The safety and feasibility Assessment of Overlap Esophagojejunostomy with Self-pulling and Latter Transection Technique in Totally Laparoscopic Total Gastrectomy.

BACKGROUND: This study presents an innovative technique in totally laparoscopic total gastrectomy (TLTG) for Overlap esophagojejunostomy, termed self-pulling and latter transection (Overlap SPLT). It evaluates the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end esophagojejunostomy incorporating self-pulling and latter transection (FETE SPLT). METHODS: From September 2018 to September 2023, this study enrolled 68 gastric cancer patients who underwent totally laparoscopic total gastrectomy (TLTG) with Overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathological characteristics, surgical and postoperative outcomes data for Overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for Overlap SPLT was 25.3 ± 7.4minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0minutes, P = 0.031). Perioperatively, one anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = 0.682). No statistically significant differences were found between the two groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs. 5.8%, P = 0.676). CONCLUSION: The Overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between Overlap SPLT and FETE SPLT, but Overlap SPLT costed one additional stapler cartridge and required a longer duration.

Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study.

BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.

Insight into immune checkpoint inhibitor therapy for colorectal cancer from the perspective of circadian clocks.

Colorectal cancer (CRC) is one of the most common malignant tumours and the third most common cause of cancer deaths worldwide, with high morbidity and mortality. Circadian clocks are widespread in humans and temporally regulate physiologic functions to maintain homeostasis. Recent studies showed that circadian components were strong regulators of the tumour immune microenvironment (TIME) and the immunogenicity of CRC cells. Therefore, insight into immunotherapy from the perspective of circadian clocks can be promising. Although immunotherapy, especially immune checkpoint inhibitor (ICI) treatment, has been a milestone in cancer treatment, greater accuracy is still needed for selecting patients who will respond positively to immunotherapy with minimal side effects. In addition, there were few reviews focusing on the role of the circadian components in the TIME and the immunogenicity of CRC cells. Therefore, this review highlights the crosstalk between the TIME in CRC and the immunogenicity of CRC cells based on the circadian clocks. With the goal to achieve the possibility that patients with CRC can benefit most from the ICI treatment, we provide potential evidence and a novel idea for building a predictive framework combined with circadian factors, searching for enhancers of ICIs targeting circadian components and clinically implementing the timing of ICI treatment for patients with CRC.

Effect of different oesophagojejunostomy methods on the quality of life of gastric cancer patients after totally laparoscopic total gastrectomy with self-pulling and latter transected technique: study protocol for a randomised trial.

INTRODUCTION: Gastric cancer is the fifth most common cancer worldwide and the detection rate of proximal gastric cancer has been increasing. Currently, surgical resection using gastrectomy and proper perigastric lymphadenectomy is the only treatment option to enhance the survival rate of patients with gastric cancer. Laparoscopic total gastrectomy (LTG) is increasingly performed for adenocarcinoma of the oesophagogastric junction. However, totally LTG (TLTG) is only performed by a few surgeons due to difficulty associated with oesophagojejunostomy (OJ), in which there is no consensus on a standardised anastomosis technique. We propose a randomised trial to compare functional end-to-end anastomosis (FETE) and side-to-side anastomosis (Overlap) for OJ. METHODS AND ANALYSIS: A prospective, randomised, open-label, single-centre, interventional trial has been designed to evaluate the quality of life (QoL) outcomes and safety of FETE and Overlap, with a 1-year follow-up as the primary endpoint. The trial began in 2020 and is scheduled to enrol 96 patients according to a previous sample size calculation. Patients were randomly allocated to the FETE or Overlap groups with a follow-up of 1 year to assess QoL after the procedure. All relevant clinical data including biological markers were collected. The primary indicator is the D-value between the postoperative and preoperative QoL. Student's t-tests will be used to compare continuous variables, while χ2 tests or Fisher's exact tests will be used to compare categorical variables. Statistical analysis will be performed with SPSS V.23.0 statistical software. A p<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: This study has been approved by the Hospital Institutional Review Board of Huashan Hospital, Fudan University (2020-1055). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000035583.

Textbook Outcome as a measure of surgical quality assessment and prognosis in gastric neuroendocrine carcinoma: A large multicenter sample analysis.

OBJECTIVE: Quality assurance is crucial for oncological surgical treatment assessment. For rare diseases, single-quality indicators are not enough. We aim to develop a comprehensive and reproducible measurement, called the "Textbook Outcome" (TO), to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma (G-NEC) patients. METHODS: Data from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed. TO included receiving a curative resection, ≥15 lymph nodes examined, no severe postoperative complications, hospital stay ≤21 d, and no hospital readmission ≤30 d after discharge. Hospital variation in TO was analyzed using a case mix-adjusted funnel plot. Prognostic factors of survival and risk factors for non-Textbook Outcome (non-TO) were analyzed using Cox and logistic models, respectively. RESULTS: TO was achieved in 56.6% of 860 G-NEC patients. TO patients had better overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) than non-TO patients (P<0.05). Moreover, TO patients accounted for 60.3% of patients without recurrence. Multivariate Cox analysis revealed non-TO as an independent risk factor for OS, DFS, and RFS of G-NEC patients (P<0.05). Increasing TO rates were associated with improved OS for G-NEC patients, but not hospital volume. Multivariate logistic regression revealed that non-lower tumors, open surgery, and >200 mL blood loss were independent risk factors for non-TO patients (P<0.05). CONCLUSIONS: TO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients. Factors predicting non-TO are identified, which may help guide strategies to optimize G-NEC outcomes.

Comparison of Survival and Patterns of Recurrence in Gastric Neuroendocrine Carcinoma, Mixed Adenoneuroendocrine Carcinoma, and Adenocarcinoma.

Importance: Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Objective: To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Design, Setting, and Participants: This cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score-matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020. Exposures: Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Main Outcomes and Measures: The main outcomes were DFS and patterns of recurrence. Results: A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P < .001) and 51.1% (95% CI, 46.0%-56.2%) for patients with gastric mixed adenoneuroendocrine carcinoma, compared with 57.8% (95% CI, 55.1%-60.5%) patients with gastric adenocarcinoma (P = .02). Multivariable analyses found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma (hazard ratio [HR], 1.64; 95% CI, 1.40-1.93) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.25; 95% CI, 1.05-1.49) were independent risk factors associated with worse DFS. Compared with matched patients with gastric adenocarcinoma, patients with gastric neuroendocrine carcinoma were more likely to have distant recurrence (268 patients [17.2%] vs 101 patients [23.7%]; P = .002), as were patients with gastric mixed adenoneuroendocrine carcinoma (232 patients [17.3%] vs 76 patients [22.8%]; P = .02). In multivariate analysis, gastric neuroendocrine carcinoma (HR, 2.22; 95% CI, 1.66-2.98) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.70; 95% CI, 1.24-2.34) were independent risk factors associated with distant recurrence. Additionally, T3 to T4 stage (odds ratio, 2.84; 95% CI, 1.57-5.14; P = .001) and lymph node metastasis (odds ratio, 2.01; 95% CI, 1.31-3.10; P = .002) were independent risk factors associated with distant recurrence of gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma. Conclusions and Relevance: This cohort study found that patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma had worse prognoses and were more prone to distant recurrence than those with gastric adenocarcinoma. Thus, different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially patients with tumors penetrating into the subserosa or deeper layers or with lymph node metastasis.

Predictive Value of Combined Preoperative Carcinoembryonic Antigen Level and Ki-67 Index in Patients With Gastric Neuroendocrine Carcinoma After Radical Surgery.

PRÉCIS: We present a valid and reproducible nomogram that combined the TNM stage as well as the Ki-67 index and carcinoembryonic antigen levels; the nomogram may be an indispensable tool to help predict individualized risks of death and help clinicians manage patients with gastric neuroendocrine carcinoma. BACKGROUND: To analyze the long-term outcomes of patients with grade 3 GNEC who underwent curative surgery and investigated whether the combination of carcinoembryonic antigen (CEA) levels and Ki-67 index can predict the prognosis of patients with gastric neuroendocrine carcinoma (GNEC) and constructed a nomogram to predict patient survival. METHODS: In the training cohort, data were collected from 405 patients with GNEC after radical surgery at seven Chinese centers. A nomogram was constructed to predict long-term prognosis. Data for the validation cohort were collected from 305 patients. RESULTS: The 5-year overall survival (OS) was worse in the high CEA group than in the normal CEA group (40.5% vs. 55.2%, p = 0.013). The 5-year OS was significantly worse in the high Ki-67 index group than in the low Ki-67 index group (47.9% vs. 57.2%, p = 0.012). Accordingly, we divided the whole cohort into a KC(-) group (low Ki-67 index and normal CEA) and KC(+) group (high Ki-67 index and/or high CEA). The KC(+) group had a worse prognosis than the KC(-) group (64.6% vs. 46.8%, p < 0.001). KC(+) and the AJCC 8th stage were independent factors for OS. Then, we combined KC status and the AJCC 8th stage to establish a nomogram; the C-index and area under the curve (AUC) were higher for the nomogram than for the AJCC 8th stage (C-index: 0.660 vs. 0.635, p = 0.005; AUC: 0.700 vs. 0.675, p = 0.020). The calibration curve verified that the nomogram had a good predictive value, with similar findings in the validation groups. CONCLUSIONS: The nomogram based on KC status and the AJCC 8th stage predicted the prognosis of patients with GNEC well.

The safety and feasibility of intra-corporeal gastroduodenostomy using a self-pulling and latter transected method (Delta SPLT) in totally laparoscopic distal gastrectomy.

BACKGROUND AND OBJECTIVES: In 2016, the self-pulling and latter transection method (named "Delta SPLT"), a modified delta-shaped gastroduodenostomy (DA) technique for totally laparoscopic distal gastrectomy, was described. Delta SPLT reduced the technical difficulty of the surgery and the quantity of cartridges required with a manageable initial safety profile. Here, the safety and feasibility of this technique are analyzed at 1 year's follow-up. METHODS: The demographic and clinicopathologic profiles, perioperative details, and postoperative outcomes of 45 consecutive patients who underwent Delta SPLT from March 2016 to March 2019 were retrospectively analyzed. The Delta SPLT technique, which consisted of one endoscopic linear stapler and four cartridges each, was used for reconstruction in every case. RESULTS: The mean operative time was 127.1 ± 38.2 min, including a reconstruction duration of 22.6 ± 7.2 min. There were no surgical or anastomotic complications. The mean postoperative stay duration was 5.8 ± 1.2 days, and the morbidity rate was 2.2% with one case of postoperative pneumonia. CONCLUSIONS: The results at the one-year follow-up suggest that Delta SPLT is a safe and feasible procedure. Delta SPLT is characterized by fewer difficulties experienced during surgery, lower surgical costs, it is easy to practice, and it is beneficial for patients who are undergoing gastroduodenostomy.

Which Staging System Is More Suitable for Gastric Neuroendocrine Cancer and Mixed Adenoneuroendocrine Carcinomas? A Multicenter Cohort Study.

PURPOSE: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). METHODS: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. RESULTS: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. CONCLUSIONS: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

Multi-institutional development and validation of a nomogram to predict recurrence after curative resection of gastric neuroendocrine/mixed adenoneuroendocrine carcinoma.

OBJECTIVE: To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. BACKGROUND: Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. METHODS: A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). RESULTS: The median follow-up time was 40 months (1-169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). CONCLUSIONS: Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.

Clinicopathological Characteristics and Prognostic Factors of Patients with Gastric Cancer Accompanying Neuroendocrine Differentiation (NEDGC).

AIM: Gastric carcinoma with neuroendocrine differentiation (NEDGC) is a relatively rare pathologic diagnosis in clinical practice, which has no specific guidelines or treatment recommendations yet. In this study, we aim to investigate the clinicopathological characteristics and prognostic factors of this disease. PATIENTS AND METHODS: We retrospectively analyzed clinicopathological data from a series of 82 NEDGC patients who underwent surgery for gastrectomy at Huashan Hospital Fudan University between January 2007 and December 2018. Furthermore, a series of 50 cases were used to analyze 3-year overall survival (OS). RESULTS: Ages of the patients ranged from 26 to 83 years (M:F, 4.8:1). The majority of patients suffered from some symptoms (97.6%), as the most common one was abdominal pain (48.8%). Most of the tumors were ≥5 cm (53.7%), in the lower part of the stomach (47.5%), and with advanced T (87.8% ≥T3) and N (67.1% ≥N1) stage. As to the neuroendocrine markers, Syn showed a slight advantage on sensitivity than CgA (79.3 and 75.6%, respectively). The 3-year OS was 54%. Advanced T stage (≥T3) of the primary tumor, positive lymphovascular invasion (LVI), large tumor size (5.5cm), high neutrophil-to-lymphocyte ratio (NLR, 2.51), and low prealbumin level (173.87 mg/L) were associated with inferior OS based on the univariate analysis. Low preoperative hemoglobin level (113.87g/L), laparoscopic-assisted gastrectomy, and advanced N stage (N3) were three independent risk factors for 3-year OS of NEDGC patients in both univariate and multivariate analysis. CONCLUSION: The TN staging system for gastric adenocarcinoma also has a prognostic value for NEDGC patients, while N3 stage works as an independent predictor of patients' survival. Since most of the NEDGC patients were in advanced stage, proper indications to perform operative laparoscopy should be selected.

IL-8 mediates a positive loop connecting increased neutrophil extracellular traps (NETs) and colorectal cancer liver metastasis.

Host and tumorous inflammation actively affect liver metastasis of colorectal cancer (CRC). Neutrophils have been recognized as one active participant in metastasis procedure, with controversial roles however. Activated neutrophils release extracellular traps (NETs) which are involved in infection and multiple pathological conditions. NETs on cancer metastasis is getting recognized but less elucidated in mechanism. How NETs interact with cancer cells is still largely unknown. In this study, we found that neutrophils from CRC patients, especially those with liver metastatic, underwent remarkably enhanced NETs. Clinically, sera and pathological NETs marker closely correlated with onset of liver metastasis. Through in vivo and in vitro studies, we proved that increased NETs positively contribute to onset of CRC liver metastasis. Digesting NETs with DNase 1 diminished the increased liver metastasis associated with NETs. In detail, NETs trapped CRC cells in liver and exerted no cytotoxicity on tumor cells, but boosted tumorous proliferation and invasion capacity. We further found this enhanced malignancy of trapped CRC cells was due to the elevated tumorous interleukin (IL)-8 expression triggered by NETs. Blocking IL-8 activity effectively abrogated the enhanced proliferation and invasion triggered by NETs. Moreover, overproduced IL-8 in turn activate neutrophils towards NETs formation, thus forming a positive loop optimizing CRC liver metastasis. Collectively, our study propose a novel positive feedback between elevated tumorous IL-8 and NETs to promote CRC liver metastasis, and identify potential strategy against liver metastasis.

Author Correction: 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers.

In the initial published version of this article, there was a mistake in the P value for the correlation between gene-expression changes and 5 hmC changes in tumors. The correct P value should be same as the P value shown in Fig. S6A: 9.8 × 10-6 (mistakenly shown as "9.8 × 106" in the main text). This correction does not affect the description of results or the conclusions of this study, since the range of P value is between 0 and 1.

A Comparative Study of Double-Tract Reconstruction and Roux-en-Y After Gastrectomy for Gastric Cancer.

BACKGROUND: The meta-analysis was performed to compare surgical and functional results of double-tract (DT) and Roux-en-Y (RY) reconstruction, applied in both partial and total gastrectomy. METHODS: PubMed, Ovid, Web of Science, Wiley, EBSCO, and the Cochrane Library Central were searched for studies comparing DT and RY after partial or total gastrectomy. Surgical, nutritional, and long-term outcomes were collected and analyzed. RESULTS: A total of 595 patients from 8 studies were included. Operative time, time to first flatus, length of hospital stays, complications, postoperative nutritional variables, and functional result were similar between 2 groups. Group DT had significantly less blood loss, shorter time to oral intake and less loss of body weight at 2 years after operation. CONCLUSIONS: DT reconstruction is comparable with RY after gastrectomy in safety, surgical outcomes including reflux symptom and postoperative recovery and shows better food intake and body weight maintenance.

[Safety evaluation on initial 100 consecutive procedures of self-pulling and latter transected esophagojejunostomy].

OBJECTIVE: To evaluate the feasibility and the short-term safety of self-pulling and latter transected esophagojejunostomy(SPLT) in totally laparoscopic total gastrectomy (TLTG). METHODS: One hundred patients with gastric cancer received TLTG-SPLT at General Surgery Department of Huashan Hospital (Fudan University) from June 2014 to January 2017(SPLT group). The clinicopathologic characteristics, surgical and postoperative outcomes were collected retrospectively and compared with the conventional group undergoing TLTG plus overlap or functional end-to-end anastomosis from October 2013 to December 2015. D2 lymph node dissection was regularly performed for all the patients. In SPLT group, a sterile hemp rope was held to ligate and drag down the esophagus to maintain "self-pulling" after the duodenum was transected by the first stapler, allowing the detachment of the posterior mediastinum. Then a hole 2-3 cm above the ligature rope was made on the right-posterior wall of the esophagus. When the mesenteric tension was checked, another hole was made at the anti-mesenteric border of the jejunum 20 cm distal to the ligament of Treitz. A side-to-side esophagojejunostomy (E-J) was then performed between the right-posterior wall of esophagus and the anti-mesenteric wall of the jejunum with the second linear stapler, forming an entry hole. The "latter transection" was applied with the third stapler inserted from the assistant's Trocar, which facilitated the esophagus and the afferent loop jejunum to be simultaneously transected above the level of the entry hole. After that, a side-to-side jejunojejunostomy(J-J) with another 2 staplers was carried out between the afferent loop stump and the Roux limb 40 cm below E-J, in which the E-J entry hole could also work as the entrance for the stapler. The TLTG-SPLT was therefore completed and the specimen was removed through the incision from the umbilical Trocar site. RESULTS: There were 66 male and 34 female patients in the SPLT group with median age of 64 years. The clinicopathologic baseline data of two groups were comparable(all P>0.05). All the patients underwent operations successfully, and none was converted to open surgery. No positive margin was found in either group. Mean operation duration was (178.2±35.9) minute in SPLT group, including (22.9±7.1) minute of reconstruction, which both were significantly shorter than those in conventional group [(204.4±55.8) minute, P=0.003; (30.5±7.2) minute, P=0.000]. Less blood loss [(74.3±72.5) ml vs. (104.2±71.6) ml, P=0.017] and earlier time to the first flatus [(1.9±1.6) days vs. (2.7±1.3) days, P=0.001] were observed in SPLT group. There were no significant differences in postoperative hospital stay and pathological findings between the two groups(all P>0.05). Postoperative operation-associated complications were found in 7 cases of SPLT group. Of these 7 patients, 1 case developed gastrointestinal bleeding, 3 pancreatic leakage, 2 chyle leakage, who all were discovered within postoperative 1 week and were cured by conservative treatment, while the other 1 case developed anastomotic fistula complicated with peritoneal infection who received laparoscopic exploration and peritoneal scavenge and drainage, then discharged 34 days later. Six patients in conventional group developed postoperative operation-associated complications, including 1 case of anastomotic bleeding, 3 cases of pancreatic leakage, 1 case of chyle leakage and 1 case of peritoneal infection. Morbidity of postoperative operation-associated complication was not significantly different between two groups [7.0%(7/100) vs. 11.5%(6/52), χ2=0.414, P=0.520]. Fifty patients from two groups underwent endoscopic examination at postoperative 6-month and 12-month, and no obvious anastomotic stenosis and esophageal reflux were observed. CONCLUSION: SPLT is a safe procedure with feasibibility in intracorporeal esophagojejunostomy.

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers.

DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.

A novel method of self-pulling and latter transected delta-shaped Billroth-I anastomosis in totally laparoscopic distal gastrectomy.

BACKGROUND: We developed a modified delta-shaped gastroduodenostomy technique in totally laparoscopic distal gastrectomy. This novel technique, which effectively reduces the required quantity of linear stapler [1-3], was named as self-pulling and latter transected delta-shaped anastomosis (Delta SPLT) [4]. METHODS: Delta SPLT was performed on 15 patients with stage cT1-2 antral cancer. We ligated the duodenum with a rope instead of transecting it and used the ligature rope to pull the duodenum during the whole progress of gastroduodenostomy. When closing the entry hole, the duodenum was transected at the same time, which saved one linear stapler. Data of clinicopathologic characteristics, surgical and postoperative outcomes were collected and expressed as means ± standard deviations. RESULTS: All the operations were successfully performed by using no more than four 60-mm linear staplers. The mean BMI of the patients is 23.0 ± 2.5 kg/m2 (range 17.0-26.0 kg/m2), and duration of the operation was 115.0 ± 33.4 min (range 75-215 min), including 22.3 ± 6.7 min (range 15-35 min) of reconstruction. Mean blood loss was 82.7 ± 71.3 mL (range 10-300 mL), and mean times to first flatus was 2.3 ± 1.1 days (range 1-5 days). A mean number of 27.5 ± 5.4 (range 18-38) lymph nodes was retrieved. Overall postoperative morbidity rate was 6.7% (1/15). There was no anastomosis-related complication, but one case of pneumonia developed on postoperative day (POD) 2 which was successfully managed by conservative methods. Patients were discharged (POD mean 5.8 ± 1.3, range 4-9) when their bowel movements recovered and no discomfort with soft diet was claimed. CONCLUSION: Delta SPLT is a safe and feasible technique and requires less clinical costs.

A comparative study of delta-shaped and conventional Billroth I anastomosis after laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Delta-shaped anastomosis (DA) is a newly developed intracorporeal gastroduodenostomy. This meta-analysis is performed to compare the safety, feasibility and clinical outcomes of DA with conventional extracorporeal Billroth I anastomosis (B-I) after laparoscopic distal gastrectomy for gastric cancer. METHODS: Both randomized controlled trials (RCTs) and nonrandomized cohort studies comparing outcomes of DA and B-I after laparoscopic distal gastrectomy for gastric cancer were searched in electronic database. Surgical outcomes, postoperative recovery, postoperative complications and outcomes were pooled and compared by meta-analysis using RevMan 5.3 software. Weighted mean differences (WMDs), odds ratios and risk differences were calculated with 95% confidence intervals (CIs). P values of <0.05 were considered statistically significant. RESULTS: Eight nonrandomized cohort studies of 2450 patients were included. Meta-analysis showed significantly less blood loss (WMD -28.72; 95% CI -49.21 to -8.23; P = 0.006), more lymph nodes retrieved (WMD 3.23; 95% CI 0.86-5.61; P = 0.008), shorter time to first soft diet (WMD -0.34; 95% CI -0.47 to -0.21, P < 0.00001), less pain and analgesic use (WMC -0.29; 95% CI -0.56 to -0.02; P = 0.03) in DA than in B-I. Both methods had similar operative time, resection margin, time to first flatus, length of hospital stay and rate of complications. Most of the postoperative symptoms were comparable between groups. The subgroup of obese patient showed more favorable outcomes in DA, and the learning curve of DA is steep. CONCLUSION: DA is a safe and feasible reconstruction method after laparoscopic distal gastrectomy, with comparable postoperative surgical outcomes, postoperative complications comparing to B-I. DA is less invasive with quicker resume of diet than B-I, especially for the obese patients.

A novel method of self-pulling and latter transected reconstruction in totally laparoscopic total gastrectomy: feasibility and short-term safety.

BACKGROUND: This study depicts a novel reconstruction method of self-pulling and latter transection (SPLT) in totally laparoscopic total gastrectomy (TLTG) and evaluates its feasibility and short-term safety by comparing its surgical and postoperative outcomes with the conventional TLTG. PATIENTS AND METHODS: Forty patients with gastric cancer from June 2014 to December 2015 received SPLT-TLTG. Data of clinicopathologic characteristics, surgical and postoperative outcomes, and follow-up findings in SPLT cases were collected and retrospectively compared with those of conventional TLTG to clarify the clinical benefits. RESULTS: The mean duration of the operation was 179.5 ± 37.7 min in SPLT-TLTG, including 23.2 ± 8.8 min of reconstruction; both were significantly shorter than the conventional TLTG (P = 0.030; P < 0.001). There were no significant differences in blood loss, time of the first flatus and postoperative hospital stays between two groups. SPLT-TLTG developed no complication beyond the conventional TLTG. CONCLUSION: SPLT-TLTG is safe, feasible and minimally invasive. It may serve as a promising procedure for gastric cancer that helps to expand the indication of TLTG to cases with even high level of tumor invasion and requires less in both surgical skills and clinical costs.