Complications in surgery for Crohn's disease after preoperative antitumour necrosis factor therapy.

BACKGROUND: The use of biological therapy (biologicals) is established in the treatment of Crohn's disease. This study aimed to determine whether preoperative treatment with biologicals is associated with an increased rate of complications following surgery for Crohn's disease with intestinal anastomosis. METHODS: All patients receiving biologicals and undergoing abdominal surgery with anastomosis or strictureplasty were identified at six tertiary referral centres. Demographic data, and preoperative, operative and postoperative details were registered. Patients who were treated with biologicals within 2 months before surgery were compared with a control group who were not. Postoperative complications were classified according to anastomotic, infectious or other complications, and graded according to the Clavien-Dindo classification. RESULTS: Some 111 patients treated with biologicals within 2 months before surgery were compared with 187 patients in the control group. The groups were well matched. There were no differences between the treatment and control groups in the rate of complications of any type (34·2 versus 28·9 per cent respectively; P = 0·402), anastomotic complications (7·2 versus 8·0 per cent; P = 0·976) and non-anastomotic infectious complications (16·2 versus 13·9 per cent; P = 0·586). In univariable regression analysis, biologicals were not associated with an increased risk of any complication (odds ratio (OR) 1·33, 95 per cent confidence interval 0·81 to 2·20), anastomotic complication (OR 0·89, 0·37 to 2·17) or infectious complication (OR 1·09, 0·62 to 1·91). CONCLUSION: Treatment with biologicals within 2 months of surgery for Crohn's disease with intestinal anastomosis was not associated with an increased risk of complications.

Clinical and proctoscopic evaluation of topical formalin application in the treatment of chronic radiation proctitis.

BACKGROUND AND AIMS: Chronic radiation proctitis is a disease associated with radiotherapy of cancer in the pelvic region. The main symptom is rectal bleeding. Several treatment modalities have been attempted, but few have demonstrated satisfactory effects. We present our experience with formalin applied locally to the rectal mucosa in the treatment of chronic radiation proctitis. Furthermore, we assess possible complications, the gravest suggested being cancer. Previous studies on the subject have reported good results, but often with a somewhat vaguely defined follow-up. Our evaluation of the treatment was based on both subjective symptoms and proctoscopic findings. MATERIAL AND METHODS: A small study (N = 11) was conducted retrospectively. All patients treated for chronic radiation proctitis with formalin in our clinic were identified, and data concerning effect and complications were collected by studying the patients' records, with a questionnaire and a follow-up interview and proctoscopy. RESULTS: The study showed a marked decrease in bleeding and objective signs of proctitis in all patients. Complete cessation of bleeding was achieved in five patients. Possible complications to the treatment detected in our study were the following: anorectal pain, tenesmus, incontinence, diarrhea, and mucous rectal discharge. No signs of neoplasia were found. CONCLUSIONS: The formalin treatment had a very good effect on chronic radiation proctitis. Possible complications were detected. Except in the case of anorectal pain, these are all of a questionable nature and can possibly be attributed to chronic radiation proctitis itself rather than the formalin treatment. Further study is warranted to confirm long-term effects of the formalin and to exclude possible complications, especially secondary anorectal cancer.

Restorative proctocolectomy in patients with ulcerative colitis: a cross-sectional Danish population study on function and quality of life.

AIM: The study evaluated function and quality of life (QoL) in all patients having restorative proctocolectomy (RPC) in Denmark for ulcerative colitis (UC) from 1980 to 2010. Inclusion of all patients in one country has never previously been achieved. METHOD: All patients who had had a RPC in Denmark, from the first case in 1980 to the last case in 2010, were studied. A cross-sectional questionnaire survey was performed, and function and QoL were assessed using a standardized questionnaire - the Short-Form 36 (SF36) - and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: The median duration of follow up was 11 (range, 1-30) years. Apart from deaths, pouch failures and research protection, data on function and QoL were obtained from 1047 (85%) of 1229 patients who had a functioning pouch at the time of the investigation. More female patients than male patients experienced urgency (56% vs 44%, P = 0.0021). The median number of bowel movements per 24 h was 7 (range, 1-23) in female patients and 6 (range, 1-20) in male patients (P < 0.001). Pad usage was more frequent among female patients than among male patients (62% vs 38%, P < 0.001). A higher incidence of major incontinence (P = 0.009) and use of pads (P = 0.01) was found among patients who had been operated on 21-30 years previously compared with those operated on 11-20 years previously. The prevalence of urgency was higher in patients who received surgery 0-10 years previously compared with 11-20 years previously (P = 0.009). The total IBDQ score was higher in male patients than in female patients (P < 0.001). Male patients scored higher in five of eight SF36 domains (P < 0.001). CONCLUSION: Female patients had more urgency, a higher frequency of defaecation and higher pad usage. This was associated with a reduced QoL. Nevertheless, RPC resulted in good function and a high degree of satisfaction in most patients.

Low complication rate after stoma closure. Consultants attended 90% of the operations.

AIM: To evaluate complications after stoma closure. METHOD: Using a retrospective review of 997 medical records, data were collected from all patients undergoing stoma closure at the Department of Surgery P, Aarhus University Hospital, Denmark, from 1996 to 2010. Patient data after Hartmann reversal and loop-ileostomy closure were compared. Data regarding the grade of the operating surgeon and assistant were extracted. RESULTS: Out of 997 patients, 700 (70.6%) had a loop-ileostomy closure and 172 (17.4%) had a Hartmann reversal. Postoperative mortality was 0.5%. Seven patients required re-operation (0.7%). Morbidity was registered in 31.9% of the patients, with 131 (13.1%) having early complications and 187 (18.8%) having late complications. Wound infection was the most frequent early complication, which occurred in 31 patients (3.1%). Only 10 patients (1%) had an anastomotic leak. Incisional hernia was the most frequent late complication, occurring in 92 patients (9.3%). A consultant attended 90% of the operations. Junior surgeons never performed stoma closure without supervision. Body mass index was significantly associated with the development of incisional hernia. Hartmann reversal was associated with higher rates of complications compared with loop-ileostomy closure. In patients with Hartmann reversal, stapled anastomosis was associated with stricture in 12 out of 95 cases (12.6%), whereas hand-sewn anastomosis was not associated with stricture (0 out of 64 patients; 0%; P < 0.05). CONCLUSION: Stoma closure is associated with low rates of leakage. A favourable case mix and high degree of consultant attendance may explain the good results.

Ileostomy revision using noncutting linear stapler.

OBJECTIVE: The study aimed to evaluate the outcome of ileostomy revision for retraction and prolapse using noncutting linear stapler. METHOD: Forty five patients undergoing a total of 94 stapled revisions between 1.1.1995 and 31.12.2005 were identified by the unique code for stomal revision. Medical records for all patients were examined. RESULTS: Thirty-five (77.8%) of the 45 patients were women. In 43 (95.6%), the indication was stomal retraction. Median follow-up was 28 months (2-122). One or more stapling procedures resulted in a normal stoma at follow-up in 18 (41.9%) of 43 patients treated for stomal retraction. When other types of repair were included, a normal stoma was achieved in 30 (69.8%) of 43 patients. Patients with a low BMI had the lowest success rate (44%), but none of the possible factors analysed for influence on success had a statistically significant impact. Two patients were treated for prolapse, and both needed other types of revision. CONCLUSIONS: Stapled ileostomy revision is easy to perform and has a low morbidity. Less than half the patients achieve a satisfactory long-term result after one or more stapling procedures. Many patients still benefit from other types of revision when stapling has failed.

Diagnostic value of self-reported symptoms in Danish outpatients referred with symptoms consistent with colorectal cancer.

OBJECTIVE: To assess the association between self-reported symptoms and a diagnosis of colorectal cancer (CRC) in symptomatic outpatients without CRC risk factors, defined by a Danish expert group. METHOD: A cross-sectional study of patients aged 40 years and older referred by general practitioners to two Danish surgical outpatient clinics for symptoms consistent with CRC during a 16-month period. CRC was diagnosed at endoscopy and through follow up. Before their first appointment, participants completed a questionnaire about symptoms. RESULTS: The study included 2172 patients. Of these, 122 were diagnosed with CRC (5.6%). Median age was 61 years (range: 40-97) and 44.0% were men. All symptoms had high (93.4-96.8%) negative predictive values for CRC. The highest positive predictive values (PPV) were found for dark rectal bleeding (PPV: 20.6%) and CRC was diagnosed in a first-degree relative over the age of 50 years (PPV: 11.2%). At multiple logistic regression analysis dark rectal blood was the most important predictor of CRC (OR: 7.4). Other predictors were age 60 years or older (OR: 3.0), change in frequency of bowel movements (OR: 2.5), CRC diagnosed in a first-degree relative over the age of 50 years (OR: 2.6), male gender (OR: 2.2) and mono-symptomatic fresh rectal blood (OR: 1.7). CONCLUSION: No self-reported symptoms presented by outpatients without CRC risk factors can be used accurately to identify patients with CRC with certainty. For clinical purposes self-reported symptoms seems thus not to be a useful accurate tool to distinguish between symptomatic outpatients with and without CRC.

Response, relapse and mucosal immune regulation after infliximab treatment in fistulating Crohn's disease.

BACKGROUND: Infliximab reduces mucosal inflammation in some, but not all, patients with Crohn's disease. AIM: To monitor clinical data and changes in mucosal cytokine levels after infliximab treatment to identify differences between responders and non-responders. METHODS: Twenty-six patients with fistulating Crohn's disease received three infliximab infusions at weeks 0, 2 and 6. Follow-up was for 1 year and included clinical examination, colonoscopy, ano-rectal ultrasound and magnetic resonance imaging. Biopsies were taken at weeks 0, 8, 26 and 52. Cell cultures were established and analysed for tumour necrosis factor-alpha, interferon-gamma and interleukin-10 levels, and related to clinical status and fistula healing. RESULTS: Eleven of 15 patients (73%) with active disease (Crohn's disease activity index > 150) obtained remission (Crohn's disease activity index < 150) at 8 weeks. In in vitro cell cultures, there was reduced tumour necrosis factor-alpha and interleukin-10 production at week 26, with the latter persistent throughout the study period. When the disease deteriorated or relapsed, there was increased interferon-gamma production in in vitro cell cultures. Fistula healing was associated with reduced production of interferon-gamma, tumour necrosis factor-alpha and interleukin-10. CONCLUSIONS: Infliximab down-regulates mucosal immune activation in Crohn's disease. Monitoring of mucosal cytokine levels after infliximab treatment by whole biopsy cultures may be useful as interleukin-10, tumour necrosis factor-alpha and interferon-gamma production are different in responders and at relapse.

Surveillance of surgical training by detailed electronic registration of logical components.

OBJECTIVE: To obtain detailed information about the degree of surgical trainee supervision and delegation of procedures in a subspecialised department. DESIGN: Operative procedures and their logical components were recorded in a database constructed in Microsoft Access. Information about operating surgeon and assistants and their grade was registered prospectively over 12 months. SUBJECTS AND METHODS: A total of 1250 intermediate or major procedures were performed by eight consultants, one staff specialist, four senior registrars, three specialist registrars, and five registrars. MAIN MEASURE: Number of components performed by surgeons in each grade and the degree of supervision and delegation. RESULTS: Eight hundred and eighty five of the operations were elective, while 365 were done as emergency procedures. Emergency procedures were far more often done by surgeons in training than by a staff surgeon, while the opposite was true for elective operations. Out of 323 elective operations done by surgeons in training, 189 were done under supervision (58.5%), while 119 out of 276 emergency operations done by surgeons in training were supervised (43.1%; p=0.0002). One hundred and twenty eight of 638 (20%) open abdominal operations were done by the most junior surgeons, and yet they closed 36% of all abdominal wounds. Although the most junior surgeons only served as operating surgeons in 39 of 334 bowel operations (12%), they constructed 24% of all stomas, and 20% of all anastomoses. Registrars and specialist registrars never constructed stomas or anastomoses without supervision. CONCLUSION: Detailed information about individual and general training and supervision was achieved by a simple registration. Significant additional information was obtained about the extent of delegation of components compared with standard registration of operative procedures.

Excessive nodular hyperplasia of Brunner glands associated with gastric hypersecretion and lipomatous atrophy of the pancreas.

The case of a 34-year-old woman complaining of diarrhoea and abdominal pain is presented. Contrast radiography and endoscopy showed multiple polypoid tumours in the second part of the duodenum. Moreover, a severe fatty infiltration of the pancreas was shown by magnetic resonance and computed tomography scans. Due to pain, pancreatoduodenectomy (Whipple operation) was performed, and subsequent histopathologic examinations showed excessive Brunner gland hyperplasia of the duodenum and severe lipomatous atrophy of the pancreas. The occurrence of these two rare conditions in one patient has not been described previously, and it is conceivable that the lipomatous atrophy and exocrine insufficiency of the pancreas may have caused a compensatory stimulation of the submucosal structures of the duodenum.

Transmitter interactions in rabbit internal anal sphincter.

The aim of the present study was to investigate the relative importance of the different putative nonadrenergic noncholinergic (NANC) mediators and their interplay with cholinergic nerves in the rabbit internal anal sphincter (IAS). IAS preparations were mounted in organ baths for recording of isometric tension. Transmural field stimulation (TMS; 5-s trains; supramaximal voltage, 140-160 V; 0.4-ms impulse duration) was applied every 2 min with frequencies varying from 0.2 to 32 Hz. TMS induced frequency-dependent relaxations that amounted to 89.3 +/- 2.2% (n = 7). N omega-nitro-L-arginine (L-NNA; 10(-7)-10(-4) M; 8 Hz) reduced relaxations and this effect was partially inhibited by preincubation with L-arginine (10(-4) M). The effect of L-NNA was attenuated by atropine preincubation. Apamin (10(-6) M) shifted the frequency-response curve to the right but left maximal relaxations in response to TMS unaffected. In the presence of L-NNA (10(-4) M) and atropine (10(-6) M), the action (area between the frequency-response curve with or without a substance) of apamin was more pronounced, but, despite the presence of both L-NNA and apamin, some relaxation still remained. The frequency-response curve (control) was significantly shifted to the right by carbachol (10(-6) M). Concentration-response experiments showed that the response to exogenous nitric oxide (NO; 10(-7)-10(-4) M) was unaffected by carbachol (10(-6) M) preincubation, whereas responses to vasoactive intestinal polypeptide (VIP) and ATP were significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of the L-arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter.

Smooth muscle specimens were taken from the oesophagogastric junction (OGJ) in patients operated on for gastrointestinal malignancies not involving the OGJ. The smooth muscle bundles of the inner, circular layer of the OGJ were richly innervated by fine nerve fibres staining positively for NADPH diaphorase. The outer longitudinal layer had a markedly lower number of NADPH-diaphorase positive nerve fibres. When the preparations were suspended in organ baths for recording of isometric tension, they developed active tension. Transmural field stimulation (TMS) induced frequency-dependent relaxations, which were abolished by NG-nitro-L-arginine (L-NNA; 10(-4) M), and were often converted to atropine-sensitive contractions. The effect of L-NNA was concentration-dependent, and the concentration-response curve for L-NNA was shifted to the right by L-arginine pre-incubation. The enantiomer NG-nitro-D-arginine (10(-4) M) also showed inhibitory actions on the responses to TMS, but significantly less than L-NNA. Relaxant responses to vasoactive intestinal polypeptide (VIP), forskolin, and sodium nitroprusside were unaffected by L-NNA pre-incubation. Exposure to a 124 mM K+ solution resulted in a biphasic relaxation of the preparations. This relaxation was not seen in preparations treated with scorpion venom (20 micrograms ml-1) or L-NNA (10(-4) M). Instead, a contractile response to 124 mM K+ solution was found. The results suggest that NANC responses to electrical stimulation of nerves in the human OGJ are mediated by a product generated from L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the L-arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins.

In human penile corpus cavernosum strips, pre-contracted by noradrenaline, electrical stimulation of nerves evoked non-adrenergic, non-cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10(-6) M, NG-nitro-L-arginine (L-NNA) 10(-7)-10(-4) M, and oxyhaemoglobin 10(-5) M, but not by methylene blue (MB) 10(-5) M. Acetylcholine-induced relaxations were also inhibited by L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M, but were unaffected by pyrogallol 10(-4) M, MB 10(-5) M, and tetrodotoxin 10(-6) M. MB 5 x 10(-4)-10(-4) M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10(-7)-10(-4) M and sodium nitroprusside 10(-9)-10(-4) M caused concentration-dependent relaxations. The NO-induced relaxations were inhibited by oxyhaemoglobin 10(-5) M, and the concentration-response curve for sodium nitroprusside was shifted to the right by MB 10(-5) M. The response to sodium nitroprusside was unaffected by L-NNA 10(-4) M, oxyhaemoglobin 10(-5) M, and pyrogallol 10(-4) M. In circumflex veins, pre-contracted by noradrenaline, no NANC-mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium-dependent relaxations, which were insensitive to L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M. NO and sodium nitroprusside caused concentration-dependent relaxations; the concentration-response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10(-5) M. Removal of the endothelium left the NO- and sodium nitroprusside-induced relaxations unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

[The role of nitrogen oxide synthesis for relaxation of the internal anal sphincter]. / Betydningen af nitrogenoxidsyntese for relaksation af den interne anale sphincter.

The purpose of the present study was to examine the role of the L-arginine-nitric-oxide pathway in neurogenic relaxation of the internal anal sphincter. Muscle strips representing the internal anal sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometetric tension. N omega-nitro-L-arginine, an agent known to inhibit the L-arginine-nitric oxide pathway, concentration-dependently reduced relaxation induced by transmural field stimulation. At the highest concentration of N omega-nitro-L-arginine (10(-4) M), no relaxation was evoked at any frequency tested (0.5-40 Hz). The inhibitory response to exogenous VIP was unaffected by N omega-nitro-L-arginine pretreatment, indicating that VIP relaxation does not utilize the L-argining-nitric oxide pathway. It is concluded that the non-adrenergic, non-cholinergic innervation of the internal anal sphincter involves an inhibitory substance generated from the L-arginine--No pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.

Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter.

Circular muscle strips from opossum lower esophageal sphincter were suspended in organ baths for measurement of isometric tension. Nonadrenergic noncholinergic (NANC) inhibitory nerves were stimulated by means of transmural field stimulation. This induced frequency-dependent relaxations of the muscle strips. Methylene blue (3 x 10(-6) M; inhibits guanylate cyclase) and pyrogallol (10(-4) M; generates superoxide anions) had no influence on relaxations, whereas oxyhemoglobin [10(-5) M; binds nitric oxide (NO) and other nitroso compounds extracellularly] inhibited relaxations at all frequencies. NO concentration dependently relaxed the muscle strips. Pyrogallol (10(-4) M) and methylene blue (3 x 10(-6) M) inhibited and oxyhemoglobin (10(-5) M) nearly abolished relaxation induced by NO. S-nitroso-L-cysteine caused concentration-dependent relaxations of the muscle strips, which were inhibited by pyrogallol (10(-4) M), whereas methylene blue (3 x 10(-6) M) augmented the action of S-nitroso-L-cysteine. Methylene blue (3 x 10(-6) M) had no influence on the concentration-dependent relaxations caused by sodium nitroprusside (SNP). Oxyhemoglobin (10(-5) M), and to a lesser extent pyrogallol (10(-4) M), both inhibited the effects of SNP. The action profiles for S-nitroso-L-cysteine, NO, and SNP differed from the action profile for NANC nerve-mediated response. Although pyrogallol inhibited the effects of SNP, the action profile generally resembled the action profile for NANC responses more closely than did the profiles for S-nitroso-L-cysteine or NO. In conclusion, of the nitroso compounds studied, SNP most closely resembled the response to NANC nerve stimulation. Neither NO nor S-nitroso-L-cysteine individually mimicked the NANC response.

Involvement of the L-arginine-nitric oxide pathway in internal anal sphincter relaxation.

The purpose of this study was to examine the role of the L-arginine-nitric oxide pathway in neurogenic relaxation of the internal anal sphincter. Muscle strips representing the internal anal sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometric tension. N omega-nitro-L-arginine, an agent known to inhibit the L-arginine-nitric oxide pathway, concentration-dependently reduced relaxations induced by transmural field stimulation. At the highest concentration of N omega-nitro-L-arginine (10(-4) mol/L), no relaxation was evoked at any frequency tested (0.5-40 Hz). The inhibitory response to exogenous vasoactive intestinal polypeptide was unaffected by N omega-nitro-L-arginine pretreatment, indicating that vasoactive intestinal polypeptide relaxation does not use the L-arginine-nitric oxide pathway. In addition, responses to forskolin and sodium nitroprusside were not influenced by N omega-nitro-L-arginine preincubation, suggesting that the effect observed was not caused by a direct influence on the adenylate or the guanylate cyclases. It is concluded that the nonadrenergic, noncholinergic innervation of the internal anal sphincter involves an inhibitory substance generated from the L-arginine-nitric oxide pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.

Motility regulating effects of galanin on smooth muscle of porcine ileum.

We studied the effect of synthetic porcine galanin on circular and longitudinal oriented strips of pig ileal muscle. Galanin 10(-11)-10(-6) M had no effect on resting tension in the two layers. In circular muscle precontracted with carbachol 10(-6) M, galanin dose-dependently inhibited the amplitude of contractions to a maximum of 33 +/- 8% at 10(-6) M. In longitudinal muscle the amplitude of contractions induced by carbachol 10(-7) M or transmural field stimulation increased after addition of galanin 10(-9)-10(-7) M to a maximum of 21 +/- 6%, while at higher concentrations inhibition occurred. Maximal inhibition was 36 +/- 14% at galanin 10(-6) M. Tetrodotoxin did not influence the effects of galanin in the preparations. The results indicate that in the homologous species galanin inhibits the circular muscle layer, possibly by a direct action on the smooth muscle. In the longitudinal muscle the effect of galanin is apparently excitatory. The inhibition observed with high concentration of galanin could be due to tachyphylaxis and desensitization. Alternatively, an additional population of low affinity, inhibitory receptors may exist.

Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter.

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC) inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.

[Treatment of esophageal achalasia]. / Behandling af achalasia esophagi.

Achalasia is a motor disease of the oesophagus which can be treated surgically (myotomy), medically or by dilatation. After myotomy satisfactory results are obtained in 84%-95% of the patients. Unacceptable results are due primarily to gastro-oesophageal reflux, inadequate or healed myotomy. Dilatation provide good results in about 70% but generally repeated dilatation is required. The remaining 30% can usually be treated surgically. Dilatation is complicated by perforation in about 3% of the patients, but reflux is not as frequent as after myotomy. At present medical treatment is only indicated temporarily prior to dilatation or surgery. Surgical treatment is recommended for patients with contemporary delayed gastric emptying, hiatal hernia, vigorous achalasia, epiphrenic diverticula and for children with achalasia. For the remaining patients both methods can be used but after 2-3 dilatations myotomy is recommended.

The actions of some beta-receptor agonists and xanthines on isolated muscle strips from the human oesophago-gastric junction.

Isolated preparations from the circular muscle layer of the human oesophago-gastric junction were mounted in organ baths and isometric tension recorded. During an equilibration period, active resting tension developed suggesting that the preparations were representing the lower oesophageal sphincter. Active tension was abolished by exposing the preparations to Ca(++)-free medium. The two xanthines theophylline and enprofylline almost equipotently relaxed the preparations in a concentration-dependent manner (10(-7)-10(-3) M). Within therapeutic concentrations, theophylline inhibited active resting tension by 30-60%, while enprofylline lowered tension by less than 20%. Inhibitory actions of adenosine were demonstrated, and this suggests that adenosine antagonism is not the mechanism of action for xanthines in the oesophagus. Non-selective beta-receptor stimulation with isoprenaline inhibited active tension by 70% (10(-7) M), while beta 2-receptor stimulation with terbutaline inhibited tension by 47% (10(-5) M). Dobutamine, believed to preferentially stimulate beta 1-receptors, inhibited active tension in a concentration-dependent manner (10(-7)-10(-4) M). Metoprolol (10(-6) M), a selective beta 1-receptor antagonist, shifted the concentration-response curve for isoprenaline to the right, but left the maximal response unchanged. It is concluded that xanthines and beta-receptor agonists have inhibitory actions on circular muscle from the human oesophagogastric junction. The experimental data suggest the presence of beta 1- as well as beta 2-receptors, both mediating inhibition of active resting tension.

Effects of transmural field stimulation in isolated muscle strips from human esophagus.

Smooth muscle strips representing longitudinal and circular muscle layers of the esophagogastric junction (EGJ) and esophageal body (EB) of the human esophagus were prepared. The strips were mounted in organ baths and isometric tension was recorded. Square wave stimulation was applied through platinum electrodes. Only responses abolished by tetrodotoxin (TTX) were considered neurogenic. Strips taken from longitudinal muscle layers of the EB and EGJ contracted during field stimulation. The responses evoked were abolished by atropine, and optimal frequency of stimulation was 40 Hz. In strips taken from the circular muscle layer of the EB, a contraction occurred after cessation of the stimulus. Atropine inhibited 90% of this response; the optimal stimulation frequency was 40 Hz. When a tone was induced in strips from this layer, a TTX-sensitive relaxation was seen during field stimulation. During stimulation of strips from the EGJ circular muscle layer, which was the only preparation developing spontaneous active tone, a relaxation was seen. A small contraction followed after termination of the stimulus. The relaxation, which was nonadrenergic, noncholinergic, reached maximum at 10 Hz. Atropine inhibited 40% of the contraction. The results suggest that in the longitudinal muscle layer of the human lower esophagus field stimulation causes postganglionic nerves to release transmitter(s) acting on muscarinic receptors. The responses of circular muscle layers seem to be mediated through release of at least two transmitters.