Short-term outcomes of sleeve gastrectomy plus uncut jejunojejunal bypass (SG-uncut JJB) in patients with obesity: a preliminary prospective cohort study.

OBJECTIVE: To compare the safety, weight loss, and metabolic outcomes of patients with obesity with sleeve gastrectomy (SG) or sleeve gastrectomy plus uncut jejunojejunal bypass (SG-uncut JJB). METHODS: This prospective study included patients with BMIs ≥ 32.5 kg/m2 or refractory metabolic disorders undergoing SG or SG-uncut JJB between January and December 2020 in our hospital (NCT04534504). Weight loss, metabolic outcomes, surgical results, and complaints during 1-year follow-up were compared between two groups. RESULTS: Forty-seven patients were enrolled, 26 in the SG and 21 in the SG-uncut JJB groups. A longer operative time was observed in the SG-uncut JJB than in the SG group (140 (110-180) min vs. 90 (70-180) min, P = 0.001). No significant differences were found in complications. Total weight loss (TWL%) and excess weight loss (EWL%) in both groups increased with the duration of follow-up (P = 0.001). TWL% was greater at 1 month ((11.1 ± 2.4)% vs. (8.2 ± 4.4)%, P = 0.011] and 12 months [(29.7 ± 6.9)% vs. (20.3 ± 7.2)%, P = 0.001) with SG-uncut JJB than with SG. SG-uncut JJB and SG had similar metabolic outcomes and complaints during the 1-year follow-up, but less nausea was reported with SG-uncut JJB (9.2% vs. 46.2%, P = 0.006). CONCLUSION: In short-term follow-up, SG-uncut JJB was a safe and effective bariatric surgery procedure in patients with obesity.

Active surveillance in long period of total neoadjuvant therapy in rectal cancer: Early prediction of poor regression response.

Aim: To analyze locally advanced rectal cancer (LARC) patients and tumor characteristics during the period of total neoadjuvant therapy (TNT) and explore the risk factors that may predict poor tumor regression in response to TNT. Materials and methods: The data of 120 LARC patients who received TNT from December 2016 and September 2019 in our hospital were retrospectively analyzed. The clinicopathological characteristics of patients with different tumor regression responses were compared. Then we divided patients into two groups according to the carcinoembryonic antigen (CEA) clearance pattern after chemoradiation to explore risk factors that might predict the tumor regression response. Results: Of 120 LARC patients, 34 (28.3%) exhibited poor regression. Stratified analysis by tumor response showed that patients with poor response to TNT were more likely to obtain elevated CEA during the course of TNT (all P < 0.05). For those with elevated pretreatment CEA, fewer patients with poor response obtained normal CEA after chemoradiation (13.6% vs. 72.7%, P < 0.001). Besides, less patients' CEA levels in the poor response group decreased by greater than 50% after chemoradiation when compared with that in the good response group (18.2% vs. 60.6%, P = 0.002). Stratified analysis by CEA clearance pattern after chemoradiation showed patients who obtained an elevated pretreatment CEA and decreased by less than 50% after chemoradiation were more likely to have poor response to TNT compared to others (76.2% vs. 18.2%, P < 0.001). Logistic multivariate analysis revealed that cN2 (95% CI 1.553-16.448), larger tumors (95% CI 2.250-21.428) and CEA clearance pattern after chemoradiation (95% CI 1.062-66.992) were independent risk factors for poor tumor regression response. Conclusion: Approximately one-fourth of LARC patients with TNT achieved a poor regression response. Here, cN2, larger tumor size before treatment and elevated CEA levels were considered predictive features of a poor response. Active surveillance of CEA levels during the TNT course are potentially important, and CEA levels after chemoradiation might have important implications for the tumor response to TNT.

Impact of total neoadjuvant therapy consisting of consolidation chemotherapy on locally advanced rectal cancer survival.

PURPOSE: The objective was to compare disease-free survival (DFS) and distant metastasis in patients with neoadjuvant chemoradiotherapy (NCRT) and total neoadjuvant therapy (TNT) for locally advanced rectal cancer. METHODS: Patients with cT3-4N0M0 or cTxN1-2M0 rectal cancer were included in this retrospective study. Patients who received NCRT (radiotherapy with concurrent capecitabine) or TNT (radiotherapy with two concurrent cycles of capecitabine and oxaliplatin (CAPOX) followed by another two cycles of CAPOX) during January 2011 and November 2016 at Beijing Chaoyang Hospital, Capital Medical University were included. All patients had received radical surgery. Adverse events, pathological response and survival outcomes in the two groups were compared. RESULTS: One hundred eighty-two patients were enrolled, 120 in the TNT and 62 in the NCRT groups. No significant between-group differences in neoadjuvant therapy-associated adverse events or surgical complications were found. TNT achieved a higher pathological complete response (pCR) rate (25.8%) compared with NCRT (12.9%, P = 0.044). Patients in the TNT group had a higher 3-year DFS rate (82.8% versus 75.7%, P = 0.041) and lower distant metastasis rate (19.2% versus 33.1%, P = 0.049) than those in the NCRT group. Multivariate analysis showed that NCRT was an independent risk factor for DFS (95%CI 2.023-13.415, P = 0.001) and distant metastasis (95% CI 2.149-20.082, P = 0.001). CONCLUSION: With similar adverse events and a higher pCR rate when compared with NCRT, TNT might be considered as a safe and effective therapeutic strategy to improve prognosis in patients with locally advanced rectal cancer.

Long-term outcomes after extra-levator versus conventional abdominoperineal excision for low rectal cancer.

PURPOSE: Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. METHODS: One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. RESULTS: Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). CONCLUSION:  Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

Transcriptome of visceral adipose tissue identifies an inflammation-related ceRNA network that regulates obesity.

Obesity is becoming an epidemic of widespread concern, but the underlying causes remain elusive. In this study, whole transcriptome RNA sequencing revealed differential profiles of noncoding (nc) RNAs and mRNAs in visceral adipose tissue from obese (BMI > 32.5 kg/m2) and lean (BMI < 20 kg/m2) individuals, with 1920 differentially expressed genes, 1466 long noncoding (lnc) RNAs, 122 micro (mi) RNAs, and 52 circular (circ) RNAs identified. Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis revealed that these ncRNAs were involved in inflammation-related pathways that included cytokine-cytokine receptor interaction, the tumor necrosis factor and nuclear factor kappa B signaling pathways. The results indicated a critical role of inflammation in the pathogenesis of obesity. The network interaction of lncRNA, circRNA, and miRNA revealed a competing endogenous (ce) RNA network that was associated with inflammation. The ceRNA network included circORC5/miR-197-5p/TNFRSF10D and circNTRK2/miR-760/LAT, which were dysregulated in obese patients. In conclusion, this whole transcriptome study provided a pool of data that will be useful for identifying biomarkers of obesity and identified an obesity-associated ceRNA network that is regulated by circORC5 and circNTRK2.

DNA methylation mediated down-regulation of ANGPTL4 promotes colorectal cancer metastasis by activating the ERK pathway.

Background: Colorectal cancer (CRC) imposes significant health burden and is increasing in incidence. NGPTL4 has been implicated in the development of CRC. The present study aimed to investigate the molecular mechanisms by which ANGPTL4 expression might regulate epithelial-mesenchymal transition (EMT) and the tumor microenvironment in CRC. Methods: CRC and para-carcinoma tissues were collected from 67 CRC patients. ANGPTL4 expression levels and DNA methylation of ANGPTL4 promoter region were determined. Next, the migration and invasion capacities of CRC cells were assessed. Immunofluorescence and Western blot were used to identify the signaling pathways by which ANGPTL4 mediated tumor metastasis. A tumorigenesis mice model with transplanted fibroblast cells and ANGPTL4 overexpressed CRC cells was established to investigate the effects of ANGPTL4 on the metastasis of cancer cells in vivo. Results: ANGPTL4 was significantly decreased in CRC tissues and DNA hypermethylation was involved in the regulation of ANGPTL4. Mechanistically, ANGPTL4 induced activation of cancer-associated fibroblasts in the tumor microenvironment and promoted EMT in CRC cells through the ERK signaling pathway. In vivo, the overexpression of ANGPTL4 was found to inhibit the metastasis of tumor cells in lung tissues. Conclusion: DNA hypermethylation induced ANGPTL4 downregulation promoted the activation of cancer-associated fibroblasts and epithelial mesenchymal transformation of CRC cells via the ERK signaling pathway, thereby promoting invasion and metastasis in CRC.

Peripheral blood CD45RO+T cells is a predictor of the effectiveness of neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

ABSTRACT: To investigate the relationship between the changes in circulating CD45RO+T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO+T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO+ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO+ratio.Circulating CD45RO+ratio of 1.07 was determined as the optimal cut-off point and CD45RO+ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO+ratio-high group was significantly higher than that in the CD45RO+ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO+ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153-0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082-0.726; P = .011).Circulating CD45RO+ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.

Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer.

BACKGROUND AND OBJECTIVES: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. METHODS: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. RESULTS: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. CONCLUSIONS: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.

Successful management of tubular colonic duplication using a laparoscopic approach: A case report and review of the literature.

BACKGROUND: Alimentary duplication is a rare congenital disease with a reported incidence of 1 per 4500 persons, although the exact incidence has been difficult to ascertain. According to previous reports, the most common site of duplication is the ileum, and colonic duplication is rare. Due to different types and locations of the duplication, the manifestations are varied, which makes establishing an accurate diagnosis before surgery a challenge. CASE SUMMARY: A 17-year-old female patient sought evaluation in our department with constipation and chronic abdominal pain for 12 years; she had difficulty defecating and had dry stools since she was a child. An abdominal computed tomography revealed two extremely enlarged loops of bowel full of stool-like intestinal contents in the left lower abdomen, which led us to consider the possibility of colonic duplication. A laparoscopic exploration was performed, which revealed a tubular duplicated colon that shared a common opening with the transverse colon. A left hemi-colectomy was performed with a side-to-side anastomosis. The pathologic results confirmed the diagnosis. At the 6-mo follow-up, the patient was doing well without constipation or abdominal pain. CONCLUSION: Colonic duplication is a rare alimentary abnormality in adults. Due to the non-specific manifestations and low incidence, it is usually difficult to make an accurate diagnosis pre-operatively. Surgery is the mainstay of treatment, even though some patients are asymptomatic.

IL36 Cooperates With Anti-CTLA-4 mAbs to Facilitate Antitumor Immune Responses.

Despite the great impact on long-term survival of some cancer patients, the immune checkpoint blockade (ICB) therapy is limited by its low response rates for most cancers. There is a pressing need for novel combination immunotherapies that overcome the resistance to current ICB therapies. Cytokines play a pivotal role in tumor immunotherapy by helping initiating and driving antitumor immune responses. Here, we demonstrated that, besides conventional CD4+ and CD8+ T cells, IL36 surprisingly increased the number of tumor-infiltrating regulatory T (Treg) cells in vivo and enhanced proliferation of Tregs in vitro. Administration of CTLA-4 monoclonal antibodies (mAbs) strongly enhanced IL36-stimulated antitumor activities through depletion of Tregs. In addition, a cancer gene therapy using the IL36-loaded nanoparticles in combination with CTLA-4 mAbs additively reduced lung metastasis of breast tumor cells. We further showed that the combined therapy of CTLA-4 mAbs and IL36 led to an increase in proliferation and IFN-γ production by CD4+ and CD8+ T cells when compared to single therapy with CTLA-4 mAbs or IL36. Collectively, our findings demonstrated a new combination therapy that could improve the clinical response to ICB immunotherapy for cancer.

Does Heterotopic Ossification in Cervical Arthroplasty Affect Clinical Outcome?

OBJECTIVE: To investigate the occurrence and progression of heterotopic ossification (HO) in patients treated by anterior cervical discectomy with arthroplasty. It was evaluated if HO affects clinical outcome and range of motion (ROM). Risk factors of HO was studied as well. METHODS: Patients who underwent anterior cervical discectomy with arthroplasty for a cervical radiculopathy because of a herniated disc from the NECK and PROCON trial were analyzed for HO at 12 and 24 months postoperatively. HO was scored according to the McAfee-Mehren classification. The index ROM was defined by a custom developed image analysis tool, and global cervical ROM was measured by Cobb's angle. Clinical outcome was evaluated by means of the Neck Disability Index and the 36-Item Short Form Health Survey. RESULTS: The occurrence of HO was 60% at 1 year, and it increased to 76% at 2-year follow-up. A total of 31% of patients were scored as high-grade HO at 1-year follow-up, and this percentage increased to 50% at 2-year follow-up. Clinical outcome does not correlate to HO grade, and no risk factor for high-grade HO could be identified. The ROM at the index level was significantly higher in low-grade HO group than those patients with high-grade HO, but in 15%-38% HO grade does not correspond to ROM. CONCLUSIONS: HO occurs in three fourths of the patients at 2 years after surgery, but does not necessarily correspond to clinical outcome, nor loss or preservation of ROM. The McAfee-Mehren classification should be combined with ROM evaluation to properly study HO.

Registration of vascular structures using a hybrid mixture model.

PURPOSE: Morphological changes to anatomy resulting from invasive surgical procedures or pathology, typically alter the surrounding vasculature. This makes it useful as a descriptor for feature-driven image registration in various clinical applications. However, registration of vasculature remains challenging, as vessels often differ in size and shape, and may even miss branches, due to surgical interventions or pathological changes. Furthermore, existing vessel registration methods are typically designed for a specific application. To address this limitation, we propose a generic vessel registration approach useful for a variety of clinical applications, involving different anatomical regions. METHODS: A probabilistic registration framework based on a hybrid mixture model, with a refinement mechanism to identify missing branches (denoted as HdMM+) during vasculature matching, is introduced. Vascular structures are represented as 6-dimensional hybrid point sets comprising spatial positions and centerline orientations, using Student's t-distributions to model the former and Watson distributions for the latter. RESULTS: The proposed framework is evaluated for intraoperative brain shift compensation, and monitoring changes in pulmonary vasculature resulting from chronic lung disease. Registration accuracy is validated using both synthetic and patient data. Our results demonstrate, HdMM+ is able to reduce more than [Formula: see text] of the initial error for both applications, and outperforms the state-of-the-art point-based registration methods such as coherent point drift and Student's t-distribution mixture model, in terms of mean surface distance, modified Hausdorff distance, Dice and Jaccard scores. CONCLUSION: The proposed registration framework models complex vascular structures using a hybrid representation of vessel centerlines, and accommodates intricate variations in vascular morphology. Furthermore, it is generic and flexible in its design, enabling its use in a variety of clinical applications.

Pulmonary Vascular Morphology Associated With Gas Exchange in Systemic Sclerosis Without Lung Fibrosis.

PURPOSE: Gas exchange in systemic sclerosis (SSc) is known to be affected by fibrotic changes in the pulmonary parenchyma. However, SSc patients without detectable fibrosis can still have impaired gas transfer. We aim to investigate whether pulmonary vascular changes could partly explain a reduction in gas transfer of SSc patients without fibrosis. MATERIALS AND METHODS: We selected 77 patients whose visual computed tomography (CT) scoring showed no fibrosis. Pulmonary vessels were detected automatically in CT images, and their local radii were calculated. The frequency of occurrence for each radius was calculated, and, from this radius histogram, 2 imaging biomarkers (α and ß) were extracted, wherein α reflects the relative contribution of small vessels compared with large vessels, and ß represents the vessel tree capacity. Correlations between imaging biomarkers and gas transfer [single-breath diffusion capacity for carbon monoxide corrected for hemoglobin concentration (DLCOc) %predicted] were evaluated with Spearman correlation. Multivariable stepwise linear regression was performed with DLCOc %predicted as the dependent variable and age, BMI, sPAP, FEV1 %predicted, TLC %predicted, FVC %predicted, α, ß, voxel size, and CT-derived lung volume as independent variables. RESULTS: Both α and ß were significantly correlated with gas transfer (R=-0.29, P-value=0.011 and R=0.32, P-value=0.004, respectively). The multivariable stepwise linear regression analysis selected sPAP [coefficient=-0.78; 95% confidence interval (CI)=-1.07, -0.49; P-value<0.001], ß (coefficient=8.6; 95% CI=4.07, 13.1; P-value<0.001), and FEV1% predicted (coefficient=0.3; 95% CI=0.12, 0.48; P-value=0.001) as significant independent predictors of DLCOc %predicted (R=0.71, P-value<0.001). CONCLUSIONS: In SSc patients without detectable pulmonary fibrosis, impaired gas exchange is associated with alterations in pulmonary vascular morphology.

The Use of Prosthetic Mesh in the Emergency Management of Acute Incarcerated Inguinal Hernias.

INTRODUCTION: Tension-free hernia repair has been regarded as a gold standard treatment for selected inguinal hernias, but the use of prosthetic mesh in acute incarcerated inguinal hernias is controversial. Our study focused on evaluating the safety and efficacy of the prosthetic mesh repair for emergency cases. METHODS: Patients with acute incarcerated inguinal hernias who underwent emergency prosthetic mesh repair during 2009 to 2014 at our department were included. Patient characteristics, operative approaches and results, and complications were retrospectively analyzed. RESULTS: A total of 167 patients were included in our study. One hundred and twenty-two patients underwent open surgery while the remaining 45 patients underwent transabdominal preperitoneal laparoscopic approach. The hernia was indirect inguinal in 133 patients (79.6%), direct inguinal in 15 patients (9.0%), and femoral in 19 patients (11.4%). The overall wound infection rate of these patients was 3%. Nonviable intestinal resection was performed in 25 patients (8.4%), only 2 of whom underwent wound infection. Another 3 patients who developed wound infection had viable hernia content. There was no mesh-related infection. There was no statistically significant difference in wound infection rates between patients with viable hernia contents and those with nonviable contents ( P < .05). CONCLUSION: The use of the prosthetic mesh in the treatment of acute incarcerated inguinal hernia is safe and effective. Nonviable intestinal resection cannot be regarded as a contradiction of the mesh repair.

Albiflorin inhibits the formation of THP-1-derived foam cells through the LOX-1/NF-κB pathway.

BACKGROUND: Foam cells are characteristic pathologic cells of atherosclerosis (AS), they are lipid-loaded macrophages present on atherosclerotic lesions. A large number of studies has shown that the pathogenesis of AS is the result of interactions between the lipid metabolism disorders and chronic inflammatory responses in the body. Albiflorin can inhibit the inflammatory response and it has shown a therapeutic effect on certain inflammatory diseases. METHODS: In this study, a human acute monocytic leukemia cell line (THP-1)-derived foam cell model was established via oxidized low-density lipoprotein (ox-LDL) to observe the effects of albiflorin on the AS-characteristic foam cells. RESULTS: Our results showed that, after the treatment with ox-LDL, macrophages induced by propylene glycol methyl ether acetate (PMA), presented large amounts of lipid deposition in their cytoplasm, indicating that the THP-1-derived foam cell model was successfully established. On the other hand, the same cells pretreated with albiflorin presented significantly reduced amounts of lipid deposition, and their contents of total cholesterol and triglyceride were also clearly lower. Besides, the expression levels of low-density lipoprotein receptor-1 (LOX-1) and nuclear factor-κB (NF-κB) were significantly decreased, and the expression levels of downstream factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also obviously decreased in the cells treated with albiflorin but not in the negative control cells. Moreover, after treatment of macrophages with different concentrations of ox-LDL, the expression levels of LOX-1 and NF-κB were up-regulated in an ox-LDL concentration-dependent manner, and so were the expression levels of IL-6 and TNF-α. And, it was found after treatment with LOX-1 neutralizing antibody or NF-κB inhibitor (during the foam cell formation induction via ox-LDL) that the lipid deposition in the cytoplasm of the cells was reduced, as in the cells treated with albiflorin. CONCLUSIONS: Taken together, our findings suggest that albiflorin decreases lipid deposition in the cytoplasm and blocks the foaming process by regulating the LOX-1/NF-κB signaling pathway.

[Application of modified purse-string closure in the wound following loop stoma reversal].

OBJECTIVE: To compare the safety and feasibility between modified circumferential purse-string closure and conventional primary linear closure of the wound following loop stoma reversal. METHODS: Clinical data of 88 consecutive patients who underwent loop colostomy or loop ileostomy closures at our hospital from July 2011 to June 2013 were retrospectively analyzed. Among them, 43 cases underwent modified purse-string technique (modified purse-string group), 45 cases underwent direct suture (direct suture group). The operation method of modified purse-string suture was as follows: (1) the circumferential subcutaneous adipose tissue was sutured with the absorbable suture, avoiding tightening at knotting and retaining a 1 cm pore;(2)absorbable suture was used to perform purse-string suture of the dermis, retaining a 0.5 cm central pore when knotting; (3) a rubber drain was placed through the pore. The clinical parameters, surgical results and postoperative complication of two groups were recorded and compared. RESULTS: There were 56 males and 32 females with age of (65.0±11.5) years old. Seventy-nine cases were malignant tumors, 6 were benign tumors and 3 were traumatic. There was no significant difference in the baseline data between two groups (all P>0.05). Compared with the direct suture group, the modified purse-string group had significantly lower wound infection rate [7.0%(3/43) vs. 24.4%(11/45), χ²=5.015, P=0.025]; significantly shorter postoperative hospital stay (mean 7.1 days vs. 8.6 days, t=-2.656, P=0.010); significantly lower total hospitalization costs (mean 25 668.4 yuan vs. 27 718.1 yuan, t=-2.488, P=0.015); however, the wound healing time of the modified purse-string group was significantly longer (mean 22.0 days vs. 13.0 days, t=5.701, P<0.001). The average healing time of the wounds in the direct suture group was 29.8 days, which was significantly longer than that of the first-stage healing cases (7.5 days, t=-15.446,P<0.001). The average wound healing time of the infected cases in the modified purse-string suture group was 22.0 days, compared with 22.1 days in the first-stage healing cases, the difference was not statistically significant(t=0.077,P=0.943). CONCLUSIONS: Modified purse-string closure after loop stoma reversal is an appropriate technique with lower stoma site infection rate, shorter postoperative hospital stay and lower hospitalization cost than conventional primary closure, although wounds may take longer to heal in this approach.

Somatic Mutations and Immune Alternation in Rectal Cancer Following Neoadjuvant Chemoradiotherapy.

Checkpoint blockade therapy triggers tumor-specific immune responses in a variety of cancer types. We presumed that rectal cancer patients could have become sensitive to immunotherapy after receiving neoadjuvant chemoradiotherapy (nCRT). In this study, we report immune alternation in post-nCRT patients compared with pretreatment conditions from gene-expression omnibus (GEO) data. Whole-exome sequencing of 14 locally advanced rectal cancer (LARC) patient samples showed that nCRT induced new mutations compared with the paired pretreatment biopsies, evidenced by appearance of a neoantigen landscape. An association was identified between mutation burden and enrichment of immune activation-related pathways. Animal experiment results further demonstrated that radiotherapy enhanced the efficacy of anti-PD-1. Mutation burden and the neoantigens of LARC patients were associated with response to nCRT. The mRNA expression profiling of 66 pretreatment biopsy samples from LARC patients showed that immune activation-related pathways were enriched in response to nCRT. PD-L1 expression was negatively correlated with disease-free survival in the CD8-low expression patient group who received nCRT in a cohort of 296 samples. Thus, nCRT was able to alter immune function in LARC patients, which may be associated with the appearance of neoantigens. Neoantigens could make rectal cancer patients potential candidates to receive checkpoint blockade immunotherapy, and mutation burden could be a useful biomarker to stratify patients into responding and nonresponding groups for immunotherapy. Cancer Immunol Res; 6(11); 1401-16. ©2018 AACR.

Preliminary Outcome of Individualized Abdominoperineal Excision for Locally Advanced Low Rectal Cancer.

BACKGROUND: The introduction of individualized abdominoperineal excision (APE) may minimize operative trauma and reduce the rate of complications. The purpose of this study was to evaluate the safety and efficacy of individualized APE for low rectal cancer. METHODS: Fifty-six patients who underwent individualized APE from June 2011 to June 2015 were evaluated retrospectively in Beijing Chaoyang Hospital, Capital Medical University. The main outcome measures were circumferential resection margin (CRM) involvement, intraoperative perforation, postoperative complications, and local recurrence. Statistical analysis was performed using SPSS version 16.0. RESULTS: Fifty (89%) patients received preoperative chemoradiotherapy: 51 (91%) patients were treated with the sacrococcyx preserved; 27 (48%) patients with the levator ani muscle partially preserved bilaterally; 20 (36%) patients with the levator ani muscle partially preserved unilaterally and the muscle on the opposite side totally preserved; 7 (13%) patients with intact levator ani muscle and part of the ischioanal fat bilaterally dissected; and 2 (4%) patients with part of the ischioanal fat and intact lavator ani muscle dissected unilaterally and the muscle on the opposite side partially preserved. The most common complications included sexual dysfunction (12%), perineal wound complications (13%), urinary retention (7%), and chronic perineal pain (5%). A positive CRM was demonstrated in 3 (5%) patients, and intraoperative perforations occurred in 2 (4%) patients. On multiple logistic regression analysis, longer operative time (P = 0.032) and more intraoperative blood loss (P = 0.006) were significantly associated with perineal procedure-related complications. The local recurrence was 4% at a median follow-up of 53 months (range: 30-74 months). CONCLUSION: With preoperative chemoradiotherapy, individualized APE may be a relatively safe and feasible approach for low rectal cancer with acceptable oncological outcomes.

[Laparoscopy combined with transperineal extralevator abdominoperineal excision for locally advanced low rectal cancer].

OBJECTIVE: To evaluate the laparoscopy combined with transperineal extralevator abdominoperineal excision (TP-ELAPE) for locally advanced low rectal caner. METHODS: Clinical data of 12 patients with locally advanced low rectal cancer undergoing laparoscopy combined with TP-ELAPE in our department from May 2013 to March 2015 were retrospectively analyzed. There were 8 male and 4 female patients with median aged of 63 (46 to 72) years. The median distance from tumor lower margin to anal verge was 3.5(2.0 to 4.0) cm. A self-made transanal suit for minimally invasive operation was used to make a sealed lacuna outside the sphincter, thus laparoscope can be applied to perform transperineal operation. RESULTS: All the patients underwent operations successfully without conversion to open abdominal operation. The median operating time was 206 (180 to 280) minutes with perineal operating time 95(80 to 120) minutes. The median intraoperative blood loss was 120(50 to 200) ml. The median postoperative hospital stay was 12(9 to 18 ) days. Postoperative pathology revealed that all circumferential margins (CRM) were negative. The area of sample horizontal section was (2 824±463) mm(2), and of outer muscularis propria was(2 190±476) mm(2). Postoperative complications included chronic sacrococcygeal region pain in 2 cases, urinary retention in 3 cases, perineal wound infection in 1 case. No perineal seroma, perineal hernia, wound dehiscence and sinus tract formation were observed. Among 8 patients with preoperative normal sexual function, sexual dysfunction occurred in 2 patients. There was no local recurrence and metastasis during a median follow-up of 21(12 to 34) months. CONCLUSION: Laparoscopy combined with TP-ELAPE has the potential to simplify the operation procedure for low rectal cancer, can ensure the radical treatment and safety of operation, and may be carried out in experienced centers.