Paul Hollington

An analysis of predictive factors for healing and mortality in patients with enterocutaneous fistulas

Background  Most studies of enterocutaneous fistula report management and outcome. Few studies examine factors predicting healing and mortality.

Perianal abscess: A pilot study comparing packing with nonpacking of the abscess cavity

PURPOSE:Perianal sepsis is traditionally treated by incision and drainage, with packing of the residual cavity until healing. This study was designed to show that perianal abscess may be safely treated by incision and drainage alone.METHODS:Healing times, analgesic requirements, pain scores, abscess recurrence, and fistula rates were compared between two randomized groups treated with and without packing of perianal abscess cavities.RESULTS:Fifty patients were recruited (7 lost to follow-up): 20 in the packing and 23 in the nonpacking arm. The groups were comparable in terms of age and gender distribution, type and size of abscess, and the presence of a fistula at operation. Mean healing times were similar (P = 0.214). The rate of abscess recurrence was similar (P = 0.61). Postoperative fistula rates were similar (P = 0.38). Pain scores at the first dressing change were similar (P = 0.296). Although pain scores appeared much reduced in the nonpacking arm, this did not attain statistical significance.CONCLUSIONS:Our pilot study indicates that perianal abscesses can be managed safely without continued packing of the cavity without any obvious complications.

A cross-sectional study comparing a blood test for methylated BCAT1 and IKZF1 tumor-derived DNA with CEA for detection of recurrent colorectal cancer

Recurrence will develop in 30–50% of colorectal cancer (CRC) cases despite apparent clearance following treatment. Carcinoembryonic antigen (CEA) is the only guideline‐recommended blood test for monitoring cases for recurrence, but its sensitivity and specificity are suboptimal. This observational study compared a novel 2‐gene (methylated BCAT1 and IKZF1 DNA) blood test with CEA for detection of recurrent CRC. We conducted a paired comparison of the BCAT1/IKZF1 test with CEA (cut‐off 5 ng/mL) in blood from patients in remission after treatment for primary CRC and undergoing surveillance. Blood collected in the 12 months prior to or 3 months after complete investigational assessment of recurrence status were assayed and the results compared by McNemars test. Of 397 patients enrolled, 220 underwent satisfactory assessment for recurrence and 122 had blood testing performed within the prescribed period. In 28 cases with recurrent CRC, CEA was positive in 9 (32%; 95% CI 16–52%) compared to 19 (68%; 95% CI 48–84%) positive for methylated BCAT1/IKZF1 (P = 0.002). All samples that were CEA positive were also BCAT1/IKZF1 positive. In 94 patients without clinically detectable recurrence, CEA was positive in 6 (6%, 95% CI 2–13%) and BCAT1/IKZF1 in 12 (13%, 95% CI 7–21%), P = 0.210. The odds ratio of a positive CEA test for recurrence was 6.9 (95% CI 2–22) compared to 14.4 (5–39) for BCAT1/IKZF1. The BCAT1/IKZF1 test was more sensitive for recurrence than CEA and the odds of recurrence given a positive test was twice that of CEA. The BCAT1/IKZF1 test should be further considered for monitoring cases for recurrence.

Timing and detection of metachronous colorectal cancer

Background:  Surveillance following surgery for colorectal cancer aims to detect treatable disease relapse or metachronous neoplasia. Metachronous cancers have been reported within a short duration of follow‐up, and may be due to missed lesions, seeding into polypectomy wounds or accelerated tumorigenesis related to genetic instability. The purpose of this study was to establish the timing and method of detection of metachronous cancers in a large population of patients in a surveillance database.

Physiological, psychological and behavioural characteristics of men and women with faecal incontinence

Background  The factors leading to faecal incontinence in males are less well understood than those in females. In this prospective study we aimed to compare the physiological, anatomical, psychological and behavioural characteristics of male and female patients presenting with symptoms of faecal incontinence.

Mechanisms Controlling Glucose-Induced Glp-1 Secretion in Human Small Intestine.

Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans. In this study, we showed that a 30-min intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1 levels. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in the ileum at ≥200 mmol/L glucose. In ex vivo tissue from the duodenum and ileum, but not the colon, 300 mmol/L glucose potently stimulated GLP-1 release. In the ileum, this response was independent of osmotic influences and required delivery of glucose via GLUT2 and mitochondrial metabolism. The requirement of voltage-gated Na+ and Ca2+ channel activation indicates that membrane depolarization occurs. KATP channels do not drive this, as tolbutamide did not trigger release. The sodium–glucose cotransporter 1 (SGLT1) substrate α-MG induced secretion, and the response was blocked by the SGLT1 inhibitor phlorizin or by replacement of extracellular Na+ with N-methyl-d-glucamine. This is the first report of the mechanisms underlying glucose-induced GLP-1 secretion from human small intestine. Our findings demonstrate a dominant role of SGLT1 in controlling glucose-stimulated GLP-1 release in human ileal L cells.

Chemoprevention of colorectal neoplasia

Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer.

Augmented capacity for peripheral serotonin release in human obesity

Background/objectivesEvidence from animal studies highlights an important role for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating hepatic glucose production, lipolysis and thermogenesis, and promoting obesity and dysglycemia. Evidence in humans is limited, although elevated plasma 5-HT concentrations are linked to obesity.Subjects/methodsWe assessed (i) plasma 5-HT concentrations before and during intraduodenal glucose infusion (4 kcal/min for 30 min) in non-diabetic obese (BMI 44 ± 4 kg/m2, N = 14) and control (BMI 24 ± 1 kg/m2, N = 10) subjects, (ii) functional activation of duodenal EC cells (immunodetection of phospho-extracellular related-kinase, pERK) in response to glucose, and in separate subjects, (iii) expression of tryptophan hydroxylase-1 (TPH1) in duodenum and colon (N = 39), and (iv) 5-HT content in primary EC cells from these regions (N = 85).ResultsPlasma 5-HT was twofold higher in obese than control responders prior to (P = 0.025), and during (iAUC, P = 0.009), intraduodenal glucose infusion, and related positively to BMI (R2 = 0.334, P = 0.003) and HbA1c (R2 = 0.508, P = 0.009). The density of EC cells in the duodenum was twofold higher at baseline in obese subjects than controls (P = 0.023), with twofold more EC cells activated by glucose infusion in the obese (EC cells co-expressing 5-HT and pERK, P = 0.001), while the 5-HT content of EC cells in duodenum and colon was similar; TPH1 expression was 1.4-fold higher in the duodenum of obese subjects (P = 0.044), and related positively to BMI (R2 = 0.310, P = 0.031).ConclusionsHuman obesity is characterized by an increased capacity to produce and release 5-HT from the proximal small intestine, which is strongly linked to higher body mass, and glycemic control. Gut-derived 5-HT is likely to be an important driver of pathogenesis in human obesity and dysglycemia.

Observation of “complete clinical response” in rectal cancer after neoadjuvant chemoradiation: The Flinders experience

Observation with close follow‐up (“watch and wait”) is a recognized treatment option in patients who achieve a complete clinical response to long course chemoradiotherapy. This review of a prospective database aims to evaluate the clinical outcomes among patients with a complete clinical response managed with observation.

Findings at surveillance colonoscopy following surgery for colorectal cancer

Colonoscopic surveillance following potentially curative surgery for colorectal cancer aims to detect treatable metachronous neoplasia. The timing and findings of colonoscopies for patients enrolled in an endoscopic surveillance programme were examined in this study.