Application of the Xi robotic platform for familial adenomatous polyposis with ultra-low rectal cancer: exploration of minimally invasive and refined therapies.

When a familial adenomatous polyposis (FAP) patient's rectal polyp undergoes malignant transformation, the surgeon needs to consider how to balance the quality of surgery with the patient's quality of life. Here, we present a case of robotic surgery in a patient with familial adenomatous polyposis and ultra-low rectal cancer. Fiberoptic colonoscopy found that hundreds of polyp-like bulges were diffusely distributed throughout the colon, and a malignant mass was found at the end of the rectum. The patient underwent total colectomy with abdominoperineal extended radical resection for rectal cancer using the Xi robotic platform. The patient recovered well in the postoperative period. The ileostomy was well used. And the patient was in good health and metastasis free at 9 months postoperatively. We identified total colectomy combined with extended radical rectal resection under the assistance of the da Vinci robot platform is of great benefit to the patient.

Long Noncoding XLOC_006390 Regulates the Proliferation and Metastasis of Human Colorectal Cancer via miR-296/ONECUT2 Axis.

Long noncoding RNA (LncRNA) XLOC_006390 has been shown to be dysregulated in cancer tissues and regulates cancer growth and development. Nonetheless, the molecular role of lncRNA-XLOC_006390 in colorectal cancer via modulation of miR-296/ONECUT2 axis is still unclear. Against this backdrop, the current study was designed to explore the role of lncRNA-XLOC_006390 in colorectal cancer proliferation and metastasis. The results revealed significant (P < 0.05) overexpression of lncRNA-XLOC_006390 in colorectal cancer tissues and cell lines, and the transcript levels increased with the advancement of the disease. Moreover, its high expression was shown to be associated with poor patient survival. Silencing of lncRNA-XLOC_006390 in colorectal cancer cells significantly (P < 0.05) suppressed their viability via onset of apoptosis and restricted cancer cell migration and invasion. In vivo tumor growth was significantly (P < 0.05) inhibited under lncRNA-XLOC_006390 repression. LncRNA-XLOC_006390 was shown to sponge the expression of miR-296-3p which in turn acted via post-transcriptional suppression of ONECUT 2 transcription factor to regulate the growth of colorectal cancer. Taken together, the results revealed the oncogenic role of lncRNA-XLOC_006390 in colorectal cancer via modulation of miR-296/ONECUT2 axis. The results also point towards its prognostic and therapeutic potential in the treatment of colorectal cancer.

Long-term oncologic outcomes of natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection in the treatment of rectal cancer: a propensity-score matching study.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has been increasingly applied in radical surgery of abdominal and pelvic organs, but it is still in the exploratory stage. There is insufficient evidence to prove its efficacy. METHODS: From January 2013 to June 2017, a total of 351 patients diagnosed with rectal cancer were eventually included in this study. Patients who underwent NOSES were assigned to the NOSES group, while patients undergoing conventional laparoscopic assisted resection were assigned as to the LAP group. Propensity score matching was used to align clinicopathological features between the two groups. RESULTS: From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (47.0 ± 60.4 ml vs 87.1 ± 101.2 ml, P = 0.011), shorter postoperative gastrointestinal recovery (50.7 ± 27.3 h vs 58.6 ± 28.5 h, P = 0.040), less postoperative analgesic use (36.8% vs 52.8%, P = 0.019), lower postoperative pain scores (P < 0.001), lower rate of postoperative complications (5.7% vs 15.5%, P = 0.020), more satisfaction with body image (P = 0.001) and cosmesis (P < 0.001) postoperatively. The NOSES group had a higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between the two groups. CONCLUSION: NOSES could be a safe and reliable technique for radical resection of rectal cancer, with better short-term outcomes than conventional laparoscopy, while long-term survival is not significantly different from that of conventional laparoscopic surgery.

Identification of the Crucial Role of CCL22 in F. nucleatum-Related Colorectal Tumorigenesis that Correlates With Tumor Microenvironment and Immune Checkpoint Therapy.

Colorectal cancer (CRC) is the third most common malignant cancer worldwide with the second highest mortality. Gut microbiota can educate the tumor microenvironment (TME), consequently influencing the efficacy of immune checkpoint inhibitors (ICIs). Fusobacterium nucleatum is one of the most crucial bacteria contributing to colorectal tumorigenesis, but the molecular mechanisms between F. nucleatum and TME or ICIs are poorly investigated. In the present study, we firstly analyzed differentially expressed genes and the biological functions between F. nucleatum-infected and uninfected CRC cell lines, with the findings that CCL22 mRNA expression was markedly upregulated after F. nucleatum infection. Moreover, the survival analysis showed that CCL22 was significantly associated with the overall survival of CRC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis suggested that CCL22 was related to immune-related terms. Furthermore, the ESTIMATE analysis indicated that the high-CCL22-expression subgroup had a higher immune/stromal/estimate score and lower tumor purity. The CIBERSORT analysis indicated that the high-CCL22-expression group had more immune-suppressive cells and less antitumor immune cells. In addition, immune checkpoint genes and cytotoxic genes were positively correlated with CCL22 expression. The immunophenoscore analysis suggested that CCL22 was associated with the IPS-CTLA4 and PD1/PD-L1/PD-L2 score. Interestingly, CCL22 expression in the KRAS and APC mutation groups was markedly reduced compared to that of the wild groups. In summary, our study provided evidence that CCL22 might play a crucial role in F. nucleatum-related colorectal tumorigenesis and correlate with TME and ICIs, which deserves further study.

Role of Phenotypes of Circulating Tumor Cells in the Diagnosis and Treatment of Colorectal Cancer.

OBJECTIVE: To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs' numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity. METHODS: We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics. RESULTS: The positive rate of M-CTCs was significantly higher in patients with tumor size ≥5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) >5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs >1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced. CONCLUSION: The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.

Genomic Analysis Reveals Heterogeneity Between Lesions in Synchronous Primary Right-Sided and Left-Sided Colon Cancer.

Background: The synchronous primary right-sided and left-sided colon cancer (sRL-CC) is a peculiar subtype of colorectal cancer. However, the genomic landscape of sRL-CC remains elusive. Methods: Twenty-eight paired tumor samples and their corresponding normal mucosa samples from 14 patients were collected from the Second Affiliated Hospital of Harbin Medical University from 2011 to 2018. The clinical-pathological data were obtained, and whole-exome sequencing was performed based on formalin-fixed and paraffin-embedded samples of these patients, and then, comprehensive bioinformatic analyses were conducted. Results: Both the lesions of sRL-CC presented dissimilar histological grade and differentiation. Based on sequencing data, few overlapping SNV signatures, onco-driver gene mutations, and SMGs were identified. Moreover, the paired lesions harbored a different distribution of copy number variants (CNVs) and loss of heterozygosity. The clonal architecture analysis demonstrated the polyclonal origin of sRL-CC and inter-cancerous heterogeneity between two lesions. Conclusion: Our work provides evidence that lesions of sRL-CC share few overlapping mutational signatures and CNVs, and may originate from different clones.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis.

Fibroblast activation protein alpha (FAP) is a marker of cancer-associated fibroblast, which is also expressed in cancer epithelial cells. However, the role of FAP in colorectal cancer (CRC) cells remains to be elucidated. Here we investigate the expression pattern of FAP in CRC tissues and cells to prove that FAP is upregulated in CRC cells. Loss- of and gain-of-function assays identified FAP promotes migration and invasion instead of an effect on cell proliferation. Microarray assays are adopted to identify the different expressed genes after FAP knockdown and gene set enrichment analysis (GSEA) is used to exploit the involved signaling pathway. Our works reveal FAP exerts a function dependent on NF-κB signaling pathway and FAP expression is associated with NF-κB signaling pathway in clinical samples. Our work shows FAP is secreted by CRC cells and soluble FAP could promote metastasis. To investigate the mechanism of FAP influencing the NF-κB signaling pathway, LC/MS is performed to identify the proteins interacting with FAP. We find that FAP binds to ENO1 and activates NF-κB signaling pathway dependent on ENO1. Blocking ENO1 could partially reverse the pro-metastatic effect mediated by FAP. We also provide evidences that both FAP and ENO1 are associated with CRC stages, and high levels of FAP and ENO1 predict a poor survival in CRC patients. In summary, our work could provide a novel mechanism of FAP in CRC cells and a potential strategy for treatment of metastatic CRC.

Comparison of natural orifice specimen extraction surgery and conventional laparoscopic-assisted resection in the treatment effects of low rectal cancer.

Natural orifice specimen extraction surgery (NOSES) is an intra-abdominal procedure that does not require an auxiliary incision to take a surgical sample from the abdominal wall through the natural orifice, but there are few systematic clinical studies on it. The aim of this study was to demonstrate the safety and feasibility of NOSES. We retrospectively analyzed the clinical data and follow-up of 165 patients with low rectal cancer who underwent NOSES or conventional laparoscopic surgery at our center from January 2013 to June 2015. From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (49.3 ± 55.8 ml vs. 75.1 ± 57.3 ml, p = 0.02), shorter postoperative gastrointestinal recovery (42.3 ± 15.5 h vs. 50.1 ± 17.0 h, p = 0.01), less postoperative analgesic use (35.6% vs. 57.6%, p = 0.02), lower postoperative pain scores, lower rate of postoperative complications (6.8% vs. 25.4%, p = 0.01), better satisfaction of the image and cosmesis of the abdominal wall postoperatively, and higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups. Overall, NOSES is a safe and reliable minimally invasive surgical technique for patients with low rectal cancer.

Long-Term Outcome Comparison Between Two Specimen Extraction Approaches for Middle Rectum Cancer: A Retrospective Study.

Objective. There are few studies comparing the long-term results of natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic-assisted resection (LA) in the treatment of middle rectal cancer. This retrospective analysis aimed to evaluate the reliability of NOSES. Method. From January 2013 to December 2017, all patients diagnosed with median rectal cancer in our hospital who underwent NOSES and LA were enrolled. We used propensity-score matching (PSM) to balance baseline data between the NOSES group and the laparoscopic group. The primary endpoint was overall survival (OS) and disease-free survival (DFS). We used the Kaplan-Meier method to estimate OS and DFS. Student's t-test was used to analyze the difference of continuous data. Categorical data were compared using the Kruskal-Wallis test or Fisher's exact test. Results. After PSM, 38 patients were included in each group. We found that surgical bleeding volume in the NOSES group was considerably lower than that in the LA group (49.5 ± 47.5 mL vs. 86.3 ± 83.5 mL, P = .01). From the short-term results, the first flatus and regular diet time in the NOSES group were shorter than those in the LA group (41.3 ± 25.2 vs. 54.0 ± 19.2 hours, P < .01 and 63.9 ± 42.6 hours vs. 105.1 ± 66.8 hours, P < .01, respectively). Long-term OS and DFS were not different between the groups. Conclusion. Therefore, NOSES is a reliable technique for middle rectal cancer treatment. Short-term outcomes are pointedly better than LA, while the two surgical approaches did not differ in the long-term outcomes or complication rate.

Long Noncoding RNA JAKMIP2-AS1 Promotes the Growth of Colorectal Cancer and Indicates Poor Prognosis.

BACKGROUND: The identification of cancer-associated long noncoding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. JAKMIP2-AS1 has not been reported in the literature, especially in the context of colorectal cancer. The aim of the present study was to examine the expression pattern of JAKMIP2-AS1 in colorectal cancer (CRC) and evaluate its biological role and clinical significance in tumor progression. METHODS: JAKMIP2-AS1 expression was analyzed in 56 CRC tissues and nine CRC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Overexpression and RNA interference (RNAi) approaches were used to investigate the biological functions of JAKMIP2-AS1. The effect of JAKMIP2-AS1 on proliferation was evaluated by CCK-8, colony formation, and EdU assays. Subcutaneous injection of cells was used to study proliferation in BALB/c nude male mice. Proliferation-related protein levels were examined by immunohistochemical analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). RESULTS: JAKMIP2-AS1 was highly expressed in both CRC samples and cell lines compared with the corresponding normal counterparts. The upregulation of JAKMIP2-AS1 expression promoted the proliferation of colorectal cancer cells. Moreover, patients with high levels of JAKMIP2-AS1 expression had a relatively poor prognosis. Inhibition of JAKMIP2-AS1 by RNAi decreased the proliferation of CRC cells in vitro and impeded cell growth in vivo. Ki-67 and PCNA levels were affected by JAKMIP2-AS1 knockdown or overexpression in vivo. CONCLUSION: Our findings indicate that JAKMIP2-AS1 is significantly upregulated in CRC tissues and regulates CRC cell proliferation. Thus, JAKMIP2-AS1 may represent a new marker of poor prognosis and is a potential therapeutic target for CRC intervention.

Long non-coding RNA TUG1 mediates 5-fluorouracil resistance by acting as a ceRNA of miR-197-3p in colorectal cancer.

One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we observed lncRNA TUG1 was associated to the 5-Fu resistance in colorectal cancer. Firstly, quantitative analysis indicated that TUG1 was significantly increased in recurrence CRC patient samples. Kaplan-Meier survival analysis indicated that high TUG1 expression in CRC tissues was significantly associated with a higher rate of disease progression. TUG1 knockdown re-sensitized the 5-Fu resistance in colorectal cancer cells, which were 5-Fu-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-197-3p could directly bind to TUG1 suggesting TUG1 might work as a ceRNA to sponge miR-197-3p. Extensively, our study also showed that TYMS was the direct target of miR-197-3p in CRC cells. Taken together, our study suggests that TUG1 mediates 5-Fu resistance in CRC via miR-197-3p/TYMS axis.

[Analysis of treatment and prognostic factors in colorectal cancer liver metastasis].

OBJECTIVE: To investigate the prognostic factors of colorectal cancer patients with liver metastasis in order to provide reference for clinical practice. METHODS: Clinicopathological and follow-up data of 264 cases of colorectal liver metastasis in our department from January 1997 to January 2012 were analyzed retrospectively. Among these 264 patients, 217 underwent primary colorectal cancer resection, 33 underwent combined resection of primary colorectal lesion plus liver metastasis, and 14 received stoma creation alone. Besides, 197 patients received adjuvant chemotherapy, 14 received adjuvant radiotherapy, and 42 underwent interventional treatment. Clinicopathological features and treatment scheme affecting prognosis were analyzed and prognostic stratification analysis was performed according to emergence time of liver metastasis (synchronous or metachronous). RESULTS: Of 264 patients, 1-, 3-, and 5-year overall survival rates were 77.0%, 31.7%, and 14.0%; median survival time was 25 months; 1-, 3-, and 5-year survival rates of synchronous colorectal liver metastasis were 68.8%, 22.3%, and 7.7%; 1-, 3-, and 5-year survival rates of metochronous colorectal liver metastasis were 95.8%, 49.0%, and 21.3%, whose difference was statistically significant (P<0.05). Multivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05). CONCLUSIONS: Radical operation and adjuvant chemotherapy should be emphasized for colorectal liver metastasis, especially for synchronous colorectal liver metastasis. Simple resection of primary tumor can not improve the overall survival of patients with colorectal liver metastasis.

[Analysis of prognostic factors and treatment of pulmonary metastasis from colorectal cancer].

OBJECTIVE: To investigate effect of the treatments and prognostic factors of patients with pulmonary metastasis from colorectal cancer. METHODS: Clinical data of 79 patients who suffered from lung metastatic diseases from colorectal cancer in 1990 - 2010 were retrospectively analyzed. The number of patients who had received lung operation was 22, and non-operated group contained 57 patients. Compared the prognosis of operated group and non-operated group and analyzed the prognostic factors. RESULTS: The median survival time after the pulmonary resections was 34.5 months; the overall survival of 1-, 3- and 5-year survival rates were 90.9%, 45.4% and 4.5%, and the overall of 1-, 3-, and 5-year survival rate in non-operated group were 59.6%, 14.0% and 0. The surgery (RR = 4.805, 95% CI: 1.864 - 12.384, P = 0.001) and the number of metastasis (RR = 2.177, 95% CI: 1.431 - 3.314, P = 0.010) were the factors that could influence the patients prognosis. CONCLUSION: The surgery for pulmonary metastases from colorectal cancer is effective.

Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy.

PURPOSE: We present the preliminary results of patients with advanced stage renal malignancy treated with high intensity focused ultrasound (HIFU), and investigate the safety and feasibility of using HIFU in the treatment of selected patients with renal tumors. MATERIALS AND METHODS: HIFU treatment was performed in 12 patients with advanced stage renal cell carcinoma and 1 patient with colon cancer metastasized to kidney. Patients were followed after treatment to observe complications and long-term therapeutic efficacy. Complications and changes in symptoms seen at presentation were recorded. Mid stream urine specimens were sent for microscopy and serum creatinine was measured postoperatively. Followup radiological examinations were performed to detect tumor response to the ablation. RESULTS: A total of 13 patients received HIFU treatment safely, including 10 who had partial ablation and 3 who had complete tumor ablation. After HIFU hematuria disappeared in 7 of 8 patients and flank pain of presumed malignant origin disappeared in 9 of 10 patients. Postoperative images showed decrease in or absence of tumor blood supply in the treated region and significant shrinkage of the ablated tumor. Of the 13 patients 7 died (median survival 14.1 months, range 2 to 27) and 6 were still alive with median followup of 18.5 months (range 10 to 27). CONCLUSIONS: This preliminary experience suggests that HIFU could be safe and feasible in the treatment of patients with advanced renal malignancy.

[Desmoplastic small round cell tumor: report of 2 cases].

OBJECTIVE: To recognize the characteristics of desmoplastic small round cell tumor (DSRCT) and improve the standard of diagnosis. METHODS: We retrospectively reviewed the clinical data on the treatment of 2 patients with DSRCT in terms of their conditions, tissue sources, pathologic characteristics, immunohistochemical methods, clinical manifestation, diagnosis, treatment and prognosis. RESULTS: Clinical manifestations were complicated. The 2 patients were mis diagnosed before operation. Their tumors consisted of irregular nests of small and round cells, with nuclear hyperchromatism and scant cytoplasm embedded in a plenty of fibrous connective tissues. The edge of the nest was clear, with different sizes and shapes. Immunohistochemically, the 2 patients were positive for CK or EMA, NSE, des and vim of the epithelium, nerve, muscle and interstitial. They died 9 months after operation. CONCLUSIONS: The tumor may occur in the abdomen, pelvic cavity and other sites, with different clinical manifestations. Routine examination should be replaced by immunohistochemical test for correct diagnosis of the tumor. Prognosis of most patients is not good.