Laparoscopic mesh hiatoplasty for paraesophageal hernias and fundoplications: a critical analysis of the available literature.

BACKGROUND: Little grade A medical evidence exists to support the use of prosthetic material for hiatal closure. Therefore, the authors compiled and analyzed all the available literature to determine whether the use of prosthetic mesh in hiatoplasty for routine laparoscopic fundoplications (LF) or for the repair of large (>5 cm) paraesophageal hernias (PEH) would decrease recurrence. METHODS: A literature search was performed using an inclusive list of relevant search terms via Medline/PubMed to identify papers (n = 19) describing the use of prosthetic material to repair the crura of patients undergoing laparoscopic PEH reduction, LF, or both. RESULTS: Case series (n = 5), retrospective reviews (n = 6), and prospective randomized (n = 4) and nonrandomized (n = 4) trials were identified. Laparoscopic procedures (n = 1,368) were performed for PEH, gastroesophageal reflux disease (GERD), hiatal hernia, or a combination of the three. Group A (n = 729) had primary suture repair of the crura, and group B (n = 639) had repair with either interposition of mesh to close the hiatus or onlay of prosthetic material after hiatal or crural closure. The use of mesh was associated with fewer recurrences than primary suture repair in both the LF and PEH groups. The mean follow-up period did not differ between the groups (20.7 months for group A vs. 19.2 months for group B). None of the papers cited any instance of prosthetic erosion into the gastrointestinal tract. CONCLUSIONS: The current data tend to support the use of prosthetic materials for hiatal repair in both routine LF and the repair of large PEHs. Longer and more stringent follow-up evaluation is necessary to delineate better the safety profile of mesh hiatoplasty. Future randomized trials are needed to confirm that mesh repair is superior to simple crural closure.

Postoperative complications are not increased in super-super obese patients who undergo laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: It has been suggested that super-super obesity (body mass index [BMI] > or =60 kg/m2) increases the risk of complications after laparoscopic Roux-en-Y gastric bypass (LapRYGB). We hypothesized that a higher BMI does not increase risk the morbidity or mortality rate. METHODS: Complication rates for patients with a BMI > or =60 kg/m2 were compared to those for patients with a BMI <60 kg/m2 who underwent LapRYGB during the same time period. Differences between the groups were analyzed by Fisher's exact test, t-tests, and analysis of variance. RESULTS: Forty-five patients with a BMI > or =60 kg/m2 and 640 patients with a BMI <60 kg/m2 underwent LapRYGB. There were no statistically significant differences between the two groups in the complication or mortality rates. Excess weight loss was less, but actual weight lost was greater in the BMI > or =60 kg/m2 group. CONCLUSIONS: The complication and mortality rates are not increased in super-super obese patients who undergo LapRYGB. Acceptable weight loss can be achieved safely in these patients.

Optimal management of the morbidly obese patient. SAGES appropriateness conference statement.

BACKGROUND: Obesity is a growing health problem that contributes to numerous life-threatening or disabling disorders, including coronary artery disease, hypertension, type 2 diabetes mellitus, hyperlipidemia, degenerative joint disease, and obstructive sleep apnea. Significant weight reduction in the morbidly obese improves or reverses associated illness and benefits well-being. The purpose of the SAGES Appropriateness Conference was to summarize the state of the art for open and laparoscopic operations for the morbidly obese. METHODS: The English literature comparing bariatric procedures was reviewed and grouped by level of evidence by three surgeons (BS, LV, and CC). From more than 1,500 articles, all conference participants were provided with reprints and table summaries of no less than 50 selected manuscripts. Ten experts were requested to present reviews and make evidence-based arguments for and against the open and laparoscopic approaches in written format. An expert panel of six surgeons, including an ethicist and patient, commented on implications of data presented. The finalized statement was e-mailed to all participants for approval and comment. RESULTS: Consensus statements were achieved on various aspects of morbid obesity, including indications for surgery, resolution of comorbid illnesses with significant weight loss, and the importance of committed bariatric program. Our panel of experts agreed, in general, to the advantages of laparoscopic approaches compared to open operations in skilled hands. CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass (RYGB) affords improved short-term recovery compared to open gastric bypass. Laparoscopic adjustable banding can be performed with lower average mortality than either RYGB or any of the malabsorptive operations, and it produces variable degrees of short-term weight loss. Prospective randomized trials are needed to compare gastric bypass, malabsorptive, and restrictive procedures.

Experience with over 3,000 open and laparoscopic bariatric procedures: multivariate analysis of factors related to leak and resultant mortality.

BACKGROUND: Intestinal leak is a potentially lethal complication of Roux en-Y gastric bypass (GBP). Identification of patients at high risk for leak may reduce complication rates of surgeons early in the procedure learning curve. METHODS: A total of 3073 patients who underwent GBP were analyzed using univariate and multivariate logistic regression analyses of the following preoperative factors: hypertension (HTN), diabetes mellitus (DM), sleep apnea (SA), age, gender, weight, body mass index (BMI), and surgery type. Multivariate logistic regression analysis was performed for each procedure type. RESULTS: There were 48 (1.5%) deaths. Independent risk factors for death included leak, weight, procedure type, and HTN. A total of 102 (3.2%) leaks were found. Independent factors for leak included age, male gender, SA, and procedure type. CONCLUSION: The data suggests that older, heavier male patients with multiple comorbid conditions are at increased risk for leak and mortality. Surgeons early in their learning curve should avoid these high-risk patients to reduce complications.

Training the novice in laparoscopy. More challenge is better.

BACKGROUND: Virtual reality simulation is effective in training the novice to perform basic laparoscopic skills. METHODS: Using the Minimally Invasive Surgery Training--Virtual Reality (MIST-VR) trainer, 27 honors high school students were tested at the easy level, prospectively randomized to eight training sessions at the easy (group A, n = 14) or medium (group B, n = 13) level, then retested at the easy level. RESULTS: Both groups were statistically similar at baseline. All scores improved significantly (50.1% to 81.3%) over the period of training (p < 0.05). Although the group A scores were significantly better than the group B scores throughout training (p < 0.05), on final testing at the easy level, group B surpassed group A for all the tasks except TransferPlace (p = 0.054). CONCLUSIONS: Virtual simulation is an effective laparoscopic training method for the novice, providing significant improvement in skill levels over a relatively short period. More challenging training seems to predict greater improvement over time and better final skill levels.

Hand-assisted laparoscopic gastric bypass does not improve outcome and increases costs when compared to open gastric bypass for the surgical treatment of obesity.

BACKGROUND: Hand-assisted laparoscopic Roux-en-Y gastric bypass (Hand-Lap GB) has been adopted by some surgeons to treat morbid obesity because it is easier to perform than the total laparoscopic procedure, but to date no study has compared the outcomes of patients undergoing the Hand-Lap GB to those obtained with the open procedure (Open GB). We hypothesized that patients undergoing Hand-Lap GB would lose a similar amount of weight when compared to Open GB patients, while experiencing no increase in complications, a shorter hospital stay, and lower overall costs of care, in part as a result of fewer incisional hernias requiring subsequent surgery. METHODS: Nonrandomized, prospective data were collected on all patients undergoing proximal GB via Hand-Lap or open approaches between May 1998 and July 1999. Our first 25 Hand-Lap GB procedures, performed in selected patients (with no extensive previous abdominal surgery) referred to two of us (E.J.D, M.A.S), were compared to all other (n = 62) concurrent open proximal GB performed by the group during this period of time in patients with body mass index (BMI) <50 kg/m2. RESULTS: Preoperatively, Hand-Lap GB patients did not differ from Open GB patients in age (40 +/- 11 vs 43 +/- 11 years), gender (92% female vs 81% female), incidence or type of preoperative comorbid conditions, preoperative weight (282 +/- 33 vs 280 +/- 37 lb), or BMI (45.5 +/- 5.4 vs 44.1 +/- 3.3 kg/m2). (Data given as mean +/- standard deviation). Although length of hospital stay did not differ between groups (3.6 +/- 1.3 vs 4.2 +/- 4.6 days), total hospital costs were significantly higher for Hand-Lap GB ($14,725 +/- 3089 vs. $10,281 +/- 3687, p <0.01 ANOVA). One patient in the Open GB group developed an anastomotic leak from the gastrojejunostomy. Follow-up revealed that Hand-Lap GB patients had a similar risk of postoperative complications as the Open GB group, including marginal ulcer (16% vs 14.5%), stomal stenosis (24% vs 23%), and, most notably, incisional hernia (20% vs 27%). There were no major wound infections or deaths in either group. One patient in each group developed a postoperative small bowel obstruction. Loss of excess weight in Hand-Lap GB patients at 12 months postoperatively was 66 +/- 14% vs 77 +/- 14% in the Open GB group. CONCLUSIONS: The Hand-Lap GB yielded good weight reduction in a population of morbidly obese patients, but at a higher cost for hospital care than Open GB. There was no decrease in the incidence of incisional hernias with the Hand-Lap GB procedure. Although Hand-Lap GB appears to be safe and effective, its failure to provide a decrease in hospital stay or risk of incisional hernia requiring subsequent surgical repair is significant. The primary role for the Hand-Lap GB procedure should therefore be to aid surgeons in developing skills to climb the steep learning curve for total laparoscopic gastric bypass, since Hand-Lap GB does not improve patient outcome and increases cost in comparison to the open GB procedure.

Laparoscopic adjustable silicone gastric banding.

Laparoscopic adjustable silicone gastric banding (LASGB) is a relatively new surgical procedure for the treatment of morbid obesity The most popular banding procedure is the vertical banded gastroplasty, however, there are risks involved in this procedure, including staple-line disruption and postoperative intractable vomiting. This article presents the advantages of using the LASGB device over former types of gastric banding.

Laparoscopic telescope with alpha port and aesop to view open surgical procedures.

Laparoscopy has advanced surgery by allowing the surgeon to operate within a patient's abdominal and pelvic cavity with minimal trauma and scarring. The coupling of a video camera to the laparoscopic telescope has had the secondary effect of allowing others to view the surgical field either on color video monitors or by watching the video feed over the Internet at a remote location. These advancements have allowed better teaching and mentoring of operations. Open procedures can benefit from this technology as well but have suffered in the past from inadequate methods to depict the open surgical field. We used the Alpha Port and Aesop robot to position a sterile laparoscopic telescope near the surgical field to view open cholecystectomies performed on five pigs and to send the video feed over the Internet to remote physicians. Viewing the video on the monitor, the surgeons performed the operation in a comfortable ergonomic upright position. Both the surgeons and the remote physicians found the quality of the video to be excellent, and the remote physicians felt comfortable learning and mentoring surgical procedures using this technique.

Risks and benefits of gastric bypass in morbidly obese patients with severe venous stasis disease.

OBJECTIVE: To determine the risks and benefits of gastric bypass-induced weight loss on severe venous stasis disease in morbid obesity. SUMMARY BACKGROUND DATA: Severe obesity is associated with a risk of lower extremity venous stasis disease, pretibial ulceration, cellulitis, and bronze edema. METHODS: The GBP database was queried for venous stasis disease including pretibial venous stasis ulcers, bronze edema, and cellulitis. RESULTS: Of 1,976 patients undergoing GBP, 64 (45% female) met the criteria. Mean age was 44 +/- 10 years. Thirty-seven patients had pretibial venous stasis ulcers, 4 had bronze edema, 23 had both, and 17 had recurrent cellulitis. All had 2 to 4+ pitting pretibial edema. Mean preoperative body mass index (BMI) was 61 +/- 12 kg/m(2) and weight was 179 +/- 39 kg (270 +/- 51% ideal body weight), significantly greater than in patients who underwent GBP without venous stasis disease. Two patients had a pulmonary embolus and four had Greenfield filters in the remote past. Additional comorbidities included obesity hypoventilation syndrome, sleep apnea syndrome, hypertension, gastroesophageal reflux, degenerative joint disease symptoms, type 2 diabetes mellitus, pseudotumor cerebri, and urinary incontinence. Comorbidities were significantly more frequent in the patients with venous stasis disease than for those without. At 3.9 +/- 4 years after surgery, patients lost 55 +/- 21 % of excess weight, 62 +/- 33 kg, reaching 40 +/- 9 kg/m(2) BMI or 176 +/- 41% ideal body weight. Venous stasis ulcers resolved in all but three patients. Complications included anastomotic leaks with peritonitis and death, fatal pulmonary embolism, fatal respiratory arrest, wound infections or seromas, staple line disruptions, marginal ulcerations treated with acid suppression, stomal stenoses treated with endoscopic dilatation, late small bowel obstructions, and incisional hernias. There were six other late deaths. CONCLUSIONS: Severe venous stasis disease was associated with a significantly greater weight, BMI, male sex, age, comorbidity, and surgical risk (pulmonary embolus, leak, death, incisional hernia) than in other patients who underwent GBP. Surgically induced weight loss corrected the venous stasis disease in almost all patients as well as their other obesity-related problems.

High failure rate after laparoscopic adjustable silicone gastric banding for treatment of morbid obesity.

OBJECTIVE: To report the results from one of the eight original U.S. centers performing laparoscopic adjustable silicone gastric banding (LASGB), a new minimally invasive surgical technique for treatment of morbid obesity. SUMMARY BACKGROUND DATA: Laparoscopic adjustable silicone gastric banding is under evaluation by the Food & Drug Administration in the United States in an initial cohort of 300 patients. METHODS: Of 37 patients undergoing laparoscopic placement of the LASGB device, successful placement occurred in 36 from March 1996 to May 1998. Patients have been followed up for up to 4 years. RESULTS: Five patients (14%) have been lost to follow-up for more than 2 years but at last available follow-up (3-18 months after surgery) had achieved only 18% (range 5-38%) excess weight loss. African American patients had poor weight loss after LASGB compared with whites. The LASGB devices were removed in 15 (41%) patients 10 days to 42 months after surgery. Four patients underwent simple removal; 11 were converted to gastric bypass. The most common reason for removal was inadequate weight loss in the presence of a functioning band. The primary reasons for removal in others were infection, leakage from the inflatable silicone ring causing inadequate weight loss, or band slippage. The patients with band slippage had concomitant poor weight loss. Bands were removed in two others as a result of symptoms related to esophageal dilatation. In 18 of 25 patients (71%) who underwent preoperative and long-term postoperative contrast evaluation, a significantly increased esophageal diameter developed; of these, 13 (72%) had prominent dysphagia, vomiting, or reflux symptoms. Of the remaining 21 patients with bands, 8 currently desire removal and conversion to gastric bypass for inadequate weight loss. Six of the remaining patients have persistent morbid obesity at least 2 years after surgery but refuse to undergo further surgery or claim to be satisfied with the results. Overall, only four patients achieved a body-mass index of less than 35 and/or at least a 50% reduction in excess weight. Thus, the overall need for band removal and conversion to GBP in this series will ultimately exceed 50%. CONCLUSIONS: The authors did not find LASGB to be an effective procedure for the surgical treatment of morbid obesity. Complications after LASGB include esophageal dilatation, band leakage, infection, erosion, and slippage. Inadequate weight loss is common, particularly in African American patients. More study is required to determine the long-term efficacy of the LASGB

Intrathoracic herniation and perforation 18 years after open Nissen fundoplication.

Nissen fundoplication is the most commonly performed surgical procedure in the management of gastroesophageal reflux disease. Esophageal and gastric perforations most commonly occur in the perioperative period and carry significant morbidity. We describe a unique case of intrathoracic gastric wrap perforation and its suspected pathophysiology almost two decades after the original procedure.

Ileal pouch anal anastomosis without ileal diversion.

OBJECTIVE: To evaluate continued experience with a one-stage stapled ileoanal pouch procedure without temporary ileostomy diversion. SUMMARY BACKGROUND DATA: Most centers perform colectomy, proctectomy, and ileal pouch anal anastomoses (IPAA) with a protective ileostomy. Following a previous report, the authors performed 126 additional stapled IPAA procedures for ulcerative colitis and familial adenomatous polyposis, of which all but 2 were without an ileostomy. Outcomes in these patients question the need for temporary ileal diversion, with its complications and need for subsequent surgical closure. METHODS: Two hundred one patients underwent a stapled IPAA since May 1989, 192 as a one-stage procedure without ileostomy, and 1 with a concurrent Whipple procedure for duodenal adenocarcinoma. Patient charts were reviewed or patients were contacted by phone to evaluate their clinical status at least 1 year after their surgery. RESULTS: Among the patients who underwent the one-stage procedure, 178 had ulcerative colitis (38 fulminant), 5 had Crohn's disease (diagnosed after IPAA), 1 had indeterminate colitis, and 8 had familial adenomatous polyposis. The mean age was 38 +/- 7 (range 7--70) years; there were 98 male patients and 94 female patients. The average amount of diseased tissue between the dentate line and the anastomosis was 0.9 +/- 0.1 cm, with 35% of the anastomoses at the dentate line. With 89% follow-up at 1 year or more (mean 5.1 +/- 2.4 years) after surgery, the average 24-hour stool frequency was 7.1 +/- 3.3, of which 0.9 +/- 1.4 were at night. Daytime stool control was 95% and night-time control was 90%. Only 2.3% needed to wear a perineal pad. Average length of hospital stay was 10 +/- 0.3 days, with 1.5 +/- 0.5 days readmission for complications. Abscesses or enteric leaks occurred in 23 patients; IPAA function was excellent in 19 of these patients (2 have permanent ileostomies). In patients taking steroids, there was no significant difference in leak rate with duration of use (29 +/- 8 with vs. 22 +/- 2 months without leak) or dose (32 +/- 13 mg with vs. 35 +/- 3 mg without leak). Two (1%) patients died (myocardial infarction, mesenteric infarction). CONCLUSIONS: The triple-stapled IPAA without temporary ileal diversion has a relatively low complication rate and a low rate of small bowel obstruction, provides excellent fecal control, permits an early return to a functional life, and can be performed in morbidly obese and older patients.

Complementary roles of laparoscopic abdominal exploration and diagnostic peritoneal lavage for evaluating abdominal stab wounds: a prospective study.

PURPOSE: To determine the roles of laparoscopic abdominal exploration (LE) and diagnostic peritoneal lavage (DPL) in the evaluation of abdominal stab wounds, we prospectively compared LE with mandatory celiotomy (MC) in 76 patients having anterior abdominal stab wounds penetrating the fascia over a 22-month period. PATIENTS AND METHODS: Twenty-two patients underwent emergency celiotomy. The remaining patients were subjected to DPL and assigned to treatment by either celiotomy or initial LE with subsequent conversion to open exploration at the discretion of the attending surgeon. RESULTS: Laparotomy was avoided in 55% of the 31 patients undergoing initial laparoscopy, and this group demonstrated a significant decrease in the incidence of nontherapeutic celiotomy, from 19% to 57% (P < 0.05), as well as decreased length of hospital stay (4 +/- 0.6 v 5.9 +/- 0.4 days; P < 0.05), and total hospital cost ($6119 +/- 756 v $8312 +/- 627; P < 0.05). There were no missed intraabdominal injuries or morbidity from laparoscopy identified in follow-up. The DPL (N = 36) was positive in 11 of the 12 patients with injury requiring surgical repair and was negative in 16 of the 25 patients not requiring repair. The sensitivity and specificity of DPL were 0.91 and 0.64 compared with 1.0 and 0.74 for laparoscopy. CONCLUSIONS: An algorithm to evaluate stable patients with anterior abdominal stab wounds and minimize overall costs of care, incidence of nontherapeutic celiotomy, and rate of missed injuries is suggested consisting of DPL followed by observation in patients with negative DPL and by laparoscopy in patients with positive DPL. Wounds to the thoracoabdominal region may be best evaluated by initial LE, as diaphragmatic wounds may result in a false-negative DPL.

Laparoscopic closure of mesenteric defects after Roux-en-Y gastric bypass.

Two case reports are presented of incarcerated small-bowel internal hernias through mesenteric defects following Roux-en-Y gastric bypass surgery (one case each of open and laparoscopic). Both patients first presented to physicians unfamiliar with bariatric surgery complaining of vague, cramping midabdominal pain, and the correct diagnosis was not revealed until laparoscopic surgery was performed. Treatment then resulted in quick recoveries. This type of hernia can evade radiologic testing. Prompt clinical recognition and treatment is necessary to prevent small-bowel infarction.

Laparoscopic intraperitoneal polytetrafluoroethylene (PTFE) prosthetic patch repair of ventral hernia. Prospective comparison to open prefascial polypropylene mesh repair.

BACKGROUND: The purpose of this study was to determine whether laparoscopic intraperitoneal polytetrafluoroethylene (PTFE) prosthetic patch (LIPP) repair of a ventral hernia is superior to open prefascial polypropylene mesh (OPPM) repair in a tertiary care university hospital in an urban environment. METHODS: Data on 39 consecutive patients undergoing either LIPP repair (n = 21) or OPPM repair (n = 18) were compared. RESULTS: Findings showed that LIPP repair is characterized by less painful recovery and shorter hospital stay, with 90% of patients treated successfully as outpatients as compared with 7% in the OPPM group. The total facility costs for the LIPP repair ($8,273+/-$2,950) was significantly lower than for the OPPM repair ($12,461+/-$5,987) (p<0.05). Two serious delayed complications in the LIPP group were treated by reoperation (colocutaneous fistula, mesh infection), but the higher readmission costs in this group did not negate the overall cost advantage for LIPP repair. In the follow-up evaluation, 1 hernia recurrence was found in the LIPP repair group, and none in the OPPM group. CONCLUSIONS: Initial experience suggests that LIPP repair has advantages over OPPM repair in terms of decreased hospitalization, postoperative pain, and disability. Refinements in the technique to reduce complications may make LIPP repair the procedure of choice for repair of ventral hernias.

Feasibility of 23-hour hospitalization after laparoscopic fundoplication.

PURPOSE: In order to reduce the costs of laparoscopic fundoplication, a pilot program for outpatient surgery was instituted in 1995. The risks and benefits of reducing postoperative hospitalization to < or =23 hours were assessed. PATIENTS AND METHODS: Patients in ASA grade I or II (N = 22) with refractory gastroesophageal reflux disease underwent laparoscopic fundoplication over a 21-month period in a hospital-affiliated outpatient facility. The results were compared with those of a similar group of 16 patients whose surgery was performed on an inpatient basis. RESULTS: Seventeen patients (77%) were discharged within 23 hours of surgery. The maximum length of stay was 3 days. There were no deaths. Nineteen patients (86%) reported excellent results. The average facility cost declined from $7,169 for the inpatient group to $4,588 for patients on operated under the outpatient protocol. The decrease resulted from a reduction in the cost of room, operating suite, supplies, and anesthesia. CONCLUSION: Laparoscopic fundoplication can be performed safely in a hospital-affiliated outpatient setting, resulting in a significant reduction in procedure costs.

Laparoscopic-assisted Roux-en-Y gastric bypass.

Eight patients underwent laparoscopic Roux-en-Y gastric bypass from May 1998 to September 1998 in which a hand-assist technique was used. The operation consisted of a 7.5-cm periumbilical midline incision along with three trocars placed in the upper abdomen. The operative times ranged from 2.25 to 4.5 h. The average preoperative body mass index was 44 kg/m2. Three-month postoperative follow-up revealed an average weight loss of 59 lb. Cosmetic results to date have been excellent even when compared with those of a total laparoscopic operation. The hand-assist technique allows the surgeon to have more control over the most difficult part of the case, which is manipulation of the small bowel in a morbidly obese abdomen.

Cholesterol enhances membrane-damaging properties of model bile by increasing the intervesicular-intermixed micellar concentration of hydrophobic bile salts.

UNLABELLED: Bile salts are potent detergents that, at concentrations attained in bile and intestine, can disrupt cell membranes. Hepatic secretion of vesicles containing lecithin and cholesterol appears to be critical in preventing bile salt damage to hepatobiliary epithelia. We hypothesize that the protective effect of biliary lipids results from lowering of the bile salt intervesicular intermixed micellar bile salt concentration (IMMC) to which epithelial membranes are exposed. We further hypothesize that increases in biliary cholesterol, by reducing association of bile salts with vesicles and mixed micelles, may increase bile toxicity by raising the bile salt IMMC. METHOD: Large unilamellar lecithin vesicles (100 nm) with varying cholesterol:lecithin molar ratios (C:L) of 0, 0.5, and 1 were added to taurochenodeoxycholate (TCDCA), taurocholate (TCA), or taurodeoxycholate (TDCA) in Tris-buffered saline, pH 7.4. Human erythrocyte ghosts (model target membrane), prepared by osmotic hemolysis and resealed with [14C]inulin trapped inside, were added and incubated at 37 degrees C for 30 min and 4 h. Plasma membrane disruption was quantified by [14C]inulin release and bile salt IMMC was determined by ultrafiltration. RESULTS: Membrane disruption started at a concentration of 0.5 mM for TDCA, 1 mM for TCDCA, and 2 mM for TCA and was complete within 4 h at concentrations of 1, 2, and 4 mM, respectively. Addition of 2 mM lecithin to 2 mM TDCA, 4 mM TCDCA, or 5 mM TCA reduced or eliminated membrane leakage and lowered the IMMC. For TDCA and TCDCA, the protective effect of vesicles was entirely attributable to reduction in IMMC; in contrast for TCA, the protective effect exceeded that which would have been expected based solely on reduction of the IMMC. Inclusion of cholesterol attenuated the binding of bile salts to vesicles and raised the IMMC, thereby reducing the protective effect of lecithin over the time course of these studies. Although there was loss of phospholipid and cholesterol from the erythrocyte membranes on addition of bile acids even in the presence of vesicles, the ratio of cholesterol to phospholipid in the erythrocyte membrane did not change. CONCLUSION: Lecithin protects against membrane disruption by hydrophobic bile salts by lowering the IMMC. Cholesterol added to lecithin raises the bile salt IMMC and reduces or eliminates this protective effect. This mechanism of potentiation of bile salt toxicity by cholesterol may be an important contributor to the pathogenesis of gallbladder disease in cholesterol cholelithiasis.