Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.

BACKGROUND: Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy. STUDY DESIGN: Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared. RESULTS: A total of 1469 patients were selected for inclusion in the study. After 1:1 propensity score matching, a total of 580 patients were matched and included in the final analysis, 290 in each group, RG vs OG. RG had longer operation time (210 vs 330 min, p < 0.0001), reduced intraoperative blood loss (155 vs 119.7 ml, p < 0.0001), time to liquid diet (4.4 vs 3 days, p < 0.0001) and to peristalsis (2.4 vs 2 days, p < 0.0001), and length of postoperative stay (11 vs 8 days, p < 0.0001). Morbidity rate was higher in OG (24.1% vs 16.2%, p = 0.017). CONCLUSION: RG significantly expedites recovery and reduces the risk of complications compared to OG. However, long-term survival is similar.

Laparoscopic Compared with Open D2 Gastrectomy on Perioperative and Long-Term, Stage-Stratified Oncological Outcomes for Gastric Cancer: A Propensity Score-Matched Analysis of the IMIGASTRIC Database.

BACKGROUND: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. RESULTS: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). CONCLUSION: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

Effects of Transcutaneous Electrical Acupoint Stimulation (TEAS) on Postoperative Recovery in Patients with Gastric Cancer: A Randomized Controlled Trial.

PURPOSE: Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy. PATIENTS AND METHODS: We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1-3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms. RESULTS: Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1-5 (average: 2.55±0.21 vs 3.10±0.42, P<0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63±16.74 vs 72.60±20.92, P<0.001) and defecation (72.20±16.24 vs 95.78±17.75, P<0.001) were shorter; the frequency of nausea were fewer (1.88±1.09 vs 2.58±0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63±0.63 vs 6.93±0.69, P<0.001); among the hematologic results, ß-endorphin (ß-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported. CONCLUSION: TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.

Short- and long-term outcomes associated with enhanced recovery after surgery protocol vs conventional management in patients undergoing laparoscopic gastrectomy.

BACKGROUND: At present, the enhanced recovery after surgery (ERAS) protocol is widely implemented in the field of gastric surgery. However, the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported. AIM: To compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy. METHODS: We retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015. The patients were divided into either an ERAS group or a conventional group. The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival. The primary outcomes were the 5-year overall and cancer-specific survival rates. The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes. RESULTS: The patient demographics and baseline characteristics were similar between the two groups after matching. Compared to the conventional group, the ERAS group had a significantly shorter postoperative hospital day (7.09 d vs 8.67 d, P < 0.001), shorter time to first flatus, liquid intake, and ambulation (2.50 d vs 3.40 d, P < 0.001; 1.02 d vs 3.64 d, P < 0.001; 1.47 d vs 2.99 d, P < 0.001, respectively), and lower medical costs ($7621.75 vs $7814.16, P = 0.009). There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group (18.1 vs 12.3, P = 0.030). Regarding inflammatory indexes, the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups (P < 0.001 and P = 0.025, respectively). The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol (P = 0.013 and 0.032, respectively). When stratified by tumour stage, only the survival of patients with stage III disease was significantly different between the two groups (P = 0.044). CONCLUSION: Adherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.

Pancreatic stellate cells facilitate pancreatic cancer cell viability and invasion.

The biological features of pancreatic cancer and the associated hypoxic environment around the cancer cells often lead to resistance to radiotherapy and chemotherapy. The present study was performed in order to explore the effect pancreatic stellate cells (PSCs) have on the proliferation of pancreatic cancer cells. In the present study, PSCs from human pancreatic cancer tissues were isolated, and the PSCs markers α-smooth muscle actin and desmin were overexpressed in the cytoplasm of PSCs. An MTT assay revealed that PSCs promoted the viability of pancreatic cancer cells. However, the viability of pancreatic cancer cells promoted by PSCs was partially blocked by SB525334. Cellular invasion analysis demonstrated that PSCs promoted the invasion ability of pancreatic cancer cells. An apoptosis assay indicated that PSCs decreased the level of apoptosis induced by gemcitabine. In vivo experiments consisting of mice bearing MIA-PaCa-2 and PSCs demonstrated an increase in the rate of tumor growth compared with MIA-PaCA-2 alone, whereas SB525334 may delay the tumor progression induced by PSCs. The present findings indicated that PSCs promoted the viability and invasion of pancreatic cancer cells, and decreased the apoptosis of pancreatic cancer cells induced by gemcitabine.

Pancreatic stellate cells increase pancreatic cancer cells invasion through the hepatocyte growth factor /c-Met/survivin regulated by P53/P21.

Pancreatic stellate cells (PSCs) are a key cellular component of the pancreatic tumor microenvironment and are considered to contribute to tumor invasion and metastasis. Multiple cytokines and growth factors derived from PSCs are involved in malignant cancer progression, including hepatocyte growth factor (HGF). However, the molecular mechanisms by which HGF regulates cancer invasion and metastasis have not been completely elucidated. Here, we report that two pancreatic cancer (PC) cell lines, Panc-1 and SW1990, displayed different invasive and migratory abilities after treatment with HGF secreted by PSCs. We found that HGF enhanced the invasive and migratory capacity of Panc-1 cells because of P53 deficiency, leading to overexpression of c-Met, which was regulated through P21. Additionally, our data showed that HGF/c-Met-mediated invasion and migration required the upregulation of survivin expression. In conclusion, PSCs promote PC cells invasion and migration via the HGF/c-Met/survivin pathway, which is negatively regulated by P53/P21.

Minimally invasive surgery for gastric cancer: A comparison between robotic, laparoscopic and open surgery.

AIM: To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes. METHODS: This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy (RG), laparoscopic gastrectomy (LG), open gastrectomy (OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided. RESULTS: The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients (RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery (P = 0.42) and stage of the disease (P = 0.16). Intraoperative blood loss was significantly lower in the LG (95.93 ± 119.22) and RG (117.91 ± 68.11) groups compared to the OG (127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG (27.78 ± 11.45), LG (24.58 ± 13.56) and OG (25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay (P < 0.0001). A similar complications rate was found (P = 0.13). The leakage rate was not different (P = 0.78) between groups. CONCLUSION: Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.

[Effects of preoperative oral carbohydrate on postoperative insulin resistance in radical gastrectomy patients].

OBJECTIVE: To investigate the effects and mechanism of postoperative insulin resistance in gastrectomy patients with preoperative oral carbohydrate. METHODS: From April to October 2011, 60 consecutive gastric cancer patients met inclusion criteria were divided into oral carbohydrate group and placebo group by randomized double-blind principles. Resting energy expenditure (REE), fasting blood glucose, insulin and triglyceride level were detected in 4 hours preoperatively. The 500 ml carbohydrate or placebo were administrated orally 2-3 hours before anaesthesia. Two group patients underwent radical distal subtotal gastrectomy under epidural compounded intravenous anesthesia. After laparotomy and before the abdomen was closed, a piece of rectus abdominis was taken and fixed in 3% glutaraldehyde. REE, fasting blood glucose, insulin and triglyceride level were detected immediately after surgery. The changes of insulin resistance index, blood triglycerides level, REE and respiratory quotient were compared pre- and post-operatively. The changes of rectus abdominis mitochondrial ultrastructure were observed by transmission electron microscopy respectively. RESULTS: There were 48 patients (34 males and 14 females) completed the trial. The 24 and 24 patients in oral placebo and carbohydrate groups respectively. In oral placebo group, post-operative insulin resistance index, REE, respiratory quotient, serum triglyceride level and the rectus abdominis mitochondrial damage index were 12.68 ± 3.13, (1458 ± 169) kcal/d, 0.73 ± 0.42, (0.53 ± 0.24) g/L and 1.14 ± 0.33, respectively. And the above items were 5.67 ± 1.40, (1341 ± 110) kcal/d, 0.79 ± 0.22, (1.04 ± 0.97) g/L and 0.92 ± 0.19 in oral carbohydrate groups respectively. All difference was statistically significant (t = 6.646, 2.851, 6.546, 2.542 and 2.730, all P < 0.05). Oral placebo group showed a markedly swollen mitochondria, steep membrane was not clear, mitochondria appeared vacuolated changes. CONCLUSIONS: Preoperative oral carbohydrate could reduce the insulin resistance and REE, improve the material metabolism status in radical gastrectomy patients. The possible mechanisms should be related to promotion of insulin release and protection of mitochondrial function.

[Prognosis analysis of 247 cases of gastrointestinal stromal tumor].

OBJECTIVE: To study the clinicopathologic features and prognostic factors of gastrointestinal stromal tumor (GIST). METHODS: Clinicopathologic data of 247 patients with GIST from January 2003 to November 2012 in the Affiliated Hospital of Qingdao University Medical College, and the prognostic factors were evaluated retrospectively by univariate and multivariate analysis with Log-rank test and Cox proportional hazard model. RESULTS: Patients were followed up with a median time of 26 months (1 to 113 months). Twenty-six patients developed recurrence or metastasis, and 18 died of GIST. The 1-, 3-, 5-year survival rates were 94%, 91% and 83% respectively. Univariate analysis showed that age, tumor location, tumor size, mitotic count and tumor rupture were predictive factors of survival after resection of primary GIST (all P<0.01). For patients at intermediate and high risk to relapse, imatinib group had a higher 5-year overall survival rate than non-imatinib group (85.7% vs. 81.0%, P<0.05). Multivariate analysis revealed that tumor size (RR=2.248, 95%CI:1.081-4.677, P=0.030), mitotic count (RR=2.220, 95%CI:1.032-4.776, P=0.041) and tumor rupture (RR=5.183, 95%CI:1.677-16.017, P=0.004) were independent prognostic factors. CONCLUSIONS: Tumor size, mitotic count and tumor rupture affect the prognosis after resection of primary GIST independently. Imatinib adjuvant therapy can improve overall survival of patients at intermediate and high risk to relapse after surgery.

Intensive versus conventional insulin therapy in type 2 diabetes patients undergoing D2 gastrectomy for gastric cancer: a randomized controlled trial.

BACKGROUND: This study was to compare the effect of intensive insulin therapy (IIT) to conventional insulin therapy (CIT) on postoperative outcomes among type 2 diabetes mellitus (DM) patients who underwent D2 gastrectomy for gastric cancer. METHODS: We randomly assigned gastric cancer patients with type 2 DM who underwent radical gastrectomy to receive IIT (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/l) with insulin infusion or CIT (maintenance of blood glucose at a level between 10 and 11.1 mmol/l) during the postoperative period. RESULTS: Of the 179 eligible patients, 92 patients were assigned to receive IIT and 87 patients to receive CIT. Mean blood glucose concentrations were lower in the intensive group (IG) than in the conventional group (CG) (5.5 ± 0.8 vs. 9.9 ± 1.0 mmol/l, P < 0.001). Hypoglycemia occurred in 6 patients (6.5%) in the IG (P = 0.029) versus in 1 patient (1.1%) in the CG. Hospital mortality did not differ significantly between two groups (4.3% vs. 5.7%, P = 0.742). However, IIT significantly reduced morbidity (from 18.4 to 7.6%, P = 0.031). Also, IIT shortened the days to suture removal, postoperative hospital stay, and postoperative duration of antibiotic use. The HOMA-IR score was lower at all time points in IG. Moreover, IIT increased the postoperative HLA-DR expression on monocytes on postoperative days 3 and 5. CONCLUSIONS: IIT significantly reduced short-term morbidity but not mortality among type 2 DM patients who underwent D2 gastrectomy for gastric cancer. Furthermore, a possible mechanism of suppression of the insulin resistance and improvement of HLA-DR expression may partially explain the benefits of IIT.

[Effect of intensive insulin therapy on the clinical results of postoperative patients with gastric cancer].

OBJECTIVE: To investigate the influence of intensive insulin therapy on the results of postoperative patients with gastric cancer. METHODS: Forty-six patients with gastric cancer underwent radical operation were randomly divided into two groups: intensive group (n=23, to control blood glucose at 4.4 to 6.1 mmol/L) and conventional group (n=23, to control blood glucose at 10.0 to 11.1 mmol/L). Fasting blood glucose( FBG), fasting insulin (FINS), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C reaction protein (CRP) in 46 patients were detected dynamically during perioperative period. Insulin resistance index (HOMA-IR) were calculated using Homeostasis Model Assessment (HOMA) to evaluate insulin sensitivity. Postoperative complications and other clinical data were recorded. RESULTS: No hypoglycemia occurred in the two groups. Compared with conventional group, morbidity and postoperative duration of fever, antibiotic use and the length of hospital stay in intensive group were significantly reduced (P < 0.05). On the day 1 and 3 after surgery, HOMA-IR and serum levels of TNF-alpha, IL-6 and CRP in patients of intensive group were significantly lower than those in conventional group (P < 0.05). CONCLUSIONS: Intensive insulin therapy could counteract the state of high-inflammation and then improve the outcome of postoperative patients.

[Effects of intensive insulin therapy on insulin resistance and serum proteins after radical gastrectomy].

OBJECTIVE: To investigate the effects of intensive insulin therapy on insulin resistance(IR) and serum proteins after radical gastrectomy. METHODS: Twenty-two gastric cancer patients were randomly divided into the control (n=11) and intensive insulin therapy group (n=11), and underwent distal radical subtotal gastrectomy under epidural anesthesia. Fasting blood glucose (FBG), fasting insulin (FINS) and serum proteins were assayed preoperatively and at day 1, 3, 7 postoperatively. Insulin resistance index was calculated using homeostasis model assessment (HOMA). The length of hospital stay and postoperative complications were recorded respectively. RESULTS: (1)The levels of FBG, FINS, lnHOMA-IR (P<0.01,P<0.05) and the incidence of insulin resistance were remarkably decreased by intensive insulin therapy after the surgical procedure.(2)The levels of serum transferrin (TRF), prealbumin (PRE) and retinal binding protein (RBP) in the intensive insulin therapy group were significantly improved as compared to control group after operation(P<0.05). (3) The duration of fever, antibiotic use, passage of gas by anus, length of hospital stay and the occurrence of postoperative complications were also significantly lower than those in control group(P<0.01,P<0.05). CONCLUSION: Compared to routine therapy, the intensive insulin therapy has more beneficial effects on the patients undergone distal radical subtotal gastrectomy in decreasing the insulin resistance, improving the status of nutrition and preventing postoperative complications.