Cost effectiveness of using Faecal Immunochemical Testing (FIT) as an initial diagnostic investigation for patients with lower gastrointestinal symptoms suggestive of malignancy.

BACKGROUND: There has been an increase in the numbers of patients presenting to primary care with suspected colorectal malignancy and subsequently an increase in demand for endoscopy. This study aims to forecast the cost of faecal immunochemical testing (FIT) compared to conventional diagnostic tests as a primary investigation for patients with symptoms suggestive of colorectal malignancy. METHODS: Retrospectively, 1950 patients with symptoms suggestive of colorectal malignancy who were referred through primary care and underwent investigations through standard endoscopic evaluation were included. These patients were used to forecast the cost of faecal immunochemical testing creating theoretical data for sensitivity and specificity. Outcome measures included: the number of investigations under current protocol; cost of current investigations; number of predicted false negatives and false positives and positive/negative predictive values using current sensitivity data for FIT; the cost forecast of using FIT as the primary investigation for colorectal malignancy. RESULTS: Median age was 65 (IQR 47-82) with 43.7% male and 56.3% female. A total of 1950 investigations were carried out with a diagnostic yield of 26 cancers (18 colon, 8 rectal), 138 polyps and 29 high risk adenomas (HGD ± > 10 mm). In total, £713,948 was spent on the investigations. The commonest investigation was colonoscopy totalling £533,169. The total cost per cancer diagnosis was £27,459. Sensitivity (92.1% CI 86.9-95.3) and specificity (85.8% CI 78.3-90.1) for FIT in colorectal cancer was taken from NICE and was costed via the manufacturer(s). The projected total cost of FIT for the same population using a ≥ 4 µg haemoglobin cut off was £415,680 (£15,554 per cancer). The total cost of high-risk polyps using ≥ 4 µg cut off was £404,427 (sensitivity 71.2% CI 60.5-87.2, specificity 79.8%CI 76.1-83.7) or £13,945 per polyp. CONCLUSIONS: FIT is a cheaper and effective alternative test with the potential to replace current expensive methods. The forecast is based on the limited data available for sensitivity/specificity in the current literature. FIT has now been commenced for symptomatic patients in the UK and therefore sensitivity may change in the future.

Ileo-anal pouch excision and permanent ileostomy - Indications and outcomes from a tertiary centre.

PURPOSE: Pouch excision is a major complication of ileoanal pouch surgery. Current practice is for this type of surgery to be performed in a specialist centre. We present a series of patients undergoing pouch excision surgery in a high volume centre in the UK and assess the outcomes in these patients. METHODS: All patients undergoing pouch excision at the Royal Liverpool Hospital between 1995 and 2015 under the care of a single surgeon were included. Demographics and outcomes were taken from patients' notes and a dedicated retrospectively compiled database. RESULTS: 35 patients underwent pouch excision surgery during this period. Around half the patients had their original pouch surgery elsewhere and were referred for management of complications. Median time to pouch excision was 13 years from the original operation. Overall complication rate was 31% with 11% requiring re-intervention post-operatively. There was no mortality in this series. CONCLUSION: Pouch excision is a complex, high-risk procedure that should be carried out in specialist centres. Our series shows that in such settings, good outcomes can be achieved for these patients.

Circumferential resection margin (CRM) positivity after MRI assessment and adjuvant treatment in 189 patients undergoing rectal cancer resection.

PURPOSE: The management of rectal cancer relies on accurate MRI staging. Multi-modal treatments can downstage rectal cancer prior to surgery and may have an effect on MRI accuracy. We aim to correlate the findings of MRI staging of rectal cancer with histological analysis, the effect of neoadjuvant therapy on this and the implications of circumferential resection margin (CRM) positivity following neoadjuvant therapy. METHODS: An analysis of histological data and radiological staging of all cases of rectal cancer in a single centre between 2006 and 2011 were conducted. RESULTS: Two hundred forty-one patients had histologically proved rectal cancer during the study period. One hundred eighty-two patients underwent resection. Median age was 66.6 years, and male to female ratio was 13:5. R1 resection rate was 11.1%. MRI assessments of the circumferential resection margin in patients without neoadjuvant radiotherapy were 93.6 and 88.1% in patients who underwent neoadjuvant radiotherapy. Eighteen patients had predicted positive margins following chemoradiotherapy, of which 38.9% had an involved CRM on histological analysis. CONCLUSIONS: MRI assessment of the circumferential resection margin in rectal cancer is associated with high accuracy. Neoadjuvant chemoradiotherapy has a detrimental effect on this accuracy, although accuracy remains high. In the presence of persistently predicted positive margins, complete resection remains achievable but may necessitate a more radical approach to resection.

Faecal occult blood testing in areas of high incidence and mortality; the effect of screening the population aged 50 to 59.

AIM: In central Liverpool, the incidence of colorectal cancer (CRC) is 119% of the national average. Currently, screening is offered to those aged 60-70 through the National Bowel Cancer screening programme. A theoretical model showing the effect of the introduction of biennial screening in individuals aged 50-59 has been applied to the population of central Liverpool. METHOD: The impact of screening using faecal occult blood testing (FOBT) in individuals aged 50-59 in central Liverpool (n = 47,440; males 23,312) was assessed by a model based on three levels of compliance. RESULTS: After modelling, the positive FOBT result for increased incidence of CRC, the positive predictive value for adenoma and cancer detection was calculated using age-specific positivity rates. The results indicate that between 120 and 162 new diagnoses of CRC per 100,000 population aged 50-59 could be detected by biennial screening, dependent on compliance rates. CONCLUSION: Screening individuals aged 50-59 can identify early cancers and significant adenomas, which may contribute to a reduction in the expected high mortality rate found in this geographical area.

Apical node metastasis independently predicts poor survival in Dukes C colorectal cancer.

AIM: The prognostic significance of apical node metastasis in node-positive colorectal cancer (CRC) is disregarded by the Fourth American Joint Committee on Cancer and the International Union Against Cancer (AJCC/UICC) TNM classification system. The influence of apical node metastases on overall 5-year survival among patients with Dukes stage C CRC was examined. METHOD: Patients who underwent operative resection for CRC between 1999 and 2003 were reviewed. RESULTS: Two-hundred and ninety patients were included in the study, including 203 with Dukes C apical node-negative cancers, 39 with Dukes C apical node-positive cancers and 48 with Dukes D cancers. The respective prevalence of extramural vascular invasion was 35%vs 64%vs 56% (P = 0.0005), T4-stage 24%vs 38%vs 48% (P = 0.013), positive resection margin 16%vs 41%vs 23% (P = 0.001), more than three positive nodes harvested 28%vs 85%vs 52% (P < 0.0001) and poorer tumour differentiation grade 9%vs 21%vs 23% (P = 0.009). Multivariate analyses of all Dukes C cancer patients (n = 242) showed a positive apical node to be a highly significant independent predictor of mortality (hazard ratio 2.281, 95% confidence interval 1.421-3.662, P = 0.0006). Extramural vascular invasion and a positive resection margin were also independent predictors of poor survival. Patients with Dukes C apical node-positive cancers had a significantly poorer overall 5-year survival compared to patients with Dukes C apical node-negative cancers (P < 0.0001) but survival was not significantly different compared to patients with distant metastases at initial presentation (P = 0.504). CONCLUSION: Apical node metastasis appears to be a strong independent, negative prognostic factor of poor survival in Dukes C CRC.

Management of iatrogenic recto-urethral fistula by transanal rectal flap advancement.

AIM: Recto-urethral fistulas are an uncommon, but devastating complication following rectal or urinary tract surgery. Repair is often difficult, and the optimal approach is unclear. We report our recent experience using an endorectal advancement flap. METHOD: A case note review of all patients undergoing repair of recto-urethral fistula in our institution was undertaken. Data on aetiology of the fistula, patient demographics, operative procedure and outcome both clinically and radiologically were extracted. RESULTS: Between 2002 and 2008, six transanal rectal advancement flaps in five patients were carried out. Four had undergone a laparoscopic radical prostatectomy, without any radiotherapy. Two types of fistula (type 1 associated with severe intra-abdominal sepsis and type 2 associated with localized sepsis) were found, with faecal diversion being less likely with the latter. Four (80%) patients underwent successful primary repair, with one patient requiring a second procedure. Postoperative cystography confirmed closure of the fistula in all five patients, and no recurrence has been observed at a mean follow-up time of 11 months. CONCLUSION: Rectal advancement flap is a simple, effective technique for iatrogenic recto-urethral fistula with minimal morbidity.

The impact of lymph node yield on Duke's B and C colorectal cancer survival.

AIM: The number of positive lymph nodes retrieved following colorectal cancer (CRC) resection impacts on the staging and further treatment of the disease. We compared 5-year survival by lymph node yield for Duke's B and C patients to assess the impact on prognosis. METHOD: A retrospective methodology was employed to review patients who underwent operative resection for Duke's B or C CRC between 1999 and 2003. RESULTS: A total of 351 patients were included in our analyses. Lymph node yield, N-stage and extramural vascular invasion were independent predictors of overall 5-year survival. A significant difference in 5-year survival by lymph node yield was seen among Duke's B patients (< 9 nodes vs ≥ 9 nodes, 45.2%vs 68.4%; P = 0.0043) and Duke's C patients (< 10 nodes vs ≥ 10 nodes, 25.6%vs 48.8%; P = 0.0099). There was a significant reduction in the relative risk of 2.8% in mortality for each additional node sampled in Duke's B and C patients (RR 0.972, 95% confidence interval 0.949-0.994, P = 0.0102). Duke's B patients who had < 9 lymph node yield and no neoadjuvant/adjuvant treatment had a similar survival to all Duke's C patients (47.8%vs 41.7%, P = 0.5136). CONCLUSION: Lymph node yield independently predicts for survival in patients with Duke's B and C CRC. Duke's B patients with < 9 lymph node yield have no better survival than patients with Duke's C disease. Therefore, prospective randomized studies are required to examine if inadequate lymph node yield could be one of the deciding factors in offering adjuvant therapy among Duke's B cancer patients.

High tie of the inferior mesenteric artery in curative surgery for left colonic and rectal cancers: a systematic review.

BACKGROUND: During surgery for left colonic and rectal cancers, the inferior mesenteric artery (IMA) can be ligated either at its aortic origin (high tie) or below the origin of the left colic artery (low tie). There is no consensus as to which method should be employed. METHODS: We searched Medline, EMBASE, Cochrane collaboration, and National Guidelines Clearinghouse databases and undertook a systematic review on the use of IMA high tie during curative resections for left colonic and rectal cancers and its impact on patient survival, peri-operative morbidity and mortality, and lymph node retrieval rates. RESULTS: Sixteen studies were eligible for systematic review, including one randomized controlled study, 7 quasi-experimental studies, and 8 retrospective cohort studies. Data on 7,649 patients were analyzed, of whom 4,847 underwent high ligation of the IMA. Despite a trend for improved survival in patients in whom high tie was employed, there is no conclusive evidence to support this. Mortality and morbidity, including anastomotic leak and autonomic nerve injury rates, are similar, while lymph node retrieval is improved. CONCLUSIONS: Although there is no undisputable evidence of improved survival, the use of IMA high tie contributes to improved lymph node retrieval rates and accuracy of tumour staging.

Screening for rectal cancer: will it improve cure rates?

Here we give an overview of colorectal cancer screening strategies with an emphasis on the diagnosis and management of rectal cancer. We review the published studies on screening in the high-risk population, including patients with a history of colorectal cancer, inflammatory bowel disease and inherited conditions. In the average-risk population, the evidence base for a number of screening strategies is evaluated, including endoscopy, contrast studies and faecal occult blood testing. Screening guidelines in the high-risk population are predominantly based on case-control studies comparing the incidence of colorectal cancer in screened and control groups. Screening the average-risk population for colorectal cancer reduces cancer-specific mortality by 15% after biennial guaiac faecal occult blood testing and 50-80% after flexible sigmoidoscopy. All of the screening strategies outlined have a greater sensitivity for distal lesions than proximal lesions.

DNA content of rectal mucosa and rectal mucosal proliferation in individuals at high risk of colorectal cancer.

Genetic changes are important in the development of colorectal cancer. Ploidy and rectal mucosal proliferation were measured in histologically normal rectal mucosa of 85 individuals (mean age 59 years, range 29-74) who had a total colonoscopy. Fifty-one subjects had an adenoma or were undergoing adenoma surveillance. Twenty-two subjects had a strong family history of colorectal cancer and 12 individuals comprised a control group who had a normal colonoscopy without a family history of colorectal cancer. An abnormal DNA content (aneuploidy) was found in the normal mucosa of nine (10.6%) individuals. There was no significant difference in rectal mucosal proliferation with those who had aneuploidy and those who had diploidy. There was a trend towards increased proliferation in those with aneuploidy and adenomas, compared with controls. Of the 35 individuals undergoing adenoma surveillance, eight had recurrent adenomas, and three of these expressed aneuploidy. In the other 27, in whom no adenomas were found, no individual expressed aneuploidy (P = 0.01, Fisher's exact test). Aneuploidy within histologically normal mucosa is an unusual feature, which requires further investigation, particularly in patients developing adenomas.

Cell kinetics of the in vitro metaphase arrest technique and the clinical applications.

The in vitro metaphase arrest technique (crypt cell production rate-CPPR) has been used to measure human rectal mucosal proliferation. Study of preincubation times, dose response curves and lag phases suggest that a concentration of vincristine of 5 micrograms/ml and 16 hour preincubation with time point increments between 25 and 125 minutes give optimal conditions for measuring rectal mucosal proliferation. Twenty individuals had rectal CCPR repeated without intervention of any kind. Close correlation was found between the two values (r = 0.89 and P = 0.0001). The effect of polyethylene glycol bowel preparation was also studied in 35 subjects. There was good correlation (r = 0.66, P = 0.007). There was close correlation between rectal and caecal CCPR as measured in 20 patients who had colonoscopy (r = 0.72, P = 0.0003). The in vitro metaphase arrest technique is a useful parameter of rectal mucosal proliferation and may be used with confidence in a number of different clinical situations.

Somatostatin receptors in human colorectal cancer.

We have previously reported that somatostatin may reduce tumour cellular proliferation in patients with colorectal carcinoma. However, it is not known what proportion of primary colorectal cancers express somatostatin receptors. We have therefore evaluated somatostatin receptor status in 50 primary colorectal cancers. Twelve (24%) of the cancers were shown to be somatostatin receptor positive. There was no correlation between receptor status and tumour stage or grade.

Size of metastatic deposits affects prognosis in patients undergoing pulmonary metastectomy for colorectal cancer.

INTRODUCTION: Pulmonary metastectomy for colorectal cancer (CRC) is a well accepted procedure although data regarding indications and prognostic outcomes are inconsistent. This study aimed to analyse our experience with resection of pulmonary CRC metastases to evaluate clinically relevant prognostic factors affecting survival. METHODS: A retrospective analysis was undertaken of the records of all patients with pulmonary metastases from CRC who underwent a thoracotomy between 2004 and 2010 at a single surgical centre. RESULTS: Sixty-six patients with pulmonary metastases from the colon (n=34) and the rectum (n=32) were identified. The 30-day hospital mortality rate was 0%, with 63 patients undergoing a R0 resection and 3 having a R1 resection. The median survival was 45 months and the cumulative 3-year survival rate was 61%. Size of pulmonary metastasis and ASA (American Society of Anesthesiologists) grade were statistically significant prognostic factors (p=0.047 and p=0.009 respectively) with lesions over 20mm associated with a worse prognosis. Sex, age, site, disease free interval (cut-off 36 months), primary tumour stage, hepatic metastases, number of metastases (solitary vs multiple), type of operation (wedge vs lobe resection), hilar lymph node involvement and administration of adjuvant chemotherapy were not found to be statistically significant prognostic factors. CONCLUSIONS: Pulmonary metastectomy has a potential survival benefit for patients with metastatic CRC. Improved survival even in the presence of hepatic metastases or multiple pulmonary lesions justifies aggressive surgical management in carefully selected patients. In our cohort, size of metastatic deposit was a statistically significant poor prognostic factor.

Small, flat colorectal cancers in the UK population: an analysis of resected specimens.

OBJECTIVES: To establish the prevalence of small, flat carcinomas in surgically resected colon. To determine whether tumour morphology influences stage at presentation. METHOD: 1763 surgically resected colorectal cancers from one UK centre excised between 1995 and 2004 were examined. Age 69 years, (42-90), M:F equal. Sixty-one tumours < or =20 mm across were identified. Slides were reviewed by a consultant histopathologist and classified using Japanese Research Society Classification, JRSC and TNM staging. Fisher's exact test was used for analysis. RESULTS: In 61 small cancers, 64% (39/61) showed flat morphology and 33% (20/61) polypoid. Two lesions were unclassifiable. Prevalence was 2.2% of all resected colorectal cancers. More T1 tumours at presentation were polypoid, (30% vs. 8%; P = 0.033). T3 tumours were more likely to be flat than polypoid, (49% vs. 20%; P = 0.016). Infiltration into musclaris mucosa occurred in 77% (30/39) flat tumours. Rates of metastases were high in both groups, (30% polypoid vs. 39% flat, not significant). CONCLUSIONS: The prevalence of small, flat cancers in resected specimens in the UK concurs with that of Japanese studies. Small, flat cancers should be staged carefully because of high rates of T3/4 disease. The results support the theory of accelerated carcinogenesis in flat cancers.

Outcomes in 2748 patients referred to a colorectal two-week rule clinic.

OBJECTIVE: To assess the 3-year outcomes of a nurse-led, one-stop, 2-week rule (TWR) clinic for suspected colorectal cancer (CRC) in a large teaching hospital. METHOD: Data were collected prospectively from January 2002 to December 2004. In total, 2748 patients were seen over the 3-year period. The ratio of male:female subjects was 1190:1558 (43%:57%). Median age at presentation was 66 years (range 17-96). RESULTS: A total of 1363 (49.6%) nonconforming referrals were made; 1300 patients (47.3%) underwent flexible sigmoidoscopy during their initial assessment in clinic; 1439 patients (52.4%) underwent a barium enema during the course of their investigation; 2503 patients (91.1%) were seen within 14 working days. The median overall wait for the initial clinic appointment was 10 days. The annual number of patients seen was similar over the 3-year period. A total of 174 cancers (6.3%) were identified which accounted for 36.4% of all CRCs diagnosed during the study period. Nineteen cancers presented in the nonconforming group (1.6% of all non-conforming patients). Rectal tumours accounted for 59.8% (n = 104) of all cancers diagnosed while right-sided tumours accounted for only 10.9% (n = 19). Advanced tumours accounted for 73.0% (n = 127) of the total; 133 (76.4%) cancer patients underwent some form of surgical intervention. CONCLUSION: A specialist nurse-led, one-stop TWR clinic for suspected colorectal cancer is sustainable and can be run successfully with over 90% of referrals seen within the targeted time period. The proportion of non-conforming referrals was high and a large number of advanced and unstaged tumours was observed. Low numbers of proximal tumours were detected.

Colorectal cancer--a prospective evaluation of symptom duration and GP referral patterns in an inner city teaching hospital.

OBJECTIVE: A high percentage of colorectal cancer patients (CRC) present as an emergency. Our aim was to evaluate delays in referral based on patient and general practitioner (GP) factors to see if there was any difference between elective and emergency patients. METHOD: Symptom questionnaires were prospectively collected from 101 consecutive patients presenting to a single colorectal unit (58 male, 43 female; median age 72 years) and entered into a database. Questionnaires assessed time from symptom onset until first GP visit, time for GP to refer, and type of admission. Symptoms and Dukes stage were noted. RESULTS: Fifty-eight (57%) patients presented electively and 43 (43%) as an emergency. Eighty-eight patients (87%) saw their GP of which 34 (39%) later presented as emergency; 13 (13%) did not see their GP. The median time before patients first sought medical advice was 30 days (0-1095 days). Median delay until treatment was 90 days (range 0-1460 days). Emergency patients waited a median of 11.5 days before visiting the GP, and elective a median of 49.5 days (P = 0.04) (Mann-Whitney U). Nine of 13 patients who did not see their GP presented as an emergency (median wait 44 days). The median time taken for a GP to refer to a hospital specialist was 28 days in elective patients and 14 days in the emergency group. (P = ns) Thirty (38%) patients took longer than six weeks to be referred (33% as an emergency). Thirty-six patients had Dukes A or B and took a median of 30 days to first presentation. Sixty-five had Dukes C or D and took a median of 32 days to first presentation. (P = ns) CONCLUSION: Emergency patients have symptoms for less time before seeking medical advice compared to elective patients. The duration of these symptoms is unrelated to the histological stage at diagnosis. Although the majority of GPs referred CRC patients within six weeks, there was no association between time taken to refer and mode of presentation. The factors that relate to disease stage occur before symptoms are acted on.

Use of the ultrathin choledochoscope in cholecystectomy.

Use of the ultrathin choledochoscope (2mm) was evaluated in 80 patients undergoing routine cholecystectomy. It was used successfully in 67 (84 per cent) patients. There were eight (12 per cent) explorations of the common bile duct and no negative explorations. The instrument was helpful in determining the nature of an equivocal on-table cholangiogram. The ultrathin choledochoscope may be useful in reducing the rate of negative common bile duct exploration.

The standard of laparoscopic intraoperative cholangiography: a quality control study.

BACKGROUND AND STUDY AIMS: One reason why many surgeons do not attempt laparoscopic cholangiography is that it is considered to be technically difficult and to produce poor-quality images. PATIENTS AND METHODS: A retrospective comparison was made of twenty randomly selected intraoperative cholangiograms taken during laparoscopic cholecystectomy for each year from 1991 to 1994 (n = 80) by assigning a score (0-4) on the basis of anatomical parameters and radiographic quality. Twenty randomly selected intraoperative cholangiograms taken during open cholecystectomy (OC) were used as controls. RESULTS: The average score for the laparoscopic cholangiograms (LCs) was significantly lower than the average for OC cholangiograms (2.3 vs. 3.4, P< 0.001). In addition, a learning curve was demonstrated, which showed significant improvement in the quality of LCs over the years. Analysis showed that in LCs, only 34 % succeeded in demonstrating the entire biliary tree and only 49% managed to show the extrahepatic duct system. Choledocholithiasis could only be ruled out in 53 % of LC films, compared with 80 % of controls. CONCLUSIONS: Despite an improvement in the quality of laparoscopic cholangiography, it remains inferior to cholangiography during open cholecystectomy. Recommendations are made regarding ways in which improvements could be achieved.

Endoscopic screening of relatives of patients with colorectal cancer.

BACKGROUND: The risk of colorectal cancer is higher among relatives of those affected. The neoplastic yield reported from screening such individuals varies enormously between studies and depends on the age and strength of the family history of those screened. AIMS: To ascertain the neoplastic yield of endoscopic screening of first degree relatives of patients with colorectal cancer by age and familial risk. SUBJECTS: A total of 330 individuals with a family history of colorectal cancer. METHOD: Endoscopic screening conducted according to a protocol. RESULTS: Adenomas were found in 12%, and adenomas larger than 1 cm in 8%, of "high risk" individuals screened primarily by colonoscopy. Of those with neoplasia, 26% had lesions at or proximal to the splenic flexure. Neoplasia was found in 9.5% of individuals at lower familial risk, screened primarily by 60 cm flexible sigmoidoscopy, 4% of whom had neoplasia larger than 1 cm in size or cancer. Neoplastic yield was greatest in the fourth and fifth decades in those at highest risk, but increased with age in those at lower risk. CONCLUSIONS: For individuals with two or more first degree relatives, or relatives who have developed colorectal cancer at a young age, colonoscopy appears to be the only satisfactory method of screening, but 60 cm flexible sigmoidoscopy may be useful in those at lower levels of risk.