Role In Rectal Cancer Research Articles

Prognostic role of platelet-to-lymphocyte ratio in patients with rectal cancer undergoing resection: a systematic review and meta-analysis.

Inflammation plays a pivotal role in tumor growth, with the platelet-to-lymphocyte ratio (PLR) emerging as a promising serum biomarker for prognostic assessment in patients with cancer. However, its specific role in rectal cancer remains controversial. A comprehensive literature review encompassing PubMed, EMBASE, and the Cochrane Library, spanning from their inception to March 2024, was conducted. The systematic review and meta-analysis strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). Quality assessment was conducted using the Newcastle-Ottawa scale (NOS). This study aimed to assess the available literature on the association of PLR with both overall survival (OS) and disease-free survival (DFS) in patients with rectal cancer undergoing resection. Twenty-three observational studies, encompassing 7577 patients, were included in the analysis. These comprised 20 retrospective and 3 prospective cohort studies, with NOS scores ranging from 5 to 8. A significant association was found between high PLR and worse OS (hazard ratio [HR] 1.00; 95% confidence interval [CI] 1.00-1.01; P = 0.01). Conversely, no significant association was observed between PLR and DFS (HR 1.14; 95% CI 0.98-1.32; P = 0.09). PLR serves as an independent clinical predictor of OS in patients with rectal cancer treated with curative surgery, but not of DFS. This easily accessible biomarker appears to be an optimal prognostic index and may aid clinicians in predicting the prognosis of rectal cancer, facilitating the development of individualized treatment strategies.

Radiotherapy Role in Rectal Cancer at Prof. Dr. R. D. Kandou General Hospital, Manado, Indonesia

Abstract: Rectal cancer (RC) remains as a major health burden, being the 3rd most common form of cancer and leading cause of death. RC effects as much as 12.8 per 100 adult population with a mortality rate as high as 9.5%.1 Efforts were made to reduce morbidity and mortality due to rectal cancer. One of them is radiotherapy acting as both neoadjuvant and adjuvant. Thus study aimed to emphasize the role of radioteraphy in treating rectal cancer patients at Prof. Dr. R. D. Kandou General Hospital, Manado. This was a retrospective study using data of all rectal cancer outpatients seeking at Prof. Dr. R. D. Kandou General Hospital, Manado. from 2017-2020 especially of those receiving radiotherapy treatment in radiology department. The results obtained a total 119 patients, 28 of them received radiotherapy based on staging and clinical judgement. From the radiotherapy group, 46.4% patient received neoadjuvant radiotherapy primary to surgical procedure, and among the neoadjuvant group 71.4% received long course radiotherapy. From the neoadjuvant radiotherapy group, 46.4% became resectable and 46.4% among them underwent Miles Procedure. In conclusion, rectal cancer is still a health problem, and radiotherapy as one of the modality play major role as neoadjuvant and adjuvant treatment.

Lymph node stain after radical resection of rectal cancer mainly increased the harvest of mini lymph node: A randomized controlled trial

The lymph node status plays an important role in rectal cancer, which depends on adequate lymph node harvest. Lymph node stain techniques increase the lymph node harvest. The aim of this prospective study is to investigate which subgroups of lymph nodes harvested were increased mostly. From May 2020 to May 2022, 172 stage II-III rectal cancer patients were randomized to methylene blue (MB) stained group or unstained group to retrieve the lymph nodes. Methylene blue solution was injected into the inferior mesenteric artery, we dissected lymph nodes by palpation and sight. The lymph nodes were divided into 3 groups depending on the anatomy (main lymph nodes, superior rectal and perirectal lymph nodes (SPLNs), and pericolic lymph nodes located beyond 10cm proximal to the tumor), and 3 groups depending on the short diameter of the nodes (big: ≥ 5mm, small: 5-2mm, mini: ≤ 2mm). The number of lymph nodes harvested with MB was significantly higher (22.0 (14.8, 32.0) vs 14.5 (11.0, 22.0); p < 0.001) without difference in positive patients or number of positive nodes. The positive rate of the big node was 3.5%, the small node was 1.9%, and the mini node was 0.2%. In the subgroup analysis, the median number of mini lymph nodes in the MB-stained group was significantly more than that of the unstained group (median (IQR): 9.0 (6.0, 14.0) vs 4.0 (2.0,6.0), p < 0.001); and the median number of SPLNs in the MB-stained group were significantly more than that of the unstained group (median (IQR): 15.0 (9.0, 19.0) vs 10.0 (6.0, 13.3), p < 0.001); these differences were existing in both patients with and without neoadjuvant treatments. Intra-arterial injection of MB can significantly increase the number of lymph nodes harvested in rectal cancers, especially those mini lymph nodes. However, methylene blue staining did not significantly increase the number of positive lymph nodes and the proportion of patients with more than 12 lymph nodes, or affect lymph node staging accuracy after radical resection of rectal cancer.

Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.

Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial. A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection. Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively). NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.

Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study.

Increasing evidence suggests that statins may have antitumor effects but their role in rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer. This study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013. In the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19-0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39-0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06-0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group. Statin use was related to improved survival in older patients with rectal cancer. This observation is important given the low cost and safety of statins as a drug.

Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy.

PurposeMismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT).Materials and MethodsFifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model.ResultsThe most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer.ConclusionThese results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.

Does baseline [18F] FDG-PET/CT correlate with tumor staging, response after neoadjuvant chemoradiotherapy, and prognosis in patients with rectal cancer?

Background[18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) may be used for tumor staging and prognosis in several tumors but its role in rectal cancer is still debated. The aim of the present study was to assess the correlation of baseline [18F] FDG-PET parameters with tumor staging, tumor response (tumor regression grade (TRG)), and outcome in a series of patients affected by locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT).MethodsOne hundred patients treated with neoadjuvant CRT and radical surgery were enrolled in the present study. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) at the baseline [18F] FDG-PET were calculated. These PET parameters were correlated with tumor staging, histopathological data (TRG1 vs. TRG2–5 and TRG1–2 vs. TRG3–5), disease-free survival, and overall survival.ResultsSUVmax and SUVmean of primary tumor were statistically associated with T4-stage. SUVmax, SUVmean, and TLG did not result statistically associated with TRG (TRG1 or TRG1–2). MTV resulted statistically associated with TRG1–2 group (OR 2.9; 95% CI 1.2–7.1). Finally, no PET parameter was significantly associated with disease-free or overall survival.ConclusionOur results showed that baseline [18F] FDG-PET parameters correlated with tumor staging, and only MTV correlated with TRG 1–2. PET parameters failed to predict disease-free and overall survival after treatment completion. The results leave open to further studies the issue of identifying patients suitable for conservative approaches.

LncRNA NKILA correlates with the malignant status and serves as a tumor-suppressive role in rectal cancer.

NF-κB interacting lncRNA (NKILA) has been found to function as a tumor-suppressive role in various human cancers. However, the role of NKILA in rectal cancer is still unknown. The objective of this study is to investigate the clinical value and biological function of NKILA in rectal cancer. The association between NKILA expression and clinical variables including prognosis was estimated in rectal cancer patients. The gain-of-function study of NKILA in rectal cancer cell was conducted to evaluate the effect of NKILA on cell proliferation, migration, invasion, and NF-κB signaling pathway. The results suggested NKILA expression was decreased in rectal cancer tissues and cells, and correlated with clinical stage, T classification, N classification and M classification. NKILA low-expression was an independent poor prognostic factor in rectal cancer patients. NKILA-inhibited rectal cancer cell proliferation, migration, and invasion via suppressing NF-κB signaling. In conclusion, NKILA serves as an antioncogenic lncRNA in rectal cancer.

Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer

BackgroundGenetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut.MethodsWe performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries.ResultsWe did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (Ptrend of = 0.0071).ConclusionsOur data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts.

The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical Outcomes in Rectal Cancer

Three-dimensional conformal radiation therapy (3DCRT) has been the standard technique in the treatment of rectal cancer. The use of new radiation treatment technologies such as intensity-modulated radiation therapy (IMRT), proton therapy (PT), stereotactic body radiation therapy (SBRT) and brachytherapy (BT) has been increasing over the past 10 years. This review will highlight the advantages and drawbacks of these techniques. IMRT, PT, SBRT and BT achieve a higher target coverage conformity, a higher organ at risk sparing and enable dose escalation compared to 3DCRT. Some studies suggested a reduction in gastrointestinal and hematologic toxicities and an increase in the complete pathologic response rate; however, the clinical benefit of these techniques remains controversial. The results of these new techniques seem encouraging despite conclusive data. Further trials are required to establish their role in rectal cancer.

Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio‐ and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre‐treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease‐free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence.

Effect of BRMS1 on tumorigenicity and metastasis of human rectal cancer.

Breast cancer metastasis suppressor gene-1 (BRMS1) is newly discovered tumor metastasis gene, which has been reported to play an important role in the progression of human tumor. However, its role in rectal cancer has never been investigated. In this present study, we evaluated the associated of BRMS1 with colorectal cancer, its value in prognosis, and its role in metastasis of rectal cancer. BRMS1 expression examined in 80 patients and the role of BRMS1 in metastasis was studied using mice model. Our results showed that BRMS1 expression was significantly associated with clinicopathological parameters in rectal cancer patients and overexpression of BRMS1 in rectal cancer xenograft led to decreased growth, invasiveness and metastasis. Our findings indicate that high expression of BRSM1 in rectal cancer plays an essential role in tumor progression.

Transanal endoscopic microsurgery: indications, results and controversies

Transanal endoscopic microsurgery (TEM) was introduced in 1983 as a minimally invasive technique allowing the resection of adenomas and early rectal carcinomas unsuitable for local or colonoscopic excision which would otherwise require major surgery. After 25 years, there is still much debate about the procedure. This article presents the TEM technique, indications, results and complications, focusing on its role in rectal cancer. The controversial points addressed include long-term results, TEM in high-risk T1 lesions, TEM associated with combined modality therapy (CMT) for invasive rectal cancer and salvage therapy after TEM. The future perspectives for TEM are promising and its association with CMT will probably expand the select group of patients who will benefit from the procedure.

Staging, prognostic factors, and therapy of localized rectal cancer

Many recent developments have taken place in the management of rectal cancer. Appropriate staging plays an increasingly important role in rectal cancer, because many treatment decisions must be based on preoperative staging. Also critical is the role of prognostic factors such as the pathologic T (tumor) and N (nodal) classification, circumferential resection margin, and response to preoperative therapy. For stage II and III rectal cancer, preoperative chemo-radiation and radiotherapy have been accepted widely as a standard of care. The German Rectal Cancer Trial demonstrated the superiority of preoperative chemoradiation over postoperative chemoradiation, whereas the trials from the European Organisation for Research and Treatment of Cancer and Fédération Francophone de Cancérologie Digestive showed the benefits of preoperative chemoradiation over preoperative long-course radiotherapy. Multiple randomized trials also have established the role of hypofractionated or short-course radiotherapy. For stage I rectal cancer, local excision is being used increasingly, but recent studies show the need for caution with the use of this technique. This article reviews recent studies on staging, prognostic factors, and therapy of localized rectal cancer.

Ergebnisse der multiviszeralen Resektion des primären kolorektalen Karzinoms

In about 10 % of all patients with colorectal cancer, the primary invention already discloses adhesions or infiltration of adjacent organs. En bloc resection of the tumor-bearing bowel segment with adjacent organs is done to give patients a chance for curation, since intraoperative differentiation is not possible. The aim of this study is characterization of the patient population as well as evaluation of the morbidity and mortality associated with this type of extensive intervention. Between 1/95 and 6/04, we analyzed all patients with progressive primary colorectal cancer, who underwent multivisceral surgery with en bloc resection of at least one other organ. The target parameters were tumor characteristics as well as postoperative morbidity and mortality. A total of 1 001 patients with colorectal cancer underwent surgery. 101 patients (10 %) required multivisceral resection. In 17 % the indication was exigent. About 70 % of the interventions involved the colon. Tumor perforation was seen in 17 % of patients with colon cancer and 16 % with rectal cancer. Resection of the inner genitals was most frequent in both colon and rectal cancer (26 and 84 %) followed by small bowel resection (21 %) and partial bladder resection (19 %). Other organs play a secondary role in rectal cancer while partial bladder resection (20 %) and abdominal wall resection (14 %) is observed more frequently in colon cancer. Resection of parenchymatous organs (kidney, suprarenal gland, spleen, pancreas, liver) and others like the stomach is quite rare in colon cancer. Actual tumor infiltration (T4 situation) was observed in 51 % of patients with colon cancer and in 64 % of those with rectal cancer. Local R0 resection (97 vs. 96 %) was successfully performed in nearly all colon and rectal cancer patients. The surgical major complication rate was 9 % in colon cancer and 19 % in rectal cancer. The mortality rate was 4 %. Multivisceral en-bloc resection enables local R0 resection in the majority of cases with primary colorectal cancer. Despite sometimes extensive surgery, this type of procedure is associated with an acceptable morbidity and mortality. Since long-term survival is comparable to that in the T category (T3 or T4), multivisceral en-bloc resection is not only justified but also absolutely required in interventions with curative intention.

Laparoscopic surgery for colorectal cancers: Current status

Laparoscopy was introduced more than 15 years ago into clinical practice. However, its role in colorectal surgery was not well established for want of better skills and technology. This coupled with high incidences of port site recurrences, prevented laparoscopic surgery from being incorporated into mainstream colorectal cancer surgery. A recent increase in the number of reports, retrospective analyses, randomized trials and multicentric trials has now provided sufficient data to support the role of laparoscopy in colorectal cancer surgery. We, thus, present a review of the published data on the feasibility, safety, short - and long-term outcomes following laparoscopic surgery for colorectal cancers. While the data available strongly favors the use of laparoscopic surgery in colonic cancer, larger well powered studies are required to prove or disprove its role in rectal cancer.

Inflammation’s Role in Rectal Cancer Following Prostate Radiotherapy, and Emerging Evidence for a Protective Role for Balsalazide

We read with great interest the manuscript by Baxter et al1 on rectal cancer following prostate radiotherapy published in the April 2005 issue of Gastroenterology, along with the accompanying editorial by Grady and Russell.2 However, our approach to addressing the important issues raised is different than that suggested in the editorial. The editorial’s authors appropriately highlight the fact that any such radiotherapy-associated rectal cancer is not likely a direct result of radiation to the prostate.

Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer

Preoperative radiotherapy improves local control and survival in rectal cancer, but may also increase postoperative morbidity and mortality rates. Establishing selection criteria for preoperative radiotherapy is crucial. The tumour level above the anus may be one such criterion. The effect of preoperative radiotherapy in relation to the distance between the tumour and the anus was therefore assessed. In 457 patients operated for cure included in the Stockholm II Trial the local recurrence rate in irradiated and non-irradiated patients was analysed in relation to the tumour location (low, mid or upper rectum). Radiotherapy reduced the local recurrence rate from 30 to 20 per cent in low rectal cancer, from 25 to 11 per cent in mid rectal cancer and from 21 to 5 per cent for tumours in the upper rectum. With conventional surgical techniques preoperative radiotherapy plays an important role in rectal cancer irrespective of the location of the tumour. To irradiate only patients with tumours in the lower rectum and to omit this treatment for patients with tumours in the mid and upper rectum cannot be recommended. Whether this statement is valid with standardized total mesorectal excision (TME) surgery is not known. Until this knowledge is available the current indications for preoperative radiotherapy should probably also be used with TME surgery.

Mechanisms of oncogenesis in colon versus rectal cancer.

Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2, p53, E-cadherin and beta-catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear beta-catenin expression (p=0.75). Rectal cancers showed significantly more nuclear beta-catenin than colon cancers (65% versus 40%, p=0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry (p<0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p=0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease-free survival (p=0.008), but not in colon cancers. Cox regression showed that p53-expression (p=0.03) was an independent predictor for disease-free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear beta-catenin in the APC/beta-catenin pathway than colon cancer and/or nuclear beta-catenin may have another role in rectal cancer independently of APC. The p53-pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered.