Search

Autophagy plays a crucial role in colorectal cancer (CRC) development. Our previous study suggested that serine/threonine protein kinase 25 (STK25) regulates aerobic glycolysis in CRC cells. Glycolysis modulates cellular autophagy during tumor growth; however, the role of STK25 in autophagy remains unclear. In this study, we found that STK25 expression was decreased in CRC tissues and CRC patients with high STK25 expression had a favorable prognosis. Functional assays suggested that STK25 inhibition promoted autophagy in CRC cells. Overexpression of STK25 exhibited the opposite effects. Moreover, the results of western blot demonstrated that silencing STK25 induced autophagy by activating the JAK2/STAT3 pathway. Therefore, STK25 could be a potential indicator for therapies targeting the JAK2/STAT3 pathway in CRC.

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.

Summary Background The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. Methods We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40–60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40–60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. Findings Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5–56·3) in the adjuvant-CapOx group, 56·5% (51·0–61·7) in the adjuvant-SOX group, and 59·4% (53·8–64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61–0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68–1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3–4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. Interpretation Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. Funding National Key Research and Development Program of China, Beijing Scholars Program 2018–2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. Translation For the Chinese translation of the abstract see Supplementary Materials section.

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.

Background Paclitaxel plus S-1(PTXS) has shown definite efficacy for advanced gastric cancer. However, the efficacy and safety of this regimen in neoadjuvant setting for locally advanced gastric cancer (LAGC) are unclear. This study aimed to compare the efficacy of neoadjuvant chemotherapy (NAC) PTXS and oxaliplatin plus S-1 (SOX) regime for patients with LAGC. Methods A total of 103 patients with LAGC (cT3/4NanyM0/x) who were treated with three cycles of neoadjuvant SOX regimen (n = 77) or PTXS regimen (n = 26) between 2011 and 2017 were enrolled in this study. NAC-related clinical response, pathological response, postoperative complication, and overall survival were analyzed between the groups. Results The baseline data did not differ significantly between both groups. After NAC, the disease control rate of the SOX group (94.8%) was comparable with that of the PTXS group (92.3%) (p = 0.641). Twenty-three cases (29.9%) in the SOX group and 10 cases (38.5%) in the PTX group got the descending stage with no statistical difference (p = 0.417). No significant differences were observed in the overall pathological response rate and the overall postoperative complication rate between the two groups (p > 0.05). There were also no differences between groups in terms of 5-year overall and disease-free survival (p > 0.05). Conclusions The validity of NAC PTXS was not inferior to that of SOX regimen for locally advanced gastric cancer in terms of treatment response and overall survival. PTXS regimen could be expected to be ideal neoadjuvant chemotherapy for patients with LAGC and should be adopted for the test arm of a large randomized controlled trial.

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.

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.

Surgical excision is currently the principal therapy for locoregional colorectal cancer (CRC). However, surgical trauma leads to controlled tissue damage, causing profound alterations in host immunity and, in turn, affecting post-operative outcomes. Surgery-induced immune alterations in CRC remain poorly defined. Here, single-cell mass cytometry was applied to serial blood samples collected pre-operatively, and on days 1, 3, and 7 post-operatively from 24 patients who underwent laparoscopic surgical resection of CRC to comprehensively monitor the perioperative phenotypic alterations in immune cells and dynamics of immune response. Characterization of immune cell subsets revealed that the post-operative immune response is broad but predominantly suppressive, supported by the decreases in total frequencies of circulating T cells and natural killer (NK) cells, as well as decreased HLA-DR expression on circulating monocytes. The proportion of T cells significantly decreased on day 1 and recovered to the pre-surgical level on day 3 after surgery. The frequency of monocytes was significantly elevated on day 1 after surgery and declined to baseline level on day 3. NK cells temporarily contracted on post-operative day 3. T cells, monocytes, DCs, NK cells, and B cells were partitioned into phenotypically different single-cell clusters. The dynamics of single-cell clusters were different from those of the bulk lineages. T cell clusters in the same response phase fluctuate inconsistently during the perioperative period. Comparing to the baseline levels, the frequencies of CD11b(+)CD33(+)CD14(+)CD16(−) classical monocytes expanded followed by contraction, whereas CD11b(+)CD33(+)CD14(high)CD16(low) intermediate monocytes remained unchanged; HLA-DR expression in monocytes were significantly reduced; the frequencies of intermediate CD56(bright)CD16(+) NK cell subsets increased; and the percentage of memory B lymphocytes were elevated after surgery. Post-operative pro- and anti-inflammatory cytokines were both altered. Furthermore, perioperative immune perturbations in some of the cell subsets were unrecovered within seven days after surgery. Chronological monitoring major immune lineages provided an overview of surgery-caused alterations, including cell augments and contractions and precisely timed changes in immune cell distribution in both innate and adaptive compartments, providing evidence for the interaction between tumor resection and immune modulation.

Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.

Circular RNA (circRNA) is a non-coding RNA molecule that lacks polyadenylated tails and is highly stable, abundant, and conserved in human cells. CircRNAs can serve as a competing endogenous RNA (ceRNA) to sponge microRNAs (miRNA) and block their effects on target mRNA expression. CircRNAs also have possible relevance to cancer and therefore may be considered as ideal biomarkers for monitoring cancer progression. Of the about 300,000 predicted human circRNAs, only a few have validated biological functions related to cancer. To better understand the ceRNA role of circRNAs in colorectal cancer (CRC), we performed genome-wide circRNA-based RNA-sequencing (RNA-Seq) on nine CRC tumor samples and their paired histologically normal adjacent tissue samples. By profiling the mRNA expression in the same patients, we further explored the expression correlation between circRNAs and mRNAs generated from the same parental gene. Focusing on the concordant differential expression between circRNAs and mRNAs, we substantially reduced the regulatory noise. In total, we identified 694 circRNA-mRNA pairs that were consistently up or downregulated between tumor and normal tissues. These 694 circRNA-mRNA pairs are from 182 protein-coding genes associated with hormone responses and chemotaxis. Of these 182 genes, 43 are downstream targets of three highly conserved miRNAs (miR-410-3p, miR-135a, and miR-30a). Interestingly, these 43 genes are highly mutated in another cohort from eight independent CRC studies, which have significant effects on patient survival time. Focusing on miR-410-3p and its target oncogene MET, we experimentally validated the ceRNA regulatory motif of circMET. Notably, circMET is substantially upregulated in CRC cell lines and could promote cell proliferation and growth. By confirming the regulatory relationship between miR-410-3p and circMET, we propose a new mechanism for the observed sustained activation of MET in CRC. In conclusion, our work identifies a novel regulatory role of circMET and provides a potential diagnostic biomarker for CRC.

Background and objectives Evidence is inconclusive regarding the prognostic significance of deficient DNA mismatch repair (dMMR) in gastric and gastroesophageal junction (GEJ) adenocarcinoma patients receiving chemotherapy. We aim to explore such associations with a large cohort. Methods We retrospectively identified a consecutive cohort of patients who had histology proven gastric or GEJ adenocarcinoma and received neoadjuvant chemotherapy plus surgery or upfront surgery plus adjuvant chemotherapy. MMR status was assessed by immunohistochemistry staining on surgical specimen. The association of MMR status with tumor regression grade (TRG), overall survival (OS), and disease-free survival (DFS) were analyzed. Results In total, 1568 patients received neoadjuvant or adjuvant chemotherapy, of which 128 (8.2%) had dMMR tumors. No significant difference was found in the frequencies of TRG categories between proficient MMR (pMMR) and dMMR tumors (p = .62). Among patients receiving neoadjuvant chemotherapy, dMMR status was associated with better OS (log-rank p = .044) and DFS (log-rank p = .022) in the univariate analysis; this association became nonsignificant after adjusting for pathologic stages and other prognostic factors. Similar results were found for patients receiving adjuvant chemotherapy. Conclusions dMMR status was not significantly associated with OS and DFS among gastric and GEJ adenocarcinoma patients with neoadjuvant and adjuvant platinum and fluorouracil-based chemotherapy.

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.

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 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 (2.7%) patients. The univariate analysis showed that age of ≤65 years (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 prolonged duration of operation (P = 0.010) was an independent risk factor for symptomatic AL after laparoscopic LAR for rectal cancer. No statistically significant differences were observed in the 3-year (P = 0.785) and 5-year (P = 0.979) overall survival rates. Conclusions A prolonged duration of operation increased the risk of symptomatic AL after laparoscopic LAR for rectal cancer. An impact of symptomatic AL on a long-term survival was not observed in this study; however, further studies are required. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033413) on May 31, 2020.

Mutated KRAS promotes the activation of the MAPK pathway and the progression of colorectal cancer (CRC) cells. Aberrant activation of the PI3K pathway strongly attenuates the efficacy of MAPK suppression in KRAS‐mutated CRC. The development of a novel strategy targeting a dual pathway is therefore highly essential for the therapy of KRAS‐mutated CRC. In this study, a quadruple‐depleting system for the KRAS, MEK1, PIK3CA, and MTOR genes based on CRISPR/SaCas9 was developed. Adenovirus serotype 5 (ADV5) was integrated with two engineered proteins, an adaptor and a protector, to form ADV‐protein complex (APC) for systemic delivery of the CRISPR system. Quadruple‐editing could significantly inhibit the MAPK and PI3K pathways in CRC cells with oncogenic mutations of KRAS and PIK3CA or with KRAS mutation and compensated PI3K activation. Compared with MEK and PI3K/MTOR inhibitors, quadruple‐editing induced more significant survival inhibition on primary CRC cells with oncogenic mutations of KRAS and PIK3CA. The adaptor specifically targeting EpCAM and the hexon‐shielding protector could dramatically enhance ADV5 infection efficiency to CRC cells and significantly reduce off‐targeting tropisms to many organs except the colon. Moreover, quadruple‐editing intravenously delivered by APC significantly blocked the dual pathway and tumor growth of KRAS‐mutated CRC cells, without influencing normal tissues in cell‐ and patient‐derived xenograft models. Therefore, APC‐delivered quadruple‐editing of the MAPK and PI3K pathways shows a promising therapeutic potential for KRAS‐mutated CRC., Aberrant activation of the PI3K pathway interferes with the therapeutic efficacies of MAPK signaling inhibitors in KRAS‐mutated colorectal cancer (CRC). However, overlapping toxicities of small molecule inhibitors limit the treatment effects of combined therapy targeting the MAPK and PI3K pathways. Multiplex genome editing may provide a novel dual‐inhibition strategy for KRAS‐mutated CRC. A quadruple‐depleting system of KRAS, MEK1, PIK3CA, and MTOR based on CRISPR/SaCas9, which were packaged by ADV5 and integrated with two engineered proteins, an adaptor and a protector, to enhance infection efficiency and specificity to CRC cells, could effectively and specifically block tumor progression of KRAS‐mutated CRC models through systemic delivery without vital organ injury, providing a potential option for CRC therapy.

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.

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.

Importance The safety of laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer remains uncertain given the lack of high-level clinical evidence. Objective To compare the safety of LTG for clinical stage I gastric cancer with that of conventional open total gastrectomy (OTG). Design, Setting, and Participants The Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group CLASS02 study was a prospective, multicenter, open-label, noninferiority, randomized clinical trial that compared the safety of LTG vs OTG with lymphadenectomy for patients with clinical stage I gastric cancer. From January 2017 to September 2018, a total of 227 patients were enrolled. Final follow-up was in October 2018. Interventions Eligible patients were randomized to LTG (n = 113) or OTG (n = 114) by an interactive web response system. Main Outcomes and Measures The primary outcome was the morbidity and mortality within 30 days following surgeries between LTG and OTG with a noninferiority margin of 10%. The secondary outcomes were recovery courses and postoperative hospital stays. Results A total of 214 patients were analyzed for morbidity and mortality (105 patients in the LTG group and 109 patients in the OTG group). The mean (SD) age was 59.8 (9.4) years in the LTG group and 59.4 (9.2) years in the OTG group, and most were male (LTG group, 75 of 105 [71.4%]; OTG group, 80 of 109 [73.4%]). The overall morbidity and mortality rates were not significantly different between the groups (rate difference, −1.1%; 95% CI, −11.8% to 9.6%). Intraoperative complications occurred in 3 patients (2.9%) in the LTG group and 4 patients (3.7%) in the OTG group (rate difference, −0.8%; 95% CI, −6.5% to 4.9%). In addition, there was no significant difference in the overall postoperative complication rate of 18.1% in the LTG group and 17.4% in the OTG group (rate difference, 0.7%; 95% CI, −9.6% to 11.0%). One patient in the LTG group died from intra-abdominal bleeding secondary to splenic artery hemorrhage. However, there was no significant difference in mortality between the LTG group and the OTG group (rate difference, 1.0%; 95% CI, −2.5% to 5.2%), and the distribution of complication severity was similar between the 2 groups. Conclusions and Relevance The results of the CLASS02 trial showed that the safety of LTG with lymphadenectomy by experienced surgeons for clinical stage I gastric cancer was comparable to that of OTG. Trial Registration ClinicalTrials.gov Identifier:NCT03007550

Background This study aimed to evaluate the short- and long-term outcomes after laparoscopic resection for low rectal cancer (LRC) compared with mid/high rectal cancer (M/HRC). Methods Patients with rectal cancer undergoing laparoscopic resection with curative intent were retrospectively reviewed between 2009 and 2015. After matched 1:1 by using propensity score analysis, perioperative and oncological outcomes were compared between LRC and M/HRC groups. Multivariate analysis was performed to identify independent factors of overall survival (OS) and disease-free survival (DFS). Results Of 373 patients who met the criteria for inclusion, 198 patients were matched for the analysis. Laparoscopic surgery for LRC required longer operative time (PP = 0.015) compared with M/HRC, and the LRC group tended to have a higher incidence of postoperative complications (16.2% vs. 8.1%, P = 0.082). There was no significant difference in local recurrence between the two groups (9.1% vs. 4.0%, P = 0.251), whereas distant metastasis was inclined to be more frequent in LRC patients compared with M/HRC (21.2% vs. 12.1%, P = 0.086). The LRC group showed significantly inferior 5-year OS (77.0% vs. 86.4%, P = 0.033) and DFS (71.2% vs. 86.2%, P = 0.017) compared with the M/HRC group. Multivariate analysis indicated that tumor location was an independent predictor of DFS (HR = 2.305, 95% CI 1.203–4.417, P = 0.012). Conclusion Tumor location of the rectal cancer significantly affected the clinical and oncological outcomes after laparoscopic surgery, and it was an independent predictor of DFS.

Background Low anterior resection syndrome (LARS) is a common functional disorder that develops after patients with rectal cancer undergo anal preservation surgery. Common approaches to assess the symptoms of patients with LARS are often complex and time-consuming. Instant messaging/social media has great application potential in LARS follow-up, but has been underdeveloped. Objective The aim of this study was to compare data between a novel instant messaging/social media follow-up system and a telephone interview in patients with LARS and to analyze the consistency of the instant messaging/social media platform. Methods Patients with R0 resectable rectal cancer who accepted several defecation function visits via the instant messaging/social media platform and agreed to a telephone interview after the operation using the same questionnaire including subjective questions and LARS scores were included. Differences between the 2 methods were analyzed in pairs and the diagnostic consistency of instant messaging/social media was calculated based on telephone interview results. Results In total, 21 questionnaires from 15 patients were included. The positive rates of defecation dissatisfaction, life restriction, and medication use were 10/21 (48%), 11/21 (52%), and 8/21 (38%) for telephone interview and 10/21 (48%), 13/21 (62%), and 5/21 (24%) for instant messaging/social media, respectively. No statistically significant difference was observed between instant messaging/social media and telephone interview in terms of total LARS score (mean 22.4 [SD 11.9] vs mean 24.7 [SD 10.7], P Conclusions Instant messaging/social media can be a major LARS screening method. However, further research on information accuracy and user acceptance is needed before implementing a mature system. Trial Registration ClinicalTrials.gov NCT03009747; https://clinicaltrials.gov/ct2/show/NCT03009747

For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

Multiple primary colorectal cancers (MPCCs) are different from solitary colorectal cancers in many aspects, which are not well studied. The aim of this study was to clarify the clinicopathological features and prognosis of MPCCs. The data of 64 patients with MPCCs out of 2300 patients with colorectal cancers (CRCs) from January 2009 to December 2017 were retrospectively analyzed. Stratified analysis was conducted based on subtypes and microsatellite status. The overall incidence of MPCC was 2.8% and the median follow-up duration was 51.5 (range 1–120) months. Metachronous CRCs (MCRCs) are more likely to appear in the right colon (p

Cancer stem cells (CSCs) are considered to be responsible for tumorigenesis and cancer relapse. EpCAM(high)CD44(+) tumor cells are putative colorectal CSCs that express high levels of stem cell genes, while the EpCAM(high)CD44(−) population mostly contains differentiated tumor cells (DTCs). This study aims to determine whether single CSC (EpCAM(high)CD44(+)) and DTC (EpCAM(high)CD44(−)) can be distinguished in terms of somatic copy number alterations (SCNAs). We applied fluorescence-activated cell sorting to isolate the CD45(−)EpCAM(high)CD44(+) and CD45(−)EpCAM(high)CD44(−) populations from two primary colon tumors, on which low-coverage single-cell whole-genome sequencing (WGS) was then performed ∼0.1x depth. We compared the SCNAs of the CSCs and DTCs at single-cell resolution. In total, 47 qualified single cells of the two populations underwent WGS. The single-cell SCNA profiles showed that there were obvious SCNAs in both the CSCs and DTCs of each patient, and each patient had a specific copy number alteration pattern. Hierarchical clustering and correlation analysis both showed that the SCNA profiles of CSCs and DTCs from the same patient had similar SCNA pattern, while there were regional differences in the CSCs and DTCs in certain patient. SCNAs of CSCs in the same patient were highly reproducible. Our data suggest that major SCNAs occurred at an early stage and were inherited steadily. The similarity of ubiquitous SCNAs between the CSCs and DTCs might have arisen from lineage differentiation. CSCs from the same patient had reproducible SCNA profiles, indicating that gain or loss in certain chromosome is required for colon cancer development.

Importance It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes among patients with locally advanced gastric cancer. Data from a multicenter, randomized clinical trial (Chinese Laparoscopic Gastrointestinal Surgical Study [CLASS]-01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy. Objective To report 5-year overall survival data from the CLASS-01 trial of laparoscopic vs open distal gastrectomy among patients with locally advanced gastric cancer. Design, setting, and patients This was a noninferiority, open-label, randomized clinical trial conducted at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 12, 2012, to December 3, 2014. Final follow-up was on December 31, 2019. Interventions Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histologic features to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main outcomes and measures The 5-year overall survival rates were updated to compare laparoscopic distal gastrectomy with open distal gastrectomy. All analyses were performed on an intention-to-treat basis. In addition, per-protocol and as-treated analyses were performed for overall survival. Results Data from 1039 patients (726 men [69.9%]; mean [SD] age, 56.2 [10.7] years) who received curative therapy were analyzed. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P = .19; hazard ratio, 1.17; 95% CI, 0.93-1.48; P = .19). After comparison for competing risk events, gastric cancer-related deaths (hazard ratio, 1.14; 95% CI, 0.87-1.49; P = .34) and deaths from other causes (hazard ratio, 1.23; 95% CI, 0.74-2.05; P = .42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage. Conclusions and relevance This study found that laparoscopic distal gastrectomy with D2 lymphadenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar 5-year overall survival compared with open distal gastrectomy among patients with locally advanced gastric cancer. Trial registration ClinicalTrials.gov Identifier: NCT01609309.

Sporadic synchronous colorectal cancer (CRC) refers to more than one primary tumor detected in a single patient at the time of the first diagnosis without predisposition of cancer development. Given the same genetic and microenvironment they raise, sporadic synchronous CRC is a unique model to study CRC tumorigenesis. We performed whole exome sequencing in 32 fresh frozen tumor lesions from 15 patients with sporadic synchronous CRC to compare their genetic alterations. This approach identified ubiquitously mutated genes in the range from 0.34% to 4.22% and from 0.8% to 7.0% in non-hypermutated tumors and hypermutated tumors, respectively, in a single patient. We show that both ubiquitously mutated genes and candidate cancer genes from different tumors in the same patient mutated at different sites. Consistently, obvious differences in somatic copy number variations (SCNV) were found in most patients with non-hypermutated tumor lesions, which had ubiquitous copy number amplification rates ranging from 0% to 8.8% and ubiquitous copy number deletion rates ranging from 0% to 8.2%. Hypermutated lesions were nearly diploid with 0% to 18.8% common copy number aberrations. Accordingly, clonal structures, altered signaling pathways and druggable genes in a single patient with synchronous CRC varied significantly. Taken together, the disparate SCNVs and mutations in synchronous CRC supported the field effect theory of tumorigenesis. Moreover, the intertumor heterogeneity of synchronous CRCs implies that analysis of all tumor lesions from the same patient is necessary for appropriate clinical treatment decisions.

Increasing evidence shows that competitive endogenous RNAs (ceRNAs) can affect the expression of other transcripts by sequestering common microRNAs (miRNAs), and participate in tumourigenesis. As a potent tumour suppressor in colorectal cancer (CRC), SMAD4 is regulated by many miRNAs. However, the regulation of SMAD4 by ceRNAs has never been examined. In the present study, we found that USP3 modulated SMAD4 expression in a miRNA dependent, and protein-coding gene independent manner. USP3 and SMAD4 were directly targeted by miR-224, and overexpression of the USP3 3′UTR could inhibit metastasis caused by the loss of USP3. The correlation of USP3, SMAD4 and miR-224 expression was further verified in CRC specimens. Additionally, the loss of USP3 was associated with distal metastasis and a poor prognosis. Altogether, our study demonstrates USP3 as a bona fide SMAD4 ceRNA. The results from this study may provide new insights into the prevention and treatment of CRC.

The majority of patients with microsatellite stable (MSS) colorectal cancer (CRC) do not benefit from the immunotherapies directed at rescuing T-cell functions. Therefore, complete understanding of T-cell phenotypes and functional status in the CRC microenvironment is desirable. Here, we applied single-cell mass cytometry to mold the T-cell phenotype in 18 patients with MSS CRC for better understanding of CRC as a systemic disease and to search for tumor-driven T-cell profile changes. We show interpatient and intrapatient phenotypic diversity of T-cell subsets. We revealed increased immunosuppressive/exhausted T-cell phenotypes at tumor lesions. CD8+ CD28- immunosenescent T cells with impaired proliferation capacity dominate the T-cell compartment. As per the transcriptome and quantitative real time-PCR analysis, the accumulation of immunosuppressive cells is driven by the tumor microenvironment. T-cell profiles are similar between patients at early and late stages, indicating that the immunosuppressive microenvironment is formulated early during CRC development. Mapping of T-cell infiltration and understanding of the mechanisms underlying their regulation may provide valuable information to boost the immune response in patients with MSS CRC.

Department of minimally invasive gastrointestinal surgery in Peking University Cancer Hospital (also named as Department of Gastrointestinal Surgery IV) was established on April 7, 2009. Up to now, ten years have passed since its foundation. As the first department built in specialized cancer hospital, which mainly focuses on laparoscopic surgery, its foundation and development has a very important historical and practical significance in the development of surgical oncology in China. Reviewing the rapid growth of the Department of Minimally Invasive Gastrointestinal Surgery over the past decade, on the one hand, it has benefited from the opportunities of the times and the support of leaders in Peking University Cancer Hospital at that time. More importantly, the progress owes to the pioneering Professor Su Xiangqian, who is brave and innovative, with indomitable spirit and advanced management philosophy. With rigorous training, the ability of the team has been steadily enhanced, the competitiveness has been gradually improved, and the development direction which focuses on laparoscopic gastric cancer surgery and laparoscopic colorectal cancer surgery has been established. Now, the Department of Minimally Invasive Gastrointestinal Surgery has become a well-known domestic gastrointestinal tumor center. In the past ten years, under the leadership of Professor Su Xiangqian, the growth of this team is innovative and comprehensive: (1) Introduce the internationally advanced Baldrige medical service management framework, and propose the "management by principle" concept to improve the core competitiveness of the department; (2) Establish an academic brand by laparoscopic standardized surgery training courses for gastrointestinal tumors, promote cooperation and exchange at home and abroad, and participate in international multi-center clinical research projects; (3) Adhere to the "formation of a research-oriented department, conducting clinical and basic research simultaneously" as the development direction; (4) Stick to the core development concept of team building and cultivate professional talents. Looking forward to the future, our team will not forget the beginning of the heart, and move forward! In the next ten years, we will break through ourselves and continue to pursue the higher level!北京大学肿瘤医院胃肠肿瘤微创外科创建于2009年4月7日，至今已走过了10年的历程，在中国肿瘤外科治疗的历史进程及行业发展中具有十分重要的历史意义和现实意义。回顾这10年的发展，一方面得益于时代机遇和医院的支持；更重要的是得益于科室全体人员勇于开拓、敢于创新的奋斗精神和学科带头人先进的管理理念。经过严苛训练的洗礼，科室能力稳步增强，竞争力逐渐提高，逐步确立了以腹腔镜胃癌手术为主，腹腔镜结直肠癌手术并重的学科发展方向，已经成为了国内知名的胃肠肿瘤微创治疗中心。这十年间，在学科带头人苏向前教授的带领下，胃肠肿瘤微创外科开放创新、全面发展，主要体现在：（1）引进国际先进的Baldrige医疗服务管理框架，提出"用制度管理科室"的先进管理理念，提高科室核心竞争力；（2）以承办胃肠道肿瘤腹腔镜标准化手术培训班来创建学术品牌，促进国内外合作交流，参与国际多中心临床研究项目；（3）坚持以"组建研究型科室，临床与基础研究齐头并进"为科室的发展方向；（4）坚持以人才培养为核心发展理念，重视团队建设，培养专业人才。展望未来，北京大学肿瘤医院胃肠肿瘤微创外科团队将不忘初心，砥砺前行！在接下来的10年中突破自我，继续迈向更高的台阶！.

Previous retrospective studies have shown that laparoscopic spleen-preserving D2 total gastrectomy (LSTG) for advanced upper third gastric cancer (AUTGC) is safe. However, all previous studies were underpowered. We therefore conducted a prospective, multicenter study to evaluate the technical safety and feasibility of LSTG for patients with AUTGC. Patients diagnosed with AUTGC (cT2-4a, N−/+, M0) underwent LSTG at 19 institutions between September 2016 and October 2017 were included. The number of No. 10 lymph node (LN) dissections, metastasis rates, intraoperative and postoperative complications were investigated. A total of 251 patients were enrolled in the study, and 242 patients were eligible for the per protocol analysis. The average numbers of No. 10 LN dissections and metastases were 2.4 and 0.1, respectively. Eighteen patients (7.4%) had No. 10 LN metastases, and among patients with advanced gastric cancer, the rate of No. 10 LN metastasis was 8.1% (18/223). pN3 status was an independent risk factor for No. 10 LN metastasis. Intraoperative complications occurred in 7 patients, but no patients required conversion to open surgery or splenectomy. The overall postoperative complication rate was 13.6% (33/242). The major complication and mortality rates were 3.3% (8/242) and 0.4% (1/242), respectively. The number of retrieved No. 10 LNs, No. 10 LN metastasis and TNM stage had no significant influence on postoperative complication rates. LSTG for AUTGC was safe and effective when performed by very experienced surgeons, this technique could be used in patients who needed splenic hilar lymph node dissection.

Importance Laparoscopic distal gastrectomy is accepted as a more effective approach to conventional open distal gastrectomy for early-stage gastric cancer. However, efficacy for locally advanced gastric cancer remains uncertain. Objective To compare 3-year disease-free survival for patients with locally advanced gastric cancer after laparoscopic distal gastrectomy or open distal gastrectomy. Design, Setting, and Patients The study was a noninferiority, open-label, randomized clinical trial at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 2012 to December 2014. Final follow-up was on December 31, 2017. Interventions Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histology to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures The primary end point was 3-year disease-free survival with a noninferiority margin of −10% to compare laparoscopic distal gastrectomy with open distal gastrectomy. Secondary end points of 3-year overall survival and recurrence patterns were tested for superiority. Results Among 1056 patients, 1039 (98.4%; mean age, 56.2 years; 313 [30.1%] women) had surgery (laparoscopic distal gastrectomy [n=519] vs open distal gastrectomy [n=520]), and 999 (94.6%) completed the study. Three-year disease-free survival rate was 76.5% in the laparoscopic distal gastrectomy group and 77.8% in the open distal gastrectomy group, absolute difference of −1.3% and a 1-sided 97.5% CI of −6.5% to ∞, not crossing the prespecified noninferiority margin. Three-year overall survival rate (laparoscopic distal gastrectomy vs open distal gastrectomy: 83.1% vs 85.2%; adjusted hazard ratio, 1.19; 95% CI, 0.87 to 1.64;P = .28) and cumulative incidence of recurrence over the 3-year period (laparoscopic distal gastrectomy vs open distal gastrectomy: 18.8% vs 16.5%; subhazard ratio, 1.15; 95% CI, 0.86 to 1.54;P = .35) did not significantly differ between laparoscopic distal gastrectomy and open distal gastrectomy groups. Conclusions and Relevance Among patients with a preoperative clinical stage indicating locally advanced gastric cancer, laparoscopic distal gastrectomy, compared with open distal gastrectomy, did not result in inferior disease-free survival at 3 years. Trial Registration ClinicalTrials.gov Identifier:NCT01609309

To compare the safety of Billroth I and Billroth II reconstruction in distal gastrectomy for gastric cancer and short-term endoscopic findings.A retrospective cohort study was carried out. Clinical data of gastric adenocarcinoma patients who received distal subtotal gastrectomy with Billroth I or Billroth II reconstruction at Department 4 of Gastrointestinal Surgery, Peking University Cancer Hospital from January 2013 to July 2017 were collected retrospectively. Patients with stage IV gastric cancer, emergent operation, preoperative chemotherapy, combined organ resection and other malignancies were excluded. A total of 277 patients were enrolled in the study with 143 patients in the Billroth I group and 134 patients in the Billroth II group. The intra-operative conditions, postoperative early recovery, postoperative complications, and postoperative 1-year endoscopic findings were compared between the two groups. The normal distribution variables were analyzed by t test; the non-normal distribution variables were analyzed by Mann-Whitney U test; sort variables were compared between groups using the χ² test or Fisher's exact test.In the Billroth I group, 93 (65.0%) cases were male, mean age was (58.1±10.9) years and body mass index was (23.3±3.2) kg/mFor distal gastrectomy, Billroth I reconstruction is easier to operate, while Billroth II reconstruction presents faster recovery of gastrointestinal function and shorter hospital stay. The morbidity of postoperative complication and short-term endoscopic findings between two groups are comparable.

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.

The epidermal growth factor receptor (EGFR) is overexpressed in several epithelial tumors. Anti-EGFR humanized monoclonal antibodies, cetuximab and panitumumab, in combination with chemotherapy have improved the prognosis for patients with wild-type RAS tumors. To identify mimotopes of EGFR and develop mimotope-based EGFR vaccines, we screened a phage display peptide library with panitumumab. Two EGFR mimotopes P19 and P26, which could be recognized by panitumumab specifically, were isolated. To enhance the immune responses, we generated recombinant proteins of P19 or P26 fused to a heat-shock cognate protein 70 (Hsc70), and evaluated the efficacy of Hsc70-P19 and Hsc70-P26 as vaccines in vivo. Immunization with Hsc70-P19 or Hsc70-P26 fusion protein stimulated the immune system to produce specific antibodies against peptides as well as EGFR. Moreover, antibodies elicited against mimotopes could induce antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and inhibit the proliferation of EGFR-overexpressing A431 cells. Treatment with Hsc70-P19 and Hsc70-P26 significantly reduced tumor growth in BALB/c transplantable lung cancer models. Although there was no sequence homology between the phage-derived peptides and EGFR by alignments, both peptides mimic the conformational structure of EGFR binding to panitumumab. In conclusion, the mimotopes we identified from phage display peptide library could be promising candidate vaccines for active anti-EGFR immunotherapy against cancers.

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Mutations in KRAS occur with the frequency of 30-50% in CRC leading to decreased therapeutic response to anti-epidermal growth factor receptor (EGFR) agents. Recently GATA2 was proven to be essential in the survival of KRAS mutant non-small cell lung cancer (NSCLC) cells. However, the association between KRAS mutation and GATA2 expression in CRC remains largely unknown. In the present study, dideoxy sequencing and immunohistochemistry were used to determine KRAS mutation and GATA2 expression, respectively, in a cohort of 236 patients. Cox proportional hazard regression and Kaplan-Meier survival analysis were performed to study the association between KRAS mutation or GATA2 expression and clinical outcomes. Kaplan-Meier analysis revealed that KRAS mutant patients with high expression of GATA2 had significantly worse long-term clinical outcomes than those with low expression of GATA2 (P

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.

The safety of laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer remains lack of clinical evidence. The Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group recently launched a multicenter randomized clinical trial (CLASS02–01) to compare the safety of LTG for clinical stage I gastric cancer with the conventional open total gastrectomy (OTG). This CLASS02–01 trial is a prospective, multicenter, randomized, controlled, open, and non-inferiority trial. Two hundred patients who met the inclusion criteria and did not accord with the exclusion criteria will be randomly divided into LTG group (n = 100) and OTG group (n = 100). The primary purpose of this study is to evaluate the early operative morbidity and mortality of LTG compared with OTG for clinical stage I gastric adenocarcinoma. The second purpose is to evaluate the recovery course and compare the postoperative hospital stay of the patients enrolled in this study. This CLASS02–01 trial is the first prospective randomized two-arm controlled study to determine the safety of LTG compared with OTG. Through this trial, we hope to show that experienced surgeons can safely perform LTG with lymphadenectomy for gastric cancer. ClinicalTrials.gov ID: NCT03007550 . December 30, 2016.

Background Serine/threonine protein kinase 25 (STK25) is critical in regulating whole-body glucose and insulin homeostasis and the accumulation of ectopic lipids. The Warburg effect, also known as aerobic glycolysis, is an essential metabolic characteristic of cancer cells. However, the effects of STK25 on aerobic glycolysis of cancer cells remain unexplored. The aim of this study is to investigate the role of STK25 in colorectal cancer (CRC) and to elucidate the underlying mechanisms. Methods The influences of STK25 on the cell proliferation were evaluated by MTT and colony formation assays. The roles of STK25 in aerobic glycolysis were determined by glucose uptake and lactate production assays. The interaction between STK25 and GOLPH3 was detected by co-immunoprecipitation, GST pull-down, and His-tag pull-down assays. Western blot was used to measure the expression of glycolytic genes, and the status of kinases in mTOR pathway. Moreover, a xenograft mouse model was used to investigate the effects of STK25 in vivo. The prognostic significance of STK25 was analyzed using public CRC datasets by a log-rank test. Results STK25 suppressed proliferation, glycolysis and glycolytic gene expression in CRC cells. STK25 interacted with GOLPH3 and mediated glycolysis through GOLPH3-regulated mTOR signaling. Consistent with these observations, silencing of STK25 promoted tumor growth and glycolytic gene expression in an in vivo xenograft mouse model. Moreover, high levels of STK25 correlated with favorable prognosis in patients with CRC. Conclusions Our results demonstrated that STK25 negatively regulates the proliferation and glycolysis via GOLPH3-dependent mTOR signaling. Accordingly, STK25 could be a potential therapeutic target for the treatment of CRC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0808-1) contains supplementary material, which is available to authorized users.

As a mitotic kinesin, kinesin family member 14 (KIF14) has been reported to serve oncogenic roles in a variety of malignancies; however, its functional role and regulatory mechanisms in colorectal cancer (CRC) remain unclear. In the present study, KIF14 was observed to be markedly overexpressed in CRC, and this upregulation was associated with tumor size and marker of proliferation Ki-67 immunostaining scores. Gain- and loss-of-function experiments were applied to identify the function of KIF14 in CRC progression. In vitro and in vivo assays revealed that KIF14 promoted CRC cell proliferation and accelerated the cell cycle via activation of protein kinase B. In addition, the present study investigated the potential mechanisms underlying KIF14 overexpression in CRC. Bioinformatics analyses and validation experiments, including reverse transcription-quantitative polymerase chain reaction, western blotting and a Dual-Luciferase reporter assay, demonstrated that, in addition to genomic amplification and transcriptional activation, KIF14 was regulated by microRNA (miR)-200c at the post-transcriptional level. Rescue experiments further demonstrated that decreased miR-200c expression could facilitate KIF14 to exert its pro-proliferative role. The expression of miR-200c was negatively correlated with KIF14 in CRC specimens. Collectively, the findings of the present study demonstrated the oncogenic role of KIF14 in colorectal tumorigenesis, and also revealed a complexity of regulatory mechanisms mediating KIF14 overexpression, which may provide insight for developing novel treatments for patients with CRC.

Patients with metachronous colorectal cancer (CRC) have been diagnosed with primary CRC more than once. Given that the genetic and microenvironment is the same in these cases, metachronous CRC is an important model for studying colorectal tumorigenesis. We performed whole exome sequencing of seven freshly frozen tumors from three patients with metachronous CRC and compared their genetic profiles. In patients with metachronous tumors of distinct genetic origins, 3.74% and 0.20% of genes were ubiquitously mutated and candidate cancer genes mutated at different sites. Tumors from the same patients were clonally unrelated, and thus druggable genes differed. In contrast, in a patient with metachronous tumors of a common genetic origin, the ubiquitously mutated genes were 61.02%, with ubiquitously mutated genes and candidate cancer genes all mutated at the same sites, tumors were clonally related, and some druggable genes were the same. Therefore, two different clonal relationships between metachronous tumors exist in CRC, one is monoclonal and the other is polyclonal. Our findings may help to advance understanding of the differences in metachronous CRCs and the genetic mechanisms of which they originate, and provide new avenues for CRC treatment.

To compare the safety and effectiveness of circular stapler and linear stapler in Billroth II( anastomosis following distal gastrectomy for gastric cancer patients.Clinical data of gastric adenocarcinoma patients who received distal gastrectomy with Billroth II( anastomosis at Ward IIII( of Gastrointestinal Cancer Center of Peking University Cancer Hospital from January 2013 to April 2017 were collected retrospectively.(1) patients identified as stage IIII( gastric cancer by preoperative clinical and postoperative pathological staging. (2) patients undergoing emergency operation due to perforation, obstruction, or bleeding of digestive tract. (3) patients receiving chemotherapy before operation. (4) patients undergoing combined organ resection due to tumor involving other organs. (5) patients complicating with other malignancies. A total of 116 cases were enrolled and divided into circular stapler (CS, 61 cases) group and linear stapler (LS, 55 cases) group according to the application of mechanical stapler. Clinicopathological characteristics, operative conditions and postoperative recovery were compared between two groups.Differences in baseline data, such as tumor size, Lauren classification, differentiation grade, and pathologic stage, between two groups were not statistically significant (all P0.05). The mean operative time (230 min vs. 234 min), median intra-operative blood loss (50.0 ml vs. 50.0 ml), median number of harvested lymph node (28.0 vs. 26.0) and median number of positive lymph node (1.0 vs. 2.0) between LS group and CS group were not significantly different (all P0.05) As compared to CS group, LS group presented shorter median time to the first flatus (3.0 days vs. 4.0 days, P=0.038), shorter median time to the first liquid diet (7.0 days vs. 8.0 days, P=0.000), shorter median time to remove the first abdominal drainage tube (7.0 days vs. 9.0 days, P=0.000) and shorter median time of postoperative hospital stay (8.0 days vs. 10.0 days, P=0.000). The morbidity of postoperative complication was 11.5% and 1.8% in CS group and LS group respectively without significant difference (P=0.092). In CS group, 1 case (1.6%) developed anastomotic hemorrhage, 3 cases (4.9%) gastric emptying disorder and 3 cases (4.9%) abdominal infection after operation, who all were cured by conservative treatment without duodenal stump fistula and re-operation. In LS group, only 1 case (1.8%) developed duodenal stump fistula and was cured by re-operation.In distal gastrectomy with Billroth II( anastomosis for gastric cancer, the application of linear stapler results in faster recovery of gastrointestinal function and shorter hospital stay, indicating more advantages.

Background Although laparoscopic surgery has been recommended as an optional therapy for patients with early gastric cancer, whether patients with locally advanced gastric cancer (AGC) could benefit from laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy remains elusive due to a lack of comprehensive clinical data. To evaluate the efficacy of LADG, we conducted a multi-institutional randomized controlled trial to compare laparoscopy-assisted versus open distal gastrectomy (ODG) for AGC in North China. Methods In this RCT, after patients were enrolled according to the eligibility criteria, they were preoperatively assigned to LADG or ODG arm randomly with a 1:1 allocation ratio. The primary endpoint was the morbidity and mortality within 30 postoperative days to evaluate the surgical safety of LADG. The secondary endpoint was 3-year disease-free survival. This trial was registered at ClinicalTrial.gov as NCT02464215. Results Between March 2014 and August 2017, a total of 446 patients with cT2-4aN0-3M0 (AJCC 7th staging system) were enrolled. Of these, 222 patients underwent LADG and 220 patients underwent ODG were included in the modified intention-to-treat analysis. The compliance rate of D2 lymph node dissection was identical between the LADG and ODG arms (99.5%, P = 1.000). No significant difference was observed regarding the overall postoperative complication rate in two groups (LADG 13.1%, ODG 17.7%, P = 0.174). No operation-related death occurred in both arms. Conclusions This trial confirmed that LADG performed by credentialed surgeons was safe and feasible for patients with AGC compared with conventional ODG.

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

Background Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. Methods We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels. Results A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different. Conclusions Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer. Electronic supplementary material The online version of this article (10.1186/s12885-017-3777-4) contains supplementary material, which is available to authorized users.

To explore the predictive value of combination detection of Pgp1 expression in cancer tissue and serum CEA level for the prognosis of colorectal cancer (CRC) patients.Clinicopathological data, complete 5-year follow-up data and CRC tissue samples of 153 CRC patients with stage I( to II( tumor undergoing radical operation in our department from January 2004 to August 2006 were retrospectively collected. Immunohistochemical staining was used to detect the expression level of Pgp1. The combined evaluation of staining intensity and positive cell percentage was performed to determine the expression level of Pgp1. Pgp1 staining (-) and (+) was defined as low expression; and staining (++) and (+++) as high expression. Electrochemiluminescence immunoassay was used to detect the level of serum CEA. CEA5 μg/L was defined as positive. χOf 153 patients, 105 were males and 48 females with mean age of 59 (27 to 90) years; 41 cases were rectal cancer, and 112 cases colon cancer; 23 patients were TNM stage I( tumor, and 130 patients stage II( tumor; median follow-up time was 64 months; 30 cases were dead. Positive rate of Pgp1 expression in colorectal cancer tissues was 66.0%(101/153). The expression of Pgp1 was associated with gender, tumor location, and survival during the follow-up (all P0.05). The preoperative positive rate of serum CEA was 28.1% (43/153). The preoperative serum CEA level was associated with tumor recurrence and survival (all P0.05). Kaplan-Meier analysis showed the overall 5-year survival rate was 81.7%. The 5-year survival rate of patients with high expression of Pgp1 was 88.1%, which was significantly higher than 69.2% of those with low expression of Pgp1(P=0.003). The 5-year survival rate of patients with preoperative positive serum CEA was 72.1%, which was significantly lower than 86.1% of those with preoperative negative serum CEA(P=0.023). Furthermore, the 5-year survival rate of patients with negative Pgp1 plus positive CEA was 66.7%, which was significantly lower than 91.0% of those with positive Pgp1 plus negative CEA(P=0.002). Univariate analysis showed that gender, Pgp1 expression level, preoperative serum CEA level, and Pgp1 combined with CEA were significantly associated with the prognosis of patients(all P0.05). Multivariate analysis showed that Pgp1 expression was an independent prognostic factor of CRC [HR(95%CI:1.261 to 64.224), P=0.028].Low expression of Pgp1 in cancer tissue indicates poor prognosis in patients with stage I( and II( tumor. Combination detection of Pgp1 expression and serum CEA can be applied to predict the prognosis of patients with stage I( and II( colorectal cancer.

With the rapid advancement of minimally invasive new technology, laparoscopic surgery and robotic surgery are now regarded as the main direction in surgical treatment for stomach cancers. Recent evidence has confirmed the safety and feasibility of laparoscopic surgery for early gastric cancer and advanced gastric cancer. However, gastrointestinal surgeons should pay more attention to complications after laparoscopic gastrectomy because of rich blood supply, complex tissue layers and lymph node metastasis. Common complications related to laparoscopic surgery are associated with laparoscopic instruments and operating, intra-abdominal bleeding, anastomotic leakage, anastomotic bleeding, pancreatic leakage, duodenal stump leakage, lymphatic leakage and so on. This article mainly focuses on the causes, prevention and treatment of the complications after laparoscopic gastrectomy.

The present study aimed to investigate the safety and short-term outcome of laparoscopy-assisted distal radical gastrectomy in treating gastric cancer among obese patients. Perioperative outcomes were compared between 67 gastric cancer patients with a body mass index (BMI) ≥25 kg/m2 (obese group) and 198 ones with BMI .05). There were significant differences between the 2 groups in operation time (non-obese: [234.2 ± 67.1] minutes vs obese group: [259.4 ± 78.5]; P = .017), postoperative hospital stay (obese group [19.7 ± 14.8] day vs non-obese [15.4 ± 7.1], P = .002), and retrieved lymph nodes ([27.6 ± 11.0] day vs non-obese [31.9 ± 12.5] day, P = .002). Obesity may prolong operation time and postoperative hospital stay, and cause less retrieved lymph nodes, but does not increase the incidence of postoperative complications. The experienced center can properly conduct laparoscopic assisted radical gastrectomy in obese patients.

To explore the expression of NF-E1b in colorectal cancer tissues and its association with various clinicopathological parameters and prognosis of the patients.Clinicopathological and follow-up data of 168 colorectal cancer patients undergoing radical operation at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from 2005 to 2012 were retrospectively analyzed, including 96 males and 72 females, with mean age of (57.8±11.2) years. The expression of NF-E1b protein was detected in samples of 168 resected colorectal cancer tissues and 45 adjacent non-cancerous tissues by immunohistochemistry. The expression rates of NF-E1b were compared among different clinicopathological features. Moreover, the association between NF-E1b expression and prognosis was analyzed.The expression of NF-E1b protein located mainly in cytoplasm. Positive rate of NF-E1b expression in adjacent non-cancerous tissues was 17.8% (8/45), which was obviously lower than 67.9%(114/168) of cancer tissues with significant difference (χ(2)=36.376, P=0.000). Clinicopathological parameters analysis suggested that the expression level of NF-E1b in cancer tissues was associated with age (χ(2)=4.862, P=0.030), TNM staging (χ(2)=10.969, P=0.002), lymph node metastasis (χ(2)=7.390, P=0.008) and distal metastasis (χ(2)=17.887, P=0.000). The median follow-up time was 23(1-77) months. The overall 5-year survival of this cohort was 33.3%. Colorectal cancer patients with high levels of NF-E1b expression showed a worse overall survival compared with those with low levels of NF-E1b expression (18.4% vs. 56.6%, P=0.000). Univariate Cox regression analysis showed that tumor location (P=0.034), tumor size (P=0.003), TNM staging (P=0.000), depth of tumor invasion (P=0.009), lymph node metastasis (P=0.000), distant metastasis (P=0.000) and NF-E1b expression level (P=0.001) were associated with the prognosis of colorectal cancer patients. Multivariate Cox regression analysis revealed that tumor diameter4 cm (HR=2.193,95% CI:1.334 to 3.603, P=0.002), distant metastasis (HR=2.064, 95% CI:1.160 to 3.672, P=0.014) and high NF-E1b expression (HR=1.994,95% CI:1.068 to 3.724, P=0.030) were independent risk factors of predicting poor prognosis of colorectal cancer patients.NF-E1b expression up-regulates in colorectal cancer tissues. High expression of NF-E1b is associated with poor prognosis of colorectal cancer patients. NF-E1b may serve as a potential target of the treatment for colorectal cancer.

Objectives To contrast and compare the spectrum of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) with rheumatoid arthritis (RA) using an illustrative case. Methods The relevant English literature of RS3PE was searched using the keywords "RS3PE" alone and in combination with terms such as neoplasia and rheumatic disease. Original and review articles were reviewed and the clinical setting was exemplified with a case report. Results RS3PE initially was reported to represent a form of RA. However, RS3PE has clinical features that are different from both early- and late-onset RA, such as lack of bony erosions and rheumatoid factor. RS3PE is thought to involve vascular endothelial growth factor, suggesting an infectious etiology, generally has an excellent prognosis, and is associated with neoplasia not commonly seen in RA, and the RA associated human leukocyte antigen (HLA) DRB1 genotype is absent. Conclusions Based on the clinical, laboratory, suspected infectious etiology, genetic differences, and types of associated malignancies, RS3PE appears to be a distinct entity rather than a subset of RA.

Aims: High expression of phosphatase of regenerating liver (PRL-3) has been implicated in cancer invasion and metastasis, indicating a close link between PRL-3 and cancer development. The aim was to investigate the significance of PRL-3 expression in the prognosis of colonic cancer. Methods and results: Expression of PRL-3 protein in tissue slides obtained from surgical resection of primary colonic cancer was measured by immunohistochemistry using a specific anti-PRL-3 monoclonal antibody. Archived tissue specimens from 273 colonic cancers and 236 matched specimens of adjacent normal colonic mucosa with a median follow-up of 57 months were examined. Multivariate analysis showed that PRL-3 was an independent prognostic marker for disease-free survival [DFS; hazard ratio (HR) 1.538, P = 0.035]. More importantly, the expression of PRL-3 showed significant negative correlation with DFS (P = 0.018) in patients in the early stages (stage I and II). Patients with high levels of PRL-3 expression in the adjacent normal mucosa also had a significant worse survival rate (DFS 0.0% versus 74.4%, P = 0.001), and PRL-3 expression remained an independent prognostic marker for DFS (HR 3.0, 95% confidence interval 1.7, 5.3, P

Laparoscopic surgery has been shown to offer more advantages than open surgery for the treatment of gastric cancer. However, the perioperative immune responses after laparoscopic surgery remain largely unexplored. Here, we analyzed the immunity of gastric cancer patients treated by laparoscopy-assisted gastrectomy (LAG) or open gastrectomy (OG) with D2 dissection. Seventy patients were randomized into LAG and OG groups. The operative details and postoperative outcomes of the two groups were compared. The immune factors were measured preoperatively as well as on the first, third, and seventh postoperative days (POD). Our results indicate that there was no significant difference between two groups in clinical characteristics. The profiles of white blood cells, neutrophils, lymphocytes, as well as the lymphocyte subpopulations, including T lymphocytes, B lymphocytes, CD4(+) T cells, and CD8(+) T cells were similar in the LAG and the OG groups. Only the natural killer cell counts were significantly higher in LAG-treated patients than in OG-treated ones on POD7. Moreover, no statistical differences were found between the two groups with respect to the levels of perioperative cytokines, including IFN-γ, IL-4, IL-6, and TNF-α. However, compared with the OG group, most of the immune factors in the LAG group had trends to return to preoperative levels on POD7. Our study demonstrates that the immune function of LAG-treated patients showed patterns similar to that of OG-treated patients, although larger prospective multicenter trials are needed to further evaluate the immunological status of LAG.