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.

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.

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.

[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.

Upregulation of circadian gene 'hClock' contribution to metastasis of colorectal cancer.

Recent studies have shown that disruption of the circadian rhythm was one of the endogenous factors contributing to tumorigenesis of various human malignancies, including colorectal cancer (CRC). However, the roles of circadian genes in the development of CRC are still unexplored. In this study, we investigated the expression pattern and the underlying mechanism of human Clock gene (hClock) in CRC progression. Multiple methods such as qRT-PCR, immunohistochemistry, and western blotting were performed to evaluate the expression pattern of the gene hClock, as well as to observe the changes of angiogenesis-related proteins and EMT-related proteins. Transwell cell migration assays and an animal tumor metastasis model were used to examine the impact of hClock on the metastatic ability of CRC cells in vitro and in vivo. Our results showed that the expression level of hClock significantly increased in human CRC tissues, which strongly associated with late TNM stage and positive lymph node metastasis. Moreover, a higher level of hClock expression was found in CRC cell lines with a higher metastatic potential. Furthermore, ectopic expression of hClock promoted the migration of SW480 CRC cells, while knockdown of hClock inhibited the tumor metastasis of SW620 CRC cells, and targeting hClock by shRNA effectively suppressed the metastatic ability of SW620 CRC cells in nude mice. Finally, we found that overexpression of hClock enhanced the expression of angiogenesis-related genes such as HIF-1α, ARNT and VEGF, and promoted epithelial-mesenchymal (-like) transition (EMT) in CRC cells, both of which are considered to be critical for tumor progression. These findings suggest that upregulation of the circadian gene hClock plays an important role in metastasis of colorectal cancer.

Circadian gene hCLOCK contributes to progression of colorectal carcinoma and is directly regulated by tumor­suppressive microRNA­124.

An abundance of studies has demonstrated that disruption of circadian rhythms is one of the factors that may contribute to the initiation and development of human colorectal carcinomas (CRCs). Recently, microRNA­124 has been demonstrated to suppress tumor growth or metastasis of CRCs. However, the mechanisms of cross­talk between microRNA­124 (miR­124) and circadian rhythms in the regulation of CRCs are poorly understood. The present study demonstrated that the protein expression levels of human circadian locomoter output cycles protein kaput (hCLOCK) is significantly increased, while miR­124 is attenuated in high­grade human CRC tissues and in the more invasive colorectal cancer cell lines SW620 and LOVO. It was further demonstrated that hCLOCK is a direct target of miR­124. Upregulation of miR­124 significantly inhibited hCLOCK expression in LOVO cells, and consequently inhibited its promoting effects on the proliferation and migration of LOVO cells. In conclusion, these data revealed that hCLOCK serves an enhancing role, whereas mir­124 serves a suppressive role, in human CRC. Attenuation of miR­124, of which hCLOCK is a direct target, leads to increased hCLOCK expression and disruption of circadian rhythms in CRC.