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.

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.

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.

How to do safe intracorporeal marking of structures during minimally invasive surgery by simple modification of a skin marking pen.

This study describes how to do safe intracorporeal marking of structures during minimally invasive surgery by simple modification of a skin marking pen. We wish to publicize the use of a skin marking pen tip held within laparoscopic graspers as an effective, simple and cheap method to mark intracorporeal structures, avoiding tissue damage.

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.

Colonic transit: what is the impact of a diverting loop ileostomy?

BACKGROUND: Diverting loop ileostomy (DLI) is used following low anterior resections (LAR) or ultra-low anterior resections (ULAR) to reduce anastomotic leak (AL). Preoperative mechanical bowel preparation (MBP) is traditionally used with DLI. However, clearance of the left colon can be achieved with a fleet enema without the physiological compromise of MBP. We aimed to assess colonic transit following DLI in this context. METHODS: A prospective, observational study was performed with patients with rectal cancer undergoing LAR or ULAR in a tertiary colorectal unit with preoperative fleet enema. Radiopaque markers were inserted into the caecum following rectal resection and formation of a DLI with placement confirmed by image intensifier and endoscopy. X-rays were performed at days 1, 3, 5 and 14 post-operation with data collected prospectively. RESULTS: Ten patients (mean age 57, nine males) were enrolled. Mean time to functioning stoma was 1.9 days (range 1-3). There was no movement in the majority of markers in all patients at Day 5 post-operation. In all seven patients with Day 14 X-rays, the majority of markers remained in the right colon. Two patients had delayed AL, with markers found within the pelvis in both of these patients. CONCLUSIONS: This is the first study to assess colonic transit following DLI using fleet enema only, with results suggesting colonic motility is abolished in this setting. The use of a fleet enema without MBP may be sufficient prior to rectal resection surgery when DLI is employed. AL may actually increase colonic transit. Further research is warranted.

Establishing a robotic colorectal surgery programme.

BACKGROUND: This paper aimed to describe the training available and the process taken to establish a robotic colorectal surgery programme in a large Australian academic private hospital. Through this we hope to guide other surgeons and hospitals planning to introduce this technology in circumstances where such guidelines do not exist. METHODS: The available training and credentialing pathways are described, including the da Vinci Surgery Training Pathway provided by Intuitive Surgical and hospital-based supports. A proposed 9-point training and credentialing pathway is presented, along with the activities undertaken by each surgeon. RESULTS: From December 2011 to December 2013, 48 robotic colorectal procedures were performed at the Cabrini Hospital. Operations performed were as follows: 23 anterior resections, seven abdominoperineal resections, 11 rectopexies, three proctectomies and ileal pouch-anal anastomosis and four right hemicolectomies. There have been no conversions, and no major complications. There were no robot-specific complications. CONCLUSION: We believe that this thorough and methodical approach to introducing robotics to colorectal surgery has been safe and effective, and should be applicable to other surgeons and hospitals wishing to introduce robotic technology to colorectal surgery.

Subtotal colectomy and cecosigmoid anastomosis for colonic systemic sclerosis: report of a case and review of the literature.

PURPOSE: We report a case of subtotal colonic involvement of systemic sclerosis, successfully managed by subtotal colectomy and cecosigmoid anastomosis, and review the literature on surgical management. METHODS: A patient had profound slow transit constipation and severe colonic involvement on nuclear transit study. Surgery was conservative, with preservation of distal sigmoid colon and the ileocecal valve. A literature search regarding management of colonic systemic sclerosis was conducted. RESULTS: The surgery was uncomplicated and near normal bowel function was restored. The literature indicates that colonic involvement is common in systemic sclerosis and that surgery is sometimes required for severe disease or the development of complications. CONCLUSIONS: If surgery is required for colonic involvement in systemic sclerosis, it should be directed at the segmental distribution of the disease, preserving the colon if possible and considering the possibility of concurrent small-bowel involvement. Nuclear colonic transit study is helpful in guiding the extent of surgery.