Recurrent Colorectal Cancer Research Articles

Impact of positron-emission tomography on the surgical treatment of locoregionally recurrent colorectal cancer

The effect of positron emission tomography (PET) on the surgical treatment of locoregionally recurrent colorectal cancer (LRRCRC) remains unclear and warrants further investigation. A total of 193 patients with LRRCRC were identified from a prospectively maintained institutional database, of whom 134 LRRCRCs were deemed resectable and underwent resection with curative intent, whereas the remaining 59 LRRCRCs were unresectable. Patients with resectable LRRCRC were further classified according to whether recurrence was detected solely by PET (n=35, PET-only group) or by a combination of computed tomography (CT)/magnetic resonance imaging (MRI) and PET (n=99, CT/MRI/PET group). Clinicopathologic features, operative morbidity/mortality, and overall survival were compared between the patient groups based on long-term follow-up for at least 5 years. Patients in the PET-only group tended to have less extensive organ resection (p=0.0074), less blood loss (p<0.0001), and shorter operation time and hospitalization (p<0.0001), but surgical complication and readmission rates were not significantly different (p>0.05) compared with the CT/MRI/PET group. Although the PET-only group had significantly higher R0 resection rate (80% vs. 54.55%, p=0.0079), they also had a higher risk (17.14% vs. 2.02%, p=0.0011) of sham operation. The estimated 5-year and 10-year survival rates significantly decreased in order (p<0.0001) from PET-only (85.71% and 57.98%) and CT/MRI/PET (41.41% and 15.93%) to unresectable group of patients (16.95% and 1.88%). Subset analysis of the CT/MRI/PET group indicated that PET improved surgical decision-making because 24 (24.2%) LRRCRCs that manifested on CT/MRI as equivocal lesions were later confirmed by PET as resectable recurrences, while 18 (19.4%) LRRCRCs that manifested on CT/MRI as resectable lesions were later diagnosed by PET as more disseminated unresectable recurrences and precluded futile surgery. PET alone can identify a subset (20.9%) of LRRCRCs with less tumor burden for timely surgery; PET in combination with CT/MRI can better define the resectability of LRRCRCs. The positive impacts of PET can translate into better surgical outcomes, with enhanced safety and patient survival.

Prediction of disease recurrence or residual disease after primary endoscopic resection of pT1 colorectal cancer—results from a large nationwide Danish study

PurposeRisk assessment of disease recurrence in pT1 colorectal cancer is crucial in order to select the appropriate treatment strategy. The study aimed to develop a prediction model, based on histopathological data, for the probability of disease recurrence and residual disease in patients with pT1 colorectal cancer.MethodsThe model dataset consisted of 558 patients with pT1 CRC who had undergone endoscopic resection only (n = 339) or endoscopic resection followed by subsequent bowel resection (n = 219). Tissue blocks and slides were retrieved from Pathology Departments from all regions in Denmark. All original slides were evaluated by one experienced gastrointestinal pathologist (TPK). New sections were cut and stained for haematoxylin and eosin (HE) and immunohistochemical markers. Missing values were multiple imputed. A logistic regression model with backward elimination was used to construct the prediction model.ResultsThe final prediction model for disease recurrence demonstrated good performance with AUC of 0.75 [95% CI 0.72–0.78], HL chi-squared test of 0.59 and scaled Brier score of 10%. The final prediction model for residual disease demonstrated medium performance with an AUC of 0.68 [0.63–0.72].ConclusionWe developed a prediction model for the probability of disease recurrence in pT1 CRC with good performance and calibration based on histopathological data. Together with lymphatic and venous invasion, an involved resection margin (0 mm) as opposed to a margin of ≤ 1 mm was an independent risk factor for both disease recurrence and residual disease.

Case report: Oxaliplatin-induced idiopathic non-cirrhotic portal hypertension: a case report and literature review

Oxaliplatin has become a widely used agent in neoadjuvant chemotherapy for gastrointestinal tract tumors and is an integral part of the therapeutic approach for managing colorectal cancer recurrences and metastases, resulting in a more favorable prognosis for patients. Nevertheless, oxaliplatin can give rise to idiopathic non-cirrhotic portal hypertension (INCPH). The emergence of INCPH can disrupt tumor chemotherapy and incite persistent adverse reactions in later stages, significantly complicating clinical management. Consequently, we have presented a case report of INCPH induced by oxaliplatin chemotherapy with the aim of advancing the diagnosis and treatment of this condition, with a particular focus on the clinical manifestations. This study has ascertained that the condition is primarily attributed to complications related to portal hypertension, such as gastrointestinal bleeding, splenomegaly, and hypersplenism. The pathological features primarily involve hepatic sinus dilation and congestion, portal obstruction, absence, stenosis, shunting, localized venous and perisinusoidal fibrosis, as well as hepatocellular atrophy. Treatment primarily concentrates on strategies typically employed for cirrhosis. Endoscopic ligation, sclerotherapy, and non-selective beta-blockers (NSBBs) can be selected to prevent and treat variceal hemorrhage. Transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation can also be chosen for severe cases. Notably, despite the timely discontinuation of oxaliplatin, most patients continue to experience disease progression, ultimately resulting in a poor prognosis due to either tumor advancement or the ongoing progression of portal hypertension. This emphasizes the importance for physicians to be aware of and consider the risk of INCPH when prescribing oxaliplatin.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Identifying individualized prognostic signature and unraveling the molecular mechanism of recurrence in early-onset colorectal cancer

BackgroundThe incidence and mortality of early-onset colorectal cancer (EOCRC; < 50 years old) is increasing worldwide, with a high recurrence rate. The inherent heterogeneity of EOCRC makes its treatment challenging. Hence, to further understand the biology and reveal the molecular mechanisms of EOCRC, a recurrence risk signature is needed to guide clinical management.MethodsBased on the relative expression orderings (REOs) of genes in each sample, a prognostic signature was developed and validated utilizing multiple independent datasets. The underlying molecular mechanisms between distinct prognostic groups were explored via integrative analysis of multi-omics data.ResultsThe prognostic signature consisting of 6 gene pairs (6-GPS) could predict the recurrence risk for EOCRC at the individual level. High-risk EOCRC classified by 6-GPS showed a poor prognosis but a good response to adjuvant chemotherapy. Moreover, high-risk EOCRC was characterized by epithelial-mesenchymal transition (EMT) and enriched angiogenesis, and had higher mutation burden, immune cell infiltration, and PD-1/PD-L1 expression. Furthermore, we identified four genes associated with relapse-free survival in EOCRC, including SERPINE1, PECAM1, CDH1, and ANXA1. They were consistently differentially expressed at the transcriptome and proteome levels between high-risk and low-risk EOCRCs. They were also involved in regulating cancer progression and immune microenvironment in EOCRC. Notably, the expression of SERPINE1 and ANXA1 positively correlated with M2-like macrophage infiltration.ConclusionOur results indicate that 6-GPS can robustly predict the recurrence risk of EOCRC, and that SERPINE1, PECAM1, CDH1, and ANXA1 may serve as potential therapeutic targets. This study provides valuable information for the precision treatment of EOCRC.

Low expression of ZHX3 is associated with progression and poor prognosis in colorectal cancer

Accumulating studies suggest that ZHX3, the member of ZHX family, is involved in a variety of biological functions such as development and differentiation. Recently, ZHX3 may also be involved in the progression of several cancer types including renal cancer, gastric cancer, liver cancer and breast cancer. However, the potential role of ZHX3 in colorectal cancer (CRC) is still unknown. In this study, we analyzed the protein levels of ZHX3 by immunohistochemistry and evaluated its relationship with the clinicopathological features and prognosis in 286 CRC patients. In vitro cell proliferation assay, plate colony formation assay and xenograft model in nude mice were applied to evaluate CRC cell proliferative ability. Our results showed that the expression of ZHX3 was significantly downregulated in CRC tissues compared with paired adjacent nontumor tissues. Furthermore, the ZHX3 expression was found to have a strong correlation with tumor size, tumor invasion depth and TNM stage. Kaplan-Meier analysis demonstrated that low ZHX3 expression was related to a poorer overall survival and disease-free survival in CRC patients. In addition, cox's proportional hazards analysis indicated that low ZHX3 expression was an independent prognostic indicator of poor prognosis. Functionally, reduced expression of ZHX3 promotes the proliferation of CRC cells both in vitro and in vivo. Conversely, overexpression of ZHX3 inhibited the growth of CRC cells, indicated that ZHX3 was significantly correlated with CRC progression. Our results indicate for the first time that ZHX3 may be a potential marker of cancer prognosis and CRC recurrence.

Relationship Between MUC4 Variants and Metastatic Recurrence in Colorectal Cancer

Relationship Between MUC4 Variants and Metastatic Recurrence in Colorectal Cancer

Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol

IntroductionThere remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory...

Tumor microbiome analysis provides prognostic value for patients with stage III colorectal cancer.

Although patients with colorectal cancer (CRC) can receive optimal treatment, the risk of recurrence remains. This study aimed to evaluate whether the tumor microbiome can be a predictor of recurrence in patients with stage III CRC. Using 16S rRNA gene sequencing, we analyzed the microbiomes of tumor and adjacent tissues acquired during surgery in 65 patients with stage III CRC and evaluated the correlation of the tissue microbiome with CRC recurrence. Additionally, the tumor tissue microbiome data of 71 patients with stage III CRC from another center were used as a validation set. The microbial diversity and abundance significantly differed between tumor and adjacent tissues. In particular, Streptococcus and Gemella were more abundant in tumor tissue samples than in adjacent tissue samples. The microbial diversity and abundance in tumor and adjacent tissues did not differ according to the presence of recurrence, except for one genus in the validation set. Logistic regression analysis revealed that a recurrence prediction model including tumor tissue microbiome data had a better prediction performance than clinical factors (area under the curve [AUC] 0.846 vs. 0.679, p = 0.009), regardless of sex (male patients: AUC 0.943 vs. 0.818, p = 0.043; female patients: AUC 0.885 vs. 0.590, p = 0.017). When this prediction model was applied to the validation set, it had a higher AUC value than clinical factors in female patients. Our results suggest that the tumor microbiome of patients with CRC be a potential predictor of postoperative disease recurrence.

Management of pT1 CRC detected on the colorectal cancer screening programme (Basque Country. Spain)

Abstract Background The Bowel Cancer Screening Programme (BCSP) started in 2009 with faecal immunochemical test (FIT, with cut-off 20µg/g faeces) every 2 years (for 50-69 year- olds). 2.518.715 people were invited until 2021. Participation rate was 70.4% with 5.3% positive rate and 92.7% adherence to colonoscopy. Colorectal cancer (CRC) detection rate was 2.28 ‰ with 70.6% found in initial stage. The PT1 (stage I) represented 40% of the total cancer detected (4,050 in the overall period). Objectives To compare the characteristics and management of pT1 CRC. Methods Retrospective cohort study including pT1 CRC Stage I diagnosed after colonoscopy in positive FIT from 2009-2017. Variables: sex, age groups, endoscopic and surgical treatment, CRC recurrence and survival. Chi-square, Logistic Regression, SPSS v.23. Results Of the 1,523 CRC detected, 585 were detected as pT1 and I stage (38.4%). 73.4% in men and by age group 59% over 60 years-old. 48.5% were treated with surgery and 51.5% with endoscopic resection. No significant differences were found adjusted by sex and age regardless of treatment. In 57.6% of patients under surgery, CRC was not reported by pathological analysis. All cases followed up by colonoscopy with variability in the number of surveillances over time. 4.1% (24) had CRC recurrence with 87% detected in the surveillance, no significant differences regardless of the treatment. 1.5% (9) died due to CRC progression. Conclusions Apart from the high number of CRC detected in early stages by the screening Programme, an important number of cases are reported as pT1 CRC. Endoscopic resection is one of the treatments of choice without significant impact either in recurrence of neoplasia or mortality. However, surgical procedure shows overtreatment because of the high number of cases without CRC after the procedure. Therefore, endoscopic resection could be the main choice to treat pT1 CRC. Key messages • Endoscopic resection is one of the treatment of choice without impact in recurrence for the pT1 CRC detected through the BCSP. • The Basque BCSP obtains excellent participation rate, reflected in early detection and treatment of pre and malignant lesions.

Harnessing Minimal Residual Disease as a Predictor for Colorectal Cancer: Promising Horizons Amidst Challenges.

Minimal Residual Disease (MRD) detection has emerged as an independent factor in clinical and pathological cancer assessment offering a highly effective method for predicting recurrence in colorectal cancer (CRC). The ongoing research initiatives such as the DYNAMIC and CIRCULATE-Japan studies, have revealed the potential of MRD detection based on circulating tumor DNA (ctDNA) to revolutionize management for CRC patients. MRD detection represents an opportunity for risk stratification, treatment guidance, and early relapse monitoring. Here we overviewed the evolving landscape of MRD technology and its promising applications through the most up-to-date research and reviews, underscoring the transformative potential of this approach. Our primary focus is to provide a point-to-point perspective and address key challenges relating to the adoption of ctDNA-based MRD detection in the clinical setting. By identifying critical areas of interest and hurdles surrounding clinical significance, detection criteria, and potential applications of basic research, this article offers insights into the advancements needed to evaluate the role of ctDNA in CRC MRD detection, contributing to favorable clinical options and improved outcomes in the management of CRC.

A case of lymphatic flow evaluation using indocyanine green fluorescence imaging for recurrence of anastomotic site after laparoscopic right hemicolectomy

BackgroundAnastomotic recurrence of colorectal cancer is rare, but reoperation improves prognosis. However, there is no clear evidence regarding the extent of dissection, and there are few reports on the details of surgery. We used intraoperative lymphatic flow imaging with indocyanine green (ICG) fluorescence as a reference to determine the range of additional resection.Case presentationThe patient was a 75-year-old man who underwent laparoscopic right hemicolectomy and extracorporeal functional terminal anastomosis for ascending colon cancer 4 years ago. Histopathological examination revealed a well-differentiated tubular adenocarcinoma, T4aN0M0, pathological stageIIB. During follow-up, anemia was observed, and colonoscopy indicated anastomotic recurrence, so additional laparoscopic resection was performed. Intraoperatively, ICG was injected into the anastomotic site, and the operation proceeded under near-infrared light observation. Lymphatic vessels along the middle colonic artery were visualized down to the root of the vessel. Using this as an indicator, the vessel was ligated from the root. Using the fact that the lymphatic vessels were also depicted in the small intestinal mesentery on the oral side of the anastomosis as an indicator, the small intestine and mesentery were resected about 7 cm from the anastomosis.ConclusionsThe optimal surgical approach for anastomotic recurrence of colorectal cancer has not been defined. Intraoperative ICG fluorescence imaging can provide images of lymphatic flow from the site of recurrence and may be an indicator of lymph node dissection in the case of anastomotic recurrence.

Development and validation of a novel radiomics nomogram for prediction of early recurrence in colorectal cancer

BackgroundEarly recurrence (ER) is a significant concern following curative resection of advanced colorectal cancer (CRC) and is linked to poor long-term survival. Reliable prediction of ER is challenging, necessitating the development of a novel radiomics-based nomogram for CRC patients. MethodsWe enrolled 405 patients, with 298 in the training set and 107 in the external test set. Radiomic features were extracted from preoperative venous-phase computed tomography (CT) images. A radiomics signature was created using univariate logistic regression analyses and the least absolute shrinkage and selection operator algorithm. Clinical factors were integrated into the analyses to develop a comprehensive predictive tool in a multivariate logistic regression model, resulting in a radiomics nomogram. Subsequently, the calibration, discrimination, and clinical usefulness of the nomogram were evaluated. ResultsThe radiomics signature, consisting of four selected CT features, was significantly associated with ER in both the training and test datasets (P < 0.05). Independent predictors of ER included TNM stage, carcinoembryonic antigen level and differentiation grade were identified. The radiomics nomogram, incorporating all these predictors, exhibited good predictive ability in both the training set with an area under the curve (AUC) of 0.82 (95 % confidence interval (CI), 0.74–0.90) and the test set with an AUC of 0.85 (95 % CI, 0.72–0.99), surpassing the performance of any single candidate factor alone. Furthermore, additional analysis demonstrated that the nomogram was clinically useful. ConclusionsWe have developed a radiomics-based nomogram that effectively predicts early recurrence in CRC patients, enhancing the potential for timely intervention and improved outcomes.

Cholinergic signaling influences the expression of immune checkpoint inhibitors, PD-L1 and PD-L2, and tumor hallmarks in human colorectal cancer tissues and cell lines

BackgroundCancer cells express immunosuppressive molecules, such as programmed death ligands (PD-L)1 and PD-L2, enabling evasion from the host’s immune system. Cancer cells synthesize and secrete acetylcholine (ACh), acting as an autocrine or paracrine hormone to promote their proliferation, differentiation, and migration.MethodsWe correlated the expression of PD-L1, PD-L2, cholinergic muscarinic receptor 3 (M3R), alpha 7 nicotinic receptor (α7nAChR), and choline acetyltransferase (ChAT) in colorectal cancer (CRC) tissues with the stage of disease, gender, age, risk, and patient survival. The effects of a muscarinic receptor blocker, atropine, and a selective M3R blocker, 4-DAMP, on the expression of immunosuppressive and cholinergic markers were evaluated in human CRC (LIM-2405, HT-29) cells.ResultsIncreased expression of PD-L1, M3R, and ChAT at stages III-IV was associated with a high risk of CRC and poor survival outcomes independent of patients’ gender and age. α7nAChR and PD-L2 were not changed at any CRC stages. Atropine and 4-DAMP suppressed the proliferation and migration of human CRC cells, induced apoptosis, and decreased PD-L1, PD-L2, and M3R expression in CRC cells via inhibition of EGFR and phosphorylation of ERK.ConclusionsThe expression of immunosuppressive and cholinergic markers may increase the risk of recurrence of CRC. These markers might be used in determining prognosis and treatment regimens for CRC patients. Blocking cholinergic signaling may be a potential therapeutic for CRC through anti-proliferation and anti-migration via inhibition of EGFR and phosphorylation of ERK. These effects allow the immune system to recognize and eliminate cancer cells.

Strain-level detection of Fusobacterium nucleatum in colorectal cancer specimens by targeting the CRISPR-Cas region.

Fusobacterium nucleatum is associated with colorectal cancer (CRC), and identical F. nucleatum strains seemed to be detected in 75% of patients who exhibited the presence of F. nucleatum in both CRC and saliva samples in our previous study; however, the validation of strain identity and the development of a method for strain-level discrimination are required for etiological studies. We confirmed that F. nucleatum isolates obtained from CRC and saliva samples derived from patients with CRC originated from their identical strains using whole-genome sequencing. We evaluated the hypervariable region of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (CRISPR-Cas) system in F. nucleatum strains isolated from the CRC and saliva specimens of CRC patients to develop a method for genotyping this bacterium at the strain level. The developed method consisted of two simple PCR steps to amplify the different lengths and sequences of the CRISPR-Cas regions from F. nucleatum strains using specific but common primers. This method could successfully detect identical strains present in both cryopreserved CRC samples and saliva obtained from the same CRC patient. Dynamic monitoring of F. nucleatum strains in saliva obtained from patients with colorectal adenoma before and after oral care showed interindividual variability in F. nucleatum strains during oral care. This study provided a simple and rapid method for comprehensively identifying F. nucleatum at the strain level in clinical samples, leading to a paradigm shift in CRC research, such as the investigation of pathogenic F. nucleatum strains and monitoring of pathogenic strains in clinical trials for preventing CRC recurrence. (This study was registered in the UMIN Clinical Trials Registry under ID UMIN000016229.) IMPORTANCE Fusobacterium nucleatum is one of the predominant oral bacteria in humans. However, this bacterium is enriched in colorectal cancer (CRC) tissues and may be involved in CRC development. Our previous research suggested that F. nucleatum is present in CRC tissues originating from the oral cavity using a traditional strain-typing method [arbitrarily primed polymerase chain reaction (AP-PCR)]. First, using whole-genome sequencing, this study confirmed an exemplary similarity between the oral and tumoral strains derived from each patient with CRC. Second, we successfully developed a method to genotype this bacterium at the strain level, targeting the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated system, which is hypervariable (defined as F. nucleatum-strain genotyping PCR). This method can identify F. nucleatum strains in cryopreserved samples and is significantly superior to traditional AP-PCR, which can only be performed on isolates. The new methods have great potential for application in etiological studies of F. nucleatum in CRC.

Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

Combined associations of a healthy lifestyle and body mass index with colorectal cancer recurrence and survival: a cohort study

PurposeColorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a healthy lifestyle and body mass index on prognosis following CRC diagnosis.MethodsTreatment and follow-up data were collected from the patient files of 1098 participants from the Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan–Meier method and Cox proportional hazards models adjusted for age, sex, and educational level.ResultsAmong 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0–1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score 4 (most healthy). Patients with the healthiest lifestyle (HL score 4) compared to the least healthy (HL score 0–1) had an improved recurrence-free survival (HL 4 vs HL 0–1, HRadj 0.51 (95% CI 0.31–0.83) and overall survival (HL 4 vs HL 0–1, HRadj 0.52 (95% CI 0.38–0.70).ConclusionAdherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I–III CRC.

PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer: a retrospective study

BackgroundFluoropyrimidine-based postoperative adjuvant chemotherapy is globally recommended for high-risk stage II and stage III colon cancer. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, discovery of novel molecular biomarkers of postoperative adjuvant chemotherapy to identify patients at increased risk of recurrent colorectal cancer is warranted. Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers. Our goal was to evaluate the relationship between single-nucleotide variants of autophagy-related genes and recurrence rates in order to identify novel biomarkers that predict the effect of adjuvant chemotherapy in colorectal cancer. MethodsWe analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer recurrence rates.ResultsWe detected 560 single-nucleotide variants and insertions/deletions in the target region. The results of Fisher’s exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single-nucleotide variants (c.1018G > A [p < 0.005] or c.1562A > C [p < 0.01]) of the mitophagy-related gene PTEN-induced kinase 1.ConclusionsThe two single-nucleotide variants of PINK1 gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.

Tumour Recurrence in peristomal skin: a case report

Peristomal skin recurrences of colorectal cancer after excision of the primary are rare. Clinically, it presents as a subcutaneous mass throughout the abdominal wall and progressively extends on the abdomen as a skin granuloma. Two colorectal cancer patients (an 83-year-old man, previously treated with left hemicolectomy and right exteriorisation for an obstructive tumour of the descending colon, Stage IV mucinous, poorly differentiated adenocarcinoma, and a 60-year-old man who finished the Hartmann's operation and small bowel resection for a perforated and locally advanced cancer of the descending colon) presented tumour recurrences in their peristomal skin. In both patients, the initial presentation was a tiny mucocutaneous skin granuloma. Subsequently, it became a large-sized, atypical, fungated tumour growth, which was complicated with persistent bleeding. A skin biopsy demonstrated an infiltration of adenocarcinoma throughout the dermis and was diagnosed as a local recurrence accompanied by peristomal skin metastasis. Although abdominal skin metastasis of colorectal cancer is rare, it is often a sign of intraabdominal recurrence. Therefore, any unusual skin lesions around the incision scar or stoma should be early biopsied to rule out local metastasis. Stoma nurse specialists play a crucial role in conducting stoma examinations, which involve both stoma and abdominal assessments. Point of care using ultrasound; clinical photos; telehealth; and patient empowerment could be advanced to facilitate early identification of stomal complications for timely investigation and treatment.

643P A phase Ib/IIa study to assess the safety, tolerability, pharmacokinetics, and antitumor activity of YYB101, hepatocyte growth factor neutralizing humanized monoclonal antibody, in combination with irinotecan in metastatic or recurrent colorectal cancer patients (NOV110501-201)

643P A phase Ib/IIa study to assess the safety, tolerability, pharmacokinetics, and antitumor activity of YYB101, hepatocyte growth factor neutralizing humanized monoclonal antibody, in combination with irinotecan in metastatic or recurrent colorectal cancer patients (NOV110501-201)