Low anterior resection syndrome phenotypes-Different symptom profiles for different patients.

AIM: Attention is increasingly being turned to functional outcomes as being central to colorectal cancer (CRC) survivorship. The current literature may underestimate the impact of evacuatory dysfunction on patient satisfaction with bowel function after anterior resection (AR) for CRC. The aim of this study was to investigate the impact of post-AR symptoms of storage and evacuatory dysfunction on patient satisfaction and health-related quality of life (HRQoL). METHOD: A cross-sectional study was performed at an Australian hospital of patients post-AR for CRC (2012-2021). The postoperative bowel function scores used were: low anterior resection syndrome (LARS), St Mark's incontinence, Cleveland Clinic constipation and Altomare obstructive defaecation syndrome scores. Eight 'storage' and 'evacuatory' dysfunction symptoms were derived. A seven-point Likert scale measured patient satisfaction. The SF36v2® measured HRQoL. Linear regression assessed the association between symptoms, patient satisfaction and HRQoL. RESULTS: Overall, 248 patients participated (mean age 70.8 years, 57.3% male), comprising 103 with rectal cancer and 145 with sigmoid cancer. Of the symptoms that had a negative impact on patient satisfaction, six reflected evacuatory dysfunction, namely excessive straining (p < 0.001), one or more unsuccessful bowel movement attempt(s)/24 h (p < 0.001), anal/vaginal digitation (p = 0.005), regular enema use (p = 0.004), toilet revisiting (p = 0.004) and >10 min toileting (p = 0.004), and four reflected storage dysfunction, namely leaking flatus (p = 0.002), faecal urgency (p = 0.005), use of antidiarrhoeal medication (p = 0.001) and incontinence-related lifestyle alterations (p < 0.001). A total of 130 patients (53.5%) had 'no LARS', 56 (23.1%) had 'minor LARS' and 57 (23.4%) had 'major LARS'. Fifty-seven (44.5%) patients classified as having 'no LARS' had evacuatory dysfunction. CONCLUSION: Postoperative storage and evacuatory dysfunction symptoms have an adverse impact on patient satisfaction and HRQoL post-AR. The importance of comprehensively documenting symptoms of evacuatory dysfunction is highlighted. Further research is required to develop a patient satisfaction-weighted LARS-specific HRQoL instrument.

Complete mesocolic excision for colon cancer: current status and controversies.

According to Hohenberger's original description, complete mesocolic excision for colon cancer involves precise dissection of the avascular embryonic plane between the parietal retroperitoneum and visceral peritoneum of the mesocolon. This ensures mesocolic integrity, access to high ligation of the supplying vessels at their origin and an associated extended lymphadenectomy. Results from centres which have adopted this approach routinely have demonstrated that oncological outcomes can be improved by the rigorous implementation of established principles of cancer surgery. Meticulous anatomical dissection along embryonic planes is a well-established principle of precision cancer surgery used routinely by the specialist colorectal surgeon. Therefore, the real question concerns the need for true central vascular ligation and associated extended (D3) lymphadenectomy or otherwise, particularly along the superior mesenteric vessels when performing a right colectomy. Whether this approach results in improved overall or disease-free survival remains unclear and its role remains controversial particularly given the potential for significant morbidity associated with a more extensive central vascular dissection. Current literature is limited by considerable bias, as well as inconsistent and variable terminology, and the results of established randomized trials are awaited. As a result of the current state of equipoise, various national guidelines have disparate recommendations as to when complete mesocolic excision should be performed if at all. This article aims to review the rationale for and technical aspects of complete mesocolic excision, summarize available short and long term outcome data and address current controversies.

Splenic flexure cancer survival: a 25-year experience and implications for complete mesocolic excision (CME) and central vascular ligation (CVL).

BACKGROUND: The management of splenic flexure cancers (SFCs) in the era of complete mesocolic excision (CME) and central vascular ligation (CVL) is challenging because of its variable lymphatic drainage. This study aimed to compare survival outcomes for SFCs and non-SFCs, and better understand the clinicopathological characteristics which may define a distinct SFC phenotype. METHODS: An observational cohort study at Concord Hospital, Sydney was conducted with patients who underwent resection for colon adenocarcinoma (1995-2019). Clinicopathological data were extracted from a prospective database. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. RESULTS: Of 2149 patients with colon cancer, 129 (6%) had an SFC. The overall 5-year OS and DFS rates were 63.6% (95% CI 62.5-64.7) and 59.4% (95% CI 58.3-60.5), respectively. SFCs were not associated with OS (P = 0.6) or DFS (P = 0.5). SFCs were more likely to present urgently (P < 0.001) with obstruction (P < 0.001) or perforation (P = 0.03), and more likely to require an open operation (P < 0.001). These characteristics were associated with poorer survival outcomes. No differences were noted between SFCs and non-SFCs with respect to tumour stage (P = 0.3). CONCLUSION: SFCs have a distinct phenotype, the individual characteristics of which are associated with poorer survival. However, the survivals of SFCs and non-SFCs are similar, possibly because the most important determinant of outcome, tumour stage, is no different between the groups. This may have implications for the surgical approach to SFCs with respect to standardization of CME and CVL surgery for these cancers.

Right hemicolectomy anastomotic leak study: a review of right hemicolectomy in the binational clinical outcomes registry (BCOR).

BACKGROUNDS: Surgery remains mainstay management for colon cancer. Post-operative anastomotic leak (AL) carries significant morbidity and mortality. Rates of, and risk factors associated with AL following right hemicolectomy remain poorly documented across Australia and New Zealand. This study examines the Bowel Cancer Outcomes Registry (BCOR) to address this. METHODS: A retrospective cohort study was undertaken of consecutive BCOR-registered right hemicolectomy patients undergoing resection for colon cancer (2007-2021). The primary outcome measure was AL incidence. Clinicopathological data were extracted from the BCOR. Factors associated with AL and primary anastomosis were identified using logistic regression. AL-rate trends were assessed by linear regression. RESULTS: Of 13 512 patients who had a right hemicolectomy (45.2% male, mean age 72.5 years, SD 12.1), 258 (2.0%) had an AL. On multivariate analysis, male sex (OR 1.33; 95% CI 1.03-1.71) and emergency surgery (OR 1.41; 95% CI 1.04-1.92) were associated with AL. Private health insurance status (OR 0.66; 95% CI 0.50-0.88) and minimally-invasive surgery (OR 0.61; 95% CI 0.47-0.79) were protective for AL. Anastomotic technique (handsewn versus stapled) was not associated with AL (P = 0.84). Patients with higher ASA status (OR 0.47; 95% CI 0.39-0.58), advanced tumour stage (OR 0.56; 95% CI 0.50-0.63), and emergency surgery (OR 0.16; 95% CI 0.13-0.20) were less likely to have a primary anastomosis. AL-rate and year of surgery showed no association (P = 0.521). CONCLUSION: The AL rate in Australia and New Zealand following right hemicolectomy is consistent with the published literature and was stable throughout the study period. Sex, emergency surgery, insurance status, and minimally invasive surgery are associated with AL incidence.

Apical Node Involvement Does Not Influence Prognosis After Potentially Curative Resection for Stage III Colorectal Cancer: A Competing Risks Analysis.

OBJECTIVE: To examine the independent prognostic value of ALN status in patients with stage III CRC. SUMMARY OF BACKGROUND DATA: Early CRC staging classified nodal involvement by level of involved nodes in the operative specimen, including both locoregional and apical node status, in contrast to the American Joint Committee on Cancer/tumor nodes metastasis (TNM) system where tumors are classified by the number of nodes involved. Whether ALN status has independent prognostic value remains controversial. METHODS: Consecutive patients who underwent curative resection for Stage III CRC from 1995 to 2012 at Concord Hospital, Sydney, Australia were studied. ALN status was classified as: (i) ALN absent, (ii) ALN present but not histologically involved, (iii) ALN present and involved. Outcomes were the competing risks incidence of CRC recurrence and CRC-specific death. Associations between these outcomes and ALN status were compared with TNM N status results. RESULTS: In 706 patients, 69 (9.8%) had an involved ALN, 398 (56.4%) had an uninvolved ALN and 239 (33.9%) had no ALN identified. ALN status was not associated with tumor recurrence [adjusted hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.84-1.26] or CRC-specific death (HR 1.14, CI 0.91-1.43). However, associations persisted between TNM N-status and both recurrence (HR 1.58, CI 1.21-2.06) and CRC-specific death (HR 1.59, CI 1.19-2.12). CONCLUSIONS: No further prognostic information was conferred by ALN status in patients with stage III CRC beyond that provided by TNM N status. ALN status is not considered to be a useful additional component in routine TNM staging of CRC.

Recurrence and colon cancer-specific death in patients with large bowel obstruction requiring urgent operation: a competing risks analysis.

AIM: Clinical presentation with large bowel obstruction has been proposed as a predictor of poor long-term oncological outcomes after resection for colorectal cancer. This study examines the association between obstruction and recurrence and cancer-specific death after resection for colon cancer. METHOD: Consecutive patients who underwent resection for colon cancer between 1995 and 2014 were drawn from a prospectively recorded hospital database with all surviving patients followed for at least 5 years. The outcomes of tumour recurrence and colon cancer-specific death were assessed by competing risks multivariable techniques with adjustment for potential clinical and pathological confounding variables. RESULTS: Recurrence occurred in 271 of 1485 patients who had a potentially curative resection. In bivariate analysis, obstruction was significantly associated with recurrence [hazard ratio (HR) 2.23, CI 1.52-3.26, p < 0.001] but this association became nonsignificant after adjustment for confounders (HR 1.53, CI 0.95-2.46, p = 0.080). Colon cancer-specific death occurred in 238 of 295 patients who had a noncurative resection. Obstruction was not significantly associated with cancer-specific death (HR 1.02, CI 0.72-1.45, p = 0.903). In patients who had a noncurative resection, the competing risks incidence of colon cancer-specific death was not significantly greater in obstructed than in unobstructed patients (HR 1.02, CI 0.72-1.45, p = 0.903). CONCLUSION: Whilst the immediate clinical challenge of an individual patient presenting with large bowel obstruction must be addressed by the surgeon, the patient's long-term oncological outcomes are unrelated to obstruction per se.

When does curatively treated colorectal cancer recur? An Australian perspective.

BACKGROUND: While most colorectal cancer (CRC) recurrences reportedly occur within 3 years following curative treatment, many studies are limited by short-term follow-up. This study examines the time to recurrence of CRC in a large Australian cohort with a long follow-up period and assesses whether time to recurrence has changed over time. METHODS: A comprehensive prospective database of patients undergoing resection for CRC is maintained at Concord Hospital, Sydney. Demographic and time to recurrence data were extracted for patients who developed a recurrence following potentially curative resection for colon cancer from 1995 to 2010 and rectal cancer from 1971 to 2010. Non-deceased patients had a minimum of 5 years follow-up. RESULTS: Between 1995 and 2010, 2575 patients with CRC underwent surgery. After exclusions, 386 had recurrence following potentially curative resection, ranging from 1 to 172.5 months (median 20.3) after treatment. Within 1 year, 27.5% recurred, 57.5% by 2 years, 74.6% by 3 years, 85.5% by 4 years and 89.6% by 5 years. There was no difference in time to recurrence between colon and rectal cancers (P = 0.674). Among patients having a potentially curative resection for rectal cancer between 1971 and 2010, 386 recurred. There was no difference in time to recurrence by decade (P = 0.863). CONCLUSION: The majority of recurrences occurred within 3 years of curative treatment. Had surveillance been limited to 5 years, detection of more than 10% of recurrences would have been delayed. Time to recurrence for rectal cancer has not changed in over 40 years, despite treatment advances.

Competing risks analysis of the effect of local residual tumour on recurrence and cancer-specific death after resection of colorectal cancer: implications for staging.

The pTNM staging system for colorectal cancer (CRC) is not entirely effective in discriminating between potentially curative and non-curative resections because it does not account for local residual tumour in patients with stages I, II or III. This study aimed to evaluate the prognostic importance of histologically verified tumour in any line of resection of the bowel resection specimen (TLR) in relation to pTNM stages and to demonstrate how TLR may be integrated into pTNM staging. Information on patients in the period 1995 to 2010 with complete follow-up to the end of 2015 was extracted from a prospective database of CRC resections. The outcome variables were the competing risks incidence of CRC recurrence and CRC-specific death. After exclusions, 2220 patients remained. In 1930 patients with pTNM stages I-III tumour, recurrence was markedly higher in those with TLR than in those without (HR 6.0, 95% CI 4.2-8.5, p < 0.001) and this persisted after adjustment for covariates associated with recurrence. CRC-specific death was markedly higher in the presence of TLR (HR 7.7, CI 5.3-11.2, p < 0.001), which persisted after adjustment for relevant covariates. These results justify removing patients with TLR from pTNM stages I to III and placing them in stage IV, thereby allowing the categorisation of all patients with any known residual tumour into three prognostically distinct groups. This study demonstrates how TLR may be integrated into pTNM staging, thus improving the definition of the three stages which are considered potentially curable (I, II and III).

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.

Reporting in studies of protein biomarkers of prognosis in colorectal cancer in relation to the REMARK guidelines.

PURPOSE: The REMARK guidelines give authors comprehensive and specific advice on the complete and transparent reporting of studies of prognostic tumor markers. The aim of this study was to use the REMARK guidelines to evaluate the quality of reporting in a sample of studies assessing tissue-based protein markers for survival after resection of colorectal cancer. EXPERIMENTAL DESIGN: Eighty pertinent articles were scored according to their conformity to 26 items derived from the REMARK criteria. RESULTS: Overall, on a scale of adequacy of reporting that potentially ranged from 26 to 78, the median for these studies was 60 (interquartile range 54-64) and several criteria were adequately covered in a large proportion of studies. However, others were either not dealt with or inadequately covered, including description of the study design (35%), definition of survival endpoints (48%), adjuvant therapy (54%), follow-up procedures and time (59%), neoadjuvant therapy (63%), inclusion/exclusion criteria (73%), multivariable modeling methods and results (74%), and discussion of study limitations (85%). CONCLUSIONS AND CLINICAL RELEVANCE: Inadequacies in presentation militate against comparability among protein marker studies and undermine the generalizability of their findings. The quality of reporting could be improved if journal editors were to require authors to ensure that their work satisfied the REMARK criteria.

Epithelial and stromal cell urokinase plasminogen activator receptor expression differentially correlates with survival in rectal cancer stages B and C patients.

Urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for colorectal cancer (CRC) patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE) or stroma-associated cells (uPARS)) and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs) could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC) patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively) reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007), reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC.

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.

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.