Hans Glise

OMEPRAZOLE OR RANITIDINE IN LONG-TERM TREATMENT OF REFLUX ESOPHAGITIS

BACKGROUND/AIMS Patients with reflux esophagitis have rapid relapses after treatment withdrawal. This study was designed to investigate the relapse rate of symptomatic esophagitis during maintenance treatment with omeprazole or ranitidine. METHODS Patients with endoscopically verified acute erosive or ulcerative esophagitis were initially treated with 20-40 mg omeprazole daily for 8-12 weeks. After healing, the patients were randomized to maintenance treatment with omeprazole (20 or 10 mg each morning) or ranitidine (150 mg twice daily). Control endoscopy was performed at the end of the healing phase and after 12 months of maintenance treatment or symptomatic relapse. RESULTS Of 426 initially treated patients, 392 were healed and entered the maintenance study. The months of maintenance treatment with 20 mg omeprazole once daily (n = 131), 10 mg omeprazole once daily (n = 133), and 150 mg ranitidine twice daily (n = 128) were 72%, 62%, and 45%, respectively. Both the 10- and 20-mg doses of omeprazole were significantly better than the dose of ranitidine (P < 0.001 and P < 0.005, respectively). There was no significant difference between the 10- and 20-mg doses of omeprazole (P = 0.06). CONCLUSIONS Maintenance treatment with omeprazole (20 or 10 mg once daily) is superior to ranitidine (150 mg twice daily) in keeping patients with erosive reflux esophagitis in remission over a 12-month period.

Complications Following Swedish Adjustable Gastric Banding: A Long-Term Follow-up

Background: The Swedish adjustable gastric band (SAGB) has been in use since 1985. The aim of this study was to analyze short and long-term complications linked to the SAGB. Materials and Methods: Between August 1990 and December 1996, we operated on a series of 326 patients (78 men and 248 women) at the Huddinge University Hospital and the Norra Älvsborg County Hospital. The mean age of patients at surgery was 40 years (range 19-62). The mean preoperative weight was 125 kg (range 81-181). The mean excess weight was 80%. Results: The mean time of follow-up was 28 months (range 6-76). Complications requiring reoperation included two (0.6%) band dislocations, six (1.8%) band leakages, and 16 (4.6%) band migrations-erosions. The most common reason for abdominal reoperation, band migration, was attributed to overfilling of the band system. In the patients in whom migration occurred, the bands had been filled with a mean volume of 12.6 ml fluid. In the remaining patients, the mean volume was 8.7 ml. The most common complication not requiring reoperation was reflux disease (4.7%). In cases with a small pouch, this complication did not seem to be a serious problem. The mean excess weight loss in the 296 patients without complications was 68%. Conclusion: The overall long-term complication rate following SAGB is reasonable. With improved operating technique and closer follow-up, it should be possible to reduce the complication rate further. Reoperation because of band migration appears to be related to overfilling of the system and should therefore be avoidable in most cases.

Laparoscopic Mesh Versus Open Preperitoneal Mesh Versus Conventional Technique for Inguinal Hernia Repair: A Randomized Multicenter Trial (SCUR Hernia Repair Study)

OBJECTIVE To evaluate the influence of the laparoscopic technique in hernia repair regarding time to full recovery and return to work, complications, recurrence rate, and economic aspects. SUMMARY BACKGROUND DATA Several studies have shown advantages in terms of less pain and faster recovery after laparoscopic hernia repair, whereas others have not, and the cost-effectiveness has been questioned. The laparoscopic technique must be thoroughly compared with the open procedures before its true place in hernia surgery can be defined. METHODS Six hundred thirteen male patients aged 40 to 75 years were randomized to the conventional procedure, preperitoneal mesh placed by the open technique, or laparoscopic preperitoneal mesh (TAPP). Follow-up was after 7 days, 8 weeks, and 1 year. RESULTS Of 613 patients undergoing surgery, 604 (98.5%) were followed for 1 year. Patients who underwent TAPP gained full recovery after 18.4 days, compared with 24.2 days for open mesh (p < 0.001) and 26.4 days for the conventional procedure (p < 0.001). Patients who underwent TAPP returned to work after 14.7 days, compared with 17.7 days for open mesh (p = 0.05) and 17.9 days for the conventional procedure (p = 0.04). They also had significantly less restriction in physical activities after 7 days. The TAPP procedure was more expensive, mainly as a result of longer surgical time and equipment costs, even after compensation for earlier return to work. Complications were more common in the TAPP group, with a varying pattern between the groups. Four recurrences in the conventional, 11 in the open mesh, and 4 in the TAPP group were recorded after 1 year (p = n.s.). CONCLUSION The laparoscopic technique results in both shorter time to full recovery and shorter time to return to work, at the price of substantially increased costs.

Preoperative Local Infiltration with Ropivacaine for Postoperative Pain Relief After Cholecystectomy

In a randomized, double‐blind, placebo‐controlled trial, we evaluated the use of preoperative local anesthesia with regard to postoperative pain. Before surgery in 66 patients scheduled for cholecystectomy, the abdominal wall along the proposed line of incision was infiltrated with 70 mL of 0.25% ropivacaine, 70 mL of 0.125% ropivacaine, or 70 mL of saline. Wound pain at rest, wound pain during mobilization, and pressure exerted to reach maximum pain tolerance were assessed after 6,26, 50, and 74 h and after 7 days. Consumption of analgesics was recorded. At the 6‐h assessment, there was a statistically significant dose‐related decrease in wound pain during mobilization (P = 0.001) and an increase of pressure exerted to reach maximum pain tolerance (P < 0.001). The tests were two‐tailed and performed at a significance level of P < 0.05. There were no significant differences between the groups at later pain control assessments. The median time to first request for postoperative analgesics was significantly shorter (P = 0.014) in the saline group than in the ropivacaine 0.25% group. These effects are suggested to be a residual anesthetic effect of ropivacaine. The study gives no support to the hypothesis that preoperative local anesthetics dampen the inflammatory response and ensuing hyperalgesia.

Quality of Life Assessments in the Evaluation of Gastroesophageal Reflux and Peptic Ulcer Disease before, during and after Treatment

BACKGROUND It has recently been suggested that Quality of Life (QOL) be used in the evaluation of new medical treatment regimens together with cost-benefit, efficacy and safety. In this overview we point out some aspects of use of the Psychological General Well-Being Index (PGWB) in patients with peptic ulcer and reflux disease gained from our own investigations in later years. METHODS QOL was assessed using questionnaires before diagnosis, during medical healing treatment and at a 1-year follow-up in peptic ulcer disease or before and after surgery in reflux disease. RESULTS Untreated patients with unknown diagnosis had low QOL scores. With treatment, scores increased rapidly to supernormal values and fell off to normal values during the follow-up year. CONCLUSION QOL evaluations seem sensitive and reflect the patients subjective feeling of disease. They add another new aspect of treatment effect not earlier included in treatment evaluations.

HLA-DRhi and CCR9 Define a Pro-Inflammatory Monocyte Subset in IBD

OBJECTIVES:It has been demonstrated that circulating monocytes relocate to the intestinal mucosa during intestinal inflammation, but the phenotype and inflammatory mechanisms of these monocytes remain poorly understood. Here, we have investigated blood monocytes expressing high levels of HLA-DR and CCR9 in patients with inflammatory bowel disease (IBD).METHODS:Fifty-one patients with mild to severe ulcerative colitis (UC; n=31; UC-DAI 3–12) or Crohn’s disease (CD; n=20; Harvey–Bradshaw indices (HBI) 2–16) were included together with 14 controls, during IBD therapy for four consecutive weeks. The frequency of CD14+HLA-DRhi monocytes was monitored weekly in peripheral blood, using flow cytometry. The surface phenotype and cytokine profile of these monocytes were established using flow cytometry and real-time PCR. Clinical parameters were assessed weekly in all patients.RESULTS:The frequency of circulating CD14+HLA-DRhi monocytes was significantly higher in IBD patients with moderate to severe disease compared with healthy controls (P<0.001). During treatment with corticosteroids and granulocyte/monocyte apheresis, the proportion of circulating CD14+HLA-DRhi monocytes was significantly reduced. CD14+HLA-DRhi monocytes produced high levels of inflammatory mediators, such as tumor necrosis factor (TNF)-α, and expressed the gut-homing receptor CCR9. Furthermore, we found that the CCR9 ligand, CCL25/TECK, was expressed at high levels in the colonic mucosa in IBD patients with active disease.CONCLUSIONS:CD14+HLA-DRhi blood monocytes were increased in patients with active IBD. These monocytes exhibit a pro-inflammatory, gut-homing phenotype with regard to their TNF-α production and expression of CCR9. Our results suggest that these monocytes are important in mediating intestinal inflammation, and provide potential therapeutic targets in IBD.

Assessment of Outcome After Antireflux Surgery

Gastroesophageal reflux disease is common, causing chronic symptoms in many people. The medical and surgical therapies that are available and effective seem to incur a variety of side effects and long-term costs. With the development of laparoscopic surgical treatment techniques, the number of patients suggested for surgery may increase, which necessitates that an evaluation of this new treatment be conducted that compares it with the possible alternatives. This evaluation should include efficacy, safety, cost benefit, and quality of life (QOL) assessments. QOL evaluations have to be used with care. It is important that the methods are validated and found reliable for the group of patients assessed. If used in the right way, a new dimension-the patients view-may influence the choice of treatment. For reflux, two self-administered questionnaires have been used, the Psychological General Well Being Index (PGWB) and the Gastrointestinal Symptom Rating Scale (GSRS). In reflux patients, results show poor values in untreated patients contrasted with normal values in patients who have had optimal medical treatment and patients who have had surgery. The assessments seem to be sensitive enough to discriminate between the different treatments, thereby adding important information concerning the treatment outcome.

Detection of micrometastases by flow cytometry in sentinel lymph nodes from patients with renal tumours

Background:Stage is an important prognostic factor in renal tumours and dissemination to regional lymph nodes is associated with poor outcomes. Lymph nodes are routinely assessed by immunohistochemistry and microscopic evaluation, a time-consuming process where micrometastases might go undiagnosed. We evaluate an alternative method for detecting metastatic cells in sentinel nodes (SNs) by flow cytometry.Methods:A total of 15 nodes from 5 patients diagnosed with renal tumours were analysed by flow cytometry. Staining for the intracellular marker cytokeratin 18 (CK18) with the surface markers carbonic anhydrase IX (CA9) and Cadherin 6 were used in flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) with the addition of known concentrations of cancer cell lines were analysed to investigate the sensitivity of micrometastasis detection.Results:Stability of the assay was marked by low intra-assay variability (coefficient of variance ⩽16%) and low inter-assay variability (R2=0.9996–1). Eight nodes in four patients were positive for metastasis; six of them were considered being micrometastatic. These metastases were undetected by routine pathology and the patients were restaged from pN0 to pN1.Conclusions:Flow cytometry is able to detect micrometastases in lymph nodes of renal tumour patients that were undetected under H&E examination.

Laparoscopic Rosetti Fundoplication

BACKGROUND Early experiences with laparoscopic fundoplication using the Rosetti technique are presented and compared with retrospective results from conventional fundoplication procedures. METHODS AND RESULTS We have performed 70 consecutive laparoscopic procedures. Conversion to open surgery was done in seven cases because of anatomical reasons and in two because of peroperative progressive subcutaneous emphysema and CO2-retention. The complication rate was low. The range of postoperative hospital stay is 1-4 days for non-converted patients. Symptomatic follow-up has hitherto been performed in 41 patients with a follow-up time of 3-9 months. The follow-up results do not differ from those achieved in patients operated upon with the conventional open Nissen (n = 41) and Rosetti (n = 36) techniques. Pre- and postoperative control of 24 h pH and lower esophageal sphincter pressure (LESP) in 19 laparoscopically treated patients showed normalization of LESP in all cases and postoperative 24 h pH < 4 ranging between 0 and 3%. CONCLUSIONS Laparoscopic and reflux surgery is effective for the treatment of reflux esophagitis. Follow-up results compare well with open surgery.

Considerations for Peptic Ulcer Trials

A drug trial concerned with peptic ulcer treatment has to be carefully planned to make possible a valid conclusion. Calculations of the number of patients required have to be made early. This depends upon factors such as: if the comparison is to be made between two active drugs or an active drug and a placebo, if the aim is to show that two treatments are almost equal or if a certain difference is expected, the number of groups to be compared, and if intermediate checks are to be made. Thus, from a few dozen patients up to several thousand may be needed. If a multicenter dosing is adopted, which is often necessary, the minimum number of patients required from each centre should be specified and a good reporting system has to be created. When presenting the results, it is preferable to calculate a confidence interval for the difference between the treatments--especially in small studies where the risk is false conclusions would otherwise be large.