Acute large bowel obstruction can be the result of mechanical causes (such as colorectal cancer) or motility disturbances, the latter being termed colonic pseudo-obstruction. Whatever the aetiology, the pathophysiology of large bowel... more
Acute large bowel obstruction can be the result of mechanical causes (such as colorectal cancer) or motility disturbances, the latter being termed colonic pseudo-obstruction. Whatever the aetiology, the pathophysiology of large bowel obstruction has clinical significance. Changes in motility augmented by increased colonic blood flow may play a role in dissemination of tumour cells and/or bacteria. Intravascular fluid depletion, especially shortly after intestinal decompression, has important haemodynamic implications. The diagnosis is often confirmed on plain abdominal X-ray, but water-soluble contrast studies are important in distinguishing a mechanical obstruction (which almost always requires an operation) from a pseudo-obstruction (which can usually be managed without surgery). Mortality and morbidity may be reduced by optimization of the patient's condition both before and after the operation using intensive care facilities and by careful timing of surgery. The surgical management of malignant large bowel obstruction is best directed by a senior surgeon. For tumours up to and including the splenic flexure, an extended right hemicolectomy is advisable since it offers adequate removal of the tumour and allows an immediate safe ileocolic anastomosis. More distal tumours should be resected if possible, and there is much to recommend on-table irrigation and immediate anastomosis, although a colostomy with a mucous fistula or Hartmann's procedure still have a place. Endoscopic diagnosis and decompression enables definitive surgery to be undertaken electively and several techniques are being evaluated. Non-operative reduction of sigmoid volvulus by rigid or flexible endoscopy is achieved with high success rates, but is not recommended for caecal volvulus. Resection is usually necessary in both to prevent recurrence. Mortality of colonic volvulus is closely related to bowel viability. Uncomplicated colonic pseudo-obstruction may be managed medically or by endoscopic decompression. It often occurs in association with systemic medical conditions, which need to be treated vigorously. Surgery is indicated if there are signs of impending or frank perforation, or if non-operative measures fail.
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Patients with familial adenomatous polyposis (FAP) are at high risk for duodenal tumors, the distribution of which suggests that bile is important in their development. Studies of the bile of FAP patients suggest that it contains an... more
Patients with familial adenomatous polyposis (FAP) are at high risk for duodenal tumors, the distribution of which suggests that bile is important in their development. Studies of the bile of FAP patients suggest that it contains an excess of active carcinogens. Defective hepatic metabolism of carcinogens might account for these findings. The isozyme glutathione S-transferase mu (GST-mu) plays a major role in the hepatic metabolism of carcinogens. Peripheral blood GST-mu status reflects hepatic GST-mu status. The concentration of GST-mu was therefore measured by enzyme-linked immunosorbent assay of heparinized peripheral blood samples taken from 31 unrelated patients with FAP and from 38 unrelated control patients. FAP and control patients were matched for age, sex, diet, and smoking status. The median GST-mu concentration (micrograms per milliliter) was 0.5 (interquartile range, 0 to 11.6) in the FAP group and 8.85 (0.9 to 29.4, p = 0.0013) in the control group. Of the 31 FAP patie...
Research Interests: Gastroenterology, Adolescent, Medicine, Humans, Internal Medicine, and 14 moreFemale, Male, Glutathione, Glutathione s-transferase, Phenotype, Aged, Middle Aged, Adult, Public health systems and services research, Isoenzymes, Adenomatous Polyposis-coli, Glutathione Transferase, Carcinogen, and Familial adenomatous polyposis
Perioperative blood transfusion has been reported to adversely affect survival in cancer patients, but the evidence is inconclusive and may be an epiphenomenon. From the Large Bowel Cancer Project, 961 patients who underwent curative... more
Perioperative blood transfusion has been reported to adversely affect survival in cancer patients, but the evidence is inconclusive and may be an epiphenomenon. From the Large Bowel Cancer Project, 961 patients who underwent curative resection and left hospital alive have been reviewed to compare the effect of perioperative blood transfusion on outcome; 591 patients (61%) had been given a blood transfusion while 370 (39%) had not been transfused. Some clinical variables were equally distributed between the two groups; ie age, sex, obstruction, perforation, tumour differentiation. Three other variables known to influence patient prognosis were not equally distributed, ie tumour site, Dukes' stage and tumour mobility. Patients with tumours of the rectum and rectosigmoid, with Dukes' stage C lesions and with some degree of tumour fixation were more likely to have received blood transfusions. Using the logrank method of multivariate analysis to allow for differences in distribut...
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ABSTRACT Fragestellung und Hintergrund Die optimale Behandlungsmethode bei hohen/komplexen Analfisteln ist unklar. Hier wurden die Ergebnisse eines Operateurs bei proximalen Fisteln über einen Zeitraum von 10 Jahren untersucht. Patienten... more
ABSTRACT Fragestellung und Hintergrund Die optimale Behandlungsmethode bei hohen/komplexen Analfisteln ist unklar. Hier wurden die Ergebnisse eines Operateurs bei proximalen Fisteln über einen Zeitraum von 10 Jahren untersucht. Patienten und Methodik Demographische und Behandlungsdaten sowie eine Fistelanatomie wurden für alle Patienten aufgezeichnet, die sich einem Eingriff wegen Analfisteln unterzogen. Es wurden die Ergebnisse aller Patienten dokumentiert, die mindestens 4 Wochen nachverfolgt worden waren. Ergebnisse Insgesamt 180 Patienten wurden untersucht. Ergebnisdaten waren für 52 niedrige und 84 hohe Fisteln verfügbar. Bei 50 niedrigen und 48 hohen Fisteln wurde eine Fistulotomie durchgeführt mit Heilungsraten von 98 bzw. 96%. Bei 2 Patienten mit proximalen Fisteln traten Rezidive auf. Die Symptome einer Kontinenzstörung waren nach Fistulotomie bei niedrigen und hohen Fisteln vergleichbar. Die Behandlung einer proximalen Fistel mittels Fadendrainage hatte gegenüber einer Fistulotomie eine geringere Rate unbeabsichtigter Inkontinenz für Flatus, aber eine ähnliche Rate von minimalem Stuhlschmieren. Schlussfolgerung Die Fistulotomie niedriger und hoher Analfisteln ist effektiv und mit einer vergleichbaren, vorhersagbaren Rate geringer Sphinkterstörungen assoziiert, wobei ein Drittel bis ein Viertel der Patienten von geringem Verlust von Flatus und Mukus betroffen sind. Patienten mit proximalen Fisteln können geheilt werden. Im Zweifelsfall sollte jedoch vor dem definitiven Eingriff eine zweite Meinung von einem Expertenzentrum eingeholt werden.
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Adrenal incidentaloma is often diagnosed in patients with familial adenomatous polyposis, because they frequently undergo abdominal imaging and have a raised incidence of adrenal incidentaloma. This study investigates the natural history... more
Adrenal incidentaloma is often diagnosed in patients with familial adenomatous polyposis, because they frequently undergo abdominal imaging and have a raised incidence of adrenal incidentaloma. This study investigates the natural history of adrenal incidentaloma in familial adenomatous polyposis, and suggests a schema for management. An original cohort of 14 familial adenomatous polyposis patients with adrenal incidentaloma, identified prospectively 12 years ago, was followed up clinically and radiologically. A further group of 16 patients was also identified. All had lesions >1 cm. For both cohorts, characteristics of patients (genotype, age at diagnosis, concomitant diagnoses) and incidentaloma (size, laterality, rate of growth, outcome) are described. Overall, 3 of 30 patients underwent adrenalectomy; one patient had pheochromocytoma and another had an adenoma of borderline malignancy. A further three lesions were radiologically suspicious for malignancy at the time of diagnosis; one was in a patient who was unfit for surgery but died of nonadrenal causes after nine years. None of the lesions radiologically benign at diagnosis showed an aggressive course, but one patient required referral for surgery after 12 years because of a slow increase in size of the lesion. There were no associations with genotype. Familial adenomatous polyposis-associated adrenal incidentaloma may warrant long-term follow-up. Although the natural history is similar to lesions occurring sporadically, these patients have concomitant familial adenomatous polyposis-associated manifestations under radiologic surveillance. In this rare condition, development of a robust protocol will require evidence from worldwide patient cohorts. However, a tailored schema is suggested as a consistent basis for future modification.
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Familial adenomatous polyposis (FAP) is associated with an almost 100% chance of colorectal cancer by the age of 50 years. Surgery is the only prophylaxis. The study compared the outcome of prophylactic laparoscopic colectomy and... more
Familial adenomatous polyposis (FAP) is associated with an almost 100% chance of colorectal cancer by the age of 50 years. Surgery is the only prophylaxis. The study compared the outcome of prophylactic laparoscopic colectomy and ileorectal anastomosis (IRA) with conventional open surgery. A case-control study was carried out including all cases of proven FAP undergoing prophylactic laparoscopic colectomy with IRA between 1 April 2006 and 31 March 2008 using a standardized technique within an enhanced recovery programme (ERAS). All data were collected prospectively. Controls were identified retrospectively from patients who underwent open prophylactic IRA before 31 March 2008 and were matched for age, gender, BMI and ASA. Outcomes included duration of surgery, complications, length of stay, readmission and mortality. During the study period 25 patients underwent laparoscopic IRA. The median operating time was longer in the laparoscopic group (235 vs 180 mins, P < 0.0001) but the median hospital stay was shorter (6 vs 9 days, P = 0.002). Overall there were fewer complications in the laparoscopic group (20%vs 40%, P = 0.3). Laparoscopic prophylactic colectomy with IRA in FAP is safe and feasible, and combined with ERAS leads to accelerated recovery and possibly fewer complications than open surgery. FAP patients undergoing prophylactic IRA should be offered laparoscopic surgery.
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To the Editor: Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), a dominantly inherited predisposition to colorectal cancer (Groden et al. 1991, Kinzler et al. 1991))... more
To the Editor: Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), a dominantly inherited predisposition to colorectal cancer (Groden et al. 1991, Kinzler et al. 1991)) Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is one of the most consistent extra-colonic manifestations associated with FAP (Blair & Trempe 1980, Lewis et al. 1984, Morton et al. 1992). Of the four types of CHRPE lesion described (Berk et al. 1988), only the oval pigmented lesions surrounded by a halo (the type A lesions) are thought to be unique to FAP patients (Polkinghome et al. 1990). These retinal lesions are detected noninvasively by examination of the fundus of the eye. About one quarter of families with FAP do not express CHRPE at all (Romania et al. 1989, Baker et al. 1988, Lyons et al. 1988), although there is some intrafamilial variability in CHRPE expression in affected individuals (Hodgson et al. 1994). Following the characterisation of the APC gene, mutation analysis has become the method of choice, where available, in determining the risk of developing FAP in pre-symptomatic patients. This mutation analysis has enabled researchers to search for genotype-phenotype correlations, including the association between the position of mutation and the presence of diagnostic CHRPE (Olschwang et al. 1993, Wallis et al. 1994, Caspari et al. 1995). This published literature suggests that FAP patients with a mutation between codons 136 (exon 3) and 302 (exon 8) or between codons 1445 and 1578 (exon 15, region h to i) of the APC gene express a CHRPE negative phenotype. Alternatively, those patients
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Cyclooxygenase-2 is a valid target for cancer prevention and treatment. This has been shown in preclinical and clinical cancer prevention studies by using a cyclooxygenase-2 inhibitor, celecoxib. When used in a randomized cancer... more
Cyclooxygenase-2 is a valid target for cancer prevention and treatment. This has been shown in preclinical and clinical cancer prevention studies by using a cyclooxygenase-2 inhibitor, celecoxib. When used in a randomized cancer prevention clinical trial on patients with the inherited autosomal dominant condition, familial adenomatous polyposis, celecoxib proved efficacious. However, a remarkable heterogeneity in patients’ responses to the chemopreventive effects of celecoxib was observed. Proteomic profiling of sera from these patients identified several markers, the expression of which was specifically modulated after treatment with celecoxib. A decision tree algorithm identified classifiers for response to celecoxib with relatively high sensitivity but moderate to low specificity. In particular, a spectral feature at m/z 16,961.4 was identified as a strong discriminator between response and nonresponse to celecoxib at the highest dose.
Research Interests: Clinical Trial, Mass Spectrometry, Cancer, Cancer Prevention, Medicine, and 14 moreColorectal cancer, Humans, Decision Tree, Adenomatous Polyposis-coli, Pyrazoles, Medicine and Health Sciences, Pharmacy and Pharmaceutical Sciences, High Sensitivity, Proteome, Blood Proteins, Celecoxib, Randomized Controlled Trials as Topic, Familial adenomatous polyposis, and Sulfonamides
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Sutureless intestinal anastomoses can be achieved either by compression, where two inverted rings of bowel are compressed by a hollow circular device that subsequently sloughs away and is passed anally, or by the use of tissue glues or... more
Sutureless intestinal anastomoses can be achieved either by compression, where two inverted rings of bowel are compressed by a hollow circular device that subsequently sloughs away and is passed anally, or by the use of tissue glues or laser welding. Compression devices used clinically with success are the Valtrac® biofragmentable anastomotic ring, the polypropylene rings described by Rosati and the AKA guns. Glued anastomoses have only been used in animals and seem to be unsafe. However, laser-welded intestinal anastomoses appear highly promising in experimental studies and further development of this technique is warranted.
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Duodenal adenomas occur almost inevitably in patients with familial adenomatous polyposis (FAP) whereas gastric adenomas are rare. FAP patients are also at high risk of duodenal cancer. Within the duodenum, adenomas cluster around the... more
Duodenal adenomas occur almost inevitably in patients with familial adenomatous polyposis (FAP) whereas gastric adenomas are rare. FAP patients are also at high risk of duodenal cancer. Within the duodenum, adenomas cluster around the ampulla of Vater, as do the majority of duodenal cancers, suggesting that bile plays a role in tumour development. We therefore tested duodenal bile from 29 postcolectomy FAP patients (27 of whom had duodenal adenomas) and 24 non-FAP patients for mutagenicity, using techniques that detect point mutations in bacteria. Results which appeared to show that FAP bile was more mutagenic than control bile could be accounted for by a feeding effect, elimination of which also eliminated ‘mutagenicity’. Under the conditions of our assays we conclude that if bile is an important factor in genesis of duodenal tumours, it does not act by inducing point mutation.
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Research Interests: Gastroenterology, Adolescent, Medicine, Family history, Multivariate Analysis, and 15 moreHumans, Internal Medicine, Female, Male, Clinical Sciences, Middle Aged, Adult, Retrospective Studies, Age Factors, Abdominal Surgery, Proportional Hazards Models, Predictive value of tests, Colectomy, Cohort Studies, and Familial adenomatous polyposis
Research Interests: Algorithms, Medicine, Humans, Female, Male, and 14 moreSepsis, Young Adult, Registries, Clinical Sciences, Anti-Bacterial Agents, Adult, Drainage, Retrospective Studies, Peritonitis, Adenomatous Polyposis-coli, X ray Computed Tomography, Cohort Studies, Combined Modality Therapy, and Familial adenomatous polyposis
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1. Tozer PJ, Burling D, Gupta A, et al. Review article: medical, surgical and radiological management of perianal Crohn’s fistulas. Aliment Pharmacol Ther 2011; 33: 5–22. 2. Fukuda A, Nakase H, Seno H, et al. Refractory enterovesical and... more
1. Tozer PJ, Burling D, Gupta A, et al. Review article: medical, surgical and radiological management of perianal Crohn’s fistulas. Aliment Pharmacol Ther 2011; 33: 5–22. 2. Fukuda A, Nakase H, Seno H, et al. Refractory enterovesical and duodenocolic fistulas in Crohn’s disease successfully managed with tacrolimus. J Gastroenterol 2005; 40: 433–5. 3. Tamaki H, Nakase H, Matsuura M, et al. The effect of tacrolimus (FK-506) on Japanese patients with refractory Crohn’s disease. J Gastroenterol 2008; 43: 774–9. 4. Uza N, Nakase H, Ueno S, et al. The effect of medical treatment on patients with fistulizing Crohn’s disease: a retrospective study. Intern Med 2008; 47: 193–9. 5. Sandborn WJ, Present DH, Isaacs KL, et al. Tacrolimus for the treatment of fistulas in patients with Crohn’s disease: a randomized, placebo-controlled trial. Gastroenterology 2003; 125: 380–8. 6. Gonzalez-Lama Y, Abreu L, Vera MI, et al. Long term oral tacrolimus therapy in refractory to inflximab fistulizing Crohn’s disease: a pilot study. Inflammatory Bowel Dis 2005; 11: 8–15. 7. Yoshino T, Nakase H, Honzawa Y, et al. Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis. Inflamm Bowel Dis 2010; 16: 2022–33. 8. Wang K, Li M, Hakonarson H. Analysing biological pathways in genome-wide association studies. Nat Rev Genet 2010; 11: 843–54.
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An experiment is presented which shows that colonic primary tumours cluster around a previously constructed anastomosis and that the choice of suture materials (but not the technique of their insertion) can influence this. In a rodent... more
An experiment is presented which shows that colonic primary tumours cluster around a previously constructed anastomosis and that the choice of suture materials (but not the technique of their insertion) can influence this. In a rodent model where dimethylhydrazine was administered 2 months after surgery, anastomotic tumours were most often seen when wire sutures — as used in the staples of anastomotic stapling guns — had been employed (10 out of 16 large bowel tumours were anastomotic as compared with 2 of 12 in a silk sutured group, P = 0·019). An explanation may be that wire sutures persist much longer than silk (in the experiment, 10 months after insertion, 4 per cent of silk sutures were still present, 15 per cent of wire, P < 0·01). This was translated into a greater degree of scarring at the anastomosis, being most severe in the presence of persisting sutures. Of the 12 anastomotic tumours found in both groups, 7 (58 per cent) were in the minority (17–26 per cent) who had p...
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Between 1978 and 1988, 12 patients with familial adenomatous polyposis (FAP) and severe duodenal polyposis underwent duodenotomy and duodenal polypectomy. The patients were from two separate institutions; all were women, with a mean age... more
Between 1978 and 1988, 12 patients with familial adenomatous polyposis (FAP) and severe duodenal polyposis underwent duodenotomy and duodenal polypectomy. The patients were from two separate institutions; all were women, with a mean age of 45.6 (range 25-62) years at the time of duodenotomy. Recurrent duodenal polyposis was detected at endoscopy in all 12 patients, at a mean of 13.3 (range 5-36) months after duodenotomy. All patients had moderate to severe duodenal polyposis at the time of the last endoscopic examination. Local excision of duodenal adenomas is an unsatisfactory treatment option in those with FAP. The ideal management of patients with FAP who have severe duodenal polyposis remains uncertain.
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Colostomy irrigation may improve patient quality of life, but is time consuming. This study tests the hypothesis that irrigation with glyceryl trinitrate solution, by inducing gastrointestinal smooth muscle relaxation, may accelerate... more
Colostomy irrigation may improve patient quality of life, but is time consuming. This study tests the hypothesis that irrigation with glyceryl trinitrate solution, by inducing gastrointestinal smooth muscle relaxation, may accelerate expulsion of stool by passive emptying, thereby reducing irrigation time. Fifteen colostomy irrigators(with more than 3 years&#39; experience) performed washout with tap water compared with water containing 0.025 mg/kg glyceryl trinitrate. Fluid inflow time, total washout time, and hemodynamic changes occurring during glyceryl trinitrate irrigation were documented by an independent observer. Subjects recorded episodes of fecal leakage and overall satisfaction on a visual analog scale. Cramps, headaches, and whether or not a stoma bag was used were expressed as a percentage of number of irrigations. Comparison of fluid inflow time, total washout time, leakage, and satisfaction was by Wilcoxon&#39;s signed-rank test and headaches, cramps, and stoma bag use was by McNemar&#39;s test. Pulse rate (paired t-test), systolic and diastolic blood pressures (Wilcoxon&#39;s test) at 20 and 240 minutes after washout with glyceryl trinitrate solution were compared with baseline. Fifteen patients (9 female), with a mean age of 53 (31-73) years, provided 30 sessions (15 with water and 15 with glyceryl trinitrate). Medians (interquartile ranges) for water vs. glyceryl trinitrate were fluid inflow time 7 (4-10) vs. 4, (3-5; P = 0.001); total washout time 40 (30-55) vs. 21, (15-24; P &lt; 0.001); leakage 0 (0-1) vs. 0, (0-0; P = 0.02), satisfaction 10 (8-10) vs. 10 (9-10; P = 0.31). The number (percentage) of stoma bags, cramps, and headaches with water vs. glyceryl trinitrate were 7 (47 percent) vs. 7 (47 percent), P = 1; 1 (7 percent) vs. 14 (93 percent), P &lt; 0.001; and 0(0 percent) vs. 14 (93 percent), P &lt; 0.001, respectively. Changes in pulse (increase) and systolic and diastolic blood pressures (decrease) from baseline were maximal at 20 minutes (P &lt; 0.001, P = 0.001, and P = 0.002, respectively) and had returned to baseline by 240 minutes (P = 0.52, P = 0.08, and P = 1, respectively). Glyceryl trinitrate solution significantly reduces colostomy irrigation time compared with the generally recommended tap water. Patients suffer fewer leakages and are highly satisfied, but side effects are potential drawbacks. Other colonoplegic agent solutions should now be evaluated.
Research Interests: Pain, Gastroenterology, Irrigation, Quality of life, Humans, and 15 moreBlood Pressure, Female, Male, Patient Satisfaction, Clinical Sciences, Aged, Middle Aged, Adult, Pulse Rate, Colostomy, Neurosciences, Nitroglycerin, Diastolic Blood Pressure, defecation, and Paediatrics and reproductive medicine
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Evacuation proctography and measurements of anorectal physiology are frequently used to clarify the pathophysiology of obstructed defaecation. In some patients these tests are normal, despite convincing clinical evidence of defaecatory... more
Evacuation proctography and measurements of anorectal physiology are frequently used to clarify the pathophysiology of obstructed defaecation. In some patients these tests are normal, despite convincing clinical evidence of defaecatory difficulty. The aim of this study was to determine whether magnetic resonance imaging (MRI) could reveal pelvic floor abnormality in patients with obstructed defaecation. Eleven women with obstructed defaecation, in whom evacuation proctography and anorectal physiology were normal, were examined by MRI, using a fast gradient echo sequence. Measurements of pelvic visceral and muscular descent were taken at rest and during straining, and compared with those obtained from 13 asymptomatic volunteers. Patients with obstructed defaecation had significantly greater pelvic visceral descent (P &amp;amp;lt; 0.05), levator muscle descent (P = 0.04), levator plate angle change (P = 0.003) and increase in the area of the pelvic floor hiatus (P = 0.0002) than asymptomatic volunteers. MRI demonstrated marked pelvic visceral and levator muscle descent in women with obstructed defaecation, despite normal evacuation proctography and anorectal physiology. MRI should be considered if these examinations have been normal.
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Background: Anti-tumor necrosis factor (TNF) therapies are used to treat fistulising perianal Crohn's disease (CD). We evaluated the clinical and radiological outcomes of patients with perianal Crohn's fistulas in the pre-anti-TNF... more
Background: Anti-tumor necrosis factor (TNF) therapies are used to treat fistulising perianal Crohn's disease (CD). We evaluated the clinical and radiological outcomes of patients with perianal Crohn's fistulas in the pre-anti-TNF and in the post-anti-TNF era. Methods: A local database of 270 consecutive patients with CD treated at our institution between 2000 and 2014 was established. Results: Ninety patients were in the non-anti-TNF group and 180 were treated with anti-TNF therapy (Infliximab or Adalimumab). Clinical response rates were significantly higher in the anti-TNF group (74% vs 62%, p=0.04). Similarly, radiological response rates were higher in the anti-TNF group (56% vs 28%, p<0.01). Cox Regression analysis demonstrated fistula duration (p=0.01) and biologic therapy (p=<0.01) to be significant at the univariate level. At the multivariate level, patients on anti-TNF therapy had a faster radiological response over a 6-year follow-up period (OR=2.25, CI= 1.14-...