Meta-Analysis Review

Authors: Roberto Falz, Christian Bischoff, René Thieme...

PURPOSE

Functional capacity is an independent indicator of morbidity in colon and rectal cancer surgery. This systematic review describes the evaluated and synthesized effects of exercise prehabilitation depending on the duration of interventions on functional and postoperative outcomes in colon and rectal cancer surgery.

METHODS

Three electronic databases (MEDLINE Pubmed, Web of Sciences, and Cochrane Registry) were systematically searched (January 2022) for controlled trials that investigated the effects of prehabilitation prior to colo-rectal cancer resection.

RESULTS

Twenty-three studies were included in this systematic review and 14 in our meta-analyses assessing these outcomes: the 6 min walk distance (6MWD), postoperative overall complications, and length of stay (LOS). We observed a significant improvement in preoperative functional capacity as measured with 6MWD (mean difference: 30.8 m; 95% CI 13.3, 48.3; p = 0.0005) due to prehabilitation. No reductions in LOS (mean difference: - 0.27 days; 95% CI - 0.93, 0.40; p = 0.5) or postoperative overall complications (Odds ratio: 0.84; 95% CI 0.53, 1.31; p = 0.44) were observed. Prehabilitation lasting more than 3 weeks tended to lower overall complications (Odds ratio: 0.66; 95% CI 0.4, 1.1; p = 0.11). However, the prehabilitation time periods differed between colon and rectal carcinoma resections.

CONCLUSION

Prehabilitation while the patient is preparing to undergo surgery for colorectal carcinoma improves functional capacity; and might reduce postoperative overall complications, but does not shorten the LOS. The studies we reviewed differ in target variables, design, and the intervention's time period. Multicenter studies with sufficient statistical power and differentiating between colon and rectal carcinoma are needed to develop implementation strategies in the health care system.

REGISTRATION

PROSPERO CRD42022310532.

Topics: Carcinoma; Colorectal Neoplasms; Humans; Postoperative Complications; Preoperative Care; Preoperative Exercise; Rectal Neoplasms

PubMed: 35695931
DOI: 10.1007/s00432-022-04088-w

Randomized Controlled Trial

Authors: Jun Watanabe, Ichiro Takemasa, Masanori Kotake...

OBJECTIVE

The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery.

BACKGROUND

The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature.

METHODS

This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population.

RESULTS

Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P =0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group ( P =0.044), and the respective reoperation rates were 0.5% and 2.4% ( P =0.021).

CONCLUSIONS

Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.

Topics: Humans; Indocyanine Green; Anastomotic Leak; Rectal Neoplasms; Perfusion; Optical Imaging; Anastomosis, Surgical

PubMed: 37218517
DOI: 10.1097/SLA.0000000000005907

Review

Authors: C Astaras, A Bornand, T Koessler...

Squamous cell carcinoma of the rectum is a rare malignancy (0.3% of all rectal cancers), with no known risk factor. These tumours are assessed as rectal cancer using immunohistochemical and radiological tests, and certain criteria (localisation, relationship with neighbouring structures) have to be fulfilled to make the diagnosis. Some clinicians used to stage them with the anal cancer TNM (tumour-node-metastasis), whereas others used the rectal cancer TNM. When localised, the tendency nowadays is to treat those tumours like squamous anal cancers with definitive chemoradiotherapy (5-fluorouracil and mitomycin) and to skip surgery. For metastatic disease there is no clearly validated regimen and treatment should be based on recommendations of squamous anal cancers because of their common histology. Concerning follow-up after a curative approach, techniques should follow those for anal cancer as well, evaluating a delayed response.

Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Fluorouracil; Humans; Rectal Neoplasms

PubMed: 34111760
DOI: 10.1016/j.esmoop.2021.100180

Meta-Analysis

Authors: Iosief Abraha, Cynthia Aristei, Isabella Palumbo...

BACKGROUND

This is an update of the original review published in 2007.Carcinoma of the rectum is a common malignancy, especially in high income countries. Local recurrence may occur after surgery alone. Preoperative radiotherapy (PRT) has the potential to reduce the risk of local recurrence and improve outcomes in rectal cancer.

OBJECTIVES

To determine the effect of preoperative radiotherapy for people with localised resectable rectal cancer compared to surgery alone.

SEARCH METHODS

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; Issue 5, 2018) (4 June 2018), MEDLINE (Ovid) (1950 to 4 June 2018), and Embase (Ovid) (1974 to 4 June 2018). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant ongoing trials (4 June 2018).

SELECTION CRITERIA

We included randomised controlled trials comparing PRT and surgery with surgery alone for people with localised advanced rectal cancer planned for radical surgery. We excluded trials that did not use contemporary radiotherapy techniques (with more than two fields to the pelvis).

DATA COLLECTION AND ANALYSIS

Two review authors independently assessed the 'Risk of bias' domains for each included trial, and extracted data. For time-to-event data, we calculated the Peto odds ratio (Peto OR) and variances, and for dichotomous data we calculated risk ratios (RR) using the random-effects method. Potential sources of heterogeneity hypothesised a priori included study quality, staging, and the use of total mesorectal excision (TME) surgery.

MAIN RESULTS

We included four trials with a total of 4663 participants. All four trials reported short PRT courses, with three trials using 25 Gy in five fractions, and one trial using 20 Gy in four fractions. Only one study specifically required TME surgery for inclusion, whereas in another study 90% of participants received TME surgery.Preoperative radiotherapy probably reduces overall mortality at 4 to 12 years' follow-up (4 trials, 4663 participants; Peto OR 0.90, 95% CI 0.83 to 0.98; moderate-quality evidence). For every 1000 people who undergo surgery alone, 454 would die compared with 45 fewer (the true effect may lie between 77 fewer to 9 fewer) in the PRT group. There was some evidence from subgroup analyses that in trials using TME no or little effect of PRT on survival (P = 0.03 for the difference between subgroups).Preoperative radiotherapy may have little or no effect in reducing cause-specific mortality for rectal cancer (2 trials, 2145 participants; Peto OR 0.89, 95% CI 0.77 to 1.03; low-quality evidence).We found moderate-quality evidence that PRT reduces local recurrence (4 trials, 4663 participants; Peto OR 0.48, 95% CI 0.40 to 0.57). In absolute terms, 161 out of 1000 patients receiving surgery alone would experience local recurrence compared with 83 fewer with PRT. The results were consistent in TME and non-TME studies.There may be little or no difference in curative resection (4 trials, 4673 participants; RR 1.00, 95% CI 0.97 to 1.02; low-quality evidence) or in the need for sphincter-sparing surgery (3 trials, 4379 participants; RR 0.99, 95% CI 0.94 to 1.04; I = 0%; low-quality evidence) between PRT and surgery alone.Low-quality evidence suggests that PRT may increase the risk of sepsis from 13% to 16% (2 trials, 2698 participants; RR 1.25, 95% CI 1.04 to 1.52) and surgical complications from 25% to 30% (2 trials, 2698 participants; RR 1.20, 95% CI 1.01 to 1.42) compared to surgery alone.Two trials evaluated quality of life using different scales. Both studies concluded that sexual dysfunction occurred more in the PRT group. Mixed results were found for faecal incontinence, and irradiated participants tended to resume work later than non-irradiated participants between 6 and 12 months, but this effect had attenuated after 18 months (low-quality evidence).

AUTHORS' CONCLUSIONS

We found moderate-quality evidence that PRT reduces overall mortality. Subgroup analysis did not confirm this effect in people undergoing TME surgery. We found consistent evidence that PRT reduces local recurrence. Risk of sepsis and postsurgical complications may be higher with PRT.The main limitation of the findings of the present review concerns their applicability. The included trials only assessed short-course radiotherapy and did not use chemotherapy, which is widely used in the contemporary management of rectal cancer disease. The differences between the trials regarding the criteria used to define rectal cancer, staging, radiotherapy delivered, the time between radiotherapy and surgery, and the use of adjuvant or postoperative therapy did not appear to influence the size of effect across the studies.Future trials should focus on identifying participants that are most likely to benefit from PRT especially in terms of improving local control, sphincter preservation, and overall survival while reducing acute and late toxicities (especially rectal and sexual function), as well as determining the effect of radiotherapy when chemotherapy is used and the optimal timing of surgery following radiotherapy.

Topics: Anal Canal; Dose Fractionation, Radiation; Humans; Neoplasm Recurrence, Local; Organ Sparing Treatments; Postoperative Complications; Preoperative Care; Quality of Life; Randomized Controlled Trials as Topic; Rectal Neoplasms; Rectum

PubMed: 30284239
DOI: 10.1002/14651858.CD002102.pub3

Authors: C V Lungulescu, S Răileanu, G Afrem...

Colorectal cancer (CRC) is a major health problem worldwide. The objective of our study was to assess the histopathological (HP) and immunohistochemical (IHC) profile of mucins from signet ring (SR) and mucinous rectal carcinoma, while evaluating their value as a prognostic factor and muco-secretive ability. The HP study (76 cases) included 4 categories of patients: pure mucinous (PM), mixed mucinous components (MM) (50-80% of the tumor cells), mixed mucinous components (Mm) (< 50% of the tumor cells) and signet ring (SR). The IHC study consisted of a total of 30 cases of MRC and was processed by the ABC/ HRP technique. The antibodies used have addressed their muco-secretive capacity: MUC1, 2 and MUC5AC. MRC cases were more frequent in the sixth decade, with a median age of 57.3 years. It could be noted that MRC tended to develop at younger ages. For the MP variant, the gender ratio was 1.37 in favor of men, while for the MM variant it was 1.16, 1.31 for the Mm and 1.6 in the case of signet ring type. Most of the MRC were moderately differentiated forms, except for the SR form, poorly differentiated forms predominating. Well-differentiated forms were the most underrepresented, being more common in the Mm version. Regarding the biochemical type of mucin, MP and SR were characterized by acid mucins and sialomucin, while in the Mm type, there was a balance of acidic and neutral mucins. The prevalence of mucin acids, respectively sulfomucin, was characteristic to younger ages and poor prognosis.

Topics: Adenocarcinoma, Mucinous; Goblet Cells; Humans; Immunohistochemistry; Middle Aged; Mucin 5AC; Mucins; Rectal Neoplasms

PubMed: 28616090
DOI: No ID Found

Authors: Robbert J C Slebos, Xia Wang, Xiaojing Wang...

Understanding proteomic differences underlying the different phenotypic classes of colon and rectal carcinoma is important and may eventually lead to a better assessment of clinical behavior of these cancers. We here present a comprehensive description of the proteomic data obtained from 90 colon and rectal carcinomas previously subjected to genomic analysis by The Cancer Genome Atlas (TCGA). Here, the primary instrument files and derived secondary data files are compiled and presented in forms that will allow further analyses of the biology of colon and rectal carcinoma. We also discuss new challenges in processing these large proteomic datasets for relevant proteins and protein variants.

Topics: Colonic Neoplasms; Databases, Protein; Electronic Data Processing; Humans; Proteomics; Rectal Neoplasms

PubMed: 26110064
DOI: 10.1038/sdata.2015.22

Review

Authors: Thian Yee Liang, Gopinathan Anil, Bertrand W L Ang...

The role of imaging in the management of rectal malignancy has progressively evolved and undergone several paradigm shifts. Unlike a few decades ago when the role of a radiologist was restricted at defining the longitudinal extent of the tumour with barium enema, recent advances in imaging techniques permit highly accurate locoregional and distant staging of the disease as well as prognostication on those who are likely to have a postoperative recurrence. Computed tomography (CT) has always been the mainstay of imaging when evaluating for distant metastasis, with the advent of positron emission tomography/CT improving its specificity. In rectal malignancy, it is the local extent of the disease that often influences the surgical decision making and need for neoadjuvant therapy. Although endoscopic ultrasound has been the traditional technique for determining the depth of tumour invasion, over the last decade magnetic resonance imaging (MRI) has emerged as a very effective tool for accurate T-staging. This review intends to address the status of various imaging modalities and their advantages and limitations in detection, pretreatment staging, and assessment of therapeutic efficacy in rectal cancer, with emphasis on MRI of high spatial resolution.

Topics: Endosonography; Humans; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Multimodal Imaging; Neoplasm Staging; Positron-Emission Tomography; Rectal Neoplasms; Rectum; Tomography, X-Ray Computed

PubMed: 23033451
DOI: 10.1102/1470-7330.2012.0034

Review

Authors: S Buczacki, R J Davies, D J Winton...

Stem cells are responsible for maintaining differentiated cell numbers during normal physiology and at times of tissue stress. They have the unique capabilities of proliferation, self-renewal, clonogenicity and multi-potentiality. It is a widely held belief that stem-like cells, known as cancer stem cells (CSCs), maintain tumours. The majority of currently identified intestinal stem cell populations appear to be rapidly cycling. However, quiescent stem cell populations have been suggested to exist in both normal intestinal crypts and tumours. Quiescent CSCs may have particular significance in the modern management of colorectal cancer making their identification and characterisation a priority. In this review, we discuss the current evidence surrounding the identification and microenvironmental control of stem cell populations in intestinal crypts and tumours as well as exploring the evidence supporting the existence of a quiescent stem and CSC population in the gut and other tissues.

Topics: Cell Cycle Checkpoints; Colorectal Neoplasms; Humans; Intestines; Neoplastic Stem Cells; Rectal Neoplasms; Stem Cells

PubMed: 21934687
DOI: 10.1038/bjc.2011.362

Authors: Max S Chiu, Vivek Verma, Nathan R Bennion...

Large, population-based analyses of rectal squamous cell carcinoma (SCC) have not been previously conducted. We assessed patterns of care, prognostic factors, and outcomes of rectal SCC and adenocarcinoma (AC) in population-based cohorts. Surveillance, Epidemiology, and End Results (SEER) registry searches were performed (1998-2011), producing 42,308 nonmetastatic rectal cancer patients (999 SCC and 41,309 AC). Patient, tumor, and treatment characteristics were compared. Based on risk factors, SCC/AC groups were subdivided into low-, intermediate-, and high-risk groups. Overall survival (OS) was compared between histological and risk groups using Kaplan-Meier method and log-rank test. Multivariate logistic regression models evaluated prognostic factors for 5-year survival. Cox regression modeling was performed on propensity-matched data. Rectal SCC, more common in females and associated with larger tumors of higher grade, was more often treated with radiotherapy (RT) than surgery. Surgery was associated with higher OS in AC but not SCC, and RT had proportionally greater benefits in SCC. These effects of RT and surgery were retained when stratified into risk groups (particularly high/intermediate-risk). Favorable prognostic factors for survival included younger age, non-black race, SCC histology, size ≤3.9 cm, localized stage, lower grade, surgery, and RT. For SCC, race, tumor grade, and surgery were not prognostic factors for survival. Cox regression modeling of propensity-matched data showed that AC histology increased risk of death versus SCC. In the largest analysis of rectal SCC to date, and in the notable absence (and unlikelihood) of prospective data, nonsurgical and RT-based treatment is recommended.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Patient Outcome Assessment; Population Surveillance; Prognosis; Propensity Score; Rectal Neoplasms; SEER Program; Survival Analysis; Tumor Burden; Young Adult

PubMed: 27781400
DOI: 10.1002/cam4.927

Review

Authors: Zhi-jie Cong, Liang-hao Hu, Jun-jie Xing...

Anastomotic dehiscence (AD) requiring reoperation is the most severe complication following anterior rectal resection. We performed a systematic review on studies that describe AD requiring reoperation and its subsequent mortality after anterior resection for rectal carcinoma. A systematic search was performed on published literature. Data on the definition and rate of AD, the number of ADs requiring reoperation, the mortality caused by AD, and the overall postoperative mortality were pooled and analyzed. A total of 39 studies with 24,232 patients were analyzed. The studies varied in incidence and definition of AD. Systematic review of the data showed that the overall rate of AD was 8.6%, and the rate of AD requiring reoperation was 5.4%. The postoperative mortality caused by AD was 0.4%, and the overall postoperative mortality was 1.3%. We found considerable risk and mortality for AD requiring reoperation, which largely contributed to the overall postoperative mortality.

Topics: Anastomosis, Surgical; Humans; Incidence; Rectal Neoplasms; Rectum; Reoperation; Surgical Wound Dehiscence

PubMed: 24670019
DOI: 10.9738/INTSURG-D-13-00059