Small bowel intramural hematoma caused by warfarin: case report and literature review.

BACKGROUND: Intramural hematoma of the small bowel is a rare yet acute gastrointestinal condition typically linked with impaired coagulation function, often posing diagnostic challenges. It is principally encountered in patients undergoing prolonged anticoagulant therapy, specifically warfarin. CASE PRESENTATION: We reported a case of intramural hematoma associated with warfarin use. The patient was admitted to hospital with abdominal pain and had received anticoagulant therapy with warfarin 2.5 mg/day for 4 years. Laboratory examination showed decreased coagulation function, abdominal CT showed obvious thickening and swelling of part of the jejunal wall, and abdominal puncture found no gastroenteric fluid or purulent fluid. We treated the patient with vitamin K and fresh frozen plasma. The patient was discharged after the recovery of coagulation function. Then we undertaook a comprehensive review of relevant case reports to extract shared clinical features and effective therapeutic strategies. CONCLUSION: Our analysis highlights that hematoma in the small intestinal wall caused by warfarin overdose often presents as sudden and intense abdominal pain, laboratory tests suggest reduced coagulation capacity, and imaging often shows thickening of the intestinal wall. Intravenous vitamin K and plasma supplementation are effective non-surgical strategies. Nevertheless, in instances of severe obstruction and unresponsive hemostasis, surgical resection of necrotic intestinal segments may be necessary. In the cases we reported, we avoided surgery by closely monitoring the coagulation function. Therefore, we suggest that identifying and correcting the impaired coagulation status of patient is essential for timely and appropriate treatment.

Midline and off-midline wound closure methods after surgical treatment for pilonidal sinus.

BACKGROUND: Pilonidal sinus disease is a common and debilitating condition. Surgical treatment remains the mainstay for managing chronic disease, with options including midline and off-midline wound closure methods. However, the optimal approach remains uncertain. Recent developments in tension-free midline techniques require further exploration. OBJECTIVES: To assess the effects of midline and off-midline wound closure methods for pilonidal sinus, and to determine the optimal off-midline flap procedures. SEARCH METHODS: In June 2022, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus EBSCO, and clinical trials registries. We also scanned the reference lists of included studies, as well as reviews, meta-analyses, and health technology reports. We applied no language, publication date, or study setting restrictions. SELECTION CRITERIA: We included parallel RCTs involving participants undergoing midline closure without flap techniques and off-midline closure for pilonidal sinus treatment. We excluded quasi-experimental studies and studies that enroled participants presenting with an abscess. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. The critical outcomes included wound healing (time to wound healing, proportion of wounds healed), recurrence rate, wound infection, wound dehiscence, time to return to work, and quality of life. We assessed biases in these outcomes utilising the Cochrane risk of bias 2 tool and appraised evidence certainty via the GRADE approach. MAIN RESULTS: We included 33 studies with 3667 analysed participants. The median or average age of the participants across the included studies ranged from 21.0 to 34.2 years, with a predominant male representation. Geographically, the trials were primarily conducted in the Middle East. We identified nine intervention comparisons. In this abstract, we focus on and present the summarised findings for the three primary comparisons. Off-midline closure versus conventional midline closure Off-midline closure probably reduces the time to wound healing (mean difference (MD) -5.23 days, 95% confidence interval (CI) -7.55 to -2.92 days; 3 studies, 300 participants; moderate-certainty evidence). However, there may be little to no difference between the two methods in the proportion of wounds healed (100% versus 88.5%, risk ratio (RR) 1.13, 95% CI 0.92 to 1.39; 2 studies, 207 participants; very low-certainty evidence). Off-midline closure probably results in lower rates of recurrence (1.5% versus 6.8%, RR 0.22, 95% CI 0.11 to 0.45; 13 studies, 1492 participants; moderate-certainty evidence) and wound infection (3.8% versus 11.7%, RR 0.32, 95% CI 0.22 to 0.49; 13 studies, 1568 participants; moderate-certainty evidence), and may lower rates of wound dehiscence (3.9% versus 8.9%, RR 0.44, 95% CI 0.27 to 0.71; 11 studies, 1389 participants; low-certainty evidence). Furthermore, off-midline closure may result in a reduced time to return to work (MD -3.72 days, 95% CI -6.11 to -1.33 days; 6 studies, 820 participants; low-certainty evidence). There were no data available for quality of life. Off-midline closure versus tension-free midline closure Off-midline closure may reduce the time to wound healing (median 14 days in off-midline closure versus 51 days in tension-free midline closure; 1 study, 116 participants; low-certainty evidence) and increase wound healing rates at three months (94.7% versus 76.4%, RR 1.24, 95% CI 1.06 to 1.46; 1 study, 115 participants; low-certainty evidence), but may result in little to no difference in rates of recurrence (5.4% versus 7.8%, RR 0.69, 95% CI 0.30 to 1.61; 6 studies, 551 participants; very low-certainty evidence), wound infection (2.8% versus 6.4%, RR 0.44, 95% CI 0.16 to 1.17; 6 studies, 559 participants; very low-certainty evidence), and wound dehiscence (2.5% versus 3.0%, RR 0.82, 95% CI 0.17 to 3.84; 3 studies, 250 participants; very low-certainty evidence) compared to tension-free midline closure. Furthermore, off-midline closure may result in longer time to return to work compared to tension-free midline closure (MD 3.00 days, 95% CI 1.52 to 4.48 days; 1 study, 60 participants; low-certainty evidence). There were no data available for quality of life. Karydakis flap versus Limberg flap Karydakis flap probably results in little to no difference in time to wound healing compared to Limberg flap (MD 0.36 days, 95% CI -1.49 to 2.22; 6 studies, 526 participants; moderate-certainty evidence). Compared to Limberg flap, Karydakis flap may result in little to no difference in the proportion of wounds healed (80.0% versus 66.7%, RR 1.20, 95% CI 0.77 to 1.86; 1 study, 30 participants; low-certainty evidence), recurrence rate (5.1% versus 4.5%, RR 1.14, 95% CI 0.61 to 2.14; 9 studies, 890 participants; low-certainty evidence), wound infection (7.9% versus 5.1%, RR 1.55, 95% CI 0.90 to 2.68; 8 studies, 869 participants; low-certainty evidence), wound dehiscence (7.4% versus 6.2%, RR 1.20, 95% CI 0.41 to 3.50; 7 studies, 776 participants; low-certainty evidence), and time to return to work (MD -0.23 days, 95% CI -5.53 to 5.08 days; 6 studies, 541 participants; low-certainty evidence). There were no data available for quality of life. AUTHORS' CONCLUSIONS: This Cochrane review examines the midline and off-midline wound closure options for pilonidal sinus, predominantly based on young adult studies. Off-midline flap procedures demonstrate there may be benefits over conventional midline closure for pilonidal sinus, with various off-midline flap techniques. When off-midline flap closures were compared to tension-free midline closure, low-certainty evidence indicated there may be improved wound healing and increased time to return to work for off-midline closure, whilst very low-certainty evidence indicated there may be no evidence of a difference in other outcomes. There may be no evidence of an advantage found amongst the off-midline techniques evaluated. The choice of either procedure is likely to be based on a clinician's preference, experience, patient characteristics, and the patients' preferences. To more accurately determine the benefits and potential harms of these closure techniques, further large-scale and meticulously-designed trials are essential. Specifically, there is a pressing need for more studies addressing the paediatric population, in addition to adult studies.

Clinicopathological and mutational characteristics of primary double mutant gastrointestinal stromal tumor: a single center study with review of the literature.

AIMS: Primary double KIT/PDGFRA mutations are very rare in gastrointestinal stromal tumours (GISTs) but have not been comprehensively studied to date. In the present study, we investigated the clinicopathologic and genetic features of eight cases of primary double-mutant GISTs, and we reviewed the literature. METHODS AND RESULTS: The tumours occurred in six males and two females (age range 57-83 years) and involved the small intestine (n = 4), stomach (n = 2), rectum (n = 1) and retroperitoneum (n = 1). Clinical manifestations were variable, ranging from indolent (no symptoms) to aggressive disease (tumour rupture and haemorrhage). All patients underwent surgical excision, and six of them were treated with imatinib. No one experienced recurrence or other complications during the follow-up time (10 to 61 months). Histologically, all the tumours exhibited mixed cell types, accompanied by variable interstitial changes. KIT mutations were detected in all cases, and the majority of them were present in different exons (n = 5). No PDGFRA exon 12, 14 or 18 mutations were found. All the mutations were validated by next-generation sequencing, and two additional variants with comparatively low allelic fractions were identified in one case. Two of the cases had available allele distribution data, one with an in cis compound mutation and the other with an in trans compound mutation. CONCLUSION: Primary double-mutant GISTs have distinctive clinicopathologic and mutational features. Studies of more cases are necessary for a better understanding of these tumours.

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.

Comparative safety and tolerability of approved PARP inhibitors in cancer: A systematic review and network meta-analysis.

BACKGROUND: We aimed to evaluate comparative safety and tolerability of the approved PARP inhibitors in people with cancer. METHODS: Eligible studies included randomized controlled trials comparing an approved PARP inhibitor (fluzoparib, olaparib, rucaparib, niraparib, or talazoparib) with placebo or chemotherapy in cancer patients. Outcomes of interest included: serious adverse event (SAE), discontinuation due to adverse event (AE), interruption of treatment due to AE, dose reduction due to AE, and specific grade 1-5 AEs. RESULTS: Ten trials including 3763 participants and six treatments (olaparib, rucaparib, niraparib, talazoparib, placebo, and protocol-specified single agent chemotherapy) were identified. SAE and discontinuation of treatment did not differ significantly among the four approved PARP inhibitors. Regarding interruption of treatment and dose reduction due to AE, statistically significant differences and statistically non-significant trend were observed. Talazoparib is associated with a higher risk of interruption of treatment and dose reduction (excluding rucaparib) due to AE as compared with the other drugs. Niraparib showed a trend of lower risk of AE related dose reduction as compared with the other drugs. Furthermore, there were significant differences in specific grade 1-5 AE among the four drugs. CONCLUSION: The safety profile of the four approved PARP inhibitors is comparable in terms of SAE and AE-related discontinuation of treatment. Statistically significant differences in the AEs spectrum and AEs related dose interruption and dose reduction demonstrated the prompt identification of AE and dose personalization seem mandatory to obtain maximal benefit from PARP inhibitors.

Impact of Surgical Margin Status on Survival in Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It is inconclusive whether R1 margin determined by postoperative pathological examination indicates worse long-term survival in gastric cancer (GC) patients after curative intent resection (CIR). Hence, we aimed to systematically pool the conflicting evidence to fill this gap. METHODS: The present study was performed according to the published protocol and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Published studies examining the impact of microscopic margin status on overall survival (OS) and 5-year OS rate in GC were systematically searched in PubMed, Embase, and Cochrane Library databases. RevMan 5.3 was used to conduct statistical analysis, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of evidence for each outcome. RESULTS: Twenty-three retrospective cohort studies including 19 992 patients were analyzed. The pooled hazard ratio for OS of 14 studies was 2.06 (95% confidence interval [CI]: 1.61-2.65, low certainty), indicating that R1 margin predicted inferior OS. Subgroup and sensitivity analyses upheld the statistical stability of this finding. The pooled odds ratio (OR) of 14 studies was .21 (95% CI: .17-.26, moderate certainty), demonstrating that the presence of R1 margins was associated with a poorer 5-year OS rate. Sensitivity analyses and most of the subgroup analyses confirmed this finding, except the "esophagogastric junction (EGJ) cancers" subgroup, which included two studies with a pooled OR of .41 (95% CI: .10-1.61). CONCLUSION: R1 margin detected by pathological examination might exhibit a high correlation with poorer OS and 5-year OS rate in GC (except EGJ cancers) patients who underwent CIR. To figure out the effect of R1 margin on survival of different stages and histological types need prospective studies with large sample sizes and standardized methods. What is the best treatment for R1 margin patients also need more in-depth and special research.

Clinicopathological features, clinical efficacy on 101 cases of rectal gastrointestinal stromal tumors, and the significance of neoadjuvant therapy.

OBJECTIVE: To investigate the clinicopathological features and clinical efficacy among 101 cases of rectal gastrointestinal stromal tumors (GISTs) and to investigate the significance of imatinib mesylate (IM) neoadjuvant therapy. METHODS: The clinicopathological features, treatment methods, perioperative data, and prognosis of the patients were summarized and analysed in 101 patients with rectal GISTs who received treatment in the Gastrointestinal Surgery of West China Hospital of Sichuan University and the Affiliated Hospital of Guizhou Medical University from August 2002 to November 2020 in China. RESULTS: A total of 101 patients, including 64 males and 37 females, were aged from 22 to 79 years (55.4 ± 12.2 years). Among the 70 patients who underwent direct surgery, 8 were very low risk cases, 10 were low risk cases, 7 were intermediate risk cases, and 45 were high risk cases. Cox regression analysis showed that postoperative IM adjuvant treatment improved the disease-free survival (DFS) and overall survival (OS) of 52 intermediate and high risk patients. Among the 31 patients who received neoadjuvant therapy, the objective response rate (ORR) was 83.9% (26/31), and the disease control rate (DCR) reached 96.8% (30/31). Subgroup analysis was also conducted based on the tumour diameter. (1) Among the 36 patients with a diameter ≤ 5 cm, two patients received IM neoadjuvant therapy, while 34 patients received direct surgery. Neither univariate nor Cox regression analysis found that neoadjuvant therapy affected DFS and OS. (2) Among the 65 patients with a diameter > 5 cm, 29 received IM neoadjuvant therapy, and 36 received direct surgery. Patients who underwent neoadjuvant therapy had less blood loss (P = 0.022), shorter postoperative hospital stay (P = 0.001), increased anal retention rate (93.1% vs. 72.2%, P = 0.031), and decreased enterostomy rate (10.3% vs. 33.3%, P = 0.037) than those who underwent direct surgery. Cox regression analysis suggested that neoadjuvant therapy and postoperative IM adjuvant therapy improved DFS. CONCLUSION: Rectal GISTs are relatively rare and highly malignant tumors. Postoperative oral IM therapy can improve the DFS and OS of intermediate and high risk patients. In patients with rectal GISTs with diameters > 5 cm, IM neoadjuvant therapy can improve anal retention rate, preserve the structure and function of the organs, reduce enterostomy rate, and improve prognosis.

Clinical, surgical characteristics and long-term outcomes of lumbar hernia.

BACKGROUND/AIM: Lumbar hernia is caused by a defect in the abdominal wall. Due to its rarity, there is no established consensus on optimal treatment for lumbar hernia yet. Thus, we here investigated the clinical, surgical characteristics and outcomes of lumbar hernia by collecting 28 such patients from our hospital. METHODS: Patients diagnosed with lumbar hernia from our institution between April 2011 and August 2020 were retrospectively collected in this study. Demographics, clinical characteristics and surgical information were recorded. RESULTS: A consecutive series of 28 patients with lumbar hernia were retrospectively collected, including 13 males (46%) and 15 females (54%). The ages of the patients ranged from 5 to 79 years (median: 55 years), with a mean age of 55.6 ± 14.9 years. A total of 7 cases had a history of previous lumbar trauma or surgery. There were 11 (39%), 15 (54%) and 2 (7.1%) cases had right, left and bilateral lumbar hernia, respectively. Superior and inferior lumbar hernia were found in 25 (89%) and 3 (11%) patients. General anesthesia was adopted in 16 cases (group A), whereas 12 patients received local anesthesia (group B). Patients in the group B had a shorter hospital stay than that of the group A (3.5 ± 1.3 days vs. 7.1 ± 3.2 days, p = 0.001), as well as total hospitalization expenses between the two groups (2989 ± 1269 dollars vs. 1299 ± 229 dollars, p < 0.001). With a median follow-up duration of 45.9 months (range: 1-113 months), only 1 (3%) lumbar hernias recurred for the entire cohort. CONCLUSIONS: Lumbar hernia is a relatively rare entity, and inferior lumbar hernia is rarer. It is feasible to repair lumbar hernia under local anesthesia.

Long-term survival among patients with gastrointestinal stromal tumors diagnosed after another malignancy: a SEER population-based study.

BACKGROUND: To explore overall survival (OS) and GISTs-specific survival (GSS) among cancer survivors developing a second primary gastrointestinal stromal tumors (GISTs). METHODS: We conducted a cohort study, where patients with GISTs after another malignancy (AM-GISTs, n = 851) and those with only GISTs (GISTs-1, n = 7660) were identified from the Surveillance, Epidemiology, and End Results registries (1988-2016). Clinicopathologic characteristics and survival were compared between the two groups. RESULTS: The most commonly diagnosed first primary malignancy was prostate cancer (27.7%), followed by breast cancer (16.2%). OS among AM-GISTs was significantly inferior to that of GISTs-1; 10-year OS was 40.3% vs. 50.0%, (p < 0.001). A contrary finding was observed for GSS (10-year GSS 68.9% vs. 61.8%, p = 0.002). In the AM-GISTs group, a total of 338 patients died, of which 26.0% died of their initial cancer and 40.8% died of GISTs. Independent of demographics and clinicopathological characteristics, mortality from GISTs among AM-GISTs patients was decreased compared with their GISTs-1 counterparts (HR, 0.71; 95% CI, 0.59-0.84; p < 0.001), whereas OS was inferior among AM-GISTs (HR, 1.11; 95% CI, 0.99-1.25; p = 0.085). CONCLUSIONS: AM-GISTs patients have decreased risk of dying from GISTs compared with GIST-1. Although another malignancy history does not seemingly affect OS for GISTs patients, clinical treatment of such patients should be cautious.

Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors.

BACKGROUND: Malignant growth and metastasis of gastrointestinal stromal tumors (GIST) occur in some patients even during the course of treatment, but their mechanisms remains poorly understand at the molecular level so far. METHODS: Profiles of protein expression in gastric GIST tissues were explored using protein microarray analysis, down-regulation of SPARCL1 (secreted protein acidic and rich in cysteine-like protein 1) was validated by RT-qPCR, western blot and immunohistochemistry. The effect of specific shRNA-induced SPARCL1 downregulation on the biological traits of GIST 882 cell was investigated. We then employed a mouse xenograft model to investigate whether the low-expression of SPARCL1 impact the metastasis ability of GIST cells in vivo. RESULTS: SPARCL1 was significantly downregulated in the gastric GIST with high-grade malignance as compared with low-grade malignance, its expression was closely correlated with tumor size, mitotic index, distant metastasis at the time of initial diagnosis and tumor progression of GIST (P < 0.05). Moreover, results of the Cox analysis showed that expression of SPARCL1 is an independent prognostic predictors for gastric GIST (P = 0.008; HR 0.157, 95% CI 0.040~ 0.612). Downregulation of SPARCL1 promoted cell migration and invasion, but did not affect proliferation, cell cycle and apoptosis of GIST 882 cells. In mouse xenograft model, GIST cells with the decreased expression of SPARCL1 presented an enhanced ability of liver metastasis (P < 0.05). CONCLUSIONS: Taken together, our present study demonstrated that SPARCL1 have a certain degree of malignancy-suppressing potential through inhibiting the metastasis of gastric GIST.

Comparative effectiveness of adjuvant treatments for resected gastric cancer: a network meta-analysis.

BACKGROUND: Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment. METHODS: We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS. RESULTS: 11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63-0.89), (HR = 0.63 with 95% CrI: 0.52-0.76), and (HR = 0.66 with 95% CrI: 0.51-0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT. CONCLUSIONS: S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.

Preoperative imatinib mesylate (IM) for huge gastrointestinal stromal tumors (GIST).

BACKGROUND: Preoperative imatinib mesylate (IM) treatment has not yet been standardized. Here, we aim to further explore such therapy on patients with gastrointestinal stromal tumors (GIST) retrospectively. METHODS: Patients experiencing preoperative IM were identified from January 2009 to February 2015. RESULTS: A total of 28 GIST patients were identified. The patients received preoperative IM treatment for a median length of 13.5 months, ranging from 5 to 37 months. PR and SD were observed in 24 (85.7%) and 4 (15.3%) patients, respectively. The tumor shrinkage occurred predominantly within 6 to 12 months, and slight tumor shrinkage could be observed after 12 months in certain patients. Nineteen patients (67.9%) received surgery, and R0 resection was acquired in 18 (94.7%) patients. The initial mean maximum diameter was 10.5 (5.2 to 19.0) cm and decreased to 5.9 (2.7 to 19.0) cm after preoperative treatment with a median length of 12 (ranging from 5 to 36) months (P < 0.001) in patients receiving operations. Three in 7 cases of rectum GIST underwent abdominoperineal resection, and four others adopted sphincter-sparing resection. Partial gastrectomy was performed in four patients. CONCLUSIONS: IM prior to surgery can effectively prevent tumor rupture and facilitate surgery with low surgical morbidity for GIST patients. Tumor shrinkage following IM occurred predominantly within 6 to 12 months, and slight tumor shrinkage could be observed after 12 months in certain patients. In selected patients, prolonged exposure to IM is seemingly advisable under close radiological surveillance.

[FAP Expression and Its Association with the Prognosis of Gastric Stromal Tumors].

OBJECTIVES: To determine the association of FAP expression with the prognosis of gastric stromal tumors (GSTs). METHODS: Paraffin-embedded GSTs samples were collected from January 2010 to December 2013 in the department of pathology of our hospital. FAP expression was examined by immunohistochemistry staining. Its correlations with clinical pathological characteristics and prognosis of GSTs were analyzed. RESULTS: A total of 98 cases were included in this study. FAP was expressed in the cytoplasm of GSTs cells, with a positive rate of 42.9%. No FAP expression was found in normal gastric tissues. No differences of FAP expression were found in patients with different gender, age and tumor mitotic counts (P >0.05). Tumor diameter and risk classification were associated with FAP expression (P <0.05). Higher levels of FAP expression were found in larger and higher risk tumors. No significant correlations between FAP expression and routine immunohistochemical markers were found. Log-rank univariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP expression were associated with recurrence free survival of GSTs patients with intermediate-high risks (P <0.05). Cox multivariate survival analysis showed that mitotic counts, tumor size, postoperative IM and FAP were independent predictors for the prognosis of GSTs patients with intermediate-high risks (P <0.05). CONCLUSION: FAP is expressed in the cytoplasm of gastric GIST cells, but not in normal gastric tissues. FAP is a predictor for the prognosis of GSTs patients with intermediate-high risks.

[Associations of Preoperative Platelet-to-lymphocyte Ratio and Derived Neutrophil-to-lymphocyte Ratio with thePrognosis of Gastrointestinal Stromal Tumor].

OBJECTIVES: To determine the associations of preoperative platelet-to-lymphocyte ratio (PLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) with the prognosis of gastrointestinal stromal tumor (GIST). METHODS: GIST patients with surgical treatment from June 2005 to February 2015 in West China Hospital of Sichuan University were enrolled in the study. The results of blood routine tests of the patients within one week prior to surgery and their clinical data were extracted. The patients were divided into high-PLR/d-NLR (PLR#>153.075, d-NLR#>1.245) and low-PLR/d-NLR (PLR≤153.075, d-NLR≤1.245) groups according to the optimal cutoff values of the receiver operating characteristic (ROC) curves. Recurrence-free survival (RFS) rates were calculated using Kaplan-Meier method. COX regression analyses were performed to identify factors associated with RFS for GIST patients without imatinib treatment. [WTHZ]. RESULTS: [WTBZ]Regardless of imatinib treatment, the patients with high PLR and d-NLR had shorter RFS than those with low PLR and d-NLR. Tumor diameter, location, mitotic counts, preoperative PLR and d-NLR were identified as factors associated with RFS in the univariate analyses. The multivariate analysis identified tumor diameter [≥5 cm, hazard ratio (HR): 4.295, 95% confidence interval (CI): 1.772-10.413, P=0.001], non-stomach (HR:2.247, 95%CI: 1.200-4.209; P=0.011), mitotic counts (>5/50 HPF: HR:4.678, 95%CI: 2.364-9.257; P<0.001) and high d-NLR (HR:2.549, 95%CI: 1.159-5.606; P=0.1020) as independent factors predicting the prognosis of GIST. The patients with high PLR or high d-NLR had shorter RFS than those with low PLR/d-NLR. [WTHZ]. CONCLUSION: [WTBZ]Preoperative d-NLR is an independent predictor of RFS in GIST. PLR and d-NLR can be used in predicting the recurrence risk of GIST.

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.

Platelet-Rich Plasma-Loaded Poly(d,l-lactide)-Poly(ethylene glycol)-Poly(d,l-lactide) Hydrogel Dressing Promotes Full-Thickness Skin Wound Healing in a Rodent Model.

Traditional therapeutic methods for skin wounds have many disadvantages, and new wound dressings that can facilitate the healing process are thus urgently needed. Platelet-rich plasma (PRP) contains multiple growth factors (GFs) and shows a significant capacity to heal soft tissue wounds. However, these GFs have a short half-life and deactivate rapidly; we therefore need a sustained delivery system to overcome this shortcoming. In this study, poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA: PLEL) hydrogel was successfully created as delivery vehicle for PRP GFs and was evaluated systematically. PLEL hydrogel was injectable at room temperature and exhibited a smart thermosensitive in situ gel-formation behavior at body temperature. In vitro cell culture showed PRP-loaded PLEL hydrogel (PRP/PLEL) had little cytotoxicity, and promoted EaHy926 proliferation, migration and tube formation; the factor release assay additionally indicated that PLEL realized the controlled release of PRP GFs for as long as 14 days. When employed to treat rodents' full-thickness skin defects, PRP/PLEL showed a significantly better ability to raise the number of both newly formed and mature blood vessels compared to the control, PLEL and PRP groups. Furthermore, the PRP/PLEL-treated group displayed faster wound closure, better reepithelialization and collagen formation. Taken together, PRP/PLEL provides a promising strategy for promoting angiogenesis and skin wound healing, which extends the potential of this dressing for clinical application.

[Characteristics of Clinicopathology and Genotype in 179 Cases with Gastrointestinal Stromal Tumor].

OBJECTIVE: To analyze the characteristics of the clinicopathology and genotypes in patients with gastrointestinal stromal tumor (GIST). METHODS: The clinicopathological and genotypic data of 179 patients with GIST, who underwent treatment and genetic testing in the Hostital of West China from September 2009 to February 2009 were collected retrospectively. RESULTS: The tumor sites of the cases were located in stomach (88 cases, 49.2%), small intestine (70 cases, 39.1%), colorectum (7 cases, 3.9%) and the other sites (14 cases, 7.8%) respectively. 94.4%, 74.9% and 93.3% of GIST patients were positive for CD117, CD34 and DOG-1 immunophenotypes respectively. C-kit and PDGFRα mutations were found in 151 cases (84.4%) and 8 cases (4.5%) except for the wild types of the rest 20 cases (11.2%). Among all the c-kit mutation, 92.2% mutation types in exon 11 were deletion mutation, point mutation and hybrid mutations, and in exon 9 the mutation types were just involving A502_Y503dup (n = 6) and Y403_F504ins (n = 14), while the mutation type were K642Q in exon 13 (n = 1) and N822K in 17 (n = 2). There were 6 patients with the mutation types of PDGFRα in exon 18, and 3 of them were type of D842V. In the GIST genotyping, DOG-1 positive rate in PDGFRα mutation patients were significantly lower than that in c-kit mutation and wild type patients (P = 0.007). In the various type of c-kit mutations, the positive rate of CD34 in point mutation patients were significantly lower than that in other mutation types (P < 0.001). The rate of high-risk patients in point mutation and insertion mutation patients were lower than that in deletion mutation and deletion + insertion mutation patients (P = 0.006). CONCLUSION: The most common localizaions of GISTs are the stomach and small intestine. The most frequent mutation type of GIST is c-kit exon 11. The individualized treatment is required for GIST patients because its high mutation rate and types.

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.

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.