Multimodality Therapy, Followed by Laparoscopic Gastrectomy, for Unresectable Gastric Cancer With Outlet Obstruction and Bulky N2 Metastases.

BACKGROUND: Patients who have gastric cancer with outlet obstruction (GCOO) and bulky N2 metastases cannot undergo curative resection and tolerate chemotherapy poorly, which may be improved by multimodality therapy (MMT) combined with laparoscopic gastrectomy. PATIENTS AND METHODS: The records of patients with GCOO and bulky N2 metastases who received MMT including nasojejunal feeding combined with preoperative chemotherapy (PCT), followed by laparoscopic exploration [enteral nutritional (EN) group] in sequence or laparoscopic gastrojejunostomy (LGJ) before PCT plus laparoscopic gastrectomy (LGJ group) were retrospectively reviewed. Prognostic Nutritional Index, gastric outlet obstruction scoring system grade, quality of life, response to PCT, surgical outcomes, and long-term survival were analyzed. RESULTS: Fifty-four consecutive patients with GCOO and bulky N2 metastases were identified. The Prognostic Nutritional Index and Nutritional Risk Screening-2002 score of patients were significantly improved as a result of multimodal therapy, but no superiority was demonstrated between the EN group and the LGJ group. The quality of life (52.6 ± 11.4 vs 68.2 ± 13.5, P = 0.036) and gastric outlet obstruction scoring system (P < 0.05) of patients in the LGJ group were better compared with the EN group. The rate of laparoscopic D2 gastrectomy (94.3% vs 92.9%, P = 0.64) and R0 resection (91.4% vs 92.9%, P = 0.53) in the EN group was similar to the LGJ group. There were no significant differences for the 5-year overall survival rate (63.2% vs 57.1, P = 0.86) and the 5-year relapse-free survival rate (42.9% vs 53.8%, P = 0.54) of patients in the EN group compared with the LGJ group. CONCLUSIONS: MMT including EN support or laparoscopic gastrojejunostomy followed by laparoscopic D2 gastrectomy is a feasible and effective treatment for patients with GCOO and bulky N2 metastases.

Development and validation of a nomogram predictive model for colorectal adenoma with low-grade intraepithelial neoplasia using routine laboratory tests: A single-center case-control study in China.

Background: Colorectal cancer (CRC) is the third most common cancer in the world and has a high mortality rate. Colorectal adenoma (CRA) is precancerous lesions of CRC. The purpose of the present study was to construct a nomogram predictive model for CRA with low-grade intraepithelial neoplasia (LGIN) in order to identify high-risk individuals, facilitating early diagnosis and treatment, and ultimately reducing the incidence of CRC. Methods: We conducted a single-center case-control study. Based on the results of colonoscopy and pathology, 320 participants were divided into the CRA group and the control group, the demographic and laboratory test data were collected. A development cohort (n = 223) was used for identifying the risk factors for CRA with LGIN and to develop a predictive model, followed by an internal validation. An independent validation cohort (n = 97) was used for external validation. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate discrimination ability, accuracy and clinical practicability of the model. Results: Four predictors, namely sex, age, albumin and monocyte count, were included in the predictive model. In the development cohort, internal validation and external validation cohort, the area under the curve (AUC) of this risk predictive model were 0.946 (95%CI: 0.919-0.973), 0.909 (95 % CI: 0.869-0.940) and 0.928 (95%CI: 0.876-0.980), respectively, which demonstrated the model had a good discrimination ability. The calibration plots showed a good agreement and the decision curve analysis (DCA) suggested the predictive model had a high clinical net benefit. Conclusion: The nomogram model exhibited good performance in predicting CRA with LGIN, which can aid in the early detection of high-risk patients, improve early treatment, and ultimately reduce the incidence of CRC.

Correlation between IFNAR1 expression in peripheral blood T lymphocytes and inflammatory cytokines, tumor-infiltrating lymphocytes, and chemosensitivity in patients with colorectal cancer.

IFN-α receptor (IFNAR) is critical for maintaining the crosstalk between cancer cells and lymphocytes. We investigated IFNAR1 expression in peripheral blood CD4+ and CD8+ T cells and explored their relationships with plasma cytokines, chemosensitivity and infiltrated T cells in the tumor microenvironment (TME) of colorectal cancer (CRC). The levels of IFNAR1, IFN-γ, and PD1 in peripheral T cells were tested using flow cytometry. Immunohistochemical staining of IFNAR1 in CRC tissues was performed. A cytometric bead array was used to determine the plasma concentrations of cytokines. In CRC patients, IFNAR1 levels were significantly increased in peripheral blood T cells, and plasma IL-6 levels were also significantly increased. Pearson correlation analysis revealed that IFNAR1 expression in CD8+ T cells was negatively associated with plasma IL-2, IFN-γ, and TNFα. IFNAR1 expression in CD4+ T cells was positively associated with TME infiltrated levels of CD8+ T cells. The levels of CD8+ T cells with IFNAR1 and plasma IFN-γ were associated with chemosensitivity. Collectively, IFNAR1 levels in CD4+ and CD8+ T cells were significantly upregulated in CRC patients and positively associated with T-cell infiltration. IFNAR1 may be a chemotherapy biomarker for predicting response.

Long-Read Nanopore Sequencing Identifies Mismatch Repair-Deficient Related Genes with Alternative Splicing in Colorectal Cancer.

Background: Alternative splicing (AS) plays a crucial role in regulating the progression of colorectal cancer (CRC), but its distribution remains to be explored. Here, we aim to investigate the genes edited by AS which show differential expression in patients with mismatch repair deficiency (dMMR)/microsatellite instability (MSI). Materials and Methods: We applied long-read nanopore sequencing to determine the mRNA profiles and screen AS genes using Oxford Nanopore Technologies (ONT) method in ten paired CRC tissues. CRC tissue and plasma samples were used to validate the differential genes with AS using real-time fluorescent quantitative PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ONT sequencing identified 404 genes were downregulated, and 348 genes were upregulated in MSI cancer tissues compared with microsatellite stability (MSS) cancer tissues. In total, 6,200 AS events were identified in 2,728 mRNA transcripts. WGCNA revealed dMMR/MSI-correlated gene modules, including INHBA and RPL22L1, which were upregulated; conversely, HMGCS2 was downregulated in MSI cancer. Overexpression of RPL22L1, INHBA, and CAPZA1 was further confirmed in CRC tissues. INHBA was found to be associated with tumor lymphatic metastasis. Importantly, the levels of INHBA in CRC plasma were significantly increased compared with those in noncancer plasma. INHBA showed a higher level in dMMR/MSI CRC than in MSS CRC, indicating that INHBA is a useful biomarker. Conclusion: Our results showed that ONT-identified genes provide a pool to explore AS-associated markers for dMMR/MSI CRC. We demonstrated INHBA as a promising signature for clinical application in predicting tumor lymphatic metastasis and screening dMMR/MSI candidates.

The Efficacy of Combined Therapy of Regorafenib with Detoxicating and Stasis Softening Chinese Herbal Spleen Tonics in Mid-/Late-Stage Hepatocellular Carcinoma.

Objective: To explore the efficacy of combined therapy of Regorafenib with detoxicating and stasis softening Chinese herbal spleen tonics (DSS-splenic tonics) in mid-/late-stage hepatocellular carcinoma. Methods: Retrospective observational data of 120 patients were obtained, 60 of which received combined therapy of DSS-splenic tonics and regorafenib. Adverse event, overall survival (OS), and time-to-progress (TTP) were analyzed. Synergistic effect of DSS-spleen tonics was found and validated in human hepatocellular carcinoma HCCLM3 cell line and xenograft mouse models. Results: Combination of regorafenib and DSS-splenic tonics also slightly extended the TTP and OS compared with treatment of regorafenib alone, suggesting DSS-splenic tonics has synergistic effect with regorafenib. Both Regorafenib and DSS-spleen tonics exerted inhibitory effect on cell viability and invasion capability of HCCLM3 cells, and combining both could enhance the antitumor effect. At molecular level, we found that VEGF, HIF-1α, MVD, and VEGF2 were all suppressed by regorafenib and DSS-splenic tonics. These results suggest that DSS-spleen tonics function synergistically with regorafenib in HCC by enhancing the regulation of regorafenib on VEGF, MMP-2, HIF-1α, and MVD, and may diminish angiogenesis during HCC progression. Conclusion: DSS-spleen tonics could exert synergistic antitumor effect with regorafenib via targeting VEGF.

Comparison of three different treatment methods for traumatic and Iatrogenic peripheral artery pseudoaneurysms.

OBJECTIVE: To compare the efficacy of open surgery (OS), endovascular interventions (EIs), and ultrasound-guided thrombin injection (UGTI) for the treatment of peripheral arterial pseudoaneurysms (PAs). METHODS: From January 1, 2001, to February 10, 2021, 38 patients diagnosed with traumatic and iatrogenic PAs treated with OS, EI, and UGTI were retrospectively analyzed. There were 18 females and 20 males, with an age of 56.47 ± 14.08 years (range,17-87 years). Anesthesia modality, operation duration, blood transfusion, duration of hospital stay, primary and secondary success rates, and complication rate were used to evaluate the surgical outcomes. RESULTS: There were 11 cases under regional anesthesia and 4 under general anesthesia in OS group, 9 under regional anesthesia and 1 under general anesthesia in EI group, and no regional or general anesthesia was required in UGTI group. There was no significant differences between any two groups (χ2  = 39.80, p < 0.05). The blood tranfusion amount (units) were 3.6 ± 6.0, 0.8 ± 2.5, 0.0 ± 0.0 for OS, EI, and UGTI groups, respectively, with significant difference between OS and UGTI groups (F = 3.03, p < 0.05). The operation duration (minutes) of OS, EI, and UGTI groups were 80.0 ± 41.9, 56.0 ± 8.4, and 22.7 ± 5.3, respectively, with significant difference between any two groups (F = 15.69, p < 0.05). The duration of hospital stay (days) were 47.7 ± 39.0, 31.5 ± 17.6, and 16.3 ± 9.5, repectively, with significant difference between any two groups (F = 47.73, p < 0.05). The primary clinical success rates were 80% (12/15), 90% (9/10), and 92.3% (12/13) in OS,EI, and UGTI groups, respectively, with no significant difference between any two groups (χ2  = 0.34, p > 0.05). The secondary clinical success rates were 100% for all three groups. The overall complication rates of OS, EI, and UGTI groups were 20% (3/15), 10% (1/10), and 7.7% (1/13), respectively, with no significant difference between any two groups (χ2  = 1.00, p > 0.05). The infection rates were 13.3% (2/15), 10% (1/10), and 0% (0/13) in OS, EI, and UGTI groups respectively, with no significant difference between any two groups (χ2  = 1.80, p > 0.05). The reintervention rates were 6.7% (1/15), 0% (0/10), 7.7% (1/13) in OS, EI, and UGTI groups, respectively, with no significant difference between two groups (χ2  = 0.95, p > 0.05). Neuralgia was relieved in all patients. CONCLUSIONS: OS, EI, and UGTI are efficacious and safe options for the treatment of appropriate patients with traumatic and iatrogenic PAs. UGTI would be considered as a first-line therapy for this condotion.

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.

Horizontal Rafting Plate for Treatment of the Tibial Plateau Fracture.

OBJECTIVE: This study aimed to investigate the value of a horizontal rafting plate in treating tibial plateau fractures. METHODS: The data of 24 patients in whom a horizontal rafting plate was used to treat a tibial plateau fracture between October 2014 and January 2018 were retrospectively analyzed, including 16 males and 8 females, aged 21-63 years old, with an average of 40 ± 14.68 years. The fractures included 13 in the left knee and 11 in the right knee. The places where the horizontal rafting plate were used included the anterior margin of tibia, anterolateral tibia, and posterolateral tibia. All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last follow-up, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the Rasmussen functional score. Computed tomography (CT) scanning and three-dimensional reconstruction were performed preoperatively and postoperatively, with the quality of reduction of the fractured articular surface clarified by the final follow-up. The flexion and extension abilities of the knee joint were also measured in the postoperative follow-up. RESULTS: Preoperative CT scanning showed that the gap of the tibial plateau was 8.00 ± 1.40 (5-24) mm. The heights of the fracture of the articular surface at all three sites during the final follow-ups were significantly different from the height before the surgery (P < 0.05). The vertical distance between the articular line and the highest point of the articular surface after reduction was 0.17 ± 0.05 mm. Anatomic reductions were obtained in 24 patients. The Rasmussen functional score after surgeries was 27.25 ± 0.94 points. Bony union was achieved in all the patients. According to the Rasmussen radiological criteria, the scores during the last follow-up were as follows: the total score was 13-18 points, with an average of 16.00 ± 1.72 points; the scores were excellent in 17 cases and good in seven cases. Therefore, 100% of results were excellent or good. No infection or fracture nonunion was found. CONCLUSION: Using a horizontal plate can be an effective method for treating special types of fractures of the tibial plateau, including the anterior margin and anterolateral and posterolateral tibial plateau, with satisfactory treatment efficacy.

Polymorphism in GRHL2 gene may contribute to noise-induced hearing loss susceptibility: a meta-analysis / Polimorfismo no gene GRHL2 pode contribuir para a suscetibilidade à perda auditivainduzida por ruído: uma metanálise

Abstract Instruction: Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting. Objective: The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss. Methods: A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association. Results: Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594-0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062-1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514-0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054-1.379). Conclusion: Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

Resumo Introdução: Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes. Objetivo: Identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído. Método: Uma pesquisa abrangente foi feita para coletar dados até 8 de julho de 2018. No fim, quatro artigos elegíveis foram incluídos nesta metanálise, abrangeram 2.410 indivíduos. As odds ratios agrupadas com intervalos de confiança de 95% foram usadas para avaliar a força da associação. Resultados: Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379). Conclusão: O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

Surgical Treatment of Lateral Tibial Plateau Fractures Involving the Posterolateral Column.

OBJECTIVE: To summarize the indications and the clinical effects of a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach in the treatment of fractures of the lateral tibial plateau involving the posterolateral column. METHODS: Eleven patients with lateral tibial plateau fractures were included in the present study. The fractures were Schatzker type II or lateral platform fractures involving posterolateral column. The anterolateral combined posterolateral approach (lateral + posterolateral locking plate fixation) was applied in 7 patients and 4 patients underwent transfibular neck osteotomy (lateral + posterolateral locking plate fixation + 1/4 tubular plate edge fixation, fibular osteotomy with Kirschner wire tension band fixation, and hollow nail fixation for upper tibiofibular joint). All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last followup, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the knee function evaluation criteria of the Hospital for Special Surgery (HSS). The Lachman test and the pivot-shift test were used to evaluate the anterior and posterior and rotational stability of the knee joint. The range of knee motion was recorded. RESULTS: Bone healing was achieved in all patients with fractures treated with a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach. At the last follow-up, both the Lachman test and the pivot-shift test results were negative. All patients had complete knee extension. For the combined anterolateral and posterolateral approach, the knee flexion angle was 110°-130°, with an average of 122.86° ± 7.56°. For the transfibular neck osteotomy approach, the knee flexion angle was 115°-130°, with an average of 120.00° ± 7.07°. For the patients in which the combined anterolateral and posterolateral approach was used, the Rasmussen score was 12-18 points, with an average of 16.00 ± 2.56 points. The results were excellent in 4 cases and good in 3 cases; therefore, 100% of results were excellent or good. For patients in which the transfibular neck osteotomy approach was used, the Rasmussen score was 10-18 points, with an average of 15.25 ± 3.77 points. The results were excellent in 2 cases, good in 1 case, and acceptable in 1 case; therefore, 75% of results were excellent or good. The HSS score for the combined anterolateral and posterolateral approach was 76-98 points, with an average of 88.43 ± 7.55 points. The results were excellent in 5 cases and good in 2 cases; therefore, 100% of results were excellent or good. The HSS score for the transfibular neck osteotomy approach was 74-96 points, with an average of 87.25 ± 9.43 points. The results were excellent in 3 cases and good in 1 case; therefore, 100% of results were excellent or good. There were no significant differences in operation time, surgical blood loss, fracture healing time, postoperative imaging score, and knee function evaluation between the two approaches. One patient who underwent transfibular neck osteotomy had a 3-mm step that gradually appeared, but no significant abnormalities were found in the width of the platform and the lower limb force line. One patient in whom the combined anterolateral and posterolateral approach was used showed numbness in the common peroneal nerve. No common peroneal nerve injury occurred through the transfibular neck osteotomy approach. CONCLUSIONS: The anterolateral combined posterolateral approach and the transfibular neck osteotomy approach are effective in the surgical treatment of lateral tibial plateau fractures involving the posterolateral column. However, the transfibular neck osteotomy approach is more suitable for the posterolateral plateau articular surface damaged with bone separation and displacement, deep collapse, cases involving a large range of the posterolateral column, especially fractures of the lateral tibial plateau in the upper tibiofibular syndesmosis area of the line connecting the anterior and posterior margin of the fibular head to the midpoint of the plateau.

Circular RNA circVAPA is up-regulated and exerts oncogenic properties by sponging miR-101 in colorectal cancer.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs with distinct properties and diverse physiological and pathological functions. However, the functions of circRNAs in colorectal cancer (CRC) remain elusive. This study aimed to investigate the functional roles of circVAPA in CRC. High-throughput RNA sequencing was performed in 4 paired CRC tissues, and circVAPA (hsa_circ_0006990), was identified as a potential functional circRNA. Using quantitative real-time polymerase chain reaction (qRT-PCR), circVAPA was found to be up-regulated in CRC patients' tissues and plasma. Furthermore, circVAPA level was associated with unfavorable clinicopathologic features in CRC. The area under curve (AUC) of ROC was 0.724, suggesting that plasma level of circVAPA could serve as a promising biomarker for CRC detection. Sanger sequencing confirmed the back-splice junction sequences of circVAPA. Actinomycin D and RNase R treatments suggested that circVAPA was highly stable compared with its linear counterpart, and qRT-PCR for the circVAPA level in nuclear and cytoplasmic fractions indicated that circVAPA was predominantly localized in the cytoplasm. Gain-of-function and loss-of-function studies in CRC cell lines indicated that circVAPA could promote CRC cell proliferation, migration, invasion, and inhibit apoptosis. miRanda software (v3.3a) was used to predict target miRNAs of circVAPA. Moreover, target miRNAs associated with the KEGG pathway of COLORECTAL CANCER (Entry: map05210; https://www.kegg.jp/) were screened using DIANA-miRPath v.3 platform (Reverse Search module; TarBase v7.0 method). The analyses by miRanda and miRPath suggested that circVAPA could potentially bind to hsa-miR-101-3p (miR-101) associated with the COLORECTAL CANCER pathway. Luciferase reporter assay confirmed a direct interaction between circVAPA and miR-101. Furthermore, circVAPA had no effect on the expression level of miR-101, and miR-101 over-expression had the similar tumor-suppressing effects as circVAPA silencing. The tumor-promoting effect of circVAPA over-expression could be reversed by the up-regulation of miR-101. These data demonstrated that circVAPA promoted CRC progression by sponging miR-101. In conclusion, we have verified that circVAPA is up-regulated in CRC patients' tissues and plasma, and exerts oncogenic properties by sponging miR-101 in CRC. CircVAPA could serve as a promising biomarker and a therapeutic target for CRC.

Long-Term Outcomes of Ligation of the Inter-Sphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-Plug) in the Treatment of Trans-Sphincteric Perianal Fistula.

BACKGROUND The ligation of the inter-sphincteric fistula tract plus bioprosthetic anal fistula plug (LIFT-plug) is a new procedure in the treatment of trans-sphincteric perianal fistulas. The aim of this study was to evaluate its long-term outcomes. MATERIAL AND METHODS Clinical data of 78 patients with trans-sphincteric perianal fistula who were managed by the LIFT-plug technique between March 2014 to October 2016 were analyzed retrospectively. The operation time, healing rate, postoperative complications, recurrences, and length of stay were reviewed. RESULTS No serious complications occurred during the operation in all patients. The median follow-up was 30 months (16 to 47 months), clinical healing of the anal fistula occurred in 75 patients (96.2%). The median operative time was 25 minutes (18 to 45 minutes). The mean complete healing time was 16 days (9 to 46 days). The median healing time for the external anal fistula opening was 2 weeks (range, 2 to 3 weeks), and the inter-sphincteric groove incision healing time was 4 weeks (range, 3 to 7 weeks). The median hospital stay after operation was 5 days. Fistula recurred in 2 patients because of spontaneous expulsion of the plug at 7 days post-surgery; perianal abscess occurred in 1 patient. The anal function was evaluated in 70 patients of the 78 patients. Perfect control of continence was recorded for 97.1% of the patients (68 out of 70 patients). Two patients were identified to a rare complication of gas incontinence (Wexner score 1). CONCLUSIONS LIFT-plug procedure for the treatment of trans-sphincteric fistulas is a simple procedure with a high healing rate, minimal invasiveness, quick healing, and without disturbance to anal function. LIFT-plug is an ideal procedure for trans-sphincteric fistula.

[Preliminary report on prospective, multicenter, open research of selective surgery after expandable stent combined with neoadjuvant chemotherapy in the treatment of obstructive left hemicolon cancer].

OBJECTIVE: To evaluate the safety and feasibility of neoadjuvant chemotherapy prior elective surgery following self-expanding metallic stents (SEMS) for complete obstructive left hemicolon cancer. METHODS: This prospective, multicenter, open-labelled trial was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University(2016-ke-161-1) and registered in Clinicaltrials.gov (NCT02972541). INCLUSION CRITERIA: (1)age between 18 and 75 years old;(2) adenocarcinoma confirmed by pathology;(3) left hemicolon cancer confirmed by clinical manifestations and imaging examinations with the distance to anal verge > 15 cm; (4) resectable cancer evaluated by imaging examination without distant metastasis; (5) Eastern Cooperative Oncology Group (ECOG) score ≤ 1 or Karnofsky Performance Scale (KPS) > 70, indicating tolerance of neoadjuvant chemotherapy and operation; (6) absence of chemotherapy or radiotherapy within past six months; (7) bone marrow system and hepatorenal function: hemoglobin ≥ 90 g/L, neutrophil ≥ 1.5×109/L, platelet ≥ 80×109/L, total bilirubin ≤ 1.5×ULN(upper limits of normal), serum transaminase ≤ 2.5×ULN, serum creatinine ≤ 1.0×ULN, endogenous creatinine clearance rate > 50 ml/min; (8) sign for informed consent. EXCLUSION CRITERIA: (1) multiple primary colorectal cancer; (2) rejection of operation;(3) presenting peritonitis or bowel perforation before SEMS; (4) unqualified conditions proved by inspector from registration data. According to inclusion criteria, 62 consecutive patients receiving neoadjuvant chemotherapy prior to elective surgery following SEMS for complete obstructive left hemicolon cancer from Beijing Chaoyang Hospital of Capital Medical University (n=31), Qilu Hospital of Shandong University (n=14), the Third Xiangya Hospital of Central South University (n=13), Zhongnan Hospital of Wuhan University (n=2), the Fourth Hospital of Hebei Medical University (n=2) between December 2015 and December 2017 were prospectively enrolled in this study. Patients were divided into neoadjuvant chemotherapy group and elective surgery group according to the investigator's clinical experience and patient's preference. Patients in the elective surgery group received surgery within one to two weeks after SEMS placement without neoadjuvant chemotherapy. Those in the neoadjuvant chemotherapy group received 2 cycles of CapeOX or 3 cycles of mFOLFOX6 neoadjuvant chemotherapy within one to two weeks after SEMS placement, and then underwent surgery within 3 weeks after finishing neoadjuvant chemotherapy. Data between groups were compared using Student t-test, chi-square analysis or Fisher exact test analysis, including basic clinical informations, operational conditions and postoperative complications. The adverse reactions during the neoadjuvant chemotherapy were recorded. Surgical difficulty was assessed using visual analog scales ranging from 1 to 10, where 1 represented the lowest and 10 the highest degree of surgical difficulty, as judged by the surgeon. RESULTS: The study included 38 males and 24 females with mean age of (64.8±8.8) years. The clinical baseline data between 2 groups were not significantly different (all P>0.05) except the average time interval between SEMS and surgery was significantly longer in neoadjuvant chemotherapy group [(61.6±13.5) days vs. (10.4±5.2) days, t=16.679, P<0.001]. There was no stent migration in either group. Three patients had perforation in the elective surgery group; one patient had perforation and one had obstruction in the neoadjuvant chemotherapy group; and all these patients received emergent surgery. Adverse reactions of neodajuvant chemotherapy were mainly degree 1 and 2 except one patient with degree 3 diarrhea. Patients in neoadjuvant chemotherapy group had significantly lower rate of stoma [4.8%(1/21) vs. 34.1%(14/41), χ²=6.538, P=0.011], higher rate of laparoscopic surgery [71.4%(15/21) vs. 36.6%(15/41), χ²=6.751, P=0.009], shorter mean operative time (147 minutes vs. 178 minutes, t=-3.255, P=0.002), less mean intraoperative blood loss (47 ml vs. 127 ml, t=-4.129, P<0.001), lower degree of surgical difficulty(3.3 vs. 5.6, t=-5.091, P<0.001), shorter mean postoperative exhausting time (56.2 hours vs. 69.0 hours, t=-2.891, P=0.006), and shorter mean postoperative hospital stay (8.5 days vs. 13.5 days, t=-2.246, P=0.028) as compared with patients in the elective surgery group. Surgical site infection rate and anastomotic leakage rate did not differ significantly between two groups(all P>0.05). CONCLUSION: Neoadjuvant chemotherapy prior elective surgery following SEMS is a relatively safe and feasible approach in the treatment for obstructive left hemicolon cancer, and is associated with less stoma, more laparoscopic surgery, shorter operative time, less blood loss, lower surgical difficulty, and faster postoperative recovery as compared with conventional elective surgery.

[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.

RNA sequencing reveals the expression profiles of circRNA and indicates that circDDX17 acts as a tumor suppressor in colorectal cancer.

BACKGROUND: Circular RNA (circRNA) is a novel class of noncoding RNAs with functions in various pathophysiological activities. However, the expression profiles and functions of circRNAs in colorectal cancer (CRC) remain largely unknown. METHODS: High-throughput RNA sequencing (RNA-seq) was performed to assess circRNA expression profiles in 4 paired CRC tissues, and significantly dysregulated circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of dysregulated circRNAs. Target miRNAs of circRNAs were predicted using miRanda software, and were further analyzed combining DIANA-miRPath v.3 platform (Reverse Search module) with KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer (Entry: map05210 and map05206). CircRNA-miRNA interaction networks were constructed using Cytoscape software. Expression levels of a significantly down-regulated circRNA, circDDX17 (hsa_circ_0002211), was detected by qRT-PCR in 60 paired CRC tissues. CircDDX17 was knockdown by siRNA, and the biological functions of circDDX17 were examined in CRC cell lines. RESULTS: Totally 448 differentially expressed circRNAs were identified, including 394 up-regulated and 54 down-regulated circRNAs. qRT-PCR validation confirmed the reliability of the RNA-Seq data. GO and KEGG analyses revealed that these dysregulated circRNAs were potentially implicated in CRC pathogenesis. Analyses by combining miRanda and miRPath softwares with KEGG pathways suggested that the miRNAs targeted by the top 10 dysregulated circRNAs were associated with the KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer, indicating that circRNA-miRNA interactions might play important functional roles in the initiation and progression of CRC. The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis. CONCLUSIONS: In conclusion, we have identified numerous circRNAs that are dysregulated in CRC tissues compared with adjacent normal mucosa tissues. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in CRC tumorigenesis. CircDDX17 functions as a tumor suppressor and could serve as a potential biomarker and a therapeutic target for CRC.

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.

Genetic effects of rs3740199 polymorphism in ADAM12 gene on knee osteoarthritis: a meta-analysis.

BACKGROUND: Knee osteoarthritis (OA) is a complex arthritic condition in which genetic factors play an important role. ADAM12 gene is one of the recognized candidate genes although the results are conflicting. To derive a more precise estimation of the association between rs3740199 polymorphism in ADAM12 gene and risk of knee OA, we performed a meta-analysis based on six related studies, including a total of 2185 cases and 3716 controls. METHODS: A comprehensive search was performed to identify related studies up to April 14, 2017. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Different genetic models were used to assess the pooled and stratified data. RESULTS: Overall, no significant association was found in all genetic models (C vs. G, OR = 0.983, 95% CI = 0.910-1.061; CC vs. GG, OR = 1.033, 95% CI = 0.851-1.255; CG vs. GG, OR = 1.030, 95% CI = 0.877-1.209; CC/CG vs. GG, OR = 1.031, 95% CI = 0.886-1.201; CC vs. CG/GG, OR = 1.017, 95% CI = 0.868-1.190). When stratified by ethnicity, no significant association was found. CONCLUSIONS: This meta-analysis suggested that the rs3740199 polymorphism does not contribute to the development of knee OA. Additional well-designed large studies are required to confirm these findings in different populations.

Effectiveness of Percutaneous Celiac Plexus Ablation in the Treatment of Severe Cancer Pain in Upper Abdomen and Evaluation of Health Economics.

OBJECTIVE: To compare the effectiveness, adverse effects, and cost-effectiveness of percutaneous neurolytic celiac plexus block (NCPB) versus traditional medication strategies for the treatment of patients with advanced cancer having severe upper abdominal cancer pain. METHODS: This retrospective study included 81 patients with advanced upper abdominal cancer admitted to The Sixth People's Hospital Affiliated to Shanghai Jiaotong University between January 2013 and July 2014. The patients were divided into percutaneous NCPB (treatment) and medication for pain (control) groups. The outcomes were measured in terms of Numeric Rating Scale (NRS) score and Karnofsky Performance Status (KPS) score before treatment and on the 3rd, 7th, 14th, and 28th days posttreatment. The effectiveness and cost-effectiveness of the therapy were assessed using analysis of the health economics. RESULTS: The improvements in NRS score (1.42 ± 1.09 vs 4.03 ± 0.96, P < .01) and KPS score (65.55 ± 9.09 vs 63.03 ± 8.961, P < .01) in the treatment group were significantly superior compared to the control group on the 7th day of treatment, followed by no significant difference between the 2 groups on the 14th and the 28th day of treatment. Health economics evaluation revealed that the medicine-specific costs and total health care costs were significantly reduced in the treatment group compared to the control group ( P < .05), but no significant differences between the 2 groups ( P > .05) were seen in the costs of hospitalization, examinations, and treatment. CONCLUSION: The percutaneous NCPB method shows promising results and better cost-effectiveness for treating patients with advanced cancer having severe upper abdominal pain.

[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.

MicroRNA 192 regulates chemo-resistance of lung adenocarcinoma for gemcitabine and cisplatin combined therapy by targeting Bcl-2.

Lung cancer is the most leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) accounting for over 80% of all lung cancer cases. Patients with NSCLC are mostly treated with platinum-based chemotherapy. Chemoresistance is a leading cause of chemo-therapy failure in NSCLC treatment. Recent studies have shown that dysregulation of microRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. In this paper, we try to test whether miR-192 regulates chemo-resistance in human carcinoma A549 mice model by targeting Bcl-2. Mice model of human lung adenocarcinoma was built up, and was used for gemcitabine and cisplatin combined chemotherapy. MTT assay, real-time RT-PCR, western blotting assay were used to investigate miR-192 expression levels, cell viability ratio and Bcl-2 protein expression levels. MiR-192 expression level in A549 cells is significantly higher than in normal human bronchial epithelial cells. MiR-192 inhibitor treated tumor exhibits sensitivity to cisplatin and gemcitabine therapy. Bcl-2 mRNA and protein expression levels up-regulated in miR-192 inhibitor treated tumor. Bcl-2 is a key regulator for miR-192 related chemotherapy resistance. In this study, we demonstrate that miR-192 regulates chemoresistance for gemcitabine and cisplatin combined chemotherapy in human adenocarcinoma lung cancer A549 cells, and Bcl-2 is the target of miR-192.