Implementation of an Enhanced Recovery after Surgery Protocol in Advanced and Recurrent Rectal Cancer Patients after beyond Total Mesorectal Excision Surgery: A Feasibility Study.

INTRODUCTION: The implementation of an Enhanced Recovery After Surgery (ERAS) protocol in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) has been deemed unfeasible until now because of the heterogeneity of this disease and low caseloads. Since evidence and experience with ERAS principles in colorectal cancer care are increasing, a modified ERAS protocol for this specific group has been developed. The aim of this study is to evaluate the implementation of a tailored ERAS protocol for patients with LARC or LRRC, requiring beyond total mesorectal excision (bTME) surgery. METHODS: Patients who underwent a bTME for LARC or LRRC between October 2021 and December 2022 were prospectively studied. All patients were treated in accordance with the ERAS LARRC protocol, which consisted of 39 ERAS care elements specifically developed for patients with LARC and LRRC. One of the most important adaptations of this protocol was the anaesthesia procedure, which involved the use of total intravenous anaesthesia with intravenous (iv) lidocaine, iv methadone, and iv ketamine instead of epidural anaesthesia. The outcomes showed compliance with ERAS care elements, complications, length of stay, and functional recovery. A follow-up was performed at 30 and 90 days post-surgery. RESULTS: Seventy-two patients were selected, all of whom underwent bTME for either LARC (54.2%) or LRRC (45.8%). Total compliance with the adjusted ERAS protocol was 73.6%. Major complications were present in 12 patients (16.7%), and the median length of hospital stay was 9 days (IQR 6.0-14.0). Patients who received multimodal anaesthesia (75.0%) stayed in the hospital for a median of 7.0 days (IQR 6.8-15.5). These patients received fewer opioids on the first three postoperative days than patients who received epidural analgesia (p < 0.001). CONCLUSIONS: The implementation of the ERAS LARRC protocol seemed successful according to its compliance rate of >70%. Its complication rate was substantially reduced in comparison with the literature. Multimodal anaesthesia is feasible in beyond TME surgery with promising effects on recovery after surgery.

Locally recurrent rectal cancer: Oncological outcomes for patients with a pathological complete response after neoadjuvant therapy.

BACKGROUND: For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR appears to be associated with improved outcomes. The aim of this retrospective cohort study was to compare the oncological outcomes of patients with locally recurrent rectal cancer with and without a pCR. METHODS: Patients who underwent neoadjuvant treatment and surgery for locally recurrent rectal cancer with curative intent between January 2004 and June 2020 at a tertiary referral hospital were analysed. Primary outcomes included overall survival, disease-free survival, metastasis-free survival, and local re-recurrence-free survival, stratified according to whether the patient had a pCR. RESULTS: Of a total of 345 patients, 51 (14.8 per cent) had a pCR. Median follow-up was 36 (i.q.r. 16-60) months. The 3-year overall survival rate was 77 per cent for patients with a pCR and 51.1 per cent for those without (P < 0.001). The 3-year disease-free survival rate was 56 per cent for patients with a pCR and 26.1 per cent for those without (P < 0.001). The 3-year local re-recurrence-free survival rate was 82 and 44 per cent respectively (P < 0.001). Surgical procedures (for example soft tissue, sacrum, and urogenital organ resections) and postoperative complications were comparable between patients with and without a pCR. CONCLUSION: This study showed that patients with a pCR have superior oncological outcomes to those without a pCR. It may therefore be safe to consider a watch-and-wait approach in highly selected patients, potentially improving quality of life by omitting extensive surgical procedures without compromising oncological outcomes.

Development of a consensus-based delineation guideline for locally recurrent rectal cancer.

BACKGROUND AND PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) is used in locally recurrent rectal cancer (LRRC) to increase chances of a radical surgical resection. Delineation in LRRC is hampered by complex disease presentation and limited clinical exposure. Within the PelvEx II trial, evaluating the benefit of chemotherapy preceding nCRT for LRRC, a delineation guideline was developed by an expert LRRC team. MATERIALS AND METHODS: Eight radiation oncologists, from Dutch and Swedish expert centres, participated in two meetings, delineating GTV and CTV in six cases. Regions at-risk for re-recurrence or irradical resection were identified by eleven expert surgeons and one expert radiologist. Target volumes were evaluated multidisciplinary. Inter-observer variation was analysed. RESULTS: Inter-observer variation in delineation of LRRC appeared large. Multidisciplinary evaluation per case is beneficial in determining target volumes. The following consensus regarding target volumes was reached. GTV should encompass all tumour, including extension into OAR if applicable. If the tumour is in fibrosis, GTV should encompass the entire fibrotic area. Only if tumour can clearly be distinguished from fibrosis, GTV may be reduced, as long as the entire fibrotic area is covered by the CTV. CTV is GTV with a 1 cm margin and should encompass all at-risk regions for irradical resection or re-recurrence. CTV should not be adjusted towards other organs. Multifocal recurrences should be encompassed in one CTV. Elective nodal delineation is only advised in radiotherapy-naïve patients. CONCLUSION: This study provides a first consensus-based delineation guideline for LRRC. Analyses of re-recurrences is needed to understand disease behaviour and to optimize delineation guidelines accordingly.

MRI tumour regression grade in locally recurrent rectal cancer.

BACKGROUND: This study aimed to investigate the agreement between magnetic resonance tumour regression grade (mrTRG) and pathological regression grade (pTRG) in patients with locally recurrent rectal cancer (LRRC). Also, the reproducibility of mrTRG was investigated. METHODS: All patients with LRRC who underwent a resection between 2010 and 2018 after treatment with induction chemotherapy and neoadjuvant chemo(re)irradiation in whom a restaging MRI was available were retrospectively selected. All MRI scans were reassessed by two independent radiologists using the mrTRG, and the pTRG was reassessed by an independent pathologist. The interobserver agreement between the radiologists as well as between the radiologists and the pathologist was assessed with the weighted kappa test. A subanalysis was performed to evaluate the influence of the interval between imaging and surgery. RESULTS: Out of 313 patients with LRRC treated during the study interval, 124 patients were selected. Interobserver agreement between the radiologists was fair (k = 0.28) using a two-tier grading system (mrTRG 1-2 versus mrTRG 3-5). For the lead radiologist, agreement with pTRG was moderate (k = 0.52; 95 per cent c.i. 0.36 to 0.68) when comparing good (mrTRG 1-2 and Mandard 1-2) and intermediate/poor responders (mrTRG 3-5 and Mandard 3-5), and the agreement was fair between the other abdominal radiologist and pTRG (k = 0.39; 95 per cent c.i. 0.22 to 0.56). A shorter interval (less than 7 weeks) between MRI and surgery resulted in an improved agreement (k = 0.69), compared with an interval more than 7 weeks (k = 0.340). For the lead radiologist, the positive predictive value for predicting good responders was 95 per cent (95 per cent c.i. 71 per cent to 99 per cent), whereas this was 56 per cent (95 per cent c.i. 44 per cent to 66 per cent) for the other radiologist. CONCLUSION: This study showed that, in LRRC, the reproducibility of mrTRG among radiologists is limited and the agreement of mrTRG with pTRG is low. However, a shorter interval between MRI and surgery seems to improve this agreement and, if assessed by a dedicated radiologist, mrTRG could predict good responders.

Locally recurrent rectal cancer: oncological outcomes with different treatment strategies in two tertiary referral units.

BACKGROUND: The optimal treatment for patients with locally recurrent rectal cancer (LRRC) is controversial. The aim of this study was to investigate different treatment strategies in two leading tertiary referral hospitals in Europe. METHODS: All patients who underwent curative surgery for LRRC between January 2003 and December 2017 in Catharina Hospital, Eindhoven, the Netherlands (CHE), or Karolinska University Hospital, Stockholm, Sweden (KAR), were studied retrospectively. Available MRIs were reviewed to obtain a uniform staging for optimal comparison of both cohorts. The main outcomes studied were overall survival (OS), local re-recurrence-free survival (LRFS), and metastasis-free survival (MFS). RESULTS: In total, 377 patients were included, of whom 126 and 251 patients came from KAR and CHE respectively. At 5 years, the LRFS rate was 62.3 per cent in KAR versus 42.3 per cent in CHE (P = 0.017), whereas OS and MFS were similar. A clear surgical resection margin (R0) was the strongest prognostic factor for survival, with a hazard ratio of 2.23 (95 per cent c.i. 1.74 to 2.86; P < 0.001), 3.96 (2.87 to 5.47; P < 0.001), and 2.00 (1.48 to 2.69; P < 0.001) for OS, LRFS, and MFS respectively. KAR performed more extensive operations, resulting in more R0 resections than in CHE (76.2 versus 61.4 per cent; P = 0.004), whereas CHE relied more on neoadjuvant treatment and intraoperative radiotherapy, to reduce the morbidity of multivisceral resections (P < 0.001). CONCLUSION: In radiotherapy-naive patients, neoadjuvant full-course chemoradiation confers the best oncological outcome. However, neoadjuvant therapy does not diminish the need for extended radical surgery to increase R0 resection rates.

Comparison of intra- and extra-corporeal laparoscopic hernia repair in children: A systematic review and pooled data-analysis.

BACKGROUND: Laparoscopic surgery is increasingly used to repair paediatric inguinal hernias and can be divided into intra- or extra-corporeal closing techniques. No statement regarding the superiority of one of the two techniques can be made. This study aims to provide evidence supporting the superiority of intra- or extra-corporeal suturing technique. METHODS: A systematic literature search was conducted using PubMed, Embase, MEDLINE, and Cochrane Library databases. Randomised controlled trials and prospective studies comparing different laparoscopic techniques were eligible for inclusion. Data were pooled using a random-effects model, comparing single-port extra-peritoneal closure to intra-peritoneal purse string suture closing. Primary outcome was recurrence rate. Secondary outcomes were duration of surgery (min), peri­ and post-operative complications (i.e. injury of spermatic vessels or spermatic cord, tuba lesions, bleeding and apnoea, haematoma/scrotal oedema, hydrocele, wound infection, iatrogenic ascent of the testis and testicular atrophy), contralateral patent processus vaginalis (CPPV) rate, post-operative pain, length of hospital stay and cosmetic appearance of the wound. RESULTS: Fifteen studies (n = 3680 patients, age range 0.5-12 years, follow-up range 3-10 months) were included is this systematic review. Intra-corporeal hernia repair was performed in 738 children and extra-corporeal repair was performed in 2942 children. A pooled data analysis could only be performed for the single port extra-corporeal closing technique and the three port intra-corporeal closing technique. We found that recurrence rate was lower in the single-port extra-corporeal closing technique compared to the intra-corporeal purse suture closing technique (0.6% vs 5.5%, 95% CI 0.107 (0.024-0.477); p < 0.001). Operation time was shorter for extra-corporeal unilateral and bilateral inguinal hernia repair compared with intra-corporeal approach, but no pooled data analysis could be performed. Due to the presence of substantial heterogeneity, it was not possible to assess other outcome measures. CONCLUSION: Single-port extra-corporeal closure seems to result in less recurrent hernias and a shorter operative time compared to intra-corporeal purse suture closing technique. No difference regarding peri­ and post-operative complications could be found and no statements regarding the length of hospital admission, post-operative pain and cosmetics could be made due to substantial heterogeneity. LEVEL OF EVIDENCE: Level II.