Histopathological features for coexistent invasive cancer in large colorectal adenomatous polyps.

BACKGROUND: Histopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma. METHODS: High-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated. RESULTS: Seventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma. CONCLUSION: Several histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.

Elderly patients have more infectious complications following laparoscopic colorectal cancer surgery.

AIM: Elderly patients may be at higher risk of postoperative complications, particularly infective, than younger patients. METHOD: We prospectively followed 163 consecutive patients undergoing elective laparoscopic resection for cancer. We compared patients < 65, 65-80 and > 80 years of age at the time of surgery. RESULTS: Seventy (42.9%) patients had no complication; 93 (57.1%) had at least one complication following surgery and in 20 (12.3%) this was major. There was no difference in major complications between the groups (P = 0.47). Patients over 65 years of age were more likely to have a complication of any severity [< 65 years, 39.3%; 65-80 years, 69.3%; and > 80 years, 63.0% (P = 0.002)]. The frequency of gastrointestinal complications (30.1%) was similar in the groups (P = 0.29), as was wound infection (25.2%) (P = 0.65). There was an increase in the frequency of infectious complications, especially chest infection, with age, from 14.8% in patients < 65 years, to 22.7% in patients 65-80 years, to 44.4% in patients > 80 years (P = 0.01). Multivariate analysis showed no increase in overall complications in elderly patients, but Stage II or Stage III cancer (OR = 2.59, P = 0.04) and increasing body mass index (BMI) (OR = 1.07 for each unit increase in BMI, P = 0.04) were related to complications. Age remained the only predictor of an infective complication on multivariate analysis. Patients > 80 years of age had 4.21 times the OR of an infective complication (P = 0.03). CONCLUSION: Older patients are more susceptible to infective complications postoperatively, particularly chest complications. Surgeons should alter their practice to reduce morbidity, such as adopting protocols requiring early physiotherapy.

Increased diverticular complications with nonsteriodal anti-inflammatory drugs and other medications: a systematic review and meta-analysis.

AIM: Complications of colonic diverticula, perforation and bleeding are a source of morbidity and mortality. A variety of drugs have been implicated in these complications. We present a systemic review and meta-analysis of the literature to assess the importance of this relationship. METHOD: A systematic review of articles in PubMed, Cochrane Reviews, Embase and Google Scholar was undertaken in February 2013. An initial literature search yielded 2916 results that were assessed for study design and topicality. Twenty-three articles were included in the review. A qualitative data synthesis was conducted using forest plots of studies comparing single medication with complications. RESULTS: Individual studies demonstrated the odds of perforation and abscess formation with nonsteridal anti-inflammatory drugs (NSAIDs) (1.46-10.30), aspirin (0.66-2.40), steroids (2.17-31.90) and opioids (1.80-4.51) and the odds of bleeding with NSAIDs (2.01-12.60), paracetamol (0-3.75), aspirin (1.14-3.70) and steroids (0.57-5.40). Pooled data showed significantly increased odds of perforation and abscess formation with NSAIDs (OR = 2.49), steroids (OR = 9.08) and opioids (OR = 2.52). They also showed increased odds of diverticular bleeding from NSAIDs (OR = 2.69), aspirin (OR = 3.24) and calcium-channel blockers (OR = 2.50). Most studies did not describe the duration or dosage of medication used and did not systematically describe the severity of diverticular complications. CONCLUSION: Various common medications are implicated in complications of diverticular disease.

Little consensus in either definition or diagnosis of a lower gastro-intestinal anastomotic leak amongst colorectal surgeons.

PURPOSE: The purposes of this study were to assess the working definition of a colorectal anastomotic leak among colorectal surgeons and to survey the current approach to investigation and management of a patient with a suspected anastomotic leak. METHODS: Online survey consisting of nine questions regarding the definition, assessment and investigation of anastomotic leaks was conducted. Of the 738 eligible ACP members contacted, 210 responded (28.4%). RESULTS: Results demonstrated that 94.2% of surgeons agreed 'extravasation of contrast on enema' and 91.8% agreed 'faecal material seen in drains/from the wound' constituted a clinical leak. Only 69.2% agreed that a leak was 'intra-abdominal sepsis requiring a laparotomy', and about half agreed that radiological collections constituted a leak when either treated with antibiotics (46.6%) or with percutaneous drainage (51.4%). Serial clinical examination was the perceived most sensitive clinical feature for a leak, with 75% of surgeons ranking this in their top three choices. Surgeons radiologically confirm a leak on average in 80.2% of cases. A CT with rectal contrast for a left-sided leak was selected by 42.9% of respondents. For a right-sided/small bowel anastomosis, 44.5% selected a CT with oral contrast and 43.4% a CT with IV contrast. CONCLUSIONS: There is still significant heterogeneity between surgeons in what they define as an anastomotic leak. Most surgeons valued clinical examination as the most sensitive initial tool for leak detection; however, radiology has a major role in the confirmation of clinical leaks in colorectal patients. There is an increasing need to be able to classify and grade anastomotic leaks, both to improve the care of patients and for audit purposes.

High-frequency mini-probe ultrasound as a useful adjunct in the management of patients with malignant colorectal polyps.

AIM: Colorectal polyps with a focus of malignancy, identified postpolypectomy, pose a management challenge of whether endoscopic treatment is adequate or whether further surgical resection is required. This study assessed 12- and 20-MHz colonoscopic ultrasound to evaluate the presence of residual disease and local lymph nodes. METHOD: Consecutive cases of all colorectal polyps with a focus of malignancy were included. Colonoscopic high-frequency ultrasound was performed (20-MHz mini-probes for residual polyps and 12-MHz ultrasound for local lymph nodes) in the region of previous polypectomy. Biopsies were taken of the polypectomy site if any abnormalities were seen. RESULTS: Twenty-one malignant polyps (sigmoid, n = 10; rectum, n = 8; transverse colon, n = 1; ascending colon, n = 1; and caecum, n = 1) were identified. All were invasive adenocarcinomas; 12 were intramucosal and nine were submucosal (seven sm1 lesions in the upper third of the submucosa; and two sm2 lesions in the middle third of the submucosa). Excision was histologically complete in 12 patients, four had involved margins and histology was uncertain in five owing to diathermy artefacts. Further colonoscopy revealed a residual abnormality in eight patients. The 12- and 20-MHz ultrasound imaging revealed mucosal irregularity with normal bowel-wall layers and no lymph-node involvement, with normal histology. High-frequency ultrasound was normal in the remaining 13 patients. At the time of writing, 15 (72%) of the 21 patients were disease free without further surgery. Six of the 21 patients underwent surgery, despite normal high-frequency ultrasound findings, because of submucosal invasion (sm1 or sm2) and uncertain completeness of resection. The specimens were free of cancer in all six patients. CONCLUSION: High-frequency ultrasound is feasible for the assessment of colorectal malignant polyps.

Stapled transanal rectal resection (STARR) for obstructive defaecation syndrome: patients with previous pelvic floor surgery have poorer long-term outcome.

AIM: Stapled transanal rectal resection (STARR) is used for patients with obstructive defaecation syndrome (ODS) not responding to conservative management. Reports indicate mixed results and there are no studies publishing the long-term outcome. METHOD: Following full investigation, 37 patients with ODS underwent a STARR procedure by one of the authors (SP) between 2005 and 2010. RESULTS: The median (range) patient age was 53.0 (28-79) years and all were female. Median (range) follow up was 13 (0-57) months, and nine (24.3%) patients were followed for longer than 24 months. Eighteen patients had undergone at least one (and often multiple) previous gynaecological procedures, including hysterectomy (n = 14), colposuspension (n = 3), vaginal rectocele repair (n = 4) and pelvic floor repair (n = 5). Four patients had had at least one previous rectal operation [stapled anopexy (n = 3) and Delorme's procedure (n = 2)]. One patient did not attend for postoperative follow up. Of the remaining 36 patients, 18 had resolution of obstructive symptoms. Of the 18 with residual symptoms, 17 eventually reported the same level of symptoms as before the STARR procedure. There was a significant correlation between the presence of residual symptoms and long-term ODS recurrence (P < 0.0005). For those with residual symptoms, the mean (95% CI) time to symptom recurrence was 3 (2.86-11.81) months. Twenty (56%) patients were satisfied with the outcome from the STARR procedure. CONCLUSION: Residual symptoms are a strong indicator of long-term failure. STARR was effective for symptom resolution in 50% of patients. Those who had undergone pelvic floor or rectal prolapse surgery were significantly more likely to experience recurrent symptoms.

A clinicopathological study of serotonin of sigmoid colon mucosa in association with chronic symptoms in uncomplicated diverticulosis.

INTRODUCTION: Neurotransmitter imbalance is hypothesised as a pathogenetic mechanism in several bowel conditions. We previously reported increased 5-HT in the sigmoid mucosa of colon resected for complicated diverticular disease (DD). We aimed to identify if abnormal 5-HT expression is associated with symptoms of uncomplicated DD. METHODS: This was a prospective, comparative study and follow-up survey of symptoms. We examined the differences in 5-HT between DD patients and controls, as well as the presence of bowel symptoms at time of endoscopy and also 2 years later. Sigmoid biopsies were collected at colonoscopy. Immunohistochemical staining for 5-HT cells was performed. RESULTS: Eighty-seven patients were recruited, 37 (42.5 %) DD and 50 (57.5 %) controls. No patients underwent surgery. There was no significant difference in total mean number of 5-HT-positive cells in DD compared to controls or between patients and controls with abdominal symptoms. Forty-one patients (47.1 %) responded to questionnaires at median 57.8 months from biopsy. Eighteen (43.9 %) were DD and 23(56.1 %) controls. 5-HT counts showed no significant association to symptom persistence. DISCUSSION: Although 5-HT expression has previously been found to be increased in complicated DD in whole bowel-resected specimens, the same is not confirmed on colonic mucosal biopsies. This raises the suggestion that 5-HT may be involved in the development of acute complications but may not be involved in the pathogenesis of chronic symptoms.

Colonoscopic high frequency mini-probe ultrasound is more accurate than conventional computed tomography in the local staging of colonic cancer.

AIM: Colonoscopic high frequency mini-probe ultrasound was compared prospectively with CT in the local staging of colonic cancer. METHOD: Consecutive patients undergoing surgical resection for colonic cancer were recruited. Preoperative 64-slice CT staging with multiplanar reconstruction was compared with colonoscopic high frequency mini-probe ultrasound using 12 MHz and 20 MHz probes. The three methods of staging (CT, 12 MHz ultrasound and 20 MHz ultrasound) were compared with the histological stage of the resected specimen. This was done using weighted kappa coefficients where weights of 0.7-0.8 were given to penalize disagreements of one level in either direction and weights of zero were given to penalize disagreements of more than one level in any direction. RESULTS: In total, 38 patients with colonic cancer were included. They were located in the sigmoid (n = 20), descending (n = 5), ascending (n = 2) and transverse colon (n = 1) and in the caecum (n = 7) and splenic (n = 2) and hepatic (n = 1) flexure. Histopathological assessment revealed seven pT1, four pT2, 25 pT3 and two pT4 cancers. In relation to the pathology the weighted kappa coefficients were 0.36 (SE = 0.14), 0.81 (SE = 0.16) and 0.81 (SE = 0.17) for CT, ultrasound 12 MHz and ultrasound 20 MHz. Histopathologically 15 (39.5%) patients were lymph node positive. The sensitivity, specificity and kappa coefficient for detection of nodal disease for CT were 80%, 47.8% and 0.25 (SE = 0.14) compared with 80%, 82.5% and 0.62 for 12 MHz ultrasound (SD = 0.14) and 23%, 90.5% and 0.15 (SD = 0.13) for 20 MHz ultrasound. CONCLUSION: Colonoscopic ultrasound is significantly more accurate than CT for T staging of colonic cancers. With respect to nodal status, 12 MHz ultrasound offers superior accuracy to CT or 20 MHz ultrasound.

Review article: the pathogenesis of diverticular disease--current perspectives on motility and neurotransmitters.

BACKGROUND: Low-fibre diet, structural abnormalities and ageing are traditional aetiological factors implicated in the development of diverticular disease. More recently, motility disorders are implicated in its causation leading to speculation that neurotransmitters play a role in mediating these disturbances. AIMS: To draw together studies on the role of neurotransmitters in the development of diverticular disease and its symptoms. METHODS: Medline, GoogleScholar and Pubmed were searched for evidence on this subject using the terms neurotransmitters, motility, diverticular disease and pathogenesis. Articles relevant to the subject were cited and linked references were also reviewed. RESULTS: Serotonin, which has been found to be an excitatory colonic neurotransmitter, has been found in early studies to be increased in colonic enterochromaffin cells. Acetylcholine, which is thought to be an excitatory neurotransmitter and cholinergic activity, has also seen to be increased in diverticular disease. These findings may suggest that an increase in excitatory neurotransmitters may result in the hypersegmentation thought to cause pulsion diverticula. Similarly, a decrease in nitric oxide which is inhibitory is found. CONCLUSIONS: There is some evidence that neurotransmitters may play a role in the motility disturbances seen in diverticular disease; however, a clear role is yet to be ascertained.

Prospective evaluation of a colorectal cancer nurse follow-up clinic.

AIM: Colorectal Nurse Specialist (CNS) clinics for postoperative follow up of colorectal cancer aim to maintain clinical efficacy while reducing costs. We prospectively studied the efficacy and financial implications of such a clinic. METHOD: This was a prospective study of all patients attending CNS clinics over 3 years. A lower-risk protocol for patients with Dukes A was used over 3 years and a higher-risk protocol for patients with Dukes B, C or D was used over 5 years. Department of Health Pricing Charts were used to cost the follow-up protocols, and adjustment was performed to calculate the cost of each quality adjusted life year (QALY) gained. RESULTS: One hundred and ninety-three patients entered into this nurse-led follow-up protocol implemented by the CNS clinic between 2005 and 2007. The Dukes stages and proportions of patients in each stage were as follows: stage A, 13%; stage B, 8%; stage C, 36.3%; and stage D, 9.3%. Ninety-seven per cent underwent curative treatment and 2.6% had palliative treatment. Twenty-one per cent of patients developed recurrent disease. Overall actuarial 5-year survival was 80% and recurrences had a 30% 5-year actuarial survival. The total cost per patient for 3 years of follow up was £1506 and £1179 for lower-risk rectal and nonrectal cancers, respectively. The adjusted cost for each QALY gained for lower-risk tumours was £1914. The total cost per patient with higher-risk tumours was £1814 and £1487 for rectal and nonrectal tumours, respectively. The adjusted cost for each QALY gained was £2180 for higher-risk tumours. CONCLUSIONS: This clinic demonstrated cost-effective detection of recurrent disease. Computed tomography (CT) was the most sensitive alert test. As all recurrences were detected within 4 years, we suggest that this is the indicated time to follow up.

A systematic review of the benefit of total parenteral nutrition in the management of enterocutaneous fistulas.

Enterocutaneous fistulas (ECFs) most commonly occur as a complication of abdominal surgery but can also occur spontaneously in inflammatory bowel disease, diverticulitis, radiation, trauma and sepsis. Although mortality and morbidity have reduced in recent years they are still a major cause of concern in patients with ECF. Nutritional support is a challenging issue in these patients and a major cause of mortality and morbidity. Total parenteral nutrition (TPN) is widely used in the management of ECF. In this review the authors examined the evidence of the use of TPN in ECF with the aim of determining the indications, benefits and outcome of this type of nutritional support in these.

Solitary rectal ulcer syndrome mimicking rectal neoplasm on MRI.

Solitary rectal ulcer syndrome (SRUS) is a rare condition that typically affects young adults and describes a spectrum of clinicopathological abnormalities. The diagnosis of SRUS is usually made on the basis of a combination of presenting symptoms and endoscopic and histological appearances. Characteristic radiological appearances have been described on transrectal and endoanal ultrasound, defecating proctography and barium enema. The radiological appearance of solitary rectal ulcer on MRI has not been previously described. MRI appearance of thickened ulcerated mucosa in the anterior rectal wall are non-specific and was indistinguishable from a malignant process. However, given that solitary rectal ulcer has a pre-disposition to occur in the anterior rectal wall, the presence on MRI of thickened rectal mucosa in this location could suggest solitary rectal ulcer in the correct clinical context.

Diverticular disease hospital admissions are increasing, with poor outcomes in the elderly and emergency admissions.

BACKGROUND: Diverticular disease has a changing disease pattern with limited epidemiological data. AIM: To describe diverticular disease admission rates and associated outcomes through national population study. METHODS: Data were obtained from the English 'Hospital Episode Statistics' database between 1996 and 2006. Primary outcomes examined were 30-day overall and 1-year mortality, 28-day readmission rates and extended length of stay (LOS) beyond the 75th percentile (median inpatient LOS = 6 days). Multiple logistic regression analysis was used to determine independent predictors of these outcomes. RESULTS: Between the study dates 560 281 admissions with a primary diagnosis of diverticular disease were recorded in England. The national admission rate increased from 0.56 to 1.20 per 1000 population/year. 232 047 (41.4%) were inpatient admissions and, of these, 55 519 (23.9%) were elective and 176 528 (76.1%) emergency. Surgery was undertaken in 37 767 (16.3%). The 30-day mortality was 5.1% (n = 6735) and 1-year mortality was 14.5% (n = 11 567). The 28-day readmission rate was 9.6% (n = 21 160). Increasing age, comorbidity and emergency admission were independent predictors of all primary outcomes. CONCLUSIONS: Diverticular disease admissions increased over the course of the study. Patients of increasing age, admitted as emergency and significant comorbidity should be identified, allowing management modification to optimize outcomes.

Review article: the current and evolving treatment of colonic diverticular disease.

BACKGROUND: Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis and consequently diverticular disease. Diverticular disease can be associated with numerous debilitating abdominal and gastrointestinal symptoms (including pain, bloating, nausea, constipation and diarrhoea). AIMS: To review the state of treatment for diverticular disease and its complications, and briefly discuss potential future therapies. METHODS: PubMed and recent conference abstracts were searched for articles describing the treatment of diverticular disease. RESULTS: Many physicians will recommend alterations to lifestyle and increasing fibre consumption. Empirical antibiotics remain the mainstay of therapy for patients with diverticular disease and rifaximin seems to be the best choice. In severe or relapsing disease, surgical intervention is often the only remaining treatment option. Although novel treatment options are yet to become available, the addition of therapies based on mesalazine (mesalamine) and probiotics may enhance treatment efficacy. CONCLUSIONS: Data suggest that diverticular disease may share many of the hallmarks of other, better-characterized inflammatory bowel diseases; however, treatment options for patients with diverticular disease are scarce, revolving around antibiotic treatment and surgery. There is a need for a better understanding of the fundamental mechanisms of diverticular disease to design treatment regimens accordingly.

Increased presence of serotonin-producing cells in colons with diverticular disease may indicate involvement in the pathophysiology of the condition.

INTRODUCTION: Serotonin is an important neuroendocrine transmitter participating in the control of colonic motor activity through neural and biochemical mechanisms in the Enteric Nervous System (ENS). A possible pathophysiological factor for diverticular disease (DD) is altered colonic motility. The study compared the distribution of serotonin cells (SC) in the colonic mucosa of patients with diverticular disease to controls. METHODS: Sixteen paraffin specimens with sigmoid diverticular disease were selected and sections of bowel without diverticula from the same specimen were used as its own control. The resection margins from sixteen colonic specimens excised for sigmoid cancer were additional controls. Immunocytochemical staining for serotonin cells was performed on 4-mum tissue sections with polyclonal antibody (NCL-SEROTp). The number of serotonin-positive cells per ten microscopic fields (x200) was assessed in all groups and the staining distribution was defined as low (0-33%), moderate (>33-66%) and high (>66%) according to the percentage of the entire cell containing contrast material. The control specimens were blinded before analysis. Student's t test was used for statistical analysis and significance level was set as P < 0.05. RESULTS: The mean number of serotonin-positive cells per ten fields in the colonic mucosa of specimens with diverticular disease was significantly higher [252.44 (SD 90.64)] than the specimen's own control [147.31 (SD 50.16)] and at normal resection margins of cancer specimens [228.38 (SD 120.10)]. The paired analysis between diverticular disease specimens and its own control (paired t test) showed significant differences for moderate (P = 0.008), high (P = 0.001) and total (P = 0.002) number of serotonin cells. There was no evidence of significance between mean DD and cancer values. DISCUSSION: Increased presence of SCs and the higher proportion of high and moderate staining cells (indicating increased hormone content) indicate the possible role of serotonin in DD. This may be contributing to the pathogenesis of the condition by altered colonic motility in the affected segments in a similar way as in irritable bowel syndrome.

Variance of surgeons versus pathologists in staging of colorectal cancer.

AIM: Accurate staging of colorectal cancer depends on adequate retrieval and reporting of lymph nodes in the specimen. The presence of positive lymph nodes is an indication for adjuvant therapy. Both surgeons and pathologists influence the number of lymph nodes that are retrieved and reported in specimens. Although several recommendations exist in the literature regarding the minimum number of lymph nodes required for reliable staging, the relationship of examined to infiltrated lymph nodes has not been clarified. The aims of this study were to examine variance among surgeons and pathologists in the retrieval and reporting of lymph nodes in colorectal cancer specimens; to examine the relationship between retrieved/examined lymph nodes and infiltrated lymph nodes; to identify in our own series the minimum number of retrieved lymph nodes required to secure accurate staging. METHODS: Cross-sectional study of 284 patients with colorectal cancer followed in our hospital and retrospective analysis of histopathology reports. Correlation analysis, ANOVA, and survival analysis were performed on the data. RESULTS: There were 127 patients with cancer of the rectum and 157 patients with cancer of the colon under follow-up. The median number of lymph nodes per specimen was 8 (range 0-29). There was no difference in the number of retrieved lymph nodes among 9 surgeons. There were 2 outliers among pathologists, with one reporting a mean of 11.4 (9.8-12.9) 95% CI nodes per specimen and another reporting a mean 4.9 (3.6-6.2) 95% CI nodes per specimen. Dukes and T stage did not affect the number of nodes. Correlation analysis revealed a linear correlation between the total number of reported lymph nodes and the existence of positive lymph nodes. From the correlation equation we calculated that, in order to have one positive node, a minimum of 8.4 nodes was required in the specimen. Therefore, in our group of patients, a minimum of 8.4 nodes was required for accurate Dukes staging. However, survival analysis did not show any difference between patients with more and patients with less than 9 reported lymph nodes. CONCLUSIONS: Variance among pathologists exists and may be at least as important as variance among surgeons. Specialisation of pathologists similar to that of surgeons as well as employment of new techniques may be required . There is a linear correlation between the number of examined lymph nodes and the presence of positive nodes in a colorectal cancer specimen. This linear correlation makes the calculation of the minimum number of lymph nodes possible. In our series a minimum of nine nodes must be examined. However, we have not demonstrated an effect of inadequate nodes numbers on survival, possibly because survival in colorectal cancer is multifactorial.