Association between microsatellite instability status and peri-operative release of circulating tumour cells in colorectal cancer

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting. For this purpose, 20 patients who underwent CRC surgery with curative intent were enrolled in the study, and peripheral venous blood was collected at pre- (t1), intra- (t2), immediately post-operative (t3), and 14–16 h post-operative (t4) time points. Of these, one patient was excluded due to insufficient blood sample. CTCs were isolated from 19 patients using the IsofluxTM system, and the data were analysed using the STATA statistical package. CTC number was presented as the mean values, and comparisons were made using the Student t-test. There was a trend toward increased CTC presence in the MSI-high (H) CRC group, but this was not statistically significant. In addition, a Poisson regression was performed adjusting for stage (I-IV). This demonstrated no significant difference between the two MSI groups for pre-operative time point t1. However, time points t2, t3, and t4 were associated with increased CTC presence for MSI-H CRCs. In conclusion, there was a trend toward increased CTC release pre-, intra-, and post-operatively in MSI-H CRCs, but this was only statistically significant intra-operatively. When adjusting for stage, MSI-H was associated with an increase in CTC numbers intra-operatively and post-operatively, but not pre-operatively

Commentary on Wibe et al.

In this issue of the journal invites the reader to consider tailoring treatment for rectal cancer rather than accepting recommended guidelines alone and I resonate with this principle. The author's aim is to highlight features, apart from tumour stage, that are known to be prognostic in rectal cancer but are not currently incorporated in treatment guidelines and to advocate that individually tailored treatment should take account of these features as well as the tumour stage

Impact of obesity on complications after resection for rectal cancer

Aim - The prevalence of obesity in Australia is high and increasing, with associated serious negative effects on health. The technical complexity of rectal cancer surgery is exacerbated in obese patients, which may compromise outcomes. The aim of this study was to examine the association between obesity and complications after resection of rectal cancer. Method - Data were drawn from a comprehensive prospective registry of rectal cancer resections performed from 2007 to 2011 by members of the colorectal surgical unit in a tertiary referral hospital and in a single private hospital with which they were affiliated. Results - Of 255 patients who had a resection for rectal cancer during the study period, 95 (37%) were classified as obese on the basis of a body mass index (BMI) ≥ 30 kg/m2. Among 24 postoperative complications the only significant differences for obese patients were higher rates of wound complications (16% vs 8%, P = 0.038), small bowel obstruction (4% vs 0%, P = 0.019) and prolonged ileus (18% vs 8%, P = 0.011). The total number of complications did not differ significantly between obese and nonobese patients, and there was no difference between obese and nonobese patients in the rates of reoperation and postoperative death. Conclusion - This study did not support an association between obesity and early postoperative complications after resection of rectal cancer

Does Denonvilliers’ fascia exist in women?

The presence or absence of Denonvilliers’ fascia in either sex has been debated for over 100 years. The original description of the fascia was based exclusively on findings observed in 12 male cadavers though Denonvilliers gave no account of its existence in women. Not surprisingly, its clinical significance in women remains controversial. Kleeman reports no similar fascia present between the rectum and vagina whilst Kraima supports its presence. In women, it is considered important in the treatment of rectocoele or when mobilising the rectum in the correct avascular plane avoiding injury to the anterior rectal wall and associated adjacent neurovascular structures. The aim of this study was to investigate the in situ detailed architecture of Denonvilliers’ fascia in female cadavers using a novel epoxy sheet plastination technique

Denonvilliers’ fascia in men : a sheet plastination and confocal microscopy study of the prerectal space and the presence of an optimal anterior plane when mobilizing the rectum for cancer

Aim:The aim of this study was to investigate the detailed, in situ, morphology of Denonvilliers fascia (DVF) in cadavers using sheet plastination and confocal microscopy and to review and describe the optimal anterior plane for mobilisation of the distal rectum..Method:Six, male cadavers (age range, 46-87 years) were prepared as six sets of transverse (x2), coronal (x1) and sagittal (x3) plastinated sections which were examined under a confocal laser scanning microscope.Results:In this study a consistent space between the anterior rectal wall and the posterior surface of the prostate and seminal vesicles above the level of the perineal body was termed the prerectal space. Within that prerectal space we identified fibres which take their origin from the external urethral sphincter (EUS), together with others from the longitudinal rectal muscle (LRM) and the connective tissue sheaths of neurovascular bundles. Neither the EUS- nor the LRM-originated fibres were continuous with the endopelvic fascia;they are interposed laterally and cranially by multiple neurovascular bundles. Further, our results suggest that the peritoneum does not descend deep within the prerectal space.Conclusion:This study reveals the undisturbed, in situ, structural detail of membrane-like structures in the prerectal space and confirms that the optimal plane for anterolateral mobilization of the rectum is posterior to the multilayered DVF

Nature and architecture of the puboprostatic ligament : a macro- and microscopic cadaveric study using epoxy sheet plastination

Objective: To investigate the nature and the architecture of the puboprostatic ligament (PPL) and its relationship with surroundings. Materials and Methods: Six adult male cadaveric pelvises (age range, 46-87 years) were prepared as serial transverse (2 sets), coronal (1 set), or sagittal (3 sets) plastinated sections, and were examined under a stereoscope and a confocal microscope. The thickness of the section was 2.5 mm, the interval between 2 adjacent sections was about 0.9 mm, and a total of about 70 serial sections per set were collected. Results: First, the musculotendinous sheet of the pubococcygeus contributed to the visceral endopelvic fascia, decussated in front of the detrusor apron, and fixed to the pubis. Second, anteriorly to the prostate, the detrusor apron split up into anterior, middle, and posterior layers, which contributed to the PPL, the fascial sheaths of the dorsal vascular complex, and the anterior fibromuscular stroma of the prostate, respectively. Third, the PPL originated from both the detrusor apron and the decussated and undecussated fibers of the pubococcygeus, and inserted onto the pubis. Conclusion: This study revealed the nature and the architecture of the PPL and its relationship with surroundings. These findings provide new insights in the "suspensory system" involving the urinary continence and may incite for future surgical techniques that aim to preserve the decussated pubococcygeus and the intactness of a pubococcygeus-detrusor apron complex during radical retropubic prostatectomy

Problem-based learning in medical education : one of many learning paradigms

In 1978, when problem-based learning (PBL) was introduced in the University of Newcastle medical faculty, the prevailing educational style in 6-year undergraduate medical programs in Australia was teacher-led learning (TLL), wherein students first acquired core knowledge in basic sciences, which were taught in large class lectures, tutorials and laboratory sessions during the 3 preclinical years of the course. They then progressed to a multilayered, sequential, integrated approach incorporating fundamental clinical skills in history-taking and eliciting and interpreting physical signs, leading to differential diagnoses and patient management. These skills were taught in small tutorial groups at the bedside, in the operating room, in outpatient clinics and in consulting rooms

Rectal mobilization : the place of Denonvilliers’ fascia and inconsistencies in the literature

Aim. Confusion remains as to what is meant by Denonvilliers’ fascia. This review searched the literature on pelvic surgical anatomy to determine whether there is agreement with Denonvilliers’ original description and its implication in defining the correct anterior plane of dissection when mobilising the rectum. Method. The original French description of the fascia was translated into English and then compared both to French and English studies identified by searching Pubmed, Medline and Scopus from 1836 to June 2015. Special emphasis was given to the years between 1980 to 2015 in order to capture the literature pertinent to and following on from the description of total mesorectal excision for rectal cancer. Results. The final literature search revealed sixteen studies from the original 2,150 citations. Much of the debate was concerned with the origin and development of the fascia, arising from either the fusion or condensation of local primitive tissue into a mature “multilayered” structure. Conclusion. Controversy as to the correct plane of rectal mobilisation is due to different interpretations understood by surgeons, anatomists and radiologists and bears little resemblance to Denonvilliers’ original description. This may reflect wide anatomical variability in the adult pelvis or a form of dissection artefact. Further study is required to investigate this. Logically for both men and women the plane of rectal mobilisation should be behind Denonvilliers’ fascia and between it and the fascia propria of the rectum

Magnetic resonance imaging cannot predict histological tumour involvement of a circumferential surgical margin in rectal cancer

Aim: Several recent studies have attempted to evaluate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting the likelihood of tumour involvement of the postoperative circumferential resection margin (CRM) in rectal cancer with the intention of selecting patients who might benefit from neoadjuvant therapy and as a guide to surgery. The aim of this study was to assess whether such studies can provide a valid answer as to whether preoperative MRI can accurately predict CRM involvement by tumour. Method: The study design and methodology of studies on this topic were critically examined. Results: Features identified as affecting the efficacy of these studies were: representativeness of patients, definition of the margin assessed by MRI and by histology, lack of blinding of surgeons and pathologists to MRI results, effect of neoadjuvant treatment, and number of patients studied. Conclusion: Because of methodological inadequacies in studies completed to date, there is insufficient evidence of the ability of a positive MRI result to predict an involved CRM. Although MRI may be able to identify a tumour that has extended to the mesorectal fascia and/or intersphincteric plane, logically, it cannot indicate where the surgical boundary of the resection will ultimately lie, and therefore cannot validly predict an involved CRM and should not be relied upon for this purpose

Trans-anal total mesorectal excision : reflections on the introduction of a new procedure

Introduction: The introduction of novel surgical techniques in the hope of improving overall patient care is currently under increasing scrutiny, for whilst such techniques may appear to lead towards greater efficacy they may also introduce a range of complications not normally associated with standard care. In Australia, there are clear guidelines to ensure that new operations or technologies are introduced safely into surgical practice. These are embodied in the Royal Australasian College of Surgeons ASERNIP-S programme and follow the UK IDEAL Collaboration recommendations. The guidelines are applicable to the procedure of transanal total mesorectal excision (TaTME) which was introduced in 2010 as a means of facilitating laparoscopic dissection of low rectal cancers