Laparoscopy alone is superior to peritoneal cytology in staging gastric and esophageal carcinoma.

BACKGROUND: Laparoscopy identifies metastatic disease in patients with upper gastrointestinal malignancies; however, it has been suggested that cytological examination of peritoneal washings may increase the diagnostic yield. We hypothesize that the addition of cytologic washings to a standardized staging laparoscopy is unnecessary for the identification of intraabdominal metastasis in patients with gastric/esophageal cancer. METHODS: Forty patients with gastric/esophageal cancer were prospectively evaluated. Patients successfully underwent a diagnostic laparoscopy protocol (with biopsies) during which peritoneal washings were obtained and processed for cytologic analysis. Laparoscopic versus cytologic identification of intraabdominal metastasis were compared. RESULTS: Forty patients successfully completed laparoscopy with collection of peritoneal washings. Laparoscopic examination of the peritoneal cavity upstaged 21 (52.5%) patients. Laparoscopic examination consistently identified a statistically significant higher number of positive patients than cytologic examination of peritoneal washings (p = 0.001) and examination of cytologic washings alone failed to identify 45% of patients with positive findings and laparoscopy. The addition of cytologic examination added no additional stage IV patients to the laparoscopy-negative group. CONCLUSION: A standardized laparoscopic examination alone is sufficient for the identification of intraabdominal metastatic disease in patients with gastric and esophageal cancer.

Comparison of video trainer and virtual reality training systems on acquisition of laparoscopic skills.

Training on a video trainer or computer-based minimally invasive surgery trainer leads to improved benchtop laparoscopic skill. Recently, improved operative performance from practice on a video trainer was reported. The purpose of this study was three fold: (a) to compare psychomotor skill improvement after training on a virtual reality (VR) system with that after training on a video-trainer, (VT) (b) to evaluate whether skills learned on the one training system are transferable to the other, and (c) to evaluate whether VR or VT training improves operative performance. For the study, 50 junior surgery residents completed baseline skill testing on both the VR and VT systems. These subjects then were randomized to either a VR or VT structured training group. After practice, the subjects were tested again on their VR and VT skills. To assess the effect of practice on operative performance, all second-year residents (n = 19) were evaluated on their operative performance during a laparoscopic cholecystectomy before and after skill training. Data are expressed as percentage of improvement in mean score/time. Analysis was performed by Student's paired t-test. The VR training group showed improvement of 54% on the VR posttest, as compared with 55% improvement by the VT group. The VR training group improved more on the VT posttest tasks (36%) than the VT training group improved on the VR posttest tasks (17%) (p <0.05). Operative performance improved only in the VR training group (p <0.05). Psychomotor skills improve after training on both VR and VT, and skills may be transferable. Furthermore, training on a minimally invasive surgery trainer, virtual reality system may improve operative performance during laparoscopic cholecystectomy.

Laparoscopic skills training.

BACKGROUND: The purpose of this study was to quantify the learning curve of a previously validated laparoscopic skills curriculum. METHODS: Second-year medical students (MS2, n = 11) and second (PGY2, n = 11) and third (PGY3, n = 6) year surgery residents were enrolled into a curriculum using five video-trainer tasks. All subjects underwent baseline testing, training (30 minutes per day for 10 days), and final testing. Scores were based on completion time. The relationship between task completion time and the number of practice repetitions was examined. Improvement (the difference in baseline and final performance) amongst groups was compared by one-way analysis of variance using the baseline score as a covariate; P <0.05 indicated significance. RESULTS: Baseline scores were not significantly different. Final scores were significantly better for MS2s versus PGY3s. Adjusted-improvement was significantly larger for the MS2s compared with PGY2s and PGY3s, and for PGY2s compared with PGY3s. The mean number of repetitions corresponding to a predicted 90th percentile score was 32. CONCLUSION: Inexperienced subjects benefit the most from skills training. For maximal benefit, we recommend that each task be practiced for at least 30 to 35 repetitions.

Laparoscopic marsupialization and hemisplenectomy for splenic cysts.

BACKGROUND: Splenic cysts are a rare clinical entity in the United States, and historically, management has consisted of either partial or total splenectomy via an open approach. Laparoscopic treatment of splenic cysts with preservation of splenic parenchyma offers several advantages. Compared with the open approach, a laparoscopic approach may result in less postoperative pain and a more rapid return to full activity. Compared with total splenectomy, splenic preservation eliminates the risk of overwhelming postsplenectomy infection. PATIENTS AND METHODS: We present two patients with splenic cysts. One patient was treated with laparoscopic marsupialization of the cyst and the other with laparoscopic hemisplenectomy. RESULTS: Both patients are without further symptoms at 26 and 5 months' follow-up, respectively. CONCLUSIONS: Laparoscopic marsupialization and hemisplenectomy are appropriate treatment options for patients with splenic cysts.

Accuracy and effectiveness of laparoscopic vs open hepatic radiofrequency ablation.

BACKGROUND: The purpose of this study was to compare the accuracy (in terms of ultrasound-guided probe placement) and the effectiveness (in terms of pathologic tumor-free margin) of laparoscopic vs open radiofrequency (RF) ablation. METHODS: Using a previously validated tissue-mimic model, 1-cm simulated hepatic tumors were ablated in 10 pigs randomized to open or laparoscopic techniques. Energy was applied until tissue temperature reached 100 degrees C (warm-up) and thereafter for 8 min. A pathologist blinded to technique examined all specimens immediately after treatment. Analysis was by Fisher's exact test and the Mann-Whitney U test; p < 0.05 was considered significant. RESULTS: Off-center distance (3.5 +/- 1.6 vs 4.2 +/- 1.4 mm), size (24.7 +/- 3.1 vs 25.6 +/- 3.8 mm), symmetry (40% vs 73%), margin positivity (33% vs 9%), and margin distance (1.1 +/- 1.2 vs 2.2 +/- 1.6 mm) were not significantly different between laparoscopic (n = 15) and open (n = 11) ablations, respectively. The proportion of round/ovoid lesions (20% vs 64%) was lower (p = 0.043), and warm-up time (20.2 +/- 14.0 vs 10.7 +/- 7.5) was longer (p = 0.049) for the laparoscopic than for the open groups, respectively. CONCLUSION: Accurate probe placement can be achieved using laparoscopic and open RF ablation techniques. The physiologic effects of laparoscopy may alter ablation shape and warm-up time. Additional studies are needed to establish effective ways of achieving complete tumor destruction.

Improving operative performance using a laparoscopic hernia simulator.

BACKGROUND: Traditionally, the acquisition of surgical skill has occurred entirely in the operating room. To meet the expanding challenges of cost containment and patient safety, novel methods of surgical training utilizing ex-vivo workstations are being developed. The purpose of our study was to evaluate the impact of a laparoscopic training curriculum on surgical residents' operative performance. METHODS: Twenty-one surgery residents completed baseline laparoscopic total extraperitoneal (TEP) hernia repairs. Operative performance was evaluated using a validated global assessment tool. Each resident was then randomized to a control group or a trained group. A CD ROM, video, and simulator were used for training. At the end of the study, each resident's operative performance was again evaluated. RESULTS: Improvement was significantly greater in the trained group in five of the eight individual global assessment areas as well as the composite score (P <0.05). Questionnaire data suggested that training resulted in improved understanding of the TEP hernia repair (P = 0.01) and an increased willingness to offer the operation to patients with nonrecurrent unilateral hernias (P = 0.02). CONCLUSIONS: A multimodality laparoscopic TEP hernia curriculum improves residents' knowledge of the TEP hernia repair and comfort in performing the procedure, and may also improve actual operative performance.

Evaluating surgical competency with the American Board of Surgery In-Training Examination, skill testing, and intraoperative assessment.

BACKGROUND: Evaluation of surgical competency should include assessment of knowledge, technical skill, and judgment. The purpose of this study was to determine the relationship between the American Board of Surgery In-Training Examination (ABSITE), skill testing, and intraoperative assessment. METHODS: Postgraduate year 2 (PGY-2) and postgraduate year 3 (PGY-3) surgery residents (n = 33) were tested by means of (1) the ABSITE, (2) skill testing on a laparoscopic video-trainer, and (3) intra-operative global assessments during laparoscopic cholecystectomy. The Pearson correlation was used to determine the correlation between the ABSITE, skill testing, and intraoperative assessments. For the comparison of PGY-2 and PGY-3 resident performance, Wilcoxon rank sum tests were used. RESULTS: The ABSITE scores did not correlate with skill testing or intraoperative assessments (not significant). Skill testing correlated with the intraoperative composite score and with 4 of 8 operative performance criteria (P<.05). The ABSITE scores and skill testing were not different for PGY-2 and PGY-3 residents (not significant). Intraoperative assessments were better in 5 of 8 criteria and the composite score for PGY-3 versus PGY-2 residents (P<.05), which demonstrated construct validity. CONCLUSIONS: The ABSITE measures knowledge but does not correlate with technical skill or operative performance. Residency programs should use multiple assessment instruments to evaluate competency. There may be a role for both skill testing and intraoperative assessment in the evaluation of surgical competency.

Laparoscopic training on bench models: better and more cost effective than operating room experience?

BACKGROUND: Developing technical skill is essential to surgical training, but using the operating room for basic skill acquisition may be inefficient and expensive, especially for laparoscopic operations. This study determines if laparoscopic skills training using simulated tasks on a video-trainer improves the operative performance of surgery residents. STUDY DESIGN: Second- and third-year residents (n= 27) were prospectively randomized to receive formal laparoscopic skills training or to a control group. At baseline, residents had a validated global assessment of their ability to perform a laparoscopic cholecystectomy based on direct observation by three evaluators who were blinded to the residents' randomization status. Residents were also tested on five standardized video-trainer tasks. The training group practiced the video-trainer tasks as a group for 30 minutes daily for 10 days. The control group received no formal training. All residents repeated the video-trainer test and underwent a second global assessment by the same three blinded evaluators at the end of the 1-month rotation. Within-person improvement was determined; improvement was adjusted for differences in baseline performance. RESULTS: Five residents were unable to participate because of scheduling problems; 9 residents in the training group and 13 residents in the control group completed the study. Baseline laparoscopic experience, video-trainer scores, and global assessments were not significantly different between the two groups. The training group on average practiced the video-trainer tasks 138 times (range 94 to 171 times); the control group did not practice any task. The trained group achieved significantly greater adjusted improvement in video-trainer scores (five of five tasks) and global assessments (four of eight criteria) over the course of the four-week curriculum, compared with controls. CONCLUSIONS: Intense training improves video-eye-hand skills and translates into improved operative performance for junior surgery residents. Surgical curricula should contain laparoscopic skills training.

Measuring operative performance after laparoscopic skills training: edited videotape versus direct observation.

BACKGROUND AND PURPOSE: Global assessment by direct observation has been validated for evaluating operative performance of surgery residents after formal skills training but is time-consuming. The purpose of this study was to compare global assessment performed from edited videotape with scores from direct observation. MATERIALS AND METHODS: Junior surgery residents (N = 22) were randomized to 2 weeks of formal videotrainer skills training or a control group. Laparoscopic cholecystectomy was performed at the beginning and end of the rotation, and global assessment scores were compared for the training and control groups. Laparoscopic videotapes were edited: initial (2 minutes), cystic duct/artery (6 minutes), and fossa dissection (2 minutes). Two independent raters performed both direct observation and videotape assessments, and scores were compared for each rater and for interrater reliability using a Spearman correlation. RESULTS: Correlation coefficients for videotape versus direct observation for five global assessment criteria were <0.33 for both raters (NS for all values). The correlation coefficient for interrater reliability for the overall score was 0.57 (P = 0.01) for direct observation v 0.28 (NS) for videotape. The trained group had significantly better overall performance than the control group according to the assessment by direct observation (P = 0.02) but not by videotape assessment (NS). CONCLUSIONS: Direct observation demonstrated improved overall performance of junior residents after formal skills training on a videotrainer. Global assessment from an edited 10-minute videotape did not correlate with direct observation and had poor interrater reliability. Efficient and valid methods of evaluating operative performance await development.

Laparoscopic live donor nephrectomy--is it safe?

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to open nephrectomy (ODN) for living kidney donation. Concerns have been raised regarding the safety of LDN, the short and long term function of kidneys removed by LDN, and a potential higher incidence of urologic complications in LDN transplant recipients. METHODS: Between October 1997 and May 1999, 80 LDNs were performed at our center. All patients were followed longitudinally with office visits and telephone interviews. These LDNs were compared with 50 ODN performed from January 1996 to October 1997. RESULTS: LDN procedures took significantly longer than ODN (4.6 vs. 3.1 hr). However, LDN was associated with significant reduction in i.v. narcotic use, a rapid return to diet, and shorter hospital stay. Of the 80 LDN procedures, a total of 75 (94%) were completed laparoscopically. Five patients were converted to laparotomy: three for hemorrhage and two for complex vascular anatomy. ODN conversion was associated with large donor body habitus and/or obesity. Seven LDN patients had minor complications and 4 had major complications. All major complications consisted of vascular injuries (2 lumbar vein injuries, 1 renal artery, and 1 aortic injury). All patients made complete recoveries. All LDN kidneys functioned immediately posttransplant. We have observed 100% patient and 97% 1-year actuarial graft survival in LDN transplant recipients. There have been no short-or long-term urologic complications in this series. CONCLUSION: With increasing experience and standardization of technique, LDN is a safe and effective procedure. Patients undergoing LDN demonstrate clinically significant, more rapid postoperative recoveries and shorter hospital stays than ODN patients. Excellent initial graft function and long-term graft survival have been observed with LDN kidneys. Urologic complications can be avoided. LDN has become the preferred surgical approach for living kidney donation at our center.

Identification of high-risk residents.

BACKGROUND: Identification of high-risk residents allows remediation and support for administrative action when necessary. This study characterizes differences in documentation of marginally performing residents in a general surgery residency. METHODS: High-risk residents were identified by the former program director. Twenty-four of one hundred fifteen residents over a 10-year period had one to four problematic areas: cognitive, synthetic, family/health, and interpersonal skills. Outcomes included finished (18), voluntary withdrawal (1), and involuntary withdrawal (5). A case-control study matching controls to cases by date of entry into the training program was used. Records were reviewed for demographics, preentry qualifications, American Board of Surgery In-Training Exam (ABSITE) scores, letters of complaint or praise, events of counseling, and monthly ratings. The records of 48 residents were reviewed. Ward evaluations were on eight categories with a 5-point Leikert scale (3-unacceptable to 7-outstanding). The evaluation score assigns points only to low ratings. High scores represent progressively poorer performance. A Wilcoxon signed ranks test was used to compare the cases and controls for continuous variables. The McNemar test was used in comparisons of categorical data with binary outcomes. Exact P values are reported. RESULTS: Objective data were similar for both groups. Study residents tended to score higher on monthly evaluations at Year 2 and by Year 3 this achieved significance (0.026). Study residents were more likely to have negative faculty letters (0.016) and events of counseling by a faculty member (0.017) and the program director (0.005). CONCLUSIONS: Identification of residents at risk should begin as early as possible during training. A combination of faculty evaluations and evidence of letters of counseling can detect high-risk residents. Programs may use such indicators to support decisions regarding remedial work or administrative action.

Inflammatory cytokines alter human gallbladder epithelial cell absorption/secretion.

Gallbladder inflammation is an early feature of gallstone formation in animal models. The inflammatory response is associated with increases in myeloperoxidase and interleukin (IL)-1 activities in the gallbladder wall. The present studies were designed to determine whether inflammatory cytokines directly affect gallbladder epithelial cell absorptive function. Studies were performed using cultured human gallbladder epithelial cells derived from a well-differentiated gallbladder carcinoma. Confluent monolayers were exposed to interleukin-1 (IL-1alpha), IL-1alpha plus its specific receptor inhibitor IL-1ra, tumor necrosis factor (TNF-alpha), lipopolysaccharide, or prostaglandin E2. Unidirectional sodium and chloride fluxes were measured and used to calculate net ion fluxes. Compared to control monolayers, lipopolysaccharide, prostaglandin E2, IL-1alpha, and TNF-alpha decreased mucosal-to-serosal and net sodium and chloride fluxes and increased serosal-to-mucosal movement of sodium and unmeasured ions. The effects of IL-1alpha were completely inhibited by its specific receptor antagonist IL-1ra. Similar to the proinflammatory agents lipopolysaccharide and prostaglandin E2, the inflammatory cytokines IL-1alpha and TNF-alpha directly affected gallbladder epithelial cell absorptive function. Because normal gallbladder absorptive function is protective against gallstone formation, alterations in absorptive function due to inflammation in the gallbladder wall may play a role in gallstone pathogenesis.

Development of an in vivo tumor-mimic model for learning radiofrequency ablation.

Radiofrequency ablation requires accurate probe placement using ultrasound guidance. The purpose of this study was to develop an in vivo tumor-mimic model for learning open and laparoscopic radiofrequency ablation. Tumor-mimics were created in ex vivo porcine livers by injecting a mixture of 3% agarose, 3% cellulose, 7% glycerol, and 0.05% methylene blue, which formed 1 cm hyperechoic, discrete lesions on ultrasound. Open and laparoscopic (using a box-trainer) ablation techniques were practiced. In vivo experiments were then conducted in 10 pigs. Three tumor-mimics were created in each animal using a laparoscopic approach. Lesions were characterized sonographically, ablated using an open (n = 5) or laparoscopic (n = 5) approach, and examined pathologically. An ablation in normal liver tissue was performed as a control. Tissue impedance was recorded. Target creation took 81 minutes per animal and 96% of injections were successful. Tissue impedance (48.8 +/- 5.8 vs. 49.6 +/- 5.4) and ablation size (25.1 +/- 3.4 vs. 24.3 +/- 5.1) were not significantly different for controls (n = 8) and tumor-mimics (n = 26), respectively. One animal died of a pulmonary embolism following injection of agarose into a hepatic vein. The agarose-based tissue-mimic creates realistic sonographic targets for learning ultrasound-guided open and laparoscopic radiofrequency ablation in an in vivo model.

Factors affecting recurrence following incisional herniorrhaphy.

The purpose of this study was to determine the influence of chronic illness, obesity, and type of repair on the likelihood of recurrence following incisional herniorrhaphy. The medical records of 77 patients who underwent elective repair of a midline incisional hernia at the Dallas Veterans Affairs Medical Center between 1991 and 1995 were reviewed. Demographic data, presence of chronic illnesses, type of repair, and presence of recurrence were noted. Ninety-six percent of the patients were men, with an average age of 59 years. More than 50% of the patients had chronic lung or cardiac diseases and more than 40% weighed > or = 120% of their ideal body weight and had a body mass index (BMI) > or = 30. Sixty-two percent of the patients underwent primary reapproximation of the fascia (tissue repair), whereas 38% underwent repair with prosthetic material (prosthetic repair). The overall recurrence rate was 45%, with a median follow-up of 45 months (range 6-73). Seventy-four percent of the recurrences presented within 3 years of repair. The recurrence rate for those patients undergoing a tissue repair was 54%, whereas the recurrence rate following prosthetic repair was 29%. The incidence of recurrence for patients with pulmonary or cardiac disease or diabetes mellitus was similar to that of patients without these illnesses. The percent ideal body weight and BMI of patients who developed a recurrent hernia, particularly following a prosthetic repair, were significantly greater than those of patients whose repairs remained intact. These data strongly support the use of prosthetic repairs for incisional hernias, particularly in patients who are overweight.

Gangrenous cholecystitis: analysis of risk factors and experience with laparoscopic cholecystectomy.

BACKGROUND: Gangrenous cholecystitis occurs in up to 30% of patients admitted with acute cholecystitis. Factors predicting gangrenous disease in patients with acute cholecystitis remain poorly defined, making preoperative diagnosis difficult. Identification of these factors and early diagnosis of gangrenous cholecystitis will indicate more aggressive treatment, earlier operation, and a lower threshold for conversion of laparoscopic to open cholecystectomy. METHODS: We reviewed our experience with acute cholecystitis during the 2-year period of 1995 to 1996. Admitting history, physical examination, operative report, laboratory and radiology data, and pathology report were analyzed for each patient. Acute cholecystitis and its gangrenous complication were diagnosed by both gross and microscopic examination. RESULTS: One hundred fifty-four patients were admitted to the hospital with acute cholecystitis and underwent cholecystectomy; gallbladder gangrene was found in 27 (18%) of these patients. Four patients with gallbladder gangrene underwent open cholecystectomy and 23 patients underwent laparoscopic cholecystectomy, of which 15 (65%) were completed laparoscopically and 8 (35%) had open conversion as a result of severe inflammation. Risk factors for gallbladder gangrene included male gender, age older than 50 years, history of cardiovascular disease, and leukocytosis greater than 17,000 white blood cells/mL. CONCLUSIONS: Older male patients (age older than 50 years) with history of cardiovascular disease, leukocytosis greater than 17,000 white blood cells/mL, and acute cholecystitis have increased risk of gallbladder gangrene and conversion of laparoscopic cholecystectomy to open cholecystectomy. Urgent laparoscopic cholecystectomy with low threshold for conversion to open cholecystectomy should be considered in these patients at high risk for gallbladder gangrene.

A learning curve for laparoscopic splenectomy at an academic institution.

BACKGROUND: Laparoscopic splenectomy is emerging as the standard for treatment of benign splenic disorders. Since splenectomy is indicated relatively infrequently, issues arise concerning training of surgeons to perform laparoscopic splenectomy. Our experience with 50 laparoscopic splenic procedures is reported with emphasis on the learning curve at an academic institution. MATERIALS AND METHODS: Data were prospectively collected on 50 consecutive patients undergoing attempted or successful laparoscopic surgical procedures on the spleen at Northwestern Memorial Hospital or The Chicago Health Care System, Lakeside Division, from April 1993 to April 1998, and on 5 patients undergoing open splenectomy from April 1993 to October 1995. Outcomes including conversion rate, operative time, day feedings were tolerated, and length of hospital stay was examined and correlated with the number of attempted cases. RESULTS: Laparoscopic splenectomy progressed from an operation requiring two advanced laparoscopic surgeons to one performed by carefully supervised senior residents. Success rates increased from 60% initially to greater than 95% recently. Likewise, operative time decreased significantly from 195 to 97 min, while length of stay declined from 2.5 to 1.5 days. High success rates, low operative times, and short length of stays were achieved during the last 20 patients while surgical residents were taught to perform the procedures. The reasons for improvement are multifactorial including use of the harmonic scalpel, a change to the lateral position, and increasing experience with the procedure. CONCLUSIONS: Laparoscopic splenectomy is a safe and effective procedure that reduces postoperative length of hospital stay. It can be performed successfully in most patients with operative times comparable to those of open splenectomy. Moreover, the procedure can (and should) be taught to residents once they master basic and advanced laparoscopic skills.

Bilateral adrenal cortical adenomas in primary hyperaldosteronism.

Bilateral adrenal cortical adenomas in the presence of primary hyperaldosteronism is an extremely rare condition. We present a case of primary hyperaldosteronism in which a unilateral hypersecreting aldosterone-producing adenoma coexisted with a large, contralateral adrenal mass ultimately found to be consistent with cortical adenoma. Management consisted of total adrenalectomy and enucleation of adenoma from the opposite adrenal. The patient is normotensive 3 years after surgery. Enucleation as a successful approach to hyperfunctioning cortical adenomas is proposed.

Inflammation and a thickened mucus layer in mice with cholesterol gallstones.

BACKGROUND: Based on previous work which suggested that biliary crystals may induce inflammation in the gallbladder wall and that inflammation is an early event during the formation of pigment gallstones in the dog, studies were performed examining mucus layer thickness, myeloperoxidase activity, and interleukin-1 (IL-1) activity in the wall of mouse gallbladder during formation and growth of cholesterol gallstones. METHODS AND MATERIALS: The inflammatory effects of cholesterol gallstones at 2 and 4 weeks were studied in BalB/C mice fed a crushed standard mouse chow with added cholesterol (1.0%) and cholic acid (0.5%). Results were compared to those of normal mice fed standard mouse chow. The presence or absence of crystals and stones was determined by gross and microscopic examination of bile. Myeloperoxidase and IL-1 activity in the gallbladder wall was measured using well-established bioassays. Mucus layer thickness was measured by darkfield microscopy. RESULTS: All mice fed a lithogenic, 1.0% cholesterol/0.5% cholic acid diet developed cholesterol crystals and gallstones at 2 and 6 weeks. No control mice developed either crystals or gallstones. Myeloperoxidase and IL-1 activities, markers of an inflammatory response, increased significantly in the gallbladder of mice with crystals at 2 weeks. Myeloperoxidase activity increased two- to three-fold, and IL-1 activity sevenfold, by 6 weeks. Mucus layer thickness also progressively increased during the 6-week period. CONCLUSIONS: It is concluded that inflammation is an early event associated with the appearance of crystals and gallstones in bile.

The inflammatory effects of crystalline cholesterol monohydrate in the guinea pig gallbladder in vivo.

BACKGROUND: The etiologic role of crystalline material in inflammatory arthritis is well established. The role of crystals in cholecystitis is unclear. We hypothesized that crystalline cholesterol monohydrate stimulates guinea pig gallbladder inflammation in vivo. METHODS: Crystalline cholesterol monohydrate, lipopolysaccharide (LPS), lysolecithin, polystyrene latex spheres (noninflammatory particles), and saline were instilled into guinea pig gallbladders for 24 to 72 hours after cystic duct ligation. Water transport across gallbladder mucosa was measured. Gallbladder tissue was analyzed for mucus layer thickness, myeloperoxidase, prostaglandin E2 (PGE2) prostaglandin F-1 alpha (PGF-1 alpha), and interleukin-1. Luminal fluid was also examined for PGE2 and PGF-1 alpha. Values for each test were compared with saline controls by using Student's test (p < 0.05). RESULTS: Crystalline cholesterol, LPS, and lysolecithin caused significant reduction in mucus layer thickness, reversed water absorption to secretion across the gallbladder mucosa, caused significant increases in myeloperoxidase and interleukin-1 in gallbladder tissue, and caused significant increases in PGE2 and PGF-1 alpha in luminal fluid. These effects were generally dose- but not time-dependent. Polystyrene latex particles caused no difference in outcomes compared with saline controls. CONCLUSIONS: Crystalline cholesterol monohydrate has dose-dependent inflammatory effects in the guinea pig gallbladder in vivo that are not simply-due to mechanical irritation of the gallbladder wall by crystalline particles. Crystals in the gallbladder may have an etiologic role in cholecystitis.

Interleukin-1 mediates guinea pig gallbladder inflammation in vivo.

Interleukin-1 (IL-1) is a cytokine with multiple immunologic and inflammatory properties. We previously demonstrated that lipopolysaccharide (LPS) stimulates release of IL-1, and IL-1 stimulates inflammation in guinea pig gallbladder in vivo. We hypothesized that IL-1 mediates LPS-induced guinea pig gallbladder inflammation in vivo. LPS and IL-1 were instilled into guinea pig gallbladder lumen alone (with cystic duct ligation) and with IL-1 ra and indomethacin, respectively (n = 4). Water transport across gallbladder mucosa, myeloperoxidase and IL-1 release from gallbladder tissue, and prostaglandin E2 (PGE2) in lumenal fluid were measured. Values for test agents and inhibitory agents were compared to saline controls using Student's t test (P < 0.05). Intralumenal LPS and IL-1 both stimulated gallbladder inflammation. LPS-induced and IL-1-induced inflammation were inhibited by both IL-1 ra and indomethacin. LPS stimulated IL-1 release and IL-1 itself caused gallbladder inflammation. LPS stimulated gallbladder inflammation as manifest by increased myeloperoxidase and PGE2 release, and water secretion into the gallbladder lumen. The inflammatory effects of LPS were inhibited by IL-1 ra. Taken together, these findings indicate that IL-1 is a mediator of LPS-induced guinea pig gallbladder inflammation in vivo.