Completion total mesorectal excision after transanal local excision of early rectal cancer: a systematic review and meta-analysis
DOI: 10.1097/DCR.0000000000002407
Journal: Diseases of the Colon & Rectum Volume 65: 5 (2022)

What is known about this subject?

Rates of transanal excision (TAE) of early rectal cancers are increasing as a means of organ preservation in a select group of patients. Historically, these cT1-2 cN0 tumours were treated by rectal resection with total mesorectal excision (TME). However, TAE may offer benefits in terms of lower morbidity and equivalent oncological safety. Despite this, some tumours resected by TAE may reveal unfavourable, high-risk features or signs incomplete resection which necessitate completion TME surgery. In such cases there have been concerns raised regarding the impact of the inflammation and fibrosis caused by TAE on the quality of the subsequent completion TME. This systematic review and meta-analysis by Wyatt et al. looks to synthesis the evidence relating to completion TME following previous TAE. They also seek to compare primary TME with completion TME in this setting.

Design

Systematic Review and Meta-analysis

Study selection

Papers reporting the outcomes of patients undergoing completion TME following previous TAE for early rectal cancer. Indications for TAE were individually defined by each author group up to a maximum staging of T2N0. Studies reporting TAE by flexible endoscope, palliative procedures and case reports were excluded

Outcome measures

Primary – histopathological specimen quality, long-term survival, and recurrence rates.
Secondary – operative time, abdominoperineal excision of rectum (APER) rate, intraoperative blood loss, postoperative morbidity, conversion to open rates, length of stay, and 30-day mortality rates.

Search strategy

Databases included PubMed, Cochrane library, MEDLINE, and Embase from 1990
to April 2021.

Key results

• Twenty-three studies (14 retrospective observational, 9 case-control, no RCTs) including 646 patients were eligible. 8 studies were included in the meta-analyses.
• Most reported transanal endoscopic microsurgery (TEM), some reported TAMIS and some reported resection with a transanal retractor only.
• Weighted average for time between TAE and completion TME was 6.8 weeks
• Completion TME was associated with incomplete mesorectal specimens (risk ratio, 3.06; 95% CI, 1.41–6.62; p = 0.005) but there was no difference in the R1 resection rate.
• Completion TME led to lower lymph node yields (standardized MD, –0.26; 95% CI, –0.47 to 0.06; p = 0.01)
• Rates of APER were higher in the completion TME group but this was not significant (RR, 1.22; 95% CI, 0.97–1.55; p = 0.09)
• Blood loss and operative time were higher in the completion TME group.
• There was no significant difference in rates of intraoperative conversion to open, or in complication rates, or in 30-day mortality between primary and completion TME.
• The weighted average of residual disease in completion TME specimens was 35% for 423 patients
• No difference in local or systemic recurrence was found and there were no significant differences in 3- or 5- year survival between primary and completion TME.

Implications for colorectal practice?

With the increase in TAE for early rectal cancer and the increase in watch and wait programmes colorectal surgeons need to be prepared to undertake completion TME in the event of unfavourable TAE specimen characteristics. This paper provides evidence to suggest that whilst morbidity and survival might be comparable between primary and completion TME we need to be aware of the risk of reduced lymph node yield and incidence of an incomplete TME. The study is limited by the quality of the available literature, particularly the lack of randomised trials. This may reflect the low incidence of completion TME in this setting. Consequently, the conclusions relating to survival and recurrence should be treated with caution. Data relating to stoma rates between groups would also have been noteworthy. Nevertheless, patients should be counselled regarding the risks and benefits of organ preservation in early rectal cancer and should be informed of the outcomes relating to completion TME if this is later required.

Pregnancy outcomes after stoma surgery for inflammatory bowel disease: The results of a retrospective multicentre audit
The PAPooSE Study Group
https://doi.org/10.1111/codi.16098
Journal: Colorectal Disease 2022;00:1-7

What is known about this subject?

Inflammatory bowel disease (IBD) affects up to 500,000 people in the UK. The diagnosis of IBD can frequently occur at a young age and those undergoing surgery can often require stoma formation – either temporary or permanent. There are data relating to the impact of IBD and stoma formation on fertility, but little information exists on the perinatal outcomes of women with a stoma. Potential problems cited in case reports include parastomal hernias, difficulties in attaching stoma appliances and obstructive symptoms. This study by the PAPooSE Group aims to capture data related to the obstetric, neonatal and stoma outcomes of pregnant women with an IBD related stoma.

Design

Retrospective audit conducted across 15 UK centres.

Study eligibility

Female patients with confirmed IBD who had a pregnancy with an existing stoma from 2014 -2020. Those with non IBD related stomas and previous stoma reversal were excluded.

Outcomes

• Co-primary: Stoma complications and obstetric mode of delivery.
• Secondary: Week of gestation, birth weight, and congenital abnormalities, IBD flare (change in medical therapy or high output stoma), incidence of intestinal obstruction, stoma prolapse, stoma herniation, and need for further stoma surgery.

Results

• 82 pregnancies in 77 women were analysed of which 61% had Crohn’s and 35% had ulcerative colitis with 4% unclassified IBD.
• Stoma types included Ileostomy in 72 (88%) and colostomy in 10 (12%) pregnancies.
• Biologics were stopped in 20 of 29 cases at a mean of 25 weeks’ gestation. In 45 patients no medical therapy for IBD was required during pregnancy.
• The overall cesarean section (CS) rate was 73% (n=58, 44 elective and 14 emergency). For reference, the population CS rate is 30.9% in the general IBD population and 29% in all national deliveries. In 19 elective CS, an IBD indication for CS was documented.
• In 20 (24%) pregnancies, serious stoma-related complications occurred – all in ileostomies. Complications included stoma prolapse (11%, n=9), new parastomal hernia (4%, n=3), small bowel obstruction (9%, n=7).
• Mean gestation was 37 weeks. 19% delivered before 37 weeks and 17% had a birth weight <2500g. Postpartum haemorrhage occurred in six (7.5%) cases, of which one required surgical intervention. Bladder injuries during CS occurred in three patients.
• Complications relating to IBD occurred in 11 cases (13%) – IBD flare, perianal sepsis, high output stoma.

Implications for colorectal practice?

This audit is the largest study of pregnancy outcomes after stoma surgery for IBD. It has found that cesarean section rates are significantly higher than the general population and the non-stoma IBD population. However, the rate of emergency CS was similar to the general population. Interestingly, IBD was only documented as the reason in 19 of 44 elective CS. It would be interesting to understand the reason for the remainder. Complications of bladder injury at CS (5%) were also much higher than the population rate (0.1% to 0.3%). Stoma complication rates were also high in the perinatal period with an overall rate for 24%. The quantification of these risks has not previously reported and will provide important information for this patient group. The study is limited by its retrospective nature and its reliance on the accuracy of existing hospital records. However, the information provided will not only assist colorectal surgeons but also obstetric teams and specialist stoma care nurses during consultations with women at an early stage of their pregnancy. Ultimately this should lead improved patient-clinician decision-making around methods of delivery and perinatal care in this patient group.

Neoadjuvant therapy versus direct to surgery for T4 colon cancer: meta-analysis
Jung F, Lee M et al.
https://doi.org/10.1093/bjs/znab382
British Journal of Surgery, Volume 109, Issue 1, January 2022, pages 30–36

What is known about this subject?

The traditional approach to colon cancer involves surgical resection with the aim of a clear resection margin followed by adjuvant chemotherapy if certain high-risk pathological features are present. Neoadjuvant chemotherapy (NAC) has an established role in many solid tumours but its use in colon cancer has remained unclear. The FOxTROT study aimed to investigate the use of NAC in T3/T4 colon cancers. The trial found that rates of incomplete resection were halved following NAC and an improved 2-year disease control, but this was not statistically significant. In this meta-analysis by Jung et al. the authors seek to further investigate the uncertainty behind the outcomes of NAC compared to straight to surgery for T4 colon cancers.

Design

Systematic review and meta-analysis

Study eligibility

Studies comparing one neoadjuvant therapy to straight to surgery or a second neoadjuvant therapy for T4 colon cancer.

Studies only evaluating earlier-stage (T1-T3), metastatic, or recurrent colonic cancer were excluded.

Notably, the authors excluded abstracts. However, they chose to make an exception for the phase III study abstract by the FOxTROT Collaborative Group which reported preliminary results from this study. They performed a supplementary analysis based on this data

Search Strategy

The authors searched 5 electronic databases up to 11th February 2020 including: MEDLINE (OVID); Embase (OVID); the Cochrane Central Register of Controlled Trials (CENTRALWeb of Science (Clarivate); and CINAHL; EbscoHost)

Outcomes

Primary – rate of R0 resection margin, major and minor 30-day morbidity, overall survival and cancer recurrence

Secondary – treatment associated adverse effects

Results

• The search found 11 846 unique citations of which 110 underwent full text review
• 4 studies were included in the data synthesis (one RCT and 3 retrospective cohort studies) comprising of 43,063 patients
• Neoadjuvant therapies included FOLFOX, 5-FU + leucovorin or radiotherapy
• Neoadjuvant therapy was associated with an increased R0 rate compared with straight to surgery, (pooled OR 2.60, 95% CI 1.12 to 6.02)
• Neoadjuvant treatment saw improved 3-year overall survival (pooled HR 1.92, [1.04 to 3.53]) and 5-year overall survival (pooled HR 1.42, [1.10 to 1.82])
• 30-day rates of minor and major adverse events were no different between neoadjuvant treatment and straight to surgery
• When data were added from the phase III abstract data of the FOxTROT trial neoadjuvant treatment was associated with decreased cancer recurrence
• Due to the small number of studies a sensitivity analyses, subgroup analysis, and meta-regressions could not be performed.

Implications for colorectal practice?

This paper has found that neoadjuvant therapy improved the rate of complete resection and overall compared with a straight to surgery approach. This suggests that neoadjuvant treatment may help to control advanced tumours prior to surgery. However, we still do not know whether this approach might alter the extent of surgical resection required, or indeed the need for a multivisceral resection. This study is limited by the heterogeneity of neoadjuvant regimes and the small number of studies included with only one RCT. The inclusion of FOxTROT data adds strength to the findings. Importantly, the work of the FOxTROT collaborative group is ongoing with plans to investigate different neoadjuvant regimes the aim of a personalised approach to neoadjuvant treatment.

The Association Between Modifiable Lifestyle Factors and Postoperative Complications of Elective Surgery in Patients with Colorectal Cancer
doi: 10.1097/DCR.0000000000001976
Diseases of the Colon & Rectum: November 2021 – Volume 64 – Issue 11 – p 1342-1353

What is known about this subject?

The use of ‘prehabilitation’ is gaining traction as a means to preoperatively increase a patient’s functional capacity before elective colorectal cancer surgery. The aim of this intervention is to reduce postoperative morbidity and accelerate postsurgical recovery. Through prehabilitation, modifiable risk factors for an individual patient are addressed. These factors may include smoking status, nutrition, alcohol consumption and physical exercise.

Design

Retrospective analysis of data from a prospectively maintained database. The study was undertaken as part of the Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence colorectal tumour recurrence, survival and quality of life” (COLON) study

Population

Patients with newly diagnosed colorectal cancer undergoing elective surgery at 11 Dutch hospitals from August 2010 and December 2018

Those who had a history of previous CRC, other bowel resection, chronic IBD, a hereditary CRC syndrome, dementia, undergoing transanal surgery or hyperthermic intraperitoneal chemotherapy were excluded.

Methods and outcomes

Patients completed self-administered questionnaires shortly after diagnosis regarding their smoking status, alcohol consumption, BMI and physical activity.

Data on postoperative outcomes were collected from the Dutch Colorectal Audit.

The authors used multivariable logistic regression to identify which preoperative lifestyle factors were associated with postoperative complications.

Primary outcome

Occurrence of postoperative complications after elective CRC surgery. Complications were recorded up to 30 days (pre-2018) or 90 days (post-2018).

Secondary outcome

The secondary outcome was length of stay.

Results

• 1564 patients were studied (68.9% colon cancer, 31.1% rectal cancer)
• 87.2% were classified as ASA I or II
• 446 patients (28.5%) experienced 1 or more postoperative complication.
• Complication increased length of stay (12 vs 5 days, p < 0.001)
• Current smoking (vs never smoking) was associated with postoperative complications (OR, 1.62; 95% CI, 1.02–2.56; p = 0.04)
• BMI, alcohol consumption, and physical activity were not independently associated with postoperative complications in general
• Among ASA class III to IV physical activity >1000 min/wk was independently associated with a reduced risk of postoperative complications (OR, 0.17; 95% CI, 0.03–0.87; p = 0.04) compared with <150 min/wk

Implications for colorectal practice?

This paper highlights the effect of smoking status on the risk of postoperative complication in elective CRC surgery. This finding serves to reinforce the need to encourage smoking cessation among newly diagnosed CRC patient. Interestingly, despite the authors hypothesis other factors such as increasing BMI and alcohol consumption showed no association.

The study was observational and did not measure the effect of modifying these named risk factors on patient outcome. It must also be acknowledged that risk factors were self-reported by patients and are reliant on the accuracy of this.

Given the results, it would be interesting to measure the effect of preoperative smoking cessation in this cohort, particularly when factoring the pressures of cancer waiting targets.

Diagnostic accuracy of C-reactive protein, procalcitonin and neutrophils for the early detection of anastomotic leakage after colorectal resection: a multicentric, prospective study. DOI: 10.1111/codi.15845. Colorectal Disease 2021;00:1–8.

What is known about this subject?

Anastomotic leak (AL) is one of the most feared complications of colorectal surgery. The consequences of AL include chronic sepsis, permanent stoma, delays in oncological treatment alongside substantial healthcare costs. Early diagnosis of AL can limit such sequelae and may reduce its associated morbidity and mortality. Therefore, the potential to identify patients with AL, through use of a biomarker, could be of significant value to the treating clinician. Biomarkers of interest include C-reactive protein (CRP), neutrophils and procalcitonin

Design

Observational, prospective, multicentre cohort study

Population

• Consecutive patients ≥18yrs undergoing elective or emergency surgery requiring colonic or rectal resection with a single anastomosis without a stoma.
• Patients receiving intraoperative intra-peritoneal chemotherapy were excluded.

Method and outcomes

• All participants were tested for CRP, procalcitonin and neutrophil levels on the 4th postoperative day.
• AL was defined as occurring up to 60 days postoperatively diagnosed either radiologically or clinically.
• The authors used receiver operating characteristic curves to analyse the reliability of each biomarker as a predictor for AL. They used the area under the curve (AUC) and Youdens statistic (a statistic that captures the performance of a dichotomous diagnostic test) to determine the cut-off of each biomarker at 90% sensitivity.

Primary outcome

Reliability of CRP, procalcitonin and neutrophils to predict AL on the 4th postoperative day

Secondary outcomes

• To determine the cut-off for each biomarker to detect the presence of AL
• To determine whether combining these biomarkers offered additional accuracy in the detection of AL
• To assess whether surgical access (open vs laparoscopic) affected the reliability of these biomarkers in detecting AL

Results

• Data from 2501 patients was analysed across 34 centres.
• The anastomotic leak rate was 8.6% (n=216)
• 60 day morbidity and mortality were 30.1% and 1.6% respectively.
• CRP was found to be the most reliable biomarker with an AUC of 0.84.
• Procalcitonin and neutrophils had an AUC of 0.75 and 0.64 respectively.
• All 3 biomarkers saw their AUC increase when patients undergoing laparoscopic surgery were analysed.
• A CRP cut-off of 119.5mg/L had a sensitivity of 70%, a specificity of 81%, a negative predictive value of 97% and a positive predictive value of 26% for AL
• The minimum cut-off for CRP for a sensitivity of 90% was 66.5mg/L
• Regression modelling showed that combining all 3 biomarkers did not increase diagnostic accuracy.

Implications for colorectal practice?

This paper reports the largest prospective multicentre study examining the accuracy of 3 biomarkers for predicting AL. The data suggest that interpretation of CRP measurement on the 4th postoperative day may be the optimal timing for this. Specifically, a level of 119.5mg/L in this cohort had a high negative predictive value of 97% (the probability that individuals with a CRP <119.5mg/L don’t have AL). The authors argue that this CRP threshold may help guide the safe discharge of patients. Furthermore, additional investigation may be prompted if such levels are exceed, perhaps with the benefit of identifying AL earlier in the clinical course. All blood indices should be interpreted within the clinical context.

Complete mesocolic excision versus conventional surgery for colon cancer: A systematic review and meta-analysis. Crane J, Hamed M, Borucki JP, El-Hadi A, Shaikh I, Stearns AT. Published: Colorectal Disease 2 May 2021. https://doi.org/10.1111/codi.15644

The study results demonstrate an overall survival benefit from CME/D3 at 3 and 5 years (relative risk reduction of 31% and 22% respectively) and disease-free survival benefit with relative risk reduction estimated at 40%, 28% and 33% respectively at 1, 3 and 5 years postoperatively.

More lymph nodes were retrieved with CME (6 nodes more than conventional surgery). And while the CME procedure took a longer operative time (28 minutes longer), there was no significant difference in overall complications, anastomotic leak or blood loss when compared with conventional surgery.

Method and outcomes

Design

Systematic review and meta-analysis

Population

Patient with colon cancer who had complete mesocolic excision (D3 dissection) versus patients who had conventional surgery (D1 and D2 dissection)

Primary outcome

Long-term oncological outcomes (overall and disease-free survival) at 1, 3 and 5 years.

Secondary outcomes

• Perioperative outcomes (operation duration, blood loss, overall complications including anastomotic leakage and 30-day mortality)
• Pathological outcomes (length of bowel resected, lymph node harvest and risk of R1 resection).

Results

• 31 studies were included in the review ( out of 2463 screened records)
• This included 13830 patients in the CME/D3 versus 12810 patients in the conventional cohort.
• Oncological outcomes:
  • Disease free survival at 1,3, and 5 years was statistically significantly better in CME group with RR 0.60 (95% CI 0.45–0.81, P < 0.001); RR 0.72 (95% CI 0.62–0.83, P = 0.001); RR 0.67 (95% CI 0.52–0.86, P < 0.001) respectively.
  • Overall survival was statistically significantly better in CME group at 3 nd 5 years RR 0.69 (95% CI 0.51–0.93, P = 0.016) and RR 0.78 (95% CI 0.64–0.95, P = 0.011) respectively. And not statistically different at year 1 RR 0.85 (95% CI 0.67–1.09, P = 0.201)
• Pathological outcomes:
  • LN yield (29 studies): significantly higher in the CME group (weighted mean of 6.1 additional LN)
  • The risk of R1 resection (12 studies): in favour of the CME group: RR 0.61 (95% CI 0.27–1.38, P = 0.234).
  • No difference in the resected bowel length.
• Perioperative outcomes:
  • No difference in overall complications (21 studies), Anastomotic leak (18 studies), blood loss (31 studies), or 30-day mortality (8 studies)
  • Increased operative time for CME (weighted mean difference 27.7 min, P = 0.041)

Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study. COVIDSurg Collaborative and GlobalSurg Collaborative. Published: Anaesthesia 09 March 2020: https://doi.org/10.1111/anae.15458

What is known about this subject?

The postoperative mortality and pulmonary complications are higher in patients with SARS-COV-2 infection and elective surgery should be delayed in this group of patients to reduce this risk. However, There has been no agreement on the time this group of patients should wait for before being offered elective surgery and whether this interval should be different according to the severity and duration of SARS-CoV-2 symptoms.

Method and outcomes

Design

International, multicentre, prospective cohort study.

Population

• Patients undergoing any type of surgery (elective or emergency) for any indication in October 2020.
• Patients with a history of preoperative SARS-CoV-2 were classified into three groups: asymptomatic; symptomatic but symptoms now resolved; or symptomatic with ongoing symptoms.
• Time from the diagnosis of SARS-CoV-2 infection to the day of surgery was collected as a categorical factor and pre-determined to be analysed in the following categories: 0–2 weeks; 3–4 weeks; 5–6 weeks; and ≥ 7 weeks.

Primary outcome

30-day postoperative mortality.

Secondary outcomes

The incidence of 30-day postoperative pulmonary complications.

Results

• 140,231 patients across 1674 hospitals in 116 countries were included.
• 3127 (2.2%) patients had a pre-operative SARS-CoV-2 diagnosis.
• The overall 30-day postoperative mortality rate was 1.5%
• The time from SARS-CoV-2 diagnosis to surgery and associated mortality:
  • 0-2 weeks in 1138 patients (36.4%) → 30-day mortality 9.1%
  • 3-4 weeks in 461 patients (14.7%) → 30-day mortality 6.9%
  • 5-6 weeks in 326 patients (10.4%) → 30-day mortality 5.5%
  • >7 weeks in 1202 patients (38.4%) → 30-day mortality 2.0%
• The 30-day mortality rate in patients who did not have a pre-operative SARS-CoV-2 infection was 1.4%
• These findings were also consistent across subgroups stratified by age, ASA physical status, and the grade and urgency of surgery.
• Patients with persistent symptoms at surgery had higher 30-day mortality compared with patients whose symptoms have resolved or were asymptomatic. This also includes patients who had surgery >7 weeks after infection.
• Similar results were reported for postoperative pulmonary complications in relation to the duration between SARS-CoV-2 infection and surgery

Implications for colorectal practice?

This study provides important data on the impact of the interval between SARS-CoV-2 infection and surgery on postoperative mortality and pulmonary complication. It provides important guidance for recovery planning and restarting elective surgery. In patients with SARS-CoV-2 infection, postoperative mortality risk is high if they undergo any surgery at the first 6 weeks from the onset of SARS-CoV-2 infection and if they have persistent symptoms. These patients should wait for at least 7 weeks before being offered elective surgery. The study findings should inform shared decision-making and help the benefit versus risk discussion between anaesthetists, surgeons and patients when more urgent surgery might be indicated such as patients with advanced cancers.

Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study. Published: The Lancet 10 Dec 2020, https://doi.org/10.1016/S2468-1253(20)30333-2

What is known about this subject?

The standard care for early rectal cancer is radical surgical resection according to the total mesorectal excision (TME) principles which comes with a mortality risk of around 2% and considerable short-term morbidity as well as long term bowel, bladder, and sexual dysfunction affecting patients’ QOL. There has been an increasing interest in the primary organ preservation approach for early rectal cancer, but this lacked the support of high-quality evidence.

Method and outcomes

Design

Multicentre randomised, open-label feasibility study done at 21 tertiary referral centres in the UK.

The study also included a non-randomised prospective registry including patients for whom randomisation was considered inappropriate because of a strong clinical indication for one treatment group.

Population

Patients aged 18 or older with early rectal cancer (T2 or lower, N0, a maximum diameter of 30 mm and no metastasis)

Intervention

Organ preservation (via short-course (25 Gy over 5-7 days) radiotherapy followed by delayed transanal endoscopic microsurgery (8-10 weeks following completion of RT).

Control

Radical surgery (TME) without preoperative chemoradiotherapy.

Primary Outcome

The cumulative randomisation at 12, 18, and 24 months.

Secondary Outcomes

The secondary outcomes included different measures of safety and efficacy.

Results

• From 152 eligible patients identified:
  •  55 randomised, 68 recruited to non-randomised registry, and 29 (19%) declined.
  • Randomised group: 27 organ preservation and 28 TME at 15 sites.
  • Non-randomised registry: 61 organ preservation and 7 TME at 17 sites.
  • The cumulative randomisation at 12, 18, 24, and 36 months was 18, 31, 39, and 55 patients.
• Organ preservation:
  • Compliance with the decision to organ preservation was high in both groups: 85% in randomised and 90% in the non-randomised group.
  • Organ preservation was achieved in 19 (70%) in randomised and 56 (92%) in the non-randomised group.
• High-risk features were present in 24 (86%) of TME (no radiotherapy) versus 16 (59%) of organ preservation (after radiotherapy) group (p=0.03)
• Pathological complete response in organ preservation groups:
  • 8 (30%) of the randomised group. 25 (41%) of non-randomised group
• Survival (Median follow-up 4.28 years) in the randomised group:
  • Overall survival and DFS: no significant difference between groups
  • Local recurrence: 3 (11%) in organ preservation (2 salvageable) vs 0 in TME
  • Systemic metastasis: 3 (11%) in organ preservation vs 2 (7%) in TME
• Serious adverse events:
  • Randomised group: 4 (15%) in organ preservation vs 11 (39%) in TME (p=0.04)
  • Non-randomised group: 10 (16%) in organ preservation vs 1 (14%) in TME
• PROMS (overall QOL, role, social and emotional function, body image and health anxiety) and symptoms (diarrhoea, stool frequency, urinary incontinence, embarrassment about bowel function):
  • 90% or greater probability of superiority for organ preservation at 36 months in many PROMs when compared to TME group.

Implications for colorectal practice?

The TREC study is the first study to randomly assign patients with early-stage rectal cancer to organ preservation (via short-course radiotherapy and delayed transanal endoscopic microsurgery) or radical surgery (total mesorectal excision) without preoperative chemoradiotherapy.

The study has shown the feasibility of developing multidisciplinary organ preservation teams, opening sites and recruiting patients into a randomised trial design.

The study has also shown that short-course radiotherapy followed by transanal endoscopic microsurgery (TEMs) achieves a high level of organ preservation with less morbidity and better QOL when compared to TME surgery for early rectal cancer. 37.5% of patients in this group achieved pathological complete response following short-course radiotherapy.

These results support the use of organ preservation surgery in patients considered unfit for radical surgery, and also the need for further research to look at the oncological outcomes of different organ preservation surgery for early rectal cancer.

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis
The CODA Collaborative, The New England Journal of Medicine, 5 October 2020
DOI: 10.1056/NEJMoa2014320

What is known about this subject?

The APPAC study showed that antibiotics can be used as an alternative to appendicectomy in the treatment of acute appendicitis with 61% of patients avoiding surgery at 5 years follow-up. Other studies were performed to answer the same question, however, these studies were criticised for issues like being very selective, having small sample sizes, or the uncertainty of diagnosis. The CODA study was designed as a pragmatic patient outcome focused study to compare antibiotics with appendicectomy for appendicitis.

What does this study add?

Design: Multicentre nonblinded, noninferiority, randomized trial including 25 U.S. centres. Intention to treat analysis was followed and subgroup analysis of patients with appendicolith was performed.

Primary endpoints: The primary outcome was 30-day health status using the European Quality of Life–5 Dimensions (EQ-5D) questionnaire. A noninferiority margin of 0.05 points was used.

Secondary endpoints: The Secondary outcomes included the rate of appendectomy in the antibiotics group and 90 days complications in both groups.

Results:

• 1552 patients were randomized (out of 8168 screened)
• 96% had appendicitis confirmed on CT (+/- USS) or MRI scan and 27% had appendicolith.
• Antibiotics were non-inferior to appendicectomy in the mean 30-day EQ-5D score (1ry outcome)
• Antibiotics group:
  • 47% were discharged home from ED but more were readmitted within 90 days (24% vs 5%)
  • 29% had appendicectomy within 90 days (41% in those with appendicolith)
  • Less work missed (5.3 days Abx vs 8.7 days Appendicectomy)
  • More complications (8% Abx vs 3.5% Appendicectomy)
• Appendiceal neoplasms were identified in nine participants (mean age, 47±17 years; range, 21 to 74). Seven in the appendectomy group and two in the antibiotics group who had undergone appendicectomy.
• The rate of use of more extensive procedures was low and similar in the two groups (1% vs. 0.8% participants).
• The percentage with perforation was higher in the antibiotics (32% vs. 16%) and even higher in those with an appendicolith (61% vs. 24%)

Implications for colorectal practice?

Unlike previous studies, the CODA study was designed as a pragmatic trial and included patients with faecolith and only patients with radiologically confirmed appendicitis. The primary outcome aimed at the patient experience. While antibiotic treatment was found to be non-inferior to surgery, the same conclusion does not apply to patients with faecolith. The diagnosis of appendicular fecolith usually requires a CT scan which is not considered as a routine practice in the UK unlike the USA and Europe.

The risk of missing appendiceal neoplasms with the antibiotic approach is important. Subsequent investigation to exclude cancer in some patients and the financial burden from readmission and repeated investigations have not been investigated yet.

Finally, the results from CODA trial support the conservative management of acute appendicitis during the COVID pandemic and should be considered in consenting patients for appendicectomy.

H. Fowler et al. Colorectal disease Oct 2020 [Epub ahead of print] https://onlinelibrary.wiley.com/doi/10.1111/codi.15366

What is known about this subject?

The two main options for a non-restorative low rectal resection are Hartmann’s procedure (HP) or abdominoperineal excision in the intersphincteric plane (IAPE). While HP is a quicker and less invasive option, it is associated with a risk of staple line disruption and pelvic sepsis. We don’t know which procedure is better.

What does this study add?

Design: This is a multicentre nonrandomized prospective cohort study including 35 centres in the UK between 1 April 2016 and 1 June 2019.

Primary endpoints: The overall surgical related complication.

Secondary endpoints: Overall complication rate, length of stay, time to adjuvant therapy and quality of life at 90 days.

Results: The study included 179 patients (HP: 112, IAPE: 67).

• Any grade of surgical complication: Similar (HP:43% vs IAPE:48%).
• Overall complication rate: Similar (HP:54% vs IAPE:52%).
• SSI: Similar. 11% pelvic abscess in HP vs 12% perineal wound complications in IAPE. More radiological drainage in HP group (67%) vs IAPE (13%) P = 0.03
• Pelvic abscess: More common in patients with palpable staple line 15% vs 2% in non palpable (higher) staple line (P = 0.03).
• Fewer Grade 3 and above medical complication in HP (5%) vs IAPE (16%) P = 0.01.
• Pelvic abscess: more common in patients with a palpable staple line (15%) vs 2% in non palpable (higher) staple line (P = 0.03).
• A significant drop in the 90 days emotional well-being scores in the IAPE (-6.25) vs HP (0) group (P = 0.008).
• Time to adjuvant chemotherapy was similar in both groups.

Implications for colorectal practice?

This is the largest prospective study to date on this topic. As expected, a higher rate of pelvic sepsis was noted after HP especially in patients with clinically palpable staple line and the authors suggested that transanal drains may benefit this group of patients. The rate of pelvic sepsis was still much lower than previously reported. On the other hand, IAPE patients developed more significant medical complications and were emotionally worse 3 months after surgery compared to the HP group.

The study main limitation is non-randomization and selection bias was evident, however, there is no doubt that the data from the HiP study will help in the preoperative discussion and will inform our future decisions in this group of patients.