Prospective randomized double-blind trial between laparoscopic Nissen fundoplication and anterior partial fundoplication.

BACKGROUND: In the operative management of gastro-oesophageal reflux, a balance must be achieved between adequate control of reflux and excessive dysphagia. The ideal technique is not known. A randomized study was performed to determine whether laparoscopic anterior fundoplication is associated with a lower incidence of postoperative dysphagia than laparoscopic Nissen fundoplication, while achieving equivalent control of reflux. METHODS: Patients presenting for laparoscopic antireflux surgery were randomized to undergo either a Nissen fundoplication (n = 53) or an anterior 180 degrees hemifundoplication (n = 54). Patients were blinded to which procedure had been performed, and follow-up was obtained by a blinded independent investigator. Standardized clinical grading systems were used to assess dysphagia, heartburn and patient satisfaction 1, 3 and 6 months after operation. Objective measurement of lower oesophageal sphincter pressure, oesophageal emptying time, distal oesophageal acid exposure and endoscopic healing of oesophagitis was also performed. RESULTS: Operating time was similar for the two procedures (58 min for the Nissen procedure versus 60 min for anterior fundoplication). Resting and residual lower oesophageal sphincter pressures were lower following anterior fundoplication (29 versus 18 mmHg, and 13 versus 6 mmHg), and oesophageal emptying times were faster (92 versus 116 s). Acid exposure times and ability to heal oesophagitis were similar. At 3 months' follow-up clinical outcomes were similar for the two procedures. At 6 months, however, patients who had undergone anterior fundoplication experienced significantly less dysphagia for solid food and were more likely to be satisfied with the clinical outcome. CONCLUSION: Laparoscopic anterior fundoplication achieved equivalent control of reflux, more physiological postoperative manometry parameters, and an improved clinical outcome at 6 months. Continued follow-up remains necessary to confirm the long-term efficacy of the partial fundoplication procedure.

Tumor implantation following laparoscopy using different insufflation gases.

BACKGROUND: Laparoscopic manipulation of malignancies is associated with an increased incidence of metastasis to port sites in experimental models. This study investigated the effect of different insufflation gases on the implantation of a tumor cell suspension following laparoscopic surgery in an established small animal model. METHODS: Forty Dark Agouti rats underwent laparoscopy and the introduction into the peritoneal cavity of a tumor cell suspension. The insufflating gas used for each procedure was one of the following gases (10 rats in each group): carbon dioxide (CO2), nitrous oxide (N2O), helium, and air. The rats were killed 7 days after surgery, and the peritoneal cavity and port sites were examined for the presence of tumor. RESULTS: Although no significant differences were seen between air, CO2, and N2O insufflation groups, tumor involvement of peritoneal surfaces was less likely following helium insufflation. CONCLUSION: The results of this study suggest that tumor metastasis to port sites following laparoscopic surgery may be influenced by the choice of insufflation gas. In this study, helium was associated with reduced tumor growth.

Efficacy of anterior, posterior and total fundoplication in an experimental model.

BACKGROUND: This study examined the effect of different types of laparoscopic fundoplication on an incompetent lower oesophageal sphincter to test their effectiveness at preventing gastro-oesophageal reflux in the early postoperative period. METHODS: An experimental porcine model was used. Initial oesophageal myotomy ensured an incompetent lower oesophageal sphincter with free reflux of 'intragastric fluid'. Anterior, posterior or total fundoplication was then performed laparoscopically in 15 laboratory pigs (five in each group). Fundoplication competence and efficacy were determined 2 weeks after laparoscopic antireflux surgery by inflating the stomach with liquid through a gastrostomy cannula. Some animals were also studied at 4 and 6 weeks. Lower oesophageal sphincter pressure was determined using a water-perfused oesophageal manometry catheter incorporating a Dent sleeve. RESULTS: All three types of fundoplication produced similar increases in postoperative resting lower oesophageal sphincter pressure and restored adequate competence to the gastro-oesophageal junction. CONCLUSION: All three variants of laparoscopic fundoplication restore gastro-oesophageal competence in the early postoperative period.

Wound metastasis after laparoscopy with different insufflation gases.

BACKGROUND: There is growing evidence that laparoscopy for malignancy is associated with an increased incidence of metastasis to port sites. This study investigated the effect of different insufflation gases on port-site metastasis after laparoscopy in an established animal model. METHODS: Forty-eight Dark Agouti rats with an established adenocarcinoma in the left flank underwent laparoscopic intraperitoneal tumor laceration. The gas used for insufflation was one of the following (12 rats in each group): (1) CO2, (2) N2O, (3) helium, or (4) air. Rats were killed 7 days after the procedure, and the port sites were examined for the presence of tumor metastasis. RESULTS: Tumor involvement of port sites was significantly less likely after helium insufflation than in the other groups (p < 0.0001). There was no significant difference between the air, CO2, and N2O groups. CONCLUSIONS: This study suggests that the development of metastases in port sites after laparoscopy may be influenced in part by the choice of insufflation gas used to create the pneumoperitoneum. In particular, helium was associated with a reduced rate of metastases.

Prospective double-blind randomized trial of laparoscopic Nissen fundoplication with division and without division of short gastric vessels.

OBJECTIVE: To determine whether division of the short gastric vessels (SGVs) and full mobilization of the gastric fundus is necessary to reduce the incidence of postoperative dysphagia and other adverse sequelae of laparoscopic Nissen fundoplication. SUMMARY BACKGROUND DATA: Based on historical and uncontrolled studies, division of the SGVs has been advocated during laparoscopic Nissen fundoplication to improve postoperative clinical outcomes. However, this modification has not been evaluated in a large prospective randomized trial. METHODS: One hundred two patients with proven gastroesophageal reflux disease presenting for laparoscopic Nissen fundoplication were prospectively randomized to undergo fundoplication with (52 patients) or without (50 patients) division of the SGVs. Patients with esophageal motility disorders, patients requiring a concurrent abdominal procedure, and patients who had undergone previous antireflux surgery were excluded. Patients were blinded to the postoperative status of their SGVs. Clinical assessment was performed by a blinded independent investigator who used multiple standardized clinical grading systems to assess dysphagia, heartburn, and patient satisfaction 1, 3, and 6 months after surgery. Objective measurement of lower esophageal sphincter pressure, esophageal emptying time, and distal esophageal acid exposure and radiologic assessment of postoperative anatomy were also performed. RESULTS: Operating time was increased by 40 minutes (median 65 vs. 105) by vessel division. Perioperative outcomes and complications, postoperative dysphagia, relief of heartburn, and overall satisfaction were not improved by dividing the SGVs. Lower esophageal sphincter pressure, acid exposure, and esophageal emptying times were similar for the two groups. CONCLUSION: Division of the SGVs during laparoscopic Nissen fundoplication did not improve any clinical or objective postoperative outcome.

Comparison of anterior, posterior and total fundoplication using a viscera model.

OBJECTIVE: To determine the contribution of mechanical factors to the function of different types of fundoplication. DESIGN AND SETTING: An experimental bench-top study using abattoir-sourced pig esophagus and stomach placed on a tray. Preliminary esophageal myotomy ensured free reflux of 'intragastric fluid'. INTERVENTIONS: Anterior, posterior, and total fundoplications were performed on each of ten sets of viscera. MAIN OUTCOME MEASURES: Lower esophageal sphincter pressure was measured using a conventional esophageal manometry catheter. Intragastric pressure was measured with a single channel intragastric manometry catheter, whilst the stomach was inflated with coloured water. The maximum intragastric pressure or the pressure measured when the fundoplication yielded to gastric distension was recorded. RESULTS: All three types of fundoplication restored adequate competence to the gastroesophageal junction, although high-volume gastric infusions resulted in fundoplication yield in 4/10 anterior and 4/10 posterior fundoplications. Gastric distension resulted in fundal dilatation and consequent compression of the adjacent esophagus. Fundoplication generated a median rise of 11-13.5 mmHg in lower esophageal sphincter pressure, comparable to pressures reported in the postoperative clinical setting. Significantly greater intragastric volumes and pressures were tolerated following total fundoplication. CONCLUSIONS: This study suggests that mechanical factors could be major contributors to the ability of a fundoplication to restore gastroesophageal competence. Anterior, posterior and total fundoplications are all effective procedures.

Changes in fibrinogen levels in patients undergoing open and laparoscopic Nissen fundoplication.

BACKGROUND: Venous thromboembolic complications may be more common after laparoscopic surgical techniques, possibly due to changes in venous flow and blood coagulability. METHODS: This study assessed fibrinogen, cross-linked fibrin degradation products (D-dimer), prothrombin international normalized ration (INR), activated partial thromboplastic time (APTT) and platelets, during and after both open and laparoscopic Nissen fundoplication to determine whether coagulability is increased by the laparoscopic approach. RESULTS: Seven patients underwent open and thirteen underwent laparoscopic Nissen fundoplication. Fibrinogen levels following open fundoplication fell from 2.8 +/- 0.3 g/L pre-operatively to 2.0 +/- 0.3 g/L following skin incision, and then increased to 4.1 +/- 0.4 g/L on the first postoperative day. Similar changes in fibrinogen occurred following laparoscopic fundoplication (2.7 +/- 0.2, 2.5 +/ 0.2 and 3.8 +/- 0.4 g/L, respectively). No significant changes in the other coagulation indices were observed. CONCLUSIONS: These results demonstrate hypercoagulability on the first postoperative day, irrespective of the operative technique. No differences between the results following laparoscopic and open fundoplication were demonstrated.

Modification of the transient outward current of rat atrial myocytes by metabolic inhibition and oxidant stress.

1. A putative function of the transient outward current (ITO) in cardiac myocytes is to modulate the shape of the action potential and, consequently, cardiac contractility. In addition, it has been suggested that this current may help protect against arrhythmias during periods of cardiac ischaemia. In our investigation of the possible anti-arrhythmic action of ITO, we have examined its response to metabolic inhibition and oxidant stress. 2. Whole-cell recordings were obtained from rat atrial myocytes using standard patch-clamp techniques. Inhibition of metabolism, using 10 mM 2-deoxy-D-glucose (2-DG) to block glycolysis with or without the addition of 2 mM cyanide to block oxidative phosphorylation, led to inhibition of ITO at a holding potential of -70 mV. Shifting the holding potential to -80 mV restored ITO, suggesting that metabolic inhibition had shifted the inactivation curve of ITO in a negative direction. 3. Quasi steady-state inactivation curves revealed a shift in ITO inactivation induced by complete metabolic inhibition with 2-DG and cyanide. Myocytes typically contracted shortly after the shift was observed. In the presence of Ruthenium Red, contraction was delayed and myocytes could undergo several exposures to the metabolic inhibitors, each time displaying a shift in ITO inactivation. The shifts ranged between -7 and -20 mV. 4. Recovery from inactivation was determined using a two-pulse protocol. The time constant of recovery at a holding potential of -80 mV reversibly shifted from 48 +/- 8 to 129 +/- 21 ms during metabolic inhibition (n = 4). 5. The activation of ITO from a holding potential of -100 mV shifted in a negative direction during metabolic inhibition, from a half-activation voltage of 0.3 +/- 3.0 to -14.7 +/- 2.5 mV (n = 5). Such a -15 mV shift increases the amplitude of ITO by approximately 30% at 0 mV. 6. A shift in ITO inactivation similar to that produced by metabolic inhibition could be shown when myocytes were subjected to oxidant stress induced by either 1 mM t-butyl hydroperoxide (TBHP) or the photoactivation of 100 nM Rose Bengal. Furthermore, an increase in pipette concentration of free Ca2+ from 20 to 200 nM also shifted ITO inactivation in a negative direction. 7. These results raise the possibility that the rise in intracellular [Ca2+] occurring during both metabolic inhibition and oxidant stress modifies activation and inactivation of ITO.(ABSTRACT TRUNCATED AT 400 WORDS)

Sulphydryl reagents trigger Ca2+ release from the sarcoplasmic reticulum of skinned rabbit psoas fibres.

1. By analogy with studies on sarcoplasmic reticulum (SR) vesicles, Ca2+ release induced by heavy metals and mercaptans (e.g. cysteine) was investigated in rabbit skinned psoas fibres through measurements of isometric tension. 2. Heavy metals (at 2-5 microM) elicited phasic contractions by triggering Ca2+ release from the SR and had the following order of potency: Hg2+ > Cu2+ > Cd2+ > Ag+ > Ni2+. Higher concentrations produced tonic contractions due to maintained high Ca2+ permeability of SR membranes. 3. Contractions induced by heavy metals required a functional and Ca(2+)-loaded SR, were dependent on [Ca2+]free, blocked by Ruthenium Red (RR), inhibited by free Mg2+ and reduced glutathione (GSH) but not by oxidized glutathione (GSSG). Such contractions were not elicited through direct interaction(s) of heavy metals with the myofilaments. 4. In the presence of catalytic concentrations of Hg2+ or Cu2+ (2-5 microM), additions of cysteine (25-100 microM) elicited rapid twitches, producing 70% of maximal force with a time to half-peak of 2 s. Contractions induced by cysteine plus a catalyst required a functional SR network, were dependent on free [Mg2+] and were blocked by RR or GSH but not by GSSG. 5. In the presence of Hg2+ (2-5 microM), low concentrations of cysteine (10 microM) elicited tonic contractures, but subsequent or higher additions of cysteine (50-100 microM) caused further SR Ca2+ release and tension, followed by rapid and full relaxation. 6. High cysteine (200-250 microM, without Cu2+ or Hg2+) blocked contractions elicited by Cl- induced depolarization of sealed T-tubules. High cysteine probably acted as a sulphydryl reducing agent which promoted rapid relaxation of the fibres through the closure of Ca(2+)-release channels and ATP-dependent re-uptake of Ca2+ by the SR. 7. In some batches of skinned fibres (approximately 10%), cysteine (5-50 microM) alone (without Hg2+ or Cu2+ catalyst) produced rapid twitches. This implied that the catalyst(s) necessary to promote the sulphydryl oxidation reaction with exogenously added cysteine may be present in intact fibres but is usually lost by the skinning procedure. 8. The data demonstrate that skeletal fibres contain a highly reactive and accessible sulphydryl site on an SR protein which can be reversibly oxidized and reduced to respectively, open and close SR Ca(2+)-release channels. A model of sulphydryl-gated excitation-contraction coupling is proposed where the voltage sensor on the T-tubule membrane directly oxidizes sulphydryl sites on SR Ca(2+)-release channels.

Effects of tetracaine and procaine on skinned muscle fibres depend on free calcium.

The local anaesthetics, tetracaine and procaine have previously been found to block, induce or potentiate Ca2+ release from the sarcoplasmic reticulum (SR) of skeletal muscle depending on the preparation, experimental conditions and design. We now show that low concentrations of tetracaine and procaine block SR Ca2+ release whereas high concentrations induce release from the SR of amphibian and mammalian skinned fibres. Both actions depend on pCa, such that a shift in pCa can alter their effect from blocking to releasing Ca2+. In skinned fibres with Ca2+-loaded SR, tetracaine (1 mM) produced a tonic contraction with a time to half-peak of 15-20 s and a magnitude reaching 80% of maximum force. Ca2+ release by tetracaine or procaine occurred at pCa less than or equal to 6.5 and was not blocked by Ruthenium Red (RR) (25 mM). This action of tetracaine was attributed to SR Ca2+ release rather than to a displacement of bound Ca2+ because fibres lacking a functional SR due to pre-treatment with quercetin (100 mM), A 23187 (100 micrograms ml-1) or Triton X-100 (1%) did not contract after additions of tetracaine. Lower concentrations of tetracaine (0.5 mM) and procaine (less than or equal to 10 mM) blocked contractions due to caffeine (at pCa greater than or equal to 6.73), sulphydryl oxidizing agents, or Ca2+-induced Ca2+ release (CICR). The inhibition of CICR as a function of pCa was difficult to measure quantitatively since lowering pCa to elicit CICR twitches was sufficient to initiate tetracaine-induced tonic contractions. Experiments with isolated SR vesicles showed that 1 mM tetracaine inhibited CICR, over a wide range of pCa but 3-5 mM tetracaine induced rapid Ca2+ release. The opposite effects of tetracaine and procaine depend mostly on their concentration in SR vesicles and/or pCa in skinned fibres. Blockade of release seems to occur via the CICR pathway, and induction of release through an increase in SR membrane permeability.

The influence of temperature upon depolarizing responses of rat isolated vagal nerve to 5-hydroxytryptamine.

In isolated cervical segments of rat vagus nerve, over the temperature range 5-45 degrees C, reversible depolarizations to 5-hydroxytryptamine (5-HT) were maximal at 10 degrees C and negligible at 45 degrees C. Dose-response curves for this depolarization were compared at 20 degrees C and 37 degrees C, with a similar sensitivity but marked proportionate reduction at 37 degrees C vs 20 degrees C, whilst the 5-HT-induced depression of vagal compound action potentials seen at 20 degrees C was abolished at 37 degrees C; such changes at 20 degrees C or 37 degrees C were insensitive to inhibitors of 5-HT-uptake (zimelidine) or MAO (pargyline). 5-HT may participate in presynaptic inhibition of C-fibre afferents.

5-Hydroxytryptamine depresses depolarizing responses to GABA in the rat isolated vagus nerve.

Axons of the rat isolated cervical vagus nerve responded to gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) with a readily reversible dose-dependent depolarization. Prior application of 5-HT at 2 or 30 microM equally depressed the depolarizing responses to GABA, shifting the GABA dose-response curve to the right and depressing the maximum; by contrast, responses to 5-HT were affected only by large doses of GABA (greater than 300 microM), and to a lesser degree. In addition, the fade in responses to high doses of GABA was also reduced in the presence of 5-HT. It is suggested that such all-or-none depressive actions may explain the blockade of GABA-induced responses by 5-HT observed in other tissues such as the guinea-pig ileum.