Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.

BACKGROUND: The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. METHODS: We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. RESULTS: Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. CONCLUSION: Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.

Association of resection margin distance with anastomotic recurrence in stage I-III colon cancer: data from the National Colorectal Cancer Cohort (NCRCC) study in China.

PURPOSE: Few studies have focused on anastomotic recurrence (AR) in colon cancer. This study aimed to clarify the association of resection margin distance with AR and compare the prognosis with nonanastomotic local recurrence (NAR). METHODS: This retrospective cohort study included the clinical data of patients who underwent radical colon cancer surgery between January 1, 2009, and December 31, 2019. RESULTS: A total of 1958 colon cancer patients were included in the study. 34 of whom (1.7%) had AR and 105 of whom (5.4%) had NAR. Multivariate analysis revealed that the lower distal resection margin distance, advanced N stage, and number of lymph nodes dissected were risk factors for AR. In the proximal resection margin, the risk of AR was lowest at a distance of 6 cm or greater, with a 3-year rate of 1.3%. In the distal resection margin, the 3-year AR risk increased rapidly if the distance was less than 3 cm. The prognosis of patients in the AR group was similar to that of patients in the NAR group, regardless of synchronous distant metastases. Furthermore, the radical surgery rate for AR was significantly higher than that for NAR, but the prognosis of AR was comparable to that of NAR. CONCLUSIONS: The distal resection margin distance, advanced N stage, and less number of lymph nodes dissected are associated with AR of colon cancer. The prognosis of patients with AR was similar to that of patients with NAR. TRIAL REGISTRATION: Clinical Trial Numbers NCT04074538 ( clinicaltrials.gov ), August 26, 2019, registered, retrospectively registered.

Development and validation of prognostic nomograms for early-onset colon cancer in different tumor locations: a population-based study.

OBJECTIVE: The prevalence of early-onset colon cancer (EOCC) among individuals below the age of 50 has shown a marked upward trend in recent years. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right-sided and left-sided colon cancers. However, the differences have not been fully researched in EOCC. Our study aims to develop and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for EOCC in different tumor locations based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Using the SEER database, a total of 5,588 patients with EOCC were extracted and divided into development and validation cohorts in a random allocation ratio of 7:3 across three groups. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors influencing OS and CSS outcomes. These factors were then utilized to construct nomogram models. The prognostic capabilities of the three models were assessed through various evaluation metrics, including the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and validation cohorts respectively. Additionally, survival curves of the low- and high-risk groups were calculated using the Kaplan-Meier method together with the log-rank test. RESULTS: Significant differences in clinical features were observed between right-sided and left-sided EOCCs, particularly in terms of OS (52 months vs 54 months) as demonstrated by Kaplan-Meier curves. Transverse-sided EOCCs exhibited clinical characteristics similar to right-sided EOCCs, suggesting a potential shared tumor microenvironment and therapeutic considerations. Advanced stage, liver metastasis, poor grade, elevated pretreatment carcinoembryonic antigen (CEA) level, chemotherapy, and perineural invasion were identified as independent prognostic factors across all three tumor locations and were incorporated into the nomogram model. Nomograms were constructed to predict the probability of 3- and 5-year OS and CSS. The C-index and calibration plots showed that the established nomograms had good consistency between actual clinical observations and predicted outcomes. ROC curves with calculated area under the curve (AUC) values exceeded 0.8 for all three groups in both the development and validation cohorts, indicating robust predictive performance for OS and CSS. Furthermore, decision curve analysis (DCA) plots revealed a threshold probability range of 0.1 to 0.9, within which the nomogram model exhibited maximum benefit. Kaplan-Meier curves exhibited significant differences between the low- and high-risk groups in EOCC for all three tumor locations in OS and CSS, further validating the prognostic value of the nomogram models. CONCLUSIONS: We successfully developed three precise nomogram models for EOCCs in different tumor locations, providing valuable support for clinicians in guiding clinical treatments and facilitating further prospective follow-up studies.

Exosomal MEF2C's Association With the Progression of CRC in Regulating CD36 Transcription.

Context: Exosomes are biologically active, extracellular vesicles that are involved in tumor-related processes, including activating tumors, facilitating tumor growth, and promoting inflammation. Objective: The study intended to investigate microRNAs (miRNAs) in exosomes that are associated with colorectal cancer (CRC). Design: The research team performed bioinformatics analysis, extracting RNA-sequencing (RNA-seq) datasets from the Cancer Genome Atlas (TCGA); ExoRBase, a database of different types of RNA information that scientists have extracted from human exosomes; and the Gene Expression Omnibus (GEO) databases, and analyzed the data. Setting: The study took place at the Department of Colorectal Surgery at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China. Participants: From October 2020 to March 2021, a total of 28 CRC patients who underwent curative resection at the National Cancer Center were enrolled. Tumor samples and tumor-adjacent normal sample were obtained from these CRC patients. Postoperative pathological characteristics all shown adenocarcinoma. The research team recruited participants from the hospitals connected with CAMS and PUMC and obtained written informed consent from them for publication of a case report and any accompanying images. The Ethics Committee of the Cancer Institute (Hospital), CAMS & PUMC has officially recognized the study (NCC 2017-YZ-026). Outcome Measures: The research team: (1) extracted RNA-seq datasets from the TCGA, exoRBase and GEO and analyzed the differentially expressed genes (DEGs); (2) performed a cluster analysis of variant genes using weighted gene co-expression network analysis (WGCNA);(3) verified expression of myocyte enhancer factor 2C-genecards (MEF2C) and cluster of differentiation 36 (CD36) in CRC tissues; (4) explored the biological function of the MEF2C by performing proliferation, migration, and invasion assays; and (5) used a chromatin immunoprecipitation (ChIP) experiment to analyze mechanisms to reveal CD36 transcription regulated by exosomal MEF2C. Results: A significant mean difference in exosomal MEF2C existed between normal and tumor tissues. By performing a correlation analysis, the research team found 609 potential target points of exosomal MEF2C (r > 0.5, P < .05). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network analysis indicated that CD36 may be the target of exosomal MEF2C. Univariate, multivariate, and Kaplan-Meier analyses showed that CD36 was closely related to the overall survival (OS) of CRC patients. Obvious differences existed in the expression levels of MEF2C and CD36 in CRC and normal tissues according to qPCR and immunohistochemical assays. Functional-experiments analysis in vitro showed that exosomal-MEF2C could be considered as an antioncogene. Mechanistically, ChIP assays showed that MEF2C regulated the transcriptional level of CD 36; thus, the expression of CD36 increased significantly. Conclusion: MEF2C is a potential biomarker of a favorable prognosis in CRC and is related to the progression of CRC. Moreover, the MEF2C-CD36 pathway may reveal the tumor regulation mechanism in CRC. The exosomal MEF2C was the hub gene in exosomes, with CD36 was identified as the potential target. Exosomal MEF2C may be a promising molecular biomarker for predicting a good prognosis and may have potential as a medical target for CRC.

Comparative short-term and survival outcomes of three specimen extraction techniques in laparoscopic low rectal cancer surgery: does it affect ileostomy closure?

INTRODUCTION: This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. MATERIALS AND METHODS: A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. RESULTS: In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P < 0.001), more intraoperative bleeding (P < 0.001), longer length of abdominal incision (P<0.001), longer time to first flatus (P < 0.001), longer time to first defecation (P < 0.001), longer time to first eat (P < 0.001), and longer postoperative hospital stays (P = 0.005) than the EXSI and EVER groups. The primary postoperative complication rate in the EXAI and EVER group was significantly higher than in the EXSI group (P = 0.005). In loop ileostomy closure, EXAI group had significantly longer operative time (P = 0.001), more bleeding volume, and longer postoperative hospital stays (P < 0.001) than the EXSI and EVER groups. For survival outcomes, the 3-year local recurrence-free survival (LRFS) is 92.6% for all patients. The 3-year LRFS for patients in EXAI, EXSI, and EVER were 90.1%, 95.4%, and 92.7%, with P = 0.476. CONCLUSIONS: Our single-center results found that in LAR-PLI surgery for low rectal cancer, the short-term outcomes of specimen extraction through the stoma incision or anus were better than that through the auxiliary incision, but the 3-year LRFS was no statistically different.

Laparoscopic radical transverse colectomy with transrectal specimen extraction: A novel natural orifice specimen extraction procedure: A case report.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Comparison of short-term outcomes between totally laparoscopic right colectomy and laparoscopic-assisted right colectomy: a retrospective study in a single institution on 300 consecutive patients.

BACKGROUND: Laparoscopic surgery has become the standard surgical approach for the treatment of colon cancer. However, the surgical procedure for right colectomy is not standardized. Selection between laparoscopy-assisted right colectomy (LARC) with extracorporeal anastomosis and totally laparoscopic procedures with intracorporeal anastomosis is still a hot topic. The aim of this study was to compare the short-term outcomes of totally laparoscopic right colectomy (TLRC) and LARC in the treatment of right colon cancer. METHODS: This was a retrospective and single-center study conducted between January 2016 and December 2019 featuring 120 TLRC patients and 180 LARC patients following the principles of the CME. We then collated and analyzed the clinicopathological characteristics, operative characteristics, and short-term outcomes. RESULTS: The baseline characteristics were balanced between two groups. TLRC was associated with a significantly lower estimated blood loss (p < 0.01), a shorter incision length (p < 0.01). In terms of postoperative recovery, patients in TLRC group were better, as confirmed by less postoperative pain (p < 0.01), less rescue analgesic usage (p = 0.04), faster to flatus (p < 0.01), defecation (p < 0.01), oral intake (p < 0.01) and discharge (p < 0.01). Incidence of postoperative complications according to Clavien-Dindo classification system was also similar in both groups. CONCLUSIONS: Our data demonstrate that TLRC is technically safe and feasible. This technique could lead to a better cosmetic outcome, a less pain experience and a faster recovery of bowel function.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

High-grade postoperative complications affect survival outcomes of patients with colorectal Cancer peritoneal metastases treated with Cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy.

BACKGROUND: This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. RESULTS: In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01-1.14; P=0.015) and grade 3-4 postoperative complications (HR, 1.86, 95% CI, 1.22-3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01-1.02; P< 0.001) was identified as an independent risk factor for developing high-grade complications. CONCLUSION: Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.

Does Additional Laparoscopic-Assisted Surgery after Endoscopic Submucosal Dissection Affect Short Outcomes in Patients with Stage T1 Colorectal Cancer? A Propensity Score-Based Analysis.

BACKGROUND: Additional surgery is necessary in cases with non-curative endoscopic submucosal dissection. It is still unknown whether preceding endoscopic submucosal dissection (ESD) for T1 colorectal carcinoma affects the short outcomes of patients who underwent additional surgery or not as compared with surgery alone without ESD. METHODS: Patients (101 pairs) with T1 colorectal cancer who underwent additional laparoscopic-assisted surgery after endoscopic submucosal dissection (additional surgery group, n = 101) or laparoscopic-assisted surgery alone (surgery alone group, n = 101) were matched (1:1). Short-term morbidity, operation outcomes, and lymph node metastasis of the resected specimen were compared. RESULTS: There were no significant differences between the additional laparoscopic-assisted surgery and laparoscopic-assisted surgery alone groups in lymph node metastasis (9.9 vs. 5.9%, respectively, p = 0.297), operative time (147.76 ± 52.00 min vs. 156.50 ± 54.28 min, p = 0.205), first flatus time (3.56 ± 1.10 days vs. 3.63 ± 1.05 days, p = 0.282), first stool time (4.30 ± 1.04 days vs. 4.39 ± 1.22 days, p = 0.293), time to intake (5.00 ± 1.18 days vs. 5.25 ± 1.39 days, p = 0.079), blood loss (44.75 ± 45.40 mL vs. 60.40 ± 78.98 mL, p = 0.603), harvest lymph nodes (18.74 ± 7.22 vs. 20.32 ± 9.69, p = 0.438), postoperative surgical complications (p = 0.733), and postoperative length of hospital stay (8.68 ± 4.00 days vs. 8.39 ± 1.94 days, p = 0.401). CONCLUSION: ESD did not increase the difficulty of additional laparoscopic-assisted surgery, hospital stay, or the incidence of postoperative complications. Additional laparoscopic-assisted surgery is safe and recommended for patients with T1 cancer at high risk of lymph node metastasis and residual cancer after non-curative ESD.

B7-H3 immune checkpoint expression is a poor prognostic factor in colorectal carcinoma.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.

Safety and survival outcomes of transanal natural orifice specimen extraction using prolapsing technique for patients with middle- to low-rectal cancer.

OBJECTIVE: The transanal approach to specimen collection, combined with the prolapsing technique, is a well-established and minimally invasive surgery for treating rectal cancer. However, reports on outcomes for this approach are sparse. We compared short- and long-term outcomes of conventional laparoscopic surgery (CLS) vs. transanal natural orifice specimen extraction (NOSE) using the prolapsing technique for patients with middle- to low-rectal cancer. METHODS: From January 2013 to December 2017, we enrolled consecutive patients with middle- to low-rectal cancer undergoing laparoscopic anterior resection. Totally, 50 patients who underwent transanal NOSE using the prolapsing technique were matched with 50 patients who received CLS. Clinical parameters and survival outcomes between the two groups were compared. RESULTS: Estimated blood loss (29.70±29.28 vs. 52.80±45.09 mL, P=0.003), time to first flatus (2.50±0.79 vs. 2.86±0.76, P=0.022), time to liquid diet (3.62±0.64 vs. 4.20±0.76 d, P<0.001), and the need for analgesics (22%vs. 48%, P=0.006) were significantly lower for the NOSE group compared to the CLS group. The incidences of overall complications and fecal incontinence were comparable in both groups. After a median follow-up of 44.52 months, the overall local recurrence rate (6% vs. 5%, P=0.670), 3-year disease-free survival (86.7% vs. 88.0%, P=0.945) and 3-year overall survival (95.6% vs. 96.0%, P=0.708), were not significantly different. CONCLUSIONS: For total laparoscopic rectal resection, transanal NOSE using the prolapsing technique is effective and safe, and associated with less trauma and pain, a faster recovery, and similar survival outcomes compared to CLS.

Participation and yield of a population-based colorectal cancer screening programme in China.

OBJECTIVE: Colorectal cancer (CRC) screening has been widely implemented in many countries. However, evidence on participation and diagnostic yield of population-based CRC screening in China is sparse. DESIGN: The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1 381 561 eligible participants aged 40-69 years from 16 provinces in China from 2012 to 2015. 182 927 participants were evaluated to be high risk for CRC by an established risk score system and were subsequently recommended for colonoscopy. Participation rates and detection of colorectal neoplasms in this programme were reported and their associated factors were explored. RESULTS: 25 593 participants undertook colonoscopy as recommended, with participation rate of 14.0%. High level of education, history of faecal occult blood test, family history of CRC and history of colonic polyp were found to be associated with the participation in colonoscopy screening. Overall, 65 CRC (0.25%), 785 advanced adenomas (3.07%), 2091 non-advanced adenomas (8.17%) and 1107 hyperplastic polyps (4.33%) were detected. Detection rates of colorectal neoplasms increased with age and were higher for men. More advanced neoplasms were diagnosed in the distal colon/rectum (65.2%). Several factors including age, sex, family history of CRC, dietary intake of processed meat and smoking were identified to be associated with the presence of colorectal neoplasms. CONCLUSION: The diagnostic yield was not optimal using colonoscopy screening in high-risk populations given the relatively low participation rate. Our findings will provide important references for designing effective population-based CRC screening strategies in the future.

Predictive risk factors for anastomotic leakage after anterior resection of rectal cancer in elderly patients over 80 years old: an analysis of 288 consecutive patients.

BACKGROUND: Anastomotic leakage (AL) is a common complication after anterior resection of rectal cancer. Few studies have been conducted to determine whether the traditional predictors of AL can be applied to elderly patients (age ≥ 80) undergoing anterior resection (AR) or low anterior resection (LAR) of rectal cancer. This study was designed to explore the predictive factors for AL after anterior resection of rectal cancer in patients over 80 years old. METHODS: From January 2007 to May 2019, consecutive elderly (age ≥ 80) rectal cancer patients undergoing AR or LAR at our institution were systematically reviewed. The general information, perioperative outcomes, and comorbidities were collected. RESULTS: A total of 288 consecutive patients were included in this study. The average age was 82.8 ± 2.4 years, and 30 (10.4%) patients developed AL. The univariate analyses showed that neoadjuvant therapy (50.0% vs. 27.9%, P = 0.013), the number of stapler firings ≥ 3 (60.0% vs. 36.0%, P = 0.011), and coronary heart disease (CHD) (46.7% vs. 17.8%, P < 0.001) were associated with an increased incidence of AL. The multivariate analysis showed that the number of stapler firings ≥ 3 (OR = 4.77, 95% CI = 1.33-15.21, P = 0.035) and CHD (OR = 8.33, 95% CI = 1.94-13.05, P = 0.003) were independent risk factors for AL. CONCLUSION: The number of stapler firings ≥ 3 and CHD were independent risk factors for AL in elderly patients (age ≥ 80) with rectal cancer. A temporary ileostomy or the Hartmann procedure is recommended for patients with CHD, male patients, patients considered to be obese, and patients with a lower tumor location, which may increase the number of stapler firings. Certainly, we recommend that the number of stapler firings should be minimized to alleviate the economic and physical burden of patients.

Laparoscopic vs open colorectal cancer surgery in elderly patients: short- and long-term outcomes and predictors for overall and disease-free survival.

BACKGROUND: Colorectal cancer is common in elderly patients. Laparoscopy is widely used to approach this kind of disease. This study was to examine short-term outcomes and long-term survival for laparoscopic and open surgery in elderly patients with colorectal cancer. METHODS: From January 2007 to December 2018, patients with colorectal cancer older than 80 operated at China National Cancer Center were included in the study. Propensity score matching (PSM) was used to minimize the adverse effects. The clinical data between open and laparoscopic surgery was compared, and the effect of factors on overall survival (OS) and disease-free survival (DFS) was analyzed by Cox proportional hazard model. RESULTS: Ninety-three pairs were selected after PSM. Patients in laparoscopic group had less intraoperative blood loss, postoperative complications, time to first flatus, time to oral feeding, postoperative hospital stay, and higher retrieved lymph node (P < 0.05). The OS and DFS rates were similar (P > 0.05), besides the CEA level, III/IV stage, and perineural invasion were independent predictors of survival (P < 0.05). CONCLUSION: In elderly patients with colorectal cancer, laparoscopic surgery had better short-term outcomes than open surgery. CEA level, III/IV stage, and perineural invasion were reliable predictors for OS and DFS.

Long-term outcomes in patients with ypT0 rectal cancer after neoadjuvant chemoradiotherapy and curative resection.

OBJECTIVE: For patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (NCRT), significant pathological response of the primary tumor has been proposed to identify candidates for organ preservation. However, this does not address metastatic lymph nodes in the mesorectum. The aim of this study was to assess the incidence of lymph node metastases in ypT0 patients treated with NCRT and curative resection and to explore risk factors associated with survival. METHODS: This was a retrospective study of patients with ypT0 rectal cancer after NCRT and curative resection at a tertiary care center in China from 2005 to 2014. RESULTS: A total of 60 (18.6%) patients who underwent surgery after NCRT and achieved ypT0 were enrolled in this study; one patient was excluded owing to lack of follow-up. Of these 59 patients, lymph node metastases were found in the mesorectum (ypT0N+) in eight (13.6%) patients. After a median follow-up of 52 months, 5-year recurrence-free survival (82.7% vs. 62.5%, P=0.014) and overall survival (OS) (90.9% vs. 70.0%, P=0.032) were much higher in ypN0 than ypN+ patients. Multivariate analyses showed that ypN+ status (P=0.009) and perioperative blood transfusion (BT) (P=0.001) were significantly independent risk factors associated with recurrence; however, no factor was correlated with 5-year OS. CONCLUSIONS: Patients with ypT0N0 rectal cancer can achieve excellent long-term outcomes; however, positive lymph nodes or tumor deposits can still be found in 13.6% of ypT0 patients. Nodal positivity in the mesorectum and perioperative BT are independent risk factors for recurrence.

Chemical shift effect predicting lymph node status in rectal cancer using high-resolution MR imaging with node-for-node matched histopathological validation.

OBJECTIVES: To evaluate the value of the chemical shift effect (CSE) as well as other criteria for the prediction of lymph node status. MATERIALS AND METHODS: Twenty-nine patients who underwent radical surgery of rectal cancers were studied with pre- and postoperative specimen MRI. Lymph nodes were harvested from transverse whole-mount specimens and compared with in vivo and ex vivo images to obtain a precise slice-for-section match. Preoperative MR characteristics including CSE, as well as other predictors, were evaluated by two readers independently between benign and metastatic nodes. RESULTS: A total of 255 benign and 35 metastatic nodes were obtained; 71.4% and 69.4% of benign nodes were detected with regular CSE for two readers, whereas 80.0% and 74.3% of metastatic nodes with absence of CSE. The CSE rendered areas under the ROC curve (AUC) of 0.879 and 0.845 for predicting nodal status for two readers. The criteria of nodal location, border, signal intensity and minimum distance to the rectal wall were also useful but with AUCs (0.629-0.743) lower than those of CSE. CONCLUSIONS: CSE is a reliable predictor for differentiating benign from metastatic nodes. Additional criteria should be taken into account when it is difficult to determine the nodal status by using only a single predictor. KEY POINTS: • CSE is good for predicting nodal status with high confidence. • Nodal border and signal intensity are useful for assessing nodal status. • Location of mesorectal nodes could facilitate the prediction of nodal status. • Primary tumour stage could be used as reference for nodal staging.

Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in colorectal cancer (CRC); however, only few CRC-related lncRNAs have been characterized. In this study, we aimed to dig out potential dysregulated lncRNAs that are highly involved in CRC development. Using a lncRNA-mining approach, we performed lncRNA expression profiling in a large CRC cohort from Gene Expression Ominus (GEO), GSE39582 test series (N = 585). We identified 31 downregulated lncRNAs and 16 upregulated lncRNAs from the GSE39582 test series patients (566 tumor patients and 19 normal controls). The reliability of lncRNA expression profiles was further confirmed by RT-qPCR in carcinoma tissues and paired adjacent normal tissues from 30 CRC patients, also in the serum from 109 CRC patients, and 99 normal individuals. We demonstrated that the expression of SLC25A25-AS1, which has not been reported previously, was significantly decreased in both the tumor tissues (27 out of 30) and serum of CRC patients. SLC25A25-AS1 overexpression significantly inhibited proliferation and colony formation in colorectal cancer cell lines, and downregulation of SLC25A25-AS1 obviously enhanced chemoresistance and promoted EMT process in vitro associated with Erk and p38 signaling pathway activation. Therefore, SLC25A25-AS1 was determined to play a tumor suppressive role in CRC. Our results might provide a lncRNA-based target for CRC treatment.

Risk Factors for Pancreatic Cancer in China: A Multicenter Case-Control Study.

BACKGROUND: Despite having one of the highest mortality rates of all cancers, the risk factors of pancreatic cancer remain unclear. We assessed risk factors of pancreatic cancer in China. METHODS: A case-control study design was conducted using data from four hospital-based cancer registries (Henan Provincial Cancer Hospital, Beijing Cancer Hospital, Hebei Provincial Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences). Controls were equally matched and selected from family members of non-pancreatic cancer patients in the same hospitals. Face-to-face interviews were conducted by trained staff using questionnaires. Conditional logistic regression models were used to assess odd ratios (ORs) and 95% confident intervals (CIs). RESULTS: Among 646 recruited participants, 323 were pancreatic cancer patients and 323 were controls. Multivariate logistic analysis suggested that pancreatic cancer family history (adjusted OR 1.23; 95% CI, 1.11-3.70), obesity (adjusted OR 1.77; 95% CI, 1.22-2.57), diabetes (adjusted OR 2.96; 95% CI, 1.48-5.92) and smoking (adjusted OR 1.78; 95% CI, 1.02-3.10) were risk factors for pancreatic cancer, but that drinking tea (adjusted OR 0.49; 95% CI, 0.25-0.84) was associated with reduced risk of pancreatic cancer. CONCLUSIONS: Cigarette smoking, family history, obesity, and diabetes are risk factors of pancreatic cancer, which is important information for designing early intervention and preventive strategies for pancreatic cancer and may be beneficial to pancreatic cancer control in China.

The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways.

Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a de-ubiquitinating enzyme, which enzymatic activity relies on the C90 site. The function of UCHL1 is controversial in different types of cancer, and its role in gastric cancer progression remains unclear. In this study, immunohistochemistry staining was applied to detect the expression of UCHL1 in primary gastric cancer and liver metastases from gastric cancer. MKN45 and BGC823 cell lines with stable expression of de-ubiquitinase active UCHL1 or inactive UCHL1-variant C90S were established by lentiviral infection. The effect of UCHL1 on cell proliferation was evaluated by MTT and colony formation assays. The abilities of cell migration and invasion were determined by transwell assay. Protein expression levels were determined by Western blot. The results indicated that UCHL1 had a significantly higher positive expression rate in liver metastases from gastric cancer compared with primary gastric cancer. Overexpression of UCHL1 in MKN45 and BGC823 cells promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity. UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion. These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer. UCHL1 could be a candidate biomarker and a therapeutic target for gastric cancer metastasis.