A new membrane anatomy-oriented classification of radical surgery for rectal cancer.

For patients with different clinical stages of rectal cancer, tailored surgery is urgently needed. Over the past 10 years, our team has conducted numerous anatomical studies and proposed the "four fasciae and three spaces" theory to guide rectal cancer surgery. Enlightened by the anatomical basis of the radical hysterectomy classification system of Querleu and Morrow, we proposed a new classification system of radical surgery for rectal cancer based on membrane anatomy. This system categorizes the surgery into four types (A-D) and incorporates corresponding subtypes based on the preservation of the autonomic nerve. Our surgical classification unifies the pelvic membrane anatomical terminology, validates the feasibility of classifying rectal cancer surgery using the theory of "four fasciae and three spaces," and lays the theoretical groundwork for the future development of unified and standardized classification of radical pelvic tumor surgery.

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 Based on Membrane Anatomy for Lower Rectal Cancer: Surgical Technique and Short-Term Outcomes.

Background: Lateral lymph node dissection (LLND) is an effective treatment for metastatic lateral lymph nodes (LLNs) in lower rectal cancer, but with high complication rates due to a complicated procedure. This study aimed to introduce a new technique for LLND based on membrane anatomy to simplify the procedure and report short-term outcomes. Methods: Twenty-three patients with clinical stage II-III lower rectal cancer underwent three-dimensional (3D) laparoscopic total mesorectal excision (TME) plus LLND between July 2018 and December 2020. Demographic data, perioperative variables, and oncologic outcomes were recorded and analyzed. Complications were graded using the Clavien-Dindo (CD) score. Results: Based on the theory of "four fasciae and three spaces," we proposed a fascia-to-space surgical approach to perform LLND. 3D laparoscopic TME plus LLND was performed successfully in all patients. The mean operating time was 172 minutes with a mean blood loss of 85 mL. Postoperative complications were present in 5 (17.4%) patients (CD I-II), including a case of urinary retention. The median number of harvested LLNs was 9, and positive LLNs were detected in 7 (30.4%) patients. After a median follow-up of 26.5 months, 2 (8.7%) patients developed liver metastases, but no local recurrence. Conclusions: Laparoscopic LLND based on membrane anatomy is a safe, feasible, and reproducible procedure and thus worthy of clinical promotion. Further studies with long-term follow-up in larger patient series are still required.

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.

MSR1 characterized by chromatin accessibility mediates M2 macrophage polarization to promote gastric cancer progression.

BACKGROUND: M2 macrophages play an important role in gastric cancer progression and metastasis, but the underlying tumor-promoting mechanisms are largely unknown. METHODS: The TCIA database was used to identify the infiltration profile of macrophages. Integrated ATAC-seq, RNA-seq, and single-cell RNA sequencing (scRNA-seq) data from GC samples were used for the analysis. Using ATAC-seq profiles and RNA-seq datasets, combined with cox univariate survival analysis, we identified prognosis-related differentially expressed genes (DEGs) with chromatin accessibility, which were identified as hub genes. The CIBERSORTx algorithm was utilized to estimate the relative infiltration level of M2 macrophages, and Pearson correlation analysis was performed to investigate the relationship between hub genes and M2 macrophages. Multidimensional database validations were carried out to avoid biases. The expression level and function of hub genes in the clusters of macrophages were evaluated by using scRNA-seq data. The role of hub genes in the alternative activation of macrophages and gastric cancer malignant behaviors, as well as their potential regulatory mechanism in gastric cancer progression, were further explored. RESULTS: 17,334 genes were acquired with chromatin accessibility in promoter regions by ATAC-seq. 2,714 genes were identified with both chromatin accessibility and differential expression based on the gene expression profiles (RNA-seq). By performing Cox univariate survival analysis, 171 survival-related DEGs with chromatin accessibility were identified as hub genes. Through the CIBERSORTx algorithm and Pearson correlation analysis, the gene MSR1 most associated with M2 macrophages was screened out. According to the scRNA-seq analysis, MSR1 was highly expressed in the clusters of macrophages and may be involved in regulating M2 macrophage polarization. In vitro experiments confirmed that M2 macrophage polarization and its induced malignant behavior of gastric cancer cells were inhibited by knockdown of MSR1. Furthermore, MSR1 mediated M2 macrophage polarization by regulating arginine and proline metabolism, thereby activating the AMPK/mTOR pathway to promote gastric cancer progression. CONCLUSION: We identified a gene-MSR1-characterized by chromatin accessibility, associated with poor prognosis in gastric cancer. This gene dictates the progression of gastric cancer by facilitating M2 macrophage polarization.

Laparoscopic total mesorectal excision with urogenital fascia preservation for mid-low rectal cancer: Anatomical basis and clinical effect - Experimental research.

BACKGROUND: Total mesorectal excision (TME) is conventionally performed according to Heald's principles through the so-called 'holy plane', between the visceral and parietal fasciae. However, urinary and sexual dysfunctions remain frequent postoperative complications. We proposed to preserve urogenital fascia (UGF) in TME, and this study aimed to clarify the anatomical basis of this technique and evaluate its efficacy and safety. MATERIALS AND METHODS: Cadaveric dissection was performed on 26 pelvises, and laparoscopic TME with UGF preservation was performed in 212 patients with mid-low rectal cancer. The fasciae and spaces related to TME were observed and described, and the clinical effect of UGF-preserving TME was analyzed. RESULTS: In the 26 cadavers, fascia propria of the rectum (FPR) presents as a fibrous capsule enveloping the mesorectum. UGF extends postero-laterally to the rectum, enveloping the hypogastric nerves and ureters. We demonstrated that the visceral fascia is actually the UGF, and FPR and visceral fascia (i.e. UGF) are two independent layers of fascia. Thus, FPR, UGF and parietal fascia form two avascular spaces behind the rectum. The plane ventral to the UGF is the real 'holy plane' for TME, rather than that dorsal to the UGF as is traditionally thought. Laparoscopic TME with UGF preservation was successfully performed in all 212 patients, with low perioperative complications (10.8%) and a low 3-year local recurrence rate (4.2%). Furthermore, the incidences of urinary and sexual dysfunctions at postoperative 6 months were only 6.1% and 10.8%, respectively. CONCLUSION: The avascular plane between the FPR and UGF (i.e. visceral fascia) is the real 'holy plane'. Laparoscopic TME with UGF preservation is a feasible radical surgery for mid-low rectal cancer, with better protection of urinary and sexual functions.

Targeted deep sequencing reveals APC mutations as predictors of overall survival in Chinese colorectal patients receiving adjuvant chemotherapy.

Objective: Targeted deep sequencing was used to characterize the mutational spectrum of APC in Chinese colorectal tumors in comparison to that in Caucasians from The Cancer Genome Atlas (TCGA) and to investigate whether APC mutations can predict overall survival in CRC patients receiving adjuvant chemotherapy.Methods: A total of 315 Chinese CRC patients including 241 stage II/III patients receiving fluorouracil-based adjuvant chemotherapy were included in this study. Next generation sequencing was carried out to detect somatic mutations on all APC exons. The associations between APC mutations and overall survival were determined by the Cox proportional hazards model.Results:APC was mutated in 221 of 315 colorectal tumors (70.2%). Chinese CRC had a much higher frequency of missense mutations (16.2% vs. 2.4%), but a lower frequency of nonsense (41.0% vs. 54.2%) and frameshift mutations (10.5% vs. 18.4%) than Caucasian CRC. Among stage II/III patients receiving fluorouracil-based adjuvant chemotherapy, APC mutations showed a significant association with worse survival (HR = 1.69; 95% CI, 1.10-2.62; p = .0179). Of the mutation types, frameshift mutations conferred the highest risk of death (HR = 2.88; 95% CI, 1.54-5.37; p =.0009). Among individual mutation sites, Arg232Ter, the most frequent mutation in Chinese CRC, exhibited the strongest negative impact on survival (HR = 2.65; 95% CI, 1.16-6.03; p =.0202).Conclusion:APC overall mutation was an independent predictor for overall survival of stage II/III CRC patients receiving fluorouracil-based chemotherapy.

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.

Comparison of surgical outcomes between video-assisted anal fistula treatment and fistulotomy plus seton for complex anal fistula: A propensity score matching analysis - Retrospective cohort study.

BACKGROUND: Video-assisted anal fistula treatment (VAAFT) is a new minimally invasive technique for treating complex anal fistula (CAF). This study aimed to compare the efficacy and safety of VAAFT with fistulotomy plus seton (FPS) for treatment of CAF. MATERIALS AND METHODS: We included 148 patients with CAF receiving surgical treatment at our hospital between January 2017 and December 2018. Propensity score matching (PSM) analysis was conducted with patients' baseline characteristics, and surgical outcomes were compared between the matched groups. Logistic analysis was performed to identify the risk factors for fistula recurrence after VAAFT. RESULTS: Among the study population, 68 and 80 patients underwent VAAFT and FPS, respectively. After PSM, 64 matched pairs of patients were created with no significant differences in baseline characteristics. Compared with FPS, VAAFT had greater efficiency of locating internal openings (90.6% vs. 100%), less intraoperative blood loss (26 ± 15 vs. 12 ± 5 mL), lower incidence of postoperative bleeding (10.9% vs. 1.5%), shorter postoperative hospital stay (6.8 ± 5.1 vs. 5.0 ± 3.3 days), reduced postoperative pain, and decreased wound secretion (all P < 0.05). VAAFT showed a significantly lower Wexner incontinence score than FPS (0.9 ± 1.7 vs. 1.9 ± 2.6, P = 0.003) at 3 months postoperatively, but no significant difference in the healing rate was observed either at 3-month or 1-year (P = 1.000) follow-up. A total of 12 patients (17.6%) developed fistula recurrence after VAAFT, and logistic analysis revealed that multiple fistula tracts, prolonged operating time and severe postoperative wound secretion were independent risk factors (odds risk = 2.18, 3.25 and 3.04, respectively, all adjusted P < 0.05). CONCLUSION: Compared with FPS, VAAFT offers some advantages for treatment of CAF, including minimal damage, less pain, rapid recovery, fewer complications and better sphincter preservation.

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.

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.

[Impact of neutrophil-to-lymphocyte ratio on the prognosis of patients with locally advanced colorectal cancer].

OBJECTIVE: To investigate the impact of neutrophil-to-lymphocyte ratio(NLR) on the prognosis of patients with locally advanced colorectal cancer (LACRC). METHODS: Clinicopathological data of 684 patients with stage II(-III( CRC undergoing radical resection at Shanghai Ruijin Hospital from January 2008 to December 2010 were analyzed retrospectively. NLR was calculated from neutrophil and lymphocyte counts on routine blood tests prior to surgery. The optimal cutoff value of NLR for predicting 5-year overall survival (OS) was determined through receiver operating characteristic (ROC) curve analysis. According to the cut-off value, patients were divided into high NLR and low NLR groups. Clinicopathological characteristics and prognosis were compared between two groups. Univariate and multivariate analyses were performed with Cox proportional hazards model to evaluate the impact of clinical factors on prognosis. RESULTS: A total of 396 male and 288 female patients were included in the study, with a median age of 62 years(range 21-92).Among these patients, 335 had rectal cancers and 349 had colonic cancers; 328 were TNM stage II( and 356 were stage III(. The end of follow-up was January 2016. ROC curve showed that the optimal cut-off value of NLR was 3.0, then patients were divided into low NLR group (NLR≤3.0, n=481) and high NLR group (NLR>3.0, n=203). Compared with low NLR group, the high NLR group was more likely to be older (median 64 vs. 61, t=-2.412, P=0.016), presented higher ratio of colonic cancer [66.0%(134/203) vs. 44.7%(215/481), χ2=25.945, P=0.000] and stage III( tumor [60.1%(122/203) vs. 48.6%(234/481), χ2=7.499, P=0.007], but lower ratio of first-degree relative cancer history [8.9%(18/203) vs. 15.6%(75/481); χ2=5.496, P=0.020]. However, no significant differences were observed between two groups in gender, smoking and drinking history, tumor differentiation grade, vessel invasion and nerve invasion (all P>0.05). The median follow-up time was 67 months (range 3-92), and the 5-year OS rates of high NLR and low NLR group were 59.6% and 73.2% respectively, with significant difference (P=0.001). Cox multivariate analysis revealed that age >65 years (HR=2.07, 95%CI=1.59-2.70, P=0.000), no first-degree relative cancer history (HR=2.01, 95%CI=1.23-3.28, P=0.005), poor differentiation grade (HR=1.65, 95%CI=1.26-2.15, P=0.000), positive vessel or nerve invasion (HR=1.92, 95%CI=1.35-2.71, P=0.000), high TNM stage(HR=2.10, 95%CI=1.59-2.77, P=0.000) and preoperative NLR>3.0(HR=1.51, 95%CI=1.14-2.00, P=0.004) were independent risk factors of prognosis for patients with LACRC. CONCLUSIONS: Preoperative NLR can influence the prognosis of patients with LACRC receiving radical surgery. High NLR is associated with poor prognosis.

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.

Preoperative combined hemoglobin, albumin, lymphocyte and platelet levels predict survival in patients with locally advanced colorectal cancer.

More than 50% of patients with colorectal cancer (CRC) are initially diagnosed with locally advanced CRC (LACRC), and half of those patients develop recurrence or metastasis after resection. Here, we investigated whether the novel index HALP, which is a combination of preoperative hemoglobin, albumin, lymphocyte and platelet levels, correlates with survival in LACRC patients. A total of 820 patients with LACRC from two independent hospitals were included in our study. The correlations between HALP and overall and cancer-specific survival were calculated using training and validation sets. Lower HALP values correlated with an increased risk of death and cancer-related death in both sets. Moreover, the risk score based on HALP allowed stratification of patients into distinct prognostic groups with greater accuracy than previously proposed indexes. These results suggest that HALP may be useful as a clinical prognostic factor for patients with LACRC.

[Preliminary efficacy of video-assisted anal fistula treatment for complex anal fistula].

OBJECTIVE: To evaluate the preliminary efficacy of video-assisted anal fistula treatment (VAAFT) for complex anal fistula. METHODS: Clinical data of 11 consecutive patients with complex anal fistula undergoing VAAFT in our department from May to July 2015 were reviewed. VAAFT was performed to manage the fistula under endoscope without cutting or resection. RESULTS: VAAFT was successfully performed in all the 11 patients. The internal ostium was closed using mattress suture in 10 cases, and Endo-GIA stapler in 1 case. The mean operative time was (42.0±12.4) min, mean hospital stay was (4.1±1.5) d. Complication included bleeding and perianal infection in 1 case respectively. After 1 to 3.2 months follow-up, success rate was 72.7%(8/11), and no fecal incontinence was observed. CONCLUSION: Video-assisted anal fistula treatment is an effective, safe and minimally invasive surgical procedure for complex anal fistula with preservation of anal sphincter function.

PPP1R12A Copy Number Is Associated with Clinical Outcomes of Stage III CRC Receiving Oxaliplatin-Based Chemotherapy.

AIM: To investigate the correlation between PPP1R12A gene copy number and clinical outcomes of oxaliplatin-based regimen in stage III colorectal cancer (CRC). METHODS: A total of 139 paraffin-embedded tissue samples of stage III CRC patients who received oxaliplatin-based treatment after radical surgery were recruited. Genomic DNA was extracted and purified from paraffin-embedded sections. Quantitative PCR methods were used to detect the relative copy number (RCN) of PPP1R12A. RESULTS: Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR = 2.186, 95% CI: 1.293-3.696; P = 0.003) and OS (HR = 2.782, 95% CI: 1.531-5.052; P < 0.001). Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIB HR = 2.870, P < 0.001; colon HR = 1.910, P = 0.037; OS: IIIB HR = 3.527, P < 0.001; IIIC HR = 2.662, P = 0.049; rectum HR = 4.229, P = 0.002). CONCLUSION: Our findings suggest the copy number of PPP1R12A can independently predict recurrence and overall survival of stage III colorectal cancer patients receiving oxaliplatin-based chemotherapy.

High-throughput RNAi screening of human kinases identifies predictors of clinical outcome in colorectal cancer patients treated with oxaliplatin.

The purpose of this study is to identify protein kinase genes that modulate oxaliplatin cytotoxicity in vitro and evaluate the roles of these genes in predicting clinical outcomes in CRC patients receiving oxaliplatin-based adjuvant chemotherapy. A high-throughput RNAi screening targeting 626 human kinase genes was performed to identify kinase genes whose inhibition potentiates oxaliplatin sensitivity in CRC cells. The associations between copy numbers of the candidate genes and recurrence-free survival and overall survival were analyzed in 142 stage III CRC patients receiving first-line oxaliplatin-based adjuvant chemotherapy who were enrolled from two independent hospitals. HT-RNAi screening identified 40 kinase genes whose inhibition potentiated oxaliplatin cytotoxicity in DLD1 cells. The relative copy number (RCN) of MAP4K1 and CDKL4 were associated with increased risks of both recurrence and death. Moreover, significant genes-based risk score and the ratios of RCN of different genes can further categorize patients into subgroups with distinctly differing outcomes. The estimated AUC for the prediction models including clinical variables plus kinase biomarkers was 0.77 for the recurrence and 0.82 for the survival models. The copy numbers of MAP4K1 and CDKL4 can predict clinical outcomes in CRC patients treated with oxaliplatin-based chemotherapy.

PIK3C2G copy number is associated with clinical outcomes of colorectal cancer patients treated with oxaliplatin.

PURPOSE: To investigate whether the copy number of PIK3C2G is associated with clinical outcomes for stage III colorectal cancer (CRC) patients treated with oxaliplatin-based chemotherapy. METHODS: A total of 142 CRC patients who received first-line oxaliplatin-based chemotherapy after curative surgery in Ruijin Hospital and The Tenth People's Hospital were recruited in this study. Patients were enrolled between June 2006 and December 2011, with follow-up to January 2014. Quantitative real-time PCR method was used to detect the copy number of PIK3C2G. Cox proportional hazards model and Kaplan-Meier curves were used to analyze the association between PIK3C2G copy number and clinical outcome. RESULTS: In patients with stage III disease, low copy number of PIK3C2G was associated with increased risk of both recurrence (HR, 2.44, 95% CI, 1.33-4.47, P=0.004) and death (HR, 2.89, 95% CI, 1.49-5.60, P=0.002). Multivariate analysis also indicated that low PIK3C2G copy number was a significant and independent predictor of OS and RFS of stage III CRC. CONCLUSIONS: PIK3C2G is capable of predicting the recurrence and overall survival of stage III CRC patients receiving oxaliplatin-based therapy.

[Laparoscopy assisted with transanal endoscopic microsurgery in the treatment of severe functional constipation].

OBJECTIVE: To investigate the feasibility and efficacy of laparoscopic subtotal colectomy and modified Duhamel procedure combined with transanal endoscopic microsurgery (TEM) in the treatment of severe functional constipation(SFC). METHODS: The clinical data of 10 patients with SFC treated by laparoscopic surgery combined with TEM between May 2010 and October 2012 in Ruijin Hospital of Shanghai Jiaotong University School of Medicine were retrospectively analyzed. The gastrointestinal quality of life index(GIQLI), Wexner constipation scale and daily frequency of defecation postoperatively during follow-up were collected. RESULTS: All the 10 operations were successfully accomplished laparoscopic subtotal colectomy combined with TEM without abdominal incision. There was no conversion to open procedure. One case had preventive terminal ileum stoma. The mean operative time was (256 ± 58) min. The mean blood loss was (178 ± 67) ml. The mean time to first flatus was (40 ± 11) h. There were no ureteric injury, anastomotic leak, pelvic sepsis and other complications postoperatively. There was one case of insufficient small bowel obstruction which was released by conservative treatments. The patients were discharged from the hospital in (9.0 ± 1.5) d postoperatively. The GIQLI in one year postoperatively was (112 ± 10) points, which indicated good results compared to (75 ± 12) points preoperatively (P=0.000). The Wexner constipation scale was 20.8 ± 2.2 preoperatively and decreased to 5.2 ± 1.8 at one year follow-up(P=0.000). CONCLUSION: Laparoscopic subtotal colectomy and modified Duhamel procedure combined with TEM provides SFC patients a safe and feasible minimally invasive surgery.