Identification of high-risk Dukes B colorectal cancer by microRNA expression profiling: a preliminary study.

AIM: MicroRNAs (miRNAs) from tumour tissue and common gene mutations were studied to determine whether they predict the development of metastasis in patients with Dukes B colorectal cancer. METHOD: Patients who underwent curative resection for Dukes B colorectal cancer who subsequently developed distant metastatic disease at some stage in the following 5 years ('high-risk B') were compared with case-matched controls of Dukes A, Dukes B (no metastases, 'low-risk B') and Dukes C patients without any detectable metastasis at 5 years of follow-up. MiRNAs from tumour and adjacent normal tissue and common gene mutations (KRAS, BRAF, PIK3CA) in primary cancer tissue were analysed to identify prognostic tissue markers for the development of metastasis in patients with Dukes B colorectal cancer. RESULTS: Expression of miR-15b and miR-135b was significantly downregulated (P < 0.001) in 'high-risk B' tumours compared with Dukes A, 'low-risk B' and C without metastasis. No significant differences were noted for mutation status and the development of metastasis. CONCLUSION: The study suggests that the development of metastasis in Dukes B tumours may be predictable based on the miRNA expression of miR-15b and miR-135b. This requires further study on a much larger cohort.

MicroRNAs are novel biomarkers of colorectal cancer.

BACKGROUND: Recent studies have identified unique small ribonucleic acids called microRNAs (miRNAs) in colonic tumour tissue and blood that may accurately diagnose the presence of colorectal cancer and help predict disease recurrence. This review explores the potential role of these biomarkers. METHODS: A literature search identified studies describing miRNAs in colorectal cancers. The outcomes of interest included diagnosis, progression and recurrence of disease, and future therapy. RESULTS: Overexpression and silencing of specific miRNAs are associated with the development and progression of colorectal cancer. Such a role in oncogenesis suggest that miRNAs may be important targets for gene therapies. Differential expression of specific miRNAs in tissues and blood offers the prospect of their use in early detection and screening for colorectal cancer. MiRNAs are implicated in metastasis and cytotoxic drug resistance. Their manipulation has potential in both prevention of recurrence and palliation. CONCLUSION: The miRNAs expression profile in tissue and blood has potential for their use in the detection, screening and surveillance of colorectal cancer. Furthermore, miRNAs may be targeted by gene therapy to treat colorectal cancer.

Assessment of a patient consultation questionnaire-based scoring system for stratification of outpatient risk of colorectal cancer.

BACKGROUND: The UK government's fast-track 2-week wait (2WW) rule and colorectal cancer guidelines aimed to detect patients at high risk of having colorectal cancer, but the yield has been poor. A patient consultation questionnaire (PCQ)-based scoring system may be an effective tool for prioritizing colorectal referrals. The aim of this study was to validate the system in a large and ethnically diverse population and to compare it with 2WW referrals. METHODS: Over a 1-year period, all colorectal referrals (2WW and traditional letters) at nine hospitals in Leicestershire were sent a PCQ to complete and return. A weighted numerical score (WNS), which reflects the patient's risk of having colorectal cancer, was calculated and compared with the hospital diagnosis. RESULTS: Of a total of 1422 PCQs returned, 83 patients were diagnosed with colorectal cancer. The 2WW referrals constituted 35.7 per cent of all referrals. The mean WNS of patients with colorectal cancer was significantly higher than that of the other patients (mean 76.3 versus 48.9 respectively; P < 0.001). For similar cancer detection rates (or sensitivity), the specificity of a WNS cut-off of 70 was significantly better than that of the 2WW system (82.7 versus 66.1 per cent; P < 0.001). CONCLUSION: The PCQ-based WNS system improves specificity for detecting colorectal cancer, particularly when the WNS exceeds 70.

Delayed presentation of life-threatening perineal sepsis following stapled haemorrhoidectomy: a case report.

Fournier's gangrene has been described after injection sclerotherapy and banding of haemorrhoids as well as after conventional haemorrhoidectomy. In addition, there have been several cases following stapled haemorrhoidopexy. A patient with this complication nearly always presents within the first week following surgery. We present an illustrative case of a patient who underwent stapled haemorrhoidopexy for prolapsed haemorrhoids and presented with fever, urinary retention and peri-anal pain 39 days later. At re-operation, there was extensive peri-anal necrosis. After wide excision and fashioning of a colostomy, the patient recovered. Our case shows that late presentation can occur.

Life-threatening sepsis following treatment for haemorrhoids: a systematic review.

INTRODUCTION: Haemorrhoids are a common complaint with estimates suggesting a prevalence of 4% of the adult population. Treatments such as rubber band ligation (RBL), sclerotherapy and excisional surgery have been in use for many years, and recently stapled haemorrhoidopexy, or procedure for prolapsing haemorrhoids (PPH) has gained acceptance. However, there have been consistent reports of severe sepsis, including a number of deaths. The purpose of this review was to assess the scale of the problem, and identify any predisposing factors, common presenting features, and treatment options in those who suffer these complications. RESULTS: Twenty-nine papers were identified, reporting 38 patients. Of these, 17 had undergone RBL, three had sclerotherapy, one had cryotherapy, 10 had excisional surgery and seven had PPH. Ten died as a result of their sepsis. The cases included 16 with perineal sepsis, seven with retroperitoneal gas and oedema, and six with liver abscesses. Common presenting features were urinary difficulties, fever, severe pain, septic shock and leucocytosis. Most were managed by means of surgery, although a minority survived having received conservative therapy. With the exception of two patients (one of whom was human immunodeficiency virus positive and the other had a drug-induced agranulocytosis) all were well prior to surgery. CONCLUSIONS: Although extremely uncommon, severe sepsis does occur post-treatment for haemorrhoids and all surgeons who treat such patients should be aware of the potential complications and alert to their presenting features. Early presentation without evidence of tissue necrosis may be managed conservatively, although most cases are managed by means of surgery.

Factors predicting early recurrence after transanal endoscopic microsurgery excision for rectal adenoma.

INTRODUCTION: Transanal endoscopic microsurgery (TEM) is an accepted way of excising rectal adenomas with low morbidity and mortality, avoiding major resectional surgery. However, there are no agreed criteria for surveillance following TEM. The purpose of this study was to identify criteria to guide surveillance programmes, thus reducing the surveillance burden for those patients at low risk of recurrence. PATIENTS AND METHODS: Patients who had undergone TEM for rectal adenomas were identified, and a retrospective review of patient, pathological and histological parameters was performed. RESULTS: Seventy-five (40 male) patients were identified; median age 70 years (39-85). There were seven tubular, 33 tubulo-villous and 35 villous adenomas. All were considered completely excised by the operating surgeon. Forty-seven (62.7%) were reported as being completely excised histologically. There was no significant association between recurrence at 6 months and sex, age, type or position of adenoma, height above the anal verge, or degree of dysplasia. Recurrence rates at six months were 0% for the completely excised adenomas and 21.4% for the incompletely excised ones; this was statistically significant (Pearson chi(2), P < 0.001). In all there were 12 recurrences, 10 in the incompletely excised group at a median follow up of 31 (6-80) months (P < 0.001). In addition, a significant association for large adenomas to recur was noted at median follow up (Armitage Trend test, P = 0.019). CONCLUSIONS: Histological assessment of completeness of excision of rectal adenoma and size of adenoma are important predictors of early recurrence and have potential to guide follow-up strategies after TEM.

Transanal endoscopic microsurgery--lessons from a single UK centre series.

OBJECTIVES: Transanal endoscopic microsurgery (TEM), a minimally invasive technique has been employed in the excision of benign and selected malignant rectal tumours since 1983. We present a single surgeon's series of 102 procedures. PATIENTS AND METHODS: A retrospective case note review of 102 procedures performed over a 6-year period between 1996 and 2001. RESULTS: One hundred and two TEM procedures were performed on 100 patients. 68 for adenomas, 19 potentially curative excisions for carcinoma, 13 palliative procedures for advanced carcinoma and 2 for solitary rectal ulcer syndrome (SRUS). Four adenomas recurred and were successfully treated by various procedures. None went on to develop malignancy, or a further recurrence. Of the cancers, six T1 and 10 T2 were excised with curative intent. Three T3 cancers were excised before endorectal ultrasound was available in the unit and went on to have definitive procedures. One T1 and two T2 carcinomas were not completely histologically excised. These patients were offered definitive procedure and there have been no recurrences. 11 patients underwent palliative TEM procedures, 2 went on to have a recurrence of symptoms. Both underwent a successful second TEM procedure. CONCLUSIONS: Although longer term follow up is still required, TEM appears to be an effective method of excising benign tumours and T1 carcinomas of the rectum. The role of TEM in the treatment of T2 carcinomas is, as yet, unclear and needs further evaluation although the results of our series and others are encouraging.

Medical causes of faecal incontinence.

Faecal incontinence can result from a disturbance in any one of the multiple factors which maintain continence. In practice, faecal incontinence is most commonly seen in women who have had children. This symptom can also be seen in other patient groups, who may in addition have had children, and this article will discuss the mechanisms involved in the loss of continence in diabetics and patients with multiple sclerosis.

Splenectomy for haematological disease.

The role of splenectomy in haematological disease appears to be changing. This single centre, retrospective study was carried out to document the indications for splenectomy and its outcome over a 7-year period and to compare it with the preceding 7-year period. Sixty-four patients underwent splenectomy in the study period, the main indication being idiopathic thrombocytopenic purpura. There was one post-operative death and morbidity was seen in 40 (63%) patients. Splenectomy was successful in achieving the desired aim in 51 (80%) patients. Approximately 40% fewer patients underwent splenectomy in the study period compared with the preceding 7 years despite there being an overall increase of 123 (633 vs. 540) patients treated for haematological disease in this period. The reason for this observation was the fall in the number of splenectomies performed for Hodgkin's disease and auto-immune haemolytic anaemia.

An unusual presentation of intestinal lymphangiectasia.

Intestinal lymphangiectasia is a rare disorder, usually presenting with protein-losing enteropathy leading to oedema and ascites. We describe a case that presented as an acute surgical emergency with pain and a mass in the right iliac fossa, which was successfully treated by resection of the involved segment of ileum.

Paradoxical puborectalis contraction is a feature of constipation in patients with multiple sclerosis.

OBJECTIVE: To study the disturbed anorectal physiology associated with constipation in multiple sclerosis. METHODS: Anorectal function in 10 patients with clinically definite multiple sclerosis and constipation has been compared with 10 normal persons and 11 patients with idiopathic constipation, without multiple sclerosis. RESULTS: All 10 constipated patients with multiple sclerosis had difficulty evacuating barium paste during defaecography. In four of these there was complete failure of puborectalis relaxation when straining to defaecate, and in another four there was incomplete puborectalis relaxation. There was no evidence of lower motor neuron involvement of pelvic floor muscles in the multiple sclerosis group. CONCLUSIONS: Paradoxical puborectalis contraction is common in patients with multiple sclerosis in whom constipation is a symptom. This may be a feature of the disturbed voluntary sphincter control mechanism, analogous to detrusor sphincter dyssnergia in the bladder.

Management of lower limb ischaemia associated with the use of intra-aortic balloon pumps during cardiac surgery.

OBJECTIVE: To audit the lower limb vascular complications associated with the use of an intraaortic balloon pump (IABP) on a cardiothoracic unit over a 12 month period. DESIGN: Retrospective analysis. SETTING: Regional university cardiothoracic unit. PATIENTS: Fifty four IABPs inserted into 51 patients. RESULTS: Seventeen patients (33%) died from cardiogenic shock in the immediate postoperative period. Of the remaining 34 patients (37 IABPs), lower limb vascular complications occurred in nine patients (26%) who underwent 11 IABP insertions (30%). Vascular complications included groin haematomas (n = 2 insertions), compartment syndrome (n = 2 insertions), femoral artery trauma (n = 7 insertions). CONCLUSIONS: Prompt management by peripheral vascular surgeons resulted in limb salvage in 10 legs and only one death from a pulmonary embolus.

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.

Pelvic floor function in multiple sclerosis.

The aim of this study was to define pelvic floor function in patients with multiple sclerosis and bowel dysfunction, either incontinence (MSI) or defecation difficulties without incontinence (MSC). Normal controls and patients with idiopathic neurogenic faecal incontinence without multiple sclerosis (FI, disease controls) were also studied. Thirty eight multiple sclerosis patients (20 incontinent, 18 incontinent) 73 normal controls, and 91 FI patients were studied. The FI group showed the characteristic combined sensorimotor deficit previously described in these patients of low resting and voluntary contraction and pressures, increased sensory threshold to mucosal stimulation, and increased pudendal nerve terminal motor latencies and fibre densities. MSI patients had significantly lower anal resting pressures (80 (30-140) cm H2O, median (range) v 98 (30-200), normal controls, p = 0.002) and both MSC and MSI patients had significantly lower anal maximum voluntary contraction pressures (65 (0-260) cm H2O, MSC and 25 (0-100), MSI v 120 (30-300), normal controls, p = < 0.0004) and higher external anal sphincter fibre densities (1.7 (1.1-2.6), MSC and 1.7 (1.1-2.4), MSI v 1.5 (1.1-1.75), normal controls, p < 0.006) compared with normal controls but pudendal nerve terminal motor latencies were similar and no sensory deficit was found. This contrasted with the idiopathic faecal incontinent patients who, in addition to significantly higher fibre densities (1.8 (1.1-3), p = 0.001) had increased pudendal latencies (2.5 (1.1-5.5) mS v 2.08 (1.4-2.6), p = 0.001) compared with normal controls. The idiopathic faecal incontinent group had significantly lower resting anal pressures (50 (10-160) cm H2O, p=0.02) than the MSI group. Comparison with the incontinent and continent multiple sclerosis groups showed that incontinence was associated with lower voluntary anal contraction pressures (25 (0-100) v 65 (0-260), p=0.03) but that there were no other differences between these two groups. Pelvic floor function is considerably disturbed in multiple sclerosis, showing muscular weakness with preservation of peripheral motor nerve conduction, providing indirect evidence that this is mainly a result of lesions within the central nervous system.