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Background: Crohn's disease (CD) is a multifactorial syndrome with genetic and environmental contributions. Mycobacterium avium subspecies paratuberculosis (MAP) has been frequently isolated from mucosal tissues of patients with CD but the cellular immune response to this bacterium has been poorly described. Our aim was to examine the influence of MAP on T-cell proliferation and cytokine responses in patients with inflammatory bowel disease (IBD)., Methods: Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph node cells (MLNCs) were obtained from IBD patients and non-IBD controls. PBMC T-cell proliferation in response to MAP was determined using CFSE labeling and flow cytometry. The specificity of cytokine responses to MAP was controlled by parallel exposure to Listeria monocytogenes (LM) or Salmonella typhimurium (ST)., Results: Coincubation of PBMCs with MAP induced significantly more T-cell proliferation (P < 0.0001) in PBMCs isolated from CD patients compared to PBMCs obtained from ulcerative colitis (UC) patients or healthy volunteers. In addition, PBMCs from CD patients secreted significantly higher (P < 0.05) levels of tumor necrosis factor-alpha (TNF-alpha; 2302 +/- 230 pg/mL) and interleukin (IL)-10 (299 +/- 48 pg/mL) in response to MAP compared to UC patients (TNF-alpha: 1219 +/- 411 pg/mL; IL-10: 125 +/- 19 pg/mL) and controls (TNF-alpha: 1447 +/- 173 pg/mL; IL-10: 127 +/- 12 pg/mL). No difference in cytokine responses was observed in response to LM or ST. MLNCs from both CD and UC patients secreted significantly more TNF-alpha and IL-8 in response to MAP compared to MLNCs from non-IBD control patients., Conclusions: Increased proliferation of T cells and an altered cytokine response suggest that prior exposure to MAP and engagement of the immune system is common in patients with CD. This does not imply causation but does support further examination of this bacterium as an environmental modifying factor.

Background: Oncological procedures may have better outcomes if performed by high-volume providers., Methods: A review of the English language literature incorporating searches of the Medline, Embase and Cochrane collaboration databases was performed. Studies were included if they involved a patient cohort from 1984 onwards, were community or population based, and assessed health outcome as a dependent variable and volume as an independent variable. The studies were also scored quantifiably to assess generalizability with respect to any observed volume-outcome relationship and analysed according to organ system; numbers needed to treat were estimated where possible., Results: Sixty-eight relevant studies were identified and a total of 41 were included, of which 13 were based on clinical data. All showed either an inverse relationship, of variable magnitude, between provider volume and mortality, or no volume-outcome effect. All but two clinical reports revealed a statistically significant positive relationship between volume and outcome; none demonstrated the opposite., Conclusion: High-volume providers have a significantly better outcome for complex cancer surgery, specifically for pancreatectomy, oesphagectomy, gastrectomy and rectal resection.

Background: Acute hepatobiliary pathology is a common general surgical emergency referral. Diagnosis requires imaging of the biliary tree by ultrasonography. The accuracy and impact of surgeon-performed ultrasonography (SUS) on the diagnosis of emergent hepatobiliary pathology was examined., Methods: A prospective study, over a 6-month period, enrolled all patients with symptoms or signs of acute hepatobiliary pathology. Patients provided informed consent and underwent both SUS and standard radiology-performed ultrasonography (RUS). SUS was performed using a 2-5-MHz broadband portable ultrasound probe by two surgeons trained in ultrasonography, and RUS using a 2-5-MHz fixed unit. SUS results were correlated with those of RUS and pathological diagnoses., Results: Fifty-three consecutive patients underwent 106 ultrasonographic investigations. SUS agreed with RUS in 50 (94.3 per cent) of 53 patients. SUS accurately detected cholelithiasis in all but two cases and no patient was inaccurately diagnosed as having cholelithiasis at SUS (95.2 per cent sensitivity and 100 per cent specificity). As an overall complementary diagnostic tool SUS provided the correct diagnosis in 96.2 per cent of patients. Time to scan was significantly shorter following SUS (3.1 versus 12.0 h, P < 0.05)., Conclusion: SUS provides a rapid and accurate diagnosis of emergency hepatobiliary pathology and may contribute to the emergency management of hepatobiliary disease.

Background: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown., Methods: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly., Results: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016)., Conclusion: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

Background: Hypertonic saline (HTS) has been noted previously to reduce neutrophil activation. The aim of this study was to elucidate the effect of hypertonic resuscitation on the development of end-organ damage in an animal model of pancreatitis., Methods: Pancreatitis was induced in Sprague-Dawley rats by intraperitoneal injection of 20 per cent L-arginine. Animals were randomized into four groups (each n = 8): controls; pancreatitis without intervention; pancreatitis plus intravenous resuscitation with normal saline (0.9 per cent sodium chloride 2 ml/kg) at 24 and 48 h; or HTS (7.5 per cent sodium chloride 2 ml/kg) at these time points. Pulmonary endothelial leakage was assessed by measurement of lung wet : dry ratios, bronchoalveolar lavage protein and myeloperoxidase activity., Results: Animals that received HTS showed less pancreatic damage than those resuscitated with normal saline (1.0 versus 3.0; P = 0.04). Lung injury scores were also significantly diminished in the HTS group (1.0 versus 3.5; P = 0.03). Pulmonary neutrophil sequestration (myeloperoxidase activity 1.80 units/g) and increased endothelial permeability (bronchoalveolar lavage protein content 1287 microgram/ml) were evident in animals resuscitated with normal saline compared with HTS (1.22 units/g and 277 microgram/ml respectively; P < 0.02)., Conclusion: HTS resuscitation results in a significant attenuation of end-organ injury following a systemic inflammatory response to severe pancreatitis.

Background: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages., Methods: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression., Results: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01)., Conclusion: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

Peroperative antegrade colonic lavage is often performed before primary anastomosis in emergency colonic surgery. The influence of colonic lavage on bacterial translocation from the obstructed colon was determined. Forty female Wistar rats were studied in four groups: (1) control; (2) non-obstructed with lavage; (3) obstructed; and (4) obstructed with lavage. Ligature obstruction of the rectum was performed in groups 3 and 4. Some 4 days later 35S-radiolabelled Escherichia coli was inoculated into the colon of all animals. Groups 2 and 4 underwent colonic lavage. Lavage in the group 4 animals with left-sided colonic obstruction significantly increased the levels of E. coli in regional nodes, liver, spleen, lung, kidney and blood (as assessed by organ culture and scintillation counting) compared with those in groups 1, 2 and 3 (P < 0.05). These results suggest that peroperative lavage of the obstructed colon significantly increases the level of bacterial translocation.

An automatic purse-string device was compared with the traditional hand-sewn method in stapled oesophageal anastomosis. Fifteen greyhound dogs underwent distal oesophagectomy with stapled gastro-oesophageal anastomosis; a purse-string suture was used to draw the distal oesophagus around the stapling device. The animals were randomized into group 1 (n = 8), in which the automatic device was used, and group 2 (n = 7), in which the oesophageal purse string was hand-sewn. The automatic device failed to incorporate the oesophageal mucosa and submucosa reliably into the anastomotic staple line. There were five defective anastomoses in group 1 and none in group 2 (P = 0.037). Anastomotic bursting pressures were significantly reduced in group 1 compared with group 2 (median (range) 47 (22-110) versus 82 (68-88) mmHg, P = 0.032). Within group 1, a significant difference in bursting pressure existed between complete anastomoses and those in which the mucosa was not fully incorporated (median (range) 75 (60-110) versus 39 (22-50) mmHg, P = 0.037). Median (range) breaking strengths where anastomoses were incomplete were lower than where all layers were incorporated (1420 (1250-2220) versus 1990 (1590-2475) g/cm, P = 0.009). This study questions the safety of the automatic purse-string device for oesophageal anastomosis when used in accordance with present recommendations. Further evaluation and possibly modification of either the instrument design or the methods recommended by the manufacturer for its use are warranted.

A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality.

Marlex (polypropylene) mesh was used to replace the abdominal wall in massive incisional herniation in 50 patients. Seventeen unsuccessful attempts at primary repair had previously been made on nine patients. Patient follow-up ranged from 6 to 120 months (mean = 45 months). There was minor hernia recurrence in four (8 per cent) patients. In each instance it was due to partial detachment of the peripheral fixation of the patch. Complications were: wound infection, four (8 per cent); wound seroma, two (4 per cent); wound haematoma, one (2 per cent); and wound sinus, six (12 per cent). Complications did not necessitate removal of the patch in any case. Inadequate peripheral attachment of the patch has been the only cause of hernia recurrence and should be avoidable.

Anastomotic integrity after a low colorectal EEA-stapled anastomosis performed for cancer was assessed by a contrast, enema in 30 patients. There was an overall 20 per cent radiological anastomotic leakage rate. The leakage rate in the last 10 cases, however, was zero. This indicates that increased familiarity with the technique results in fewer complications.

Minor difficulties with continence may occur after low anterior resection. Intraoperative injury to the internal anal sphincter or its nerve supply may contribute to this. To study the effect of low anterior resection on the anal sphincter mechanism, anal manometry was performed on 20 patients before and 10 days after resection. Fifteen patients were studied again 6 months after operation. Resting, maximum squeeze and squeeze increment pressures were recorded. Intraoperative manometry (n = 11) and presacral nerve stimulation (n = 6) were performed to determine whether peroperative injury to the internal anal sphincter had occurred. Resting and maximum squeeze anal canal pressures were reduced by low anterior resection, and did not recover. The squeeze pressure increment did not change. Division of the inferior mesenteric artery, full mobilization of the rectum and mesorectum, and rectal transection did not affect resting anal pressure, which was reduced after EEA anastomosis (mean (s.e.m.) before, 40(5) mmHg; after, 27(4) mmHg; P less than 0.05, n = 5). Presacral nerve stimulation produced relaxation of the internal sphincter. Anal sphincter pressures are reduced after low anterior resection. The external anal sphincter and the nerve supply to the internal anal sphincter appear intact. A direct injury to the internal sphincter is postulated.

The technique of pullthrough resection with delayed anastomosis for carcinoma of the rectum as performed at the Cleveland Clinic is described. A series of 84 cases of rectal cancer treated in this way is reported. The average tumour diameter was 4.5 cm, the average margin of resection was 4.1 cm and the average distance of the tumour from the anus was 7.6 cm. The incidence of necrosis of the pullthrough was 1.2 per cent. The overall 5-year survival was 63 per cent with 100 per cent, 57 per cent and 53 per cent for Dukes' A, B and C tumours respectively. The quality of bowel function following surgery is described in detail. It is felt that this procedure has an important place in sphincter conservation in carcinoma of the middle third of the rectum.

In 126 consecutive patients operated on for carcinoma of the lower two-thirds of the rectum, a consistent policy of sphincter preservation resulted in 100 (79 per cent) having anterior resection and 22 (17 per cent) abdominoperineal resection. Perioperative complications in the anterior resection group were: death (two patients), clinical leakage (three patients), pulmonary embolism (five patients), pelvic haematoma (one patient), small bowel obstruction (one patient) and wound sepsis (six patients). Of 55 patients who had a potentially curative anterior resection with follow-up of at least 2 years, one developed local recurrence. Five per cent of patients had significant continence problems. Low anterior resection for carcinoma is associated with low perioperative morbidity, satisfactory functional results and acceptable local recurrence rates.