Identification of a Novel Immune-Related CpG Methylation Signature to Predict Prognosis in Stage II/III Colorectal Cancer.

With the increasing incidence of colorectal cancer (CRC) and continued difficulty in treating it using immunotherapy, there is an urgent need to identify an effective immune-related biomarker associated with the survival and prognosis of patients with this disease. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of autoimmunity, aging, and cancer. In this study, we aimed to identify a novel immune-related methylated signature to aid in predicting the prognosis of patients with CRC. We investigated DNA methylation patterns in patients with stage II/III CRC using datasets from The cancer genome atlas (TCGA). Overall, 182 patients were randomly divided into training (n = 127) and test groups (n = 55). In the training group, five immune-related methylated CG sites (cg11621464, cg13565656, cg18976437, cg20505223, and cg20528583) were identified, and CG site-based risk scores were calculated using univariate Cox proportional hazards regression in patients with stage II/III CRC. Multivariate Cox regression analysis indicated that methylated signature was independent of other clinical parameters. The Kaplan-Meier analysis results showed that CG site-based risk scores could significantly help distinguish between high- and low-risk patients in both the training (P = 0.000296) and test groups (P = 0.022). The area under the receiver operating characteristic curve in the training and test groups were estimated to be 0.771 and 0.724, respectively, for prognosis prediction. Finally, stratified analysis results suggested the remarkable prognostic value of CG site-based risk scores in CRC subtypes. We identified five methylated CG sites that could be used as an efficient overall survival (OS)-related biomarker for stage II/III CRC patients.

LncRNA-SNHG7 interferes with miR-34a to de-sensitize gastric cancer cells to cisplatin.

Gastric cancer (GC) remains poor prognosis and survival issues due to the resistance of chemotherapies, such as cisplatin. The long non-coding RNA small nucleolar RNA host gene 7 (lncRNA-SNHG7) is known as an oncogenic molecule in diverse cancers. Here, we demonstrate that SNHG7 was significantly upregulated in gastric cancer and positively correlated with cisplatin resistance of gastric cancer cells that SNHG7 was significantly upregulated in cisplatin resistant cells. Silencing SNHG7 dramatically sensitized cisplatin resistant cells. In contrast, a negative correlation between lncRNA-SNHG7 and miR-34a was found that miR-34a was downregulated in gastric cancer patient tissues and significantly sensitized cisplatin resistant gastric cancer cells. Intriguingly, bioinformatical analysis indicated miR-34a has putative biding site for SNHG7 and such negative association between SNHG7 and miR-34a was verified in gastric cancer tissues. The cisplatin resistant cells displayed increased glycolysis rate and SNHG7 promoted cellular glycolysis rate of gastric cancer cells. Luciferase assay illustrated LDHA, a glycolysis enzyme, was the direct target of miR-34a. Importantly, inhibiting SNHG7 successfully suppressed LDHA expressions and sensitized cisplatin resistant cells and such inhibitory effects could be recovered by further anti-miR-34a. These findings suggest an important regulator mechanism for the SNHG7-mediated cisplatin resistance via miR-34a/LDHA-glycolysis axis.

Effect of colorectal resection combined with intraoperative radiofrequency ablation in treating colorectal cancer with liver metastasis and analysis of its prognosis.

PURPOSE: To explore the efficacy and safety of colorectal resection combined with intraoperative radiofrequency ablation (RFA) in the treatment of colorectal cancer (CRC) with liver metastasis. METHODS: The clinical data of 106 CRC patients with liver metastasis were retrospectively analyzed. There were 53 cases treated with CRC resection combined with RFA (RFA group) and 53 cases treated with surgical resection of CRC and liver metastasis (surgery group). The clinicopathological features, and perioperative and postoperative complications were compared between the two groups, and the patient's survival and tumor recurrence were recorded via follow-up. Moreover, the risk factors for survival and recurrence in patients were analyzed via univariate and multivariate Cox regression analyses. RESULTS: In the RFA group, the amount of intraoperative blood loss and the number of cases of blood transfusion were significantly smaller than those in the surgery group, and the postoperative hospital stay was obviously shorter than that in the surgery group. In the surgery group, the median recurrence-free survival was 16.4 months, and the 1-, 2- and 3-year tumor-free survival rates were 56.6%, 37.7% and 15.1%, respectively. In the RFA group, the median recurrence-free survival was 10.5 months, and the 1-, 2- and 3-year tumor-free survival rates were 41.5%, 17.0% and 7.5%, respectively. Log-rank test showed no statistically significant difference in overall survival between the two groups (p=0.151), but found in tumor-free survival (p=0.028). Besides, the results of univariate and multivariate analyses showed that the number of metastases, the maximum diameter of liver metastases and the N stage of the primary tumor were independent influencing factors for the postoperative overall survival of patients. The number of metastases >1, N1-2 stage of primary tumor and combined RFA were independent risk factors for tumor recurrence in patients. CONCLUSIONS: Compared with resection of CRC and liver metastasis, colorectal resection combined with RFA can significantly reduce the intraoperative blood loss and shorten the hospital stay, with a comparable long-term survival, but the tumor recurrence rate is higher than that in patients with resection.

Laparoscopy versus conventional laparotomy in the management of abdominal trauma: a multi-institutional matched-pair study.

BACKGROUND: Laparoscopy is being increasingly applied as either a diagnostic or therapeutic intervention in the management of abdominal trauma. However, its outcomes in comparison with conventional laparotomy remain unclear, especially in terms of therapeutic management. METHODS: This retrospective cohort study included patients from three trauma centers in Beijing, China. Fifty-four patients undergoing laparoscopic interventions for abdominal trauma by experienced laparoscopists were enrolled in the laparoscopy group (LP group). Another 54 patients who underwent laparotomy (LT group) were matched according to the patients' baseline characteristics, causes of injury, and hemodynamic parameters. Perioperative clinical parameters and short-term survival were compared between these two groups. RESULTS: The baseline characteristics were comparable between these two groups (LP vs. LT: Age, p = 0.112; Sex, p = 0.820; Injury severity score, p = 0.158; Cause distribution, p = 0.840). The most common cause was traffic accident (36.1%) and the most frequent surgical intervention was bowel repair/resection (34.3%) in our study. The operation time was similar in these two groups (LP vs. LT: 202.2 ± 72.58 vs. 194.11 ± 82.95 min, p = 0.295) while post-operative complication rate was slightly reduced in LP group (7.7% vs. 13.5%) with no statistical significance (p = 0.383). Opioid use was lower in the LP than LT group (11.67 ± 4.08 vs. 26.0 ± 13.42 morphine equivalents (MEQ), p = 0.034). The hospital stay was significantly shorter in the LP group (13.48 ± 10.9 vs. 18.64 ± 14.73 days, p = 0.021). One patient in the LT group died of an intra-abdominal abscess and multiple organ dysfunction syndrome 19 days postoperatively, while all patients in the LP group recovered and were discharged. CONCLUSION: Laparoscopy is feasible and safe in treating abdominal trauma patients in hemodynamically stable conditions performed by experienced surgeons. Laparoscopy might have the advantages of reduced pain and quicker recovery with similarly favorable clinical outcomes.

Significance of measurements of herniary area and volume and abdominal cavity volume in the treatment of incisional hernia: application of CT 3D reconstruction in 17 cases.

OBJECTIVE: To investigate the value of CT 3D reconstruction in the diagnosis and treatment of incisional hernia and the related factor of abdominal cavity volume. METHODS: Abdominal wall defect and herniary volume were measured using 3D reconstruction based on plain CT scans in 17 patients with incisional hernias. RESULTS: The herniary diameter, area and volume could be measured in the 17 patients and the abdominal cavity volume was also measured in 10 patients using the 3D reconstruction technique. The correlation indices of the abdominal cavity volume with the patient's height, weight and body mass index (BMI) were all less than 0.01. CONCLUSION: Herniary area and volume and abdominal cavity volume can be accurately calculated through CT 3D reconstruction. The patch area should be more than 5 times as large as the defect area; combined with the perioperative overlap margin measurement method, this results in more scientific surgical management. The ratio of the herniary volume to the abdominal cavity volume may be conducive to preoperative assessment of the risk of abdominal compartment syndrome (ACS); however, the ratio that may lead to postoperative ACS remains to be determined. There are correlations of abdominal cavity volume with patient height, weight and BMI, especially with weight. We therefore propose that the abdominal cavity volume should be evaluated with internationally accepted indices.

[Effectiveness analysis of laparoscopic repair of parastomal hernia using CK Parastomal patch].

OBJECTIVE: To summarize the surgical technique and the effectiveness of CK Parastomal patch in laparoscopic repair of parastomal hernia. METHODS: The clinical data were retrospectively analysed from 24 patients who received laparoscopic repair of parastomal hernia using CK Parastomal patch between June 2006 and March 2010. There were 15 males and 9 females with a median age of 55 years (range, 47-80 years). Among them, 19 patients were with colon parastomal hernia in the left lower quadrant and 5 patients with ileum parastomal hernia in the right lower quadrant. The parastomal hernia duration was 1 to 4 years (mean, 2.4 years). The maximal diameter of the hernia ring was 3 to 7 cm (mean, 5.2 cm). All patients did not receive hernia repair. RESULTS: Laparoscopic repair of parastomal hernia was successfully performed in 18 cases, and open repair was used in 6 cases because of extensive adhesion. The average operating time was 121 minutes (range, 78 to 178 minutes). All wounds healed by first intention. Wound seroma occurred in 8 cases at 3 to 7 days after operation and disappeared by aspiration. Eleven patients complained of pain in the operative area within 1 month after operation and it disappeared without intervention. All patients were followed up 6 to 39 months (mean, 27 months). One recurrence occurred at 3 months after operation, and no recurrence occurred in the other patients. CONCLUSION: Laparoscopic repair of parastomal hernia using CK Parastomal patch is a safe and feasible procedure with a satisfactory short-term effectiveness, but the long-term effectiveness should be further observed.

[Preventive effect of polypropylene mesh bonded norvancomycin slow-release microsphere on Staphylococcus aureus infection of incisional hernia repair model].

OBJECTIVE: Mesh infection may occur after incisional hernia repair using prosthetic mesh. Preparation of antibiotics-bonded meshes to prevent infection is one of the solutions. To evaluate the anti-infection effect of polypropylene mesh bonded norvancomycin slow-release microsphere by preparing the rat model of incisional hernia repair contaminated with Staphylococcus aureus. METHODS: The norvancomycin slow-release microspheres were prepared by emulsion and solvent evaporation method and they were bonded to polypropylene mesh (50 mg/mesh). The appearance of the microspheres was observed using scanning electronic microscope (SEM). The content of norvancomycin in microspheres and the release rate of the norvancomycin in norvancomycin-bonded polypropylene mesh were detected using high performance liquid chromatography method. The rat models of incisional hernia were developed in 40 healthy Sprague Dawley rats, aged 10-11 weeks and weighing 200-250 g. The rats were divided randomly into the experimental group (norvancomycin-bonded polypropylene mesh repair, n=20) and the control group (polypropylene mesh repair, n=20). And then the mesh was contaminated with Staphylococcus aureus. The wound healing was observed after operation. At 3 weeks after operation, the mesh and the tissue around the mesh were harvested to perform histological observation and to classify the inflammatory reaction degree. RESULTS: The norvancomycin microsphere had integrated appearance and smooth surface with uniform particle diameter, 64% of particle diameter at 60 to 100 microm, and the loading-capacity of norvancomycin was 19.79%. The norvancomycin-bonded polypropylene patch had well-distributed surface and the loading-capacity of norvancomycin was (7.90 +/- 0.85) mg/cm2. The release time of norvancomycin in vitro could last above 28 days and the accumulative release rate was 72.6%. The rats of 2 groups all survived to experiment completion. Wound infection occurred in 2 rats of the experimental group (10%) and 20 rats of the control group (100%), showing significant difference (chi2 = 32.727 3, P = 0.0000). The inflammatory reaction in experimental group was not obvious, grade I in 16 rats and grade II in 4 rats, and numerous inflammatory cell infiltration occurred in the control group, grade II in 3 rats and grade III in 17 rats, showing significant difference (chi2 = 32.314, P = 0.000). CONCLUSION: The polypropylene mesh bonded norvancomycin slow-release microsphere has definite anti-infection effect in rat model of incisional hernia repair contaminated by Staphylococcus aureus.

Repair of large abdominal wall defects using the Proceed™ surgical mesh with open intra-peritonium onlay method.

OBJECTIVE: To report our experience with the use of Proceed™, Ethicon, Norderstedt, Germany surgical mesh in the management of large abdominal wall defects with the open intra-peritonium onlay method. METHODS: Thirty-six patients with large incisional hernia or defects resulting from tumor resection carried out at the Department of General Surgery, the First Affiliated Hospital, General Hospital of People's Liberation Army, China between May 2007 and June 2010 were studied. The abdominal wall defect was repaired using Proceed™ mesh with the intra-peritonium onlay method. Different parameters were evaluated considering the complications such as seroma, hematoma, wound infection, mesh infection, chronic pain, wound sinus, and recurrences. RESULTS: All 36 defects were repaired using Proceed™ mesh. The mean size of the defects was 160 cm2 (range = 120-600 cm2). Eleven patients (30.6%) developed a complication (6 seromas, one minor wound infection, one wound sinus, 2 pulmonary infection, and one urinary tract infection). The mean follow-up period was 28 months (range 6-36 months). There were no cases of intestinal fistula or problems related to intestinal adhesion and chronic wound pain. No hernia recurrence, or mesh infection occurred. CONCLUSION: The intra-peritoneum repair technique for a large abdominal wall defect using Proceed™ mesh is a feasible and safe method, with no major complications.

[Use of allogenic acellular dermal matrix in abdominal wall hernia and defect repair in 31 cases].

OBJECTIVE: To summarize the clinical effect of allogenic acellular dermal matrix in repair of abdominal wall hernia and defect. METHODS: The clinical data were analyzed retrospectively from 31 patients with abdominal wall hernia and defect repaired by allogenic acellular dermal matrix between March 2007 and November 2009. There were 19 males and 12 females with an age range of 10-70 years (median, 42 years), including 6 abdominal wall defects caused by abdominal wall tumor resection, 4 patches infection after abdominal wall hernia repair using prosthetic mesh, 2 incisional hernia, 1 parastomal hernia, 1 recurrent parastomal hernia receiving mesh repair, 1 mesh infection caused by parastomal hernia repair using prosthetic patch, 3 mesh infection caused by tension free inguinal after hernia repair, and 13 inguinal hernia. There were 12 patients with contaminated or infectious wound. The disease duration was from 1 to 34 months (6 months on average). The defect size of abdominal wall ranged from 6 cm x 4 cm to 19 cm x 10 cm. Abdominal wall hernia or defect underwent repair using allogenic acellular dewall matrix. RESULTS: Of the 31 patients, 29 patients recovered with primary wound healing. Chronic sinus tract occurred in 1 patient and the wound was cured by change dressing. Wound dehiscence and patch exposure occurred in 1 patient, and second healing was achieved after change dressing. All the 31 patients were followed up 6-36 months, no abdominal wall hernia or hernia recurrence occurred in other patients except 1 patient who had abdominal bulge. And no foreign body sensation or chronic pain in wound area occurred. CONCLUSION: It is feasible and safe to use allergenic acellular dermal matrix patch for repair of abdominal wall hernia or soft tissue defect, especially in contaminated or infectious wound.

[In situ repair of parastomal hernia with Sublay methods in 34 cases].

OBJECTIVE: To summarize the therapeutic method and effectiveness of parastomal hernia repair in situ with sublay methods. METHODS: Between February 2003 and May 2009, 34 patients with parastomal hernia were treated with Sublay methods using primary midline incision approach and polypropylene patch. There were 23 males and 11 females with an average age of 58.4 years (range, 43-78 years). The disease duration was 1 to 17 years (mean, 4.7 years). Of 34 patients, 6 had recurrent parastomal hernia. The diameter of hernia ring was 5-12 cm (mean, 7.2 cm). RESULTS: Sublay technique repair was successfully performed in all patients. The operative time was 96-160 minutes (mean, 116 minutes). The gastric tube was pulled out 12 hours to 5 days (mean, 3 days) after operation. The drainage tube was taken out at 2-7 days (mean, 4 days) after operation. The postoperative hospitalization time was 7 to 15 days (mean, 9 days). And the incisions of 32 patients healed by first intention. Incisional fat liquefaction occurred in 1 case and infection in 1 case, and their incisions healed after dressing change. Seroma at the upper of the patch occurred in 7 patients and was cured by 2 to 3 times of percutaneous puncture and local pressure. Thirty-two patients were followed up 6-75 months (mean, 32 months). No chronic pain, lumping sensation, or local expansion in wound area occurred. Two recurrences occurred 3 months and 7 months after operation, respectively, and patients restored after expectant treatment or re-operation. CONCLUSION: The in situ Sublay methods using primary midline incision approach and nonabsorbable patch is a feasible and safe method for parastomal hernia repair.