving Escherichia coli endotoxin (2 mg/kg) intravenously, the mean systolic blood pressure decreased from 141.1 +/- 25 to 71.5 +/- 17 mm Hg. The absolute net release from the leg of valine, isoleucine, and leucine and their net release relative to net proteolysis (arterial-femoral venous difference in concentration of each branched-chain amino acid relative to that of phenylalanine) were decreased, indicating increased transamination of these amino acids in skeletal muscle. However, the net release of the branched-chain alpha-keto acids formed by transamination, relative to net proteolysis (arterial-venous difference in concentration of each alpha-keto acid relative to that of phenylalanine), was not increased. The findings indicate that in dogs with E. coli endotoxin shock, there is increased oxidative decarboxylation in muscle of the alpha-keto acids derived from valine, isoleucine, and leucine.

Renal and cardiovascular response to nonhypotensive sepsis in a large animal model with peritonitis.

We studied the functional effects of intraperitoneal sepsis on systemic hemodynamics in general, and on renal function in particular, in sheep in whom bacterial peritonitis was induced by cecal perforation. In the first group of seven sheep (group 1) fluid was administered throughout the period of sepsis to maintain pulmonary capillary wedge pressure as close to presepsis values as possible. These sheep exhibited hemodynamic changes known to be associated with sepsis in man: increased cardiac output and decreased systemic vascular resistance. In a second group of seven sheep (group 2) fluid intake was restricted; compared with group 1, these sheep demonstrated a smaller increase in cardiac output that did not persist and that was associated with an increase in the systemic vascular resistance during the septic period. Plasma renin levels increased fivefold in group 2 but were unchanged in group 1. Serial renal biopsies during the septic period revealed that all sheep had evidence of tubular cell damage on electron microscopy: cell swelling, loss of the microvillous brush border, and cell necrosis. Both groups of sheep also demonstrated marked tubular proteinuria similar to that found in humans with generalized sepsis. Despite this, sheep in group 1 exhibited no functional renal changes: creatinine clearance levels rose slightly from control values, urine concentrating ability was unimpaired, and fractional excretion of sodium increased appropriately in response to a sodium load. In contrast, group 2 sheep exhibited a fall in creatinine clearance levels but fractional sodium excretion did not fall as would have been expected were renal function entirely normal. The results suggest that generalized "hyperdynamic" sepsis induces tubular cell damage and tubular proteinuria by an unknown mechanism. However, this does not necessarily produce renal impairment since the glomerular filtration rate does not fall unless volume contraction is also allowed to occur.

Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man.

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.

Insulin decreases muscle protein loss after operative trauma in man.

Seventy-two hours after major operative trauma, nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acid/m2/day) showed a negative nitrogen balance, increased muscle catabolism, as measured by 3-methylhistidine excretion, increased amino acid efflux from muscle, and decreased circulating levels of insulin. When 5 U of insulin/hr were added to the infusate, arterial insulin levels rose significantly from 39.7 +/- 4.1 microU/ml to approximately the pretrauma levels (74.6 +/- 7.7 microU/ml). Despite this normalization of insulin levels, excretion of nitrogen and 3-methylhistidine and the efflux of amino acids from forearm muscle fell but did not return to pretraumatic levels, suggesting some insulin resistance. Visceral gluconeogenesis from amino acids appeared to decrease, since insulin infusion decreased the efflux of alanine from skeletal muscle with no change in its arterial level. Insulin also significantly reduced the efflux of isoleucine, tyrosine, phenylalanine, glutamine, and total amino acid nitrogen from forearm muscle. These findings, along with the partial reduction in the excretion of 3-methylhistidine and nitrogen, suggest that insulin, in combination with infused calories and protein, decreases the loss of muscle protein after trauma.

Arterial plasma amino acids in patients with serious postoperative infection and in patients with major fractures.

Arterial plasma amino acids were measured in 27 patients with serious septic complications after operation, 15 patients following reduction of femoral shaft fractures and nine control patients on the first and third days following uneventful major abdominal surgery. Amino acid concentrations in the controls were similar to those which have been reported during early starvation. The amino acid patterns seen in all groups did not resemble that previously observed following glucocorticoid administration. In the patients with infection, mean phenylalanine concentration (108.0 +/- 46.9 mumoles per liter) was significantly greater than in the controls on the first (p greater than 0.001) or third (p less than 0.001) postoperative days. Four of the septic patients with hyperphenylalaninemia also had elevated arterial methionine concentrations. These observations suggest that many of the patients with sepsis had seriously impaired liver metabolism. In patients with fractures, the concentrations of ornithine (p less than 0.001), taurine (p less than 0.05), and aspartic acid (p less than 0.05) were lower than in controls. No other significant differences of amino acid concentrations were observed. It is difficult to relate these differences to a specific metabolic abnormality.

The effects of glucagon on protein metabolism in normal man.

Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gmday), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 +/- 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 +/- 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strong suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.

Femoral arteriovenous amino acid differences in septic patients.

Femoral arteriovenous differences and flux of amino acids across the leg were measured in seven septic patients and compared with those of six nonseptic patients on days 1 and 3 following major surgery. The septic patients were seriously ill and judged clinically to be catabolic. The postoperative patients, although not septic, were expected to have a maximal catabolic response to operation during the first 3 days after operation. Both groups had increased release of phenylalanine from the leg, an index of muscle proteolysis. Septic patients had decreased femoral arteriovenous differences (--20 vs --74 and --60 mumoles/liter) and decreased flux (34 vs 169 and 128 nm/100 gm of calf muscle) of the branched-chain amino acids as compared with the nonseptic postoperative patients on days 1 and 3. The arterial plasmal levels of the branched-chain amino acids and alanine were not different, but phenylalanine was elevated in the septic patients (88 vs 49 and 55 mumoles/liter). The insulin:glucagon molar ratio was lower in the septic patients (2.4 vs 4.4 and 5.5). These findings suggest that in the catabolism of sepsis there is greater oxidation of branched-chain amino acids in muscle than in the catabolism associated with uncomplicated surgery.

2,3-Dihydroxybenzoic acid. Effect on mortality rate in a septic rat model.

Neutrophil-derived oxygen-free radicals may play a role in organ dysfunction associated with generalized sepsis. A rat model was used to test the effects of two free radical scavengers, dimethyl sulfoxide (DMSO) and 2,3-dihydroxybenzoic acid (2,3-DHB), on mortality from intra-abdominal sepsis produced by cecal ligation and perforation. Being an iron-chelating agent, 2,3-DHB may have an additional bacteriostatic effect. Therapeutic regimens included no treatment; gentamicin sulfate (2 mg given intraperitoneally [IP] every eight hours); DMSO (2 g/24 hr given IP every eight hours in divided doses); 2,3-DHB (35 mg/kg given IP every eight hours); and combinations of gentamicin with each free radical scavenger. No statistically significant improvement in survival was obtained by therapeutic intervention with gentamicin alone, DMSO alone, 2,3-DHB alone, or gentamicin in combination with DMSO. When used in combination with gentamicin, 2,3-DHB yielded a statistically significant improvement in survival when compared with gentamicin alone or with no treatment. These results show that 2,3-DHB when used in combination with gentamicin has a beneficial effect on mortality following intra-abdominal sepsis in this model.

Transhiatal esophagectomy for carcinoma of the esophagus and cardia. Experience with 160 cases.

We reviewed our experience from 1979 to 1990 with 160 cases of transhiatal esophagectomy for carcinoma of the lower esophagus and cardia to evaluate trends in patient selection, management, and outcome. Patients treated in the past 6 years (n = 110) and those treated before 1985 (n = 50) were similar in terms of age and sex distribution, medical history, and weight loss. The majority of tumors seen were adenocarcinoma, with patients in the latter group having significantly lower stages. Significant decreases in anesthetic time, units of blood transfusions, chest tube insertions, length of postoperative ventilation, incidence of postoperative pneumonia, and length of hospital stay were seen during the past 6 years. Wound infections increased significantly during the same period. The decrease in the 30-day mortality rate from 6% to 0.9% was not significant. Survival rates did not differ between groups, with overall rates of 62%, 40%, and 21% at 1, 2, and 5 years, respectively.

Laparoscopic Heller myotomy improves esophageal emptying and the symptoms of achalasia.

HYPOTHESIS: Laparoscopic Heller esophageal myotomy improves esophageal clearance and symptoms of achalasia in the early and late postoperative periods. DESIGN: We followed up 98 consecutive patients attending a referral center between February 1, 1994, and July 1, 2000, who underwent laparoscopic myotomy. Operative time, complications, and length of stay were recorded. Postoperative outcomes were assessed using Van Trappen symptom scores (1 indicates no symptoms; 2, symptoms occurring less than once a week; 3, symptoms occurring more than once weekly; and 4, persistent symptoms) and scintigraphic esophageal transit studies. RESULTS: Of 98 patients, 91 underwent anterior fundoplication. There were no open conversions and 1 mucosal perforation, which was closed laparoscopically without complications. Mean operative times and postoperative days were 3.2 hours and 4.3 days, respectively, in the first 32 patients and 1.7 hours and 2.3 days, respectively, in the last 32 patients (P<.001). Postoperative complications included pneumothorax (4% of patients), atelectasis (5%), and delayed gastric emptying (1%). Seventy-five percent of patients gained weight after surgery. At longest follow-up, 91% of patients were satisfied with the outcome of the procedure. Mean Van Trappen scores for dysphagia improved from 4.0 in the preoperative period to 1.2 at early and late follow-up (P<.001). Fluid retention at 10 minutes in the upright position was 47% in the preoperative period and improved at early and late follow-up to 21% and 20%, respectively (P<.001). CONCLUSIONS: Laparoscopic Heller myotomy can safely reverse the symptoms of achalasia and improve esophageal transit. These benefits, realized during the early postoperative period, were maintained at longest follow-up.

A new technique for delivering the stomach or colon to the neck following total esophagectomy.

After total esophagectomy, swallowing is usually restored by stomach or colon interposed to the neck. The use of a new technique to facilitate the passage of these conduits to the neck for anastomosis to the cervical esophagus is described.

Effect of routine fibrin glue use on the duration of air leaks after lobectomy.

The effectiveness of fibrin glue as a sealant to reduce postoperative air leaks after pulmonary lobectomy was evaluated in 28 consecutive patients between November 1988 and May 1989. A fibrin glue spray was used in 14 patients, and 14 patients served as controls. Assignment of either group was made before thoracotomy. Nine male and 5 female patients with a mean age of 63.8 years were in the fibrin glue experimental group, and 8 male and 6 female patients with a mean age of 59 years, in the control group. An equal number of complete and incomplete fissures were in each group. All fissures were handled in the same way (stapled). Two milliliters of fibrin glue was applied through a double-syringe delivery system and sprayed on the staple line and any cut surface of the inflated lung just before thoracotomy closure. The fibrin glue-treated group had a mean air leak duration of 2.3 +/- 3.7 days, chest tube drains for 6 +/- 4.1 days, and a postoperative hospitalization of 9.8 +/- 3.1 days. The control group had a mean air leak duration of 3.3 +/- 3.3 days (p = 0.94), chest tube drains for 5.9 +/- 3.9 days (p = 0.95), and a postoperative hospitalization of 11.5 +/- 3.9 days (p = 0.21). We conclude that the routine use of a fixed quantity of fibrin glue is not effective in reducing the duration of air leaks, chest tube drainage, or hospitalization after uncomplicated pulmonary lobectomy.

The management of nonmalignant intrathoracic esophageal perforations.

Eight patients with nonmalignant intrathoracic esophageal perforations recognized more than 48 hours (48 hours to 14 days) after rupture were treated at Toronto General Hospital between 1973 and 1978. Perforation was due to postemetic rupture in 7 patients and to instrumentation in 1. The patients were seen with pain (8), vomiting (7), fever (7), shock (4), respiratory insufficiency (5), pleural effusion (7), pulmonary infiltrates (7), and leukocytosis (6). All patients were managed with thoracotomy. Direct suture closure of the perforation was carried out in 4 patients with midesophageal perforations. Postoperative localized leaks developed in 2 of these patients but healed with conservative management. Cervical esophagostomy and esophageal diversion were used in 1 patient in whom a severe empyema developed in the postoperative period. Direct suture closure, reinforced with a gastric patch, was used to close three lower esophageal perforations. None of these patients had a postoperative leak but all developed subsequent reflux esophagitis. All 8 patients survived. In patients with delayed recognition of a nonmalignant intrathoracic esophageal perforation, elimination of continued chemical and bacterial contamination can be achieved by a clear definition and closure of the esophageal mucosal margins. The obliteration of potential pleural spaces by good tube drainage, lung decortication, and the elective use of mechanical ventilation with positive end-expiratory pressure decreases the incidence of uncontrolled intrapleural sepsis.

Esophagogastrectomy and the variant left hepatic artery.

A variant left hepatic artery occurs at a rate of approximately 10%. In standard esophagogastrectomy and some proximal gastric operations this variant artery is sacrificed, which has led to reported fatalities secondary to hepatic necrosis. We report our method of esophagogastrectomy in the presence of an aberrant left hepatic artery.