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Background: Lateral lymph node (LLN) metastasis is a poor prognostic factor for rectal cancer patients. However, the effect of LLNs without malignant characteristics on the prognosis of rectal cancer patients has been uncertain. Methods: Consecutive patients who underwent laparoscopic-assisted low anterior resection were included. Patients with MRI-detected LLNs, but without malignant characteristics, were compared with patients with no MRI-detected LLNs. Results: The local recurrence rate was higher in the LLN-present group than in the LLN-absent group (9.8% vs 2.5%; p = 0.056). The overall survival of patients with no MRI-detected LLNs was significantly better than that of patients with MRI-detected LLNs (p = 0.021). Conclusion: The presence of LLNs, even without malignant features, may lead to worse local control and overall survival.

Distal resection margin (DRM) is closely associated with sphincter-preserving surgery and oncological safety for patients with mid-low rectal cancers. However, the optimal DRM has not been determined.Data of 378 rectal cancer patients who underwent laparoscopic-assisted sphincter-preserving surgery from 2009 to 2015 were retrospectively analysed. Patients were divided into two groups based on DRM: ≤1 cm (n = 74) and1 cm (n = 304). To minimize the differences between the two groups, propensity-score matching on baseline features was performed.Before propensity-score matching, no significant differences in 5-year disease-free survival (DFS) (92.8% versus 81.3%, P = 0.128) and 5-year overall survival (OS) (83.7% versus 82.2%, P = 0.892) were observed in patients with DRMs of ≤1 cm (n = 74) and1 cm (n = 304), respectively. After propensity-score matching (1:1), there were also no significant differences in DFS (88.1% versus 78.2%, P = 0.162) and OS (84.5% versus 84.9%, P = 0.420) between the DRM of ≤1 cm group (n = 65) and1 cm group (n = 65), respectively. A total of 44 patients received preoperative chemoradiotherapy (CRT). In this cohort, the 5-year local recurrence (LR) rates (P = 0.118) and the 5-year DFS rates (P = 0.298) were not significantly different between the two groups. A total of 334 patients received surgery without neoadjuvant CRT. There were also no significant differences in the 5-year LR rates (P = 0.150) and 5-year DFS rates (P = 0.172) between the two groups.When aiming to achieve at least a 1-2 cm distal clinical resection margin, a histological resection margin of1 cm on the DRM gave equivalent clinical outcomes to a DRM of1 cm.

Background: This study aimed to explore the role of postoperative neutrophil-to-lymphocyte ratio in predicting symptomatic anastomotic leakage in patients who underwent laparoscopic low anterior resection for rectal cancer. Methods: In this retrospective cohort study, we analyzed data of patients who underwent laparoscopic low anterior resection from May 2009 to May 2019. A receiver operating characteristic curve analysis was performed to evaluate the cut-off values with the best predictive efficacy of a symptomatic anastomotic leakage. In addition, a propensity score-matched analysis was performed by considering all covariate variables, and 61 patients with or without symptomatic anastomotic leakage were included in the analysis. Results: The present study included 306 patients; of these, 17 (5.56%) developed symptomatic anastomotic leakage after surgery. On postoperative day 5, compared with patients without symptomatic anastomotic leakage, those with leakage had significantly higher neutrophil-to-lymphocyte levels. Notably, a neutrophil-to-lymphocyte cut-off score of 6.54 indicated the best area under the curve of 0.818 (95% confidence interval: 0.697–0.940, p < 0.001) in predicting symptomatic anastomotic leakage, with a sensitivity and specificity of 76.5% and 79.4%, respectively. Conclusions: Although evidence for the predictive role of neutrophil-to-lymphocyte ratio is accumulating, it remains inconclusive. In addition, neutrophil-to-lymphocyte levels should be considered a predictive biomarker for symptomatic anastomotic leakage; however, it can more accurately be viewed as an adjunct that helps increase the clinical suspicion of emerging symptomatic anastomotic leakage.

Intracorporeal esophagojejunostomy remains a challenging technique in totally laparoscopic total gastrectomy (TLTG) because of the lack of an established standard anastomosis method. However, π-shaped esophagojejunostomy in TLTG is reportedly safe and feasible. Therefore, we evaluated the short-term surgical outcomes of our modified π-shaped esophagojejunostomy in TLTG.This study involved patients without neoadjuvant therapy diagnosed with gastric cancer who underwent TLTG by the same surgeon with modified π-shaped esophagojejunostomy from April 2018 to October 2019. Clinicopathologic data were collected and retrospectively analyzed.Forty patients diagnosed with gastric cancer were included. The mean operative time and estimated blood loss were 264.6 ± 56.9 minutes and 68.5 ± 53.3 mL, respectively. Postoperative flatus occurred at 4.6 ± 1.7 days. The mean time to resumption of diet was 7.4 ± 1.7 days postoperatively. One patient was diagnosed with anastomotic leakage and managed with conservative therapy. Pleural effusion was the most common complication, occurring in four (10%) patients. One patient developed intra-abdominal bleeding that required reoperation. Other complications were atrial fibrillation and wound infection. No mortality occurred during the 6-month follow-up.Modified π-shaped esophagojejunostomy is safe and feasible for intracorporeal anastomosis in TLTG and showed favorable surgical outcomes in this study.

Purpose The application of laparoscopic-assisted total gastrectomy (LATG) for resectable gastric cancer (GC) remains controversial compared with open total gastrectomy (OTG), especially for advanced gastric cancer (AGC) patients according to the inconsistent results demonstrated in the previous studies. The aim of this study was to evaluate the short-term and long-term outcomes between LATG and OTG in a population with more than 80% AGC patients by applying propensity score matching (PSM) method. Methods The data of 365 clinical stage I–III GC cases who underwent total gastrectomy with D2 lymphadenectomy were retrospectively collected from January 2011 to April 2018 in the Department of Gastrointestinal Surgery IV of Peking University Cancer Hospital. Propensity scores were generated through taking all covariates into consideration and 131 pairs of patients receiving either LATG or OTG were matched. Intraoperative, postoperative, and survival parameters were compared in the matched groups accordingly. Risk factors for postoperative complications and overall survival were further analyzed. Results Patient characteristics in the LATG and OTG groups were well balanced after PSM. LATG showed advantages with respect to shorter time to ambulation, first flatus, and first whole liquid diet intake. No significant differences were found between the two groups with regard to postoperative complications as well as overall survival in terms of different pathological stage. Older age was found as an independent risk factor for postoperative complications, and pathological stage for overall survival as well. Conclusion LATG appears to have comparable surgical and oncological safety with OTG by experienced surgeons.

Jiadi Xing,* Maoxing Liu,* Kai Xu,* Pin Gao, Fei Tan, Zhendan Yao, Nan Zhang, Hong Yang, Chenghai Zhang, Ming Cui, Xiangqian Su Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, Beijing 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangqian Su KeyLaboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital and Institute, NO. 52 Fucheng Road, Haidian District, Beijing 100142, People’s Republic of ChinaTel +86-13801262916Email suxiangqian@bjmu.edu.cnBackground: Few studies have evaluated the outcomes of transhiatal and right thoracoabdominal resection of Siewert type II adenocarcinoma of the esophagogastric junction. This study investigated the relative effect of these two methods in the surgical treatment of Siewert type II adenocarcinoma of the esophagogastric junction.Methods: Clinical data for 211 Siewert type II cancer patients were collected and classified into transhiatal group (n = 181) and right thoracoabdominal group (n = 30) according to surgical approach. Short-term outcomes were compared between these two groups. A 1:1 propensity score matching was performed using a logistic regression model. Recurrence-free survival and overall survival were compared between the matched groups.Results: The right thoracoabdominal group had significantly greater intraoperative blood loss and longer operative time compared with transhiatal group. Complications corresponding to Clavien–Dindo grade III or higher were 4.4% in transhiatal group and 30% in right thoracoabdominal group (P < 0.05). The right thoracoabdominal group exhibited greater blood loss, longer operative time, longer hospitalization, and a smaller number of lymph nodes retrieved than the transhiatal group as evidenced by PSM analysis, and patients in transhiatal group also experienced significantly better survival than patients in right thoracoabdominal group.Conclusion: In this study, the transhiatal approach was associated with more favorable short-term and oncological outcomes than the right thoracoabdominal group approach for Siewert type II adenocarcinoma of the esophagogastric junction. The transhiatal approach with total gastrectomy appears to be an optional choice for this type of tumor, especially for esophagus invasion ≤ 2 cm. Well-designed randomized control trials are necessary to validate our findings.Keywords: adenocarcinoma of the esophagogastric junction, Siewert type II, transhiatal resection, right thoracoabdominal resection

The ligation site of the inferior mesenteric artery (IMA) during laparoscopic radical resection for rectal cancer has been controversial. Consecutive patients (n = 205) with rectal cancer who underwent laparoscopic-assisted low anterior resection from January 2009 to December 2015 were retrospectively analyzed. The patients were divided into high ligation (n = 126) and improved low ligation groups (n = 79). A total of 205 rectal cancer patients underwent laparoscopic assisted anterior resection: 126 patients in the high ligation group and 79 patients in the improved low ligation group. The improved low ligation group was better than the high ligation group in terms of postoperative flatus time and postoperative defecation time. There were no differences between the groups in terms of blood loss, operation time, total number of lymph nodes, anastomotic leakage, postoperative time to first liquid diet and postoperative hospital stay. There were also no differences in 5-year overall survival (OS). Compared to high ligation, the improved low ligation ensures the extent of lymph node dissection, and promotes the early recovery of postoperative gastrointestinal function, but does not increase the operation time, bleeding risk, or anastomotic leakage. A ligation site of the IMA in laparoscopic rectal cancer surgery may not influence oncological outcomes.

This study was performed to compare the short- and long-term outcomes of laparoscopic extralevator abdominoperineal resection (LELAPR) versus laparoscopic abdominoperineal resection (LAPR) in patients with lower rectal cancer.Consecutive patients who underwent LELAPR or LAPR in our unit from September 2009 to December 2015 were retrospectively reviewed. The patients' clinicopathological data and short- and long-term outcomes were compared and analyzed.Of the 111 patients included in this study, 58 (52%) patients underwent LAPR and 53 (48%) LELAPR. A negative circumferential resection margin was achieved in all the two groups of patients. The LELAPR group had a longer operation time (P = 0.049), more intraoperative blood loss (P = 0.037), shorter hospitalization after surgery (P = 0.002), fewer lymph nodes harvested (P = 0.001), fewer positive lymph nodes (P = 0.002), and a shorter maximum tumor diameter (P 0.001) compared with the LAPR group. There were also lower rates of intraoperative perforation (P = 0.039) and death (P = 0.013) in the LELAPR group. However, there were no significant differences in the rates of local recurrence (P = 0.144), metastasis (P = 0.111), overall survival (P = 0.404), disease-free survival (P = 0.515), or progression-free survival (P = 0.210) between the two groups. There were no significant differences in postoperative complications including postoperative hernia (P = 0.918), urinary retention (P = 0.579), intestinal obstruction (P = 1.0), and perineal wound complications (P = 0.252).Compared with LAPR, the LELAPR approach significantly reduced the rate of intraoperative perforation and postoperative death without increasing postoperative complications. LELAPR was beneficial to patients with ulcerative, anterior and advanced lower rectal cancer.

Background This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. Methods We retrospectively identified 428 patients with stage II–III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7–8 cycles every 3 weeks or 10–12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4–6 cycles every 3 weeks or 6–9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. Results The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4–6/6–9 and 7–8/10–12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). Conclusions To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4–6 cycles every 3 weeks or FOLFOX regimen for 6–9 cycles every 2 weeks might be a favorable option for patients with stage II–III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.

Although the acceptance of laparoscopy-assisted gastrectomy (LAG) for the treatment of gastric cancer (GC) has been increasing, it is still controversial that LAG is an applicable treatment method for elderly patients since elderly patients are usually complicated with other diseases. Therefore, this study aimed to investigate the prognostic differences between elderly patients and non-elderly patients after receiving LAG.Patients (n = 306) who received LAG for the treatment of GC from April 2009 to December 2014 were included in the study. The patients were divided into the elderly group (≥ 65 years old, n = 120) and the non-elderly group (65 years old, n=186). The postoperative outcomes as well as the morbidity and the survival rates were compared between the two groups.American Society of Anesthesiologists (ASA) score and comprehensive complication index (CCI) score in the elderly group were significantly higher than those in the non-elderly group (p0.05). In terms of surgical outcomes, there was no significant difference in blood loss or postoperative hospital stay between the elderly group and the non-elderly group. As for postoperative comorbidities, there were significant differences in intraperitoneal hemorrhage and pleural effusion between the elderly group and the non-elderly group. Moreover, the median follow-up time was 38.5 months, and the overall survival of elderly patients with comorbidities was significantly lower than that of the elderly patients without comorbidities (p0.05).LAG can be performed safely and successfully in the elderly population with acceptable postoperative and long-term results.

Background: Postoperative symptomatic anastomotic leakage (AL) is a serious complication after low anterior resection (LAR) for rectal cancer. AL can potentially affect short-term patient outcomes and long-term prognosis. This study aimed to explore the risk factors and long-term survival of symptomatic AL after laparoscopic LAR for rectal cancer.Methods: From May 2009 to May 2015, 298 consecutive patients who underwent laparoscopic LAR for rectal cancer with or without a defunctioning stoma were included in this study. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for symptomatic AL. Survival analysis was performed using Kaplan–Meier curves, and log-rank tests were used for group comparisons.Results: Among the 298 patients enrolled in this study, symptomatic AL occurred in eight patients (2.7%). The univariate analyses showed that the age≤65 (P = 0.048), neoadjuvant therapy (P = 0.095), distance from the anal verge (P = 0.078), duration of operation (P = 0.001), and pathological tumor (T) category (P = 0.004) were associated with symptomatic AL. The multivariate analysis demonstrated that only the duration of operation (P = 0.010) was an independent risk factor for symptomatic AL after laparoscopic LAR for rectal cancer. In the survival analysis, no statistically significant differences in the 3-year (P = 0.785) and 5-year (P = 0.979) overall survival rates were observed.Conclusions: A prolonged duration of operation increased the risk of symptomatic AL after laparoscopic LAR for rectal cancer. An impact of symptomatic AL on long-term survival was not observed in this study, but it needs to be studied more.Trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033413).

Background: Intracorporeal esophagojejunostomy remains a challenging technique in totally laparoscopic total gastrectomy (TLTG) without established standard anastomosis method. π-shaped esophagojejunostomy in TLTG was reported to be safe and feasible. Therefore, this study aimed to depict our modified π-shaped esophagojejunostomy in TLTG and evaluate its short-term surgical outcomes.Methods: From April 2018 to October 2019, 40 patients with gastric cancer who underwent TLTG by the same surgeon with modified π-shaped esophagojejunostomy were enrolled. Clinicopathologic data including age, gender, body mass index, American Society of Anesthesiologists score, tumor size, tumor location, depth of tumor invasion, number of harvested lymph nodes, nodal metastasis and TNM stage, operative time, estimated blood loss, time to resume diet, postoperative hospital stays, complication, and mortality were collected and retrospectively analyzed.Results: The mean operative time and estimated blood loss were 264.6 ± 56.9 min and 68.5 ± 53.3 mL, respectively. Postoperative flatus occurred at 4.6 ± 1.7 days. The mean time to resume diet was 7.4 ± 1.7 days postoperatively. One patient was diagnosed with anastomotic leakage and managed with conservative therapy. Pleural effusion, occurring in 4 (10%) patients, was the most common complication. One patient experienced intra-abdominal bleeding requiring reoperation. Other complications were atrial fibrillation and wound infection. No mortality occurred during the 6-month follow-up.Conclusions: Modified π-shaped esophagojejunostomy is a safe and feasible method for intracorporeal anastomosis in TLTG, which showed favorable surgical outcomes.

Background: Neoadjuvant chemoradiotherapy (CRT) can downstage rectal carcinoma, resulting in superior resectability, better local control and survival benefits. However, it is unclear whether patients treated with CRT and those who did not have similar outcomes at the same pathological stage. This study aimed to investigate the long-term outcomes of ypT1-3N0 mid-low rectal cancer who received neoadjuvant CRT followed by total mesorectal excision (TME) compared with pT1-3N0 rectal cancer immediately managed with surgery. Methods: We retrospectively enrolled 180 patients with pT1-3N0 or ypT1-3N0 rectal cancer located within 10cm from the anal edge who underwent TME between 2009 and 2015. Of these patients, 63 received neoadjuvant CRT, while 117 underwent radical proctectomy without preoperative therapy. The disease-free survival (DFS) and cancer-specific survival (CSS) were compared between the two groups. Results: Within a median follow-up time of 65 months, the 5-year DFS was lower in the CRT group than the non-CRT group (74.9% vs. 92.6%, P=0.001), and the 5-year CSS presented a similar trend as well (89.6 % vs. 97.1%, P=0.054). By subgroup analysis, the difference in DFS and CSS was mainly caused by the difference between ypT3N0 and pT3N0 disease (71.1% vs. 96.1%, P＜0.001 and 90.9% vs. 100%, P=0.029, respectively). However, patients with ypT1-2N0 had an analogous prognosis to those with pT1-2N0 disease (77.9% vs. 89.0%, P=0.225 and 88.1% vs. 94.2%, P=0.292, respectively). Multivariate analysis indicated that neoadjuvant CRT was not an independent predictor of DFS. Conclusion: After neoadjuvant CRT followed by TME, patients with ypT1-2N0 rectal cancer had an analogous prognosis to those with initial pT1-2N0 disease, whereas patients with ypT3N0 rectal cancer had worse prognosis compared with that of pT3N0 disease.

Progressive liver fibrosis, caused by chronic viral infection and metabolic disorders, results in the development of cirrhosis and hepatocellular carcinoma. However, no antifibrotic therapies have been approved to date. In our previous study, adeno‑associated virus (AAV) short hairpin RNAs (shRNAs) targeting hepatitis B virus (HBV) and transforming growth factor (TGF)‑β administration could persistently inhibit HBV replication and concomitantly prevent liver fibrosis. However, the differentially expressed proteins and critical regulatory networks of AAV‑shRNA treatment remain unclear. Accordingly, in the present study, we aimed to analyze differentially expressed proteins in the liver of AAV‑shRNA‑treated mice with HBV infection and liver fibrosis using isobaric tags for relative and absolute quantitation (iTRAQ)‑based quantitative proteomics and to elucidate the underlying antifibrotic mechanisms. In total 2,743 proteins were recognized by iTRAQ‑based quantitative proteomics analysis. Gene Ontology analysis revealed that the differentially expressed proteins mostly participated in peptide metabolism in the biological process category, cytosolic ribosomes in the cell component category, and structural constituents of ribosomes in the molecular function category. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that oxidative stress and the peroxisome proliferator‑activated receptor (PPAR) signaling pathway were activated after treatment. Verification studies revealed that AAV‑shRNAs inhibited hepatic stellate cell activation and inflammation by suppressing nuclear factor‑κB p65 phosphorylation and α‑smooth muscle actin expression via upregulation of PPAR‑γ. Hepatocytes steatosis was also decreased by activating the PPAR signaling pathway and improving lipid metabolism. The expression level of TGF‑β was decreased due to upregulation of PPAR‑γ expression and direct inhibition using AAV‑shRNA targeting TGF‑β. TGF‑β‑induced oxidative stress was suppressed by increasing glutathione S‑transferase Pi 1 and reducing peroxiredoxin 1. Collectively, the present results indicated that AAV‑shRNAs were effective in modulating liver fibrosis by reducing oxidative stress, inflammation and activating the PPAR signaling pathway.

Summary Background Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. Methods This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18–75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes—intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only—are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov , NCT02619942 . Study recruitment is complete, and follow-up is ongoing. Findings Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, −2·2% [95% CI −7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I–II complications were similar between groups (91 [18%] vs 92 [18%], difference, −0·0% [95% CI −4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III−IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], −2·2% [−4·1 to −0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes. Interpretation Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. Funding The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.

Background Distal resection margin (DRM) is closely associated with sphincter-preserving surgery and oncologic safety for patients with mid-low rectal cancers. However, the optimal DRM has not been determined. The purpose of this study to assess the impact of a DRM of ≤ 1 cm on oncologic safety. Methods Data of 378 patients who underwent laparoscopic-assisted sphincter-preserving surgery from 2009 to 2015 were retrospectively analyzed. Patients were divided into two groups based on DRM: ≤ 1 cm (n = 74) and > 1 cm (n = 304). Stratified analysis was performed according to neoadjuvant chemoradiotherapy. Results On the whole, no significant differences in 5-year disease-free survival (DFS) (92.8 vs. 81.3%; P = 0.128) and 5-year overall survival (OS) (83.7 vs. 82.2%; p = 0.892) were observed in patients with DRMs of ≤ 1 and > 1 cm, respectively. A total of 44 patients received preoperative chemoradiotherapy. In this cohort, the 5-year local recurrence (LR) rates ( p = 0.118) and the 5-year DFS rates ( p = 0.298) were not significantly different between the two groups. A total of 334 patients received surgery without neoadjuvant chemoradiotherapy. There were also no significant differences in the 5-year LR rates ( p = 0.150) and 5-year DFS rates ( p = 0.172) between the two groups. Conclusions No matter whether patients with rectal cancers received neoadjuvant therapy or not, sphincter-preserving surgery with a DRM ≤ 1 cm may be acceptable in low rectal cancer without jeopardizing oncologic safety.

Purpose Recently, totally laparoscopic gastrectomy has been gradually accepted by surgeons worldwide for gastric cancer treatment. Complete dissection of the lymph nodes and the establishment of the surgical margin are the most important considerations for curative gastric cancer surgery. Previous studies have demonstrated that indocyanine green (ICG)-traced laparoscopic gastrectomy significantly improves the completeness of lymph node dissection. However, it remains difficult to identify the tumor location intraoperatively for gastric cancers that are staged ≤T3. Here, we investigated the feasibility of ICG fluorescence for lymph node mapping and tumor localization during totally laparoscopic distal gastrectomy. Materials and methods Preoperative and perioperative data from consecutive patients with gastric cancer who underwent a totally laparoscopic distal gastrectomy were collected and analyzed. The patients were categorized into the ICG (n=61) or the non-ICG (n=75) group based on whether preoperative endoscopic mucosal ICG injection was performed. Results The ICG group had a shorter operation time and less intraoperative blood loss. Moreover, significantly more lymph nodes were harvested in the ICG group than the non-ICG group. No pathologically positive margin was found and there was no significant difference in either the proximal or distal surgical margins between the 2 groups. Conclusions Near-infrared fluorescence imaging with ICG can be successfully used in totally laparoscopic distal gastrectomy, and it contributes to both the completeness of D2 lymph node dissection and confirmation of the gastric transection line. Well-designed prospective randomized studies are needed in the future to fully validate our findings.

Background: This study aimed to explore the risk factors associated with esophagojejunal anastomotic leakage (EJAL) in curative total gastrectomy combined with D2 lymph node dissection for gastric cancer.Methods: 390 consecutive patients receiving Roux-en-Y esophagojejunostomy reconstruction after surgery were reviewed. Multivariate analysis was performed using a logistic regression model to identify independent risk factors for EJAL.Results: Of the 390 patients enrolled in this study, EJAL occurred in 10 patients (2.6%). One patient (1/10) with EJAL died. Univariate analysis identified age (P = 0.025), alcohol consumption (P = 0.019), pulmonary insufficiency (P = 0.049), and intraoperative blood loss (P = 0.015) as risk factors for EJAL. Of these four risk factors, age (P = 0.043) and alcohol consumption (P = 0.043) were retained as independent risk factors by multivariate analysis.Conclusions: Surgeons should be very careful about anastomotic leakage during the perioperative period, especially in patients with advanced age and a history of alcohol consumption. Pulmonary insufficiency and intraoperative blood loss, although not being identified as independent risk factors, should also be considered.

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This multicentre randomised controlled trial (RCT) aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. Methods: This superiority phase III trial was undertaken at 17 hospitals in 9 provinces of China. Patients with adenocarcinoma located between the cecum and the right third of the transverse colon, without evidence of distant metastases, were randomly assigned (in a 1:1 ratio) to receive either CME or D2 dissection during laparoscopic right colectomy. Morbidity and mortality in the first 30 days after surgery were compared between the two groups using a modified intention-to-treat (mITT) analysis. Findings: A total of 1072 patients were enrolled between January 11, 2016, and December 26, 2019. Of these patients, 995 (495 CME patients, 500 D2 patients) were included in the mITT analysis. The 30-day postoperative morbidity rate was 19·6% in the CME group vs. 21·8% in the D2 group (difference, -2·2% [95%CI, -0·07, - 0·03]; P = 0·34); no deaths occurred in either group. The CME procedures harvested significantly more lymph nodes (26·0 vs 23·0, difference, 3·4 [95%CI, 2·0, 4·9]; P

Background: Progressive liver fibrosis, caused by chronic viral infection and metabolic disorders, results in the development of cirrhosis and hepatocellular carcinoma. However, no antifibrotic therapies have been approved to date. In our previous study, adeno-associated virus (AAV) short hairpin RNAs (shRNAs) targeting hepatitis B virus (HBV) and transforming growth factor (TGF)-β administration could persistently inhibit HBV replication and concomitantly prevent liver fibrosis. However, the differentially expressed proteins and critical regulatory networks of AAVshRNA treatment remain unclear. Accordingly, in this study, our major goal was we aimed to analyze differentially expressed proteins in the liver of AAV-shRNAs-treated mice with HBV infection and liver fibrosis using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics and to elucidate the underlying antifibrotic mechanisms. Results: In total 2743 proteins were recognized by iTRAQ-based quantitative proteomics analysis. Gene ontology analysis suggested that the differentially expressed proteins were mostly participated in peptide metabolism in the biological process category, cytosolic ribosomes in the cell component category, and structural constituents of ribosomes in the molecular function category. Kyoto Encyclopedia of Genes and Genomespathway analysis indicated that oxidative stress and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were actived after treatment. Verification studies showed that AAVshRNAs inhibited hepatic stellate cell activation and inflammation by suppressing nuclear factor-κB p65 phosphorylation and α-smooth muscle actin expression via upregulation of PPAR-γ. Hepatocytes steatosis was also decreased by activating PPAR signaling pathway and improving lipid metabolism. TGF-β level was decreased owning to increase PPAR-γ expression and directly inhibition using AAVshRNAs targeting TGF-β. TGF-β-induced oxidative stress was suppressed by increasing glutathione S-transferase Pi 1 and reducing peroxiredoxin 1. Conclusions: Our results indicated that AAV-shRNAs were effective for modulating liver fibrosis by reducing oxidative stress, inflammation and activating PPAR signaling pathway.

To investigate the risk factors of postoperative pulmonary infection (PPI) in patients over 60 years of age with gastric cancer after radical gastrectomy.Clinicopathological data of 373 patients over 60 years of age who underwent radical gastrectomy at Department IV of Gastrointestinal Cancer Center, Peking University Cancer Hospital, from April 2009 to December 2016 were retrospectively collected in this case-control study. The clinicopathological characteristics of patients with postoperative pulmonary infection (including postoperative atelectasis) and those without pulmonary infection were compared. A Student t-test (reported as Mean±SD if data matching normal distribution) or Mann-Whitney U test [reported as median (quartile) if data did not conform to normal distribution] was used to analyze continuous variables. A χ² test or Fisher exact tests (reported as number and percentage) was used for categorical variables. Multivariable logistic regression was used to analyze the risk factors for pulmonary infection after operation of gastric cancer.PPI was defined as postoperative patients with elevated body temperature (38.0 degrees centigrade) for more than 24 hours; cough and expectoration; positive sputum bacteria culture;recent infiltration, consolidation or atelectasis confirmed by chest imaging examination.Among 373 patients, 50 cases had PPI(13.4%, PPI group), 323 cases had no PPI(86.6%, non-PPI group). There were 39 (78.0%) and 178(55.1%) patients with comorbidities (including hypertension, diabetes and cardiopulmonary disease) preoperatively in PPI and non-PPI group, respectively. The difference between two groups was statistically significant (χ²=9.325,P=0.002). The incidence of preoperative hypoalbuminemia in PPI group was also significantly higher than that in non-PPI group [10.0%(5/50) vs. 3.1% (10/323),χ²=4.098, P=0.048]. Compared to non-PPI group, the rate of total gastrectomy [54.0%(27/50) vs. 34.4% (111/323), χ²=12.501, P=0.002], postoperative wound pain [34.0%(17/50) vs. 11.8% (38/323),χ²=16.928, P0.001], secondary operation [6.0%(3/50) vs. 0.6% (2/323), χ²=6.032, P=0.014] and the rate of gastric tube removal later than 7 days postoperatively [96.0%(48/50) vs. 84.5%(273/323),χ²=4.811, P=0.028] were significantly higher in PPI group, respectively. The postoperative hospital stay was also prolonged in PPI group [16.0(9.5) days vs. 12.0(5.0) days, U=4 275.0, P0.001]. Multivariate logistic regression analysis showed that preoperative comorbidities (OR=4.008, 95%CI:1.768-9.086, P=0.001), abdominal infection (OR=3.164, 95%CI:1.075-9.313, P=0.037), and wound pain (OR=3.428, 95%CI:1.557-7.548, P=0.002) were independent risk factors for PPI in patients over 60 years of age with gastric cancer. Furthermore, 50 patients with pulmonary infection were classified according to the length of latency and the type of infection. The patients with PPI latency ≤ 3 days were classified as early onset (34 cases, 68.0%), and those with latency ≥ 4 days as delayed onset (16 cases, 32.0%); PPI combined with surgical infection (including anastomotic leakage, abdominal infection, duodenal stump leakage, wound infection, etc.) was classified into mixed infection group (13 cases, 26.0%), with non-surgical infection as simple infection group (37 cases, 74.0%). The results showed that the pulmonary infection occurred 0 to 12 days (median 3 days) before surgical infection in mix infection group. The incidence of previous chronic obstructive pulmonary disease (COPD) in patients with early onset was significantly higher than that in patients with delayed onset [17.6%(6/34) vs. 0, χ²=5.005, P=0.025], and the incidence of mixed infection in patients with delayed onset was significantly higher than that in patients with early onset [50%(8/16) vs. 14.7%(5/34), χ²=6.730, P=0.009],but there was no significant difference in postoperative hospital stay between the two groups[17.0(9.8) days vs. 14.0(9.5) days, U=224.0, P=0.317].Postoperative pulmonary infection is common in gastric cancer patients over 60 years of age. Preoperative comorbidities, abdominal infection and wound pain are independent risk factors for postoperative pulmonary infection. Pulmonary infection within 3 days after operation is associated with preoperative COPD. For patients suffering from PPI after the 4th day,attentions should be paid to abdominal infection and anastomotic leakage.

To evaluate the safety and feasibility of laparoscopy-assisted total gastrectomy in gastric cancer patients over 65 years old.Clinical, pathological and follow-up data of 188 gastric cancer patients who underwent laparoscopy-assisted total gastrectomy at Department IV of Gastrointestinal Cancer Center, Peking University Cancer Hospital, from April 2009 to December 2016 were collected for a retrospective cohort study.ECOG performance score 0-1; preoperative gastroscopy discovered gastric masses, and pathological biopsy confirmed adenocarcinoma; distant metastases were excluded by image examination; preoperative cardiopulmonary function was normal; preoperative blood routine test, liver and renal function, and coagulation function were normal; laparoscopy-assisted total gastrectomy was performed.intraoperative laparoscopic exploration indicated abdominal and/or pelvic peritoneal metastasis; free cancer cells in peritoneal cavity; conversion to laparotomy during laparoscopic surgery. Patients were divided by age into 2 groups, ≥ 65 years old group(59 cases) and65 years old group (129 cases). The perioperative conditions and postoperative complications between two groups were compared, and the high risk factors of postoperative complications in patients over 65 years old were analyzed.All the patients were operated by the same operation team. The incidence of comorbidities was 44.1%(26/59) in the ≥ 65 years old group, which was significantly higher than 20.2% (26/129) in the65 years old group (χ²=11.570, P=0.001). The incidence of cardia/fundus cancer was 64.4%(38/59) in the ≥ 65 years old group, which was also significantly higher than 40.3% (52/129) in the65 years old group (χ²=16.625, P=0.001). The number of retrieved lymph nodes in the ≥65 years old group was significantly lower than that in the65 years old group (28.9±10.7 vs. 36.1±15.4, t=3.271, P=0.001). The total morbidity of complications was 13.8%(21/188) and the mortality within 30 days after operation was 1.6%(3/188). The morbidity of postoperative complications and the mortality within 30 days after operation were 20.3%(12/59) and 3.4%(2/59,respectively) in the ≥ 65 years old group, which were slightly higher than those in the65 years old group [10.9%(14/129) and 0.8%(1/129)], without significant difference(both P0.05). Multivariate logistic regression analysis showed that preoperative comorbidities(OR=0.223, 95%CI:0.053 to 0.944, P=0.041) was an independent risk factor for postoperative complications in patients aged ≥ 65 years old undergoing laparoscopy-assisted total gastrectomy. The median survival time was 21.3 months and the overall 5-year survival rate was 50.0%. The 5-year survival rate was 45.5% and 57.5% in patients aged ≥ 65 and65 years, respectively, and there was no significant difference(P=0.205).Laparoscopy-assisted total gastrectomy is safe and effective in the treatment of gastric cancer patients ≥ 65 years old. Age is not a contraindication of laparoscopy-assisted total gastrectomy.

To establish a method for efficient expression and purification of the human serotonin type 3A receptor (5-HT3A) that is suitable for structural studies. Codon-optimized cDNA of human 5-HT3A was inserted into a modified BacMam vector, which contained an IgG leader sequence, an 8×His tag linked with two-Maltose Binding Proteins (MBP), and a TEV protease cleavage site. The BacMam construct was used to generate baculoviruses for expression of 5-HT3A in HEK293F cells. The proteins were solubilized from the membrane with the detergent C12E9, and purified using MBP affinity chromatography. The affinity tag was removed by TEV protease treatment and immobilized metal ion affinity chromatography. The receptors were further purified by size-exclusion chromatography (SEC). Western blot and SDS-PAGE were used to detect 5-HT3A during purification. The purified receptor was used in crystallization and analyzed with negative stain electron microscopy (EM). The BacMam system yielded 0.5 milligram of the human 5-HT3A receptor per liter of cells. MBP affinity purification resulted in good yields with high purity and homogeneity. SEC profiles indicated that the purified receptors were pentameric. No protein crystals were obtained; however, a reconstructed 3D density map generated from the negative stain EM data fitted well with the mouse 5-HT3A structure. With the BacMam system, robust expression of the human 5-HT3A receptor is obtained, which is monodisperse, therefore enabling 3D reconstruction of an EM map. This method is suitable for high-throughput screening of different constructs, thus facilitating structural and biochemical studies of the 5-HT3A receptor.

To report our methods for expression and purification of α7 nicotinic acetylcholine receptor (α7-nAChR), a ligand-gated pentameric ion channel and an important drug target. α7-nAChRs of 10 different species were cloned into an inducible BacMam vector with an N-terminal tag of a tandem maltose-binding protein (MBP) and a TEV cleavage site. This α7-nAChR fusion receptor was expressed in mammalian HEK293F cells and detected by Western blot. The expression was scaled up to liters. The receptor was purified using amylose resin and size-exclusion chromatography. The quality of the purified receptor was assessed using SDS-PAGE gels, thermal stability analysis, and negative stain electron microscopy (EM). The expression construct was optimized through terminal truncations and site-directed mutagenesis. Expression screening revealed that α7-nAChR from Taeniopygia guttata had the highest expression levels. The fusion receptor was expressed mostly on the cell surface, and it could be efficiently purified using one-step amylose affinity chromatography. One to two milligrams of the optimized α7-nAChR expression construct were purified from one liter of cell culture. The purified α7-nAChR samples displayed high thermal stability with a Tm of 60 °C, which was further enhanced by antagonist binding but decreased in the presence of agonist. EM analysis revealed ring-like structures with a central hydrophilic hole, which was consistent with the pentameric assembly of the α7-nAChR channel. We have established methods for crystallization scale expression and purification of α7-nAChR, which lays a foundation for high-resolution structural studies using X-ray crystallography or single particle cryo-EM analysis.

Colon cancer nomogram designed by Memorial Sloan-Kettering Cancer Center (MSKCC) is an online prediction tool to predict overall survival for individual patient after curative resection. However, this model was never externally validated. We evaluated the accuracy of this nomogram in an independent external Chinese cohort. Clinical data from 1005 patients who underwent primary curative-intent surgery at Peking University Cancer Hospital & Institute between 1996 and 2008 were used for external validation. Clinicopathologic characteristics and the performance of the MSKCC nomogram for prediction of overall survival were evaluated for 985 patients with complete data by using concordance index (C-index) and calibration plot. The C-index for the MSKCC nomogram was 0.71 in the Chinese cohort, compared with 0.67 for American Joint Committee on Cancer (AJCC) stage (P