Definition of large bowel obstruction by primary colorectal cancer:A systematic review

Aim: Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies. Method: A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements. Results: A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07). Conclusion: In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT):a multicentre, open-label, randomised, controlled trial

Background: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. Methods: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1–2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. Findings: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11–22) before surgery for intravenous iron and 19 days (IQR 13–27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55–2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87–4·58]; p&lt;0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). Interpretation: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. Funding: Vifor Pharma.</p

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 degrees C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival

Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: study protocol of a randomised controlled multicentre trial (BIOPEX-2 study)

BACKGROUND: Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer. METHODS: Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function. DISCUSSION: The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place. TRIAL REGISTRATION: The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019

Endoscopic vacuum-assisted surgical closure (EVASC) of anastomotic defects after low anterior resection for rectal cancer; lessons learned

Background: Endoscopic vacuum-assisted surgical closure (EVASC) is an emerging treatment for AL, and early initiation of treatment seems to be crucial. The objective of this study was to report on the efficacy of EVASC for anastomotic leakage (AL) after rectal cancer resection and determine factors for success. Methods: This retrospective cohort study included all rectal cancer patients treated with EVASC for a leaking primary anastomosis after LAR at a tertiary referral centre (July 2012—April 2020). Early initiation (≤ 21 days) or late initiation of the EVASC protocol was compared. Primary outcomes were healed and functional anastomosis at end of follow-up. Results: Sixty-two patients were included, of whom 38 were referred. Median follow-up was 25 months (IQR 14–38). Early initiation of EVASC (≤ 21 days) resulted in a higher rate of healed anastomosis (87% vs 59%, OR 4.43 [1.25–15.9]) and functional anastomosis (80% vs 56%, OR 3.11 [1.00–9.71]) if compared to late initiation. Median interval from AL diagnosis to initiation of EVASC was significantly shorter in the early group (11 days (IQR 6–15) vs 70 days (IQR 39–322), p < 0.001). A permanent end-colostomy was created in 7% and 28%, respectively (OR 0.18 [0.04–0.93]). In 17 patients with a non-defunctioned anastomosis, and AL diagnosis within 2 weeks, EVASC resulted in 100% healed and functional anastomosis. Conclusion: Early initiation of EVASC for anastomotic leakage after rectal cancer resection yields high rates of healed and functional anastomosis. EVASC showed to be progressively more successful with the implementation of highly selective diversion and early diagnosis of the leak. Graphical abstract: [Figure not available: see fulltext.]

Snapshot Study on the Value of Omentoplasty in Abdominoperineal Resection with Primary Perineal Closure for Rectal Cancer

Background: Perineal wound complications are often encountered following abdominoperineal resection (APR). Filling of the pelvic space by omentoplasty (OP) might prevent these complications, but there is scant evidence to support its routine application. Objective: The aim of this study was to evaluate the impact of OP on perineal wound complications. Methods: All patients undergoing APR with primary perineal closure (PPC) for non-locally advanced rectal cancer in 71 Dutch centers in 2011 were selected from a cross-sectional snapshot study. Outcomes were compared between PPC with or without OP, which was based on variability in practice among surgeons. Results: Of 639 patients who underwent APR for rectal cancer, 477 had a non-locally advanced tumor and PPC was performed. Of those, 172 (36%) underwent OP. Patients with OP statistically more often underwent an extralevator approach (32% vs. 14%). Median follow-up was 41 months (interquartile range 22–47). There were no significant differences with or without OP in terms of non-healing of the perineal wound at 30 days (47% vs. 48%), non-healing at the end of follow-up (9% vs. 5%), pelvic abscess (12% vs. 13%) or re-intervention for ileus (5% vs. 3%). Perineal hernia developed significantly more often after OP (13% vs. 7%), also by multivariable analysis (odds ratio 2.61, 95% confidence interval 1.271–5.364; p = 0.009). Conclusions: In contrast to previous assumptions, OP after APR with PPC appeared not to improve perineal wound healing and seemed to increase the occurrence of perineal hernia. These findings question the routine use of OP for primary filling of the pelvic space

Iatrogenic injury of the urinary tract during salvage procedures for pelvic sepsis: Experience of a national referral centre

Aim: This study aimed to determine the incidence, consequences and outcomes of iatrogenic urinary tract injury (IUI) during salvage surgery for pelvic sepsis. Method: Patients who underwent salvage surgery for pelvic sepsis after prior low anterior resection or Hartmann's procedure for rectal cancer were prospectively maintained in a database between 2010 and 2020 and reviewed retrospectively. The primary endpoint was the incidence of IUI. Secondary endpoints were timing of diagnosis (intra- vs. postoperative), reinterventions related to the IUI and healing of IUI. Results: In total 126 consecutive patients were included, and IUI occurred in 13 patients (10%). A ureteric injury occurred in eight patients, bladder injury in four patients and a urethral injury in one patient. All patients with an IUI had radiotherapy as neoadjuvant treatment. The IUI was diagnosed postoperatively in 63% (n = 8/13) with a median duration between surgery and diagnosis of the IUI of 10 days (IQR: 6–15). The median number of reinterventions was five (range 1–31) in the group with a postoperative diagnosis and one (range 0–1) in the group with an intraoperative diagnosis. Four patients required a surgical reintervention, all concerning injuries diagnosed postoperatively. At the end of follow-up, 85% of patients (n = 11/13) had a healed IUI. Conclusion: Iatrogenic urinary tract injury is not uncommon in salvage procedures for pelvic sepsis, even in an experienced tertiary referral centre. Most injuries were diagnosed postoperatively which affects the severity of these complications, emphasising the need to improve intraoperative diagnostic modalities

Endoscopic vacuum therapy and early surgical closure after pelvic anastomotic leak: meta-analysis of bowel continuity rates

BACKGROUND: Endoscopic vacuum therapy (EVT) with or without early surgical closure (ESC) is considered an effective option in the management of pelvic anastomotic leakage. This meta-analysis evaluated the effectiveness of EVT in terms of stoma reversal rate and the added value of ESC. METHODS: A systematic search of PubMed, MEDLINE, and the Cochrane Library was conducted in November 2021 to identify articles on EVT in adult patients with pelvic anastomotic leakage. The primary outcome was restored continuity rate. Following PRISMA guidelines, a meta-analysis was undertaken using a random-effects model. RESULTS: Twenty-nine studies were included, accounting for 827 patients with leakage who underwent EVT. There was large heterogeneity between studies in design and reported outcomes, and a high risk of bias. The overall weighted mean restored continuity rate was 66.8 (95 per cent c.i. 58.8 to 73.9) per cent. In patients undergoing EVT with ESC, the calculated restored continuity rate was 82 per cent (95 per cent c.i. 50.1 to 95.4) as compared to 64.7 per cent (95 per cent c.i. 55.7 to 72.7) after EVT without ESC. The mean number of sponge exchanges was 4 (95 per cent c.i. 2.7 to 4.6) and 9.8 (95 per cent c.i. 7.3 to 12.3), respectively. Sensitivity analysis showed a restored continuity rate of 81 per cent (95 per cent c.i. 55.8 to 99.5) for benign disease, 69.0 per cent (95 per cent c.i. 57.3 to 78.7) for colorectal cancer, and 65 per cent (95 per cent c.i. 48.8 to 79.1) if neoadjuvant radiotherapy was given. CONCLUSION: EVT is associated with satisfactory stoma reversal rates that may be improved if it is combined with ESC