[Surgical Management of Peritoneal Surface Malignancy with Respect to Tumour Type, Tumour Stage and Individual Tumour Biology]. / Chirurgische Therapie der peritonealen Metastasierung in Abhängigkeit von Tumorentität, -stadium und -charakteristik(a).

Peritoneal tumour dissemination is still considered as a terminal disease. For the last two decades, cytoreductive surgery (CRS) combined with intraoperative hyperthermic chemotherapy (HIPEC) has been popularised by Paul Sugarbaker almost doubling survival in selected patients compared with systemic chemotherapy alone. Nowadays, this particular treatment protocol is available in comprehensive cancer centres with reasonable mortality and morbidity. However, patient selection is still challenging. In general, CRS and HIPEC is indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei as well as in peritoneal metastases derived from gastrointestinal malignancies and ovarian cancers. Since systemic tumour spread is uncommon in patients with peritoneal metastases, peritoneal tumour dissemination was defined as localised disease within the "compartment abdomen". However, CRS and HIPEC are only beneficial as long as complete cytoreduction is achieved (CC-0 or CC-1). Histopathological parameters, the Sugarbaker peritoneal carcinomatosis index (PCI) and general condition of the patient have been established as patient selection criteria. In primary peritoneal cancers, individual tumour biology is the predominant criterium for patient selection as opposed to intraabdominal tumour load in peritoneal metastases derived from gastrointestinal cancers. In gastric cancer, CRS and HIPEC should be restricted to synchronous limited disease because of its biological aggressiveness. In patients with free floating cancer cells without macroscopic signs of peritoneal spread, however, CRS and HIPEC following preoperative "neoadjuvant" chemotherapy preserves chances for cure. So far, there is no general recommendation for CRS and HIPEC by clinical practice guidelines. In the recent S3 guideline for treatment of colorectal cancer, however, CRS and HIPEC have been included as possible treatment options.

[Laparoscopic Resection Rectopexy for the Treatment of External Rectal Prolapse]. / Die laparoskopische Resektionsrektopexie zur Behandlung des externen Rektumprolapses.

Laparoscopic resection rectopexy is one of the surgical options for the treatment of external rectal prolapse. A standardised and reproducible procedure for this operation is a decisive advantage for such cases. The operation can be divided in 11 substeps, so-called nodal points, which must be reached before further progress can be made and simplify the operation by dividing the procedure into substeps. This manuscript and the accompanying film demonstrate the standardised laparoscopic resection rectopexy as taught in the "Surgical Training Center Tübingen," and performed at the University Hospital of Tübingen.

Impact of perioperative immunosuppressive medication on surgical outcome in Crohn's Disease (CD).

INTRODUCTION: Patients with Crohn's disease [CD] carry an 80 - 90 % lifetime risk of undergoing surgery. Many of these patients are on immunosuppressive medication at the time of surgery. The aim of this study was to evaluate the effect of immunosuppression on the surgical outcome in CD patients. METHODS: We retrospectively analyzed 484 consecutive abdominal operations for CD from 1995 to 2008 for surgical complications. RESULTS: A total of 241 operations (= 49.8 %) were performed under perioperative immunosuppression (corticoids and thiopurine). The overall complication rate was 18.6 %, the major complication rate was 8.7 % and the anastomotic leakage rate was 3.3 %. No differences were observed between patients without immunosuppression compared to those with immunosuppression. Patients with colo-rectal resections showed a higher complication rate than patients with small bowel resection independently of immunosuppression. CONCLUSION: Nearly 50 % of the patients undergoing abdominal surgery for CD are receiving immunosuppressive medication during surgery. However, perioperative immunosuppression with corticoids, thiopurine or the combination of both does not significantly alter the surgical complication rate. Therefore the decision of a required surgery should not be delayed due to the fact that the patient is under immunosuppressive medication.

Changes in peptidergic neurotransmission during postoperative ileus in rat circular jejunal muscle.

BACKGROUND: Our aim was to explore unknown changes in neurotransmission with vasoactive intestinal peptide (VIP) and Substance P (Sub P) during postoperative ileus (POI). METHODS: Contractile activity of rat circular jejunal muscle strips was studied in five groups (n = 6/group): Naïve controls, sham controls 12 h and 3 days after laparotomy, and rats 12 h, 3 days after induction of POI. Dose-responses to VIP (10(-10) -10(-7) M), Sub P (3 × 10(-10) -3 × 10(-7) M), and electrical field stimulation (EFS, to study endogenous release of neurotransmitters) were studied with different antagonists. Intestinal transit, inflammatory cells and immunoreactivity for VIP and Sub P were investigated in the bowel wall and cellular Finkel osteo sarcoma expression was determined in vagal afferent and efferent nuclei of the brainstem. KEY RESULTS: Postoperative ileus characterized by delayed intestinal transit and intramural inflammation was associated with an increased inhibitory effect of VIP on contractile activity. A biphasic impact was observed for Sub P with a decrease in its excitatory potential on contractility at 12 h, followed by a later increase 3 days postoperatively. Inhibitory response to EFS was increased, whereas the excitatory response decreased in ileus animals. VIP expression was increased in all postoperative animals while only animals 3 days after ileus induction showed increased Sub P expression in the myenteric plexus. These changes were associated with an activation of afferent but not efferent vagal nuclei in the brain stem. CONCLUSIONS & INFERENCES: Specific, time-dependent changes in peptidergic neurotransmission with VIP and Sub P occur during POI that are associated with vagal afferent activation, but are independent of the activation of efferent vagal pathways.

Effort, safety, and findings of routine preoperative endoscopic evaluation of morbidly obese patients undergoing bariatric surgery.

BACKGROUND: Obesity is becoming an epidemic health problem and is associated with concomitant diseases, such as sleep apnea syndrome and gastroesophageal reflux disease (GERD). There is no standardized diagnostic workup for the upper gastrointestinal tract in obese patients; many patients have no upper gastrointestinal symptoms, and few data are available on safety of endoscopy in morbidly obese patients. METHODS: Sixty-nine consecutive diagnostic upper gastrointestinal endoscopies in morbidly obese patients (26 men, 43 women; mean age 43.4 +/- 10.9 years) were prospectively evaluated from January to December 2008 in an outpatient setting before bariatric procedures. Sedation was administered with propofol. Data on sedation, critical events, and examination times were recorded, as well as pathological findings. RESULTS: The patients' mean body mass index was 47.6 +/- 7.9 (range, 35.1-73.3) kg/m(2); 17.4% reported GERD symptoms. The mean duration of the endoscopy procedure (including sedation) was 20.3 +/- 9.3 (range, 5-50) min, and the whole procedure (including preparation and postprocessing) took 58.2 +/- 19 (range, 20-120) min. The mean propofol dosage was 380 +/- 150 (range, 80-900) mg. Two patients had critical events that required bronchoscopic intratracheal O(2) insufflation due to severe hypoxemia (<60% SaO: (2)). Nearly 80% of patients had pathological findings in the upper gastrointestinal tract. Only 20% reported upper gastrointestinal symptoms. Pathologic conditions were found in the esophagus in 23.2% of the patients, in the stomach in 78.2%, and in the duodenum in 11.6%. The prevalence of Helicobacter pylori infection was 8.7%. CONCLUSIONS: Upper gastrointestinal endoscopy can be performed safely. However, careful monitoring and anesthesiological support are required for patients with concomitant diseases and those receiving sedation. Because 80% of the patients with pathological findings were asymptomatic, every morbidly obese patient should undergo endoscopy before bariatric surgery because there may be findings that might change the surgical strategy.

Neuronal activation in the nucleus of the solitary tract following jejunal lipopolysaccharide in the rat.

INTRODUCTION: Inflammation during systemic lipopolysaccharide (LPS) seems to be modulated by the CNS via afferent and efferent vagal pathways. We hypothesized that similar to systemic inflammation, local LPS in the gut lumen may also activate central neurons and aimed to identify potential molecular mechanisms. METHODS: Male Wistar rats were equipped with an exteriorized canula in the proximal jejunum. LPS or vehicle were administered into the jejunum (10 mg ml(-1)). For further study of molecular mechanisms, LPS or vehicle were administered systemically (1 mg kg(-1)). Brain stem activation was quantified by Fos-immunohistochemistry in the vagal nucleus of the solitary tract (NTS) and the Area postrema which is exposed to systemic circulation. Serum LPS concentrations were also determined. RESULTS: Jejunal LPS exposure entailed 91+/-12 (n=7) Fos-positive neurons in the NTS compared to 39+/-9 in controls (n=6; p<0.01), while serum LPS concentrations and Fos-positive neurons in the Area postrema were not different. Systemic LPS triggered 150+/-25 (n=6) and vehicle 52+/-6 Fos-positive neurons (n=7; p<0.01). The Fos count after systemic LPS was reduced to 99+/-30 following pretreatment with the cyclooxygenase inhibitor Naproxen (10 mg kg(-1); p>0.05 versus vehicle controls) and increased to 242+/-66 following the iNOS-inhibitor Aminoguanidine (15 mg kg(-1); p<0.01). In the Area postrema, 97+/-17 (n=6) neurons were counted in animals pretreated with systemic LPS compared to 14+/-4 in controls (n=7, p<0.001). CONCLUSIONS: Central neuronal activation following inflammation after systemic LPS is modulated by cyclooxygenase and NO pathways. Local exposure to bacterial LPS in the gut lumen activates the NTS which may set the stage for efferent vagal modulation of intestinal inflammation.

[Operative technique and outcome after laparoscopic adjustable gastric banding]. / Operative Technik und deren Outcome in der metabolischen Chirurgie: Adjustable Gastric Banding (AGB).

Laparoscopic gastric banding is an easy to perform procedure with low morbidity and mortality. The benefits of the operation on the metabolic outcome have been demonstrated in long-term studies and are directly proportional to the amount of weight loss. Beside a closely monitored interdisciplinary follow-up, patient compliance is an essential prerequisite for success.

Intestinal afferent nerve sensitivity is increased during the initial development of postoperative ileus in mice.

INTRODUCTION: Neuronal reflex inhibition of gastrointestinal motility is a key mechanism in the development of postoperative ileus (POI). The aim of our study was to determine whether intestinal afferent nerve fibers are sensitized during the first hours after surgery contributing to this mechanism. METHODS: Under enflurane anesthesia, C57BL/6 mice underwent laparotomy followed by sham treatment or standardized small bowel manipulation to induce POI. After 1, 3, or 9 h, extracellular multi-unit mesenteric afferent nerve recordings were performed in vitro from 2 cm segments of jejunum (subgroups n = 6) superfused with Kreb's buffer (32 degrees C, gassed with O(2)/CO(2) mixture). Segments were cannulated to monitor luminal pressure and intestinal motility. Afferent impulses as response to bradykinin (0.5 microM) and to mechanical ramp distension of the intestinal lumen from 0 to 80 cmH(2)O were recorded. RESULTS: At 1 h, amplitudes of intestinal contractions were 0.8 +/- 0.2 cmH(2)O after induction of POI and 5.0 +/- 0.8 cmH(2)O in sham controls (mean +/- SEM; p < 0.01). A similar difference was observed for segments harvested at 3 and 9 h. Afferent firing to serosal bradykinin was increased at 1, 3, and 9 h in POI segments compared to sham controls (p < 0.05 at 1 h, p < 0.01 at 3 and 9 h). During distension with high pressures, afferent firing rate was increased at 1 and 3 h in segments after induction of POI compared to sham controls. Nine hours postoperatively, contracted and dilated segments were observed during POI that were investigated separately. While afferent firing in dilated segments was increased to 176 +/- 16 imp s(-1) at 80 cmH(2)O luminal distension (p < 0.01), it was 46 +/- 5 imp s(-1) in contracted segments (p < 0.001) compared to 77 +/- 4 imp s(-1) in sham controls. CONCLUSIONS: Afferent firing to bradykinin and high threshold distension is augmented in the early phase of POI. As these stimuli are known to sensitize predominantly spinal afferents, this mechanism may contribute to reflex inhibition of intestinal motility during POI.

[No influence of physiotherapy on outcome after open repair of achilles tendon ruptures?]. / Kein Einfluss der Physiotherapie auf das klinische Ergebnis nach operativ behandelter Achillessehnenruptur?

AIM: Many studies have been performed to analyse the influence of surgical techniques and the postoperative aftercare after Achilles tendon ruptures on the outcome. However, there is no study investigating the influence of physiotherapy on outcome after surgical repair and standardised early functional rehabilitation of Achilles tendon rupture, so that this was the objective of the present study. PATIENTS AND METHODS: In this retrospective study, 104 patients with Achilles tendon ruptures, all treated by open repair followed by a standardised early rehabilitation, were evaluated by the Thermann score. The average age was 42 years. We could identify 3 patient groups. Group I (n=23) did not receive any physiotherapy. Group II (n=41) received physiotherapy for 3-6 weeks, and group III (n=40) received more than 6 weeks of physiotherapy. Physiotherapy consisted of 3 units per week. Each unit lasted for 30 min. All groups were compared statistically via variance analysis. RESULTS: Group I scored on average 88.8 points, group II 88.6 and group III 87.0 points. There were no statistically significant differences between the three groups (p=0.50). The age of patients had also no relevant influence on the outcome (p=0.48). CONCLUSIONS: Physiotherapy and age of the patients involved were not found to influence the outcome after open augmented repair of Achilles tendon ruptures followed by a standardised early rehabilitation. These results should be confirmed by a prospective randomised trial. Also elderly patients participating in demanding sport activities should receive a surgical repair.

[Selection criteria for peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) in peritoneal carcinomatosis]. / Selektion zur Peritonektomie mit hyperthermer intraoperativer Chemotherapie (HIPEC) bei Peritonealkarzinose.

BACKGROUND: Cytoreductive peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) is an established therapy for patients with gastrointestinal, gynaecological metastasised peritoneal carcinomatosis as well as primary peritoneal carcinomatous tumours. METHODS: On the basis of a literature review and our personal experience, selection criteria for peritonectomy are discussed. RESULTS: Computed tomography (CT) scans and diagnostic laparoscopy are not sufficient for the diagnosis of peritoneal carcinomatosis. The combination of fluorodeoxyglucose positron emission tomography (FDG-PET) and CT seems to be the most reliable diagnostic imaging method. In our institution, all patients undergo PET / CT prior to peritonectomy. CONCLUSION: The PET / CT scan may play an important role in forecasting the operability of patients with peritoneal carcinomatosis.

Intestinal lipid absorption increases cold ischemia of the small bowel in rats.

UNLABELLED: The short cold ischemic tolerance of the gut is a major problem in small bowel transplantation. We have shown that intestinal lipid administration is beneficial during systemic inflammation like sepsis. METHODS: Rats were intestinally infused with either water or 1% olive oil for 12 hours. The small bowel was removed and stored in HTK solution on ice. At t = 0, t = 60, t = 120, t = 180, t = 240, t = 300, t = 360, t = 420, and t = 480 minutes, a tissue sample of the gut was fixed, stained, and analyzed by three independent observers. Damage score was calculated (0 = no damage, 1 = minor damage, 2 = major damage, 3 = loss of structure) for integrity of the mucosa, integrity of the basal membrane of the mucosa, and integrity of villy. The damage score was allocated when all three observers agreed on the same or a higher damage score. RESULTS: In all control animals minor damage for the integrity of the basal membrane occurred within 60 minutes, but in only 50% of the lipid-treated rats. In all control rats, major damage for both integrity of mucosa and villi occurred within 300 minutes or less, but only in 50% of the lipid-treated rats. In all control rats, the structure of the villi was completely lost within 480 minutes or less, whereas only 50% of the lipid treated animals reached maximal damage scores for either mucosa or villi. CONCLUSION: Intestinal lipid administration before cold storage clearly decreases histologic damage of the small bowel and might increase the tolerance for cold ischemia. Lipids or their metabolites stored in enterocytes may act as an antiinflammatory. Intestinal lipid administration in organ donors might be useful to increase cold ischemic tolerance of the small bowel.

Effects of neurotrophin 3 on gastric and colonic motility in awake rats.

Neurotrophin 3 (NT3) and its receptors are expressed throughout the gastrointestinal tract, especially in the enteric nervous system. However, little is known about the effects of NT3 on gastrointestinal motility. To investigate the effects of NT3 on gastric or colonic motility under baseline conditions, after subdiaphragmatic vagotomy and in a model of postoperative ileus. Sprague-Dawley rats were equipped with strain gauge transducers on the gastric or colonic wall. Motility was recorded for 30 min, followed by i.v. administration of NT3 and motility-recording for another 60 min. Experiments were performed on three consecutive days and separately in a postoperative ileus model. To evaluate a vagal pathway, experiments were also performed on vagotomized rats. NT3 inhibited gastric motility. This inhibitory effect was reduced by subdiaphragmatic vagotomy. Preoperative treatment with NT3 prolonged the postoperative gastric ileus compared to vehicle treatment. Colonic motility in the intact animal was unchanged by NT3, but was increased postoperatively. NT3 treatment inhibited gastric but not colonic motility. This inhibition of gastric motility seems to be partly mediated by the vagus nerve. NT3 aggravates gastric postoperative ileus but attenuates colonic postoperative ileus, which corresponds to the observed positive effects of NT3 on constipated patients.

Risk of fecal diversion in complicated perianal Crohn's disease.

The purpose of the study was to determine the overall risk of a permanent stoma in patients with complicated perianal Crohn's disease, and to identify risk factors predicting stoma carriage. A total of 102 consecutive patients presented with the first manifestation of complicated perianal Crohn's disease in our outpatient department between 1992 and 1995. Ninety-seven patients (95%) could be followed up at a median of 16 years after first diagnosis of Crohn's disease. Patients were sent a standardized questionnaire and patient charts were reviewed with respect to the recurrence of perianal abscesses or fistulas and surgical treatment, including fecal diversion. Factors predictive of permanent stoma carriage were determined by univariate and multivariate analysis. Thirty of 97 patients (31%) with complicated perianal Crohn's disease eventually required a permanent stoma. The median time from first diagnosis of Crohn's disease to permanent fecal diversion was 8.5 years (range 0-23 years). Temporary fecal diversion became necessary in 51 of 97 patients (53%), but could be successfully removed in 24 of 51 patients (47%). Increased rates of permanent fecal diversion were observed in 54% of patients with complex perianal fistulas and in 54% of patients with rectovaginal fistulas, as well as in patients that had undergone subtotal colon resection (60%), left-sided colon resection (83%), or rectal resection (92%). An increased risk for permanent stoma carriage was identified by multivariate analysis for complex perianal fistulas (odds ratio [OR] 5; 95% confidence interval [CI] 2-18), temporary fecal diversion (OR 8; 95% CI 2-35), fecal incontinence (OR 21, 95% CI 3-165), or rectal resection (OR 30; 95% CI 3-179). Local drainage, setons, and temporary stoma for deep and complicated fistulas in Crohn's disease, followed by a rectal advancement flap, may result in closing of the stoma in 47% of the time. The risk of permanent fecal diversion was substantial in patients with complicated perianal Crohn's disease, with patients requiring a colorectal resection or suffering from fecal incontinence carrying a particularly high risk for permanent fecal diversion. In contrast, patients with perianal Crohn's disease who required surgery for small bowel disease or a segmental colon resection carried no risk of a permanent stoma.

Alterations of neuropeptides in the human gut during peritonitis.

BACKGROUND AND AIMS: Gastrointestinal motility is reduced during sepsis but the pathomechanism involved is poorly understood. We investigated the expression of substance P (SP) and vasoactive intestinal peptide (VIP) in the myenteric plexus during peritonitis in human small bowel. MATERIALS AND METHODS: Tissue samples of the small bowel were gathered from healthy patients and from patients with peritonitis. Immunohistochemistry for myeloperoxidase (MPO), SP, and VIP was performed in whole mount sections. To determine the level of inflammation, MPO-positive cells were counted in the circular muscle layer. SP and VIP immunoreactivity was analyzed in myenteric plexus neurons. The area of positive immunoreactivity for either neuropeptide within the plexus was analyzed and set in relation to the total area of the plexus and consecutively expressed as percentage. RESULTS: During peritonitis, MPO-positive cells significantly increased by approximately fourfold as compared to healthy tissue. The immunoreactivity for SP was significantly reduced by approximately 80% in myenteric plexus neurons during peritonitis. In contrast, the immunoreactivity for VIP significantly increased by nearly twofold during peritonitis. CONCLUSIONS: During peritonitis, the inflammatory reaction within the gut is increased. The neuropeptide expression in myenteric plexus neurons was observed as shifting towards increased expression of VIP, known to inhibit intestinal motility, and towards decreased expression of the prokinetic neuropeptide SP.

STW 5 (Iberogast) reduces afferent sensitivity in the rat small intestine.

INTRODUCTION: A limited number of drugs are available for the treatment of functional dyspepsia and irritable bowel syndrome. The efficacy of STW 5 (Iberogast) was previously shown in clinical trials. Since visceral hypersensitivity seems to be the prime pathomechanism of functional gastro-intestinal disorders, the aim of this study was to explore whether STW 5 reduces intestinal afferent sensitivity in the upper gastrointestinal tract. METHODS: Two groups of male Wistar rats were pretreated with either the herbal preparation STW 5 or its vehicle (30.8% ethanol). Then, after 2h, general anesthesia was induced by pentobarbitone (60 mg kg(-1)i.p.) and extracellular multi-unit afferent recordings were obtained from mesenteric afferents innervating the proximal jejunum. The intestinal afferent nerve response to increasing doses of 5-HT and bradykinin were quantified as well as afferent discharge following a ramp distension of the adjacent intestinal loop from 0 to 60 cm H(2)O. RESULTS: Afferent discharge to 5-HT and bradykinin increased dose-dependently. Following the different doses of 5-HT, the peak in afferent nerve discharge was always reduced after pretreatment with STW 5 compared to controls with a response of 110+/-5 imp s(-1) after STW 5 and 128+/-3 in vehicle controls at the maximum dose (40 microg kg(-1); p<0.05; mean+/-SEM). For bradykinin, afferent responses were reduced following STW 5 at the 20 and 40 microg kg(-1) dose but not at 10 microg kg(-1) (40 microg kg(-1)176+/-7 imp s(-1) following STW 5 versus 200+/-6 imp s(-1) in controls; p<0.05). The ramp distension of the intestinal loop stimulated a rise in intestinal afferent nerve discharge that was always lower in the STW 5 pretreated group compared to vehicle controls with the exception of the discharge rate at the pressure level of 0 and 20 cm H(2)O (all other pressures up to 60 cm H(2)O p<0.05). CONCLUSIONS: Sensitivity of intestinal afferents to mechanical and chemical stimuli is reduced following treatment with the herbal preparation STW 5. This mechanism may help to explain why STW 5 relieves dyspeptic and bowel symptoms in patients.

Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats.

BACKGROUND: Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model. METHODS: In Sprague-Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, L-NMMA (NO synthase inhibitor), D-NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after L-NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed. RESULTS: L-NMMA decreased gastric motility to 60+/-8% for about 15 min, but continuously increased small intestinal motility to 221+/-22% and colonic motility to 125+/-7% compared to baseline (baseline=100%; p<0.01 for all comparisons). L-NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13+/-2%; small intestine, 8+/-1%; colon, 16+/-5%; p<0.01 vs. baseline for all comparisons). L-NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (L-NMMA vs. vehicle, 0-60 min postoperatively; stomach, 90+/-9% vs. 53+/-3%; small intestine, 101+/-5% vs. 57+/-3%; colon, 134+/-6% vs. 60+/-5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and L-NMMA treated rats postoperatively). CONCLUSIONS: Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.

Long-term outcome of conservative treatment in patients with diverticulitis of the sigmoid colon.

INTRODUCTION: The indication for surgery after conservative treatment of acute diverticulitis is still under debate. This is partly as a result of limited data on the outcome of conservative management in the long run. We therefore aimed to determine the long-term results of conservative treatment for acute diverticulitis. METHODS: The records of all patients treated at our institution for diverticulitis between 1985 and 1991 were reviewed (n=363, median age 64 years, range 29-93). Patients who received conservative treatment were interviewed in 1996 and 2002 [follow-up time 7 years 2 months (range 58-127 months) and 13 years 4 months (range 130-196 months). RESULTS: A total of 252 patients (69%) were treated conservatively, whereas 111 (31%) were operated on. At the first follow-up, 85 patients treated conservatively had died, one of them from bleeding diverticula. A recurrence of symptoms was reported by 78 of the remaining 167 patients, and 13 underwent surgery. At the second follow-up, one patient had died from sepsis after perforation during another episode of diverticulitis. Thirty-one of the 85 patients interviewed reported symptoms and 12 had been operated on. In summary, at the second follow-up interview, 34% of patients treated initially had had a recurrence and 10% had undergone surgery. No predictive factors for the recurrence of symptoms or later surgery could be determined. CONCLUSION: Despite a high rate of recurrences after conservative treatment of acute diverticulitis, lethal complications are rare. Surgery should thus mainly be undertaken to achieve relief of symptoms rather than to prevent death from complications.

Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins.

Bacterial translocation across the intestinal mucosal barrier leads to a macrophage-mediated inflammatory response, visceral hyperalgesia, and ileus. Our aim was to examine how mediators released into mesenteric lymph following LPS treatment influence intestinal afferent sensitivity and the role played by prostanoids in any sensitization. Intestinal lymph was collected from awake rats following treatment with either saline or LPS (5 mg/kg ip). Extracellular multiunit afferent recordings were made from paravascular mesenteric nerve bundles supplying the rat jejunum in vitro following arterial administration of control lymph, LPS lymph, and LPS. Mesenteric afferent discharge increased significantly after LPS lymph compared with control lymph. Peak discharge occurred within 2 min and remained elevated for 5 to 8 min. This response was attenuated by pretreatment with naproxen (10 microM), and restored upon addition of prostaglandin E(2) (5 microM) in the presence of naproxen, but AH6809 (5 microM), an EP(1)/EP(2) receptor(s) antagonist, failed to decrease the magnitude of LPS lymph-induced response. LPS itself also stimulated mesenteric afferent discharge but was unaffected by naproxen. TNF-alpha was significantly increased in LPS lymph compared with control lymph (1,583 +/- 197 vs. 169 +/- 38 pg/ml, P < 0.01) but exogenous TNF-alpha failed to evoke any afferent nerve discharge. We concluded that inflammatory mediators released from the gut into mesenteric lymph during endotoxemia have a profound effect on afferent discharge. These mediators influence afferent firing via the release of local prostaglandins.

Prevalence of vertebral alterations and the effects of calcium and vitamin D supplementation on calcium metabolism and bone mineral density after gastrectomy.

BACKGROUND: Bone disease is common after gastrectomy, resulting in decreased bone mass and an increased risk of fracture. No proven therapy is currently available. METHODS: Serum markers of calcium metabolism in 98 patients after partial or total gastrectomy were compared with those in 30 age- and sex-matched healthy controls. Patients with disorders of calcium metabolism were investigated by conventional radiography and single-energy computed tomography of the spine. Forty patients participated in a 1-year follow-up study to investigate the effects of vitamin D and calcium supplementation on calcium metabolism and bone mineral density. RESULTS: Altered serum markers of calcium and phosphate metabolism were observed in 77 (79 per cent) of 98 patients. Sixty (79 per cent) of these had vertebral alterations. Vertebral fractures were detected in 22 patients, grade I vertebral deformities in 50 patients, grade II deformities in 22 patients and osteopenia (Z-score less than - 1) in 30 patients. Calcium and vitamin D supplementation resulted in an increase in 25-hydroxy-vitamin D (P < 0.001), 1,25-dihydroxy-vitamin D (P = 0.048) and osteocalcin (P = 0.045), whereas levels of parathyroid hormone were decreased (P = 0.007). Bone mineral density did not change over time. CONCLUSION: Disturbances of calcium and bone metabolism are common after gastrectomy. Calcium and vitamin D supplementation normalized levels of markers of calcium metabolism and might have prevented age-related bone mass loss, although it did not increase bone mineral density after 1 year.