Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer.

AIM: Lymph node (LN) metastases are present in up to 17% of early colorectal cancers (pT1). Identification of associated histopathological factors would enable counselling of patients regarding this risk. METHOD: Pubmed and Embase were employed utilizing the terms 'early colorectal cancer', 'lymph node metastasis', 'submucosal invasion', 'lymphovascular invasion', 'tumour budding' and 'histological differentiation'. Analysis was performed using REVIEW MANAGER 5.1. RESULTS: Twenty-three cohort studies including 4510 patients were analysed. There was a significantly higher risk of LN metastasis with a depth of submucosal invasion > 1 mm than with lesser degrees of penetration (OR 3.87, 95% CI 1.50-10.00, P = 0.005). Lymphovascular invasion was significantly associated with LN metastasis (OR 4.81, 95% CI 3.14-7.37, P < 0.00001). Poorly differentiated tumours had a higher risk of LN metastasis compared with well or moderately differentiated tumours (OR 5.60, 95% CI 2.90-10.82, P < 0.00001). Tumour budding was found to be significantly associated with LN metastasis (OR 7.74, 95% CI 4.47-13.39, P < 0.001). CONCLUSION: Meta-analysis of the current literature demonstrates that in early colorectal cancer a depth of submucosal invasion by the primary tumour of > 1 mm, lymphovascular invasion, poor differentiation and tumour budding are significantly associated with LN metastasis.

Variations in surgical management from a national bowel cancer screening programme.

OBJECTIVE: Population screening for colorectal cancer (CRC) was introduced to Wales in October 2008. The aim of this study was to evaluate the early impact of screening on CRC services. DESIGN: Prospectively collected data from the Bowel Screening Wales (BSW) programme and the Welsh Bowel Cancer Audit (WBCA) were used to identify all screen-detected (SD) CRC diagnoses in Wales between April 2009 and March 2011. Data from the WBCA were used to calculate surgical outcomes. RESULTS: 444 SD cancers were registered during the study period representing 11% of all CRC diagnoses. There was a 9.9% increase in CRC incidence following the introduction of the BSW. SD patients presented with earlier stage disease; SD Dukes' A 35.1% vs 13.9% symptomatic patients (p<0.001) and SD Dukes' D 7.4% vs 21.8% symptomatic, (p<0.001). There were more colonic cancers among the SD population (p<0.001). The resection rate for SD cancers was 89%, significantly higher than symptomatic cancers (67.7%; p<0.0001). There was variability in the use of polypectomy as a definitive procedure to treat CRC between units. Overall laparoscopic resection was used in 52% of cases but with considerable interunit variability (0-92%). CONCLUSIONS: The introduction of screening has increased the workload of the colorectal multidisciplinary teams in Wales. This has occurred through both an increase in case volume and the identification of more patients with early stage disease. There is considerable interunit variability in the use of techniques of local excision and rates of laparoscopic resection that need to be addressed.

A five-year audit of anal cancer in Wales.

OBJECTIVES: A retrospective audit has been undertaken of Squamous (epidermoid) type of anal cancer diagnosed and treated in the principality of Wales over a five-year period (1995-99) with follow-up until 2005. The referral pattern, distribution, presenting symptoms, predisposing conditions, clinical findings and staging modalities were documented. The surgical and oncological treatment together with their outcome was analysed. METHODS: Patients were identified from the Welsh Cancer Registry and the pathology databases of the 17 acute hospitals in Wales. Data was collected from the clinical and oncology case notes onto a purpose designed Microsoft access database. RESULTS: There was a wide variation in data quality from the individual units. Twenty-six anal cancers were diagnosed per year in the region. Median age was 69 years. Ten percent had documented perianal Human Papilloma Virus related disease. Radiology was inconsistently used for staging. Eighty percent were referred for an oncology opinion; 50% had chemo-radiotherapy with a curative intent. The over-all Stoma rate was 35% and of these 18% had an abdomino perineal resection. The overall five-year survival was 45%. CONCLUSIONS: This is a unique regional audit of anal cancer. Improvements need to be made in documentation particularly of staging, treatment, pathology reporting and outcome. This study concurs that Human Papilloma Virus appears to predispose to Squamous anal cancer. Radiological staging needs to be standardized according to best clinical practice. As recommended by NICE all patients should be referred to a multidisciplinary anal cancer team, which can provide individual treatment plans. Increased specialization could mean specialist regional MDTs for anal cancer.

Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging?

In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (kappa=0.81, s.e.=0.05; kappa(W)=0.83), compared with very poor agreements of 65% for DRE (kappa=0.08, s.e.=0.068, kappa(W)=0.16) and 69% for EUS (kappa=0.17, s.e.=0.065, kappa(W)=0.17). The resource benefits resulting from the use of MRI rather than DRE was 67164 UK pounds and 92244 UK pounds when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients.

Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging.

BACKGROUND: The aim was to determine the accuracy of preoperative magnetic resonance imaging (MRI) in the evaluation of pathological prognostic factors that influence local recurrence and survival in rectal cancer. METHODS: Ninety-eight patients undergoing total mesorectal excision for biopsy-proven rectal cancer were assessed prospectively using high-resolution MRI for tumour (T) and nodal (N) staging using the tumour node metastasis classification, depth of extramural tumour spread, the presence or absence of extramural venous invasion, a threatened circumferential resection margin and serosal involvement at or above the peritoneal reflection. Preoperative magnetic resonance assessment of these prognostic factors was compared with histopathological findings in carefully matched whole-mount sections of the resection specimen. RESULTS: There was 94 per cent weighted agreement (weighted kappa = 0.67) between MRI and pathology assessment of T stage. Agreement between MRI and histological assessment of nodal status was 85 per cent (kappa = 0.68). Although involvement of small veins by tumour was not discernible using MRI, large (calibre greater than 3 mm) extramural venous invasion was identified correctly in 15 of 18 patients (kappa = 0.64). MRI predicted circumferential resection margin involvement with 92 per cent agreement (kappa = 0.81). Seven of nine patients with peritoneal perforation by tumour (stage T4) were identified correctly using MRI. CONCLUSION: High-resolution MRI of the rectum allows preoperative identification of important surgical and pathological prognostic risk factors. This may allow both better selection and assessment of patients undergoing preoperative therapy.

Rectal carcinoma: thin-section MR imaging for staging in 28 patients.

PURPOSE: To evaluate the accuracy of thin-section magnetic resonance (MR) imaging (in-plane resolution, 0.6 x 0.6 mm) in the preoperative assessment of the depth of extramural tumor infiltration, which is a major prognostic indicator in rectal cancer. MATERIALS AND METHODS: In a prospective study of 28 consecutive patients, preoperative MR imaging was performed. The tumor stage according to the TNM classification system and the measured depth of extramural tumor invasion in matched MR images and histopathologic slices were compared. RESULTS: Preoperative MR imaging correctly indicated the histopathologic tumor stage in all 25 patients in whom comparisons were possible. The difference between the depth of extramural tumor measured on preoperative MR images and corresponding measurements on histopathologic slices of the resection specimen ranged from -5.0 mm to +5.5 mm (mean difference, +0.13 mm; 95% CI: -2.72, +2.98 mm), indicating good agreement. The mesorectal fascia, and the relation of the tumor to it, could be visualized in every case. In all five patients with involvement of the circumferential excision margins of resection specimens, extensive extramural invasion was identified on preoperative MR images. CONCLUSION: Preoperative thin-section MR imaging accurately indicates the tumor stage of rectal cancer and depth of extramural tumor infiltration. It provides valuable information for identifying T3 tumors for preoperative adjuvant therapy in patients who are at high risk of failure of complete excision.

Surgeons' follow-up practice after resection of colorectal cancer.

Consultant surgeons in two United Kingdom Health Regions were invited to complete a questionnaire on details of their personal management of patients with colon and rectal cancer, with particular emphasis on follow-up. Replies from 140 (94%) were analysed by the surgeon's subspecialty of colorectal and gastrointestinal surgery (group 1) and all others (group 2). There was a wide variation in the duration of followup, but no difference between the two groups. More group 1 surgeons carried out investigations as a routine after colonic (P < 0.01) and rectal (P < 0.01) resection. Colonoscopy was used more frequently by group 1 (P < 0.0001) and barium enema by group 2 surgeons (P < 0.05). Investigations to detect asymptomatic metastases were used as a routine by 33.3% of surgeons, in whom there was no concordance over the choice or combination of tests and no difference between the two groups of surgeons. There is no consensus among surgeons as to the ideal duration, intensity and method of follow-up after resection for colorectal cancer and little difference between the practice of colorectal and gastrointestinal surgeons and that of other specialists, except in the use of colonoscopy and barium enema. These results reflect the continuing lack of evidence on which to base the follow-up of patients after surgery for colorectal cancer.

Colorectal cancer pathology reporting: a regional audit.

AIMS: To audit the information content of pathology reports of colorectal cancer specimens in one National Health Service region. METHODS: All reports of colorectal cancer resection specimens from the 17 NHS histopathology laboratories in Wales during 1993 were evaluated against: (a) standards previously agreed as desirable by pathologists in Wales; and (b) standards considered to be the minimum required for informed patient management. RESULTS: 1242 reports were audited. There was notable variation in the performance of different laboratories and in the completeness of reporting of individual items of information. While many items were generally well reported, only 51.5% (640/ 1242) of rectal cancer reports contained a statement on the completeness of excision at the circumferential resection margin and only 30% (373/1242) of all reports stated the number of involved lymph nodes. All of the previously agreed items were contained in only 11.3% (140/1242) of reports on colonic tumours and 4.0% (40/1242) of reports on rectal tumours. Seventy eight per cent (969/1242) of colonic carcinoma reports and 46.6% (579/ 1242) of rectal carcinoma reports met the minimum standards. CONCLUSIONS: The informational content of many routine pathology reports on colorectal cancer resection specimens is inadequate for quality patient management, for ensuring a clinically effective cancer service through audit, and for cancer registration. Template proforma reporting using nationally agreed standards is recommended as a remedy for this, along with improved education, review of laboratory practices in the light of current knowledge, and further motivation of pathologists through their involvement in multidisciplinary cancer management teams.

Population-based audit of colorectal cancer management in two UK health regions. Colorectal Cancer Working Group, Royal College of Surgeons of England Clinical Epidemiology and Audit Unit.

BACKGROUND: To obtain information on the contemporary management of colorectal cancer in the UK to assist in the development of management guidelines, an independent, 1-year population audit was carried out in Trent Region and Wales. METHODS: Data were collected on all patients admitted to hospital with a new diagnosis of colorectal cancer in a 1-year period. RESULTS: Of 3520 patients, 3221 (91.5 per cent) had surgery. Emergency/urgent operations were carried out as the first procedure in 552 (17.1 per cent). Resection of the primary disease was achieved in 2859 (81.2 per cent) and this was deemed curative in 2070 (58.8 per cent). Twenty-one per cent of all patients had metastatic disease at presentation. Overall, 30-day operative mortality was 7.6 per cent (21.7 per cent for emergency/urgent and 5.5 per cent for scheduled/elective procedures). Anastomotic dehiscence occurred in 105 patients (4.9 per cent); this was 3.9 per cent after colonic resections and 7.9 per cent after anterior rectal resections. Elective rectal excision resulted in a permanent stoma in 486 of 1054 patients (46 per cent). CONCLUSION: This initial report from a comprehensive, independent audit of colorectal cancer management shows improvement in some aspects of treatment as evidenced by improved anastomotic dehiscence and stoma rates when compared with previous studies. However, there has been little improvement in the proportion of patients presenting with advanced disease, and curative resection rates remain low.

Laparoscopically assisted trephine stoma formation.

A trephined stoma allows a quick postoperative recovery when a concomitant laparotomy is not necessary. However, both colostomies and ileostomies are associated with a significant short- and long-term complication rate. Review of 25 conventional trephine colostomies showed a complication rate of 20% over 5 years (three hernias and three prolapses in five patients). A laparoscopically assisted method for trephine stoma formation is described that overcomes the disadvantages of the conventional trephine technique; namely the tendency to enlarge the trephine to mobilize the mesentery, leading to prolapse; tension on an inadequately mobilized mesentery, leading to retraction; and difficulties in the orientation of an end stoma. This method was used to fashion six colostomies and one ileostomy with no complications. There was a shorter convalescence and initial stoma care was easier. This procedure is preferred for temporary or permanent stoma formation when a laparotomy is not necessary because it allows a precise trephine mobilization of the mesentery and confirmation of orientation of the bowel.

Anovaginal and rectovaginal fistulas in Crohn's disease.

Between 1957 and 1985, 886 women with Crohn's disease and an intact distal large bowel were seen at St. Mark's Hospital. Ninety of these patients developed a fistula between the vagina and anus or rectum at an average age of 34 years. The track of the fistula was clearly documented in 80 patients and was extrasphincteric or suprasphincteric in 36, transsphincteric in 42 (high 13, low 29), and superficial in two. Of the 90 patients, 12 (13 percent) were managed throughout without recourse to surgery. Twelve (13 percent) had the fistula laid open or drainage of an abscess as the only surgery. Twelve (13 percent) underwent repair of the fistula and, of these, eight remain symptomatically cured. One has had further symptoms but no surgery while three later underwent proctectomy for rectal disease. In eight patients the colon was removed and the rectum defunctioned and in 34 the rectum was excised as the initial surgery after development of the fistula. The remaining 12 (13 percent) underwent later proctectomy for rectal disease or failed conservative management of the fistula. Extensive colonic involvement, rectal disease, or associated anal lesions were the main reasons for rectal excision in 38 patients. In only ten was the rectovaginal fistula a prominent indication for proctectomy. As medical treatment, repair, or other local surgery were successful in one third of the patients, these options should always be considered in the first instance.

Retroperitoneal abscess following sclerotherapy for hemorrhoids.

A case report of a patient who underwent submucosal injection sclerotherapy for hemorrhoids is presented. Subsequent necrosis of the underlying tissues produced a rectal perforation and retroperitoneal abscess, which necessitated emergency laparotomy and defunctioning colostomy. Healing of the perforation allowed later closure of the stoma. A brief review of the known complications of this technique has been made. It would appear that necrosis and perforation with abscess formation can be added to this list.

Intraoperative antegrade irrigation of the large intestine.

The technique described herein permits antegrade irrigation of the intestine peroperatively to empty the obstructed or loaded colon of feces. This procedure extends the indication for safe primary anastomosis of the colon during surgical treatment of the left colon, and our experience with 64 patients is described.

Ketone-glucose interaction in fed, fasted, and fasted-infected sheep.

Ketosis following starvation was suppressed by hindlimb infection in seven fasted sheep. Glucose production determined following the primed constant infusion of [6-3H(N)]glucose was elevated in the fasted-infected animals (9.50 +/- 1.11 mmol X kg-1 X min-1 (mean +/- SE) versus fasted controls (5.56 +/- 2.2). To determine if the ketonemia following sepsis contributed to the increased glucogenesis associated with catabolic disorder, glucose production and arterial substrates were measured before and after infusion of sodium-DL-beta-hydroxybutyrate (beta-OHB, 20 mumol X kg-1 X min-1) in fed, fasted, and fasted-infected animals. Following 3 h of beta-OHB infusion in the awake conditioned animals, beta-OHB and acetoacetate blood concentrations more than doubled. With infusion, blood glucose and alanine concentrations decreased in the fed and fasted sheep but not in the fasted-infected group. Glucose production fell significantly from 10.11 +/- 1.33 to 8.44 +/- 1.05 in the fed animals and from 5.05 +/- 0.28 to 4.11 +/- 0.33 in the fasted group. Glucose production was unaffected by beta-OHB infusion in the fasted-infected animals (9.50 +/- 1.83 vs. 9.11 +/- 1.44). The accelerated rate of glucose production in sheep following infection is not a consequence of the hypoketonemic state associated with sepsis.

The hourly pattern of urine solute and electrolyte excretion following standard surgical trauma.

Although urine volume (and, less frequently, concentration) is often measured in the perioperative period, little attempt has been made to separate temporal phases of the intra- and postoperative response to surgery. In 7 patients undergoing standard severe single trauma and managed by a conventional regimen which included intraoperative Hartmann's solution, we have investigated the hourly pattern of urine solute and electrolyte excretion over the first 48 h. Contrary to expectation, in the first 5 h Na+ excretion increases in association with overall solute excretion, and thereafter progressively diminishes. K+ excretion increases 4 h postoperatively and remains elevated for 24 h, after which it returns to normal, even though Na+ excretion remains low. Free water excretion is negative for the first 24 h, though urine osmolality does not suggest a maximal antidiuretic response by the kidney--the highest concentration achieved being just below 800 mosmol/kg. In order to distinguish between the physiological adaptive changes due to starvation and those due to injury, the hourly pattern of urine solute and electrolyte excretion was further investigated in 12 healthy volunteers mimicking postoperative conditions. Apart from the early postoperative period, the hourly pattern of Na+, K+ and osmolar excretion shows no discernible difference from the operated group. These results show that, particularly in relation to Na+, the changes seen in the post-injury patient, even after major uncomplicated surgery, are largely adaptive, and this is especially striking at 24 h after surgery.

Transcellular movement and intracellular concentration of sodium in erythrocytes after surgery and in seriously ill patients.

Erythrocyte intracellular sodium concentration and transmembrane sodium flux were measured in nine healthy patients undergoing uncomplicated elective abdominal surgery. Intracellular sodium concentration was determined by in vitro washing of cells in a solution approximating to intracellular constituents and measuring extracellular sodium contamination with 51Cr EDTA. Sodium flux was determined by radioactive 22Na tracer both as influx and efflux. No change in erythrocyte intracellular sodium concentration or in sodium flux was found postoperatively. In 14 seriously ill surgical patients, all of whom had plasma sodium levels outside the tolerance range of our surgical population, erythrocyte intracellular sodium concentration decreased, but not significantly, compared with patients undergoing uncomplicated surgery (p = 0.16). Furthermore, sodium flux in seriously ill patients was proportional to intracellular sodium concentration. These results are at variance with the hypothesis of 'sick cell syndrome' which is said to be typified by a high intracellular sodium concentration and a reduced sodium efflux. In the surgical patients studied, it is more likely this hyponatremia does not result from a change in sodium flux but is dilutional.

Extracellular fluid volume expansion and third space sequestration at the site of small bowel anastomoses.

Intestinal surgery is usually associated with the parenteral administration of sodium and water, sometimes in amounts considerably in excess of excretory capacity. We have studied the effect of this situation on the water content of the gut at and 5 cm from a single-layer end-to-end anastomosis in the rabbit. Water content was measured by desiccation. One group of animals (group 1) did not receive intravenous therapy. The second group (group 2) received 5 ml kg-1 h-1 of Hartmann's solution during the operative period and thereafter to a total volume of 200 ml by 48 h. In group 1 there was a 5-10 per cent increase in tissue weight both at the anastomotic site and at 5 cm (P less than 0.01, Mann-Whitney U test) on the first 3 days. Thereafter, water content at the anastomosis persisted, but resolved in normal gut. In group 2 a further 5 per cent increase in weight over group 1 occurred (P less than 0.01), persistent at the anastomotic site over 5 days, though resolving elsewhere after 2 days. Extracellular fluid volume expansion exaggerates an anatomical third space present in the region of an anastomosis. At the suture line, oedema so induced is persistent and could be deleterious.