Local excision and radical excision for rectal gastrointestinal stromal tumors: a meta-analysis protocol.

Background: To date, several studies have compared the surgical and oncological outcomes of local excision (LE) and radical excision (RE) for rectal gastrointestinal stromal tumors (GISTs), but some have limited numbers of small series. This protocol outlines the planned scope and methods for a systematic review and meta-analysis that will compare the surgical and oncological outcomes of LE and RE in patients with rectal GISTs. Methods: This protocol is presented in accordance with the PRISMA-P guideline. PubMed, Embase, Web of Science, Cochrane Library and Wanfang database will be systematically searched. Furthermore, reference lists of all included articles will be screened manually to add other eligible studies. We will include randomized controlled trials (RCTs) and non-randomized studies (NRS) in this study. The primary outcomes evaluated will be R0 resection rate and disease-free survival, while the secondary outcomes will contain overall survival, length of stay, tumor rupture rate and complications. Two reviewers will independently screen and select studies, extract data from the included studies, and assess the risk of bias of the included studies. Preplanned subgroup analyses and sensitivity analyses are detailed within this protocol. The strength of the body of evidence will be assessed using GRADE. Discussion: This review and meta-analysis will provide a comprehensive evaluation of the current evidence concerning the application of LE and RE in patients with rectal GISTs. The findings from this review will serve as a foundation for future research and emphasize the implications for clinical practice. Systematic review registration: PROSPERO (CRD42017078338), https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=387409, PROSPERO CRD42017078338.

The KDM6A-SPARCL1 axis blocks metastasis and regulates the tumour microenvironment of gastrointestinal stromal tumours by inhibiting the nuclear translocation of p65.

BACKGROUND: It is urgent to explore the pathogenic mechanism of gastrointestinal stromal tumours (GISTs). KDM6A, a histone demethylase, can activate gene transcription and has not been reported in GISTs. SPARCL1 may serve as a metastasis marker in GIST, but the molecular mechanism remains to be further explored. This study aimed to explore the biological function and molecular mechanism of KDM6A and SPARCL1 in GIST. METHODS: CCK-8, live cell count, colony formation, wound-healing and Transwell migration and invasion assays were employed to detect the cell proliferation, migration and invasion. A xenograft model and hepatic metastasis model were used to assess the role of KDM6A and SPARCL1 in vivo. RESULTS: KDM6A inhibited the proliferation, migration and invasion of GIST cells. Mechanistically, KDM6A promotes the transcription of SPARCL1 by demethylating histone H3 lysine trimethylation and consequently leads to the inactivation of p65. SPARCL1 affected the metastasis of GIST cells in a mesenchymal-epithelial transition- and matrix-metalloproteinase-dependent manner. SPARCL1 knockdown promoted angiogenesis, M2 polarisation and macrophage recruitment by inhibiting the phosphorylation of p65. Moreover, KDM6A and SPARCL1 inhibited hepatic metastasis and macrophage infiltration in vivo. CONCLUSIONS: Our findings establish the critical role of the KDM6A-SPARCL1-p65 axis in restraining the malignancy of GIST.

Prognoses in patients with primary gastrointestinal neuroendocrine neoplasms based on the proposed new classification scheme.

AIM: The aim of this study is to investigate the clinicopathological characteristics, as well as explore the prognostic accuracy of the proposed new classification in gastrointestinal NENs (GI-NENs) patients. METHODS: Patients diagnosed with GI-NENs were retrospectively indentified from existing databases of the pathological institute at our institution from January 2009 to November 2015. RESULTS: We identified 414 patients with GI-NENs, 250 cases were diagnosed as neuroendocrine tumor G1 (NET G1), 25 as neuroendocrine tumor G2 (NET G2), 53 as neuroendocrine tumor G3 (NET G3), 55 as neuroendocrine carcinoma G3 (NEC G3), and 31 as mixed adenoneuroendocrine carcinoma (MANEC); the overall survival (OS) rate at three years were 94.9%, 91.7%, 74.3%, 62.7% and 38.1%, respectively. The difference in progression-free survival (PFS) duration among the patients with NET G1, NET G2, NET G3, NEC G3, and MANEC was statistically significant (P < 0.001). However, the PFS of NEC G3 and MANEC was low and similar (P = 0.090). In multivariate analysis of patients with GI-NENs, surgical margin, comorbidity, proposed new classification and tumor location were useful predictors of OS (P < 0.05). CONCLUSION: Our findings suggest that the proposed new classification can accurately reflect the clinical outcome, together with surgical margin, comorbidity, and tumor location may be meaningful prognostic factors for the OS of GI-NENs.

Surgical treatment and prognosis of gastric neuroendocrine neoplasms: a single-center experience.

BACKGROUND: Gastric neuroendocrine neoplasms (G-NENs) are uncommon, and data on their management is limited. We here investigated the clinicopathological characteristics, surgical and survival outcomes in G-NENs among Chinese. Moreover, we will discuss their prognostic value. METHODS: From existing databases of the West China Hospital, we retrospectively identified 135 consecutive patients who were surgically treated and pathologically diagnosed as G-NENs from January 2009 to August 2015. RESULTS: This entire cohort comprised 98 males and 37 females, with a median age of 60 years. Twenty-five patients underwent endoscopic resection, while 110 patients underwent open/laparoscopic surgery. Thirty-nine patients had neuroendocrine tumor G1 (NET G1), seven patients had neuroendocrine tumor G2 (NET G2), 69 patients had neuroendocrine carcinoma G3 (NEC G3) and 20 patients had mixed adenoneuroendocrine carcinoma (MANEC). The median survival was not achieved for both NET G1 and NET G2 versus 19 months (range 3-48) for NEC G3 and 10.5 months (range 3-45) for MANEC. The 3-year survival rates for stage I, II, III, and IV were 91.1 %, 78.6 %, 51.1 % and 11.8 %, respectively (P < 0.001). As for the prognostic analysis, both surgical margin and the newly updated World Health Organization (WHO) classification were independent predictors of overall survival (OS). CONCLUSIONS: G-NENs are a kind of rare tumors, and patients with NET G3 and MANEC have unfavorable prognosis even surgically treated. Moreover, surgical margin and the new 2010 WHO criteria are closely associated with OS for G-NENs.

Duodenal gastrointestinal stromal tumors: clinicopathological characteristics, surgery, and long-term outcome.

BACKGROUND: Duodenal gastrointestinal stromal tumors (DGIST) are rare, and data on their management is limited. We here report the clinicopathological characteristics, different surgical treatments, and long-term prognosis of DGIST. METHODS: Data of 74 consecutive patients with DGIST in a single institution from June 2000 to June 2014 were retrospectively analyzed. The overall survival (OS) and recurrence/metastasis-free survival rates of 74 cases were calculated using Kaplan-Meier method. RESULTS: Out of 74 cases, 42 cases were female (56.76%) and 32 cases (43.24%) were male. Approximately 22.97, 47.30, 16.22, and 13.51% of the tumors originated in the first to fourth portion of the duodenum, respectively, with a tumor size of 5.08 ± 2.90 cm. Patients presented with gastrointestinal bleeding (n = 37, 50.00%), abdominal pain (n = 25, 33.78 %), mass (n = 5, 6.76%), and others (n = 7, 9.76%). A total of 18 patients (24.3%) underwent wedge resection (WR); 39 patients (52.7%) underwent segmental resection (SR); and 17 cases (23%) underwent pancreaticoduodenectomy (PD). The median follow-up was 56 months (1-159 months); 19 patients (25.68%) experienced tumor recurrence or metastasis, and 14 cases (18.92 %) died. The 1-, 3-, and 5-year recurrence/metastasis-free survival rates were 93.9, 73.7, and 69%, respectively. The 1-, 3- and 5-year OS were 100, 92.5, and 86%, respectively. The recurrence/metastasis-free survival rate in the PD group within 5 years was lower than that in the WR group (P = 0.047), but was not different from that in the SR group (P = 0.060). No statistically significant difference was found among the three operation types (P = 0.294). CONCLUSIONS: DGIST patients have favorable prognosis after complete tumor removal, and surgical procedures should be determined by the DGIST tumor location and size.

Treatment and Prognoses in Patients With Primary Gastrointestinal Stromal Tumors ≥10  cm: A Single-Institution Experience in China.

Data on treatments and specific outcomes of primary gastrointestinal stromal tumors (GISTs) ≥10  cm are limited. We here report the treatments and survival outcomes concerning a subgroup of primary giant GISTs. Data of 83 consecutive patients with primary GISTs ≥10  cm in a single institution were retrospectively collected. Fifty-eight patients underwent surgery before imatinib mesylate (IM) treatment (Group A), 10 underwent surgical resection following IM therapy (Group B), whereas 15 patients took IM as drug therapy alone (Group C). The baseline clinical characteristics were similar among the 3 groups. However, a lower proportion in Group A had metastatic disease at the time of diagnosis or surgery compared with Groups B and C (8.6% vs 40.0% vs 40.0%, P < 0.05). The median follow-up duration was 21.5 months. No statistically significant differences were observed on progression-free survival (PFS) among the groups. However, patients in Group B showed significantly better overall survival (OS) compared with those in Group C (P = 0.044). Multivariate analysis showed that patients treated with adjuvant IM were associated with better PFS (hazard ratio [HR] 3.01; 95% confidence interval [CI] 1.13-7.97; P = 0.027) and OS (HR 29.11; 95% CI 3.32-125.36; P = 0.004). The subgroup with mitotic count >10/50 high-power fields (HPF) showed worse PFS (HR 3.50; 95% CI 1.19-10.25; P = 0.022) and OS (HR 20.04; 95% CI 1.67-143.79; P = 0.018) than that of mitotic count ≤5/50 HPF. Clinical treatment patterns for primary giant GISTs are different, and the outcomes of different interventions vary. The optimal treatments for these subgroup of patients still require further long-term investigation. Moreover, mitotic count and adjuvant IM are closely associated with PFS and OS in giant GISTs.

Clinicopathological characteristics, diagnosis, treatment, and outcomes of primary gastric adenosquamous carcinoma.

BACKGROUND: Primary gastric adenosquamous carcinoma (ASC) is a rare subset of ASC. This study aims to investigate the clinicopathological features, diagnosis, treatment, and outcomes of primary gastric ASC. METHODS: The medical records of 13 consecutive patients with primary gastric ASC between January 2010 and July 2014 from a single institutional database were reviewed. RESULTS: Male predominance was observed (M/F = 10/3) among the patients, and their median age was 62 years (range: 43 to 79 years). The primary lesions were most often found in the upper third of the stomach, with a median tumor size of 5 cm (range: 2.25 cm to 10.5 cm). Ten patients underwent radical resections (R0 resection, 76.9%), while three patients had palliative resections (R1/R2 resection, 23.1%). Twelve patients had lymph node metastasis at the time of surgery. Adenocarcinoma and squamous cell carcinoma components in lymph node were found in eight and two cases, respectively, while two patients had both squamous cell carcinoma and adenocarcinoma components. In terms of the TNM staging system, stages IIB, IIIA, IIIB, IIIC, and IV were detected in 2 (15.4%), 2 (15.4%), 1 (7.7%), 5 (38.5%), and 3 (23.1%) patients, respectively. The median follow-up period was 22 months (range: 5 to 52 months); during which, four patients were still alive and eight patients died because of tumor progression. The 1-, 2-, and 3-year survival rates were 76.9%, 46.2%, and 15.4%, respectively. CONCLUSIONS: Primary gastric ASC has a very poor prognosis, and both squamous cell carcinoma and adenocarcinoma components have distant metastasis potential.

Synchronous occurrence of gastrointestinal stromal tumors and other digestive tract malignancies in the elderly.

BACKGROUND/AIMS: Elderly patients with gastrointestinal stromal tumors (GISTs) synchronous with other digestive tract malignancies have been rarely reported. In this study, clinicopathological characteristics were evaluated among elderly patients with GISTs with or without coexisting digestive tract malignancies. METHODS: A total of 161 patients (≥65 years) were retrospectively reviewed at the West China Hospital, Sichuan University from January 2009 to June 2014. RESULTS: Sixty-one patients were diagnosed with synchronous digestive tract malignancies (synchronous group), whereas 100 patients were diagnosed with no synchronous condition (no-synchronous group). The synchronous group exhibited a higher percentage of males (70.49% vs. 53.00%, P = 0.028) and poorer Eastern Cooperative Oncology Group performance status than the no-synchronous group (P = 0.029). The three-year overall survival (OS) rate was significantly lower among patients with synchronous digestive tract malignancies than that among patients without synchronous condition (64.5% vs. 84.0%, P = 0.003). Multivariate analysis showed that the presence of synchronous digestive tract malignancies (P = 0.002), co-morbidity (P = 0.004), and mitotic count ≥10 mitoses/50 high power fields (P = 0.012) were associated with poor OS. CONCLUSIONS: A synchronous condition with other digestive tract malignancies is common in elderly patients with GISTs. OS primarily depends on synchronous digestive tract malignancies, mitotic count, and co-morbidity.

Endoscopic versus open resection for small gastric gastrointestinal stromal tumors: safety and outcomes.

Endoscopic resection has been performed to treat small gastric neoplasms. However, this technique for small gastric gastrointestinal stromal tumors (GISTs) remains controversial. This study aims to compare the safety and surgical outcomes of endoscopic versus open resection of small gastric GISTs.The medical records of 54 consecutive gastric GISTs patients with tumor size of ≤2 cm, who were surgically treated with endoscopic resection (endoscopic group) or open surgery (laparotomy group) in a single institution from March 2010 to June 2014, were retrospectively analyzed. The clinical and tumor characteristics, surgical safety, and tumor-related outcomes were evaluated.Of 54 patients, 32 and 22 patients underwent endoscopic resection and laparotomy, respectively. Patients who underwent endoscopic resection yielded a significantly shorter hospital stay compared with patients who underwent laparotomy (P < 0.001). Compared with patients in the endoscopic group, patients in the laparotomy group had more intraoperative blood loss (P < 0.001), had longer nasogastric tube retention (P < 0.001), and required longer operative time (P < 0.001). More laparotomy patients required postoperative analgesic drugs than those in the endoscopic group (n = 9 vs 4; P = 0.016). Gastric perforation occurred in 1 case during operation in the endoscopic group. Patients who underwent these 2 procedures did not differ with respect to tumor size (P = 0.168), perioperative transfusion (P = 1.000), reoperation (P = 1.000), early satiety (P = 0.560), and postoperative bleeding (P = 1.000). With a median follow-up time of 34.5 months, 1 high-risk patient in each group experienced tumor recurrence/metastasis postoperatively.The endoscopic procedure allows safe resection with good surgical outcomes for small gastric GISTs compared with laparotomy. Moreover, larger randomized controlled trials are warranted to confirm endoscopic application for small gastric GISTs.