Effect of short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy on organ preservation in locally advanced rectal cancer.

PURPOSE: We analyzed the effectiveness, safety, and mid-term oncological outcomes of short-course radiotherapy (SCRT) and oxaliplatin-based consolidation chemotherapy in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively evaluated 64 patients with LARC who underwent SCRT and tegafox (tegafur-uracil/leucovorin plus oxaliplatin) or mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) consolidation chemotherapy before surgery between January 2015 and December 2020. Tumor response, patient compliance, toxicity, surgical outcomes, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: Sixty-four patients with a mean age of 58.67 years (44 males) were included; 48 (75%) had tumors within 5 cm of the anal verge. Additionally, 93.8% of the patients underwent at least 2 months of chemotherapy, and three required dose reduction. Grade III toxicity occurred in 2 patients, and 10 had a clinical complete response and opted for non-operative management. One patient experienced tumor progression and underwent further treatment without surgery. Among the 53 patients who underwent surgery, 51 (96.2%) had sphincter preservation, 3 had Clavien-Dindo grade III complications, and no mortality occurred. The complete response rate for the entire cohort was 23.4%. Moreover, 47 patients (74.6%) had a neoadjuvant rectal score of < 16 after treatment. After a median follow-up time of 32.01 months, 6 (9.3%) had local recurrence, and 17 (26.6%) had distant metastasis. The 3-year OS, DFS and stoma-free rates were 89.5%, 65.5%, and 78.1% respectively. CONCLUSION: SCRT followed by oxaliplatin-based consolidation chemotherapy is safe and effective for tumor downstaging in LARC, further improving the sphincter preservation rate.

MicroRNA-based signature for diagnosis and prognosis of colorectal cancer using residuum of fecal immunochemical test.

BACKGROUND: Colorectal cancer (CRC) is still among the most lethal and prevalent malignancies in the world. Despite continuous efforts, the diagnosis and prognosis of CRC have never been satisfying, especially the non-invasive assays. METHODS: Our study comprised three independent cohorts of 835 qualified stool samples. From 46 literature-identified miRNA candidates, four miRNA ratios were selected and developed into a miRNA-based signature after applied to the training and test sets. The clinical performances of this signature were further evaluated in the prospective cohorts. RESULTS: Four miRNA ratios with significant alterations and the highest discriminating power between the CRC and control groups in the training set were successfully validated in the test set. In the training dataset, combining these four miRNA ratios using a logistic regression model improved the area under the curve value to 0.821 and obtained a sensitivity of 73.6% and specificity of 78.9%. This miRNA signature showed consistent performances in the other two sample cohorts, with the highest sensitivity of 85.7% in the prospective cohort. Additionally, the higher miRNA signature was associated with worse disease-free survival (hazard ratio = 2.27) and overall survival (hazard ratio = 1.83) of CRC patients. For fecal immunochemical test (FIT)-positive populations, the positive predictive value for CRC detection in miRNA-positive subjects was 3.43-fold higher in the prospective cohort, compared to FIT alone. CONCLUSION: This stool miRNA signature is highly associated with poor outcome of CRC and can be added to FIT tests to help identify the most at-risk group to receive prompt colonoscopy examination.

Transanal Total Mesorectal Excision (TaTME) versus Laparoscopic Total Mesorectal Excision for Lower Rectal Cancer: A Propensity Score-Matched Analysis.

Studies have reported positive short-term and histopathological results of transanal total mesorectal excision (TaTME) for mid-low rectal cancer. The long-term oncological outcomes are diverse, and concerns regarding the high local recurrence (LR) rate of TaTME have recently increased. We retrospectively analyzed 298 consecutive patients who underwent Laparoscopic TME (LapTME) or TaTME between January 2015 and December 2019. Propensity score-matching (PSM) was performed with patients matched for demographics and stage. After PSM, 63 patients were included in each group. The TaTME group had a longer mean operative time (394 vs. 333 min, p < 0.001). The blood loss, diverting stoma rate, and conversion rate were similar. Postoperatively, TaTME and LapTME had compatible complications, recovery, and hospital stay. A similar specimen quality was detected in both groups. After a mean follow-up period of 41−47 months, TaTME had less LR than LapTME (9.5% vs. 23.8%, p = 0.031). The 3-year overall survival was 80.3% in the TaTME group and 73.6% in the LapTME group (p = 0.331). The 3-year disease-free survival (DFS) rate was 72.0% in the TaTME group and 56.6% in the LapTME group (p = 0.038). In conclusion, better DFS and fewer LR events were observed after TaTME; thus, TaTME can be considered a safe and feasible approach in patients with low rectal cancer.

Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy.

It is controversial whether patients who achieve clinical complete remission (cCR) of rectal cancer should be treated with the "watch and wait" (W&W) or radical resection (RR) strategy. Our study aimed to compare the survival outcomes and ostomy rate of the W&W and RR strategies. Between January 2008 and December 2015, we investigated 26 patients who achieved pathologic complete remission after undergoing RR and 36 patients who adopted the W&W strategy because of cCR. The tumor regrowth, salvage surgery, recurrence, disease-free, and overall survival (OS) rates were assessed. In our study, recurrences occurred in nine and two patients from the W&W and RR groups, respectively. Each patient in the RR group had a temporary or permanent ostomy, but only three (8.3%) had an ostomy in the W&W group. The 5-year recurrence rate was 25.0% in the W&W group and 7.7% in the RR group. Six patients (16.7%) had tumor regrowth in the W&W group, and all were resectable when regrowth. The 5-year OS rates between the two groups were nonsignificant. There is no specific risk factor for recurrence and OS. Under close surveillance, the W&W group achieved similar OS to the RR group and benefited from a lower ostomy rate.

Comprehensive functional genomic analyses link APC somatic mutation and mRNA-miRNA networks to the clinical outcome of stage-III colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC. METHODS: From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I-IV CRC from Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared. RESULTS: The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition. CONCLUSION: For stage III CRC, patients with mutated APC had better overall and recurrence free survival.

Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy before Surgery for Treating Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) is an alternative treatment for locally advanced rectal cancer (LARC). We performed this systematic review and meta-analysis to explore the tumor response and oncological outcomes of this new approach compared to conventional chemoradiotherapy (CRT). An online search of the PubMed, Embase, and Cochrane Library databases was performed. This review included 7507 patients from 14 different cohorts. The pCR rate was higher with SCRT + CCT than that with CRT (RR: 1.60; 95% CI: 1.35−1.91; p < 0.01). SCRT + CCT provided a higher ypN0 response (RR: 1.06; 95% CI: 1.01−1.12; p = 0.02). There were no differences in R0 resection and positive CRM rates; however, more sphincter-preservation surgeries were performed in the SCRT + CCT arm (RR: 1.06; 95% CI: 1.01−1.11; p = 0.02). There was no difference in the OS and DFS between the SCRT + CCT and the CRT arms (OS: HR: 0.85, p = 0.07; DFS: HR: 0.88, p = 0.08). The compliance and toxicity were comparable between the SCRT and CRT groups. In the subgroup analysis, patients who underwent four or more cycles of CCT had better pCR and DFS events. Therefore, SCRT followed by consolidation chemotherapy might be an effective alternative treatment for LARC.

Tegafur-Uracil/Leucovorin Plus Oxaliplatin (TEGAFOX) as Consolidation Regimen after Short-Course Radiotherapy Is Effective for Locally Advanced Rectal Cancer.

This study aimed to explore the safety and efficacy of neoadjuvant SCRT and tegafur−uracil/leucovorin plus oxaliplatin (TEGAFOX) for LARC in comparison to those of the modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-6) regimen. We retrospectively evaluated 15 and 22 patients with LARC who underwent SCRT, followed by consolidation chemotherapy with TEGAFOX and mFOLFOX-6 before surgery, respectively, between January 2015 and December 2019. The primary endpoint was the tumor response rate. The secondary endpoints were compliance, toxicity, complications, overall survival (OS), and disease-free survival (DFS). The dose reduction rate was lower in the TEGAFOX group (0 vs. 9.1% (n = 2)). No grade III-IV toxicities occurred in the TEGAFOX group. Two and four patients in the TEGAFOX and mFOLFOX-6 groups, respectively, achieved clinical complete responses. The pathologic complete response rate was lower in the TEGAFOX group (7.7% vs. 17.6%). Overall, 11 (73.3%) and 17 (81.0%) patients had a neoadjuvant rectal (NAR) score of <16 in the TEGAFOX and mFOLFOX-6 groups, respectively. All patients in this study received sphincter-preservation surgery. One patient in each group developed Clavien−Dindo grade III complications. There were no significant between-group differences in the 3-year OS (81.8% vs. 84.8%, p = 0.884) and 3-year DFS (72% vs. 71.6%, p = 0.824) rates. TEGAFOX, as consolidation chemotherapy after SCRT, achieves good tumor downstaging and patient compliance in LARC. The toxicity, complications, and surgical outcomes are similar to those of mFOLFOX-6. Thus, TEGAFOX can be considered a chemotherapy option for rectal cancer treatment.

Preoperative risk stratification of permanent stoma in patients with non-metastatic mid and low rectal cancer undergoing curative resection and a temporary stoma.

BACKGROUND: Although a temporary stoma can mitigate the severity of anastomotic leakage, some rectal cancer patients retain a permanent stoma after sphincter-preserving surgery. Therefore, this study aimed to identify independent preoperative risk factors for permanent stoma and establish a prediction model for mid-and low-rectal cancer patients who underwent sphincter-preserving surgery and temporary stoma. METHODS: We retrospectively reviewed consecutive patients with non-metastatic rectal cancer between 2000 and 2015. The risk factors for permanent stomas were collected and analyzed. RESULTS: A total of 1020 rectal cancer patients with temporary stoma were included. The overall rate of permanent stoma was 17.5% (n = 179). Cancer progression and anastomotic complications are major causes of permanent stomas. Multivariate analysis showed that preoperative risk factors such as advanced age, male sex, preoperative CEA ≥ 10 ng/ml, T4 stage, N stage, low rectal tumor, and ASA ≥ III were independent preoperative risk factors after adjustment. The ROC curve of the risk factors and permanent stoma showed an AUC of 0.689, a cut-off value of 2.5, a sensitivity of 0.689, and a specificity of 0.622. The permanent stoma rates were significantly higher between risk scores ≤ 2 and > 2 (29.9% vs. 11.3%, p < 0.001). CONCLUSION: Preoperative CEA ≥ 10 ng/ml, T4 stage, N stage, low rectal tumor, advanced age, ASA ≥ III, and male sex were independent preoperative prognostic factors for a permanent stoma. The risk was higher with a score greater than two. Therefore, the risk of subsequent permanent stoma should be evaluated and informed to the patient prior to the primary surgery.

Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon.

BACKGROUND: The purpose was to examine the effect of negative lymph nodes (NLN) number on survival in stage III colon cancer. To reduce the interference of acute inflammation, we included patients with stage III colon cancer who had undergone elective surgery and excluded those who had tumor perforation, obstruction, ischemia, or massive tumor bleeding. METHODS: This retrospective cohort study included 2244 patients with stage III colon cancer between 1995 and 2016 at a single center. The effect of NLN on 5-year relapse-free survival (RFS), 5-year overall survival (OS), and comparison of multivariate factors was assessed according to tumor locations. RESULTS: The two optimal cutoff values of NLN for proximal and distal colon, namely 27 and 12, were determined by plotting the time-dependent receiver operating characteristic curve. Overall, 499 of 891 and 1020 of 1353 patients with right-side and left-side colon cancer, respectively, had high NLN. In right-side colon cancer, patients with high NLN (≥ 27) had superior OS (74.9% vs. 62.7%, P <  0.001) and RFS (75.0% vs. 61.9%, P <  0.001) than did those with low NLN. Moreover, in left-side colon cancer, patients with high NLN (≥12) experienced significantly superior OS (80.8% vs. 68.6%, P <  0.001) and RFS (77.3% vs. 66.2%, P <  0.001) than did those with low NLN. Among the different subgroups of stage III colon cancer, the high NLN group showed significantly superior RFS and OS in stage IIIB (RFS: 77.0% vs. 68.0%, P = 0.001; OS: 78.6% vs. 67.9%, P <  0.001) and IIIC (RFS: 58.2% vs. 44.1%, P = 0.001; OS: 65.7% vs. 51.1%, P <  0.001) colon cancer. However, in stage IIIA colon cancer, high NLN only showed survival benefit in OS (91.5% vs. 89.8%, P = 0.041). Multivariate analyses confirmed that high NLN, high carcinoembryonic antigen (≥ 5 ng/mL) level, and stage IIIC status are three independent prognostic factors in both the proximal and distal colon. CONCLUSIONS: NLN is a crucial prognostic factor for stage III colon cancer in various tumor locations or in the subgroups of stage III disease. In advanced stage III colon cancer, the importance of NLN and its role in anti-cancer immune response could be highlighted.

A high density of PD-L1-expressing immune cells is significantly correlated with favorable disease free survival in nonmetastatic colorectal cancer.

ABSTRACT: The impact of immune cells (ICs) expressing various markers remains poorly understood in nonmetastatic colorectal cancer patients who have undergone colectomy. Here, we aimed to clarify the correlation between IC density and clinical parameters and survival.Programmed death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), clusters of differentiation (CD)-3, CD-8, and CD45RO immunostaining was performed for 421 patients using tissue microarray and automatic counting. Tumor stroma area immune density was assessed in comparison to clinical histological factors and surgical outcomes.High-density CD-8 expression was significantly associated with current smoking habits or a smoking history (P = .006). High-density of PD-1 expression was correlated with Lynch syndrome patients (P < .001) and with patients who did not consume alcohol (P = .034). A significant decrease in CR45RO expression density was associated with aging (P = .002 and r = -0.014), and high-density CD-3, CD-8, and PD-1 expression was significantly associated with right colon tumor location (P < .001). High CD-3 and PD-L1 expression was significantly associated with early tumor T-staging (P = .018 and P = .002). High-density PD-1 expression was significantly correlated with mucinous type adenocarcinoma (P = .027) and poor differentiation (P < .001). For treatment outcomes, multivariate analysis confirmed that patients exhibiting high-density PD-L1 expression possessed significantly longer disease free survival (adjusted hazard ratio: 0.752, 95% confidence interval [CI]: 0.61-0.92, P = .006) and overall survival (adjusted hazard ratio: 0.872, 95% CI: 0.75-1.91, P = .064)Significantly varied density in IC subsets was related to distinct demographic or clinic-histological factors. The presence of high-density PD-L1-expressing ICs is an independent favorable prognostic factor for disease free survival and overall survival among stage I to III colorectal cancer patients.

Smoking cessation for less than 10 years remains a risk factor of anastomotic leakage in mid-to-low rectal cancer patients undergoing sphincter-preserving surgery.

PURPOSE: Although cigarette smoking is a well-known risk factor for anastomotic leakage during rectal surgery, the proper duration of smoking cessation that can decrease anastomotic leakage in patients undergoing sphincter-preserving surgery is unclear. This study aimed to investigate the optimal duration of smoking cessation that can reduce this complication. METHODS: Between January 1, 2000, and December 31, 2012, we enrolled 1246 consecutive patients who underwent curative-intent sphincter-preserving surgery without preventive stoma at the Division of Colorectal Surgery of a tertiary referral center in Taiwan. Questionnaires were used to record their pre-surgical smoking status. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off duration of smoking cessation. Multivariate analysis was used to verify the effect of cigarette cessation on anastomotic leakage. RESULTS: The ROC curve showed a cut-off value of 10.5 years of cessation duration. Therefore, the former-smoker group was further divided using a cessation duration of 10 years. The overall anastomotic leakage rate was 5.29%. However, the anastomotic leakage rate in current smokers (9.3%) and in those who quit for < 10 years (12.9%) was significantly higher than that in non-smokers (3.3%) and those who quit for ≥ 10 years (4.5%). On multivariate analysis, current smokers (p = 0.022), former smokers with < 10 years of smoking cessation (OR 2.725; p = 0.029), male sex (p = 0.015), and low rectal cancer (p < 0.001) were all independently related to the development of anastomotic leakage. CONCLUSION: Smoking cessation for < 10 years remains a risk factor for anastomotic leakage in patients with mid-to-low rectal cancer undergoing sphincter-preserving surgery.

The Clinical Utility of the Geriatric Nutritional Risk Index in Predicting Postoperative Complications and Long-Term Survival in Elderly Patients with Colorectal Cancer after Curative Surgery.

Research on the relationship between the geriatric nutritional risk index (GNRI) and postoperative complications/oncological outcomes in elderly colorectal cancer (CRC) patients is limited. This study investigated the prognostic value of the GNRI in aged CRC patients. We retrospectively analyzed 1206 consecutive CRC patients aged over 75 years who underwent curative-intent surgery from January 2008 to December 2015 and categorized them into high GNRI (≥98) and low GNRI (<98) groups according to a receiver operating characteristic (ROC) curve analysis. Uni- and multivariate logistic regression analysis were used to explore the association of the GNRI with postoperative complications. Kaplan-Meier survival analyses and the Cox proportional hazard model were used to explore the association between GNRI and survival. We discovered that GNRI is an independent risk factor for postoperative complications (HR: 1.774, p = 0.037). Surgical site infection, wound dehiscence and pneumonia were more common in patients with GNRI < 98. Survival analysis showed significantly worse overall survival and disease-free survival in the low GNRI group (both p < 0.001). In the multivariate analysis, GNRI < 98 was an independent risk factor for OS (HR: 1.329, p = 0.031) and DFS (HR: 1.312, p = 0.034). Thus, preoperative GNRI can be effectively used to predict postoperative complications and long-term survival in elderly CRC patients after curative surgery.

Colon Tissues Classification and Localization in Whole Slide Images Using Deep Learning.

Colorectal cancer is one of the leading causes of cancer-related death worldwide. The early diagnosis of colon cancer not only reduces mortality but also reduces the burden related to the treatment strategies such as chemotherapy and/or radiotherapy. However, when the microscopic examination of the suspected colon tissue sample is carried out, it becomes a tedious and time-consuming job for the pathologists to find the abnormality in the tissue. In addition, there may be interobserver variability that might lead to conflict in the final diagnosis. As a result, there is a crucial need of developing an intelligent automated method that can learn from the patterns themselves and assist the pathologist in making a faster, accurate, and consistent decision for determining the normal and abnormal region in the colorectal tissues. Moreover, the intelligent method should be able to localize the abnormal region in the whole slide image (WSI), which will make it easier for the pathologists to focus on only the region of interest making the task of tissue examination faster and lesser time-consuming. As a result, artificial intelligence (AI)-based classification and localization models are proposed for determining and localizing the abnormal regions in WSI. The proposed models achieved F-score of 0.97, area under curve (AUC) 0.97 with pretrained Inception-v3 model, and F-score of 0.99 and AUC 0.99 with customized Inception-ResNet-v2 Type 5 (IR-v2 Type 5) model.

A Prediction Model for Metachronous Peritoneal Carcinomatosis in Patients with Stage T4 Colon Cancer after Curative Resection.

(1) Background: The aim of this study was to develop a prediction model for assessing individual mPC risk in patients with pT4 colon cancer. Methods: A total of 2003 patients with pT4 colon cancer undergoing R0 resection were categorized into the training or testing set. Based on the training set, 2044 Cox prediction models were developed. Next, models with the maximal C-index and minimal prediction error were selected. The final model was then validated based on the testing set using a time-dependent area under the curve and Brier score, and a scoring system was developed. Patients were stratified into the high- or low-risk group by their risk score, with the cut-off points determined by a classification and regression tree (CART). (2) Results: The five candidate predictors were tumor location, preoperative carcinoembryonic antigen value, histologic type, T stage and nodal stage. Based on the CART, patients were categorized into the low-risk or high-risk groups. The model has high predictive accuracy (prediction error ≤5%) and good discrimination ability (area under the curve >0.7). (3) Conclusions: The prediction model quantifies individual risk and is feasible for selecting patients with pT4 colon cancer who are at high risk of developing mPC.

Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?

BACKGROUND: Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients. PATIENTS AND METHODS: Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses. RESULTS: Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257-0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172-.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219-1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346-9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788-7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found. CONCLUSIONS: Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.

Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis.

BACKGROUNDS: The inflammatory biomarker "C-reactive protein to albumin ratio (CAR)" has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. METHODS: We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. RESULTS: A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808-2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321-2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. CONCLUSIONS: High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

The risk factors of local recurrence and distant metastasis on pT1/T2N0 mid-low rectal cancer after total mesorectal excision.

BACKGROUND: Radical resection is associated with good prognosis among patients with cT1/T2Nx rectal cancer. However, still some of the patients experienced cancer recurrence following radical resection. This study tried to identify the postoperative risk factors of local recurrence and distant metastasis separately. METHODS: This retrospective, single-center study comprised of 279 consecutive patients from Linkou branch of Chang Gung Memorial Hospital in 2005-2016 with rectal adenocarcinoma, pT1/T2N0M0 at distance from anal verge ≤ 8cm, who received curative radical resection. RESULTS: The study included 279 patients with pT1/pT2N0 mid-low rectal cancer with median follow-up of 73.5 months. Nineteen (6.8%) patients had disease recurrence in total. Nine (3.2%) of them had local recurrence, and fourteen (5.0%) of them had distant metastasis. Distal resection margin < 0.9 (cm) (hazard ratio = 4.9, p = 0.050) was the risk factor of local recurrence. Preoperative carcinoembryonic antigen (CEA) ≥ 5 ng/mL (hazard ratio = 9.3, p = 0.0003), lymph node yield (LNY) < 14 (hazard ratio = 5.0, p = 0.006), and distal resection margin < 1.4cm (hazard ratio = 4.0, p = 0.035) were the risk factors of distant metastasis. CONCLUSION: For patients with pT1/pT2N0 mid-low rectal cancer, current multidisciplinary treatment brings acceptable survival outcome. Insufficient distal resection margin attracted the awareness of risk factors for local recurrence and distant metastasis as a foundation for future research.

Short- and medium-term outcomes of intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a propensity score-matched study.

BACKGROUNDS: Though better short-term outcomes were frequently reported, differences in specimen parameters and the rate of subsequent peritoneal recurrence between intracorporeal anastomosis (IA) and extracorporeal anastomoses (EA) for laparoscopic right hemicolectomy have not been analyzed. We aimed to compare the pathologic differences and oncological outcomes between these two approaches. METHODS: We retrospectively analyzed 217 consecutive patients who underwent laparoscopic right hemicolectomies from September 2016 to April 2018 and classified them into IA and EA groups, based on the approach used. Propensity score matching analysis was performed, after which 101 patients were included in each group with the patients matched for demographics, tumor stage, and localization. RESULTS: The IA group had a longer operative time, shorter length of stay, shorter time to first flatus and tolerating a soft diet, and better pain scale scores at postoperative day 3. No inter-group differences in conversion, postoperative complication, mortality, or readmission rates were found. The IA group had a longer resected colon length (23.67 vs. 19.75 cm, p = 0.010) and nearest resected margin (7.51 vs. 5.40 cm, p = 0.010) for cancer near the hepatic flexure. There are comparable 3-year overall survival (87.7% vs. 89.6%, p = 0.604) and disease-free survival (75.0% vs. 75.7%, p = 0.842) between the IA and EA groups. The rate of peritoneal recurrence was similar between the two groups (5.9% vs. 7.9%, p = 0.580). CONCLUSIONS: The overall survival, disease-free survival, and the rate of peritoneal recurrence were comparable between the IA and EA procedures. IA ensures better recovery and comparable complications to EA and achieved a more precise tumor excision; thus, IA can be considered a safe procedure for patients with right-sided colon lesions.

Taiwan Society of Colon and Rectum Surgeons (TSCRS) Consensus for Anti-Inflammatory Nutritional Intervention in Colorectal Cancer.

Malnutrition and systemic inflammatory response (SIR) frequently occur in patients with colorectal cancer (CRC) and are associated with poor prognosis. Anti-inflammatory nutritional intervention is not only a way to restore the malnourished status but also modulate SIR. Nine experts, including colorectal surgeons, physicians and dieticians from 5 hospitals geographically distributed in Taiwan, attended the consensus meeting in Taiwan Society of Colon and Rectum Surgeons for a 3-round discussion and achieved the consensus based on a systematic literature review of clinical studies and published guidelines. The consensus recommends that assessment of nutritional risk and SIR should be performed before and after CRC treatment and appropriate nutritional and/or anti-inflammatory intervention should be adapted and provided accordingly.

Pathogenic Germline Mutations of DNA Repair Pathway Components in Early-Onset Sporadic Colorectal Polyp and Cancer Patients.

Given recent increases in the proportion of early-onset colorectal cancer (CRC), researchers are urgently working to establish a multi-gene screening test for both inherited and sporadic cancer-susceptible individuals. However, the incidence and spectrum of germline mutations in young sporadic CRC patients in East Asian countries and, especially, in sporadic polyp carriers and normal individuals are unknown. Peripheral blood samples were collected from 43 colonoscopy-proved normal controls and from 50 polyp patients and 49 CRC patients with no self-reported family history of cancer. All participants were under 50 years old. Next-generation sequencing with a panel of 30 CRC-associated susceptibility genes was employed to detect pathogenic germline mutations. The germline mutation carrier rates were 2.3%, 4.0%, and 12.2% in the normal, polyp, and cancer groups, respectively. A total of seven different mutations in six DNA repair pathway-related genes (MLH1, BRCA1, BRCA2, CHEK2, BLM, and NTHL1) were detected in nine participants. One frameshift mutation in BRCA2 and one frameshift mutation in the CHEK2 gene were found in a normal control and two colorectal polyp patients, respectively. One young sporadic CRC patient carried two heterozygous mutations, one in MLH1 and one in BRCA1. Three mutations (MLH1 p.Arg265Cys, MLH1 p.Tyr343Ter and CHEK2 p.Ile158TyrfsTer10) were each found in two independent patients and were considered "founder" mutations. This is the first report to demonstrate high percentage of germline mutations in young sporadic colorectal polyp, CRC, and general populations. A multi-gene screening test is warranted for the proactive identification of cancer-predisposed individuals.