Postoperative pain after transvaginal cholecystectomy: single-center, double-blind, randomized controlled trial.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has the potential to reduce postoperative pain. We compared postoperative pain in the hybrid NOTES procedure transvaginal video-assisted cholecystectomy (TVC) with standard conventional laparoscopic cholecystectomy (CLC). DESIGN: Single-center, double-blind, randomized controlled trial in a level II hospital between June 2008 and June 2012. METHODS: Female patients, older than 18 years of age with symptomatic cholecystolithiasis were randomized to receive either TVC or CLC. The follow-up period was 7 days and the primary outcome of the study was postoperative pain. We hypothesized that there is no reduction of pain (Visual Rating Scale ≥1) while resting or coughing over a 48-h period after the operation. Secondary outcome included wound infections, complications, and patient reported outcomes. Sealed envelopes with computer-generated randomization information were kept for allocation in theater. All patients received opaque wound dressing, as in standard four-trocar cholecystectomy and a vaginal tamponade. Theater protocol and surgical notes were kept separate after the procedure. RESULTS: Overall, 97 of 426 patients assessed for participation were randomized for either TVC or CLC. A total of 41 patients had a TVC and 51 had a CLC. Five patients were excluded from the analysis. There was no difference in age, body mass index, American Society of Anesthesiologists (ASA) grade, or hospital stay, but anesthetic and surgical times were significantly longer in TVC (p < 0.001). There was no statistical difference in postoperative pain between the two groups while resting or coughing. Complications included conversion to laparotomy, bleeding, wound infections, and re-admission. No difference in the rate of complications between the two groups was seen. Overall, 86 and 93% of CLC and TVC patients, respectively, would recommend the procedure to other patients. CONCLUSION: In this study, no significant difference in pain on days 1 and 2 postoperatively between the two methods was found. The safety profile of TVC is comparable to CLC, and TVC patients would generally recommend this procedure to other patients.

Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.

IMPORTANCE: The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated. OBJECTIVE: To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival. DESIGN, SETTING, AND PATIENTS: CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. INTERVENTIONS: After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up. RESULTS: A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%). CONCLUSIONS AND RELEVANCE: Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN34802808.

Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial.

BACKGROUND: The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. METHODS: This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. FINDINGS: Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53­1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. INTERPRETATION: Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. FUNDING: German Federal Ministry of Education and Research.

Lack of evidence for Epstein-Barr virus infection in myasthenia gravis thymus.

A role for Epstein-Barr virus (EBV) in myasthenia gravis pathogenesis has been suggested recently. Using in situ hybridization for the detection of the EBV-encoded RNAs and EBNA1-specific immunohistochemistry, we found no latently infected cells in a series of thymus specimens from patients with myasthenia gravis showing lymphofollicular thymitis. In addition, using immunohistochemistry and an antibody specific for the viral immediate early protein BZLF1, no evidence of lytic EBV infection was seen in these cases. Our results therefore do not support a direct role of thymic EBV infection in the pathogenesis of myasthenia gravis.

Prospective evaluation of transvaginal assisted cholecystectomy.

BACKGROUND: Transvaginal video-assisted cholecystectomy (TVC) has so far not been prospectively evaluated using an internationally recognized health-related quality of life (HRQoL) assessment. We report the results of a prospectively studied cohort of patients with clinical and quality of life data. METHODS: Prospectively controlled study of 128 patients undergoing TVC and 147 patients with conventional laparoscopic cholecystectomy (CLC). Data reported include patient demography, body mass index, anesthetic risk score (ASA), laboratory data, surgical times, length of hospital stay, pain score, analgesic medication used, complications, and quality of life scores using the combined method of SF-36 and GIQoL. RESULTS: Ninety-five TVC and 96 CLC patients fully completed pre- and postoperative HRQoL questionnaires. Patients with incomplete or missing questionnaires were excluded as well as patients with signs of acute cholecystitis. Differences included cardiovascular comorbidity and previous surgical procedures, but there was no difference in age (p = 0.4), body mass index (p = 0.4), ASA grade (p = 0.4), or preoperative quality of life. No difference was seen in laboratory data, surgical times, or length of hospital stay. Pain score and analgesic medication showed a clear trend and significant differences in favor of TVC. There was no difference in complications. Quality of life and postoperative sexual function did not show any differences between the two groups. CONCLUSIONS: This is the first study to report HRQoL outcomes after TVC using a recognized combined HRQoL assessment method. Although differences do exist in patient comorbidity and previous surgical experience, both groups were comparable. Less postoperative pain and no difference in HRQoL in TVC patients underlines this new procedure as a feasible standard approach in female patients. This study also is the first to differentiate between acute cholecystitis and symptomatic cholecystolithiasis in patients undergoing TVC.

The German registry for natural orifice translumenal endoscopic surgery: report of the first 551 patients.

OBJECTIVE: To analyze patient outcome in the first 14 months of the German natural orifice translumenal endoscopic surgery (NOTES) registry (GNR). SUMMARY BACKGROUND DATA: NOTES is a new surgical concept, which permits scarless intra-abdominal operations through natural orifices, such as the mouth, vagina, rectum, or urethra. The GNR was established as a nationwide outcome database to allow the monitoring and safe introduction of this technique in Germany. METHODS: The GNR was designed as a voluntary database with online access. All surgeons in Germany who performed NOTES procedures were requested to participate in the registry. The GNR recorded demographical and therapy data as well as data on the postoperative course. RESULTS: A total of 572 target organs were operated in 551 patients. Cholecystectomies accounted for 85.3% of all NOTES procedures. All procedures were performed in female patients using transvaginal hybrid technique. Complications occurred in 3.1% of all patients, conversions to laparoscopy or open surgery in 4.9%. In cholecystectomies, institutional case volume, obesity, and age had substantial effect on conversion rate, operation length, and length of hospital stay, but no effect on complications. CONCLUSIONS: Despite the fact that NOTES has just recently been introduced, the technique has already gained considerable clinical application. Transvaginal hybrid NOTES cholecystectomy is a practicable and safe alternative to laparoscopic resection even in obese or older patients.

Transvaginal video-assisted cholecystectomy in clinical practice.

BACKGROUND: Transvaginal video-assisted cholecystectomy with rigid instruments is a new procedure that combines natural orifice surgery (NOS) with classic laparoscopy. This hybrid technique requires conventional laparoscopy via an umbilical incision. To date it is unclear if this procedure is safe and feasible in routine practice. METHODS: We report on a case series of 128 women who consented to transvaginal cholecystectomy. Data, including visual analog scores (VAS), were collected prospectively via a standard digital spreadsheet. Patients completed satisfaction questionnaires within 10 days after discharge from hospital. We report on outcomes, age, body mass index, operating time, complications, pain scores, and patient satisfaction. RESULTS: In 115 (89.8%) patients the procedure was performed as a transvaginal operation. In 11 women (8.6%), we converted to standard laparoscopy, and in 2 cases (1.6%), we converted to an open procedure. Mean age was 52.4 years (range = 23-78 years) and mean body mass index was 27.8 (range = 18.8-42). Mean operating time was 60.6 min (range = 22-110 min). Other procedures were combined with hybrid cholecystectomy in six cases. Complications following transvaginal access included one vaginal bleeding, one perforation of the urinary bladder, and one superficial lesion of the rectum. In one case the hepatic duct had to be stented due to leakage after the procedure via endoscopic retrograde cholangiography. Mean VAS on day 1 was 2.26 (± 0.31 SEM) and on day 2 it was 1.53 (± 0.35 SEM). In a postoperative questionnaire, 95% of patients indicated that they would recommend this procedure to other patients. CONCLUSIONS: Transvaginal cholecystectomy is a safe and easy-to-learn procedure. Possible complications are different than those of standard laparoscopic procedures. Trauma to the abdominal wall and scarring is minimal. Postoperative pain scores were not different than those of standard laparoscopy and a high percentage of patients are satisfied with the procedure.

International multicenter trial on clinical natural orifice surgery--NOTES IMTN study: preliminary results of 362 patients.

OBJECTIVES: Natural orifice translumenal endoscopic surgery (NOTES) is evolving as a promising alternative for abdominal surgery. IMTN Registry was designed to prospectively document early results of natural orifice surgery among a large group of clinical cases. METHODS: Sixteen centers from 9 countries were approved to participate in the study, based on study protocol requirements and local institutional review board approval. Transgastric and transvaginal endoscopic natural orifice surgery was clinically applied in 362 patients. Intraoperative and postoperative parameters were prospectively documented. RESULTS: Mean operative time for transvaginal cholecystectomy was 96 minutes, compared with 111 minute for transgastric cholecystectomy. A general complication rate of 8.84% was recorded (grade I-II representing 5.8%, grade III-IV representing 3.04%). No requirement for any analgesia was found in one fourth of cholecystectomy and appendectomy patients. CONCLUSIONS: Results of clinical applications of NOTES in the IMTN Study showed the feasibility of different methods of this new minimally invasive alternative for laparoscopic and open surgery.

Differentiation between pancreaticobiliary and upper gastrointestinal adenocarcinomas: is analysis of cytokeratin 17 expression helpful?

Metastatic adenocarcinoma of unknown primary site, eg, to lymph nodes, liver, or lung, may originate from many organs. Microscopic differentiation of adenocarcinomas from the pancreaticobiliary and upper gastrointestinal tracts may be difficult because of shared histologic and immunohistologic features. A high prevalence of cytokeratin (CK)17 expression in pancreaticobiliary adenocarcinoma was reported, and preliminary data indicate infrequent or missing expression in gastric adenocarcinoma. The prevalence of CK17 expression in gastric cardiac and esophageal adenocarcinomas has not been studied. We studied CK17 expression in tissue microarrays of 67 distal gastric, 71 gastric cardiac, and 46 esophageal adenocarcinomas and compared it with expression in 55 pancreatic, 23 extrahepatic bile duct, and 49 colorectal adenocarcinomas. CK17 expression was as follows: pancreatic, 88%; bile duct, 59%; esophageal, 30%; distal gastric, 28%; gastric cardiac, 27%; and colorectal adenocarcinoma, 6%. These differences were statistically significant for all tumor types except in comparisons of esophageal, cardiac, and distal gastric adenocarcinoma. The prevalence of CK17 expression in pancreatic and extrahepatic bile duct adenocarcinomas is substantially higher than in upper gastrointestinal tract and colorectal adenocarcinomas. However, in individual cases of adenocarcinoma of unknown primary site, CK17 results alone are insufficient to differentiate the analyzed tumor entities.

Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.

CONTEXT: The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists. OBJECTIVE: To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more. DESIGN, SETTING, AND PATIENTS: Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups. INTERVENTION: Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175). MAIN OUTCOME MEASURES: Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat). RESULTS: More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank). CONCLUSIONS: Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN34802808.

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial.

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Thoracoscopic thymectomy in the treatment concept for myasthenia gravis.

Myasthenia gravis (MG) is a chronic autoimmune disease that usually responds positively to treatment with thymectomy. Standard surgical procedures have been shown to result in a beneficial outcome. This Chapter includes discussions regarding what are controversial, and opinions as to what constitutes the optimal access to be used for thymectomy. In a prospective study conducted between 8/97 and 12/03, 137 patients with MG underwent thoracoscopic thymectomy, for which a left-sided approach was generally applied. An analysis of the intraoperative and postoperative course was performed, as well as of the impact of the surgical procedure on further development of the disease. The results obtained were compared with those published in the literature, with particular reference to results obtained with open surgery. The patients in this study were 96 females and 41 males, with a mean age of 35.8 (range: 9-83) years. The mean preoperative duration of the disease was 22.9 (range: 1-140) months. In 8 (5.8%) patients, the procedure was converted to an anterolateral thoracotomy or sternotomy. The postoperative morbidity rate was 5.8%, one (0.7) patient died and the mean follow up was 24.7 (range: 1-57) months. Complete remission was noted in 19.4%, and improvements reflected either in a reduction in the medication required or a decrease in symptom severity, in a total of 76.8%. Complete thoracoscopic thymectomy is a technically feasible operation, equally as effective as conventional open surgery. Remissions or symptomatic improvements were observed in more than 70% of the patients. The low morbidity rate, coupled with excellent cosmetic results, have led to increasing acceptance of the operation both by patients and Neurologists. Therefore, thoracoscopic thymectomy represents a new, alternative method for use in patients with MG.

The barrier-free trocar technique in three laparoscopic standard procedures.

BACKGROUND: Numerous technical and surgical innovations took place in laparoscopic surgery in the recent past. It is debatable whether single-access surgery or natural orifice surgery (NOS) will establish for several standard procedures. Most of the NOS-procedures are controversial and single-access surgery still has to prove its equality in controlled trials. In the intention to reduce the ingress incisons and to facilitate instrumentation, we decided to test the barrier-free AirSeal(®)-trocar in clinical practice. MATERIALS AND METHODS: Laparoscopically we performed a cholecystectomy, gastric wedge-resection and a fundoplication using the barrier-free AirSeal(®) 12-mm-trocar. This trocar works without any mechanical barrier so that via this trocar the use of two instruments is possible. RESULTS: All three operations were successful. CONCLUSION: Laparoscopic standard procedures are feasible using this barrier-free trocar without a higher degree of difficulty. Because of the facilitated instrumentation, it is possible to work more efficiently and to maintain the focus on the surgical field.

Thoracoscopic removal of a transesophageal ingested mediastinal foreign body.

Transesophageal migration of a foreign body into the mediastinum in human adults is rare. This event can result in life-threatening situations and is associated with a high mortality rate. Only a few case reports of thoracoscopic removal of a foreign body in adults have been published so far. The authors describe the case of a successfully performed thoracoscopic approach to remove an ingested needle from the mediastinum posterior of a 69-year-old patient. The authors are discussing why, in similar cases, removal of the foreign body should be performed and they describe the preliminary conditions for this method. A video file is attached.

The impact of the risk factor "age" on the early postoperative results of surgery for colorectal carcinoma and its significance for perioperative management.

The risks and benefits of surgery for colorectal cancer in old patients have not been unequivocally defined. The present investigation was carried out in 309 hospitals as a prospective multicenter study. In the period between 1 January 2000 and 31 December 2001, a total of 19,080 patients were recruited for the study; 16,142 (84.6%) patients were younger than 80 years (<80) and 2932 (15.4%) were 80 years and older (> or =80). Significant differences between the age groups were observed for general postoperative complications (22.3% for <80 years; 33.9% for > or =80). Specific postoperative complications were identical in both groups. Overall, significantly elevated morbidity and mortality rates were found with increasing age (morbidity: 33.9% vs. 43.5%; mortality: 2.6% vs. 8.0%). The distribution of tumor stages revealed a significantly higher percentage of locally advanced tumors in the older age group (stage II: 28.0% vs. 34.4%). In contrast, no increase in metastasizing tumors was found in the older age group (stage IV: 17.4% vs. 14.1%). Logistic regression showed that, in concert with a number of other parameters, age is a significant influencing factor on postoperative morbidity and mortality. The increase in postoperative morbidity and mortality rates associated with aging is a result of the increase in general postoperative complications, in particular, pneumonia and cardiovascular complications. Age as such does not represent a contraindication for surgical treatment. The short-term outcome and quality of life are of overriding importance for the geriatric patient.

A prospective two-center study comparing wireless capsule endoscopy with intraoperative enteroscopy in patients with obscure GI bleeding.

BACKGROUND: Capsule endoscopy enables noninvasive diagnostic examination of the entire small intestine. However, sensitivity and specificity of capsule endoscopy have not been adequately defined. We, therefore, compared capsule endoscopy by using intraoperative enteroscopy as a criterion standard in patients with obscure GI bleeding. METHODS: Forty-seven consecutive patients with obscure GI bleeding (11 with ongoing overt bleeding, 24 with previous overt bleeding, and 12 with obscure-occult bleeding) from two German gastroenterologic centers were included. All patients who had a prior nondiagnostic evaluation, including upper endoscopy, colonoscopy with a retrograde examination of the distal ileum, and push enteroscopy, underwent capsule endoscopy followed by intraoperative enteroscopy. RESULTS: Capsule endoscopy identified lesions in 100% of the patients with ongoing overt bleeding, 67% of the patients with previous overt bleeding, and 67% of the patients with obscure-occult bleeding. Angiectasias were the most common source of bleeding (n = 22). Capsule endoscopy showed the source of bleeding in 74.4% of all patients. The method was more effective in patients with ongoing bleeding. Compared with intraoperative enteroscopy sensitivity, specificity, and positive and negative predictive values of capsule endoscopy were 95%, 75%, 95%, and 86%, respectively. CONCLUSIONS: Capsule endoscopy has high sensitivity and specificity to detect a bleeding source in patients with obscure GI bleeding. Thus, wireless capsule endoscopy can be recommended as part of the routine work-up in patients with obscure GI bleeding.

Inhibition of chemokine production from human airway smooth muscle cells by fluticasone, budesonide and beclomethasone.

Human airway smooth muscle cells (HASMC) contribute to the process of airway wall remodelling in asthma by virtue of their secretory functions. This study was performed to investigate the effectiveness of the commonly used steroids beclomethasone, budesonide and fluticasone in downregulating HASMC production of RANTES and IL-8. HASMC (n=5) were cultured from dissected bronchi using collagenase digestion. Confluent HASMC were exposed to TNFalpha and IL-1beta (10 ng/ml) for 24 h. All stimulations were set with and without pre-treatment with beclomethasone, budesonide or fluticasone for 2 h at concentrations of 10(-9)-10(-6)M. IL-8 and RANTES mRNA expression was assessed by RT-PCR and protein secretion was determined by ELISA. Pre-treatment with beclomethasone, budesonide or fluticasone reduced TNFalpha- and IL-1beta-stimulated IL-8 and RANTES release from HASMC in a dose dependent manner. However, beclomethasone was 22-28% less effective than fluticasone and budesonide in inhibiting chemokine production. TNFalpha- and IL-1beta-induced RANTES and IL-8 expression was reduced on the transcriptional level by pre-treatment with fluticasone and budesonide. The results suggest that the topical steroids fluticasone, budesonide and to a lesser extent beclomethasone may have beneficial effects on airway inflammation in asthma by reducing RANTES and IL-8-induced leukocyte infiltration into the airway wall.