Rectal cancer treatment and outcomes in elderly patients treated with curative intent.

The elderly population comprises a significant proportion of patients diagnosed with rectal cancer. However, there is a lack of evidence to guide treatment decisions in this group. Thus, this multicentre study compares the histopathology, treatment patterns and outcomes between the elderly and young populations with non-metastatic rectal cancer. The present study reported on the clinicopathological variables, treatment modalities and survival outcomes in 736 patients diagnosed with non-metastatic rectal cancer between 2006 and 2015. Patients were divided into the following two groups, <70 and ≥70 years of age, which were compared using Chi-square and survival outcome analysis using Kaplan-Meier. Elderly patients made up nearly half of the cohort and were less likely to undergo trimodality therapy or be discussed in a multidisciplinary meeting. Surgery in the elderly patients was associated with increased mortality. Elderly patients had worse cancer-specific survival (75 vs. 85%), which was particularly evident in stage III disease (hazard ratio, 2.1). Elderly patients in this subgroup treated with trimodality therapy had similar survival outcomes to younger patients. Elderly patients with locally advanced rectal cancer comprise a large proportion of the patient cohort. Consideration should be given for trimodality therapy in this group, taking into account biological age, especially in the context of increasing life expectancy and improvement in the management of age-related comorbidities.

Statistical, Clinical, Methodological Evaluation of Local Recurrence Following Transanal Total Mesorectal Excision for Rectal Cancer: A Systematic Review.

BACKGROUND: A recent Norwegian moratorium challenged the status quo of transanal total mesorectal excision for rectal cancer by reporting increased early multifocal local recurrences. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the local recurrence rates following transanal total mesorectal excision as well as to assess statistical, clinical, and methodological bias in reports published to date. DATA SOURCES: The PubMed and MEDLINE (via Ovid) databases were systematically searched. STUDY SELECTION: Descriptive or comparative studies reporting rates of local recurrence at a median follow-up of 6 months (or more) after transanal total mesorectal excision were included. INTERVENTIONS: Patients underwent transanal total mesorectal excision. MAIN OUTCOME MEASURES: Local recurrence was any recurrence located in the pelvic surgery site. The untransformed proportion method of 1-arm meta-analysis was utilized. Untransformed percent proportion with 95% confidence interval was reported. Ad hoc meta-regression with the Omnibus test was utilized to assess risk factors for local recurrence. Among-study heterogeneity was evaluated: statistically by I2 and τ2, clinically by summary tables, and methodologically by a 33-item questionnaire. RESULTS: Twenty-nine studies totaling 2906 patients were included. The pooled rate of local recurrence was 3.4% (2.7%-4.0%) at an average of 20.1 months with low statistical heterogeneity (I2 = 0%). Meta-regression yielded no correlation between complete total mesorectal excision quality (p = 0.855), circumferential resection margin (p = 0.268), distal margin (p = 0.886), and local recurrence rates. Clinical heterogeneity was substantial. Methodological heterogeneity was linked to the excitement of novelty, loss aversion, reactivity to criticism, indication for transanal total mesorectal excision, nonprobability sampling, circular reasoning, misclassification, inadequate follow-up, reporting bias, conflict of interest, and self-licensing. LIMITATIONS: The studies included had an observational design and limited sample and follow-up. CONCLUSION: This systematic review found a pooled rate of local recurrence of 3.4% at 20 months. However, given the substantial clinical and methodological heterogeneity across the studies, the evidence for or against transanal total mesorectal excision is inconclusive at this time.

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.

Perceptions of shared care among survivors of colorectal cancer from non-English-speaking and English-speaking backgrounds: a qualitative study.

BACKGROUND: Colorectal cancer (CRC) survivors experience difficulty navigating complex care pathways. Sharing care between GPs and specialist services has been proposed to improve health outcomes in cancer survivors following hospital discharge. Culturally and Linguistically Diverse (CALD) groups are known to have poorer outcomes following cancer treatment but little is known about their perceptions of shared care following surgery for CRC. This study aimed to explore how non-English-speaking and English-speaking patients perceive care to be coordinated amongst various health practitioners. METHODS: This was a qualitative study using data from face to face semi-structured interviews and one focus group in a culturally diverse area of Sydney with non-English-speaking and English-speaking CRC survivors. Participants were recruited in community settings and were interviewed in English, Spanish or Vietnamese. Interviews were recorded, transcribed, and analysed by researchers fluent in those languages. Data were coded and analysed thematically. RESULTS: Twenty-two CRC survivors participated in the study. Participants from non-English-speaking and English-speaking groups described similar barriers to care, but non-English-speaking participants described additional communication difficulties and perceived discrimination. Non-English-speaking participants relied on family members and bilingual GPs for assistance with communication and care coordination. Factors that influenced the care pathways used by participants and how care was shared between the specialist and GP included patient and practitioner preference, accessibility, complexity of care needs, and requirements for assistance with understanding information and navigating the health system, that were particularly difficult for non-English-speaking CRC survivors. CONCLUSIONS: Both non-English-speaking and English-speaking CRC survivors described a blend of specialist-led or GP-led care depending on the complexity of care required, informational needs, and how engaged and accessible they perceived the specialist or GP to be. Findings from this study highlight the role of the bilingual GP in assisting CALD participants to understand information and to navigate their care pathways following CRC surgery.

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. This article is protected by copyright. All rights reserved.

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.

Trends in pathology and long-term outcomes after resection of colorectal cancer: 1971-2013.

BACKGROUND: The aim of this study was to describe temporal trends in tumour pathology and long-term outcomes in 5217 patients recorded in a registry of colorectal cancer resections initiated at Concord Hospital, Sydney, Australia, in 1971. METHODS: This report is based on consecutive resections up to December 2013, with no exclusions. Categories in variables examined were expressed as percentages over annual totals of relevant patients or annual mean values. The statistical significance of temporal trends was examined by least squares regression. RESULTS: The percentages of patients with local spread beyond the muscularis propria, nodal metastasis, distant metastasis and tumour in a line of resection all declined significantly. In consequence, the percentage of stage D patients fell, whereas the percentage in stage A rose. Other tumour variables that increased significantly were polypoid morphology, contiguous adenoma and invasion of a free serosal surface. Tumours in which an adherent adjacent structure was partly or completely removed also increased. There were significant declines in high-grade malignancy, venous invasion and tumour size. The recurrence rate for rectal cancers declined significantly, whereas for rectal and colonic cancers combined, both the overall 5-year survival rate and the 5-year cancer-specific survival rate increased markedly. CONCLUSION: These results show a reduction in adverse pathology findings and favourable trends in recurrence and survival after colorectal cancer resections in a high-incidence country over a period of 43 years.

Trends in short-term outcomes after resection of colorectal cancer: 1971-2013.

BACKGROUND: The aim of this study was to describe temporal trends in presentation, surgical management and immediate postoperative outcomes in patients recorded in a registry of colorectal cancer resections that was initiated at Concord Hospital, Sydney, Australia, in 1971. A companion paper describes tumour pathology and long-term recurrence and survival. METHODS: This report is based on 5217 consecutive resections up to 2013, with no exclusions. Categories in variables examined were expressed as percentages over annual totals of relevant patients or annual mean values. The statistical significance of trends was examined by least squares regression. RESULTS: The percentage of asymptomatic patients increased over time, whereas urgent presentations declined. Tumour size declined. The percentage of rectal cancers fell but the percentage of low rectal tumours rose. Initially, restorative rectal resections increased rapidly but later remained stable. There was no trend in medical complications, whereas surgical complications declined. Anastomotic leakage after restorative rectal resections declined but it was low and stable for colonic tumours. The rate of early reoperation remained stable, whereas 30-day mortality declined. Neoadjuvant radiotherapy for rectal cancer and adjuvant chemotherapy for stages B and C were introduced in 1992 and applied increasingly thereafter. CONCLUSION: Our findings, based on a 43-year prospective study, indicate sustained trends towards the earlier diagnosis of colorectal cancer and favourable short-term outcomes following bowel resection.

Management of sub-5 mm rectal carcinoids with lymph node metastases.

Minute (<5 mm) and small (5-10 mm) rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive, and the management and surveillance of patients with this entity are usually limited. We present the case of a 61-year-old Chinese female with multiple sub-5 mm carcinoid tumours in the rectum without any computed tomography (CT) evidence of lymph node or distant metastases. She underwent an ultra-low anterior resection for a sessile rectal polyp with the histological appearance of a moderately differentiated adenocarcinoma. Seven foci of minute carcinoids in the rectum and perirectal lymph node metastastic spread from the carcinoid tumours were also discovered on histopathology. There were no lymph node metastases originating from adenocarcinoma. This case report and review of the literature suggests that minute rectal carcinoids are at risk of metastasizing and that these patients should be investigated for lymph node and distant metastatic spread with CT and somatostatin receptor scintigraphy or its equivalent, as this would influence prognosis and surgical management of these patients. Findings relating to lymphovascular invasion, perineural invasion, high Ki-67, mitotic rate, depth of tumour invasion, central ulceration, multifocal tumours and size are useful in predicting metastases and may be used in scoring tools. Size alone is not a good predictor of metastastic spread.

Complications after resection of colorectal cancer in a public hospital and a private hospital.

BACKGROUND: To our knowledge, immediate post-operative complication rates after resection of colorectal cancer (CRC) have not been compared between public and private hospitals in the Australian health care system. We compared the frequency of surgical and medical complications between a public tertiary referral hospital and a private hospital. METHODS: Data were drawn from a prospective registry of all patients having a resection for CRC between 2000 and 2010 performed by members of the Concord Hospital colorectal surgical unit, either at this hospital or at a single private hospital with which they were affiliated. Complication rates were compared after adjustment for preoperative and perioperative features by logistic regression. RESULTS: Among the 16 surgical complications, the only significant difference after adjustment for other features was a higher rate of septicaemia in the public hospital (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.6). Among the seven medical complications, the only significant differences were a higher risk of cardiac complications in patients with cardiac co-morbidity (OR 1.8, 95% CI 1.1-3.0) and of respiratory complications in patients without respiratory co-morbidity (OR 3.1, 95% CI 2.2-5.9) in the public hospital. CONCLUSION: In this study, where the same group of surgeons performed all reported CRC resections in the two hospitals, no independent effect of the type of hospital was found on 15 of 16 surgical complications and 5 of 7 medical complications. Type of hospital had no impact on rates of specific complications apart from septicaemia and cardiorespiratory complications, which were higher in the public hospital.

Effect of neoadjuvant chemoradiation on tumor-infiltrating/associated lymphocytes in locally advanced rectal cancers.

BACKGROUND: Lymphocytes and natural killer cells (NK) appear to be important in colorectal cancer. Their role in chemoradiotherapy for rectal cancers is unclear. We evaluated T-lymphocytes (CD3), sub-groups CD4 and CD8, and NK cells (CD56+CD57) in normal and rectal tumor tissues pre- and post-chemoradiotherapy, and investigated their relationship to tumor regression grade, disease-free survival and pathological stage. MATERIALS AND METHODS: Tissue microarrays from colonoscopic biopsies, resection specimens and normal tissues, from 52 patients, were immunostained. RESULTS: NK cell counts were significantly lower in tumor samples compared to normal tissues (p=0.007). T-lymphocyte counts were higher in post-treatment compared to pre-treatment samples (p=0.025), specifically in the CD8 subgroup after long-course treatment. The results suggested an association between post-treatment CD8 and NK cell counts with higher tumor regression. No associations were found with regard to stage or disease-free survival. CONCLUSION: NK cell counts were significantly reduced in rectal cancers compared to normal tissues, while total T-lymphocyte counts increased post-chemoradiotherapy. Both appeared important in tumor regression.

Mural and extramural venous invasion and prognosis in colorectal cancer.

BACKGROUND: Extramural venous invasion is a known independent predictor of poor prognosis after resection of colorectal adenocarcinoma, but the prognostic value of mural venous invasion alone and the association between venous invasion and prognosis within tumor stages has received little research attention. OBJECTIVE: This study aimed to determine whether associations between mural and extramural venous invasion and outcome differ among tumor stages after adjustment for other factors known to influence prognosis. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: Data were drawn from a registry of 3040 consecutive patients undergoing resection between 1980 and 2005 under the care of specialist surgeons in a tertiary referral public hospital and an affiliated private hospital. A standardized protocol was used for the pathological assessment of specimens. MAIN OUTCOME MEASURES: The primary outcomes measured were overall survival, cancer-specific survival, and recurrence. RESULTS: There was no significant association between venous invasion and survival in stages A (n = 544) or B (n = 1078). In stage C (n = 899), overall survival time was significantly shorter in patients with mural invasion alone or extramural invasion (both p < 0.001) than in those without invasion, and this persisted after adjustment for other prognostic variables. Equivalent bivariate associations were found in stage D, but only the effect of extramural invasion persisted after adjustment. LIMITATIONS: Our findings arise from the experience of a single surgical group and may not be generalizable to other settings. Only hematoxylin and eosin staining was used. CONCLUSIONS: The association between venous invasion and prognosis was stage specific. Both mural venous invasion alone and extramural venous invasion independently predicted overall survival in patients with stage C tumors, but not in patients with stages A, B, or D tumors. Although mural invasion alone was rare, the separate reporting of both mural and extramural invasion in patients with stage C tumor is informative and desirable.

KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer.

Colonic and rectal cancers differ in their clinicopathologic features and treatment strategies. Molecular markers such as gene methylation, microsatellite instability and KRAS mutations, are becoming increasingly important in guiding treatment decisions in colorectal cancer. However, their association with clinicopathologic variables and utility in the management of rectal cancer is still poorly understood. We analyzed CDKN2A gene methylation, CpG island methylator phenotype (CIMP), microsatellite instability and KRAS/BRAF mutations in a cohort of 381 rectal cancers with extensive clinical follow-up data. BRAF mutations (2%), CIMP-high (4%) and microsatellite instability-high (2%) were rare, whereas KRAS mutations (39%), CDKN2A methylation (20%) and CIMP-low (25%) were more common. Only CDKN2A methylation and KRAS mutations showed an association with poor overall survival but these did not remain significant when analyzed with other clinicopathologic factors. In contrast, this prognostic effect was strengthened by the joint presence of CDKN2A methylation and KRAS mutations, which independently predicted recurrence of cancer and was associated with poor overall and cancer-specific survival. This study has identified a subgroup of more aggressive rectal cancers that may arise through the KRAS-p16 pathway. It has been previously shown that an interaction of p16 deficiency and oncogenic KRAS promotes carcinogenesis in the mouse and is characterized by loss of oncogene-induced senescence. These findings may provide avenues for the discovery of new treatments in rectal cancer.

Risk factors for prolonged ileus after resection of colorectal cancer: an observational study of 2400 consecutive patients.

OBJECTIVE: Prolonged ileus-the failure of postoperative ileus to resolve within a few days after major abdominal surgery-leads to significant medical consequences for the patient and costs to the hospital system. The aim of this retrospective analysis of prospectively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer. METHODS: Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995-2009. Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression. RESULTS: Prolonged ileus occurred in 14.0% of patients. Statistically significant independent predictors of prolonged ileus were male sex (OR: 1.7, P < 0.001), peripheral vascular disease (OR: 1.8, P < 0.001), respiratory comorbidity (OR: 1.6, P < 0.001), resection at urgent operation (OR: 2.2, P < 0.001), perioperative transfusion (OR: 1.6, P < 0.010), stoma constructed (OR: 1.4, P < 0.001), and operation lasting ≥3 hours (OR: 1.6, P < 0.001). CONCLUSIONS: These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them. These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment.

Body image as a predictor of psychopathology in surgical patients with colorectal disease.

OBJECTIVE: This study aimed to test the relevance of a cognitive behavioural model of body image in a prospective study of colorectal surgery patients and to determine if pre-existing body image disturbance influenced psychological adjustment following surgery. METHODS: Sixty-seven adult consecutive colorectal surgery patients completed measures assessing psychopathology, body image related beliefs and health related quality of life during pre-admission for surgery using a questionnaire battery. Each participant was followed up three months after surgery. RESULTS: Depression and anxiety were positively correlated with body image disturbance and self evaluation at baseline. Those patients who went on to receive stomas experienced a significant deterioration in their body image that was not observed in those whose surgery did not result in the formation of a stoma. In the regression analysis, body image disturbance was a significant predictor of baseline levels of depression and emotional quality of life. Initial levels of body image disturbance remained a significant predictor of depression and anxiety at follow up assessment after medical variables and baseline levels of depression and anxiety, respectively, had been controlled for. CONCLUSION: Our findings support the hypothesis that pre-existing vulnerabilities in body image influence emotional adjustment during the recovery phase following surgery. Further research on screening for body image disturbance in surgical patients in order to promote adjustment is warranted.