Telerobotic gastrointestinal surgery: phase 2--safety and efficacy.

BACKGROUND: The Federal Drug Administration (FDA) approved the da Vinci surgical system for all abdominal operations in July 2000. In the past 6 years, virtually all gastrointestinal operations have been accomplished using telerobotic techniques. The purpose of this review is to summarize the short-term outcomes achieved with telerobotic gastrointestinal operations. METHODS: All case series of telerobotic gastrointestinal operations identified by PubMed searches are included in this review. RESULTS: Case series document the safety and efficacy of telerobotic cholecystectomy, fundoplication, Heller myotomy, gastric bypass, colectomy, gastrectomy, and pancreatectomy. The procedures were accomplished with low rates of conversion to laparoscopic operations, mortality, and morbidity. When comparison groups were available, the analysis shows that telerobotic operations required more time than the laparoscopic operations, although for telerobotic cholecystectomy and telerobotic fundoplication, this difference disappeared in 10 to 20 operations. Specific patient advantages were not identified for telerobotic operations compared with laparoscopic operations, except for a decreased esophageal perforation rate during telerobotic Heller myotomy. Surgeons benefited from the three-dimensional imaging, the handlike motions of the robotic instruments, and an ergonomically comfortable position. CONCLUSION: All telerobotic gastrointestinal operations are feasible and can be performed with safety and efficacy. It is difficult to demonstrate patient-specific advantages of telerobotic surgery over laparoscopic operations. Nonetheless, telerobotic surgical systems offer distinct advantages to surgeons and may facilitate an increase in the number of surgeons performing advanced laparoscopic gastrointestinal operations. In addition, telerobotics offer a digital information platform that enables surgical simulation and augmented-reality surgery.

Short-term changes in insulin resistance following weight loss surgery for morbid obesity: laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGBP) both effectively treat the insulin resistance associated with type 2 diabetes mellitus (T2DM). Restriction of caloric consumption, alterations in the entero-insular axis or weight loss may contribute to lowering insulin resistance after these procedures. The relative importance of these mechanisms, however, following LAGB and LRYGBP remain unclear. The aim of this study was to compare directly the short-term changes in insulin resistance following LAGB and LRYGBP in similar populations of patients. METHODS: Patient preference determined operation type. The Homeostasis Model Assessment for Insulin Resistance (HOMA IR) was used to measure insulin resistance. Preoperative values were compared to postoperative levels obtained within 90 days of surgery. Significant differences between groups were tested by ANOVA. RESULTS: There were no significant preoperative differences between groups. The 56 LAGB patients had a mean age of 42.5 years (25.7-63), BMI of 45.5 kg/m(2) (35-66) and preoperative HOMA IR of 4.1 (1.4-39.2). 75% of LAGB patients were female and 43% had T2DM. The 61 LRYGBP patients had a median age of 39.9 years (22.1-64.3), BMI of 45.0 kg/m(2) (36-62), and preoperative HOMA IR of 5.0 (0.6-56.5). 79% of LRYGBP patients were women and 44.3% had T2DM. Median follow-up for LAGB patients was 45 days (18-90) and for LRYGBP patients 46 days (8-88 days). LAGB patients had a median of 14.8% excess weight loss (6.9%-37.0%) and LRYGB patients 24.2% (9.8%-51.4%). Postoperative HOMA IR was significantly less after LRYGBP, 2.2 (0.7-12.2), than LAGB, 2.6 (0.8-29.6), although change in HOMA IR was not significantly different. Change in HOMA IR for both groups did not vary with length of follow-up or weight loss but correlated best with preoperative HOMA IR (LAGB r=0.8264; LRYGBP r=0.9711). CONCLUSIONS: Both LAGB and LRYGBP significantly improved insulin resistance during the first 3 months following surgery. Both operations generated similar changes in HOMA IR, although postoperative HOMA IR levels were significantly lower after LRYGBP. These findings suggest that caloric restriction plays a significant role in improving insulin resistance after both LAGB and LRYGBP.

Robotic-assisted laparoscopic low anterior resection with total mesorectal excision for rectal cancer.

BACKGROUND: With advanced stereoscopic vision, lack of tremor, and the ability to rotate the instruments surgeons find that robotic systems are ideal laparoscopic tools. Because of its high operating cost, however, robotic surgery should be reserved to procedures in which the technology can be of maximum benefit, usually when precise dissections in confined spaces are required. Because conventional laparoscopic total mesorectal excision is a challenging procedure, we have sought to assess the utility of the DaVinci robotic system in laparoscopic low anterior resections for cancer of the rectum. METHODS: Between November 2004 and May 2005 robotic-assisted low anterior resection with total mesorectal excision was performed on six consecutive patients with rectal cancer. These cases were compared with six consecutive low anterior resections performed with conventional laparoscopic techniques by the same surgeon. RESULTS: There were no conversions in either group. Operative and pathological data, complications, and hospital stay were similar in the two groups. Robotic operations appeared to cause less strain for the surgeon. CONCLUSIONS: Robotic-assisted laparoscopic low anterior resection for rectal cancer is feasible in experienced hands. This technique may facilitate minimally invasive radical rectal surgery.

Laparoscopic Roux-en-Y gastric bypass: defining the learning curve.

BACKGROUND: Increasing numbers of laparoscopic surgeons are performing laparoscopic Roux-en-Y gastric bypass (LGB). Our aim was to determine the length of the learning curve for a skilled laparoscopic surgeon. METHODS: The study population consisted of the first 225 consecutive LGB procedures attempted by one laparoscopic surgeon (HJS). Outcome parameters included mortality, morbidity, operative time, and conversion to an open procedure. RESULTS: Average operative time decreased from 189 min (first 75 patients) to 125 minutes (last 75 patients). Most of the improvement in operative time occurred over the first 75 patients. The perioperative complication rate decreased from 32% (first 75 patients) to 15% (second and third groups of 75 patients). Complication rates did not significantly decrease after the first 75 patients. Low mortality and conversion rates were achieved early in the series. CONCLUSION: Low mortality rates and low conversion rates can be achieved early in the learning curve for LGB. Complication rates plateau after approximately 75 LGBs, and operative times decrease substantially over the initial 75 cases. Operative times continue to decrease at a slower rate beyond 75 cases.

Robotic surgery, telerobotic surgery, telepresence, and telementoring. Review of early clinical results.

Although laparoscopic cholecystectomy rapidly became the standard of care for the surgical treatment of cholelithiasis, very few other abdominal or cardiac operations are currently performed using minimally invasive surgical techniques. The inherent limitations of traditional laparoscopic surgery make it difficult to perform these operations. We, and others, have attempted to use robotic technology to (a) provide a stable camera platform, (b) replace two-dimensional with three-dimensional (3-D) imaging, (c) simulate the fluid motions of a surgeon's wrist to overcome the motion limitations of straight laparoscopic instruments, and (d) offer the surgeon a comfortable, ergonomically optimal operating position. In this article, we review the early published clinical experience with surgical robotic and telerobotic systems and assess their current limitations. The voice-controlled AESOP robot replaces the cameraperson and facilitates the performance of solo-surgeon laparoscopic operations. AESOP provides a stable camera platform and avoids motion sickness in the operative team. The telerobotic Zeus and da Vinci surgical systems permit solo surgery by a surgeon from a remote sight. These telerobots hold the camera, replace the surgeon's two hands with robotic instruments, and serve in a master-slave relationship for the surgeon. Their robotic instruments simulate the motions of the surgeon's wrist, facilitating dissection. Both telerobots use 3-D imaging to immerse the surgeon in a three-dimensional video operating field. These robots also provide operating positions for the surgeon console that are ergonomically superior to those required by traditional laparoscopy. The technological advances of these telerobots now permit telepresence surgery from remote locations, even locations thousands of miles away. In addition, telepresence permits the telementoring of novice surgeons who are performing new procedures by expert surgeons in remote locations. The studies reviewed here indicate that robotics and telerobotics offer potential solutions to the inherent problems of traditional laparoscopic surgery, as well as new possibilities for telesurgery and telementoring. Nonetheless, these technologies are still in an early stage of development, and each device entails its own set of challenges and limitations for actual use in clinical settings.

Laparoscopic wedge resection of a gastric leiomyoma.

Gastric stromal tumors represent a small percentage of gastric neoplasms. Establishing a diagnosis when these lesions are encountered usually is not possible with limited biopsies. Benign and malignant gastric stromal tumors require only local excision for definitive treatment. However, most lesions are not amenable to endoscopic excision. As a result, laparoscopic local excision offers the ideal method to establish a diagnosis and to treat patients with gastric smooth muscle tumors. We present a minimally invasive local excision of a gastric stromal tumor. We also review the previously published management of gastric stromal tumors and show how it is being influenced by laparoscopy.

Laparoscopic cryoablation of a metastatic carcinoid tumor.

Carcinoid tumors are rare, slow-growing neuroendocrine neoplasms that can cause a carcinoid syndrome. The majority of carcinoid syndromes are the result of multiple hepatic metastases and are usually unresectable. Medical therapy has not proven effective and often causes intolerable side effects. Cryoablation has emerged as a promising treatment for various hepatic lesions when resection is not an option and medical therapy has been exhausted. With the addition of laparoscopy, surgeons now possess a new technique to treat primary and various secondary liver lesions. We report for the first time laparoscopic cryoablation for the treatment of a carcinoid metastatic to the liver.

Octreotide acetate inhibits motility in the rabbit distal colon.

Octreotide, the long-acting somatostatin analogue, has been reported to modulate gastrointestinal motility in both animals and humans. A role in colonic peristalsis and a possible clinical application in common disorders, such as chronic constipation and irritable bowel syndrome, have not been evaluated. It has been previously suggested that octreotide promotes the descending relaxation of the peristaltic reflex arc. We hypothesized that this effect may involve inhibition of the motility index (MI) of the distal colon. To test this proposal, we studied peristalsis in isolated rabbit colons and also in the intact distal colons of anesthetized rabbits undergoing octreotide administration. Left colons of New Zealand white rabbits were harvested, placed in an isolated organ chamber and perfused with Krebs-Ringer bicarbonate solution via the inferior mesenteric artery. In a separate preparation, the colons were left in situ. Motility was quantified with a 6-port continuous infusion manometry catheter. The MI (mm Hg/min) was calculated by integration of the area of the digitalized signal (8/s), which reflected high-pressure peaks of different magnitudes. High-pressure waves were defined as > 20 mm Hg. Octreotide was infused via the inferior mesenteric artery in the isolated specimen or the lateral ear vein in the anesthetized animals in concentrations of 10(-12) to 10(-6) M. Octreotide inhibited high-pressure waves in a dose-dependent manner. These effects resulted in a decreased MI, with the maximum inhibition of 24.6% at 10(-11) M (p < 0.05 by ANOVA). At that concentration, the number of peaks > 20 mm Hg were reduced by 62.2%. The data indicate that octreotide decreases the MI by inhibition of high-pressure waves in the distal rabbit colon. These findings are consistent with the proposal that somatostatin may augment descending relaxation of the peristaltic reflex arc. This effect is independent of neural modulation.

Laparoscopic colon and rectal surgery at a VA hospital. Analysis of the first 50 cases.

BACKGROUND: Laparoscopic techniques were utilized for all colon and rectal procedures undertaken by a single surgeon at the West Haven VA Hospital beginning in August of 1991. METHODS: All patients were entered into a registry, and data was gathered prospectively. This report comprises the first 50 patients. These patients were compared with 34 consecutive patients undergoing open operations during the same time period. RESULTS: Overall, 33 patients (66%) were completed laparoscopically. This increased to 87% after the first 20 patients. Patients undergoing laparoscopic procedures showed significant improvement over the open and converted patients in several areas. Operative blood loss was decreased. They ate sooner (3.7 days) and required less postoperative pain medication. Major complications were less common after laparoscopic operations. Average length of stay was 8.3 days, compared with 13.9 days and 14.5 days in the converted and open groups, respectively. There was no difference in the operative time between laparoscopic and open cases; time for converted cases was significantly longer. There was no difference in lymph node counts among the three groups in patients with resections for cancer. CONCLUSIONS: Laparoscopic colorectal surgery is safe and effective, although its efficacy in malignant disease is uncertain. Patients enjoy the same benefits derived from other laparoscopic procedures. Although there appears to be a longer learning curve associated with the procedure, minimally invasive techniques should become utilized more frequently for patients with colorectal disease.

Alterations of cardiovascular performance during laparoscopic colectomy: a combined hemodynamic and echocardiographic analysis.

We investigated cardiovascular performance in 12 patients (mean age 66 +/- 12 yr) with significant coexisting cardiopulmonary disease (hypertension, coronary artery disease, chronic obstructive pulmonary disease) during laparoscopic colectomy under general anesthesia. Hemodynamic monitors included arterial and pulmonary artery catheters in combination with transesophageal echocardiography. Hemodynamic and echocardiographic data were obtained at five epochs: baseline (after induction of anesthesia), insufflation (after pneumoperitoneum, supine position), Trendelenburg 5 (5 min after placement into Trendelenburg's position), Trendelenburg 20 (at 20 min in Trendelenburg's position), and end (after release of the pneumoperitoneum, supine position). Hemodynamic responses to peritoneal insufflation resulted in significant increases in systemic vascular resistance (SVR) as well as endsystolic area (ESA) and significant decreases in cardiac index (CI) and ejection fraction area (EFa) compared with baseline. Trendelenburg's positioning augmented ventricular preload and performance, resulting in significant increases in pulmonary capillary wedge pressure, CI, end-diastolic area, and EFa compared with insufflation. At the final epoch, end, a hyperdynamic state occurred as evidenced by a significantly decreased ESA and SVR while heart rate, CI, and EFa increased significantly compared to baseline and insufflation. In an elderly population with significant coexisting cardiopulmonary disease, intraoperative maneuvers required for laparoscopic colectomy resulted in previously undescribed alterations of cardiovascular performance, which persisted after release of the pneumoperitoneum.

Octreotide inhibition of serotonin-induced ileal chloride secretion.

Octreotide (SMS, synthetic miniature somatostatin) effectively alleviates the secretory diarrhea of the malignant carcinoid syndrome. Although SMS inhibits tumor release of serotonin (5HT) and other bioactive agents, it also inhibits the diarrhea in patients who continue to exhibit elevated serum levels of 5HT. This observation suggest that SMS may directly inhibit mediator-stimulated intestinal ion secretion at the mucosal level. To test this hypothesis, intestinal ion secretion was studied in rabbit ileal mucosa mounted in Ussing chambers. Maximal changes in short circuit current (delta Isc) were observed as an indicator of mucosal ion secretion. The application of pathophysiologic concentrations of 5HT (10(-5) M) to the mucosal preps resulted in a delta Isc of 52 +/- 6 microA/cm2. This 5HT-stimulated delta Isc was significantly inhibited by serosal furosemide (10(-3) M) or use of a chloride-depleted medium, indicating that 5HT stimulates electrogenic chloride secretion in the rabbit ileum. Pretreatment with a therapeutic concentration of SMS (10(-8) M) resulted in a significant inhibition of 5HT-stimulated electrogenic Cl- secretion (9 +/- 1 microA/cm2) (P < 0.005). This inhibitory effect of SMS was not seen in tissue pretreated with pertussis toxin. The results of these experiments demonstrate that octreotide inhibits 5HT-stimulated electrogenic chloride secretion at the mucosal level. Additionally this inhibitory effect of octreotide is likely mediated by activation of the inhibitory subunit of membrane-bound GTP-binding regulatory proteins. These results thus provide experimental evidence in support of the ability of SMS to ameliorate the carcinoid diarrhea by a direct effect on stimulated mucosal ion secretion.

Laparoscopic-assisted colorectal surgery: review of results in 752 patients.

I summarize the early results of 652 laparoscopic-assisted colorectal operations published in 16 series and 100 operations done by the author. Operations for colorectal neoplasms accounted for two thirds of the procedures. The average age of patients was 63 years. Operations were performed in men and women with equal frequency. Right hemicolectomies and sigmoid colectomies were the most common operations (65.3%). On average, 77% of attempted procedures were converted to open operations. After the first 20 operations, however, the author maintained approximately a 90% success rate. The average length of operation for 542 successful laparoscopic-assisted operations was 170 minutes (range, 45-540 min). The average number of lymph nodes harvested from 226 laparoscopic specimens was 10.5 (range, 0-35). In 3 institutions, the yield of nodes in 80 laparoscopic specimens was 8.8, and in 88 open specimens, it was 7.5. The need for postoperative parenteral injections was decreased for patients after laparoscopic-assisted colorectal operations compared with open operations. The rate of major complications was 16.7% for 647 attempted laparoscopic-assisted operations, and the rate of mortality was 0.8%. The average length of postoperative stay after 543 successful laparoscopic-assisted colorectal operations was 5.9 days. Among 329 patients treated in private hospitals, the average postoperative length of stay was 4.7 days. The cost of laparoscopic-assisted operations was greater than that of open operations. The total cost of hospitalization for patients undergoing laparoscopic-assisted colorectal operations, however, was less than or approximately equal to that for open colorectal operations. The shortened stay offset the increased cost of operation. These results suggest that following laparoscopic-assisted colorectal operations, patients suffer fewer complications, decreased mortality, less pain, and shortened length of stay than patients after traditional open operations. These data, however, have been compiled from selected patients, and demonstration of these preliminary conclusions will require testing by randomized trials.

PYY inhibition of VIP-stimulated ion transport in the rabbit distal ileum.

Vasoactive intestinal polypeptide (VIP) is the pathophysiologic mediator of several small intestinal hypersecretion states. VIP exerts its effect by binding mucosal receptors and ultimately increasing intracellular levels of cAMP. Peptide YY (PYY), a GI hormone concentrated in the distal ileum and colon, has been demonstrated to decrease VIP-mediated secretion in the colon through a specific Y4 mucosal receptor. Characterization of PYY's effect on VIP-stimulated small intestinal secretion may provide a basis for future therapeutic interventions. We hypothesized that ion transport in the small intestine is mediated through a novel Y receptor subtype. We performed Ussing chamber ion transport studies on rabbit ileum using VIP, PYY, and other pancreatic polypeptide (PP)-fold peptides in order to specifically examine: (1) the effects of VIP and PYY on basal and VIP-stimulated short circuit current (Isc), and (2) the changes in VIP-stimulated Isc in response to NPY, PP, leucine31,proline31 neuropeptide Y fragment, ([Leu31,Pro34]NPY) and the carboxy-terminal fragment of NPY (NPY13-36). VIP increased basal Isc in a concentration-dependent manner, while PYY decreased basal Isc. Graded concentrations of PYY decreased VIP-stimulated increases in Isc. PYY added prior to VIP had no effect on VIP-stimulated increases in ISC. Inhibition of VIP-stimulated Isc increases was seen with NPY, but not with [Leu31,Pro34]NPY, PP, or NPY13-36. This distinct pattern of binding affinity characterizes a novel Y receptor subtype. Additionally, increases in Isc by VIP despite pretreatment with PYY suggests that VIP-stimulated ion transport is mediated through mechanisms other than increases in cAMP.

Laparoscopic local excision of a proximal rectal carcinoid.

Early carcinoids of the distal rectum have been treated effectively by transanal local excision. Unfortunately, small carcinoids of the proximal rectum may be unreachable by transanal approaches, and as a result patients have been subjected to more extensive, transabdominal colorectal resections. The recent introduction of minimally invasive techniques for treatment of colorectal diseases has opened new approaches for the treatment of proximal rectal carcinoids. We describe a patient with a 0.5 cm rectal carcinoid located just above the peritoneal reflection in whom transanal local excision was not feasible. We report the first laparoscopic, full-thickness excision of a proximal rectal carcinoid. Intraoperative colonoscopy was used to localize the lesion. This combined laparoscopic and colonoscopic approach spared the patient from the potential morbidity of a low anterior resection and anastomosis.

Sensitivity versus cost effectiveness in postoperative follow-up for colorectal cancer.

The incidence of colorectal cancer is increasing. Approximately 20% of patients present with untreatable, disseminated disease. The remaining 80% are generally treated by intended curative resection. Unfortunately, about 40% of the Dukes B2 and C patients will develop recurrent disease. Of these patients, about one third will develop hepatic metastases, one fifth pulmonary metastases, one fifth intra-abdominal metastases, one tenth retroperitoneal metastases, and one twentieth anastomotic recurrences. Rectal cancer patients may have pelvic recurrence rates as high as one third. Unfortunately, only about one fifth of the Dukes B2 and C patients will initially develop recurrences at only one site and are, thus, potentially curable. Indeed, when considering all colorectal cancer patients, resectable recurrences will be detected in the liver in only 2%, regional recurrences in about 10%, in the lungs in 2%, anastomotic recurrences in less than 1%, and in the ovaries in 1%. In general, long-term survival can be achieved in about 30% of these patients with salvage surgery. The goal of intensive follow-up programs has been to identify these sole site recurrences at an earlier, asymptomatic stage and thereby improve survival. Unfortunately this laudable goal has not been achieved. Intensive (and expensive) follow-up programs consistently achieve long-term survival in 0% to 4% of patients. Reliance on symptoms, however, achieves remarkably similar end results.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium modulation of the effects of serotonin, carbachol, and histamine on rabbit ileal ion transport.

In mammalian intestine, a number of secretagogues have been shown to work through either cyclic nucleotide or calcium mediated pathways to elicit ion secretion. Because excessive intestinal electrolyte and fluid secretion is central to the pathogenesis of a variety of diarrheal disorders, understanding of these processes is essential to the development of future clinical treatments. In the current study, the effects of serotonin (5HT), histamine, and carbachol on intestinal ion transport were examined in in vitro preparations of rabbit ileum. All three agonists induced a rapid and transient increase short-circuit current (delta Isc) across ileal mucosa. Inhibition of the delta Isc response of all three agents in chloride-free solution or in the presence of bumetanide confirmed that chloride is the main electrolyte involved in electrogenic ion secretion. Pretreatment of tissue with tetrodotoxin or atropine did not effect secretagogue-mediated electrolyte secretion. While tachyphylaxis of delta Isc response was shown to develop after repeated exposure of a secretagogue to tissue, delta Isc responses after sequential addition of different agonists indicate that cross-tachyphylaxis between agents did not occur. Serotonin, histamine, and carbachol have previously been reported to mediate electrolyte secretion through calcium-dependent pathways. To access the role of extracellular calcium in regulating ion secretion, the effect of verapamil on each agent was tested; verapamil decreased 5HT-induced delta Isc by 65.2% and histamine response by 33.5%, but had no effect on carbachol-elicited chloride secretion. An additive secretory effect was found upon simultaneous exposure of 5HT and carbachol to the system; no other combination of agents produced a significant additive effect. Findings from this study support previous work which has suggested that multiple calcium pathways may be involved in mediating chloride secretion in mammalian intestine.

Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.

Cyclic AMP-mediated release of peptide YY (PYY) from the isolated perfused rabbit distal colon.

We have investigated the role of the colonic nervous system in regulating the release of peptide YY (PYY) from the isolated perfused rabbit distal colon. In addition, we have studied the role of cAMP- and Ca(2+)-dependent mechanisms in mediating the release of PYY. We investigated three agents which stimulate increases in intracellular cAMP (vasoactive intestinal polypeptide (VIP), cholera toxin, and forskolin) and three agents which raise intracellular Ca2+ concentrations (substance P, carbachol, and the calcium ionophore A23187). The three cAMP-dependent agents, VIP (10(-7) M and 3 x 10(-7) M), cholera toxin (100 micrograms), and forskolin (10(-6) M and 10(-5) M) significantly stimulated release of PYY (P < 0.05). Tetrodotoxin (3 x 10(-6) M) did not alter forskolin (10(-5) M) stimulated release of PYY. Substance P (10(-9) M and 10(-8) M), carbachol (10(-5) M), and A23187 (10(-6) M) failed to stimulate the release of PYY. These results suggest that the colonic neurotransmitter VIP participates in the modulation of PYY release from rabbit distal colons. Further, these studies suggest that release of PYY is mediated by cAMP-dependent pathways.