Robotic colon surgery in obese patients: a systematic review and meta-analysis.

BACKGROUND: Colon cancer resection can be technically difficult in the obese (OB) population. Robotic surgery is a promising technique but its benefits remain uncertain in OB patients. The aim of this study is to compare OB versus non-obese (NOB) patients undergoing robotic colon surgery, as well as OB patients undergoing robotic versus open or laparoscopic colonic surgery. METHODS: A systematic review and meta-analysis was performed. Primary outcome measures included length of stay (LOS), surgical site infection (SSI) rate, complications, anastomotic leak and oncological outcomes. RESULTS: A total of eight studies were included, with five comparing OB and NOB patients undergoing robotic colon surgery included in meta-analysis. A total of 263 OB patients and 400 NOB patients formed the sample for meta-analysis. There was no significant difference between the two groups in operative time, conversion to open, LOS, lymph node yield, anastomotic leak and postoperative ileus. There was a trend towards a significant increase in overall complications and SSI in the OB group (32.3% OB versus 26.8% NOB for complications, 14.2% OB versus 9.9% NOB for SSI). The three included studies comparing surgical techniques were too heterogeneous to undergo meta-analysis. CONCLUSION: Robotic colon surgery is safe in obese patients, but high-quality prospective evidence is lacking. Future studies should report on oncological safety and the cost-effectiveness of adopting the robotic technique in these challenging patients.

The National Aeronautics and Space Administration-task load index: NASA-TLX: evaluation of its use in surgery.

BACKGROUND: The technical difficulty an operation creates for a surgeon is difficult to measure. Current measures are poor surrogates. In both research and teaching settings it would be valuable to be able to accurately measure this degree of difficulty. The National Aeronautics and Space Administration Task Load Index (NASA TLX) is a multi-dimensional scale designed to obtain workload estimates relating to a task. This study aimed to evaluate the NASA TLX as an objective measure of technical difficulty of an operation. METHODS: Seven surgeons performed 127 pre-defined operations (minimally invasive right hemicolectomy & re-do bariatric surgery) and recorded a NASA TLX score after each operation. These scores were compared to numerous clinical parameters and the score was correlated with the subjective measure of whether the surgeon categorized the operation as "easy", "moderate" or "difficult". RESULTS: The NASA TLX score was significantly correlated with operative duration, blood loss, previous abdominal surgery and the surgeons' assessment of difficulty. It did not correlate with intra-operative or post-operative complications, conversion to open surgery or length of stay. CONCLUSIONS: The NASA TLX score provides a graded numerical score that that correlated significantly with the surgeon's assessment of the technical difficulty, and with operative duration, intra-operative blood loss and previous abdominal surgery. This novel application of this tool could be employed in both research and teaching settings to score surgical difficulty and monitor a trainee's proficiency over time.

Melbourne colorectal collaboration: a multicentre review of the impact of COVID-19 on colorectal cancer in Melbourne, Australia.

BACKGROUND: As coronavirus (COVID-19) cases continue to rise, healthcare workers have been working overtime to ensure that all patients receive care in a timely manner. Our study aims to identify the impact and outcomes of COVID-19 on colorectal cancers presentations across the five major colorectal units in Melbourne, Australia. METHODS: This is a retrospective study from a prospectively collected database from the binational colorectal cancer audit (BCCA) registry, as well as inpatient records. All patients with colorectal cancer between Pre-COVID-19 period (1 July 2018-2030 June 2019) and COVID-19 period (1 July 2020-2030 June 2021) were compared. Benign pathology and other cancer types were excluded. RESULTS: A total of 1609 patients were included in the study (700 Pre-COVID-19 period, 906 COVID-19 period). During COVID-19 period, there was a higher proportion of emergency surgery (28.1% vs. 19.8%; P < 0.001), a higher nodal (P = 0.024) and metastatic stage (P = 0.018) at presentation, but no increase in the rate of return to operating theatres (P = 0.240), inpatient death (P = 0.019) or 30-day readmission (P = 0.000). There was also no difference in the post-operative surgical complications (P = 0.118). Utility of neoadjuvant therapy did not increase during the pandemic (P = 0.613). CONCLUSION: The heightened measures in the healthcare system ensured CRC patients still received their surgery in a timely fashion. With the current rise in the new strain of COVID-19 (Omicron), we have to continue to come up with new strategies to provide timely access to CRC care.

Surgical Techniques for Abdominoperineal Resection for Rectal Cancer: One Size Does Not Fit All.

Abdominoperineal resection (APR) of rectal cancer is associated with poorer oncological outcomes than anterior resection. This may be due to higher rates of intra-operative perforation (IOP) and circumferential resection margin (CRM) involvement causing higher recurrence rates and surgical complications. To address these concerns, several centers advocated a change in technique from a standard APR to a more radical extra-levator abdominoperineal excision (ELAPE). Initial reports showed that ELAPE reduced IOP rates and CRM involvement but increased wound complications and longer surgical duration. However, many of these studies had unacceptable rates of IOP and CRM before retraining in ELAPE. This may indicate that it was a sub-optimal surgical technique, which improved upon training, that had influenced the high CRM and IOP rates rather than the technique itself. Subsequent studies demonstrated that the CRM involvement rate for ELAPE was not always lower than for standard APR and, in some cases, significantly higher. The morbidity of ELAPE can be high, with studies reporting higher adverse events than APR, especially in terms of wound complications from the larger perineal incision required in ELAPE. Whether ELAPE improves short- or long-term oncological outcomes for patients has not been clearly demonstrated. The authors propose that all centers performing rectal cancer surgery audit surgical outcomes of patients undergoing APR or ELAPE and examine CRM involvement, IOP rates, and local recurrence rates, preferably through a national body. If rates of adverse technical or oncological outcomes exceed acceptable levels, then retraining in the appropriate surgical techniques may be indicated.

Latest evidence on the management of early-stage and locally advanced rectal cancer: a narrative review.

Rectal cancer is a challenging disease process to manage, with a rising incidence in young adults. Several clinical advances have been made in the past decade with regards to optimal treatment strategies in early-stage (T1-2, node negative tumours) and locally advanced cancers (T3-4 and/or nodal positivity) utilizing a multimodal approach of surgery, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy, all aiming to optimize oncological outcomes, while minimizing associated morbidity. This narrative review aimed to summarize trial level evidence apropos the management of early and locally advanced rectal cancer. All relevant prospective clinical trials were identified through a computer-assisted search of PubMed, EMBASE, Medline databases between 1990 and 30 June 2021. With regards to early rectal cancer, there is limited trial-level evidence in the literature. Total mesorectal excision (TME) is the current standard of care, but local excision could be considered in select patients with pT1 tumours, or patients with near or complete clinical response to neoadjuvant CRT. As for locally advanced rectal cancer, the current standard of care consists of long-course chemotheradiotherapy or short-course radiotherapy, followed by TME. However, the role of total neoadjuvant therapy is promising, with respect to both oncological outcomes, as well as in reducing toxicity. Both induction and consolidation chemotherapy treatment approaches have been described in literature, with encouraging early results. The optimal management of rectal cancer is constantly evolving. More research is needed to investigate the long-term oncological and functional outcomes following new multimodal therapies in the management of early-stage and locally advanced rectal cancer.

Comparison of colorectal cancer outcomes in young adults and octogenarians.

BACKGROUND: This study aimed to characterise the outcomes associated with colorectal cancer (CRC), comparing young adults (<50 years), patients of screening age (50-79 years), and octogenarians (>80 years). METHODS: All consecutive CRC resections with curative intent were recruited into this study from a prospectively maintained CRC database at a tertiary academic centre. RESULTS: A total of 745 eligible cases were identified. Five-year survival in young adults was poorer than that of patients of screening age. Young adults had the highest incidence of rectal cancer resections, and presented with the most advanced tumour stages. Independent associations for poorer survival in young adults were increased nodal stage, the presence of distal metastases, and loss of MLH1/PMS2 staining on immunohistochemistry. Young adults had similar survival to octogenarians, when comparing patients treated with curative intent, regardless of oncological treatment.

Predictive factors for distant recurrence of colorectal cancer in patients after curative resection for stage I-III colorectal cancer in Australia.

PURPOSE: Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery. METHODS: All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer. RESULTS: A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2 years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50 years of age having the best overall 5-year survival. CONCLUSION: Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features.

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy.

INTRODUCTION: In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients. METHODS: A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression. RESULTS: From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery. CONCLUSIONS: There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

Non-operative management for small bowel obstruction in a virgin abdomen: a systematic review.

BACKGROUND: Small bowel obstruction (SBO) is a common general surgical presentation and there has been a shift towards non-operative management (NOM) for patients with previous abdominal surgery. Historically, exploratory surgery has been mandated for SBO in patients with a virgin abdomen. However, there is increasing evidence for NOM in this group of patients. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search was undertaken between 1995 and 2020 on Ovid MEDLINE, EMBASE and PubMed. Primary outcome measures were success and failure rates, whereas secondary outcome measures were morbidity, mortality rates and identifying underlying aetiologies. RESULTS: Six observational studies were included, with 205 patients in the NOM and 211 patients in the operative group. There was a high success rate of 95.6% and low morbidity rate of 3.1% in the NOM group compared to 88.6% and 26% in the operative group, respectively. Both groups reported no mortalities. The most common aetiologies for SBO in a virgin abdomen were adhesions (63%), malignancy (11%), foreign body/bezoar (5%), internal hernia (4%) and volvulus (4%). CONCLUSION: NOM for SBO is a safe and feasible option for a select group of clinically stable patients with a virgin abdomen without features of closed-loop obstruction. Adhesions are the most common cause of SBO in this group of patients. Further large-scale prospective clinical studies with standardized NOM modality, homogenous clinical resolution indicators and long-term follow-up data are warranted to allow for quantitative analysis to reinforce this evidence.

Utility of intra-operative flexible sigmoidoscopy to assess colorectal anastomosis: a systematic review and meta-analysis.

BACKGROUND: Anastomotic leak (AL) after colorectal resection leads to increased oncological and non-oncological, morbidity and mortality. Intra-operative assessment of a colorectal anastomosis with intra-operative flexible sigmoidoscopy (IOFS) has become increasingly prevalent and is an alternative to conventional air leak test. It is thought that intra-operative identification of an AL or anastomotic bleeding (AB) allows for immediate reparative intervention at the time of anastomosis formation itself. We aim to assess the available evidence for the use of IOFS to prevent complications following colorectal resection. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic review of the literature between January 1980 and June 2020 was performed. Comparative studies assessing IOFS versus conventional air leak test were compared, and outcomes were pooled. RESULTS: A total of 4512 articles were assessed, of which eight were found to meet the inclusion criteria. A total of 1792 patients were compared; 884 in the IOFS arm and 908 in the control arm. IOFS was associated with an increase in the rate of positive leak test (odds ratio (OR) 5.21, P > 0.001), a decrease in AL (OR 0.45, P = 0.006) and a decrease in post-operative AB requiring intervention (OR 0.40, P = 0.037). CONCLUSION: In a non-randomized meta-analysis, IOFS increases the likelihood of identifying an anastomotic defect or bleeding intra-operatively. This allows for immediate intervention that decreases the rate of AL and AB. This adds impetus for performing routine IOFS after a left-sided colorectal resection with anastomosis and highlights the need for randomized controlled trial to confirm the finding.

Perianal sepsis in neutropaenic patients with haematological malignancies: the role of magnetic resonance imaging and surgery.

BACKGROUND: Perianal sepsis occurs in up to 10% of neutropaenic patients with haematological malignancy and is associated with significant morbidity and mortality. The management of this condition is challenging in neutropaenic patients due to its atypical pathophysiology. The aim of this study is to assess the role of magnetic resonance imaging (MRI) and surgery in neutropaenic patients with perianal sepsis. METHODS: A retrospective chart review was performed on all neutropenic patients with a haematological malignancy who had a diagnosis of perianal sepsis during the inpatient admission between 2008 and 2017. Patient characteristics, symptoms, haematological data, MRI result, surgical intervention, intraoperative findings and outcomes including recurrence and mortality were collected. RESULTS: Nineteen neutropaenic patients with haematological malignancy were treated for perianal sepsis, eight (42%) patients were managed conservatively and 11 (58%) were managed surgically. Nine patients underwent MRI, which identified a collection in 88% of cases despite severe neutropaenia. In patients with a collection identified on MRI prior to surgery, 80% had a drainable collection confirmed intraoperatively. Post-operative complications included two cases of sepsis from a presumed perianal source and one death. A total of 82% of patients experienced symptom resolution after surgery compared to 88% of patients managed conservatively. CONCLUSION: This study has demonstrated that MRI is a useful diagnostic tool in evaluating perianal sepsis in patients with haematological malignancy, even during periods of severe neutropenia. We found that both conservative and surgical management strategies lead to resolution of symptoms.

Oncological safety of laparoscopic versus open colorectal cancer surgery in obesity: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer resection in the obese (OB) patients can be technically challenging. With the increasing adoption of laparoscopic surgery, the benefits remain uncertain. Hence, the aim of this study is to assess the short- and long-term outcomes of laparoscopic compared to open colorectal cancer resection in the OB patients. METHODS: A systematic review and meta-analysis was performed according to the PRISMA guidelines. The outcome measures were 5-year disease-free survival, overall survival, circumferential resection margin and local and distant recurrence. RESULTS: A total of 20 studies were included, with a total number of 6779 participants, of whom 1785 (26.3%) were OB and 4994 (73.7%) were non-obese (NOB) participants. The OB patients had higher R1 resection (OB 6.9% versus NOB 3.1%; P = 0.011) and lower mean number of lymph nodes harvested, with standard mean difference of -0.29; P = 0.023, favouring the NOB patients. However, there was no statistical difference for local (OB 2.8% versus NOB 3.4%) or distant recurrence (OB 12.9% versus NOB 15.2%) rate between the two cohorts. There was no difference in 5-year disease-free survival (OB 81% versus NOB 77.4%; odds ratio 1.25, P = 0.215) and overall survival (OB 89.4% versus NOB 87.9%; odds ratio 1.16, P = 0.572). Lastly, the OB group had higher mean total blood loss, total operative time and length of hospital stay when compared to NOB patients. CONCLUSION: From a pooled non-randomized study, laparoscopic colorectal cancer resection is safe in OB patients with equivalent long-term outcomes compared to NOB patients. However, there is a higher morbidity rate with an increased demand on hospital resources for the OB cohort.

Clinical evaluation of anal intraepithelial neoplasia: are we missing the boat?

BACKGROUND: Anal intraepithelial neoplasia (AIN) is dysplasia in the epithelium of the anus and is a pre-malignant condition associated with a low rate of progression to invasive squamous cell carcinoma (SCC). The natural history of progression for AIN to anal SCC is poorly defined. This study aims to review our experience with AIN and investigate the natural history of progression. METHODS: Data on all patients with AIN from January 2005 to December 2015 were retrospectively reviewed. Three separate databases were searched - Colorectal, Radiation Oncology and Infectious Diseases. All databases were cross-referred to obtain a complete but non-duplicated data set. Electronic charts were reviewed to obtain clinical information. RESULTS: Twenty-eight patients were identified with AIN of various grades. There were 25 males, three females. Twenty of the male patients were human immunodeficiency virus (HIV) positive. Mean length of follow up was 56 months. Complete regression of AIN to normal was noted in 13 patients (46%). Four patients had persisting AIN III with no evidence of regression or malignant transformation. Nine patients with pre-existing AIN developed SCC (32%). Seven were positive for HIV infection (all males). Median time to progression was 36 months. None of the patients demonstrated clear linear pattern of progression of AIN to SCC. CONCLUSION: High grade AIN may progress to anal SCC and surveillance is indicated. The exact natural history of progression for AIN is difficult to predict. There is no linear progression over time evident. HIV patients with AIN are at higher risk of developing SCC.

Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon cancer: A cohort study of two cancer centres.

BACKGROUND/OBJECTIVES: Adjuvant chemotherapy for Stage II colon cancer offers a small (2-3%) overall survival benefit and is not universally recommended. Mismatch repair deficiency (dMMR) confers an improved prognosis identifying patients unlikely to benefit from adjuvant chemotherapy. The aim of this study was to investigate the use of dMMR immunohistochemistry in two major cancer treatment centres. METHODS: Prospective data were collected on all patients with resected Stage II colon cancer between 2010 and 2015 across two large Australian hospitals. Data collected included patient demographics, tumour histology, dMMR immunohistochemistry, chemotherapy use, and outcomes. RESULTS: All 355 patients (56.1% female, median age 81) with resected Stage 2 Colon cancer entered on to the surgical database were included in this analysis. MMR testing was performed on 167 patient samples (47%), most occurred post-2013 (73.1% vs. 26.9% patients). dMMR rates were 34.1%. 25 (7.3%) received adjuvant chemotherapy, with no patient >80 years receiving treatment. Presence of ≥2 high-risk feature increased the likelihood of adjuvant chemotherapy. Only 3.6% dMMR patients received chemotherapy; both were young with high-risk features. 27/288 (7.6%) patients (with follow up) relapsed, with 7 disease-free post-resection of metastatic disease, 9 are alive with metastatic disease, and 11 deceased. CONCLUSIONS: Unlike clinical trial populations, Stage 2 colon cancer patients are often elderly, have high rates of dMMR tumours, are rarely offered chemotherapy, yet still have excellent outcomes. dMMR immunohistochemistry is being increasingly used to identify Stage 2 patients who do not require chemotherapy.

Enterocutaneous fistula: analysis of clinical outcomes from a single Victorian tertiary referral centre.

BACKGROUND: Enterocutaneous fistulas (ECFs) are complex and can result in significant morbidity and mortality. The study aimed to evaluate ECF outcomes in a single tertiary hospital. METHODS: A retrospective study of all patients treated with ECF between the period of January 2009 and June 2014 was conducted. Baseline demographic data assessed included the primary aetiology of the fistula, site of the fistula and output of the fistula. Outcomes measures assessed included re-fistulation rate, return to theatre, wound complications, fistula closure rate and death over the study period. RESULTS: A total of 16 patients with ECF were recorded within the study period. Mean age of the patient cohort was 55.8 ± 11.8 years with a female predominance (11 females, 5 males). Primary aetiology were Crohn's disease (31%), post intra-abdominal surgery not related to bowel neoplasia (50%) and post intra-abdominal surgery related to bowel neoplasia (19%). Majority of the fistulas developed from the small bowel (75%) and had low output (63%). Operative intervention was required in 81% of patients with an overall closure rate of 100%. Median operations required for successful closure was 1.15 operations. Mean duration between index operation and curative operation was 8 ± 12.7 months. CONCLUSION: Appropriate bundle of care (perioperative care, surgical timing and surgical technique) can produce excellent results in patients with ECF.

Botulinum toxin therapy for chronic anal fissures: where are we at currently?

BACKGROUND: Botulinum toxin (Botox) injection for chronic anal fissure (CAF) is commonly performed, yet there remains no consensus on optimal dosage or frequency of injections required to achieve complete resolution of anal fissure. The aim of this study was to determine the effectiveness of Botox and side-effect profile in the management of CAF. METHODS: A retrospective clinical study of patients between 2010 and 2014 who underwent a Botox injection for CAF at a tertiary centre was performed. The effectiveness of Botox was measured using standardized outcomes including overall healing rate, presence of anal pain, recurrence and need for repeat botulinum injection. Binary outcomes were assessed using logistic regression model. The analysis was performed using Stata version 13 (StataCorp, College Station, TX, USA). RESULTS: One hundred and one patients underwent 126 Botox injections within the study period. The mean first post-operative visit was at 1 month. The overall recurrence rate was 32%. The majority of patients were given 33 U. No statistically significant relationship between dose and recurrence was identified. The presence of pain at the first post-operative visit was a predictor of future recurrence (odds ratio 3.92, confidence interval 1.58-9.74, P = 0.003). CONCLUSION: Botox is an effective strategy for CAF. Low doses can be given with good efficacy as highlighted by our audit and has the potential for great cost saving. The best predictor of recurrence is the presence of pain at the first post-procedure visit.

Complete Pathological Response After Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer and Its Relationship to the Degree of T3 Mesorectal Invasion.

BACKGROUND: Many studies have shown significantly improved outcomes (reduced local recurrence and improved overall survival) for patients achieving a complete pathological response from neoadjuvant chemoradiotherapy. OBJECTIVE: This study aimed to document the complete pathological response rate and outcomes in patients receiving preoperative long-course chemoradiotherapy stratified for the extent of T3 mesorectal invasion measured on preoperative imaging. DESIGN: This is a retrospective study of prospectively collected data, of patients with rectal cancer in the Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from Cabrini Hospital and The Alfred Hospital, identifying patients entered between January 2010 and June 2014. PATIENTS AND SETTINGS: One hundred eighteen patients with T3 rectal cancer met the selection criteria for the study; 26 achieved complete pathological response (22%). MAIN OUTCOME MEASURES: Outcomes in terms of complete pathological response and oncological outcomes such as disease-free and overall survival were analyzed. RESULTS: Patients with complete pathological response had significantly less preoperative invasion than those with no complete pathological response (p < 0.001). Depth of invasion was the only variable associated with complete pathological response (p < 0.002), and the likelihood of complete pathological response decreased by 35% for every millimeter of invasion. Complete pathological response was associated with increased disease-free survival (p = 0.018) and a lower risk of cancer progression (p = 0.046). Depth of invasion was associated with an increased risk of death after surgery; HR increased by 1.07 (95% CI, 1.00-1.15) for each 1-mm increase in invasion. LIMITATIONS: This was a retrospective study with the usual limitations, although these were minimized through the use of a clinician-driven prospective database. CONCLUSIONS: The smaller the degree of T3 invasion, the higher the chance of achieving complete pathological response (up to 35%), which is associated with improved disease-free and overall survival. A higher complete pathological response rate is observed in early T3 disease in comparison with more extensive T3 invasion.

ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer.

Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts.