Anatomical study of the left colic artery in laparoscopic-assisted colorectal surgery.

BACKGROUND: It is important for lymph node dissection around the inferior mesenteric artery (IMA) with preservation of the left colic artery (LCA) to be aware of the track and the length of the LCA. We aimed to investigate the branching pattern and trajectory of LCA and measure the distances from the root of the IMA to the origin of the LCA (D mm) and from the origin of LCA to intersection of LCA and IMV (d mm) during laparoscopic left-sided colorectal operations. METHODS: We analyzed 106 patients who underwent laparoscope-assisted left-side colorectal surgery during laparoscopic surgery. The branching patterns among the IMA, LCA, and sigmoidal trunk were evaluated; the trajectory of LCA was examined; the D mm and d mm were measured using a length of silk in the surgical operation. RESULTS: In 59.5% patients, the LCA arose independently from the sigmoidal trunk (type A); in 8.5% patients, the LCA and sigmoidal trunk arose from the IMA at the same point (type B); in 29.2% patients, the LCA and sigmoidal trunk had a common trunk (type C); the LCA did not exist in 2.8% (type D).The D mm and d mm for all cases ranged from 15.0 to 65.3 mm (median, 43.1 mm) and from 20.3 to 46.2 mm (median, 34.8 mm), respectively. 74.8% of the LCA went straight upper left and upward to proximal part of descending colon (type I), 25.2% went to the lower left at first, then turned to travel straight upward to proximal part of descending colon (type II). CONCLUSION: This study showed the anatomic variations of LCA during laparoscopic left-sided colorectal operation, which would help surgeons safely perform laparoscopic surgery in the left-side colon and rectum.

Nanocarriers of Fe3O4 as a Novel Method for Delivery of the Antineoplastic Agent Doxorubicin Into HeLa Cells in vitro.

Here we report the synthesis and in vitro characterization of a redox-sensitive, magnetically inducible nanoparticle carrier system based on the doxorubicin (DOX) drug delivery model. Each quantal nanocarrier unit consists of a magnetite Fe3O4 nanoparticle core that is further encapsulated in self-assembled micelles of the redox-responsive polyethylene glycol derivative, DSPE-SS-mPEG. The nanocarrier system was prepared using a combination of ultrasonication and dialysis to produce the microenvironment sensitive delivery system. The final synthesized and DOX-loaded magnetic nanocarriers had an average size of ~150 nm when assembled with a 6.9% DOX payload. The release rate of DOX from these redox-responsive magnetic nanocarriers was shown to be accelerated in vitro when in the presence of glutathione (GSH). Furthermore, we demonstrated that more redox-responsive magnetic nanocarriers could be taken up by HeLa cells when a local magnetic field was applied. Once internalized within a cell, the micelles of the outer nanocarrier complex were broken down in the presence of higher concentrations of GSH, which accelerated the release of DOX. This produces a particle with dual operating characteristics that can be controlled via a specific cellular environment coupled with an exogenously applied signal in the form of a magnetic field triggering release.

Artificial intelligence system of faster region-based convolutional neural network surpassing senior radiologists in evaluation of metastatic lymph nodes of rectal cancer.

BACKGROUND: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. METHODS: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. RESULTS: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. CONCLUSION: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. TRIAL REGISTRATION: www.chictr.org.cn (No. ChiCTR-DDD-17013842).

Security and Radical Assessment in Open, Laparoscopic, Robotic Colorectal Cancer Surgery: A Comparative Study.

PURPOSE: This retrospective study was designed to assess the safety and effectiveness of open, laparoscopic, robotic colorectal cancer surgery. METHODS: Three hundred patients with colorectal cancer who underwent curative resection in the First Affiliated Hospital of Zhengzhou University between February 2014 and May 2016 were included. Patients were classified into open surgery group, laparoscopic surgery group, and robot-assisted group. RESULTS: The blood loss in laparoscopic surgery group was less than that in open surgery group, and the blood loss in robot-assisted group less was than the open surgery group. The number of lymph node dissection in robot-assisted group was significantly larger than that in the open group ( P < .05). The distance between the lower edge of the tumor group and the distal margin in robotic group was longer than that of the laparoscopic surgery group and the open group ( P < .05). Three (2.8%) cases of urinary retention occurred in the open surgery group, 4 (3.92%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group, while 2 (1.87%) cases of sexual dysfunction occurred in the open surgery group, 2 (1.96%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group. The urinary retention and sexual dysfunction rate did not differ between the 3 groups ( P > .05), but the minimally invasive group showed a certain advantage over the open group. CONCLUSION: Compared to the traditional open surgery, minimally invasive surgery (especially in robot-assisted group) has advantages such as less intraoperative bleeding, rapid postoperative recovery, and radical cure; open group, laparoscopic surgery group, and robot-assisted group have a similar incidence of postoperative complications, but reduction in the incidence of anastomotic leakage and intestinal obstruction. Robot-assisted group has the potential advantage for pelvic autonomic nerve protection.

Long non-coding RNA LINC00959 predicts colorectal cancer patient prognosis and inhibits tumor progression.

Long non-coding RNAs (lncRNAs) are increasingly implicated in tumorigenesis and cancer progression. This study focused on the relationship between the lncRNA LINC00959 and colorectal cancer (CRC). We found that LINC00959 expression was lower in CRC tissues than normal colorectal mucosae. High LINC00959 expression was negatively associated with TNM stage, distant metastasis, and lymphatic metastasis, and correlated with a better prognosis in 87 CRC cases. In vitro, LINC00959 knockdown enhanced colon cancer cell proliferation, invasion, and migration; upregulated N-cadherin and vimentin; and downregulated E-cadherin and Caspase-3. LINC00959 overexpression produced the opposite effects. These data suggest that LINC00959 inhibits tumor cell invasion and migration by suppressing epithelial-mesenchymal transition and promotes apoptosis through Caspase-3. LINC00959 may be a tumor suppressor and useful prognostic biomarker in CRC.

MiR-590-3p promotes proliferation and metastasis of colorectal cancer via Hippo pathway.

Studies reported that miR-590-3p was involved in human cancer progression. However, its roles of oncogene or anti-oncogene in malignancies still remain elusive. This study was aimed to investigate the effect of miR-590-3p on the cell proliferation and metastasis via Hippo pathway in colorectal cancer (CRC). In our study, miR-590-3p was demonstrated highly expressed in CRC tissues, compared with adjacent normal tissues (P<0.05). In addition, miR-590-3p was positively associated with TNM stage and distant metastasis. Survival analysis showed that high miR-590-3p was related with poor overall survival rate. Then, over-expressed miR-590-3p was demonstrated to promote proliferation, invasion and migration of colon caner cells. What's more, MST1, LATS1 and SAV1 mRNA were showed lowly expressed and YAP1 expression in mRNA and protein levels were highly expressed in CRC tissues, compared with adjacent normal tissues (all P<0.05). miR-590-3p expression was negatively associated with LATS1 and SAV1 mRNA respectively and positively related with YAP1 mRNA in CRC tissues, meanwhile, there was no relationship between miR-590-3p and MST1 mRNA. Furthermore, over-expressing miR-590-3p inhibited expressions of LATS1 and SAV1, promoted YAP1 expression and didn't effect MST1 expression in colon cancer cells. And luciferase assay showed that miR-590-3p over-expression inhibited the luciferase activity of LATS1 and SAV1 3'UTR, meanwhile it had no effect on the mutated form of these two plasmids. Taken together, these data suggest that highly-expressed miR-590-3p promotes biological effect of proliferation and metastasis via targeting Hippo pathway, and predicts worse clinical outcomes of CRC patients.

Prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer from multiple centers in China.

AIM: To explore the features and prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer (CRC). METHODS: In all, 321 cases of T1-stage CRC were selected from 10132 patients with CRC who received surgical therapy in six large-scale hospitals in China and were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for lymphatic metastasis. A survival analysis was then performed to analyze the prognostic value of lymph node metastasis. RESULTS: The occurrence rate of T1 stage was 3.17% (321/10132); of these patients, the lymph node metastasis rate was 8.41% (27/321), and the non-lymph node metastasis rate was 91.59% (294/321). Univariate analysis showed that preoperative serum CEA, preoperative serum CA199, preoperative serum CA724, vascular invasion, and degree of differentiation were associated with lymph node metastasis in T1-stage CRC (P < 0.05 for all). Multivariate analysis indicated that preoperative serum CA724, vascular invasion, and degree of differentiation were closely related to lymph node metastasis (P < 0.05 for all). Log-rank survival analysis showed that age, preoperative serum CEA, preoperative serum CA199, vascular invasion, degree of differentiation, and lymph node metastasis (χ2 = 24.180, P < 0.001) were predictors of 5-year overall survival (OS) (P < 0.05 for all). COX regression analysis demonstrated that preoperative serum CA199 and lymph node metastasis (HR = 5.117; P < 0.05; 95%CI: 0.058-0.815) were independent prognostic indicators of 5-year OS in patients with T1-stage CRC (P < 0.05 for both). CONCLUSION: The morbidity of T1-stage CRC was 3.17% for all CRC cases. Preoperative serum CA724, vascular invasion, and degree of differentiation are independent risk factors for lymph node metastasis. Lymph node metastasis is an independent prognostic factor for OS in patients with T1-stage CRC.

Modification of chemokine receptor expression to enhance levels of trafficking receptors on autologous cytokine-induced killer cells derived from patients with colorectal cancer.

Cytokine-induced killer (CIK) cells have achieved therapeutic benefit in treatment of solid tumors in clinic. However, some patients show no response after CIK treatment. Animal assays have shown that successful infiltration of CIK cells to the tumor sites could affect the outcome. Chemokines play important roles in lymphocyte trafficking. Understanding the molecular mechanism of chemokines in the process of CIK cell homing is important for further modification of CIK therapy. In this study, we investigated the spectrum of chemokine ligands in the colorectal cancer sites and observed that chemokine ligands CCL20 and CXCL10 were overexpressed in the CRC tumor tissues compared with adjacent tissues. Although the corresponding receptors CCR6 and CXCR3 increased on CIK cells compared with PBMCs, their expression on CIK cells derived from CRC patients had lower levels than healthy donors, which might be a limited factor for autologous-CIK cells trafficking to tumor site. Importantly, stimulation with chemokines CCL20 and CXCL10 promotes the expression levels of CCR6 and CXCR3 on CIK cells, thus augmenting the relative migration of CIK cells in vitro. Our results suggest that modification of surface chemokine receptors may enhance the homing ability of CIK cells for better therapeutic achievements.

[Alterations of Cajal cells in the colon of slow transit constipation rats].

OBJECTIVE: To investigate the association of expression of c-kit (marker of interstitial cells of Cajal, ICC) in colon with slow transit constipation (STC) in rats. METHODS: Slow transit constipation (STC) rat model was induced by intragastric administration of compound diphenoxylate. Western blotting was used to measure the expression of c-kit in colon of STC rats (model group) and normal rats (control group). Gray scale ratio of c-kit to ß-actin was used as the relative quantity of c-kit. RESULTS: Fecal quantity per day of STC group was (1.3±0.7) g/100 g, significantly lower than that in normal rats [(1.6±0.9) g/100 g, t=10.798, P<0.05]. In model rats, the time of discharge of the first black fecal was (461.6±150.8) min, significantly longer than that in normal rats [(351.3±119.9) min, t=2.291, P<0.05]. Western blotting revealed that the average values of gray scale ratio of c-kit in proximal colon were 0.277±0.077 and 0.576±0.081 (t=10.719, P<0.05), in distal colon were 0.280±0.075 and 0.571±0.079 (t=10.700, P<0.05) in model group and control group respectively. CONCLUSION: Down-regulation of c-kit expression in proximal colon and distal colon is associated to the pathogenesis of slow transit constipation in rats.

[Expression of aquaporin 3, 4, and 8 in colonic mucosa of rat models with slow transit constipation].

OBJECTIVE: To investigate the expression of aquaporin 3, 4, and 8 in the colonic mucosa of rat models with slow transit constipation (STC). METHODS: STC rat model was established by giving the rats the compound solution of diphenoxylate. Real time polymerase chain reaction (RT-PCR) was used to measure the expression of aquaporin mRNA in colonic mucosa of STC rat models (study group,n=16) and normal rats (control group,n=16). Gray scale ratio of aquaporin to ß-action (internal reference) was used for quantification. RESULTS: RT-PCR revealed that the mean gray scale ratios of aquaporin 3 in the proximal colon of the study group and control group were 0.344 and 0.602 (P<0.05), and were 0.419 and 0.509 in the distal colon (P>0.05), respectively. The mean gray scale ratios of aquaporin 4 in the proximal and the distal colon were 0.764 and 0.759 in the study group (P>0.05), and were 0.776 and 0.736 in the control group (P>0.05), respectively. However, there was no expression of aquaporin 8 in the proximal and the distal colon in either the study group or the control groups. CONCLUSIONS: Expression of aquaporin 3 in the proximal colon of STC rat models is down-regulated, which regulates water absorption. There are no significant changes in the expressions of aquaporin 4 and 8.

[Expression and significance of aquaporin 4 in the colonic mucosa of patients with slow transit constipation].

OBJECTIVE: To explore the relationship between the expression of aquaporin 4 (AQP4) and slow transit constipation(STC). METHODS: The expression of AQP4 in the ascending colon mucosa of 45 patients with STC was detected by immunohistochemistry. The transit time of stool was measured with barium sulfate suspensions. Stool was classified using Bristol stool chart. The difference between the pre- and post-operation groups was analyzed. RESULTS: Of 45 STC patients, 36 had high AQP4 expression (high expression group) and 9 had low AQP4 expression(low expression group). Preoperatively 30(83.3%) patients in the high expression group and 3(3/9) patients in the low expression group presented dry and hard stool (type I( or II()(P<0.01). Postoperatively, stool pattern was improved in all the patients of high expression group. One patient in low expression group still presented dry and hard stool(P<0.01). Preoperatively the transit time was(127.3+/-28.2) h in high expression group and (64.2+/-12.9) h in low expression group(P<0.01). Postoperatively, the transit time was (17.3+/-7.0) h in high expression group and (28.0+/-12.6) h in low expression groups(P<0.01). CONCLUSION: High expression of AQP4 accelerates the water absorption in colon mucosa and may be one of the crucial events in the development of STC.

[Expression and significance of aquaporin 3 and aquaporin 9 in colonic mucosa of patients with functional constipation].

OBJECTIVE: To study the expression and distribution of aquaporin 3 (AQP3) and aquaporin 9 (AQP9) in colonic mucosa of patients with functional constipation, and to examine the relationship of constipation with AQP3 and AQP9. METHODS: Immunohistochemistry and semi-quantitative Western blotting were used to detect the expression and distribution of AQP3 and AQP9 in colonic mucosa of 45 patients with functional constipation (trial group) and 21 cases without constipation (control group). Gray scale ratios of AQP3 and AQP9 to beta-actin protein as interior reference were relative amounts of AQP3 and AQP9. RESULTS: Immunohistochemistry showed that AQP3 was distributed mainly in basement and cavosurface membrane of epithelial cell of colonic mucosa and AQP9 mainly in basement membrane of goblet cell in cavosurface colonic mucosa. Western blotting revealed that the average values of gray scale ratios of AQP3 in ascending colon of trial group and control group were 0.905 and 0.798 (P<0.05),while those of AQP9 were 0.544 and 0.543 (P>0.05), respectively. The average values of gray scale ratios of AQP3 in descending colon of trial group and control group were 0.697 and 0.701 (P>0.05), while those of AQP9 were 0.575 and 0.732 (P<0.05), respectively. CONCLUSIONS: Up-regulated expression of AQP3 in ascending colon and down-regulated expression of AQP9 in descending colon are presented in patients with functional constipation as compared to patients without functional constipation. AQP3 and AQP9 may play a significant role in the onset and development of constipation.