Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery: a multicentre retrospective cohort series.

PURPOSE: Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR. METHODS: This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up. RESULTS: Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p < 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008). CONCLUSION: Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.

Local Excision for Early Rectal Cancer.

Local excision is an established treatment for significant benign rectal tumours and early-stage cancers. It provides cure for most patients with pT1 disease, with minimum impact on quality of life. It is particularly suitable for elderly or comorbid patients. Local excision is associated with a risk of local recurrence, and this may vary from 5 to 30%, as determined by pathological risk factors. Recurrent cancer may be challenging to manage, but this may be mitigated by early detection with intensive surveillance and the use of adjuvant radiotherapy. This approach offers a realistic option for organ preservation in carefully selected early-stage disease compared with primary treatment with radiotherapy or total neoadjuvant treatment.

The Long and the Short of it: the Role of Short-course Radiotherapy in the Neoadjuvant Management of Rectal Cancer.

Total mesorectal excision is the cornerstone of treatment for rectal cancer. Multiple randomised trials have shown a reduction in local recurrence rates with the addition of preoperative radiotherapy, either as a 1-week hypofractionated short-course (SCRT) or a conventionally fractionated long-course (LCRT) schedule with concurrent chemotherapy. There is also increasing interest in the addition of neoadjuvant chemotherapy to radiotherapy with the aim of improving disease-free survival. The relative use of SCRT and LCRT varies considerably across the world. This is reflected in, and is probably driven in part by, disparity between international guideline recommendations. In addition, different approaches to treatment may exist both between and within countries, with variation related to patient, disease and treatment centre and financial factors. In this review, we will specifically focus on the use of SCRT for the treatment of rectal cancer. We will discuss the literature base and current guidelines, highlighting the challenges and controversies in clinical application of this evidence. We will also discuss potential future applications of SCRT, including its role in optimisation and intensification of treatment for rectal cancer.

Rectal cancer lateral lymph nodes: multicentre study of the impact of obturator and internal iliac nodes on oncological outcomes.

BACKGROUND: In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes. METHODS: Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response. RESULTS: More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease. CONCLUSION: Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.

Local recurrence after local excision of early rectal cancer: a meta-analysis of completion TME, adjuvant (chemo)radiation, or no additional treatment.

BACKGROUND: The risks of local recurrence and treatment-related morbidity need to be balanced after local excision of early rectal cancer. The aim of this meta-analysis was to determine oncological outcomes after local excision of pT1-2 rectal cancer followed by no additional treatment (NAT), completion total mesorectal excision (cTME) or adjuvant (chemo)radiotherapy (aCRT). METHODS: A systematic search was conducted in PubMed, Embase and the Cochrane Library. The primary outcome was local recurrence. Statistical analysis included calculation of the weighted average of proportions. RESULTS: Some 73 studies comprising 4674 patients were included in the analysis. Sixty-two evaluated NAT, 13 cTME and 28 aCRT. The local recurrence rate for NAT among low-risk pT1 tumours was 6·7 (95 per cent c.i. 4·8 to 9·3) per cent. There were no local recurrences of low-risk pT1 tumours after cTME or aCRT. The local recurrence rate for high-risk pT1 tumours was 13·6 (8·0 to 22·0) per cent for local excision only, 4·1 (1·7 to 9·4) per cent for cTME and 3·9 (2·0 to 7·5) per cent for aCRT. Local recurrence rates for pT2 tumours were 28·9 (22·3 to 36·4) per cent with NAT, 4 (1 to 13) per cent after cTME and 14·7 (11·2 to 19·0) per cent after aCRT. CONCLUSION: There is a substantial risk of local recurrence in patients who receive no additional treatment after local excision, especially those with high-risk pT1 and pT2 rectal cancer. The lowest recurrence risk is provided by cTME; aCRT has outcomes comparable to those of cTME for high-risk pT1 tumours, but shows a higher risk for pT2 tumours.

ANTECEDENTES: Tras una resección temprana de un cáncer de recto localizado, hay que considerar el equilibrio entre el riesgo de recidiva local y la morbilidad relacionada con el tratamiento. El objetivo de este metaanálisis era determinar los resultados oncológicos tras la resección de un cáncer de recto pT1-T2 seguida de ningún tratamiento adicional (no additional treatment, NAT), escisión total del mesorrecto (completion total mesorectal excision, cTME) o quimiorradioterapia adyuvante (adjuvant chemoradiotherapy, aCRT). METHODS: Se llevó a cabo una búsqueda sistemática en PubMed, Embase y biblioteca Cochrane. La variable principal de resultado era la recidiva local (local recurrence, LR). En el análisis estadístico se calcularon las medias ponderadas de proporciones. RESULTADOS: Se incluyeron en el análisis 76 estudios con un total de 4.793 pacientes. NAT fue evaluada en 72 estudios, cTME en 13 y aCRT en 28. La tasa de LR para NAT en tumores pT1 de bajo riesgo era de 6,7% (i.c. del 95% 4,8-9,3). No se observaron casos de LR en tumores pT1 de bajo riesgo tras cTME o aCRT. La tasa de LR para tumores pT1 de alto riesgo fue de 13,6% (i.c. del 95% 8,0-22,0) para la resección local como único tratamiento, 4,1% (i.c. del 95% 1,7-9,4) para cTME y 3,9% (i.c. del 95% 2,0-7,5) para aCRT. La tasa de LR para tumores pT2 fue de 28,9% (i.c. del 95% 22,3-36,4) para NAT, 4,3% (i.c. del 95% 1,4-12,5) para cTME y 14,7% (i.c. del 95% 11,2-19,0) para aCRT. CONCLUSIÓN: Tras la resección local de cáncer pT1 de alto riesgo y pT2, existe un riesgo sustancial de recidiva local en ausencia de tratamiento adicional. La escisión total del mesorrecto se asocia con el menor riesgo de recidiva. La quimiorradioterapia adyuvante ofrece resultados similares a la escisión total del mesorrecto en tumores pT1 de alto riesgo, pero presenta un mayor riesgo en tumores pT2.

Minimally invasive organ-preserving approaches in the management of mesh erosion after laparoscopic ventral mesh rectopexy.

AIM: This is a systematic approach for minimally invasive methods in the management of mesh erosion after laparoscopic ventral mesh rectopexy. METHODS: All patients managed with organ-preserving techniques for mesh erosion were identified from a prospective database and clinical records were reviewed. Each patient was contacted via telephone and a structured questionnaire was applied. A Likert score was used to assess patient symptoms and overall satisfaction with management. One or more of the following techniques were used: (i) transanal or transvaginal trimming/excision of exposed mesh and sutures, with or without using transanal endoscopic micro surgery or transanal minimally invasive surgery; (ii) laparoscopic pelvic assessment and detachment of mesh from the sacral promontory. RESULTS: Eleven patients were managed for mesh erosion with organ-preserving techniques. All were women with a median age of 60 years [interquartile range (IQR) 53.5-68.5]. Vaginal, rectal, perineal erosion and recto-vaginal fistulation occurred in five, four, one and one patient respectively. Vaginal erosions presented at a median of 51 months (IQR 36-56) after index laparoscopic ventral mesh rectopexy compared to 17.5 months (IQR 14.5-27.25) for the rectal erosions. Median follow-up time was 24 months (IQR 19-49). Four of the meshes (36%) were removed completely whereas seven (63%) were partially removed. Vaginal erosions required a median of two procedures to achieve resolution as opposed to five for rectal. Out of 11 patients, eight were satisfied with the outcome of their management, whereas two were not and one remained ambivalent. CONCLUSION: An organ-sparing minimally invasive approach is feasible in managing mesh erosions but requires multiple procedures and months to complete.

Transperineal minimally invasive APE: preliminary outcomes in a multicenter cohort.

BACKGROUND: Abdominoperineal excision (APE) for rectal cancer is associated with a relatively high risk of positive margins and postoperative morbidity, particularly related to perineal wound healing problems. It is unknown whether the use of a minimally invasive approach for the perineal part of these procedures can improve postoperative outcomes without oncological compromise. The aim of this study was to evaluate the feasibility of minimally invasive transperineal abdominoperineal excision (TpAPE) METHODS: This multicenter retrospective cohort study included all patients having TpAPE for primary low rectal cancer. The primary endpoint was the intraoperative complication rate. Secondary endpoints included major morbidity (Clavien-Dindo ≥ 3), histopathology results, and perineal wound healing. RESULTS: A total of 32 TpAPE procedures were performed in five centers. A bilateral extralevator APE (ELAPE) was performed in 17 patients (53%), a unilateral ELAPE in 7 (22%), and an APE in 8 (25%). Intraoperative complications occurred in five cases (16%) and severe postoperative morbidity in three cases (9%). There were no perioperative deaths. A positive margin (R1) was observed in four patients (13%) and specimen perforation occurred in two (6%). The unilateral extralevator TpAPE group had worse specimen quality and a higher proportion of R1 resections than the bilateral ELAPE or standard APE groups. The rate of uncomplicated perineal wound healing was 53% (n = 17) and three patients (9%) required surgical reintervention. CONCLUSIONS: TpAPE seems to be feasible with acceptable perioperative morbidity and a relatively low rate of perineal wound dehiscence, while histopathological outcomes remain suboptimal. Additional evaluation of the viability of this technique is needed in the form of a prospective trial with standardization of the procedure, indication, audit of outcomes and performed by surgeons with vast experience in transanal total mesorectal excision.

Neoadjuvant radiotherapy in rectal cancer - less is more?

AIM: There is significant international variation in the use of neoadjuvant radiation prior to total mesorectal excision. The MERCURY group advocate selective neoadjuvant chemoradiotherapy (CRT). We have performed a retrospective, single-centre study of patients treated with CRT, where only the circumferential resection margin is threatened, with the aim of identifying whether a more selective approach to CRT provides acceptable local relapse rates (LRRs). METHOD: All consecutive patients who underwent radical surgery for rectal adenocarcinoma over a 5-year period (2007-2012) in the Oxford University Trust were considered. Electronic hospital systems were reviewed to obtain patient and tumour demographics, treatment and follow-up information. All patients were classified into risk categories according to National Institute for Health and Care Excellence guidance. Data were analysed using Microsoft Excel and R. RESULTS: Two hundred and seventy-two patients were identified: 123, 89 and 60 in the high-, intermediate- and low-risk categories, respectively. Seventy-nine per cent of those in the high-risk group, 6% in the intermediate and 5% in the low-risk group underwent CRT. The overall 5-year LRR and distant recurrence rate (DRR) were 5.2% and 17.8%, respectively. The 5-year LRR for those who went straight to surgery was 2.0% and for those who had neoadjuvant CRT it was 7.4%. The DRR for these two groups was 8.5% and 18.9%, respectively. CONCLUSION: Our series demonstrates that the use of CRT only in margin-threatening tumours, results in an exceptionally low LRR for those without margin-threatening disease. In routine clinical care, this strategy can minimize the significant morbidity of multimodal treatment and allow earlier introduction of systemic therapy to minimize distant recurrence.

Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis.

INTRODUCTION: Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function. METHODS: PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed 'conditioned media' (CM). Human umbilical vein endothelial cells (HUVEC) were cultured with PsA SFC or RA SFC-CM (20%). HUVEC tube formation, migration, and PBMC adhesion were assessed by matrigel tube formation, wound repair, and PBMC adhesion assays. HUVEC cell surface expression of ICAM, VCAM, and E-Selectin was assessed by flow cytometry. Transcriptome analysis of genes promoting angiogenesis was performed by real-time PCR. Finally, a MSD multiplex angiogenic assay was performed on PsA SFC and RA SFC supernatants. RESULTS: Macroscopic synovitis and vascularity were similar in PsA and RA patients; however, significant differences in vascular morphological pattern were recorded with tortuous, elongated vessels observed in PsA compared to straight regular branching vessels observed in RA. Transcriptome analysis showed strong upregulation of the pro-angiogenic signature in HUVEC primed with PsA SFC-CM compared to RA SFC-CM and basal control. In parallel, paired PsA SFC-CM significantly induced HUVEC tube formation compared to that of RA SFC-CM. Furthermore, PsA SFC-CM induced HUVEC migration was paralleled by a significant induction in VEGFA, PFKFB3, ICAM-1, and MMP3 mRNA expression. A significant increase in PBMC adhesion and cell surface expression of VCAM-1, ICAM-1, and E-Selectin expression was also demonstrated in PsA SFC-CM-primed HUVEC compared to RA SFC-CM. Finally, VEGF, TSLP, Flt-1, and Tie-2 expression was elevated in PsA SFC-CM compared to RA SFC-CM, with no significant difference in other pro-angiogenic mediators including MIP-3, bFGF, PIGF, and MCP-1. CONCLUSION: PsA SFC and RA SFC secreted factors differentially regulate endothelial cell function, with soluble mediators in the PsA joint microenvironment inducing a more pro-angiogenic phenotype compared to the RA.

Patient-reported functional and quality-of-life outcomes after transanal total mesorectal excision.

Follow-up of more than 1 year after transanal total mesorectal excision for rectal cancer demonstrated improved quality of life and stable or improved functional outcomes. Continued experience and operative efficiency hold promise for improved overall outcomes with this emerging technology. Key patient-reported outcomes.

Adjuvant radiotherapy after local excision of rectal cancer.

BACKGROUND: Local excision is now accepted as a standard treatment option for certain patients with early rectal cancer. However, there is a higher risk of local recurrence than after radical surgery with total mesorectal excision. Adjuvant radiotherapy after local excision may reduce this excess risk, and yet retain the benefits of local excision, with rectal preservation. METHODS: A review of the literature pertaining to the use of adjuvant radiotherapy after local excision of rectal cancer and a discussion of current practice. RESULTS: We first considered local excision as a treatment option for early rectal cancer, looking at technical developments and the risks and benefits of organ preservation, in particular, the advantages for quality of life and the risk of leaving residual disease which may result in local recurrence. We then looked at reported outcomes for studies using adjuvant radiotherapy after local excision. Few of the studies routinely used modern endoscopic methods of local excision and only the recent used chemoradiation. Local recurrence rates after adjuvant radiotherapy have improved over time, with rates of around 3.5% in the recent studies. Adverse effects of adjuvant radiotherapy are not commonly described, but generally, they are relatively mild when described. We then discussed current practice regarding adjuvant radiotherapy, including pathological criteria, discussion of local recurrence risk with the patient and the importance of a surveillance regime to detect any recurrence at an early stage. CONCLUSION: We conclude that the current state of knowledge regarding adjuvant radiotherapy after local excision suggests a potential role in decreasing the risk of local recurrence but further studies are required to better define this effect, clarify which patients will gain the most benefit from this pathway, and identify those who should avoid exposure to the risks of radiotherapy.

Radiotherapy after local excision of rectal cancer may offer reduced local recurrence rates.

AIM: Early rectal cancer can be managed effectively with local excision, which is now the standard of care for many T1 lesions. However, the presence of unexpected adverse histopathological factors may indicate an increased risk of local recurrence, prompting consideration of completion radical surgery. Many patients are unfit or prefer to avoid radical surgery, relying instead on surveillance and early detection of recurrent disease. Recently, radiotherapy has shown promise as an adjuvant therapy in this group. This study assesses local recurrence rates after local excision with adjuvant radiotherapy at a single centre. METHOD: This was a retrospective review of a prospective database of all patients undergoing transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10-year period were analysed. RESULTS: Of 197 patients undergoing TEM for rectal cancer, 33 (17%) had adjuvant radiotherapy because of adverse histopathological features. At 3.2 years' median follow-up, there were three instances of local recurrence (9.1%). Estimated local recurrence at 1 and 3 years was 0% and 6.9%, compared to 16.8% and 21.2% in a propensity-score-matched group who were followed by surveillance alone. Local recurrence was diagnosed at a median of 23 months post-TEM in the radiotherapy group, compared to 8 months in the matched group. CONCLUSION: Radiotherapy after TEM is associated with a trend towards a reduced rate of local recurrence, even for high-risk disease. Radiotherapy would appear to offer a viable alternative to radical completion surgery in the presence of unforeseen adverse histopathological features, as long as a meticulous surveillance programme is in place.

Session 4: Shaping radiotherapy for rectal cancer: should this be personalized?

Preoperative radiotherapy continues to be widely used in patients with operable rectal cancer. However, the indications and goals for such treatment are evolving. Professor Marijnen reviews the historic and current evidence base for the use of preoperative neoadjuvant radiotherapy and the future challenges in tailoring the therapy according to the patients' needs and tumour stage.

Multicentre phase II trial of near-infrared imaging in elective colorectal surgery.

BACKGROUND: Decreasing anastomotic leak rates remain a major goal in colorectal surgery. Assessing intraoperative perfusion by indocyanine green (ICG) with near-infrared (NIR) visualization may assist in selection of intestinal transection level and subsequent anastomotic vascular sufficiency. This study examined the use of NIR-ICG imaging in colorectal surgery. METHODS: This was a prospective phase II study (NCT02459405) of non-selected patients undergoing any elective colorectal operation with anastomosis over a 3-year interval in three tertiary hospitals. A standard protocol was followed to assess NIR-ICG perfusion before and after anastomosis construction in comparison with standard operator visual assessment alone. RESULTS: Five hundred and four patients (median age 64 years, 279 men) having surgery for neoplastic (330) and benign (174) pathology were studied. Some 425 operations (85·3 per cent) were started laparoscopically, with a conversion rate of 5·9 per cent. In all, 220 patients (43·7 per cent) underwent high anterior resection or reversal of Hartmann's operation, and 90 (17·9 per cent) low anterior resection. ICG angiography was achieved in every patient, with a median interval of 29 s to visualization of the signal after injection. NIR-ICG assessment resulted in a change in the site of bowel division in 29 patients (5·8 per cent) with no subsequent leaks in these patients. Leak rates were 2·4 per cent overall (12 of 504), 2·6 per cent for colorectal anastomoses and 3 per cent for low anterior resection. When NIR-ICG imaging was used, the anastomotic leak rates were lower than those in the participating centres from over 1000 similar operations performed with identical technique but without NIR-ICG technology. CONCLUSION: Routine NIR-ICG assessment in patients undergoing elective colorectal surgery is feasible. NIR-ICG use may change intraoperative decisions, which may lead to a reduction in anastomotic leak rates.

Improved urethral fluorescence during low rectal surgery: a new dye and a new method.

BACKGROUND: The aim of this study was to demonstrate highlighting of the urethra during surgery through the use of two different methods: a new near-infrared fluorophore IRDye800BK, and indocyanine green (ICG) mixed with silicone. METHODS: Male cadavers from the department of anatomy at the University of Oxford were used to visualise the urethra during near-infrared fluorescence excitation. To assess IRDye800BK, a perineal incision was utilised after infiltrating the urethra directly with an IRDye800BK solution mixed with Instillagel. ICG-silicone was assessed when the urethra was purposely exposed as part of a simulated transanal total mesorectal dissection. ICG was previously mixed with ethanol and silicone and left to set in a Foley catheter. Fluorescence was visualised using an in-house manufactured fluorescence-enabled laparoscopic system. RESULTS: IRDye800BK demonstrated excellent penetration and visualisation of the urethra under fluorescence at an estimated tissue depth of 2 cm. An ICG-silicone catheter demonstrated excellent fluorescence without leaving any residual solution behind in the urethra after its removal. CONCLUSIONS: The newly described ICG-silicone method opens up the possibility of new technologies in this area of fluorescence guided surgery. IRDye800BK is a promising alternative to ICG in visualising the urethra using fluorescence imaging. Its greater depth of penetration may allow earlier detection of the urethra during surgery and prevent wrong plane surgery sooner.

Farming characteristics and self-reported health outcomes of Irish farmers.

Background: Irish farmers represent a 'high-risk' group for non-communicable diseases, which, arguably, pose a greater occupational health challenge for farmers. To date, there has been little exploration of the farming characteristics associated with farmers' poor health outcomes. Aims: To examine the relationship between farming and male farmers' self-reported health outcomes and to compare the study findings to national health studies to explore which factors specifically are associated with Irish farmers' poorer health outcomes relative to the general population. Methods: This cross-sectional survey research used self-reported quantitative data on the health outcomes and health behaviours of male farmers from the South-East of Ireland. Data were entered into SPSS and descriptive and binary regression techniques were used for data analysis. Results: There were 314 participants (99% response rate). Age, full-time farming and dairy farming significantly impacted self-reported health outcomes and health behaviours. There was a high prevalence of self-reported arthritis compared with the national average of Irish males. 'Younger' farmers (<45 years) were more likely to engage in harmful health behaviours such as smoking and 'binge-drinking' one or more times per week. Conclusions: This study identified self-reported patterns of risky lifestyle behaviours among particular subgroups of Irish farmers for whom targeted health interventions are warranted. Interventions are particularly important for younger farmers who may see themselves as invincible and impregnable to ill-health.