Hand-assisted laparoscopic resection versus total laparoscopic gastric surgery for primary gastric gastrointestinal stromal tumors (GISTs): an analysis from a high-volume institution.

BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) is technically feasible and associated with favorable outcomes. We compared the clinical efficacy of hand-assisted laparoscopic surgery (HLS) and total laparoscopic surgery (TLS) for gastric GISTs. METHODS: We retrospectively analyzed the clinical data of 69 consecutive patients diagnosed with a gastric GIST in a tertiary referral teaching hospital from December 2016 to December 2020. Surgical outcomes were compared between two groups. RESULTS: Fifty-three patients (TLS group: n = 36; HLS group: n = 17) were included. The mean age was 56.9 and 58.1 years in the TLS and HLS groups, respectively. The maximum tumor margin was significantly shorter in the HLS group than in the TLS group (2.3 ± 0.9. vs. 3.0 ± 0.8 cm; P = 0.004). The operative time of the HLS group was significantly shorter than that of the TLS group (70.6 ± 19.1 min vs. 134.4 ± 53.7 min; P < 0.001). The HLS group had less intraoperative blood loss, a shorter time to first flatus, and a shorter time to fluid diet than the TLS group (P < 0.05). No significant difference was found between the groups in the incidence or severity of complications within 30 days after surgery. Recurrence or metastasis occurred in four cases (HLS group; n = 1; TLS group; n = 3). CONCLUSIONS: This study demonstrated that compared with TLS, HLS for gastric GISTs has the advantages of simpler operation, shorter operative time, and faster postoperative recovery.

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.

Large Scale, Multicenter, Prospective Study of Apatinib in Advanced Gastric Cancer: A Real-World Study from China.

BACKGROUND: In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes. METHODS: This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician's discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile. RESULTS: A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p<0.01) and median overall survival (mOS; 8.72 vs 5.92 months, p<0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel (p=0.02) and experience of apatinib-related specific AEs (p<0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported. CONCLUSION: In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treatment. Combination with paclitaxel and the occurrence of apatinib-specific AEs were independent factors associated with better survival outcomes. TRIAL REGISTRATION: NCT03333967.

Effectiveness and safety of low-dose apatinib in advanced gastric cancer: A real-world study.

Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low-dose apatinib for the treatment of gastric cancer in real-world practice. We performed a prospective, multicenter observation study in a real-world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low-dose apatinib (500 mg or 250mg per day) therapy. The median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47-6.28), and mOS was 7.5 months (95% CI 6.74-8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand-foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand-foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3-4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment-related death was observed during the treatment of apatinib. The prospective study suggested that low-dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world. Trial registration: NCT03333967.

Prognostic Value of Upregulation of Myristoylated Alanine-Rich C-Kinase Substrate in Gastric Cancer.

BACKGROUND Accumulating evidence suggests a connection of Myristoylated alanine-rich C-kinase substrate (MARCKS) with several physiological and pathological processes. However, the relevance of MARCKS in gastric cancer (GC) needs to be elucidated. MATERIAL AND METHODS The abundance of MARCKS in GC tissues was assessed using techniques of immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). Moreover, the MARCKS expression profile in the TCGA database was analyzed through an online website analysis. We also investigated MARCKS function using cell wounding and Matrigel invasion assays. RESULTS TCGA analysis and our data suggest that transcript abundance and protein level of MARCKS was higher in GC tumor samples compared with peri-tumor tissues. There was a remarkable association of upregulated MARCKS with the cell differentiation (P<0.001), T stage (P=0.034), and N stage (P=0.002) followed by advanced TNM phase (P=0.008). Furthermore, it was predicted that higher expression of MARCKS is linked to poor overall survival (P=0.015) and disease-free survival (P=0.020), and that high levels of MARCKS function as an independent prognostic marker, as shown by multivariate Cox regression analysis in prediction of poor overall (HR=0.408; 95% confidence interval=0.247-0.674; P<0.001) and disease-free survival rates (HR=0.525; 95% confidence interval=0.216-0.584; P<0.001). GC cells showed significant reduction in cell migration and invasion upon depletion of MARCKS as noted through Matrigel invasion and cell wounding assays. Further analyses showed that silencing MARCKS impeded the epithelial-mesenchymal transition (EMT). CONCLUSIONS Our study indicates that elevated expression of MARCKS is significantly associated with metastatic capability of GC cells, and MARCKS overexpression can serve as a biomarker of GC poor prognosis.

High Expression of Peroxiredoxin 1 Is Associated with Epithelial-Mesenchymal Transition Marker and Poor Prognosis in Gastric Cancer.

BACKGROUND Recent studies show that peroxiredoxin 1 (Prdx1) contributes to the progression and poor prognosis of carcinoma through multiple mechanisms. However, there is little information on its expression and prognostic value in gastric cancer. This study investigated the expression of Prdx1 in gastric cancer, along with evaluating its clinical-pathological and prognostic importance. MATERIAL AND METHODS A total of 189 pairs of gastric cancer and paracarcinomatous tissues were assessed for Prdx1 expression and its association with clinical characteristics. The molecular mechanism was further investigated through in vitro experimentation. RESULTS The mRNA and protein levels of Prdx1 in the GC tissues were higher than in the peri-tumor tissues. We also found that high Prdx1 expression was positively correlated with the lymph node invasion and poor prognosis. It also served as an autonomous prognostic factor for patients with gastric cancer. Moreover, Prdx1 regulates the invasion and metastasis of GC cell lines through inhibiting E-Ca expression. CONCLUSIONS Prdx1 can promote epithelial-mesenchymal transition and gastric cancer progression. Therefore, it might be a therapeutic target and prognostic indicator for gastric cancer patients.

Efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer.

The present study evaluated the efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer. Forty patients were enrolled. Targeted arterial infusion of verapamil was done once a month, 3-5 times per patient, along with chemotherapy. After 2 bouts of combined treatment, the efficacy was evaluated. Primary gastric tumor was confirmed in 38/40 patients, and unconfirmed in 2/40 patients due to adhesion of tumors to surrounding tissue. Combined treatment was administered in 38 patients with defined tumors. Complete response to the treatment was in 5/38 (13.1 %) patients, partial response in 27/38 (71.1 %) patients, stable disease in 4/38 (10.5 %) patients, and progressive disease in 2/38 (5.26 %) patients. The effective rate (i.e., complete + partial response) comprised 84.2 %. There were 31 patients with liver metastases; 10/31 (32.3 %) patients showed complete response, 16/31 (51.6 %) patients showed partial response, 3/31 (9.7 %) patients had stable disease, and 2/31 (6.5 %) patients had progressive disease. The effective rate in these patients was 83.8 %. Thirty-seven patients were followed up, and 27/37 (73.0 %) patients were alive for 6 months or longer, 19/37 (51.3 %) for 12 months, 8 (35.1 %) for 18 months, and 8/37 (21.6 %) for 24 months. In conclusion, in patients with advanced gastric cancer, chemotherapy is more effective when combined with targeted arterial infusion of verapamil, leading to extended patients' survival and improved quality of life.

[Study of operative procedures of laparoscopy and laparoscopically assisted sigmoid transplantation for vaginal construction].

OBJECTIVE: To explore the procedures and the clinical significance of laparoscopy and laparoscopically assisted sigmoid transplantation for vaginal construction. METHODS: Nine cases were assigned randomly to laparoscopically assisted sigmoid colpopoiesis and laparoscopic sigmoid colon colpopoiesis. The procedure of laparoscopically assisted sigmoid colpopoiesis: with the auxiliary of laparoscopy, dissected the distal portion of the sigmoid with endoscopic linear cutter, then a 4-cm incision was made in the left lower abdomen to retract and dissect the proximal portion of sigmoid. After the proximal portion of transplant-sigmoid was closed, the proximal cut end of reserved-sigmoid was placed with the anvil and made a purse-string suture, then put back sigmoid into the peritoneal cavity. A curved intraluminal stapler was inserted from the anus to the most distal cut end of reserved-sigmoid to end-end anastomose the reserved-sigmoid. Finally, an artificial canal was made between urethravesicae and rectum and the transplant-sigmoid with the blood supply was placed into the artificial canal to create an artificial vagina. The procedure of laparoscopic sigmoid colpopoiesis was performed under laparoscopy thoroughly. RESULTS: We have successfully completed the operations for 9 patients, and made 1 - 19 month following-up. The results of the artificial vaginae of all cases were satisfactory; the abdominal scar was small with remarkable cosmetic effects. Moreover, 5 cases had pleasant sexual intercourses. CONCLUSION: The procedures of laparoscopy and laparoscopically assisted sigmoid transplantation for vaginal construction can replace the traditional laparotomy.