British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines.
Gut
These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address:Which patients should commence surveillance post-polypectomy and post-cancer resection?What is the appropriate surveillance interval?When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG's guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant.two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise :two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); five or more premalignant polyps This cohort should undergo a one-off surveillance colonoscopy at 3 years. Post-CRC resection patients should undergo a 1 year clearance colonoscopy, then a surveillance colonoscopy after 3 more years.
10.1136/gutjnl-2019-319858
A novel faecal marker for the non-invasive diagnosis of colorectal adenoma and cancer.
Liang Jessie Qiaoyi,Li Tong,Nakatsu Geicho,Chen Ying-Xuan,Yau Tung On,Chu Eagle,Wong Sunny,Szeto Chun Ho,Ng Siew C,Chan Francis K L,Fang Jing-Yuan,Sung Joseph J Y,Yu Jun
Gut
OBJECTIVE:There is a need for early detection of colorectal cancer (CRC) at precancerous-stage adenoma. Here, we identified novel faecal bacterial markers for diagnosing adenoma. DESIGN:This study included 1012 subjects (274 CRC, 353 adenoma and 385 controls) from two independent Asian groups. Candidate markers were identified by metagenomics and validated by targeted quantitative PCR. RESULTS:Metagenomic analysis identified '' from a sp., () and () to be significantly enriched in adenoma. Faecal and were significantly increased from normal to adenoma to CRC (p<0.0001, linear trend by one-way ANOVA) in group I (n=698), which was further confirmed in group II (n=313; p<0.0001). Faecal may perform better than in distinguishing adenoma from controls (areas under the receiver operating characteristic curve (AUROCs) =0.675 vs =0.620, p=0.09), while performed better in diagnosing CRC (AUROCs =0.862 vs =0.741, p<0.0001). At 78.5% specificity, and showed sensitivities of 48.3% and 33.8% for adenoma, and 62.1% and 77.8% for CRC, respectively. In a subgroup tested with faecal immunochemical test (FIT; n=642), performed better than FIT in detecting adenoma (sensitivities for non-advanced and advanced adenomas of 44.2% and 50.8% by (specificity=79.6%) vs 0% and 16.1% by FIT (specificity=98.5%)). Combining with FIT improved sensitivity of for advanced adenoma to 56.8%. The combination of with , , and FIT performed best for diagnosing CRC (specificity=81.2% and sensitivity=93.8%). CONCLUSION:This study identifies a novel bacterial marker for the non-invasive diagnosis of colorectal adenoma.
10.1136/gutjnl-2019-318532
Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:The risk of immune checkpoint inhibitor therapy-related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS:We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS:Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn's disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event-related deaths were recorded. Anti-cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; = .058, respectively). CONCLUSION:Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.
10.1200/JCO.19.01674
Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer.
Cell research
Metastasis, the development of secondary malignant growths at a distance from a primary tumor, is the cause of death for 90% of cancer patients, but little is known about how metastatic cancer cells adapt to and colonize new tissue environments. Here, using clinical samples, patient-derived xenograft (PDX) samples, PDX cells, and primary/metastatic cell lines, we discovered that liver metastatic colorectal cancer (CRC) cells lose their colon-specific gene transcription program yet gain a liver-specific gene transcription program. We showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers. Further, we identified that the liver-specific transcription factors FOXA2 and HNF1A can bind to the gained enhancers and activate the liver-specific gene transcription, thereby driving CRC liver metastasis. Importantly, similar transcription reprogramming can be observed in multiple cancer types. Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.
10.1038/s41422-019-0259-z
Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer.
Gut
OBJECTIVE:To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). DESIGN:We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as 'positive' and 'less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. RESULTS:We initially identified 18 independent variants at 16 loci that were classified as 'positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as 'less-credible positive' SNPs; 72.2% of the 'positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to 'less-credible' positive (reducing the 'positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-analyses found no evidence to support their associations with CRC risk. CONCLUSION:The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.
10.1136/gutjnl-2019-319313
Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
Gastroenterology
BACKGROUND & AIMS:Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS:We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS:Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS:In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
10.1053/j.gastro.2019.12.012
Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group.
Annals of oncology : official journal of the European Society for Medical Oncology
BACKGROUND:The bevacizumab-Avastin® adjuVANT (AVANT) study did not meet its primary end point of improving disease-free survival (DFS) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III colon cancer (CC). We report here the long-term survival results (S-AVANT). PATIENTS AND METHODS:Patients with curatively resected stage III CC were randomly assigned to FOLFOX4, FOLFOX4-bevacizumab, or XELOX-bevacizumab. RESULTS:A total of 2867 patients were randomized: FOLFOX4: n = 955, FOLFOX4-bevacizumab: n = 960, XELOX-bevacizumab: n = 952. With a median of 6.73 years follow-up (interquartile range 5.51-10.54), 672 patients died, of whom 198 (20.7%), 250 (26.0%), and 224 (23.5%) were in the FOLFOX4, FOLFOX4-bevacizumab, and XELOX-bevacizumab arms, respectively. The 10-year overall survival (OS) rates were 74.6%, 67.2%, and 69.9%, (P = 0.003) and 5-year disease-free survival (DFS) rates were 73.2%, 68.5%, and 71.0% (P = 0.174), respectively. OS and DFS hazard ratios were 1.29 [95% confidence interval (CI) 1.07-1.55; P = 0.008] and 1.16 (95% CI 0.99-1.37; P = 0.063) for FOLFOX4-bevacizumab versus FOLFOX4 and 1.15 (95% CI 0.95-1.39; P = 0.147) and 1.1 (95% CI 0.93-1.29; P = 0.269) for XELOX-bevacizumab versus FOLFOX4, respectively. CC-related deaths (n = 542) occurred in 157 (79.3%) patients receiving FOLFOX4, 205 (82.0%) receiving FOLFOX4-bevacizumab, and 180 (80.4%) receiving XELOX-bevacizumab (P = 0.764), while non-CC-related deaths occurred in 41 (20.7%), 45 (18.0%), and 44 (19.6%) patients, respectively. Cardiovascular-related and sudden deaths during treatment or follow-up were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in the FOLFOX4, FOLFOX4-bevacizuamb, and XELOX-bevacizumab arms, respectively (P = 0.789). Treatment arm, sex, age, histological differentiation, performance status, T/ N stages, and localization of primary tumor were independent prognostic factors of OS in stage III. CONCLUSIONS:S-AVANT confirms the initial AVANT report. No benefit of the bevacizumab addition to FOLFOX4 adjuvant therapy in patients with stage III CC was observed in terms of DFS with a negative effect in OS, without increase in non-CC related deaths. CLINICAL TRIAL IDENTIFICATION:NCT00112918.
10.1016/j.annonc.2019.12.006
Secondary Bile Acids and Short Chain Fatty Acids in the Colon: A Focus on Colonic Microbiome, Cell Proliferation, Inflammation, and Cancer.
Zeng Huawei,Umar Shahid,Rust Bret,Lazarova Darina,Bordonaro Michael
International journal of molecular sciences
Secondary bile acids (BAs) and short chain fatty acids (SCFAs), two major types of bacterial metabolites in the colon, cause opposing effects on colonic inflammation at chronically high physiological levels. Primary BAs play critical roles in cholesterol metabolism, lipid digestion, and host⁻microbe interaction. Although BAs are reabsorbed via enterohepatic circulation, primary BAs serve as substrates for bacterial biotransformation to secondary BAs in the colon. High-fat diets increase secondary BAs, such as deoxycholic acid (DCA) and lithocholic acid (LCA), which are risk factors for colonic inflammation and cancer. In contrast, increased dietary fiber intake is associated with anti-inflammatory and anticancer effects. These effects may be due to the increased production of the SCFAs acetate, propionate, and butyrate during dietary fiber fermentation in the colon. Elucidation of the molecular events by which secondary BAs and SCFAs regulate colonic cell proliferation and inflammation will lead to a better understanding of the anticancer potential of dietary fiber in the context of high-fat diet-related colon cancer. This article reviews the current knowledge concerning the effects of secondary BAs and SCFAs on the proliferation of colon epithelial cells, inflammation, cancer, and the associated microbiome.
10.3390/ijms20051214
Relationship between colonic diverticulosis and colon neoplasms in Japanese patients.
Nakahara Ryotaro,Amano Yuji,Murakami Daisuke,Ogawa Sayaka,Ujihara Tetsuro,Iwaki Tomoyuki,Katsuyama Yasushi,Hayasaka Kenji,Harada Hideaki,Tada Yasumasa,Yuki Takafumi,Miyaoka Youichi,Kushiyama Yoshinori,Fujishiro Hirofumi,Ishihara Shunji
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society
BACKGROUND AND AIM:Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. METHODS:We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. RESULTS:The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0 years, male 64.0%) and 3834 without CD (66.0 years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P = 0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95% CI 1.01-1.04, P = 0.010), laxatives use (OR 1.76, 95% CI 1.17-2.64, P = 0.007), gastric neoplasms (OR 2.16, 95% CI 1.23-3.81, P = 0.008), and CD (OR 1.64, 95% CI 1.16-2.31, P = 0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P = 0.001). CONCLUSION:In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).
10.1111/den.13745
Prognostic Significance of Tumor Deposits in Combination with Lymph Node Metastasis in Stage III Colon Cancer: A Propensity Score Matching Study.
Zheng Peilin,Lai Chen,Yang Weimin,Chen Zhikang
The American surgeon
Tumor deposits in colon cancer are related to poor prognosis, whereas the prognostic power of tumor deposits in combination with lymph node metastasis (LNM) is controversial. This study aimed to compare the overall survival between LNM alone and LNM in combination with tumor deposits, and to verify whether the number of tumor deposits can be considered LNM in patients with both LNM and tumor deposits in stage III colon cancer by propensity score matching (PSM). Patients carrying resected stage III adenocarcinoma of colon cancer were identified from the Surveillance, Epidemiology, and End Results database (2010-2015). The Kaplan-Meier method, Cox proportional hazard models and PSM were used. On the whole, 23,168 patients (20,451 (88.3%) with only LNM and 2,717 (11.7%) with both LNM and tumor deposits) were selected. After undergoing PSM, patients with both LNM and tumor deposits showed worse overall survival (hazard ratio = 1.33, 95% confidence interval: 1.20-1.47, < 0.001). After the number of tumor deposits was added with that of positive regional lymph nodes, patients with both LNM and tumor deposits seemed to have prognostic implications similar to those with LNM alone (hazard ratio = 1.02, 95% confidence interval: 0.93-1.12, = 0.66). The simultaneous presence of LNM and tumor deposits, as compared with the presence of only LNM, had an association with a worse outcome. Tumor deposits should be considered as LNM in patients with both tumor deposits and LNM in stage III colon cancer.
Young age increases the risk for lymph node metastasis in patients with early Colon Cancer.
Xie Xin,Yin Jianhao,Zhou Zhangjian,Dang Chengxue,Zhang Hao,Zhang Yong
BMC cancer
BACKGROUND:The risk of lymph node positivity in early-stage colon cancer is a parameter that impacts therapeutic recommendations. However, little is known about the effect of age on lymph node positivity in colon cancer with mucosal invasion. In this study, we aimed to quantify the effect of younger age on lymph node positivity in colon cancer with mucosal invasion. METHODS:All patients were identified between 2004 and 2014 in the Surveillance, Epidemiology, and End Results database. Patients were stage T1-T2, did not undergo preoperative radiotherapy, had at least one lymph node examined, and underwent a standard colon cancer operation. Demographics and pathological data were compared between different age ranges. A nomogram model was built to estimate the probability of nodal involvement according to different characteristics. Decision curve analysis was performed by calculating the net benefits for a range of threshold probabilities. RESULTS:This study identified 41,490 patients who met the eligibility criteria for our study. 1.4% (n = 620) of patients were under 40 years old; 5.9% (n = 2571) were between 40 and 49 years old. Within each T stage, positive lymph node rates decreased with increasing age. In univariate analyses, the positive lymph node rates for patients 20 to 39 years of age were significantly higher than in patients in the reference group for stages T1 and T2. After dividing the colon into the left and right parts, these trends remained. The lymph node metastatic rate was higher in the right colon than in the left colon in terms of different age ranges. The nomogram prediction system represents a novel model with which to estimate lymph node metastasis in early T stage colon adenocarcinomas based on four risk factors with a C-index of 0.657 (95% CI: 0.658-0666). CONCLUSIONS:Our study demonstrates that the risk of lymph node metastasis was higher in young (< 40 years) patients with early-stage colon adenocarcinomas. Therefore, more aggressive screening and therapeutic strategies should be considered for young patients with colon adenocarcinoma.
10.1186/s12885-019-5995-4
Patterns of metastasis in colon and rectal cancer.
Riihimäki Matias,Hemminki Akseli,Sundquist Jan,Hemminki Kari
Scientific reports
Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis.
10.1038/srep29765
Stage IV colorectal cancer primary site and patterns of distant metastasis.
Robinson Jamaica R,Newcomb Polly A,Hardikar Sheetal,Cohen Stacey A,Phipps Amanda I
Cancer epidemiology
BACKGROUND:Although colorectal cancer (CRC) usually metastasizes to the liver and/or lungs, factors influencing the anatomic pattern of metastases remain poorly understood. METHODS:We assessed the relationship between primary CRC site and pattern of synchronous metastasis among 1202 individuals diagnosed with incident metastatic CRC between 2010 and 2014 and identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between primary tumor site and synchronous metastatic pattern. RESULTS:Compared to patients with proximal colon primaries, patients with rectal primaries were more likely to present with lungs-only or liver and lungs metastases versus liver-only metastases (OR: 2.39, 95% CI: 1.35-4.24, OR: 2.20, 95% CI: 1.46-3.32). CONCLUSION:These findings suggest that patients with rectal primaries are more likely than patients with colon primaries to present with synchronous lung metastases.
10.1016/j.canep.2017.04.003
Nomogram for predicting overall survival in colorectal cancer with distant metastasis.
Liu Zheng,Xu Yao,Xu Guijun,Baklaushev Vladimir P,Chekhonin Vladimir P,Peltzer Karl,Ma Wenjuan,Wang Xin,Wang Guowen,Zhang Chao
BMC gastroenterology
BACKGROUND:Colorectal cancer (CRC) is a major cancer burden, and prognosis is determined by many demographic and clinicopathologic factors. The present study aimed to construct a prognostic nomogram for colorectal cancer patients with distant metastasis. METHODS:Colorectal cancer patients with distant metastasis diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict survival, and validation was performed. RESULTS:A total of 7099 stage IV colorectal cancer patients were enrolled in the construction cohort. The median overall survival was 20.0 (95% CI 19.3-20.7) months. Age at diagnosis, marital status, race, primary tumour site, tumour grade, CEA level, T stage, N stage, presence of bone, brain, liver and lung metastasis, surgery for primary site and performance of chemotherapy were independent prognostic factors. The nomogram was constructed and the calibration curve showed satisfactory agreement. The C-index was 0.742 (95% CI 0.726-0.758). In the validation cohort (7098 patients), the nomogram showed satisfactory discrimination and calibration with a C-index of 0.746 (95% CI 0.730-0.762). CONCLUSION:A series of factors associated with the survival of CRC patients with distant metastasis were found. Based on the identified factors, a nomogram was generated to predict the survival of stage IV colorectal cancer patients. The predictive model showed satisfactory discrimination and calibration, which can provide a reference for survival estimation and individualized treatment decisions.
10.1186/s12876-021-01692-x
Primary tumor location in stage III colon cancer has prognostic impact on subsequent liver metastasis.
Liao Chun-Kai,Chiang Jy-Ming,Tsai Wen-Sy,You Jeng-Fu,Hsieh Pao-Shiu,Hung Hsin-Yuan,Chen Hong-Hwa,Tang Rei-Ping,Chen Jinn-Shiun,Yeh Chien-Yuh
Journal of surgical oncology
BACKGROUND AND OBJECTIVES:We aim to investigate whether a difference exists between right-sided and left-sided colon cancer at the same disease stage and subsequent liver metastasis and identify whether tumor location can independently influence survival. METHODS:Right-sided colon cancer was defined as malignancy arising from the cecum to the transverse colon; left-sided colon cancer was defined as malignancy arising from the splenic flexure to the sigmoid colon. Clinicopathological features and survival data were collected for analysis. RESULTS:Overall, 1442 patients were included for analysis. The median follow-up time was 58.2 months. Patients with left-sided colon cancer had better 5-year overall survival (75.2% vs 61.7%, P = 0.005), 5-year cancer-specific survival (81.6% vs 73.4%, P = 0.001), and 5-year recurrence-free survival (70.9% vs 66.5%, P = 0.033) compared with patients having right-sided colon cancer. After the presentation of subsequent liver metastasis, patients with primary left-sided colon cancer had better 3-year cancer-specific survival ( P < 0.001). In the multivariate analysis, cancer location was an independent prognostic factor for cancer-specific survival (right vs left, HR: 1.276, 95% CI: 1.002-1.625). CONCLUSIONS:The primary tumor location can serve as a prognostic factor for treatment outcomes either in primary stage III colon cancer or subsequent liver metastasis.
10.1002/jso.25270
Clinical impact of preoperative liver MRI in the evaluation of synchronous liver metastasis of colon cancer.
Kim Cherry,Kim So Yeon,Kim Min-Ju,Yoon Yong Sik,Kim Chan Wook,Lee Jae Hoon,Kim Kyu-Pyo,Lee Seung Soo,Park Seong Ho,Lee Moon-Gyu
European radiology
OBJECTIVES:To investigate whether additional MRI including gadoxetic acid enhancement is associated with survival rate (SR) in patients with synchronous liver metastasis of colon cancer (sCLM), compared with patients assessed only with CT. METHODS:Fifty-two patients underwent only CT (CT group) and 65 underwent additional MRI (CT+MRI group) for preoperative work-up of sCLM. In the CT+MRI group, the discrepancy between CT and MRI was analyzed. The 5-year SR was compared between the groups, and affecting factors were investigated. The inverse probability treatment weighting analysis (IPTW) adjusted by propensity scores was performed. RESULTS:In the CT+MRI group, 44 (67.7%) showed a discrepancy in the number of sCLMs between CT and MRI. MRI detected 39 additional sCLMs initially missed on CT in 26 patients. The number of detected sCLMs was better correlated with the pathologic findings in the CT+MRI group than in the CT group (p = 0.008). The estimated 5-year SR in the CT+MRI group was 70.8%, while that in the CT group was 48.1%. On adjusted multivariate analyses after the IPTW, the CT+MRI group showed a significantly lower risk of overall mortality than the CT group. CONCLUSION:Additional preoperative evaluation by MRI allowed us to more precisely detect sCLM and was associated with a better SR. KEY POINTS:• CT+MRI group showed significantly higher 5-year survival rates than CT group. • CT+MRI group was an independent prognostic factor of overall mortality. • MRI facilitates more accurate detection and better lesion characterization. • MRI selected better candidates for curative treatment. • The benefits of MRI were reflected by better survival.
10.1007/s00330-018-5422-2
Incidence, risk factors, and a predictive model for lymph node metastasis of submucosal (T1) colon cancer: A population-based study.
Hu Dong Ya,Cao Bin,Li Shi Han,Li Peng,Zhang Shu Tian
Journal of digestive diseases
OBJECTIVE:This study aimed to assess the incidence, identify independent factors, and develop a lymph node metastasis (LNM) prediction model for patients with T1 colon cancer. METHODS:Statistics were drawn from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. A multivariate logistic regression analysis was performed to determine independent predictors of LNM. A nomogram for predicting the possibility of LNM was developed based on those factors. RESULTS:A total of 5397 patients with T1 colon cancer were identified. The overall LNM rate was 15.0% (808/5397). A multivariate analysis showed that age (odds ratio [OR] 0.97, P < 0.001), tumor size (OR 1.01, P < 0.001), moderate (OR 1.77, P = 0.001) or poorly differentiated/undifferentiated tumor (OR 5.60, P < 0.001), right colon cancer (OR 1.39, P = 0.008), and a positive carcinoembryonic antigen level (OR 1.51, P = 0.004) were independent predictive factors for LNM. The area under the receiver operating characteristic curve was 0.68 (95% confidence interval [CI] 0.65-0.71) in the training set and 0.65 (95% CI 0.61-0.67) in the validation set. A calibration plot showed good consistency between the bias-corrected prediction and the ideal reference line with 1000 additional bootstraps (mean absolute error = 0.007). CONCLUSIONS:The incidence of LNM was high in patients with T1 colon cancer. A nomogram for predicting the probability of LNM for T1 colon cancer may be used to help determine the optimal treatment for these patients.
10.1111/1751-2980.12754
Clinical Significance of Lymph Node Metastasis in the Mesentery of the Terminal Ileum in Patients With Right-sided Colon Tumors at Different Locations.
Kang Sung Il,Kim Duck-Woo,Shin Eun,Kim Myung Jo,Son Il Tae,Oh Heung-Kwon,Kang Sung-Bum
Diseases of the colon and rectum
BACKGROUND:There are limited reports on peri-ileal lymph node metastasis in patients with right-sided colon cancer, and little is known about their clinical significance. OBJECTIVE:This study aimed to examine the role of tumor location in the prevalence and clinical significance of peri-ileal lymph node metastasis in patients with right-sided colon cancer. DESIGN:This is a retrospective study from a prospective cohort database. SETTINGS:The study was conducted at a tertiary referral hospital. PATIENTS:Patients with right-sided colon cancer treated with radical surgery in a hospital between May 2006 and September 2016 were included. MAIN OUTCOME MEASURES:The frequency of peri-ileal lymph node metastasis in the study cohort and the role of tumor location and the clinical characteristics of patients with peri-ileal lymph node metastasis were determined. RESULTS:We examined 752 cases with right-sided colon cancer including 82 cecal, 554 ascending colon, and 116 hepatic flexure cancer. Twenty patients (2.7%) had peri-ileal lymph node metastasis. The incidence of metastasis to peri-ileal lymph nodes was 7.3% (6/82) in patients with cecal cancer, 2.2% (12/554) in patients with ascending colon cancer, and 1.7% (2/116) in patients with hepatic flexure cancer. Three patients had stage III cancer and 17 had stage IV. All 3 patients with positive peri-ileal lymph nodes and stage III cancer had cecal tumors. In contrast, all patients with ascending colon or hepatic flexure cancer and positive peri-ileal lymph nodes had stage IV cancer. LIMITATIONS:The results were limited by the retrospective design of the study and the small number of patients with peri-ileal lymph node metastasis. CONCLUSIONS:Peri-ileal lymph node metastasis was rare even in right-sided colon cancer and occurred mainly in stage IV. However, it occurred in some patients with locally advanced cecal cancer. These results suggest that optimal resection of the mesentery of the terminal ileum might have clinical benefit, especially in curative surgery for cecal cancer. See Video Abstract at http://links.lww.com/DCR/A556.
10.1097/DCR.0000000000001048
Oncologic significance of para-aortic lymph node and inferior mesenteric lymph node metastasis in sigmoid and rectal adenocarcinoma.
Lee Seung Hyung,Lee Jong Lyul,Kim Chan Wook,Lee Han Il,Yu Chang Sik,Kim Jin Cheon
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
BACKGROUND:Recurrence patterns or survival in colorectal cancer patients might differ according to inferior mesenteric lymph node (IMLN) metastasis. However, few studies have compared para-aortic lymph node (PALN) metastasis and IMLN metastasis. The aim of the current study is to identify survival and recurrence patterns in patients with sigmoid colon and rectal adenocarcinoma with either PALN or IMLN metastasis and to evaluate the prognostic significance of PALN and IMLN metastasis. METHODS:A retrospective study involving 3076 patients with stage III and IV sigmoid and rectal cancer, who underwent curative surgery between January 2000 and December 2009, was performed. Clinicopathologic features, recurrence patterns, and survival outcomes of 27 patients with PALN metastasis were compared with those of 47 patients with IMLN metastasis. Patients with both IMLN and PALN metastasis were included in the PALN+ group. RESULTS:After curative resection, there was no significant difference in the 5-year disease-free and overall survival rates between the PALN+ and IMLN+ groups (27.5% vs. 29.8%, p = 0.24, and 37% vs. 39.2%, p = 0.19, respectively). Furthermore, there were no significant differences in recurrence rate (PALN+ group, 70.4%; and IMLN+ group, 63.8%; p = 0.69) or recurrence patterns. CONCLUSIONS:The results suggest that IMLN metastasis, similar to PALN metastasis, is associated with adverse oncologic outcomes and has prognostic significance. Therefore, it is preferable that IMLN metastasis should be considered under the category of systemic metastasis (M1).
10.1016/j.ejso.2017.08.014
Novel nomograms to predict lymph node metastasis and liver metastasis in patients with early colon carcinoma.
Yan Yongcong,Liu Haohan,Mao Kai,Zhang Mengyu,Zhou Qianlei,Yu Wei,Shi Bingchao,Wang Jie,Xiao Zhiyu
Journal of translational medicine
BACKGROUND:Lymph node status and liver metastasis (LIM) are important in determining the prognosis of early colon carcinoma. We attempted to develop and validate nomograms to predict lymph node metastasis (LNM) and LIM in patients with early colon carcinoma. METHODS:A total of 32,819 patients who underwent surgery for pT1 or pT2 colon carcinoma were enrolled in the study based on their records in the SEER database. Risk factors for LNM and LIM were assessed based on univariate and multivariate binary logistic regression. The C-index and calibration plots were used to evaluate LNM and LIM model discrimination. The predictive accuracy and clinical values of the nomograms were measured by decision curve analysis. The predictive nomograms were further validated in the internal testing set. RESULTS:The LNM nomogram, consisting of seven features, achieved the same favorable prediction efficacy as the five-feature LIM nomogram. The calibration curves showed perfect agreement between nomogram predictions and actual observations. The decision curves indicated the clinical usefulness of the prediction nomograms. Receiver operating characteristic curves indicated good discrimination in the training set (area under the curve [AUC] = 0.667, 95% CI 0.661-0.673) and the testing set (AUC = 0.658, 95% CI 0.649-0.667) for the LNM nomogram and encouraging performance in the training set (AUC = 0.766, 95% CI 0.760-0.771) and the testing set (AUC = 0.825, 95% CI 0.818-0.832) for the LIM nomogram. CONCLUSION:Novel validated nomograms for patients with early colon carcinoma can effectively predict the individualized risk of LNM and LIM, and this predictive power may help doctors formulate suitable individual treatments.
10.1186/s12967-019-1940-1
The prognostic effect of adjuvant chemotherapy in the colon cancer patients with solitary lymph node metastasis.
Yeom Seung-Seop,Lee Soo Young,Kim Chang Hyun,Kim Hyeong Rok,Kim Young Jin
International journal of colorectal disease
PURPOSE:Previous studies have reported paradoxical survival prognoses for some node-negative and node-positive colon cancer patients. However, current guidelines recommend adjuvant chemotherapy (CT) only for node-positive patients. This study investigated the efficacy of adjuvant CT for patients who underwent radical surgery for colon cancer with solitary lymph node (LN) metastasis. METHODS:This study included 281 patients treated between 2004 and 2015. Patients were classified into no-CT (n = 39) and CT (n = 242) groups, and the survival outcomes and recurrence-related follow-up data were analyzed. RESULTS:The groups exhibited similarities in tumor sidedness, tumor differentiation, and pathologic stage. However, the age, ASA class, and preoperative CEA level were relatively lower in the CT group. Although the CT group had a higher 5-year overall survival (OS) rate than the no-CT group (88.4% vs. 65.3%, p < 0.001), the groups did not differ in terms of 5-year disease-free survival (DFS) (CT, 84.1% vs. no-CT, 83.3%, p = 0.490). A multivariate analysis identified adjuvant CT as an independent factor for OS but not for DFS. A highly examined LN count (≥ 12) was associated with improved DFS improvement. However, D3 LN dissection was not associated with DFS or OS. For DFS, intermediate/apical positive LNs received a high hazard ratio relative to pericolic/epicolic LNs (2.080, 95% confidence interval: 0.979-4.416), but this was not significant (p = 0.057). CONCLUSIONS:Adjuvant chemotherapy did not provide clear advantages for colon cancer with solitary LN metastasis. Further large studies that analyze several prognostic factors are needed to establish tailored adjuvant CT administration guidelines.
10.1007/s00384-019-03346-7
MicroRNAs and their role for T stage determination and lymph node metastasis in early colon carcinoma.
Rammer Melanie,Webersinke Gerald,Haitchi-Petnehazy Sophie,Maier Eva,Hackl Hubert,Charoentong Pornpimol,Malli Theodora,Steinmair Maria,Petzer Andreas L,Rumpold Holger
Clinical & experimental metastasis
Worldwide, colon cancer is among the most common cancer entities. Understanding the molecular background is the key to enable accurate stage determination, which is crucial to assess optimal therapy options. The search for preoperative biomarkers is ongoing. In recent years, several studies have proposed a diagnostic and prognostic role for miRNAs in cancer. Aim of this study was to evaluate miRNA expression patterns correlating with tumor stage, especially lymph node metastasis, in primary colon carcinoma tissue. Screening was accomplished using GeneChip miRNA v3.0 arrays (Thermo Fisher Scientific, Waltham, MA, USA) and validated via TaqMan qPCR assays (Thermo Fisher Scientific, Waltham, MA, USA) to investigate miRNA expressions in 168 FFPE and 83 fresh frozen colon carcinoma samples. Regarding lymph node status, analyses displayed no significantly differential miRNA expression. Interestingly, divergent expression of miR-18a-5p, miR-20a-5p, miR-21-5p, miR-152-3p and miR-1973 was detected in stage pT1. Although miRNAs might not represent reliable biomarkers regarding lymph node metastasis status, they could support risk assessment in stage T1 tumors.
10.1007/s10585-017-9863-9
Effect of Primary Tumor Location on Postmetastasectomy Survival in Patients with Colorectal Cancer Liver Metastasis.
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
BACKGROUND:The effects of primary tumor location on colorectal liver metastasis (CRLM) and post-hepatic-metastasectomy overall survival (OS) are controversial. This study evaluated the difference in post-hepatic-metastasectomy OS among right-sided colon, left-sided colon, and rectal cancer groups. METHODS:In total, 381 patients who underwent curative-intent CRLM resection were enrolled. Patients were grouped based on the primary tumor location (right-sided, left-sided, and rectum). The Kaplan-Meier analysis and log-rank test were performed for survival analysis. The univariate and multivariate analyses of clinical and pathological factors were performed using the Cox proportional hazards model. RESULTS:Significant OS difference was noted among the three groups (log-rank, p = 0.014). The multivariate analysis revealed a 32% lower death risk in left-sided colon cancer compared with right-sided colon cancer (hazard ratio [HR] 0.68, p = 0.042), whereas no OS difference was noted between the rectal cancer and right-sided colon cancer groups. The left- versus right-sided OS advantage was noted only in the KRAS wild-type subgroup (HR 0.46, p = 0.002), and a rectal versus right-sided OS disadvantage was noted in the KRAS mutant subgroup (HR 1.78, p = 0.03). CONCLUSIONS:The CRLM post-hepatic-metastasectomy OS was superior in left-sided colon cancer than in right-sided colon cancer and was similar in rectal and right-sided colon cancer. The OS difference in different primary tumor locations is dependent on KRAS mutation status, with a decreased left- versus right-sided death risk noted only in KRAS wild-type colon cancer and an increased rectal versus right-sided death risk noted only in KRAS mutant colon cancer.
10.1007/s11605-020-04855-5
Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis.
Na Heya,Liu Xiaoli,Li Xiaomeng,Zhang Xinsheng,Wang Yu,Wang Zhaohui,Yuan Menglang,Zhang Yu,Ren Shuangyi,Zuo Yunfei
Journal of hematology & oncology
BACKGROUND:Tumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process. METHODS:Colon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined. RESULTS:In our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis. CONCLUSIONS:These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment.
10.1186/s13045-016-0383-x
Risk factors for lymph node metastasis in early colon cancer.
Lee You Jin,Huh Jung Wook,Shin Jung Kyong,Park Yoon Ah,Cho Yong Beom,Kim Hee Cheol,Yun Seong Hyeon,Lee Woo Yong
International journal of colorectal disease
BACKGROUND:The aim of the study was to determine factors predicting lymph node metastasis in patients with T1 or T2 colon cancer. METHODS:A total of 906 patients with T1 or T2 colon cancer who underwent colon resection with regional lymphadenectomy in a tertiary hospital, from January 2008 to December 2013, were analyzed. The prognostic factors for LN metastasis and the risk factors for survival were analyzed. RESULTS:There were 728 patients (80.4%) without lymph node metastasis (LN-negative group) and 178 patients (19.6%) with lymph node metastasis (LN-positive group). Tumor invasion depth (P < 0.001), lymphatic invasion (P < 0.001), and perineural invasion (P = 0.008) were significantly different between the two groups. During the median follow-up period of 69 months, the 5-year disease-free survival rate was 98.6% for the LN-negative group and 92.8% for the LN-positive group (P ≤ 0.001). In multivariate analysis, influencing factors associated with disease-free survival rate were LN metastasis (P = 0.001) and perineural invasion (P = 0.040). Female, depth of tumor invasion (P = 0.001), and lymphatic invasion (P < 0.001) were significant independent predictive factors for lymph node metastasis in multivariate analysis. CONCLUSION:Positive LN status predicted poor disease-free survival in patients with early cancer. This suggests that depth of tumor invasion ≥ sm2 and the presence of lymphatic invasion in early colon cancer provide useful information to determine which patients would benefit from radical surgery.
10.1007/s00384-020-03618-7
The Preoperative Peripheral Blood Monocyte Count Is Associated with Liver Metastasis and Overall Survival in Colorectal Cancer Patients.
Hu Shidong,Zou Zhenyu,Li Hao,Zou Guijun,Li Zhao,Xu Jian,Wang Lingde,Du Xiaohui
PloS one
BACKGROUND:Colorectal cancer (CRC) is the third most common malignancy in males and the second most common in females worldwide. Distant metastases have a strong negative impact on the prognosis of CRC patients. The most common site of CRC metastases is the liver. Both disease progression and metastasis have been related to the patient's peripheral blood monocyte count. We therefore performed a case-control study to assess the relationship between the preoperative peripheral blood monocyte count and colorectal liver metastases (CRLM). METHODS:Clinical data from 117 patients with colon cancer and 93 with rectal cancer who were admitted to the Chinese People's Liberation Army General Hospital (Beijing, China) between December 2003 and May 2015 were analysed retrospectively, with the permission of both the patients and the hospital. RESULTS:Preoperative peripheral blood monocyte counts, the T and N classifications of the primary tumour and its primary site differed significantly between the two groups (P < 0.001, P < 0.001, P = 0.002, P < 0.001), whereas there were no differences in the sex, age, degree of tumour differentiation or largest tumour diameter. Lymph node metastasis and a high preoperative peripheral blood monocyte count were independent risk factors for liver metastasis (OR: 2.178, 95%CI: 1.148~4.134, P = 0.017; OR: 12.422, 95%CI: 5.076~30.398, P < 0.001), although the risk was lower in patients with rectal versus colon cancer (OR: 0.078, 95%CI: 0.020~0.309, P < 0.001). Primary tumour site (P<0.001), degree of tumour differentiation (P = 0.009), T, N and M classifications, TNM staging and preoperative monocyte counts (P<0.001) were associated with the 5-year overall survival (OS) of CRC patients. A preoperative peripheral blood monocyte count > 0.505 × 109 cells/L, high T classification and liver metastasis were independent risk factors for 5-year OS (RR: 2.737, 95% CI: 1.573~ 4.764, P <0.001; RR: 2.687, 95%CI: 1.498~4.820, P = 0.001; RR: 4.928, 95%CI: 2.871~8.457, P < 0.001). CONCLUSIONS:The demonstrated association between preoperative peripheral blood monocyte count and liver metastasis in patients with CRC recommends the former as a useful predictor of postoperative prognosis in CRC patients.
10.1371/journal.pone.0157486
Impact of Anatomic Extent of Nodal Metastasis on Adjuvant Chemotherapy Outcomes in Stage III Colon Cancer.
Woo In Teak,Park Jun Seok,Kang Byung Woog,Park Soo Yeun,Kim Hye Jin,Choi Gyu-Seog,Gwang Kim Jong
Diseases of the colon and rectum
BACKGROUND:An oxaliplatin-based chemotherapy regimen improves the survival outcomes of patients with stage III colon cancer. However, its complications are well-known. OBJECTIVE:The purpose of this study was to distinguish between the survival outcomes of patients who underwent curative resection for stage III colon cancer with oxaliplatin chemotherapy and those who underwent such resection without oxaliplatin chemotherapy. DESIGN:This was a retrospective analytical study based on prospectively collected data. SETTINGS:This study used data on patients who underwent surgery at our hospital between January 2010 and December 2014. PATIENTS:A cohort of 254 consecutive patients who underwent curative resection for stage III colon cancer was included in this study. The patients were divided into 2 groups: patients with isolated pericolic lymph node metastasis (n = 175) and those with extrapericolic lymph node metastasis (n = 79). MAIN OUTCOME MEASURES:Clinicopathologic features and 3-year survival outcomes were analyzed with and without oxaliplatin therapy in the pericolic lymph node group. RESULTS:The pericolic lymph node group showed significantly improved overall survival compared with the extrapericolic lymph node group at a median follow-up of 48.5 months (95.8% vs 77.8%; p < 0.001). In contrast, there was no significant difference in overall survival (99.0% vs 92.0%; p = 0.137) and disease-free survival (89.1% vs 88.2%; p = 0.460) between the oxaliplatin and nonoxaliplatin subgroups of the pericolic lymph node group. Multivariate analysis showed that the administration of oxaliplatin chemotherapy to the pericolic lymph node group did not lead to a significant difference in the overall survival (p = 0.594). LIMITATIONS:The study was limited by its retrospective design and single institutional data analysis. CONCLUSIONS:This study suggests that the anatomic extent of metastatic lymph nodes could affect patient prognosis, and the effect of oxaliplatin-based adjuvant chemotherapy may not be prominent in stage III colon cancer with isolated pericolic lymph node metastasis.
10.1097/DCR.0000000000001790
Role of MicroRNAs in the Progression and Metastasis of Colon Cancer.
Sampath Shruthi Sanjitha,Venkatabalasubramanian Sivaramakrishnan,Ramalingam Satish
Endocrine, metabolic & immune disorders drug targets
MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours, while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn's disease and Ulcerative colitis, which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc, will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.
10.2174/1871530320666200825184924
Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver.
Cancer cell
Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases.
10.1016/j.ccell.2021.03.004
Intestinal adenosquamous carcinoma with a synchronous skin metastasis: a immunohistochemical and molecular analysis.
Parente Paola,Covelli Claudia,Parrella Paola,Latiano Tiziana Pia,Fiordelisi Fabiola,Pellico Maria Teresa,Maiello Evaristo,Graziano Paolo
International journal of colorectal disease
INTRODUCTION:Intestinal adenosquamous carcinoma (ASC) is a rare colorectal neoplasm frequently occurring at onset as a locally advanced disease with distant metastases. The liver is the most common site of metastasis, followed by the peritoneum and the lung. Cutaneous metastases from usual colorectal adenocarcinoma occur in about 3% of cases, both at the time of diagnosis in advanced disease and during the follow-up. To the best of our knowledge, skin metastasis from ASC has never been described, and no biological landscape of ASC has ever been investigated. METHODS:We report a case of synchronous intestinal ASC and cutaneous single facial metastasis in a 70-year-old man with morphological, immunohistochemical, and molecular analysis of primary and metastatic lesions. RESULTS:Primary and metastatic ASC showed the same morphological and immunohistochemical features. Target sequencing analysis revealed, both in primary tumor and metastasis, a pathogenic KRAS gene missense mutation c.38G > A p.(Gly13Asp) and a likely pathogenic CTNNB1 gene missense mutation c.94G > A p.(Asp32Asn). A nuclear localization of β-catenin protein in adenocarcinomatous component of primary and metastatic lesions was observed on immunohistochemistry. CONCLUSION:We describe a case of single synchronous facial cutaneous metastasis from intestinal ASC showing KRAS and CTNN1B mutations both on primary and metastatic lesions.
10.1007/s00384-019-03464-2
The role of the immunoescape in colorectal cancer liver metastasis.
Takasu Chie,Yamashita Shoko,Morine Yuji,Yoshikawa Kozo,Tokunaga Takuya,Nishi Masaaki,Kashihara Hideya,Yoshimoto Toshiaki,Shimada Mitsuo
PloS one
The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.
10.1371/journal.pone.0259940
The prognostic significance of apical lymph node metastasis in patients with high-risk stage III colon cancer.
Ishii Kenichi,Watanabe Jun,Goto Kouki,Suwa Yusuke,Nakagawa Kazuya,Suwa Hirokazu,Ozawa Mayumi,Ishibe Atsushi,Kunisaki Chikara,Endo Itaru
Scientific reports
The effect of apical lymph node (APN) metastasis on the prognosis of colon cancer is unknown. The present study investigated the impact of APN metastasis on the prognosis of the patients with high-risk stage III colon cancer. This retrospective multi-institutional study included patients with pathological high-risk stage III colon cancer who underwent surgery between April 2009 and December 2014. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors for overall survival (OS) and relapse-free survival (RFS). A total of 185 patients were collected. The 5-year OS rates of patients with and without APN metastasis were 35.0% and 72.1%, respectively (p = 0.0014). The 5-year RFS rates of patients with and without APN metastasis was 16.2% and 57.2%, respectively (p = 0.0002). The rate of distant metastasis in patients with APN metastasis was significantly higher than that in patients without APN metastasis (68.8% vs. 36.7%, p = 0.012). The univariate analysis revealed that the differentiation, lymph node ratio, and APN metastasis were significantly associated with 5-year OS, and the preoperative CEA and CA19-9 levels and APN metastasis were significantly associated with 5-year RFS. The multivariate analysis showed that APN metastasis was an independent risk factor for 5-year OS and RFS. APN metastasis may be independently associated with the prognosis of patients with high-risk Stage III colon cancer.
10.1038/s41598-022-06054-5
Proteomic Analysis of Primary Colon Cancer and Synchronous Solitary Liver Metastasis.
Kim Eun-Kyung,Song Min-Jeong,Jung Yunjae,Lee Won-Suk,Jang Ho Hee
Cancer genomics & proteomics
BACKGROUND/AIM:Colon cancer is prone to distant metastases to other sites and the risk of recurrence is relatively high. Therefore, the identification of liver metastasis-related factors is important for the diagnosis or treatment of colon cancer. The aim of this study was to identify the metastasis-related factors that are differentially expressed in synchronous solitary liver metastasis compared to primary colon cancer. MATERIALS AND METHODS:Tissues of primary colon cancer and associated with liver metastases of five patients were used for mass spectrometry. Identified proteins were validated by western blotting. The in silico analysis was performed using the STRING database and GeneMANIA. RESULTS:We identified 58 differentially expressed proteins (DEPs), including 51 under-expressed and 7 over-expressed proteins among a total of 164 identified proteins. Major hubs of protein-protein networks were ACTC1, PRDX6, TPI1, and ALDH1A1. DEPs were located in the extracellular region and cytoplasm and were involved in the regulation of enzymatic activity. The metabolic process was significantly enriched in biological processes and an involvement in the KEGG pathway. CONCLUSION:These DEPs can potentially be used as biomarkers for the diagnosis of liver metastasis and they may provide a new strategy for developing anti-metastatic liver drugs in colon cancer patients.
10.21873/cgp.20161
Predictive Value of Circulating miRNAs in Lymph Node Metastasis for Colon Cancer.
Lee In Hee,Kim Gyeonghwa,Kwak Sang Gyu,Baek Dong Won,Kang Byung Woog,Kim Hye Jin,Park Su Yeon,Park Jun Seok,Choi Gyu-Seog,Hur Keun,Kim Jong Gwang
Genes
(1) Background: Lymph node (LN) status is an indubitable prognostic factor for survival among colon cancer patients. MicroRNAs (miRNAs) have been implicated in the development and progression of many cancers and are potential biomarkers for cancer diagnosis and prognosis. Therefore, we validated candidate biomarkers using circulating miRNAs by analyzing the plasma miRNA concentrations from patients with colon cancer to predict LN metastasis. (2) Methods: This study included 79 blood samples from patients diagnosed with colon cancer. The NanoString assay was used for screening, and TaqMan miRNA assays for quantitative real-time polymerase chain reaction (RT-PCR) test was used for validation. In a discovery set, we compared the expression of 800 circulating miRNAs in 24 samples (stage 0/I/IIA versus IIIB/IIIC). For validation, a total 79 samples were tested using quantitative RT-PCR. (3) Results: In the discovery set, 10 candidate circulating miRNAs were detected (4 up-regulated miRNAs: miR-323a-3p, miR-382-5p, miR-29a-3p, and miR-376a-3p; 6 down-regulated miRNAs: miR-26a-5p, let-7g-5p, miR-15b-5p, miR-142-3p, miR-374a-5p, and let-7b-5p). In the validation set, higher expression of three circulating miRNAs (miR-323a-3p, miR-382-5p, and miR-376a-3p) was significantly associated with LN metastasis ( = 0.0063, 0.0107, and 0.0022). (4) Conclusions: High expression of circulating miR-323a-3p, miR-382-5p, and miR-376a-3p was significantly associated with LN metastasis in colon cancer patients. These miRNAs could be circulating biomarker candidates that predict the presence of LN metastasis.
10.3390/genes12020176
Anti-tubulin agent vinorelbine inhibits metastasis of cancer cells by regulating epithelial-mesenchymal transition.
Liu Hongyu,Fu Qingshan,Lu Yao,Zhang Wenqiang,Yu Peng,Liu Zhen,Sun Xiaosheng
European journal of medicinal chemistry
Cancer invasion and metastasis are the leading causes of death. The process of metastasis or tumor cell dissemination is still much of a mystery. Emerging evidence has shown that epithelial-mesenchymal transition (EMT) plays a vital role in the progression of malignant tumor including the inducing cell invasion and metastasis as well as promoting drug resistance. Vinorelbine is a traditional chemotherapeutic agent for treatment of lung cancer and breast cancer by the selectivity to mitotic microtubules. The aim of this study was to investigate the effect of vinorelbine on three metastatic cancer cells including lung cancer (H1975), liver cancer (HepG2), and colon cancer (HCT116) cells through inhibition of metastatic abilities and EMT program. Vinorelbine inhibited the cancer cell proliferation by MTT and colony formation assays and inducing G2/M arrest and cell apoptosis via regulation of Bax, Bcl-2, and Bcl-xL. Vinorelbine decrease the migration and invasion ability of the cancer cells by wound healing assay and Tran swell test. The molecular mechanisms of vinorelbine suppressing the metastatic phenotypes of cancer cells through modulation of E-cadherin, N-cadherin, vimentin and transcription factors Snail, MMP-2 and MMP-9. Our results demonstrated that vinorelbine inhibited the cancer cell metastasis through a reduction in metastatic mobility, such as migration, invasion, and the EMT. It provided the evidence that vinorelbine can be used alone or with other agents for treatment of metastatic lung cancer, liver cancer and colon cancer.
10.1016/j.ejmech.2020.112332
The Effect of Gene Mutations on Metastasis and Overall Survival in Metastatic and Nonmetastatic Colon Cancers.
Asian Pacific journal of cancer prevention : APJCP
OBJECTIVE:It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers. METHODS:A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated. RESULTS:The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05). CONCLUSION:We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.
10.31557/APJCP.2021.22.12.3839
Helicobacter pylori but not gastrin is associated with the development of colonic neoplasms.
Selgrad Michael,Bornschein Jan,Kandulski Arne,Hille Carla,Weigt Jochen,Roessner Albert,Wex Thomas,Malfertheiner Peter
International journal of cancer
Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n = 138; 36.6%), the overall prevalence of colonic neoplasms was more frequent compared to H. pylori negative patients (n = 239; 63.4%) (OR = 2.73, 95% CI: 1.76-4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR = 2.66, 95% CI: 1.23-5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR = 1.85, 95% CI: 1.14-2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n = 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR = 2.25, 95% CI: 1.29-3.94). Hypergastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm.
10.1002/ijc.28758
Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms.
Inoue Izumi,Kato Jun,Tamai Hideyuki,Iguchi Mikitaka,Maekita Takao,Yoshimura Noriko,Ichinose Masao
World journal of gastroenterology
To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.
10.3748/wjg.v20.i6.1485
Statin Therapy Is Associated With Decreased 90-Day Postoperative Mortality After Colon Cancer Surgery.
Diseases of the colon and rectum
BACKGROUND:There have been conflicting reports regarding a protective effect of statin therapy after colon cancer surgery. OBJECTIVE:This study aimed to evaluate the association between statin therapy and the postoperative mortality following elective colon cancer surgery. DESIGN:This population-based cohort study is a retrospective analysis of prospectively collected data from the Swedish Colorectal Cancer Register. SETTINGS:Patient inclusion was achieved through a nationwide register. PATIENTS:All adult patients undergoing elective surgery for colon cancer between January 2007 and September 2016 were included in the study. Patients who had received and collected a prescription for statins pre- and postoperatively were allocated to the statin-positive cohort. MAIN OUTCOME MEASURES:The primary and secondary outcomes of interest were 90-day all-cause mortality and 90-day cause-specific mortality. RESULTS:A total of 22,337 patients underwent elective surgery for colon cancer during the study period, of whom 6,494 (29%) were classified as statin users. Statin users displayed a significant survival benefit despite being older, having a higher comorbidity burden, and being less fit for surgery. Multivariate analysis illustrated significant reductions in the incidence risk for 90-day all-cause mortality (Incidence Rate Ratio = 0.12, p < 0.001) as well as 90-day cause-specific deaths due to sepsis, due to multiorgan failure, or resulting from a cardiovascular and respiratory origin. LIMITATIONS:The limitations of this study include its observational retrospective design, restricting the ability to perform standardized follow-up of statin therapy. Confounding from other uncontrolled variables cannot be excluded. CONCLUSIONS:Statin users had a significant postoperative benefit regarding short-term mortality following elective colon cancer surgery in the current study; however, further research is needed to ascertain whether this relationship is causal. See Video Abstract at http://links.lww.com/DCR/B738. LA TERAPIA CON ESTATINAS SE ASOCIA CON UNA DISMINUCIN DE LA MORTALIDAD POSOPERATORIA A LOS DAS DESPUS DE LA CIRUGA DE CNCER DE COLON:ANTECEDENTES:Ha habido informes contradictorios con respecto al efecto protector de la terapia con estatinas después de la cirugía de cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar la asociación entre la terapia con estatinas y la mortalidad postoperatoria después de la cirugía electiva por cáncer de colon.DISEÑO:Este estudio de cohorte poblacional es un análisis retrospectivo de datos recopilados prospectivamente del Registro Sueco de Cáncer Colorrectal.AJUSTES:La inclusión de pacientes se logró mediante la inclusión a través de un registro a nivel nacional.PACIENTES:Se incluyeron en el estudio todos los pacientes adultos sometidos a cirugía electiva por cáncer de colon en el período de enero de 2007 y septiembre de 2016. Los pacientes que habían recibido y recogido una receta de estatinas antes y después de la operación fueron asignados a la cohorte positiva de estatinas.PRINCIPALES MEDIDAS DE DESENLACES:Los desenlaces primarios y secundarios de interés fueron la mortalidad por cualquier causa a los 90 días y la mortalidad por causas específicas a los 90 días.RESULTADOS:Un total de 22.337 pacientes se sometieron a cirugía electiva por cáncer de colon durante el período de estudio, de los cuales 6.494 (29%) se clasificaron como usuarios de estatinas. Los usuarios de estatinas mostraron un beneficio significativo en la supervivencia a pesar de ser mayores, de tener una mayor carga de comorbilidad y de estar menos acondicionado para la cirugía. El análisis multivariado ilustró reducciones significativas en el riesgo de incidencia de mortalidad por cualquier causa a 90 días (índice de tasa de incidencia = 0,12, p < 0,001), así como muertes específicas ena 90 días debidas a sepsis, falla multiorgánica o dea enfermedades de origen cardiovascular y respiratorio.LIMITACIONES:Las limitaciones de este estudio incluyen su diseño observacional retrospectivo, que restringe la capacidad de realizar un seguimiento estandarizado de la terapia con estatinas. No se puede excluir confusión a partir de otras variables no controladas.CONCLUSIONES:Los usuarios de estatinas tuvieron un beneficio posoperatorio significativo con respecto a la mortalidad a corto plazo después de cirugía electiva por cáncer de colon en el estudio actual, sin embargo, se necesita más investigación para confirmar si eexiste una relación es causal. Consulte Video Resumen en http://links.lww.com/DCR/B738.
10.1097/DCR.0000000000001933
MRI at Restaging After Neoadjuvant Therapy for Rectal Cancer Overestimates Circumferential Resection Margin Proximity as Determined by Comparison With Whole-Mount Pathology.
Diseases of the colon and rectum
BACKGROUND:Current guidelines recommend restaging with MRI after neoadjuvant therapy for rectal cancer, but the accuracy of restaging MRI in estimating circumferential margin involvement requires additional clarification. OBJECTIVE:The objective of this study was to measure the accuracy of circumferential resection margin assessment by MRI after neoadjuvant therapy and identify characteristics associated with accuracy. DESIGN:MRI data were retrospectively analyzed for concordance with the findings of whole-mount pathology analysis of the corresponding surgical specimens. Univariate and multivariate logistic regression analyses were performed to identify characteristics associated with accuracy. SETTING:This study was conducted at a comprehensive cancer center. PATIENTS:Included in the study were consecutive patients who underwent total mesorectal excision for rectal cancer between January 2018 and March 2020 after receiving neoadjuvant therapy and undergoing restaging with MRI. MAIN OUTCOME MEASURES:The primary outcome of this study included accuracy, sensitivity, specificity, and positive and negative predictive values for categorizing the circumferential resection margin as threatened; mean and paired mean differences were in proximity of the margin. RESULTS:Of the 94 patients included in the analysis, 39 (41%) had a threatened circumferential resection margin according to MRI at restaging, but only 17 (18%) had a threatened margin based on pathology. The accuracy of MRI in identifying a threatened margin was 63.8%, with margin proximity overestimated by 0.4 cm on average. In multivariate logistic regression, anterior location of the margin and tumor proximity to the anal verge were independently associated with reduced MRI accuracy. LIMITATIONS:A limitation was the retrospective design at a single institution. CONCLUSIONS:The knowledge that MRI-based restaging after neoadjuvant therapy overestimates circumferential margin proximity may render some surgical radicality unnecessary and thereby help avoid the associated morbidity. With the recognition that MRI-based assessment of margin proximity may not be reliable for anterior margin and for distal tumors, radiologists may want to use greater caution in interpreting images of tumors with these characteristics and to acknowledge the uncertainty in their reports. See Video Abstract at http://links.lww.com/DCR/B814. LA IRM EN LA REESTADIFICACIN LUEGO DE TERAPIA NEOADYUVANTE EN EL CNCER DE RECTO SOBRESTIMA LA PROXIMIDAD DEL MARGEN DE RESECCIN CIRCUNFERENCIAL SEGN LO DETERMINADO COMPARATIVAMENTE CON LA PIEZA DE ANATOMOPATOLOGA:ANTECEDENTES:Las pautas actuales recomiendan la re-estadificación por medio de la resonancia magnética luego de terapia neoadyuvante en los casos de cáncer de recto, pero la precisión de la reevaluación con la IRM para estimar el grado de implicación del margen circunferencial requiere aclaraciones adicionales.OBJETIVO:Medir el grado de exactitud en la evaluación del margen de resección circunferencial mediante resonancia magnética después de la terapia neoadyuvante e identificar las características asociadas con la precisión.DISEÑO:Se analizaron retrospectivamente los datos de resonancia magnética para determinar la concordancia entre los hallazgos del análisis de la pieza de anatamopatología y las muestras quirúrgicas correspondientes. Se realizó el análisis de regresión logística univariada y multivariada para identificar las características asociadas con la exactitud.AJUSTE:Centro oncológico integral.PACIENTES:Todos aquellos que se sometieron consecutivamente a una excisión total del mesorrecto por cáncer rectal entre Enero 2018 y Febrero 2020 luego de recibir terapia neoadyuvante y someterse a una re-estadificación por imágenes de resonancia magnética (IRM).PRINCIPALES MEDIDAS DE RESULTADO:La exactitud, la sensibilidad y especificidad; los valores predictivos positivos y negativos para categorizar el margen de resección circunferencial como amenazado; la diferencia media y las medias pareadas de proximidad a los margenes.RESULTADOS:De los 94 pacientes incluidos en el análisis, 39 (41%) tenían un margen de resección circunferencial amenazado según la resonancia magnética en la re-estadificación, pero solo 17 (18%) tenían un margen amenazado basado en la patología. La precisión de la resonancia magnética para identificar un margen amenazado fue del 63,8%, con la proximidad del margen sobreestimada en 0,4 cm en promedio. En la regresión logística multivariada, la ubicación anterior de los bordes de resección y la proximidad del tumor al margen anal se asociaron de forma independiente con la reducción en la precisión de la resonancia magnética.LIMITACIONES:Diseño retrospectivo en una institución única.CONCLUSIONES:El saber que la re-estadificación basada en la IRM, luego de terapia neoadyuvante sobreestima la proximidad de la lesión a los márgenes circunferenciales, hace innecesaria cierta radicalidad quirúrgica complementaria, lo que ayuda a evitar morbilidad asociada. Reconociendo que la evaluación de proximidad de los márgenes de resección basada en la resonancia magnética, no puede ser confiable en casos de márgenes anteriores y en casos de tumores distales. Los radiólogos recomiendan tener más precaución en la interpretación de imágenes de tumores con estas características y reconocen cierto desasosiego en sus informes. Consulte Video Resumen en http://links.lww.com/DCR/B814.
10.1097/DCR.0000000000002145
Is High-Grade Tumor Budding an Independent Prognostic Factor in Stage II Colon Cancer?
Diseases of the colon and rectum
BACKGROUND:Risk factors, including lymphatic, vascular, and perineural invasion, are considered indications for adjuvant treatment in stage II colon cancer. However, tumor budding is not included in the above risk factors. OBJECTIVE:This study aimed to assess the value of tumor budding as a prognostic factor in stage II colon cancer. DESIGN:This is a retrospective cohort study. SETTINGS:This study was conducted in a tertiary referral center. PATIENTS:This study examined 1390 patients with stage II colon cancer who received curative resection from 2007 to 2013 at an institution. INTERVENTIONS:These patients were classified according to tumor budding status: low-grade tumor budding (less than 10 buds) and high-grade tumor budding (10 buds or more). Differences between the 2 groups were corrected by propensity score matching. MAIN OUTCOME MEASURES:Disease-free survival and overall survival were the primary end points. RESULTS:Among 1390 patients, 146 (10.5%) had high-grade tumor budding. The high-grade tumor budding group showed adverse histological characteristics such as advanced T stage, histological grade of differentiation, and presence of lymphatic/perineural invasion. After matching, the 5-year disease-free survival rate for the high-grade tumor budding group was significantly lower than for the low-grade group. We also compared survival outcomes according to tumor budding grade for patients who did not have risk factors and did not receive adjuvant treatment. The 5-year overall survival was similar between the 2 groups. However, the 5-year disease-free survival decreased significantly in the high-grade tumor budding group than in the low-grade tumor budding group. LIMITATIONS:This was a retrospective study with a single-center design. CONCLUSIONS:High-grade tumor budding is a poor prognostic factor in stage II colon cancer and is considered one of the risk factors for adjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B962 . ES LA GEMACIN TUMORAL UN FACTOR PRONSTICO INDEPENDIENTE EN EL CNCER DE COLON EN ESTADIO II:ANTECEDENTES:Los factores de riesgo, incluida la invasión linfática/vascular/perineural, se consideran indicaciones para el tratamiento adyuvante en el cáncer de colon en estadio II. Sin embargo, la gemación tumoral (desdiferenciación tumoral aislada), no está incluida en los factores de riesgo anteriores.OBJETIVO:El objeto de este estudio fue evaluar el valor de la gemación tumoral como factor pronóstico en el cáncer de colon en estadio II.DISEÑO:Este es un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un centro de referencia terciario.PACIENTES:Este estudio analizó 1390 pacientes con cáncer de colon en estadio II que recibieron una resección curativa entre 2007 y 2013 en una institución.INTERVENCIONES:Estos pacientes se clasificaron según el estado de gemación tumoral: gemación tumoral de bajo grado (<10 yemas) y gemación tumoral de alto grado (≥10 yemas). Las diferencias entre los dos grupos se corrigieron mediante el emparejamiento por puntaje de propensión.PRINCIPALES MEDIDAS DE VALORACIÓN:La supervivencia libre de enfermedad y la supervivencia global fueron los puntos finales primarios.RESULTADOS:Entre 1.390 pacientes, 146 (10,5%) tenían brotes tumorales de alto grado. El grupo de gemación tumoral de alto grado mostró características histológicas adversas como estadio T avanzado, grado histológico de diferenciación y presencia de invasión linfática/perineural. Después del emparejamiento, la tasa de supervivencia libre de enfermedad a cinco años para el grupo de brotes de tumores de alto grado fue significativamente menor que para el grupo de bajo grado. También comparamos los resultados de supervivencia según el grado de gemación del tumor para pacientes que no tenían factores de riesgo y que no recibieron tratamiento adyuvante. La supervivencia global a cinco años fue similar entre los dos grupos. Sin embargo, la supervivencia libre de enfermedad a cinco años disminuyó significativamente en el grupo de brotes de tumores de alto grado que en el grupo de brotes de tumores de bajo grado.LIMITACIONES:Este fue un estudio retrospectivo con un diseño de centro único.CONCLUSIÓNES:La gemación tumoral de alto grado es un factor de mal pronóstico en el cáncer de colon estadio II y se considera uno de los factores de riesgo para el tratamiento adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B962 . (Traducción-Dr. Ingrid Melo ).
10.1097/DCR.0000000000002345
Neoadjuvant Immune Checkpoint Inhibition Improves Organ Preservation in T4bM0 Colorectal Cancer With Mismatch Repair Deficiency: A Retrospective Observational Study.
Diseases of the colon and rectum
BACKGROUND:Colorectal cancer with mismatch repair deficiency is usually less aggressive and associated with a lower risk of distant metastasis. Immune checkpoint inhibition, rather than traditional chemoradiotherapy, has shown great advantages in treating such patients. OBJECTIVE:This study aimed to verify the hypothesis that locally very advanced (T4b) colorectal cancer without distant metastases might present with higher probability of mismatch repair deficiency and be more sensitive to neoadjuvant immune checkpoint inhibition. DESIGN:This study was designed as a single-center retrospective observational study. SETTINGS:The study was conducted in a tertiary referral center in China. PATIENTS:The study included patients who were clinically diagnosed with T4bM0 colorectal cancer from 2008 to 2019. MAIN OUTCOME MEASURES:Clinicopathological characteristics, mismatch repair status, and survival outcomes of patients with mismatch repair deficiency were analyzed. RESULTS:A total of 268 patients were included. The incidence of patients with mismatch repair deficiency in the T4bM0 population was 27.6% (75/268), with 84.0% (63/75) in the colon and 16.0% (12/75) in the rectum. For tumors located in the proximal colon, 45.0% (50/111) exhibited mismatch repair deficiency, whereas the incidence of mismatch repair deficiency in sigmoid colon cancer and rectal cancer was only 15.9% (25/157). Neoadjuvant immune checkpoint inhibition significantly reduced the open surgery rate ( p = 0.000) and multivisceral resection rate ( p = 0.025). The pathological complete remission rate in the neoadjuvant immune checkpoint inhibition group was significantly higher than that in neoadjuvant chemoradiotherapy/chemotherapy group (70.0% vs 0%; p = 0.004). No tumor downstaging was observed after neoadjuvant chemotherapy. Neoadjuvant immune checkpoint inhibition provided significantly better disease-free survival ( p = 0.0078) and relatively longer overall survival ( p = 0.15) than other groups. LIMITATIONS:This study is limited by the possible selection bias and small sample size. CONCLUSIONS:Our data depicted the high incidence of mismatch repair deficiency in T4bM0 mismatch repair deficiency and the effectiveness of the neoadjuvant immune checkpoint inhibition group in organ preservation. Precision oncology requires identification of the protein status of mismatch repair at initial diagnosis to make a rational treatment decision for these patients. See Video Abstract at http://links.lww.com/DCR/B952 . LA INHIBICIN DEL PUNTO DE CONTROL INMUNITARIO NEOADYUVANTE MEJORA LA PRESERVACIN DE RGANOS EN EL CNCER COLORRECTAL TBM CON DEFICIENCIA DE REPARACIN DE ERRORES DE COINCIDENCIA UN ESTUDIO OBSERVACIONAL RETROSPECTIVO:ANTECEDENTES:Los pacientes con cáncer colorrectal con deficiencia en la reparación de desajustes suelen (dMMR) ser menos agresivos y se asocian con un menor riesgo de metástasis a distancia. La inhibición del punto de control inmunitario, en lugar de la quimiorradioterapia tradicional, ha mostrado grandes ventajas en el tratamiento de estos pacientes.OBJETIVO:Este estudio tuvo como objetivo verificar nuestra hipótesis de que el CCR localmente muy avanzado (T4b) sin metástasis a distancia podría presentarse con una mayor probabilidad de dMMR y ser más sensible a la inhibición del punto de control inmunitario neoadyuvante.DISEÑO:Este estudio fue diseñado como un estudio observacional retrospectivo de un solo centro.CONFIGURACIÓN:El estudio se realizó en un centro de referencia terciario en China.PACIENTES:Se incluyeron pacientes con diagnóstico clínico de CCR T4bM0 desde 2008 hasta 2019.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron las características clinicopatológicas, el estado de MMR y los resultados de supervivencia de los pacientes con dMMR.RESULTADOS:Se incluyeron un total de 268 pacientes. La incidencia de dMMR en la población T4bM0 fue del 27,6% (75/268), con un 84,0% (63/75) en colon y un 16,0% (12/75) en recto. Para los tumores ubicados en el colon proximal, el 45,0% (50/111) exhibió dMMR, mientras que la incidencia de dMMR en el cáncer de colon sigmoideo y el cáncer de recto fue solo del 15,9% (25/157). La inhibición del punto de control inmunitario neoadyuvante redujo significativamente la cirugía abierta y la tasa de resección multivisceral ( p = 0,000 y p = 0,025, respectivamente). La tasa de PCR en el grupo de inhibición del punto de control inmunitario neoadyuvante fue significativamente mayor que en el grupo de quimiorradioterapia/quimioterapia neoadyuvante (70,0% frente a 0%, p = 0,004). No se observó reducción del estadio del tumor después de la quimioterapia neoadyuvante. La inhibición del punto de control inmunitario neoadyuvante proporcionó una supervivencia sin enfermedad significativamente mejor ( p = 0,0078) y una supervivencia general relativamente más larga ( p = 0,15) que otros grupos.LIMITACIONES:Este estudio está limitado por el posible sesgo de selección y el pequeño tamaño de la muestra.CONCLUSIONES:Nuestros datos representan la alta incidencia de dMMR en T4bM0 CRC y la eficacia del grupo de inhibición del punto de control inmunitario neoadyuvante en la preservación de órganos. La oncología de precisión requiere la identificación del estado de la proteína MMR en el diagnóstico inicial para tomar una decisión de tratamiento racional para estos pacientes especiales. Consulte el Video Resumen en http://links.lww.com/DCR/B952 . (Traducción-Dr. Yesenia Rojas-Khalil ).
10.1097/DCR.0000000000002466
Cost Consequences of Age and Comorbidity in Accelerated Postoperative Discharge After Colectomy.
Diseases of the colon and rectum
BACKGROUND:Prospective payment models have incentivized reductions in length of stay after surgery. The benefits of abbreviated postoperative hospitalization could be undermined by increased readmissions or postacute care use, particularly for older adults or those with comorbid conditions. OBJECTIVE:The purpose of this study was to determine whether hospitals with accelerated postsurgical discharge accrue total episode savings or incur greater postdischarge payments among patients stratified by age and comorbidity. DESIGN:This was a retrospective cross-sectional study. SETTING:National data from the 100% Medicare Provider Analysis and Review files for July 2012 to June 2015 were used. PATIENTS:We included Medicare beneficiaries undergoing elective colectomy and stratified the cohort by age (65-69, 70-79, ≥80 y) and Elixhauser comorbidity score (low: ≤0; medium: 1-5; and high: >5). Patients were categorized by the hospital's mode length of stay, reflecting "usual" care. MAIN OUTCOMES MEASURES:In a multilevel model, we compared mean total episode payments and components thereof among age and comorbidity categories, stratified by hospital mode length of stay. RESULTS:Among 88,860 patients, mean total episode payments were lower in shortest versus longest length of stay hospitals across all age and comorbidity strata and were similar between age groups (65-69 y: $28,951 vs $30,566, p = 0.014; 70-79 y: $31,157 vs $32,044, p = 0.073; ≥80 y: $33,779 vs $35,771, p = 0.005) but greater among higher comorbidity (low: $23,107 vs $24,894, p = 0.001; medium: $30,809 vs $32,282, p = 0.038; high: $44,097 vs $46641, p < 0.001). Postdischarge payments were similar among length-of-stay hospitals by age (65-69 y: ∆$529; 70-79 y: ∆$291; ≥80 y: ∆$872, p = 0.25) but greater among high comorbidity (low: ∆$477; medium: ∆$480; high: ∆$1059; p = 0.02). LIMITATIONS:Administrative data do not capture patient-level factors that influence postacute care use (preference, caregiver availability). CONCLUSIONS:Hospitals achieving shortest length of stay after surgery accrue lower total episode payments without a compensatory increase in postacute care spending, even among patients at oldest age and with greatest comorbidity. See Video Abstract at http://links.lww.com/DCR/B624. CONSECUENCIAS DE LA EDAD Y LAS COMORBILIDADES ASOCIADAS, EN EL COSTO DE LA ATENCIN EN PACIENTES SOMETIDOS A COLECTOMA EN PROGRAMAS DE ALTA POSOPERATORIA ACELERADA:ANTECEDENTES:Los modelos de pago prospectivo, han sido un incentivo para reducir la estancia hospitalaria después de la cirugía. Los beneficios de una hospitalización posoperatoria "abreviada" podrían verse afectados por un aumento en los reingresos o en la necesidad de cuidados postoperatorios tempranos luego del periodo agudo, particularmente en los adultos mayores o en aquellos con comorbilidades.OBJETIVO:Determinar si los hospitales que han establecido protocolos de alta posoperatoria "acelerada" generan un ahorro en cada episodio de atención o incurren en mayores gastos después del alta, entre los pacientes estratificados por edad y por comorbilidades.DISEÑO:Estudio transversal retrospectivo.AJUSTE:Revisión a partir de la base de datos nacional del 100% de los archivos del Medicare Provider Analysis and Review desde julio de 2012 hasta junio de 2015.PACIENTES:Se incluye a los beneficiarios de Medicare a quienes se les practicó una colectomía electiva. La cohorte se estratificó por edad (65-69 años, 70-79, ≥80) y por la puntuación de comorbilidad de Elixhauser (baja: ≤0; media: 1-5; y alta: > 5). Los pacientes se categorizaron de acuerdo con la modalidad de la duración de la estancia hospitalaria del hospital, lo que representa lo que se considera es una atención usual para dicho centro.PRINCIPALES MEDIDAS DE RESULTADO:En un modelo multinivel, comparamos la media de los pagos por episodio y los componentes de los mismos, entre las categorías de edad y comorbilidad, estratificados por la modalidad de la duración de la estancia hospitalaria.RESULTADOS:En los 88,860 pacientes, los pagos promedio por episodio fueron menores en los hospitales con una modalidad de estancia más corta frente a los de mayor duración, en todos los estratos de edad y comorbilidad, y fueron similares entre los grupos de edad (65-69: $28,951 vs $30,566, p = 0,014; 70-79: $31,157 vs $32,044, p = 0,073; ≥ 80 $33,779 vs $35,771, p = 0,005), pero mayor entre los pacientes con comorbilidades más altas (baja: $23,107 vs $24,894, p = 0,001; media $30,809 vs $32,282, p = 0,038; alta: $44,097 vs $46,641, p <0,001). Los pagos generados luego del alta hospitalaria fueron similares con relación a la estancia hospitalaria de los diferentes hospitales con respecto a la edad (65-69 años: ∆ $529; 70-79 años: ∆ $291; ≥80 años: ∆ $872, p = 0,25), pero mayores en aquellos con más alta comorbilidad (baja ∆ $477, medio ∆ $480, alto ∆ $1059, p = 0,02).LIMITACIONES:Las bases de datos administrativas no capturan los factores del paciente que influyen en el cuidado luego del estado posoperatorio agudo (preferencia, disponibilidad del proveedor del cuidado).CONCLUSIONES:Los hospitales que logran una estancia hospitalaria más corta después de la cirugía, acumulan pagos más bajos por episodio, sin un incremento compensatorio del gasto en la atención pos-aguda, incluso entre pacientes de mayor edad y con mayor comorbilidad. Consulte Video Resumen en http://links.lww.com/DCR/B624. (Traducción-Dr Eduardo Londoño-Schimmer).
10.1097/DCR.0000000000002020
Effect of Tumor Location on Outcome After Laparoscopic Low Rectal Cancer Surgery: A Propensity Score Matching Analysis.
Diseases of the colon and rectum
BACKGROUND:Dissection of the distal anterolateral aspect of the mesorectum remains a surgical challenge for low rectal cancer, posing a higher risk of residual mesorectum, which might lead to the increased incidence of local recurrence for patients with anterior wall involvement. OBJECTIVE:This study aimed to assess the effect of tumor location on outcome after laparoscopic low rectal cancer surgery. DESIGN:This is a single-center, retrospective study. SETTINGS:The study was conducted at West China Hospital in China. PATIENTS:Patients with low rectal cancer who underwent laparoscopic total mesorectal excision from 2011 to 2016 were enrolled. Patients were divided into anterior and nonanterior groups according to tumor location. Propensity score matching analysis was used to reduce the selection bias. MAIN OUTCOME MEASURES:The primary end point was local recurrence. The secondary end points included overall survival, disease-free survival, and the positive rate of circumferential resection margin. RESULTS:A total of 404 patients were included, and 176 pairs were generated by propensity score matching analysis. Multivariate analysis showed that anterior location was an independent risk factor of local recurrence (HR, 12.6; p = 0.006), overall survival (HR, 3.0; p < 0.001), and disease-free survival (HR, 2.3; p = 0.001). For patients with clinical stage II/III or T3/4, anterior location remained a prognostic factor for higher local recurrence and poorer survival. Local recurrence was rare in patients with clinical stage II/III (1.4%) or T3/4 (1.5%) tumors that were not located anteriorly. LIMITATIONS:This study was limited by its retrospective nature. CONCLUSIONS:Anterior location is an independent risk factor of local recurrence, overall survival, and disease-free survival for low rectal cancer. More strict and selective use of neoadjuvant therapy should be considered for patients who have clinical stage II/III or T3/4 tumors that are not located anteriorly. A larger cohort study is warranted to validate the prognostic role of anterior location for low rectal cancer. See Video Abstract at http://links.lww.com/DCR/B622. IMPACTO DE LA LOCALIZACIN DEL TUMOR EN EL RESULTADO POSTERIOR A CIRUGA LAPAROSCPICA DE CNCER DE RECTO INFERIOR UN PUNTAJE DE PROPENSIN POR ANLISIS DE CONCORDANCIA:ANTECEDENTES:La disección de la cara anterolateral distal del mesorrecto sigue siendo un desafío quirúrgico en el cáncer de recto inferior, constituyendo un alto riesgo de mesorrecto residual, que podría ocasionar una mayor incidencia de recurrencia local en pacientes con compromiso de la pared anterior.OBJETIVO:El objetivo del estudio fue evaluar el efecto de la localización del tumor en el resultado posterior a la cirugía laparoscópica de cáncer de recto inferior.DISEÑO:Estudio restrospectivo de un único centro.ÁMBITO:El estudio se realizó en el West China Hospital en China.PACIENTES:Pacientes con cáncer de recto inferior que se sometieron a excisión mesorrectal total laparoscópica entre 2011 y 2016. Los pacientes se dividieron en grupos, anterior y no anterior, según la localización del tumor. Se utilizó un puntaje de propensión por análisis de concordancia para reducir el sesgo de selección.PRINCIPALES VARIABLES EVALUADAS:El objetivo principal fue la recurrencia local. Los objetivos secundarios incluyeron la sobrevida global, la sobrevida libre de enfermedad y la tasa de positividad del margen de resección circunferencial.RESULTADOS:Se incluyeron un total de 404 pacientes y se generaron 176 pares mediante un puntaje de propensión por análisis de concordancia. El análisis multivariado mostró que la localización anterior era un factor de riesgo independiente de recidiva local (HR = 12,6, p = 0,006), sobrevida global (HR = 3,0, p <0,001) y sobrevida libre de enfermedad (HR = 2,3, p = 0,001). En pacientes con estadio clínico II /III o T3/4, la ubicación anterior continuó como un factor pronóstico para una mayor recurrencia local y una menor sobrevida. La recidiva local fue excepcional en pacientes con tumores en estadio clínico II / III (1,4%) o T3 / 4 (1,5%) que no estaban localizados hacia anterior.LIMITACIONES:Este estudio estuvo limitado por su carácter retrospectivo.CONCLUSIONES:La localización anterior es un factor de riesgo independiente de recidiva local, sobrevida global y sobrevida libre de enfermedad para el cáncer de recto inferior. Se debe considerar un uso más estricto y selectivo de la terapia neoadyuvante para pacientes en estadio clínico II / III o T3 /4 de tumores que no se localizan hacia anterior. Se justifica un estudio de cohorte más grande para validar el impacto pronóstico de una ubicación anterior del cáncer de recto inferior. Consulte Video Resumen en http://links.lww.com/DCR/B622. (Traducción-Dr. Lisbeth Alarcon-Bernes).
10.1097/DCR.0000000000001965
Mid-transverse Location in Primary Colon Tumor: A Poor Prognostic Factor?
Diseases of the colon and rectum
BACKGROUND:The location of colonic tumors has been linked to different clinical and oncologic outcomes. Transverse colon cancers are generally included as right colon cancers. Furthermore, hepatic and splenic flexure tumors are usually included as components of the transverse colon. OBJECTIVE:This study was aimed at comparing the clinicopathologic characteristics and long-term outcomes between mid-transverse and right and left colon cancers and determining the prognostic impact of the primary tumor location in the mid-transverse colon. DESIGN:This was a retrospective study. SETTINGS:Two specialized colorectal centers were included. PATIENTS:Patients who underwent curative surgery for colon cancer were analyzed. Tumors located in the transverse colon, excluding the flexures, were defined as mid-transverse colon cancers. MAIN OUTCOME MEASURES:Demographic characteristics, operative outcomes, pathologic results, and long-term outcomes were the primary outcome measures. RESULTS:Of the 487 patients, 41 (8.4%) had mid-transverse, 191 (39.2%) had right, and 255 (52.4%) had left colon cancers. For mid-transverse colon cancers, the mean length of hospital stay, mean length of the resected specimen, and the mean number of harvested lymph nodes were significantly higher. For patients with stage I to III cancer, the 5-year overall and disease-free survival rates were significantly worse in the mid-transverse colon cancers than in the right and left colon cancers (overall survival: 55.5% vs 82.8% vs 85.9%, p = 0.004, and disease-free survival; 47.7% vs 72.4% vs 79.5%, p = 0.003). After adjustment for other clinicopathologic factors, mid-transverse colon cancers were significantly associated with a poor prognosis (HR = 2.19 [95% CI, 1.25-3.83]; p = 0.006). LIMITATIONS:Molecular and genetic information were unavailable in this retrospective study. CONCLUSIONS:In our case series, colon cancers located in the mid-transverse colon showed poorer prognosis than cancers in other locations. The impact of tumor location in the mid-transverse colon on prognosis, including molecular and genetic markers, should be investigated further in prospective studies. See Video Abstract at http://links.lww.com/DCR/B631. LOCALIZACIN TRANSVERSA MEDIA EN EL TUMOR DE COLON PRIMARIO UN FACTOR DE MAL PRONSTICO:ANTECEDENTES:La ubicación de los tumores de colon se ha relacionado con diferentes resultados clínicos y oncológicos. Los cánceres de colon transverso se incluyen generalmente como cánceres de colon derecho. Además, los tumores del ángulo hepático y esplénico suelen incluirse como un componente del colon transverso.OBJETIVO:Este estudio tuvo como objetivo comparar las características clínico-patológicas y los resultados a largo plazo entre los cánceres de colon transverso medio y derecho e izquierdo y determinar el impacto pronóstico de la ubicación del tumor primario en el colon transverso medio.DISEÑO:Este fue un estudio retrospectivo.AJUSTE ENTORNO CLINICO:Se incluyeron dos centros colorrectales especializados.PACIENTES:Se analizaron los pacientes que fueron sometidos a cirugía curativa por cáncer de colon. Los tumores ubicados en el colon transverso, excluidos los ángulos, se definieron como "cánceres de colon transverso medio".PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:Las características demográficas, los resultados quirúrgicos, los resultados patológicos y los resultados a largo plazo fueron las principales medidas de resultado valoracion.RESULTADOS:De los 487 pacientes, 41 (8,4%) tenían cáncer de colon transverso medio, 191 (39,2%) derecho y 255 (52,4%) cáncer de colon izquierdo. Para los cánceres de colon transverso medio, la duración media de la estancia hospitalaria, la duración de la muestra resecada y el número medio de ganglios linfáticos extraídos fueron significativamente mayores. Para los pacientes en estadio I-III, las tasas de supervivencia general y sin enfermedad a 5 años fueron significativamente peores en los cánceres de colon transverso medio que en los cánceres de colon derecho e izquierdo (supervivencia general: 55,5% frente versus a 82,8% frente versus a 85,9%, p = 0,004 y supervivencia libre de enfermedad; 47,7% frente a 72,4% frente a 79,5%, p = 0,003, respectivamente). Después del ajuste por otros factores clínico-patológicos, los cánceres de colon transverso medio se asociaron significativamente con un pronóstico desfavorable (Razón de riesgo: 2,19; intervalo de confianza del 95%: 1,25-3,83; p = 0,006).LIMITACIONES:La información molecular y genética no estuvo disponible en este estudio retrospectivo.CONCLUSIONES:En nuestra serie de casos, los cánceres de colon localizados en el colon transverso medio mostraron un peor pronóstico que los cánceres en otras localizaciones. El impacto de la ubicación del tumor en el colon transverso medio sobre el pronóstico, incluidos los marcadores moleculares y genéticos, debe investigarse más a fondo en estudios prospectivos. Consulte Video Resumen en http://links.lww.com/DCR/B631. (Traducción-Dr Adrián Ortega).
10.1097/DCR.0000000000002083
Application of Multigene Panel Testing in Patients With High Risk for Hereditary Colorectal Cancer: A Descriptive Report Focused on Genotype-Phenotype Correlation.
Diseases of the colon and rectum
BACKGROUND:The genetic test solely based on the clinical features of hereditary colorectal cancer has limitations in clinical practice. OBJECTIVE:This study aimed to analyze the results of comprehensive multigene panel tests based on clinical findings. DESIGN:This was a cross-sectional study based on a prospectively compiled database. SETTING:The study was conducted at a tertiary hospital. PATIENTS:A total of 381 patients with high risk for hereditary colorectal cancer syndromes were enrolled between March 2014 and December 2019. MAIN OUTCOME MEASURES:The primary outcome was to describe the mutational spectrum based on genotype-phenotype concordance and discordance. RESULTS:Germline mutations were identified in 89 patients for polyposis hereditary colorectal cancer genes (76 in APC; 4 in PTEN; 4 in STK11; 3 in BMPR1A; 1 in POLE; 1 in POLD1), 89 patients for nonpolyposis hereditary colorectal cancer genes (41 in MLH1; 40 in MSH2; 6 in MSH6; and 2 in PMS2), and 12 patients for other cancer predisposition genes (1 in ATM; 2 in BRCA1; 1 in BRCA2; 1 in BRIP1; 1 in MLH3; 1 in NBN; 1 in PMS1; 1 in PTCH1; 1 in TP53; and 2 in monoallelic MUTYH). If we had used direct sequencing tests of 1 or 2 major genes based on phenotype, 48 (25.3%) of 190 mutations would not have been detected due to technical differences (12.1%), less frequent genotype (4.2%), unclear phenotype (3.7%), and genotype-phenotype discordance (4.7%). The genotype-phenotype discordance is probably linked to compound heterozygote, less distinctive phenotype, and insufficient information for colorectal cancer risk. LIMITATIONS:This study included a small number of patients with insufficient follow-up duration. CONCLUSIONS:A comprehensive multigene panel is expected to identify more genetic mutations than phenotype-based direct sequencing, with special utility for unclear phenotype or genotype-phenotype discordance. See Video Abstract at http://links.lww.com/DCR/B844. APLICACIN DE PRUEBAS DE PANEL MULTIGNICO EN PACIENTES CON ALTO RIESGO DE CNCER COLORRECTAL HEREDITARIO INFORME DESCRIPTIVO ENFOCADO EN LA CORRELACIN GENOTIPOFENOTIPO:ANTECEDENTES:La prueba genética basada únicamente en la característica clínica del cáncer colorrectal hereditario tiene limitaciones en la práctica clínica.OBJETIVO:Este estudio tuvo como objetivo analizar el resultado de pruebas integrales de panel multigénico basadas en hallazgos clínicos.DISEÑO:Este fue un estudio transversal basado en una base de datos recopilada prospectivamente.AJUSTE:El estudio se realizó en un hospital terciario.PACIENTES:Se inscribió un total de 381 pacientes con alto riesgo de síndromes de cáncer colorrectal hereditario entre marzo del 2014 y diciembre del 2019.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue describir el espectro mutacional basado en la concordancia y discordancia genotipo-fenotipo.RESULTADOS:Se identificaron mutaciones de la línea germinal en 89 pacientes para genes de cáncer colorrectal hereditario con poliposis (76 en APC; 4 en PTEN; 4 en STK11; 3 en BMPR1A; 1 en POLE; 1 en POLD1), 89 pacientes para genes de CCR hereditario sin poliposis (41 en MLH1; 40 en MSH2; 6 en MSH6; y 2 en PMS2) y 12 pacientes por otro gen de predisposición al cáncer (1 en ATM; 2 en BRCA1; 1 en BRCA2; 1 en BRIP1; 1 en MLH3; 1 en NBN; 1 en PMS1; 1 en PTCH1; 1 en TP53; y 2 en MUTYH monoalélico). Si hubiéramos utilizado pruebas de secuenciación directa de uno o dos genes principales basados en el fenotipo, 48 (25,3%) de 190 mutaciones no se habrían detectado debido a diferencias técnicas (12,1%), genotipo menos frecuente (4,2%), fenotipo poco claro (3,7%) y discordancia genotipo-fenotipo (4,7%). La discordancia genotipo-fenotipo probablemente esté relacionada con el heterocigoto compuesto, el fenotipo menos distintivo y la información insuficiente para el riesgo de cáncer colorrectal.LIMITACIONES:Este estudio incluyó una pequeña cantidad de pacientes con una duración de seguimiento insuficiente.CONCLUSIONES:Se espera que un panel multigénico completo identifique más mutaciones genéticas que la secuenciación directa basada en el fenotipo, con especial utilidad para la discordancia de fenotipo o genotipo-fenotipo poco clara. Consulte Video Resumen en http://links.lww.com/DCR/B844. Traducción- Dr. Francisco M. Abarca-Rendon).
10.1097/DCR.0000000000002039
Short- and Long-term Outcomes After Laparoscopic Emergency Resection of Left-Sided Obstructive Colon Cancer: A Nationwide Propensity Score-Matched Analysis.
Diseases of the colon and rectum
BACKGROUND:The role of laparoscopy for emergency resection of left-sided obstructive colon cancer remains unclear, especially regarding impact on survival. OBJECTIVE:This study aimed to determine short- and long-term outcomes after laparoscopic versus open emergency resection of left-sided obstructive colon cancer. DESIGN:This observational cohort study compared patients who underwent laparoscopic emergency resection to those who underwent open emergency resection between 2009 and 2016 by using 1:3 propensity-score matching. Matching variables included sex, age, BMI, ASA score, previous abdominal surgery, tumor location, cT4, cM1, multivisceral resection, small-bowel distention on CT, and subtotal colectomy. SETTING:This was a nationwide, population-based study. PATIENTS:Of 2002 eligible patients with left-sided obstructive colon cancer, 158 patients who underwent laparoscopic emergency resection were matched with 474 patients who underwent open emergency resection. INTERVENTIONS:The intervention was laparoscopic versus open emergency resection. MAIN OUTCOME MEASURES:The main outcome measures were 90-day mortality, 90-day complications, permanent stoma, disease recurrence, overall survival, and disease-free survival. RESULTS:Intentional laparoscopy resulted in significantly fewer 90-day complications (26.6% vs 38.4%; conditional OR, 0.59; 95% CI, 0.39-0.87) and similar 90-day mortality. Laparoscopy resulted in better 3-year overall survival (81.0% vs 69.4%; HR, 0.54; 95% CI, 0.37-0.79) and disease-free survival (68.3% vs 52.3%; HR, 0.64; 95% CI, 0.47-0.87). Multivariable regression analyses of the unmatched 2002 patients confirmed an independent association of laparoscopy with fewer 90-day complications and better 3-year survival. LIMITATIONS:Selection bias was the limitation that cannot be completely ruled out because of the retrospective nature of this study. CONCLUSIONS:This population-based study with propensity score-matched analysis suggests that intentional laparoscopic emergency resection might improve outcomes in patients with left-sided obstructive colon cancer compared to open emergency resection. Management of those patients in the emergency setting requires proper selection for intentional laparoscopic resection if relevant expertise is available, thereby considering other alternatives to avoid open emergency resection (ie, decompressing stoma). See Video Abstract at http://links.lww.com/DCR/B972 . RESULTADOS A CORTO Y LARGO PLAZO DESPUS DE LA RESECCIN LAPAROSCPICA DE EMERGENCIA EN CNCER DE COLON IZQUIERDO OBSTRUCTIVO UN ANLISIS EMPAREJADO POR PUNTAJE DE PROPENSIN A NIVEL NACIONAL:ANTECEDENTES:El papel de la laparoscopia en la resección de emergencia en cáncer de colon izquierdo obstructivo sigue sin estar claro, especialmente con respecto al impacto en la supervivencia.OBJETIVO:El objetivo de este estudio fue determinar los resultados a corto y largo plazo después de la resección de emergencia laparoscópica versus abierta en cáncer de colon izquierdo obstructivo.DISEÑO:Estudio observacional de cohortes comparó pacientes que se sometieron a resección de laparoscópica de emergencia versus resección abierta de emergencia entre 2009 y 2016, mediante el uso de emparejamineto por puntaje de propensión 1: 3. Las variables emparejadas incluyeron sexo, edad, IMC, puntaje ASA, cirugía abdominal previa, ubicación del tumor, cT4, cM1, resección multivisceral, distensión del intestino delgado en la TAC y colectomía subtotal.ENTORNO CLINICO:A nivel nacional, basado en la población.PACIENTES:De 2002 pacientes elegibles con cáncer de colon izquierdo obstructivo, 158 pacientes con resección laparoscópica s de emergencia e emparejaron con 474 pacientes con resección abierta de emergencia.INTERVENCIONES:Resección laparoscópica de emergencia versus abierta.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la mortalidad a 90 días, complicaciones a 90 días, estoma permanente, recurrencia de la enfermedad, supervivencia general y supervivencia libre de enfermedad.RESULTADOS:La laparoscopia intencional dió como resultado significativamente menos complicaciones a los 90 días (26,6 % vs 38,4 %, cOR 0,59, IC del 95 %: 0,39-0,87) y una mortalidad similar a los 90 días. La laparoscopia resultó en una mejor supervivencia general a los 3 años (81,0 % vs 69,4 %, HR 0,54, IC del 95 % 0,37-0,79) y supervivencia libre de enfermedad (68,3 % vs 52,3 %, HR 0,64, IC del 95 % 0,47-0,87). Los análisis de regresión multivariable de los 2002 pacientes no emparejados confirmaron una asociación independiente de la laparoscopia con menos complicaciones a los 90 días y una mejor supervivencia a los 3 años.LIMITACIONES:El sesgo de selección no se puede descartar por completo debido a la naturaleza retrospectiva de este estudio.CONCLUSIONES:Estudio poblacional con análisis emparejado por puntaje de propensión sugiere que la resección laparoscópica de emergencia intencional podría mejorar los resultados a corto y largo plazo en pacientes con cáncer de colon izquierdo obstructivo en comparación con resección abierta de emergencia, lo que justifica la confirmación en estudios futuros. El manejo de esos pacientes en el entorno de emergencia requiere una selección adecuada para la resección laparoscópica intencional si se dispone de experiencia relevante, considerando así otras alternativas para evitar la resección abierta de emergencia (es decir, ostomia descompresiva). Consulte Video Resumen en http://links.lww.com/DCR/B972 . (Traducción- Dr. Francisco M. Abarca-Rendon & Dr. Fidel Ruiz Healy).
10.1097/DCR.0000000000002364
Specialization Reduces Costs Associated With Colon Cancer Care: A Cost Analysis.
Diseases of the colon and rectum
BACKGROUND:Colorectal surgeons have been reported to have superior outcomes to general surgeons in the management of colon cancer, but it is unclear whether this leads to a difference in costs associated with cancer care. OBJECTIVE:This study aimed to investigate whether colorectal surgeons versus general surgeons performing elective colectomies for colon cancer resulted in cost savings. DESIGN:A decision analysis model was built to evaluate the cost of care. One-way and Monte Carlo sensitivity analyses were performed to test the assumptions of the model. SETTING:Data for the model were taken from previously published studies. PATIENTS:This study included a simulated cohort of patients undergoing elective colectomy for colon cancer. MAIN OUTCOME MEASURES:Total cost of care from the societal and health care system perspectives. RESULTS:In the base case scenario, from the societal perspective, colectomy performed by a colorectal surgeon costs $38,798 during the 5-year window versus $46,571 when performed by a general surgeon (net savings, $7773). From the health care system perspective, surgery performed by a colorectal surgeon costs $25,125 versus surgery performed by a general surgeon, which costs $29,790 (net savings, $4665). In probabilistic sensitivity analyses, surgeries performed by colorectal surgeons were cost saving or equivalent to those performed by general surgeons in 997 of 1000 simulations in the societal perspective and 989 of 1000 simulations in the health care system perspective. Overall, this finding was primarily driven by differences in reported overall recurrence rates and patient loss of productivity. LIMITATIONS:The limitation of this study was reliance on published data, some of which included rectal cancer cases. CONCLUSIONS:In our decision analysis model, elective colectomies for colon cancer had lower associated costs when performed by colorectal versus general surgeons. See Video Abstract at http://links.lww.com/DCR/B974 . LA ESPECIALIZACIN REDUCE LOS COSTOS ASOCIADOS CON LA ATENCIN DEL CNCER DE COLON UN ANLISIS DE COSTOS:ANTECEDENTES: Se ha informado que los cirujanos colorrectales obtienen mejores resultados que los cirujanos generales en el tratamiento del cáncer de colon, pero no está claro si esto conduce a una diferencia en los costos asociados con la atención del cáncer.OBJETIVO: Investigar si los cirujanos colorrectales que realizan colectomías electivas para el cáncer de colon generaron ahorros de costos en comparación con los cirujanos generales.DISEÑO: Se construyó un modelo de análisis de decisiones para evaluar el costo de la atención. Se realizaron análisis de sensibilidad unidireccional y de Monte Carlo para probar los supuestos del modelo.AJUSTE: Los datos para el modelo se tomaron de estudios publicados previamente.PACIENTES: Una cohorte simulada de pacientes sometidos a colectomía electiva por cáncer de colon.PRINCIPALES MEDIDAS DE RESULTADO: Costo total de la atención y desde la perspectiva de la sociedad y del sistema de salud.RESULTADOS: El escenario del caso base incluyó suposiciones sobre las diferencias en los resultados, incluida la recurrencia general y local, el porcentaje de recurrencia operable, la mortalidad a los 30 días, la duración de la estadía, el porcentaje de cirugía mínimamente invasiva, las complicaciones y los costos asociados. En el escenario de caso base, desde la perspectiva social, la colectomía con un cirujano colorrectal costó $38 798 durante la ventana de cinco años, frente a $46 571 con un cirujano general (ahorros netos, $7 773). Desde la perspectiva del sistema de atención médica, la cirugía realizada por un cirujano colorrectal fue de $25 125 frente a $29 790 con la cirugía realizada por un cirujano general (ahorro neto, $4665). En los análisis de sensibilidad de probabilidad, los cirujanos colorrectales ahorraron costos o fueron equivalentes a los cirujanos generales en 997 de 1000 simulaciones en la perspectiva social y 989 de 1000 simulaciones en la perspectiva del sistema de salud. En general, este hallazgo se debió principalmente a las diferencias en las tasas de recurrencia generales informadas y la pérdida de productividad de los pacientes.LIMITACIONES: Dependencia de los datos publicados, algunos de los cuales incluyeron casos de cáncer de rectoCONCLUSIONES: En nuestro modelo de análisis de decisiones, las colectomías electivas por cáncer de colon tuvieron menores costos asociados cuando las realizaron cirujanos colorrectales versus generales. Consulte Video Resumen en http://links.lww.com/DCR/B974 . (Traducción-Dr Yolanda Colorado).
10.1097/DCR.0000000000002370