Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

BACKGROUND: Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. METHODS: Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. KEY RESULTS: Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. CONCLUSIONS & INFERENCES: Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration.

A randomised controlled trial of transverse skin crease vs. vertical midline incision for right hemicolectomy.

BACKGROUND: A transverse skin crease incision for right hemicolectomy may result in more rapid recovery than traditional vertical midline incision. This hypothesis was tested with a prospective randomised trial. METHODS: Patients from 2 centres undergoing right hemicolectomy were randomised to received a midline or transverse incision. Incision lengths were sufficient to enable unrestricted resection of the right colon. Patients and carers were blinded to the incisions using strategically placed dressings. Analgesia and oral intake were controlled by the patient. Operative details and recovery parameters were compared. RESULTS: A total of 28 patients were randomised. Demographic data and tumour characteristics of the two treatment groups were similar. The transverse incision group had a slightly shorter median wound (10 cm vs. 11 cm, p<0.05). Operative time, analgesia requirements, recovery parameters (time to discharge, 6.5 vs. 6.5 days) and frequency of complications were otherwise comparable. CONCLUSIONS: A transverse skin crease incision for right hemicolectomy results in a slightly smaller wound but no other advantages were demonstrated compared with a traditional vertical midline incision.

The management of persistent and recurrent chronic anal fissures.

There are numerous definitive reviews concerning aetiology and management of acute and chronic anal fissures. The problem of persistence and recurrence after surgical and nonsurgical therapy has not been specifically addressed and there is little evidence-based guidance for the management of this difficult group of patients. A review of the literature with particular reference to persistence and recurrence of chronic anal fissures is presented and an algorithm of management incorporating evidence-based data is suggested.

Inadequacy of colonoscopy revealed by three-dimensional electromagnetic imaging.

INTRODUCTION: It is generally accepted that clinicians performing colonoscopy should reach the cecum in at least 90 percent of examinations. However, little attention has been paid to whether the endoscopist correctly estimates the amount of colon actually seen. METHODS: During colonoscopy, endoscopists were asked to state how far they had reached. This was compared with the amount of colon actually seen, as assessed by a novel electromagnetic imaging device that recorded a three-dimensional position of the scope within a magnetic field pervading the patient's abdomen. If electromagnetic imaging showed that the cecum had not been reached, the endoscopist was asked to use the electromagnetic imaging system to determine whether it helped advance the colonoscope further. RESULTS: In 119 patients undergoing colonoscopy, clinical assessment of position reached was correct in only 92 (77.3 percent). When the endoscopists stated that cecal landmarks had been seen (n = 85), the scope was distal to the cecum in seven cases (8.2 percent). When cecal landmarks had not been seen (n = 34), the endoscopist's assessment of the position of the scope was accurate in only 14 (41.2 percent). The use of electromagnetic imaging in this latter group assisted passage to the cecum in 26 cases (76.5 percent). CONCLUSION: Despite assumed visualization of the cecum, inadequate colonoscopy highlights the potential for missing significant pathology in the right colon.

The immunomodulatory effect of levamisole is influenced by postoperative changes and type of lymphocyte stimulant.

The results of both laboratory and clinical research into the immunomodulatory activity of levamisole have shown a considerable degree of inconsistency and sometimes contradiction. This is probably a reflection of the lack of understanding of the mechanism(s) of action of levamisole and it is therefore necessary to base conclusions about its immunomodulatory efficacy in the treatment of disease on experimental assays that take into consideration the in vivo conditions. This investigation was designed to compare the immunomodulatory activity of levamisole under clinically achievable and non-achievable conditions as judged by changes in the perioperative proliferative response of lymphocytes from 30 patients with colorectal cancer. The results obtained showed that proliferation in antigen (purified protein derivative, PPD)-stimulated, but not phytohaemagglutinin(PHA)- or staphylococcal-enterotoxin-B(SEB)-stimulated, lymphocyte cultures was consistently and significantly augmented by levamisole in concentrations of 25 ng-25 micrograms/ml. High concentrations of levamisole (25 micrograms/ml and 100 micrograms/ml) were inhibitory to PHA- and SEB-stimulated, but not PPD-stimulated, lymphocyte cultures, especially in the postoperative period. Of particular interest was the observation that, although levamisole temporarily lost its stimulatory activity in the postoperative period (third postoperative day), it did enhance antigen-stimulated lymphocytes at the time of the nadir of the postoperative suppression of lymphocyte proliferation (first postoperative day). Clinically achievable concentrations of levamisole are therefore effective both before and after operation in enhancing the response of lymphocytes to antigens.

Role of circumferential margin involvement in the local recurrence of rectal cancer.

Local recurrence after resection for rectal cancer remains common despite growing acceptance that inadequate local excision may be implicated. In a prospective study of 190 patients with rectal cancer, we examined the circumferential margin of excision of resected specimens for tumour presence, to examine its frequency and its relation to subsequent local recurrence. Tumour involvement of the circumferential margin was seen in 25% (35/141) of specimens for which the surgeon thought the resection was potentially curative, and in 36% (69/190) of all cases. After a median 5 years' follow-up (range 3.0-7.7 years), the frequency of local recurrence after potentially curative resection was 25% (95% CI 18-33%). The frequency of local recurrence was significantly higher for patients who had had tumour involvement of the circumferential margin than for those without such involvement (78 [95% CI 62-94] vs 10 [4-16]%). By Cox's regression analysis tumour involvement of the circumferential margin independently influenced both local recurrence (hazard ratio = 12.2 [4.4-34.6]) and survival (3.2 [1.6-6.53]). These results show the importance of wide local excision during resection for rectal cancer, and the need for routine assessment of the circumferential margin to assess prognosis.