The lymph node ratio does not provide additional prognostic information compared with the N1/N2 classification in Stage III colon cancer.

AIM: The ratio of positive nodes to total nodes, the lymph node ratio (LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer. METHOD: Patients with Stage III colon cancer were identified from a prospectively maintained database (1996-2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut-off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000-fold was performed. This was then repeated for disease-specific survival. RESULTS: The specificity and sensitivity of the N1/N2 classification in predicting 3-year overall survival in this cohort (n = 402) was 62.2% and 52.1%, respectively. The cut-off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease-specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44). CONCLUSION: Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease-specific survival for a given cut-off point.

Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

BACKGROUND: Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. METHODS: Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. RESULTS: Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p < 0.001). For Stage I and II disease MSI was associated with improved disease free survival (DSS) compared with MSS colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. CONCLUSION: MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes.

Brain metastasis from colorectal carcinoma: a single cancer centre experience.

PURPOSE: Brain metastases (BM) from colorectal cancer (CRC) are rare. As survival increases in patients with metastatic CRC, it is hypothesised that new metastatic patterns will emerge: for instance, as CRC with limited metastatic involvement of the liver and lung can now be successfully resected, we propose that sites, previously rarely involved in metastatic spread, will become more common. The objective of this study was to describe the experience with BM from CRC in a single cancer centre. METHODS: A prospectively compiled database (1988-2012) of patients with CRC treated in a tertiary referral hospital was retrospectively examined. Patients with a histological diagnosis of CRC and radiologically documented BM were included. Clinical information (including patient demographics, primary and metastatic disease factors) was obtained from medical records. RESULTS: Eleven patients (0.3 % of 4219 patients) were identified (8 male, 3 female). The median age at CRC diagnosis was 70 years (range 55-80 years) while the median age at diagnosis of BM was 73 years (range 56-83 years). Three patients diagnosed with synchronous metastases underwent palliative treatment while eight patients had undergone surgical resection of the primary tumour with curative intent a median of 24 months (range 0-48 months) prior to diagnosis of BM. 10/11 patients were symptomatic at diagnosis of BM. All were diagnosed using computed tomography and managed palliatively. The cerebellum was most the frequently involved site. The median overall survival time following diagnosis of BM was 2.5 months (range 2-9 months). Notably, 8/11 patients were diagnosed in the latter 8 years of the study period (between 2004 and 2012). CONCLUSION: With increased survival, improved systemic therapy and aggressive approaches to surgical management of "classical" metastases from CRC, it is likely that a changing pattern of metastases will emerge. As survival rates increase, we propose that metastatic sites, which were previously considered rare (e.g. brain), will now become more common and thus, surgeons must recognise pertinent symptomatology.

Primary colorectal lymphoma - A single centre experience.

PURPOSE: The incidence of primary colorectal lymphoma (PCL) is rare (0.2-0.6% of large bowel malignancy). Up to one third of Non-Hodgkin's lymphoma will present with extra-nodal manifestations only. Extra-nodal lymphomas arise from tissues other than the lymph nodes and even from sites, which contain no lymphoid tissue. The incidence of Non-Hodgkin's lymphoma has increased over the past fifty years. The objective of this study was to examine our experience of PCL. METHODS: A prospectively-compiled database (1988-2012) of patients with colorectal cancer was retrospectively examined for cases of colorectal lymphoma. A retrospective chart review identified cases of PCL based on Dawson's criteria. Clinical information was obtained from case notes. RESULTS: Eleven patients (0.3% of 4219 patients) were identified (6 male, 5 female). The median age at diagnosis was 63 years. Mode of presentation varied; abdominal pain, a palpable mass and per rectal bleeding being the most frequent. The caecum was the most frequently involved site (5/11). Nine patients underwent surgical management, one had chemotherapy alone and one had radiotherapy alone. All cases were non-Hodgkin's lymphoma, with diffuse large B-cell lymphoma in majority. The median event-free survival of those treated with surgery and post-operative chemotherapy was 10 months (range 5-120 months). CONCLUSION: Primary colorectal lymphoma is rare. Management is multidisciplinary and dependent on the subtype of lymphoma. Due to the rarity of diagnosis, there is a paucity of randomised control trials. Most information published is based on individual case reports and there is, thus, no clear treatment algorithm for these cases.

Open versus laparoscopic abdominal rectopexy: an examination of early postoperative outcomes.

BACKGROUND: Abdominal rectopexy is used to treat full thickness rectal prolapse and obstructed defecation syndrome, with good outcomes. Use of a laparoscopic approach may reduce morbidity. The current study assessed short-term operative outcomes for patients undergoing laparoscopic or open rectopexy. METHODS: Rectopexy cases were identified from theater logs in two tertiary referral centers. Patient demographics, intra-operative details and early postoperative outcomes were examined. RESULTS: There were 62 patients included over 10 years, a third of whom underwent laparoscopic rectopexy. Laparoscopy was associated with a longer operative time (195.9 versus 129.6 min, p = 0.003), but this did not affect postoperative outcomes, with no significant differences found for complication rates and length of stay between the two groups. Univariable analysis found no influence of laparoscopic approach on the likelihood of postoperative complications, and no factor achieved significance with multivariable analysis. This study included the first laparoscopic cases performed in the involved institutions, and a "learning curve" existed as seen with a decreasing operative duration per case over time (p = 0.002). CONCLUSIONS: Laparoscopic rectopexy has similar short-term outcomes to open rectopexy.

Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive.

BACKGROUND: Tumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs. METHODS: Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA. RESULTS: TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs. CONCLUSION: Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC.

Management of colorectal cancer in patients with inflammatory bowel disease.

BACKGROUND: This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC). METHODS: A retrospective review was performed on a prospectively maintained institutional database (1981-2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed. RESULTS: A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn's disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups. CONCLUSIONS: Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.

Management of synchronous rectal and prostate cancer.

PURPOSE: Although well described, there is limited published data related to management on the coexistence of prostate and rectal cancer. The aim of this study was to describe a single institution's experience with this and propose a treatment algorithm based on the best available evidence. METHODS: From 2000 to 2011, a retrospective review of institutional databases was performed to identify patients with synchronous prostate and rectal cancers where the rectal cancer lay in the lower two thirds of the rectum. Operative and non-operative outcomes were analysed and a management algorithm is proposed. RESULTS: Twelve patients with prostate and rectal cancer were identified. Three were metachronous diagnoses (>3-month time interval) and nine were synchronous diagnoses. In the synchronous group, four had metastatic disease at presentation and were treated symptomatically, while five were treated with curative intent. Treatment included pelvic radiotherapy (74 Gy) followed by pelvic exenteration (three) and watchful waiting for rectal cancer (one). The remaining patient had a prostatectomy, long-course chemoradiotherapy and anterior resection. There were no operative mortalities and acceptable morbidity. Three remain alive with two patients disease-free. CONCLUSIONS: Synchronous detection of prostate cancer and cancer of the lower two thirds of the rectum is uncommon, but likely to increase with rigorous preoperative staging of rectal cancer and increased awareness of the potential for synchronous disease. Treatment must be individualized based on the stage of the individual cancers taking into account the options for both cancers including EBRT (both), surgery (both), hormonal therapy (prostate), surgery (both) and watchful waiting (both).

How I do it: the stapled ileal J pouch at restorative proctocolectomy.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) following proctocolectomy is the preferred option for patients with medically refractory ulcerative colitis, indeterminate colitis, and familial adenomatous polyposis. However, it remains a procedure associated with morbidity and mortality. Pelvic sepsis, pouch fistulae, and anastomotic dehiscence predispose to pouch failure. We report our experience with an adaptation for the formation of the stapled ileal J pouch using the GIA™ 100 stapling device (Covidien, Mansfield, Massachusetts, USA). When creating the J pouch, we remove the bevelled plastic protector from the thin fork of the stapling device, allowing the staple line to be completed to the tip of the stapled efferent limb of the pouch, thereby minimizing potential blind ending in the efferent limb and injury to the transverse staple line. METHODS: Patients undergoing elective IPAA at our institution over a 5-year period using this adapted stapling technique for creation of the ileal J pouch were reviewed. Data were collected from a prospectively maintained inflammatory bowel disease database, theater records, and patient chart review. RESULTS: Forty-one patients underwent IPAA using this technique at our institution during the study period. Postoperative morbidity was encountered in 11 of 41 patients including pelvic sepsis, pouch fistulae, anastomotic stricture, or leak. There was no morbidity observed related to a blind efferent limb or transverse staple line disruption. No mortality was observed in this series. CONCLUSION: Maximizing the length of the efferent fork of the GIA stapling device can reduce the length of redundant efferent J limb of the ileal J pouch. This may reduce the incidence of torsion, volvulus, distension, fistulae/sinuses, and pelvic sepsis/anastomotic leak following IPAA.

Use of an electrothermal bipolar sealing device in ligation of major mesenteric vessels during laparoscopic colorectal resection.

BACKGROUND: A variety of approaches are available for division of major vascular structures during laparoscopic colorectal resection. Ultrasonic coagulating shears (UCS), vascular staplers, plastic or titanium clips and electrothermal bipolar vessel sealing (EBVS) are currently available. We report our experience with an EBVS device, LigaSure™ (Covidien AG), used in division of the ileocolic, middle colic and inferior mesenteric arteries during laparoscopic colorectal resection. METHODS: We report the immediate outcome of 802 consecutive unselected patients who underwent elective laparoscopic colorectal cancer resection performed with use of the LigaSure™ (5 and 10 mm) at our institution over a 5-year period. Operative procedures included right hemicolectomy (n = 180), left hemicolectomy (n = 96), sigmoid colectomy (n = 347) and anterior resection (n = 179). Data were collected from a prospectively maintained cancer database and operative records. The procedures were performed primarily by three consultant surgeons with an interest in laparoscopic colorectal resection. RESULTS: Of 802 cases in which the LigaSure™ device was employed to divide major vascular structures, immediate effective vessel sealing was achieved in 99.8% (n = 800). Two patients experienced related adverse events both following division of the inferior mesenteric artery with a 5 mm LigaSure™. Both patients had immediate uncontrolled haemorrhage that required laparotomy. CONCLUSIONS: Use of the LigaSure™ device to seal and divide the major mesenteric vessels during laparoscopic colorectal resection is very effective, with a high success rate of 99.8%. Caution should be exercised in elderly atherosclerotic patients, particularly when using the 5-mm LigaSure™ device.

A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Locally advanced rectal cancer is frequently treated with neoadjuvant chemoradiotherapy to reduce local recurrence and possibly improve survival. The tumor response to chemoradiotherapy is variable and may influence the prognosis after surgery. This study assessed tumor regression and its influence on survival in patients with rectal cancer treated with chemoradiotherapy followed by curative surgery. METHODS: One hundred twenty-six patients with locally advanced rectal cancer (T3/T4 or N1/N2) were treated with chemoradiotherapy followed by total mesorectal excision. Patients received long-course radiotherapy (50 Gy in 25 fractions) in combination with 5-flourouracil over 5 weeks. By means of a standardized approach, tumor regression was graded in the resection specimen using a 3-point system related to tumor regression grade (TRG): complete or near-complete response (TRG1), partial response (TRG2), or no response (TRG3). RESULTS: The 5-year disease-free survival was 72% (median follow-up 37 months), and 7% of patients had local recurrence. Chemoradiotherapy produced downstaging in 60% of patients; 21% of patients experienced TRG1. TRG1 correlated with a pathological T0/1 or N0 status. Five-year disease-free survival after chemoradiotherapy and surgery was significantly better in TRG1 patients (100%) compared with TRG2 (71%) and TRG3 (66%) (P = .01). CONCLUSION: Tumor regression grade measured on a 3-point system predicts outcome after chemoradiotherapy and surgery for locally advanced rectal cancer.

Outbreak of Legionnaires' disease in West Fife: review of environmental guidelines needed.

OBJECTIVES: The objectives of this study were to investigate the source of and outbreak of Legionnaires' disease in West Fife in 2004; to control the spread of legionella from this source; and to make recommendations for future practice based on the findings from the investigation. STUDY DESIGN: Outbreak investigation. METHODS: A multi-agency team investigated links between the cases of legionellosis using detailed interviews, movement mapping, a timeline and extensive environmental sampling. RESULTS: The investigation found evidence that individuals affected by legionella during this outbreak had been in, or near (within 800 m), sullage tanks in Rosyth Dockyard within a period of 4 months. CONCLUSIONS: In the absence of laboratory isolation of Legionella spp. from the human cases, it was impossible to state definitely that a previously unrecognized source of environmental legionella aerosolization was responsible for the outbreak. However, strong epidemiological and environmental evidence would support this hypothesis.

Laparoscopic colorectal resection: initial experience in a specialist unit.

The adoption of the laparoscopic approach to colorectal resection has been slow amongst colorectal surgeons principally due to concerns regarding oncological safety. Recent randomized controlled trials have confirmed both the safe and some advantage of this procedure have been performing laparoscopic assisted colorectal resection since 2002 and have now performed over 100 cases on non consecutive and selected patients. We have reviewed our experience with the introduction of this technique. 61 patients were operated on for cancer and 39 for benign disease mainly Crohn's and diverticular disease. Operative time was a median of 128 minutes over the course of study. Conversion rate was 5%. Pathological analysis of the resected specimens in the cancer cases revealed adequate lymph node harvest and margins. No patient had a positive margin and no port site metastasis have been seen. Duration of ileus and length of stay were a median of 0 and 6 days. Post operative morbidity and mortality were comparable to open colorectal surgery with the exception of port site herniation which occurred in 4% of patients. This study suggests that a laparoscopic approach to colorectal resection can be successfully introduced in an Irish hospital setting. The challenge facing Irish surgery is to disseminate this technique in a controlled and safe manner for Irish patients.

Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

AIMS: To standardize the pathological analysis of total mesorectal excision specimens of rectal cancer following neoadjuvant chemoradiotherapy for locally advanced disease (T3/T4), including tumour regression. METHODS AND RESULTS: Standardized dissection and reporting was used for 60 patients who underwent total mesorectal excision following long-course chemoradiotherapy. Tumour regression was scored by two pathologists (K.S., D.G.) using both an established 5-point tumour regression grade (TRG), and a novel 3-point grade. Both scores were evaluated for interobserver variability. A complete or near-complete pathological response (3-point TRG 1) was found in 10 patients (17%). Using the 5-point TRG, there was good agreement between both pathologists (kappa = 0.64). Using the 3-point grade, agreement was excellent (kappa = 0.84). No disease recurrence has been reported in patients with a complete, or near complete pathological response (3-point TRG 1), after a mean follow-up of 22 months. CONCLUSION: Tumour regression grade is a useful method of scoring tumour response to chemoradiotherapy in rectal cancer. TRG 1 and 2 can be regarded as a complete pathological response (ypT0). A modified 3-point grade has the advantage of better reproducibility, with similar prognostic significance.

Diagnosis and treatment of enterovesical fistulae.

OBJECTIVE: Enterovesical fistulae are a recognized complication of a variety of inflammatory and neoplastic conditions. Despite advances in imaging and treatment the diagnosis may be delayed and the management remains diverse. We describe our experience with their diagnosis and management. PATIENTS AND METHODS: This retrospective study encompassed all patients referred over a 10-year period with clinical suspicion of or confirmed enterovesical fistula. Demographics, clinical presentation, aetiology and clinical outcome were evaluated. Mean follow-up was 18 months (range 6-50 months). RESULTS: Thirty patients were studied. The mean age was 63.5 years (range 23-92 years). Fifteen (50%) patients presented with classical urinary symptoms (pneumaturia, faecaluria and recurrent urinary tract infections). The commonest investigations (n, % positive) included CT (15, 80), cystoscopy (16, 87.5), endoscopy (11, 54.5) and barium enema (8, 50). There were 20 inflammatory and 10 neoplastic aetiologies. Five patients were treated conservatively and 25 patients underwent surgery. Surgery resulted in symptomatic cure in the majority of cases (22/25). CONCLUSION: Classical urinary symptoms were only evident in 50% of patients with confirmed fistulae. We advocate CT scanning as the optimum imaging modality before surgical intervention. Surgical treatment in a specialized unit remains the most effective treatment of enterovesical fistulae.

Perianal Crohn's disease and infliximab therapy.

INTRODUCTION: Perianal manifestations occur in almost half of patients with Crohn's disease and often respond poorly to conventional therapies. The introduction of anti-tumour necrosis factor alpha agents (e.g. infliximab) has altered the management of patients who fail first and second line medical and surgical therapies. METHODS: We performed a literature search of the PubMed database using the Medical Search Headings infliximab, perianal Crohn's disease, fistulae, cost and safety. We also performed a manual search using references from these articles, review articles and proceedings from major gastroenterology meetings. RESULTS: Use of infliximab, at a dose of 5mg/kg at intervals of 0, 2 and 6 weeks, results in significant improvement in disease in approximately 70% of patients with fistulae. Prior examination under anaesthesia with placement of non-cutting seton sutures in fistula tracks is a useful adjunct in many patients. Preliminary results show a benefit from maintenance infliximab therapy and from concomitant use of immunosuppressants such as azathioprine. No clinical or biochemical markers have been identified which predict non-response to infliximab, although its use is contraindicated in patients with strictures. Acute infusion reactions are the most common side-effect of infliximab therapy and they are usually mild. Despite initial fears, the incidence of opportunistic infection is low. There is inadequate information, at present, regarding a possible increase in incidence of lymphoma with infliximab therapy. Infliximab is expensive compared with established therapies and its use will increase the lifetime cost of treating Crohn's disease. CONCLUSION: While infliximab is a useful adjunct in selected patients, the cornerstones of management of perianal Crohn's are essentially unchanged.

Expression of Cathepsin B and L antigen and activity is associated with early colorectal cancer progression.

Cathepsin B and Cathepsin L are cysteine proteases important in the process of invasion and metastasis. The aim of our study was to assay antigen and activity levels of these enzymes and to correlate these with established clinical and pathological prognostic parameters including patient survival. 99 patients undergoing operations for colorectal cancer were included in this study. We quantitated cathepsin B and L levels in matched normal mucosa and cancer samples using an enzyme-linked immunosorbent assay (ELISA) and specific activity assays and expressed the results as tumour/normal ratios. Significant correlations were found between tumour/normal cathepsin B and L antigen and activity ratios. Cathepsin B and L tumour/normal activity ratios were greater than 1 in early stage disease and there were gradual reductions in cathepsin B (P = 0.02) and L (P = 0.03) activity ratios with advancing tumour stage. Survival of patients with potentially curative disease was inversely related to both cathepsin B (P = 0.007) and L (P = 0.001) activity ratio, in addition to cathepsin L antigen ratio (P = 0.008). Our findings suggest that cysteine proteases play an important role in colorectal cancer progression.