Thymosin ß4, a potential marker of malignancy and prognosis in hepatocellular carcinoma.

BACKGROUND: The lack of effective early diagnostic markers is an obstacle in clinical diagnosis and treatment of hepatocellular carcinoma (HCC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an increasing popular approach for identification of clinically relevant parameters including biomarkers. PATIENTS AND METHODS: 540 subjects, including 274 HCC, 119 liver cirrhosis, 89 hepatitis, and 58 healthy volunteers were enrolled. MALDI-TOF MS was used to select potential novel biomarkers from serum of HCC patients. Its clinical application was evaluated by experiments and clinical data analysis. RESULTS: We identified Thymosin ß4 (Tß4) in serum by MALDI-TOF MS. The expression of Tß4 was detected up-regulating in HCC cells and tissues which enhanced motility of HCC cells. More important, the level of serum Tß4 was significantly elevated in HCC patients. The AUROC showed the optimum diagnostic cut-off was 1063.6 ng/mL, ROC and 95% CI of Tß4 (0.908; 0.880-0.935) were larger than that of serum AFP (0.712; 0.662-0.762; p < 0.001). The sensitivity (91.3% vs 83.1%) and specificity (81.2% vs 20.3%) of serum Tß4 were higher than alpha-fetoprotein (AFP). In AFP-negative HCC, the sensitivity could reach to 80.5%. ROC analysis showed serum Tß4 had a better performance compared with AFP in distinguishing early-stage and small HCC. Tß4 is correlated with TNM stage (p = 0.016) and vascular invasion (p = 0.005). Survival analysis indicated the survival time of Tß4 positive patients was shorter (p < 0.001). Cox analysis suggested Tß4 could be an independent factor for HCC prognosis. CONCLUSION: Tß4 may serve as a novel biomarker for HCC diagnosis and prognosis.

Nomogram for Predicting Risk of Intestinal Complications After Colorectal Cancer Surgery.

BACKGROUND Intestinal complications are a major cause of morbidity after colorectal cancer surgery. This study aimed to develop an effective nomogram for predicting risk of intestinal complications following colorectal cancer surgery. MATERIAL AND METHODS We retrospectively analyzed 1876 patients who underwent colorectal cancer surgery at Yangpu and Zhuji hospitals from January 2013 to October 2018. Intestinal complications were defined as intestinal obstruction, leakage or bleeding, or peritonitis within 30 days after surgery. A logistic regression model was used to identify the risk factors associated with postoperative intestinal complications, and a nomogram for intestinal complications was established. The predictive accuracy of the nomogram was assessed using area under the receiver operating characteristic curve (AUC) and calibration plot. RESULTS A total of 164 patients (8.7%) developed intestinal complications after colorectal cancer surgery; 35 (21.3%) of whom died in the postoperative period. Multivariate logistic analysis showed that male gender, history of abdominal surgery, preoperative intestinal obstruction/perforation, metastatic cancer, and lower level of hemoglobin and prognostic nutrition index were independent risk factors (P<0.05 for all). A nomogram was then constructed, and it displayed good accuracy in predicting postoperative intestinal complications with an AUC of 0.76. The calibration plot also showed an excellent agreement between the predicted and observed probabilities. CONCLUSIONS We constructed a nomogram based on clinical variables, which could provide individual prediction of postoperative intestinal complications with good accuracy.

Video-Assisted Anal Fistula Treatment (VAAFT) for Complex Anal Fistula: A Preliminary Evaluation in China.

BACKGROUND Although many attempts have been made to advance the treatment of complex anal fistula, it continues to be a difficult surgical problem. This study aimed to describe the novel technique of video-assisted anal fistula treatment (VAAFT) and our preliminary experiences using VAAFT with patients with complex anal fistula. MATERIAL AND METHODS From May 2015 to May 2016, 52 patients with complex anal fistula were treated with VAAFT at Yangpu Hospital of Tongji University School of Medicine, and the clinical data of these patients were reviewed. RESULTS VAAFT was performed successfully in all 52 patients. The median operation time was 55 minutes. Internal openings were identified in all cases. 50 cases were closed with sutures, and 2 were closed with staplers. Complications included perianal sepsis in 3 cases and bleeding in another 3 cases. Complete healing without recurrence was achieved in 44 patients (84.6%) after 9 months of follow-up. No fecal incontinence was observed. Furthermore, a significant improvement in Gastrointestinal Quality of Life Index (GIQLI) score was observed from preoperative baseline (mean, 85.5) to 3-month follow-up (mean, 105.4; p<0.001), and this increase was maintained at 9-months follow-up (mean, 109.6; p<0.001). CONCLUSIONS VAAFT is a safe and minimally invasive technique for treating complex anal fistula with preservation of anal sphincter function.

Prognostic Value of the Combination of Preoperative Hemoglobin, Lymphocyte, Albumin, and Neutrophil in Patients with Locally Advanced Colorectal Cancer.

BACKGROUND Systemic inflammatory response and nutritional status are important to the prognosis of patients with colorectal cancer (CRC). This study aimed to investigate the prognostic value of the combination of preoperative hemoglobin, lymphocyte, albumin, and neutrophil (HLAN) in patients with locally advanced CRC (LACRC). MATERIAL AND METHODS We performed a retrospective analysis in 536 LACRC patients undergoing radical surgery. The value of HLAN was defined as follow: HLAN=Hemoglobin (g/L)×Lymphocyte (/L)×Albumin (g/L)/Neutrophil (/L)/100. The X-tile program was used to determine the optimal cut-point of HLAN, and the prognostic value of HLAN for overall survival (OS) was evaluated with the Cox proportional hazard model. RESULTS The cut-point of HLAN was set at 19.5. Compared with the high-HLAN group, the low-HLAN group had a 1.50-fold (95% confidence interval 1.09-2.05) increased risk of death and a significantly lower OS rate (P<0.001). Furthermore, the risk stratification model based on HLAN (AUC=0.72) displayed better accuracy in OS prediction than the TNM system (AUC=0.61). CONCLUSIONS HLAN is a valuable prognostic marker for patients with LACRC.

New classification system for radical rectal cancer surgery based on membrane anatomy.

BACKGROUND: Total mesorectal excision along the "holy plane" is the only radical surgery for rectal cancer, regardless of tumor size, localization or even tumor stage. However, according to the concept of membrane anatomy, multiple fascial spaces around the rectum could be used as the surgical plane to achieve radical resection. AIM: To propose a new membrane anatomical and staging-oriented classification system for tailoring the radicality during rectal cancer surgery. METHODS: A three-dimensional template of the member anatomy of the pelvis was established, and the existing anatomical nomenclatures were clarified by cadaveric dissection study and laparoscopic surgical observation. Then, we suggested a new and simple classification system for rectal cancer surgery. For simplification, the classification was based only on the lateral extent of resection. RESULTS: The fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side around the rectum and form three spaces (medial, middle and lateral), and blood vessels and nerves are precisely positioned in the fascia or space. Three types of radical surgery for rectal cancer are described, as are a few subtypes that consider nerve preservation. The surgical planes of the proposed radical surgeries (types A, B and C) correspond exactly to the medial, middle, and lateral spaces, respectively. CONCLUSION: Three types of radical surgery can be precisely defined based on membrane anatomy, including nerve-sparing procedures. Our classification system may offer an optimal tool for tailoring rectal cancer surgery.

Laparoscopic lateral lymph node dissection in two fascial spaces for locally advanced lower rectal cancer.

BACKGROUND: The procedure for lateral lymph node (LLN) dissection (LLND) is complicated and can result in complications. We developed a technique for laparoscopic LLND based on two fascial spaces to simplify the procedure. AIM: To clarify the anatomical basis of laparoscopic LLND in two fascial spaces and to evaluate its efficacy and safety in treating locally advanced low rectal cancer (LALRC). METHODS: Cadaveric dissection was performed on 24 pelvises, and the fascial composition related to LLND was observed and described. Three dimensional-laparoscopic total mesorectal excision with LLND was performed in 20 patients with LALRC, and their clinical data were analyzed. RESULTS: The cadaver study showed that the fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side in a medial-lateral direction constituting the dissection plane for curative rectal cancer surgery, and the last three fasciae formed two spaces (Latzko's pararectal space and paravesical space) which were the surgical area for LLND. Laparoscopic LLND in two fascial spaces was performed successfully in all 20 patients. The median operating time, blood loss and postoperative hospitalization were 178 (152-243) min, 55 (25-150) mL and 10 (7-20) d, respectively. The median number of harvested LLNs was 8.6 (6-12), and pathologically positive LLN metastasis was confirmed in 7 (35.0%) cases. Postoperative complications included lower limb pain in 1 case and lymph leakage in 1 case. CONCLUSION: Our preliminary surgical experience suggests that laparoscopic LLND based on fascial spaces is a feasible, effective and safe procedure for treating LALRC.

PIK3CA and TP53 mutations predict overall survival of stage II/III colorectal cancer patients.

AIM: To investigate the predictive value of PIK3CA and TP53 mutation status in colorectal cancer (CRC) patients treated with 5-fluorouracil-based chemotherapy. METHODS: In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage II/III CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected. Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3CA and TP53 mutation status with overall survival (OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method. RESULTS: Among the 241 patients with stage II/III in this cohort, the PIK3CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3CA and TP53 double mutations. The PIK3CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3CA and TP53 mutations, those with double PIK3CA-TP53 mutations showed a significantly worse survival (univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors (multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status (Log-rank P = 0.041). CONCLUSION: Double mutation of PIK3CA and TP53 is correlated with a shorter OS in stage II/III CRC patients treated with 5-fluorouracil-based therapy.

Inhibition of Girdin enhances chemosensitivity of colorectal cancer cells to oxaliplatin.

AIM: To investigate the effect of Girdin knockdown on the chemosensitivity of colorectal cancer cells to oxaliplatin and the possible mechanisms involved. METHODS: Four siRNAs targeting Girdin were transfected into the chemoresistant colorectal cancer cell line DLD1. Real-time polymerase chain reaction (PCR) was employed to assess Girdin mRNA expression and the most effective siRNA was chosen for conversion into shRNA. Then, DLD1 cells were infected with lentiviruses expressing the Girdin shRNA and a scramble control, respectively, and Girdin mRNA and protein expression levels were assessed by real-time PCR and Western blotting. Furthermore, microarray experiments were used to assess global gene expression profile after Girdin suppression in DLD1 cells. Finally, the cytotoxic effect of simultaneous treatment with oxaliplatin and adriamycin (an inhibitor of a significantly downregulated gene after Girdin suppression in DLD1 cells) was examined by MTT assay. RESULTS: The most effective siRNA suppressed Girdin expression with an inhibition efficiency of 57%. Compared with the scramble control, DLD1 cells infected with the Girdin shRNA displayed decreased Girdin mRNA and protein levels (P < 0.05), and Girdin knockdown significantly enhanced chemosensitivity to oxaliplatin in colorectal cancer cells (P < 0.05). Microarray data revealed that 381 and 162 genes were upregulated and downregulated in response to Girdin reduction, respectively, with ratios > 1.2 or < 0.8 (P < 0.01). Interestingly, TOP2B (DNA topoisomerase 2-ß) was downregulated (ratio = 0.78, P = 0.0001) and oxaliplatin/adriamycin combination resulted in increased cell death compared with treatments with individual agents (P < 0.05). CONCLUSION: Girdin knockdown enhances chemosensitivity of colorectal cancer cells to oxaliplatin via TOP2B down-regulation. These findings provide a promising approach to overcome the chemoresistance of colorectal cancer cells.