A clinical model to predict the risk of synchronous bone metastasis in newly diagnosed colorectal cancer: a population-based study.

BACKGROUND: The early detection of synchronous bone metastasis (BM) in newly diagnosed colorectal cancer (CRC) affects its initial management and prognosis. A clinical model to individually predict the risk of developing BM would be attractive in current clinical practice. METHODS: A total of 55,869 CRC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, of whom 317 patients were diagnosed with synchronous BM. Risk factors for BM in CRC patients was identified using multivariable logistic regression. A weighted scoring system was built with beta-coefficients (P < 0.05). A random sample of 75% of the CRC patients was used to establish the risk model, and the remaining 25% was used to validate its accuracy of this model. The performance of risk model was estimated by receiver operating curve (ROC) analysis. RESULTS: The risk model consisted of 8 risk factors including rectal cancer, poorly-undifferentiation, signet-ring cell carcinoma, CEA positive, lymph node metastasis, brain metastasis, liver metastasis and lung metastasis. The areas under the receiver operating curve (AUROC) were 0.903 and 0.889 in the development and validation cohort. Patients with scores from 0 to 4 points had about 0.1% risk of developing BM, and the risk increased to about 30% in patients with scores ≥15 points. CONCLUSIONS: This clinical risk model is accurate enough to identify the CRC patients with high risk of synchronous BM and to further provide more individualized clinical decision.

Current practice patterns of preoperative bowel preparation in colorectal surgery: a nation-wide survey by the Chinese Society of Colorectal Cancer.

BACKGROUND: The optimal preoperative bowel preparation for colorectal surgery remains controversial. However, recent studies have established that bowel preparation varies significantly among countries and even surgeons at the same institution. This survey aimed to obtain information on the current practice patterns of bowel preparation for colorectal surgery in China. METHODS: A paper-based survey was circulated to the members of the Chinese Society of Colorectal Cancer (CSCC). The survey responses were collected and analyzed. Statistical analysis was performed for all the categorical variables according to the responses to individual questions. RESULTS: Three hundred forty-one members completed the questionnaire. Regarding surgical practice, 203 (59.5%) performed > 50% of the colorectal operations laparoscopically or robotically; the use of mechanical bowel preparation (MBP) alone was significantly higher (63.5 vs 31.9%; P < 0.001). The respondents who performed > 200 colonic or rectal resections provided significantly more MBP alone (79.6 vs 39.1%, P < 0.001; 76.6 vs 43.2%, P < 0.001; respectively). Among hospitals with fewer than 500 beds, 52.4% of the respondents used MBP + oral antibiotics preparation (OAP) + enema, a significantly higher percentage than the respondents of hospitals with more than 500 beds (P < 0.001). Nearly 40% of the respondents prescribed OAP in regimens; meanwhile, 74.8% prescribed preoperative intravenous antibiotics. CONCLUSIONS: The study demonstrates considerable variation among members from the CSCC. These findings should be considered when developing multicenter trials and to provide more definitive answers.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

[A retrospective analysis of clinic-pathological characteristics and prognostic factors for 204 cases of primary gastric lymphoma].

OBJECTIVE: To explore the clinicopathological characteristics and prognostic factors of primary gastric lymphoma (PGL). METHODS: The clinical data of 204 patients with PGL was reviewed and analyzed. There were 106 males and 98 females, their age were 19 to 85 years (average age was 53.7 years). The Focal areas included gastric fundus lesions 41 cases (20.1%), stomach body lesions 127 cases (62.3%), distal gastric lesions 105 cases (51.5%), cardia lesions 13 cases (6.4%), duodenal bulb lesion 1 cases (0.5%). The clinical characteristics and the outcomes in patients with influence were analysed. RESULTS: In 204 PGL patients, the most common complaints were abdominal pain (62.3%) and weight loss (52.9%). Most of the PGL patients appeared ulcerative (76.0%) and results showed that 62.7% patients involved single location. As to the factors of cellulate grading and pathological characteristics, most patients (87.7%) show low-grade or intermediate-grade lymphoma, Musshoff stages I and II (74.0%). In 186 patients with complete follow-up data, survival rates of 1-, 3- and 5-year were 75.8%, 63.4% and 60.2% respectively. The median overall survival time was 50.0 months. In univariate survival analysis, age (χ(2) = 5.030), level of LDH (χ(2) = 40.084), cellulate grading (χ(2) = 35.238), Musshoff stage (χ(2) = 71.601), tumor diameter (χ(2) = 12.018) and option of managements (χ(2) = 14.140) were obviously correlated with the prognosis (all P < 0.05). Musshoff stage (RR = 2.230, 95%CI: 1.372 - 3.625) and cellulate grading (RR = 1.892, 95%CI: 1.010 - 3.543) were independent prognostic factors in multivariable analysis (both P < 0.05). There was no prognostic difference between surgery and chemotherapy in stage I and II (χ(2) = 1.223, P = 0.542). CONCLUSIONS: Musshoff stage and grade malignancy are independent prognostic factors. For patients with stage I and II, surgical resection is not the first-choice for clinical therapy.

lncRNA-PACER upregulates COX-2 and PGE2 through the NF-κB pathway to promote the proliferation and invasion of colorectal-cancer cells.

BACKGROUND: p50-associated cyclooxygenase-2 extragenic RNA (PACER) is a recently identified antisense long non-coding RNA (lncRNA) located on the upstream of the promoter region of cyclooxygenase-2 (COX-2). Preliminary studies have suggested that PACER is involved in the regulation of COX-2 expression in macrophagocyte and osteosarcoma cells. However, the role of this lncRNA in colorectal cancer (CRC) remains elusive. Here, we investigated the expression of PACER and its effect on cell proliferation and invasion to explore the role of PACER in CRC. METHODS: Real-time quantitative PCR (RT-qPCR) analysis was used to evaluate the expression of PACER in CRC tissues and cells. Methyl thiazolyl tetrazolium (MTT) analysis was then used to investigate the inhibition effect of PACER knock-down in cell proliferation. The promoting role of this lncRNA on invasion by CRC cells was analysed by wound-healing assays, colony-formation assay, and transwell assays. We then used fluorescence in situ hybridization (FISH) to establish the subcellular localization of PACER. COX-2 protein levels were quantified by Western blot analysis and grayscale scanning analysis following the knock-down of PACER. Luciferase assay was carried out to monitor the modulation of the COX-2 promoter region by PACER. Tumor xenografts models were used to investigate the impact of PACER on the tumorigenesis of CRC cells in vivo. Enzyme-linked immunosorbent assay (ELISA) was then used to quantify prostaglandin E2 (PGE2) production upon knock-down of PACER. RESULTS: RT-qPCR analysis revealed that PACER was highly expressed in CRC tissues and cells, and a high PACER-expression level was associated with poor prognosis. MTT assay, wound-healing assay, colony-formation assay, and transwell assay revealed that PACER enhanced CRC-cell proliferation, invasion, and metastasis in vitro. Analysis of lncRNA localization by FISH showed that it mainly resided in the nucleus. RT-qPCR showed that PACER increased mRNA levels of COX-2. Western blot analysis demonstrated, under normal circumstances, that knock-down of PACER decreased the COX-2 protein level. In the case of p50 absence, COX-2 protein increased rapidly and remained highly expressed after knocking down PACER. Luciferase assay revealed that PACER modulated the COX-2 promoter region. Mouse xenograft models of CRC revealed that PACER promoted colorectal tumorigenesis in vivo. ELISA revealed that PACER knock-down inhibited PGE2 production. CONCLUSIONS: PACER modulates COX-2 expression through the nuclear factor kappa B (NF-κB) pathway in CRC. An increased level of PACER enhances proliferation, migration, and invasion of tumor cells by increasing COX-2 and PGE2 synthesis.

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study.

BACKGROUND: Brain metastasis (BM) from colorectal cancer (CRC) is rarely encountered clinically, and its prognosis has not been fully evaluated. AIM: To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC. METHODS: A retrospective study of 371 patients with synchronous BM from CRC was performed, using the data from 2010 to 2014 from the Surveillance, Epidemiology, and End Results database. Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models, respectively. A scoring system was developed using the independent prognostic factors, and was used to measure the survival difference among different patients. RESULTS: For the 371 patients, the median overall survival was 5 mo, survival rates were 27% at 1 year and 11.2% at 2 years. Prognostic analysis showed that age, carcinoembryonic antigen level and extracranial metastasis to the liver, lung or bone were independent prognostic factors. A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups (scores of 0-1, 2-3, and 4). The median survival of patients with scores of 0-1, 2-3 and 4 was 14, 5 and 2 mo, respectively (P < 0.001). Subgroup analysis showed that there were significant differences in prognosis among the groups. Score 2-3 vs 0-1: hazard ratio (HR) = 2.050, 95%CI: 1.363-3.083; P = 0.001; score 4 vs 0-1: HR = 3.721, 95%CI: 2.225-6.225; P < 0.001; score 2-3 vs 4: HR = 0.551, 95%CI: 0.374-0.812; P = 0.003. CONCLUSION: The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC. These results are helpful in providing a reference for guiding therapy.

Evaluation of clinical significance of claudin 7 and construction of prognostic grading system for stage II colorectal cancer.

BACKGROUND: Claudin 7 is often abnormally expressed in cancers and promotes the progression of some malignancies. However, the role of claudin 7 in stage II colorectal cancer (CRC) has not been studied. AIM: To assess the expression and prognostic value of claudin 7 in stage II CRC. METHODS: We retrospectively studied 231 stage II CRC patients who underwent radical surgery at our hospital from 2013 to 2014. The protein expression level of claudin 7 was assessed and its relationship with clinicopathological features and prognosis was statistically analyzed. The independent prognostic factors were identified by Cox proportional hazards models. A prognostic grading system was constructed to stratify the survival of CRC patients. RESULTS: The expression of claudin 7 was significantly reduced in cancer tissues compared with normal tissues (P < 0.001), and its low expression was closely related to recurrence of the disease (P = 0.017). Multivariate analysis confirmed that claudin 7 low expression (claudin 7-low) (P = 0.028) and perineural invasion positivity (PNI+) (P = 0.026) were independent predictors of poor disease-free survival (DFS). A prognostic grading system based on the status of claudin 7 and PNI classified the patients into three prognostic grades: grade A (claudin 7-high and PNI-), grade B (claudin 7-low and PNI-, claudin 7-high and PNI+), and grade C (claudin 7-low and PNI+). The DFS was significantly different among the three grades (grade B vs grade A, P = 0.032; grade C vs grade A, P < 0.001; grade C vs grade B, P = 0.040). CONCLUSION: Claudin 7 can be used as a new prognostic marker to predict the DFS of patients with stage II CRC. The prognostic grading system with the addition of claudin 7 can further improve prognosis stratification of patients.

A prognostic index model to individually predict clinical outcomes for colorectal cancer with synchronous bone metastasis.

Background: The prognosis of synchronous bone metastasis (BM) in colorectal cancer (CRC) is poor and rarely concerned. A clinical tool to evaluate the prognosis and clinical outcomes for BM would be attractive in current clinical practice. Methods: A total of 342 CRC patients with synchronous BM were identified from Surveillance, Epidemiology, and End Results (SEER) database. The cancer specific survival (CSS) was estimated with the Kaplan-Meier method. Prognostic factors were identified from multivariate Cox model, and the final clinical nomogram was developed to predict the CSS. The concordance index (C-index) was used to assess the discriminative ability. Calibration curves were provided to internally validate the performance of the nomogram. Results: The nomogram finally consisted of 6 prognostic factors including age, tumor grade, AJCC N stage, carcinoembryonic antigen (CEA) levels, primary tumor resection and chemotherapy, which translated the effects of prognostic factors into certain scores to predict the 1-, 2- and 3-year CSS for the synchronous BM in CRC patients. The nomogram presented a good accuracy for predicting the CSS with the C-index of 0.742. The calibration of the nomogram predictions was also accurate. Conclusions: This nomogram was accurate enough to predict the CSS of CRC patients with synchronous BM using readily available clinicopathologic factors and could provide individualized clinical decisions for both physicians and patients.

The Distinction of Clinicopathological Characteristics, Treatment Strategy and Outcome in Colorectal Cancer Patients With Synchronous vs. Metachronous Bone Metastasis.

Background: The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC. Methods: We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS. Results: Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; p < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; p = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis (p < 0.001). The median CSS was 11 months in both SBM and MBM group (p = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM. Conclusion: The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.

GGN Promotes Tumorigenesis by Regulating Proliferation and Apoptosis in Colorectal Cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. GGN is a germ cell-specific gene, but its function in CRC has been rarely reported to date. The aim of this study was to investigate the potential role of GGN in CRC tumorigenesis. Therefore, in this study, we examined the expression of GGN in CRC cell lines and tissues and its effects on cellular proliferation and apoptosis. We then explored the underlying mechanism. Our results showed that GGN was significantly overexpressed in both CRC cell lines and tissues. Silencing GGN robustly inhibited proliferation of CRC cells, and it also promoted apoptosis of CRC cells. Moreover, knockdown of GGN inhibited the expression of p-Akt in CRC cells. Taken together, these results showed that knockdown of GGN inhibits proliferation and promotes apoptosis of CRC cells through the PI3K/Akt signaling pathway. Our findings revealed for the first time a potential oncogenic role for GGN in CRC progress. This finding may provide a unique perspective on how a germ cell-specific gene might serve as a biomarker, or even as a therapeutic target, for CRC.

Validity and necessity of sub-classification of N3 in the 7th UICC TNM stage of gastric cancer.

BACKGROUND: The 7th TNM staging is the first authoritative standard for evaluation of effectiveness of treatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed. In particular, the N3 sub-stage is becoming more conspicuous. METHODS: Clinical data of 302 pN3M0 stage gastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital from January 2001 to May 2006 were retrospectively analyzed. RESULTS: Location of tumor, depth of invasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate of lymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastric cancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis than other sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0. T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. In multivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors. CONCLUSIONS: The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should therefore be applied in the TNM stage system.

[Treatment and prognostic analysis of early stage of primary gastric diffuse large B-cell lymphoma].

OBJECTIVE: To explore the prognostic factors and to compare chemotherapy alone versus surgical resection plus chemotherapy for early stage primary gastric diffuse large B-cell lymphomas (DLBCL). METHODS: Clinical data of 75 patients who were diagnosed as primary gastric DLBCL between January 1993 and August 2008 in Cancer Institute and Hospital of Tianjin Medical University were reviewed retrospectively. RESULTS: Among these 75 patients, 20 patients received chemotherapy alone and 55 underwent surgical resection plus chemotherapy. Complete remission rates were 65.0% (13/20) and 83.6% (46/55), effective rates were 75.0% (15/20) and 92.7% (51/55), and 5-year survival rates were 86.9% and 78.7% respectively in chemotherapy alone group and resection plus chemotherapy group, while the differences were not statistically significant (all P>0.05). Multivariate Cox regression model showed that international prognosis index (IPI) was the only independent prognostic factor (P<0.05, HR=11.350, 95%CI:1.011-127.371). CONCLUSIONS: In early stage of DLBCL, IPI is the only independent prognostic factor. The clinical outcomes are comparable between chemotherapy alone and surgical resection plus chemotherapy.

[Clinicopathological characteristics and prognostic analysis of bone metastasis in gastric cancer patients].

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of bone metastasis in gastric cancer patients. METHODS: Clinicopathological data of 66 gastric cancer patients with bone metastasis, who were treated at the Tianjin Medical University Cancer Institute and Hospital from October 1997 to September 2011, were analyzed retrospectively. The clinicopathological characteristics of the primary cancer and bone metastasis were summarized and the prognosis was analyzed. RESULTS: Of 66 patients, 4 underwent operation, 28 chemotherapy, 32 inhibitors of bone resorption,8 local treatment and 23 symptomatic treatment alone. The median survival time of these 66 patients was 5 months (95%CI:3.3-6.7 months). The 1-, 2- and 3-year survival rates were 9.1%, 3.0% and 1.5%, respectively. Univariate Log-rank test indicated that gender, bone metastasis combined with other distant metastasis and chemotherapy were significant prognostic factors (all P<0.05). Multivariate analysis revealed bone metastasis combined with other distant metastasis was an independent prognostic factor (P=0.011, RR=2.067, 95%CI:1.178-3.626). CONCLUSIONS: Prognosis of patients with bone metastasis from gastric cancer is poor. Chemotherapy-based comprehensive treatment may improve the prognosis of these patients.

[Risk factors for early recurrence after radical resection of proximal gastric cancer].

OBJECTIVE: To explore the risk factors for early recurrence (recurrence within 2 years) of proximal gastric cancer after radical resection. METHODS: The clinical data of 367 proximal gastric cancer patients who underwent radical resection in the Cancer Institute and Hospital of Tianjin Medical University between January 2000 and May 2006 were reviewed. Among them, there are 71 patients (19.3%) with early recurrence. Univariate analysis and multivariate analysis were applied to investigate risk factors for early recurrence. RESULTS: Univariate analysis showed that Borrmann type (P<0.01), histology type (P<0.01), depth of invasion (P<0.05), negative lymph nodes count (P<0.05) were risk factors for early recurrence of proximal gastric. On multivariate analysis, histology type (P<0.05), depth of invasion (P<0.05), negative lymph nodes counts (P<0.05) were independent risk factors for early recurrence of proximal gastric cancer. Negative lymph nodes in early recurrence patients were 8.4 ± 7.2, which were significantly less as compared to patients without early recurrence (10.7 ± 8.7) (P<0.05). CONCLUSION: For T3 proximal gastric adenosquamous cancer, extended resection and lymphadenectomy should be considered. Intraoperative or postoperative adjuvant treatment should be administered as routine.