Renal impairment after ileostomy formation: a frequent event with long-term consequences.

AIM: High stoma output and dehydration is common following ileostomy formation. However, the impact of this on renal function, both in the short term and after ileostomy reversal, remains poorly defined. We aimed to assess the independent impact on kidney function of an ileostomy after rectal cancer surgery and subsequent reversibility after ileostomy closure. METHODS: This retrospective single-site cohort study identified patients undergoing rectal cancer resection from 2003 to 2017, with or without a diverting ileostomy. Renal function was calculated preoperatively, before ileostomy closure, and 6 months after ileostomy reversal (or matched times for patients without ileostomy). Demographics, oncological treatments and nephrotoxic drug prescriptions were assessed. Outcome measures were deterioration from baseline renal function and development of moderate/severe chronic kidney disease (CKD ≥ 3). Multivariate analysis was performed to assess independent risk factors for postoperative renal impairment. RESULTS: Five hundred and eighty-three of 1213 patients had an ileostomy. Postoperative renal impairment occurred more frequently in ileostomates (9.5% absolute increase in rate of CKD ≥ 3; P < 0.0001) vs no change in patients without an ileostomy (P = 0.757). Multivariate analysis identified ileostomy formation, age, anastomotic leak and renin-angiotensin system inhibitors as independently associated with postoperative renal decline. Despite stoma closure, ileostomates remained at increased risk of progression to new or worse CKD [74/438 (16.9%)] compared to patients without an ileostomy [36/437 (8.2%), P = 0.0001, OR 2.264 (1.49-3.46)]. CONCLUSIONS: Ileostomy formation is independently associated with kidney injury, with an increased risk persisting after stoma closure. Strategies to protect against kidney injury may be important in higher risk patients (elderly, receiving renin-angiotensin system antihypertensives, or following anastomotic leakage).

Diverticular disease in younger patients--is it clinically more complicated and related to obesity?

AIM: The aims of this systematic review were to determine the presentations of diverticular disease in patients under 40 years of age and to assess whether obesity is an important factor. METHOD: The PubMed and EMBASE databases and the Cochrane Library were searched to identify all original articles published between 1990 and 2011 on diverticular disease severity in obese patients (body mass index of ≥ 30 kg/m(2) ) under 40 years of age. RESULTS: Twenty-three clinical case series (two of which were prospective) were identified plus two large aetiological population-based studies. These reported that young patients with diverticular disease were presenting more frequently, that diverticular disease in this age group was less likely to be complicated but that emergency operation rates were higher. The majority (63.1-96.5%) of patients under 40 years of age with diverticular disease were obese. CONCLUSION: The studies suggest that in the young, obese patient with lower abdominal pain, diverticulitis and appendicitis are included in the differential diagnosis. CT and/or laparoscopy should be considered where the diagnosis is in doubt.

Risk factors for anal sphincter disruption during child birth.

BACKGROUND AND AIMS: The objective of our study was to analyse the risk factors in a cohort of women who suffered anal sphincter disruption (third-degree tear) and compare the results with a similar cohort of women who underwent an uncomplicated vaginal delivery (without a clinically detectable laceration) during the same period. MATERIALS AND METHODS: A retrospective analysis was carried out on 54 women (group 1) who suffered a third-degree tear and 71 women who had undergone uncomplicated vaginal delivery during the same period (group 2). The risk factors considered were forceps delivery, parity, second stage of labour longer than 1 h, episiotomy, birth weight over 4 kg, gestational age and maternal age at delivery. The Cleveland Incontinence Score was completed. RESULTS: Multiple logistic regression analysis of obstetric risk factors for third-degree perineal tear indicated forceps delivery (p = 0.0001), primiparity (p = 0.004), foetal birth weight over 4 kg (p = 0.030) and delay in the second stage of labour (p = 0.031) to be significant risk factors for a third-degree tear. Mediolateral episiotomy was shown to be a significant protective factor (p = 0.0001). Gestational age and the maternal age at delivery (p = 0.340) were not shown to be significant risk factors (p = 0.336). CONCLUSION: Primary prevention and identification of women with risk factors is recommended. In some cases, counselling regarding the potential risks and benefits of both vaginal and caesarean delivery may be appropriate.

Recurrent endometriosis following total hysterectomy with oophorectomy mimicking a malignant neoplastic lesion: a diagnostic and therapeutic challenge.

CASE REPORT: A woman with a previous hysterectomy and bilateral salpingo-oophorectomy for endometriosis presented with painless vaginal bleeding. Imaging revealed a heterogeneous soft tissue pelvic mass suggestive of a malignant neoplastic lesion. Radical surgery was performed including excision of the pelvic mass and anterior resection of the sigmoid colon. Histopathology revealed endometriosis. CONCLUSION: The risk of malignant transformation and the difficulty in achieving a preoperative diagnosis make radical surgery inevitable in the management of recurrent endometriosis. The use of hormone replacement therapy after bilateral salpingo-oophorectomy for endometriosis remains controversial and requires careful counseling about recurrence and close follow-up.

Comparison of vector symmetry index and endoanal ultrasonography in the diagnosis of anal sphincter disruption.

BACKGROUND: Anal pressure vectography is an anorectal physiology study that evaluates the radial pressures in the anal canal from which a symmetry index that indicates the anatomical integrity of the anal sphincter can be calculated. However, there are conflicting opinions of its validity. Since endoanal ultrasonography (EAUS) has been recognized as the gold standard for detecting anal sphincter disruption, the aim of this pilot study was to observe whether a vector symmetry index (VSI) determined at the level of injury shown in EAUS has a better sensitivity than the overall VSI in detecting anal sphincter disruption. METHODS: A group of 11 women in whom EAUS had shown defects in both the internal and the external anal sphincters underwent anorectal manometry using a water-perfused vector manometry catheter, and the overall VSI and the VSI at the level of sphincter disruption (shown on EAUS) were calculated. RESULTS: Overall VSI at rest indicated internal sphincter injury in 7 women (64%) but the VSI at the level of disruption indicated internal sphincter injury in all 11 women (100%, p=0.0137). Similarly, the overall VSI at squeeze indicated external sphincter injury in 6 women (55%), but the VSI at the level of disruption indicated external sphincter injury in 10 women (91%, p=0.0049). CONCLUSIONS: Our pilot study showed that EAUS and VSI are equally sensitive in diagnosing a localized anal sphincter defect, provided a segment-for-segment comparison is carried out.

Long-term anal continence and quality of life following postpartum anal sphincter injury.

OBJECTIVE: Anal incontinence occurs as a result of damage to pelvic floor and the anal sphincter. In women, vaginal delivery has been recognized as the primary cause. To date, figures quoted for overt third degree anal sphincter tear vary between 0% and 26.9% of all vaginal deliveries and the prevalence of anal incontinence following primary repair vary between 15% and 61%. Our aim was to analyse the long-term (minimum 10 years post primary repair) anorectal function and quality of life in a cohort of women who suffered a third degree tear (Group 1) and compare the results with a cohort of women who underwent an uncomplicated vaginal delivery (Group 2) or an elective caesarean delivery (Group 3). METHOD: In all, 107 patients who suffered a third degree tear between 1981 and 1993 were contacted with a validated questionnaire. The two control groups comprised of 125 patients in each category. Those who responded to the questionnaire were invited for anorectal physiology studies and endoanal ultrasound. RESULTS: Of the total number contacted, 54, 71 and 54 women from the three groups returned the completed questionnaire. In the three groups, a total of 28 (53%), 13 (19%) and six (11%) complained of anal incontinence (P < 0.0001) respectively. Comparison of quality of life scores between the groups showed a poorer quality of life in those who suffered a tear (P < 0.0001). In addition, in spite of primary repair, 13 (59%) patients in group 1 showed a persistent sphincter defect compared to one (4%) occult defect in Group 2 and none in Group 3. CONCLUSION: Our study indicates that long-term results of primary repair are not encouraging. It therefore emphasizes the importance of primary prevention and preventing further sphincter damage in those who have already suffered an injury (during subsequent deliveries).

Do calcium channel blockers and antimuscarinics protect against perforated colonic diverticular disease? A case control study.

BACKGROUND: The aetiology of perforated colonic diverticular disease (PCDD) remains largely unknown. Perforation may result from a combination of high intracolonic pressures, secondary to excessive colonic segmentation, and impairment of the mucosal barrier. Calcium channel blockers and antimuscarinic drugs, which reduce colonic contractility and tone, could potentially protect against perforation. The aim of this study was to test this hypothesis using a case control design. METHODS: All cases of acute PCDD were identified over a five year period in two hospitals in Norfolk, UK. Each case was matched for age, sex, and date of admission to two controls groups: (1) patients undergoing cataract surgery and (2) patients with basal cell carcinoma. Data on drug use prior to hospital admission were obtained from medical and nursing records and compared between cases and controls. RESULTS: A total of 120 cases of PCDD were identified and matched to 240 controls in each group. A statistically significant protective association was seen between calcium channel blocker use and PCDD using both control groups. The odds ratios were 0.41 (95% confidence interval (CI) 0.18-0.93) using the ophthalmology control group and 0.36 (95% CI 0.16-0.82) using the dermatology control group. CONCLUSIONS: This study has shown for the first time that a protective association exists between calcium channel blockers and PCDD. The validity of this association is supported by the consistent finding in both control groups and the plausible biological mechanisms. Further studies are required to confirm this association but calcium channel blockers may represent a potential preventive therapy in PCDD.

Anti-inflammatory drugs, analgesics and the risk of perforated colonic diverticular disease.

BACKGROUND: Acute perforated colonic diverticular disease has a mortality rate of up to 30 per cent, but little is known about its aetiology. The aim of this study was to test the hypothesis that three classes of drugs, namely non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics and corticosteroids, are risk factors for perforated diverticular disease. METHODS: All patients with confirmed perforated colonic diverticular disease were identified over a 5-year period in two hospitals in Norfolk, UK. Two control groups were selected and matched for age, sex and hospital of admission. Data on medication use were obtained from hospital records. Odds ratios for each drug were calculated using conditional logistic regression. RESULTS: Opioid analgesics, NSAIDs and corticosteroids were all positively associated with perforated colonic diverticular disease. The odds ratio for opioid analgesics was 1.8 (95 per cent confidence interval (c.i.) 1.1 to 3.0) in the analysis with ophthalmology controls and 3.1 (95 per cent c.i. 1.8 to 5.5) in that with dermatology controls. Respective odds ratios for NSAIDs were 4.0 (95 per cent c.i. 2.1 to 7.6) and 3.7 (95 per cent c.i. 2.0 to 6.8), and those for corticosteroids were 5.7 (95 per cent c.i. 2.2 to 14.4) and 7.8 (95 per cent c.i. 2.6 to 23.3). CONCLUSION: Opioid analgesics, NSAIDs and corticosteroids are all positively associated with perforated colonic diverticular disease. The consistency of these associations, together with plausible biological mechanisms, suggests that these drugs may have a causative role in this condition.

Epidemiology of perforated colonic diverticular disease.

Perforated colonic diverticular disease results in considerable mortality and morbidity. This review appraises existing evidence on the epidemiology and mechanisms of perforation, highlights areas of further study, and suggests an epidemiological approach towards preventing the condition. Computerised searches were used to identify published articles relating to the epidemiology, pathophysiology, and clinical features of perforated colonic diverticular disease. Several drug and dietary exposures have potential biological mechanisms for causing perforation. Of these only non-steroidal anti-inflammatory drugs have been consistently identified as risk factors in aetiological studies. The causes of perforated colonic diverticular disease remain largely unknown. Further aetiological studies, looking specifically at perforation, are required to investigate whether cause-effect relationships exist for both drug and dietary exposures. The identification of risk factors for perforation would allow primary public health prevention, secondary risk factor modification, and early prophylactic surgery to be aimed at people at high risk.

Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor.

The distribution of polymorphisms in the glutathione S-transferase (GST) family genes has been studied in 355 healthy controls and 206 cancer (59 proximal and 147 distal) patients. All controls were subjected to flexible sigmoidoscopy. Odds ratios (OR) after stratification by age, gender and smoking were slightly higher in the cancer group as a whole for GSTM1-null (*0/*0), GSTT1-null (*0/*0) and GSTM3 *A/*B or *B/*B when compared with the control group, but the differences did not reach statistical significance. GSTP1 variants had no effect. Separate analysis of patients with proximal and distal tumours has shown stronger associations for the distal cancers, the GSTM3*B allele presence being significantly more frequent in these patients [OR = 1.77; 95% confidence interval (CI) = 1.15-2.74]. Taking into account strong linkage between the GSTM1*A and GSTM3*B alleles, a separate analysis of the GSTM1-nulled individuals was undertaken. The combination of GSTM1-null genotype with GSTM3*B allele presence (*A/*B or *B/*B) was significantly overrepresented among patients with proximal and distal tumours taken together (OR = 2.12; 95% CI = 1.24-3.63), and especially in distal cancer patients (OR = 2.75; 95% CI = 1.56-4.84). Male individuals displayed a stronger association between the presence of the GSTM1-null in combination with GSTM3 *A/*B or *B/*B and distal tumours with a higher odds ratio (OR = 3.57; 95% CI = 1.73-7.36). In contrast, the frequency of GSTM1 *B/*0 or *B/*B combined with GSTM3 *A/*A was significantly lower in patients with distal colorectal cancer, especially in males (OR = 0.37; 95% CI = 0.15-0.92). Neither of these combinations was associated with proximal tumours. Our findings suggest that interactions of polymorphic genotypes within the GSTM gene cluster affect individual susceptibility to colorectal carcinogenesis, the GSTM3*B variant presence being a risk factor especially in combination with the GSTM1-null genotype.

K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.

It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.

Consumption of fish oil leads to prompt incorporation of eicosapentaenoic acid into colonic mucosa of patients prior to surgery for colorectal cancer, but has no detectable effect on epithelial cytokinetics.

Fish oil (FO) was previously reported to partially normalize colorectal crypt cell cytokinetics in patients with colorectal neoplasms. We determined the effect of FO on the fatty acid composition of colonic mucosa and mesenteric adipose tissue and on rectal crypt cell proliferation in patients undergoing surgery for colonic carcinoma. Patients (49-28 males; 21 females) were randomly assigned to consume FO capsules (2 g b.d.; FO group) containing 1.4 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid per day, or safflower oil capsules (2 g b.d.; placebo group) for an average of 12.3 +/- 0.5 d prior to surgery. Rectal biopsies were obtained at entry, at surgery, and 8-12 wk postsurgery. Colonic biopsies and samples of mesenteric adipose tissue were analyzed for fatty acids by gas-liquid chromatography. Mitosis was determined in whole crypt mounts. The proportion of EPA (g/100 g total fatty acids) in mucosal lipids was significantly greater in FO patients compared to the placebo group, but there was no effect on mesenteric adipose tissue. However self-reported use of FO supplements prior to surgery was associated with higher levels of EPA in adipose tissue. There was no significant effect of FO on the frequency or spatial distribution of crypt cell mitosis. EPA from marine oil supplements is rapidly incorporated into the colonic mucosal lipids of humans, but the levels achieved in the present study did not modify colorectal cytokinetics.

Pharmacology of the internal anal sphincter and abnormalities in faecal incontinence.

Studies of anorectal physiology and in-vivo experiments on the innervation of the anorectum have provided considerable information about anorectal function. Additional information regarding the receptors and nerves involved in the control of the internal anal sphincter function has been obtained from in-vitro studies of isolated muscle strips of the internal anal sphincter.

Abnormal internal anal sphincter fibrosis and elasticity in fecal incontinence.

PURPOSE: We aimed to investigate the changes in the proportion of collagen and in the elasticity of the internal anal sphincter in patients with neurogenic fecal incontinence. METHODS: Collagen content was studied in ten patients with neurogenic fecal incontinence (mean age, 51.5 years) and ten controls (age, 58.6 years) using histologic techniques to determine differences between incontinence and health and to determine the effect of aging. Changes in elasticity were also measured in 8 controls (mean age, 63 years) and 13 patients with neurogenic incontinence (mean age, 60 years) by recording the in vitro length-tension relationship of the freshly excised internal anal sphincter. RESULTS: Incontinent patients had a significantly higher collagen content than controls (55 percent vs. 33 percent; P = 0.013). In incontinent patients the amount of collagen and the patients' ages correlated significantly (P = 0.001). There was a greater increase in stable tension per increase in muscle length in the strips from incontinent patients compared with controls. CONCLUSIONS: Changes in fibrous tissue content are likely to influence muscle tone and responsiveness of the sphincter in fecal incontinence.

CO2 laser haemorrhoidectomy--does it alter anorectal function or decrease pain compared to conventional haemorrhoidectomy?

Carbon dioxide (CO2) laser haemorrhoidectomy is feasible and safe provided it is used with care. It is associated with a reduced requirement for post-operative analgesia. The CO2 laser caused no significant alteration in anorectal physiology.

Effect of age, sex and parity on anorectal function.

Ninety-one healthy subjects (51 women; age range 16-85 years) were studied prospectively to determine the effect of age, sex and parity on anorectal function. Maximum resting pressure, voluntary contraction pressure, rectal sensation to distension, rectal and mid-anal electrosensitivity, perineal descent, pudendal nerve terminal motor latency and fibre density of the external and sphincter were measured. Sex influenced mean(s.d.) voluntary contraction pressure (148(56) versus 95(43) cmH2O for men versus women, P < 0.0001), perineal descent on straining (1.0(0.5) versus 1.3(0.4) cm, P = 0.02) and fibre density (1.43(0.14) versus 1.52(0.15), P = 0.02). Age influenced resting pressure (r = -0.43, P = 0.0001), perineal position at rest (r = -0.55, P < or = 0.0001), mid-anal electrosensitivity (r = 0.42, P = 0.0001) and rectal electrosensitivity (r = 0.54, P < 0.0001). Parity affected mean(s.d.) voluntary contraction pressure (105(53) versus 75(20) cmH2O for nulliparous versus parous women, P = 0.04) and mid-anal electrosensitivity (5.3(2.3) versus 4.5(2.3) mA, P = 0.02). Increasing age leads to perineal descent at rest, slowed pudendal nerve conduction, a fall in resting anal pressure and decreased anorectal sensory function. Women have a lower and squeeze pressure, greater perineal descent, longer pudendal nerve terminal motor latency and a greater muscle fibre density than men. Parity leads only to lower squeeze pressure.

Audit of postanal repair in the treatment of fecal incontinence.

PURPOSE: The short-term results of postanal repair for idiopathic fecal incontinence are satisfactory but data on long-term outcome are lacking. This study was carried out to document the short-term and long-term results of this operation and to determine whether preoperative tests predict long-term outcome. METHODS: Thirty-six patients (33 females; mean age, 57 years) with major idiopathic fecal incontinence operated on by one surgeon were studied. Patients had resting and voluntary contraction anal pressures and pudendal nerve terminal motor latencies (PNTML) measured preoperatively. Symptoms were evaluated at 6 months after operation and again at a median of 25 (range, 6-72) months in all 36 patients. Symptoms were classified as: Group C, no improvement or worse; Group B, minor improvement; and Group A, marked improvement in comparison to the patient's preoperative symptoms. Seventeen patients had postoperative physiology performed. RESULTS: At 6 months there were 6 (17 percent) patients in Group C, 12 (33 percent) in Group B, and 18 (50 percent) in Group A. At final follow-up there were 17 (47 percent) in Group C, 9 (25 percent) in Group B, and 10 (28 percent) in Group A. Comparison of the preoperative data in the final outcome groups showed (mean +/- SE): Groups A and B vs. Group C--resting pressure, 24.6 +/- 6 cm H2O vs. 40.5 +/- 12.2 (P = 0.2), voluntary contraction pressure, 23.7 +/- 5.7 vs. 11.8 +/- 3.6 (P = 0.09), and PNTML, 3.2 +/- 0.75 mS vs. 3.3 +/- 0.99 (P = 0.8). Mean differences between post-operative and preoperative results were: resting pressure, 28 +/- 8.2 cm H2O (P = 0.003); voluntary contraction pressure, 19.5 +/- 6.7 (P = 0.01); and PNTML, -0.3 +/- 0.29 mS (P = 0.3). CONCLUSIONS: At 6 months 83 percent of patients had obtained some benefit from postanal repair but only 53 percent maintained this improvement with only 28 percent being markedly better. There was a trend toward a more favorable outcome in patients with greater squeezing pressures preoperatively but other tests were not of long-term predictive value.

Neuropeptides in the internal anal sphincter in neurogenic faecal incontinence.

The internal anal sphincter has both an intrinsic and extrinsic innervation which modulates its activity. While the nature of the extrinsic innervation has been well characterised, the same is not true of the intrinsic innervation. Although a variety of neurotransmitters have been identified in the human internal anal sphincter, their physiological role in health, and possible involvement in disease processes, have received little attention. Using immunohistochemistry we have studied the distribution and nerve fibre densities of a range of neuropeptides in the internal anal sphincter from 12 cancer patients (controls) and from 16 patients with neurogenic faecal incontinence. We have also studied the in vitro effect of vasoactive intestinal peptide, neuropeptide tyrosine, and galanin on isolated preparations of the internal anal sphincter from 11 cancer controls and 5 patients with neurogenic faecal incontinence. There was no difference in either the distribution or density of the neuropeptides between the 2 groups of patients, and there was no qualitative difference in the in vitro responses of the sphincter to the neuropeptides. These findings suggest that these neuropeptide components of the intrinsic innervation of the internal anal sphincter are unaffected in patients with neurogenic faecal incontinence.