Pathophysiology of gastroesophageal reflux disease-which factors are important?

BACKGROUND: Pathophysiology of gastroesophageal reflux disease (GERD) shows a multifactorial background. Different anatomical and functional alterations can be determined such as weakness of the lower esophageal sphincter (LES), changes in anatomy by a hiatal hernia (HH), an impaired esophageal motility (IEM), and/or an associated gastric motility problem with either duodeno-gastro-esophageal reflux (DGER) or delayed gastric emptying (DGE). The purpose of this study is to assess a large GERD-patient population to quantitatively determine different pathophysiologic factors contributing to the disease. METHODS: For this analysis only patients with documented GERD (pathologic esophageal acid exposure) were selected from a prospectively maintained databank. Investigations: history and physical, body mass index, endoscopy, esophageal manometry, 24 h-pH-monitoring, 24 h-bilirbine-monitoring, radiographic-gastric-emptying or scintigraphy, gastrointestinal quality of life index (GIQLI). RESULTS: In total, 728 patients (420 males; 308 females) were selected for this analysis. Mean age: 49.9 years; mean BMI: 27.2 kg/m2 (range, 20-45 kg/m2); mean GIQLI of 91 (range: 43-138; normal level: 121); no esophagitis: 30.6%; minor esophagitis (Savary-Miller type 1 or Los Angeles Grade A): 22.4%; esophagitis [2-4]/B-D: 36.2%; Barrett's esophagus 10%. Presence of pathophysiologic factors: HH 95.4%; LES-incompetence 88%, DGER 55%, obesity 25.6%, IEM 8.8%, DGE 6.8%. CONCLUSIONS: In our evaluation of GERD patients, the most important pathophysiologic components are anatomical alterations (HH), LES-incompetence and DGER.

Sleeve gastrectomy for treatment of delayed gastric emptying-indications, technique, and results.

INTRODUCTION: Delayed gastric emptying (DGE) can be caused by gastric motility disorders such as gastroparesis with idiopathic background, diabetic neuropathy, or postsurgical nerve damage. Currently, a variety of endoscopic and surgical treatment options are available. We noted clinical improvement of gastric emptying with reduction of the gastric fundus following both fundoplication and fundectomy. As a consequence, we explored the effect of sleeve gastrectomy on gastric emptying. The focus of this paper is to investigate the role of laparoscopic sleeve gastrectomy (LSG) in the treatment of gastroparesis. METHODS: Patients with symptoms suggestive of gastroparesis received diagnostic work-up (gastric emptying scintigraphy and/or Radiographic Barium-Sandwich Emptying studies). Patients with fundic emptying problems and moderate gastric dilation were selected for a LSG. All perioperative parameters were documented regarding patients characteristics, complications, and outcomes expressed as symptoms and quality of life (GIQLI gastrointestinal quality of life index). Assessment of DGE: Barium Emptying Radigraphy Index (BERI) 0-5. RESULTS: From 122 patients with gastroparesis, 19 patients were selected for LSG (mean age 54 years (23-68); 10 males/9 females. Morbidity 2/19; no mortality; follow-up mean 24 months (12-60); preop/postop: BERI: 2, 31/1, 27 (p < 0.01); we noted significant improvement of the quality of life (preoperative GIQLI 78 (44-89)) to postoperative values of 114 (range 87-120) (p < 0.0001). Preoperative median BMI of these 19 patients was 24 [1-10], which was not significantly changed in the 15 patients at > 1 year follow-up with 23 [1-8]. Postoperative recurrence of DGE occurred in 3 patients who were reoperated after >1 year follow-up. CONCLUSION: LSG is a potential surgical treatment option for selected patients with gastroparesis and fundic emptying problems.

Transanal hybrid colon resection: techniques and outcomes for benign colorectal diseases.

BACKGROUND: Transanal hybrid rectal and colon resection have been introduced in recent years at dedicated surgical centers. The anus is used as a natural orifice for large size access. The use of transanal hybrid colectomy techniques is still in its infancy with outcomes and unique complications being identified. The purpose of this work is the evaluation of outcomes for transanal hybrid colon resections (ta-CR), including intra operative and postoperative complications, results, and advantages. METHODS: A prospectively maintained database was analyzed. Inclusion criteria were any patient who underwent ta-CR for rectal prolapse, slow transit, obstructive defaecation, and chronic sigmoid diverticulitis. Patients were excluded from ta-CR if BMI > 30, major previous abdominal surgery, or presence of a large inflammatory mass in diverticulitis. Transanal access was used for all operative steps requiring access of more than 5 mm, such as staplers, large graspers, and specimen retrieval. Data acquisition and analysis was performed for operative time, complications, and postoperative quality of life. RESULTS: From 2012 to 2017, 82 patients underwent ta-CR [33 males, 49 females, median age 58 (24-80)]. Transanal-subtotal colectomy and ta-CR for constipation was performed in 12 patients; ta-CR and rectopexy in 31, and ta-CR for diverticulitis was performed in 39 patients. Conversion to traditional approach was required in 3 cases (3.6%). Intraoperative complication included 1 rectal tear requiring intervention. Post-op complications included 3 leaks requiring laparoscopic and 1 open revision, the latter developed wound infection and an incisional hernia. Gastrointestinal Quality of Life Index (GIQLI) improved significantly from preoperative 89 to postoperative 119 (p < 0.001). No patients with ta-CR without open revision developed a hernia post-op with median 18 months follow-up. CONCLUSIONS: ta-CR is a safe and effective NOTES Hybrid technique for colorectal procedures in selected patients with benign colon disorders. GIQLI shows improvement and this technique can have the potential in preventing wound and hernia complications.

Clinical Presentation of Gastroesophageal Reflux Disease: A Prospective Study on Symptom Diversity and Modification of Questionnaire Application.

INTRODUCTION: Symptoms occurring in gastroesophageal reflux disease (GERD) such as heartburn, regurgitation, thoracic pain, epigastric pain, respiratory symptoms, and others can show a broad overlap with symptoms from other foregut disorders. The goal of this study is the accurate assessment of symptom presentation in GERD. METHODS: Patients with foregut symptoms were investigated for symptoms as well as endoscopy and gastrointestinal-functional studies for presence of GERD and symptom evaluation by standardized questionnaire. Questionnaire included a graded evaluation of foregut symptoms documenting severity and frequency of each symptom. The three types of questionnaires include study nurse solicitated, self-reported, and free-form self-reported by the patient. RESULTS: For this analysis, 1,031 GERD patients (572 males and 459 females) were enrolled. Heartburn was the most frequently reported chief complaint, seen in 61% of patients. Heartburn and regurgitation are the most common (82.4/58.8%, respectively) in overall symptom prevalence. With regard to modification in questionnaire technique, if patients fill in responses without prompting, there is a trend toward more frequent documentation of respiratory symptoms (up to 54.5% [p < 0.01]), fullness (up to 93.9%), and gas-related symptoms (p < 0.001). Self-reported symptoms are more diverse (e.g., throat-burning [12%], mouth-burning [9%], globus [6%], dyspnea [9%], and fatigue [7%]). CONCLUSIONS: GERD symptoms are commonly heartburn and regurgitation, but overall symptom profile for patients may change depending on the type of questionnaire.

Do patients with gastroesophageal reflux disease and somatoform tendencies benefit from antireflux surgery?

BACKGROUND: The clinical presentation of gastroesophageal reflux disease (GERD) shows a large symptom variation also in different intensities among patients. As several studies have shown, there is a large overlap in the symptomatic spectrum between proven GERD and other disorders such as dyspepsia, functional heartburn and/or somatoform disorders. AIM: To prospectively evaluate the GERD patients with and without somatoform disorders before and after laparoscopic antireflux surgery. METHODS: In a tertiary referral center for foregut surgery over a period of 3 years patients with GERD, qualifying for the indication of laparoscopic antireflux surgery, were investigated prospectively regarding their symptomatic spectrum in order to identify GERD and associated somatoform disorders. Assessment of symptoms was performed by an instrument for the evaluation of somatoform disorders [Somatoform Symptom Index (SSI) > 17]. Quality of life was evaluated by Gastrointestinal Quality of Life Index (GIQLI). RESULTS: In 123 patients an indication for laparoscopic antireflux surgery was established and in 43 patients further medical therapy was suggested. The portion of somatoform tendencies in the total patient population was 20.48% (34 patients). Patients with a positive SSI had a preoperative GIQLI of 77 (32-111). Patients with a normal SSI had a GIQLI of 105 (29-140) (P < 0.0001). In patients with GERD the quality of life could be normalized from preoperative reduced values of GIQLI 102 (47-140) to postoperative values of 117 (44-144). In patients with GERD and somatoform disorders, the GIQLI was improved from preoperative GIQLI 75 (47-111) to postoperative 95 (44-122) (P < 0.0043). CONCLUSION: Patients with GERD and associated somatoform disorders have significantly worse levels of quality of life. The latter patients can also benefit from laparoscopic fundoplication, however they will not reach a normal level.

EAES recommendations for the management of gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most frequent benign disorders of the upper gastrointestinal tract. Management of GERD has always been controversial since modern medical therapy is very effective, but laparoscopic fundoplication is one of the few procedures that were quickly adapted to the minimal access technique. The purpose of this project was to analyze the current knowledge on GERD in regard to its pathophysiology, diagnostic assessment, medical therapy, and surgical therapy, and special circumstances such as GERD in children, Barrett's esophagus, and enteroesophageal and duodenogastroesophageal reflux. METHODS: The European Association of Endoscopic Surgery (EAES) has tasked a group of experts, based on their clinical and scientific expertise in the field of GERD, to establish current guidelines in a consensus development conference. The expert panel was constituted in May 2012 and met in September 2012 and January 2013, followed by a Delphi process. Critical appraisal of the literature was accomplished. All articles were reviewed and classified according to the hierarchy of level of evidence and summarized in statements and recommendations, which were presented to the scientific community during the EAES yearly conference in a plenary session in Vienna 2013. A second Delphi process followed discussion in the plenary session. RESULTS: Recommendations for pathophysiologic and epidemiologic considerations, symptom evaluation, diagnostic workup, medical therapy, and surgical therapy are presented. Diagnostic evaluation and adequate selection of patients are the most important features for success of the current management of GERD. Laparoscopic fundoplication is the most important therapeutic technique for the success of surgical therapy of GERD. CONCLUSIONS: Since the background of GERD is multifactorial, the management of this disease requires a complex approach in diagnostic workup as well as for medical and surgical treatment. Laparoscopic fundoplication in well-selected patients is a successful therapeutic option.

Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study.

Pilot studies have indicated that peroral endoscopic myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective, international, multicenter study to determine the outcomes of 70 patients who underwent POEM at 5 centers in Europe and North America. Three months after POEM, 97% of patients were in symptom remission (95% confidence interval, 89%-99%); symptom scores were reduced from 7 to 1 (P < .001) and lower esophageal sphincter pressures were reduced from 28 to 9 mm Hg (P < .001). The percentage of patients in symptom remission at 6 and 12 months was 89% and 82%, respectively. POEM was found to be an effective treatment for achalasia after a mean follow-up period of 10 months.

The EURO-NOTES clinical registry for natural orifice transluminal endoscopic surgery: a 2-year activity report.

BACKGROUND: The EURO-NOTES Clinical Registry (ECR) was established as a European database to allow the monitoring and safe introduction of Natural Orifice Transluminal Endoscopic Surgery (NOTES). The aim of this study was to analyze different techniques applied and relative results during the first 2 years of the ECR. METHODS: The ECR was designed as a voluntary database with online access. All members of the European Society for Gastrointestinal Endoscopy and the European Association for Endoscopic Surgery were requested to participate in the registry. Demographic and therapy data as well as data on the postoperative course are recorded in the ECR in an anonymous way. RESULTS: A total of 533 patients who underwent NOTES procedures were included in the study. Four different hybrid techniques for 435 cholecystectomies were described, registering postoperative complications in 2.8% of patients, addition of a single trocar in 5.3%, and conversions to laparoscopy in 0.5%. Both flexible endoscopic and rigid laparoscopic cholecystectomy techniques proved to be safe and effective with minor differences. There was a shorter operative time in the rigid laparoscopic group. Thirty-three appendectomies were reported by transgastric and transvaginal techniques, with transvaginal techniques scoring shorter operative time and hospital stay, but with a frequent need to add more trocars. Overall complications occurred in 14.7% of patients but they did not differ significantly among the different techniques. One transvaginal and 31 transanal sigmoidectomies were included for prolapse and diverticulitis, with four postoperative complications (12.5%), but none needing further treatment. Twenty peroral esophageal myotomies were included with three postoperative complications (15.0%), but none needing further treatment. CONCLUSIONS: Five years since the introduction of NOTES into clinical practice, hybrid techniques have gained considerable clinical application. Several NOTES hybrid cholecystectomy and appendectomy techniques are practicable and safe alternatives to laparoscopic procedures. Also, sigmoidectomies and peroral esophageal myotomies were described, proving feasibility and safety. Nevertheless, the real benefit of NOTES for patients still needs to be assessed.

Transanal hybrid colon resection: from laparoscopy to NOTES.

BACKGROUND: Reducing access size and trauma are important issues in natural orifice transluminal endoscopic surgery (NOTES). The combination of experience with laparoscopic colorectal surgery and transanal endoscopic microsurgery has helped in the use of the transanal approach as a realistic option of NOTES techniques to introduce transanal hybrid laparoscopic-assisted colon resection into clinical practice. The purpose of this study was to assess the clinical introduction of transanal hybrid colon resection in terms of feasibility and patient safety. METHODS: Patients with pelvic floor disorders, prolapse, and slow-transit constipation in whom a colon resection was indicated were recruited. Patients were followed prospectively with a postoperative well-being score, a pain score, and a quality-of-life score. All complications were prospectively documented. The essential change was the reduction of the number and size of ports by using the transanal route. A camera and two 5-mm ports for grasping forceps and delivering ultrasonic energy were the laparoscopic components. All tasks requiring a port diameter of >5 mm were applied via the transanal route, such as positioning of the proximal stapler anvil, application of linear stapling for resection, specimen retrieval, stapler anastomosis, and closing the bowel. RESULTS: Fifteen patients with benign colorectal disease underwent transanal hybrid colon resection, and 11 had additional rectopexy. All patients were women with a mean age of 61 (range, 28-86) years and a body mass index of 26 kg/m(2). One patient was converted to full laparoscopy. One complication--bleeding that required no reintervention--was recorded. The procedure lasted a mean of 131 (range, 55-184) min. The Gastrointestinal Quality of Life Index was 96 before surgery and 117 after surgery. CONCLUSIONS: From this initial experience, transanal hybrid colon resection seems a feasible and safe hybrid NOTES procedure that can be usefully introduced into clinical practice.

Transgastric small bowel resection with the new multitasking platform EndoSAMURAI™ for natural orifice transluminal endoscopic surgery.

BACKGROUND: Recently, natural orifice transluminal endoscopic surgery has been introduced using flexible endoscopic technology. Traditional endoscopes lack several capabilities that are needed to perform complex surgical procedures safely. The purpose of this study was to evaluate the new multitasking platform for transgastric small bowel resection including dissection of the mesentery and suturing an anastomosis. METHODS: A new prototype of endoscopic multifunctional platform, EndoSAMURAI™ (ES), was tested. A standardized in vitro setting was established with segments of small bowel and an anastomosis was sutured with the device and compared with that by stapler (ST) and hand-sewn (HS). Leak pressure was measured. In addition, the system was tested in an experimental in vivo situation by performing a transgastric small bowel segmental resection under general anesthesia. RESULTS: Median time to perform an anastomosis in the bench test was 41 min; median leak pressure for the anastomosis by ES was 14 mmHg, by ST 25 mmHg, and HS 15 mmHg. For the in vivo study, the median total procedure time was 110 min and leak pressure 53 mmHg. These results show that the end-to-end small bowel anastomosis can be sutured sufficiently. CONCLUSIONS: This study has shown that with a multifunctional platform such as the EndoSAMURAI™, the majority of complex surgical tasks can be performed if technically independently moving instruments can be used via an ergonomic workstation interface that allows for laparoscopy-like maneuvers by the operator. Even with the shortcomings of the prototype, it was possible to perform an anastomosis of the small bowel of acceptable quality within a reasonable time.

Experience with flexible stapling techniques in laparoscopic and conventional surgery.

BACKGROUND: Currently, advanced minimal-access surgery cannot be realized without the application of modern stapling devices. The introduction of stapling devices with a flexible shaft and computer-assisted steering abilities was followed by the technical basis to provide just these features. This study aimed to assess the clinical application of stapling devices connected to a flexible shaft supported by a computer-assisted drive for maneuvering the system and to study its feasibility, learning curve problems, and clinical safety criteria regarding morbidity of the patients. METHODS: The experience with laparoscopic and open gastrointestinal and colorectal surgery was evaluated. Patients with esophageal, gastric, and colorectal diseases were selected. The stapling system consisted of a power console connected to a flexible shaft and a remote control unit. On the tip of the flexible shaft stapler, loading units could be attached and operated by the remote control. A circular loading unit, size 29 mm, was used for esophageal, gastric, and rectal anastomoses. The linear stapler (length, 55/75 mm) was applied for the gastric tube after esophageal resection, for the jejunal pouch after total gastrectomy, and for division and closure of small bowel. It also was used during laparoscopic sleeve gastrectomy or laparoscopic fundoplication with COLLIS-gastroplasty. All data from the procedures were prospectively assessed and documented. A literature analysis was performed to compare morbidity data and leak rates with those of the current study. RESULTS: During an 8-year period, 394 patients (253 men and 141 women) were included in this study, and laparoscopic technique was performed in 52% of the cases. The mean age of the patients was 63 years (range, 16-93 years), and 33% of the patients had an American Society of Anesthesia classification of 3 or 4. A total of 1,258 firings were performed. The procedures included 54 esophageal resections, 90 gastric operations, and 197 colorectal resections. In the early experience, computer failures occurred for 2.9% of 173 patients (5 of 144 cartridge firings, 3.5%). Later, the problems and leak rate dropped from the initial 6.6% (11/173) to 3.2% (7/221). The complication and morbidity rates were similar to those in the literature. The flexible system had the advantage of enabling stapler application in special indications such as performance of intraabdominal laparoscopic COLLIS-Plasty by bending the system along the subphrenic area. CONCLUSIONS: Application of the described stapling system was thought to be advantageous, especially for minimal-access surgery and special indications that required a flexible shaft. This advantage allows for introduction of innovative techniques in gastrointestinal and colorectal surgery.

Transgastric small bowel resection and anastomosis: a survival study.

BACKGROUND: Recently, natural orifice transluminal endoscopic surgery has emerged with new ideas of a transgastric access. The authors have evaluated the possibility of transgastric bowel resection with several modifications. This study aimed to evaluate transgastic small bowel resection using an automated stapling device via an assisting trocar. In a survival experiment, the possible technical problems, medical complications, and safety of the procedure were investigated as well as the postoperative course and follow-up care. METHODS: The study protocol was submitted to the animal research committee and approved. A total of 13 swine with a body weight of 25 kg (range, 20-46 kg) were investigated and entered into the study. General anesthesia was induced by certified personnel using ketamine, halothan, oxygen, and nitrous oxide. One trocar was used for laparoscopic assistance. A needleknife was used to complete a 1.5-cm-long gastrotomy. The gastroscope was advanced into the peritoneal cavity, and a small bowel loop was identified. Through the second channel of the scope, a coag-grasper was used to dissect the mesentery. A linear stapler was inserted through the assisting trocar, and the resection was performed. Afterward, the bowel ends were reopened, and the stapler was reinserted for a side-to-side anastomosis. The specimen was removed via the stomach. Gastric closure was completed using laparoscopic mini-instruments. All problems were prospectively documented. Follow-up evaluation was performed over 2 weeks. The animals were killed and reopened, and evidence of adhesions, infection, and abscess formation was evaluated. RESULTS: In this study, 13 female animals with a body weight of 25 kg (range, 20-46 kg) underwent surgery. No mortality or postoperative complications occurred. The animals had stable weight development. After a follow-up period of 2 weeks, the animals were killed. The findings included minor adhesions, no abscess, and no inflammation. CONCLUSION: Transgastric bowel resection with minor laparoscopic assistance is a safe experimental procedure when performed by surgeons with adequate and extensive training. These experimental procedures should be evaluated carefully and critically in clinical practice.

Experience with a training program for transgastric procedures in NOTES.

INTRODUCTION: The transgastric approach to the abdominal cavity has been under experimental investigation in recent years as a method of natural orifice transluminal endoscopic surgery (NOTES). In this study our team, consisting of surgeons and gastroenterologists, focused on training techniques with currently available instruments to perform transgastric procedures. The purpose of this paper is to evaluate the learning process during the establishment of a training program for NOTES. Therefore several procedures were tested in terms of training issues such as the applicability of instruments and techniques for both gastroenterologists and surgeons. METHODS: After initial testing of the basic steps, a defined training program was initialized in an animal facility of a medical company. Permission for animal training was applied for and granted by the local government. Ten training sessions were performed on a porcine model using animals with a median weight of 65 kg (40-85 kg). General anesthesia was performed in all cases. Transgastric tube resection (TTR), cholecystectomy (TCE), cardiomyotomy (TMY), and small bowel segmental resection (TSBR) were performed. The learning process was evaluated, including handling issues for flexible instruments, access, closure problems, and special technical issues. Procedure duration, as a marker of the learning curve effect, was evaluated. RESULTS: Intra-esophageal friction, lack of platform stability, lack of precision in tissue retraction, and lack of independence of endoscopic vision were the most difficult technical problems encountered. The operative time range was 25-85 min for TTR, 75-185 min for TCE, 95-220 min for TMY, and 100-260 min for TSBR. CONCLUSIONS: A learning curve was demonstrated for each investigated technique. These results are promising in terms of the ability of surgeons and gastroenterologists to develop these procedures into a clinical applicable version. Technical limitations were more important than differences in medical education, providing that there is a certain level of experience in both flexible endoscopy and laparoscopy, as well as a team approach.

Endoscopic full-thickness plication for the treatment of GERD by application of multiple Plicator implants: a multicenter study (with video).

BACKGROUND: The full-thickness Plicator allows transmural suturing at the gastroesophageal (GE) junction to restructure the antireflux barrier. Studies of the Plicator procedure to date have been limited to placement of a single transmural suture to create the endoscopic gastroplication. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of placing multiple transmural sutures for the treatment of GERD. DESIGN: Open-label, prospective, multicenter study. SETTING: Four tertiary-referral centers. PATIENTS: Subjects with symptomatic GERD who require daily maintenance proton pump inhibitor (PPI) therapy. Study exclusions were hiatal hernia >3 cm, grades III and IV esophagitis, Barrett's epithelium, and esophageal dysmotility. INTERVENTIONS: Forty-one patients received two or more transmural sutures placed linearly in the anterior gastric cardia approximately 1 cm below the GE junction. MAIN OUTCOME MEASUREMENTS: Six months after the procedure, median GERD-health-related quality of life (HRQL) improved 76% compared with off-medication baseline (6.0 vs 25.0, P < .001), with 75% of patients (32/40) achieving >50% improvement in their baseline GERD-HRQL score. Six months after the procedure, daily PPI therapy was eliminated in 70% of patients (28/40). Heartburn symptoms improved 80% compared with off-medication baseline (16.0 vs 84.0, P < .001). Median esophagitis grade improved 75% compared with baseline (0.0 vs 1.0, P = .005). Esophageal pH assessed as median distal esophageal-acid exposure (percentage time pH < 4.0) improved 38% compared with baseline (9.0 vs 11.0, P < .020; nominal P value for a single statistical test: significance removed upon the Bonferroni adjustment for multiple testing of data) and manometric outcomes were also improved compared with baseline (median lower esophageal sphincter resting pressure improved 25% [10.0 vs 6.0, P < .017; nominal P value for a single statistical test: significance removed upon the Bonferroni adjustment for multiple testing of data]) and median amplitude of contraction improved 11% (70.0 vs 62.0, P < .037; nominal P value for a single statistical test: significance removed upon the Bonferroni adjustment for multiple testing of data). LIMITATIONS: Small sample size. No randomized comparison with a single implant group. CONCLUSIONS: Endoscopic full-thickness plication with multiple serially placed implants was safe and effective in reducing GERD symptoms, medication use, esophageal-acid exposure, and esophagitis.

Establishment of a colonic adenoma cell line (GEKI-2): spectral karyotype analysis and functional characterization.

BACKGROUND AND AIMS: On the genetic level colonic carcinogenesis is best described by the adenoma-carcinoma sequence, but it may be modulated by exogenous factors, particularly by dietary factors and chemopreventive agents. The protective effects of exogenous factors are thought to be exerted rather in the early stages of the adenoma-carcinoma sequence. Thus, an in vitro model consisting of cells stemming from an colon adenoma would be desirable. However, establishing such a cell line has proven difficult. MATERIALS AND METHODS: We report the establishment of a colon adenoma cell line. The cells were generated from a colon adenoma and propagated as a stable cell line for more than 40 passages. The cells are microsatellite stable and confirmed to be of epithelial origin by cytokeratin staining. RESULTS: In contrast to commercially available colon cancer cell lines, cytogenetic analysis with spectral karyotype analysis revealed no chromosomal alterations in this adenoma cell line. Incubation with butyrate resulted in a time- and dose-dependent inhibition of proliferation and in an significant increase in cellular differentiation. The cdk inhibitor p21/waf which plays a pivotal role in growth inhibition and differentiation is expressed consecutively in GEKI-2 cells. The expression of cdk1 and cdk2, important regulatory elements in the cell cycle, is downregulated following treatment with butyrate. CONCLUSION: The presented colon adenoma cell line GEKI-2 may prove a versatile tool for further exploring the underlying mechanisms of protective and promoting factors in early colon cancerogenesis.