Comparison of Clinical Characteristics, Therapy, and Short-Term Prognosis between Blunt and Penetrating Abdominal Trauma: A Multicentric Retrospective Cohort Study.

Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

Head-to-head comparison of perfluorobutane contrast-enhanced US and multiparametric MRI for breast cancer: a prospective, multicenter study.

BACKGROUND: Multiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency. PATIENTS AND METHODS: This was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions. RESULTS: In total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online. CONCLUSIONS: PFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability. Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020. IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

Fourth-line targeted drugs for the long-term treatment of patients with secondary gastrointestinal stromal tumors with multisite mutations: a case report.

BACKGROUND: The surgical treatment of small intestinal stromal tumors is mainly based on the common experience of gastrointestinal stromal tumors (GISTs). The biological characteristics of tumors and secondary gene mutations during disease progression cause many difficulties in clinical treatment. Advanced GISTs usually have no chance to surgery especially after multiple lines of drug therapy and multiple surgeries. This case report provides a good example of rensformational surgery for advanced GIST. CASE DESCRIPTION: In this report, we describe the case of a patient that is male 57 years old with a small intestinal stromal tumor (stage IV) treated in our center (The First Medical Centre, Chinese PLA General Hospital, Beijing, China) who underwent more than 20 years of first- to fourth-line tyrosine kinase inhibitor (TKI) drug treatment and three rounds of surgical treatment. In June 2020, the patient developed extensive metastases in the abdominal cavity, pelvic cavity, and liver, and could not be treated surgically. The patient was enrolled in the "two-arm clinical trial of bridge therapy with ripretinib and sunitinib in China", started four cycles of ripretinib drug therapy and tumor evaluation, and eventually achieved tumor remission. The patient received surgical treatment following conversion therapy and postoperative tumor recurrence. After continued targeted therapy with TKIs, disease progression was controlled, and the patient's survival was prolonged. CONCLUSIONS: Type II TKIs such as ripretinib and avapritinib have enhanced the typically expected therapeutic effects of many advanced GISTs. For the late-line treatment of advanced GIST, new TKI drugs can be tried for conversion therapy while monitoring the whole process, grasp the timing of surgery to provide more effective treatment.

Postoperative imatinib in patients with intermediate risk gastrointestinal stromal tumor.

AIM: To determine whether imatinib adjuvant treatment improved recurrence-free survival (RFS) in gastrointestinal stromal tumor (GIST) with intermediate risk. MATERIALS & METHODS: Patients who had undergone complete tumor resection with intermediate risk were enrolled. RESULTS: A total of 99 patients received imatinib adjuvant therapy and 93 patients only received observation. The RFS in patients who received adjuvant therapy was superior to RFS in control group (p = 0.004). GIST with location of intestine or rectum and GIST with exon 11 deletion mutation had longer RFS. CONCLUSION: Adjuvant imatinib improves RFS of GIST with intermediate risk of recurrence, particularly in GIST with intestinal and rectal location or c-kit gene exon 11 deletion mutation.

YAP promotes breast cancer metastasis by repressing growth differentiation factor-15.

The transcriptional co-activator Yes-associated protein (YAP) has been implicated as an oncogene and is found to promote breast cancer metastasis. However, the pro-metastatic mechanism of YAP remains unclear. Here, we demonstrated that YAP functions as a transcriptional repressor of growth differentiation factor-15 (GDF15), a divergent member of the transforming growth factor superfamily, in several breast cancer cell lines. Functionally, knockdown of YAP decreased, whereas knockdown of GDF15 increased, the metastatic potential of breast cancer cells. More than that, the reduced metastasis in YAP-depleted cells could be reversed by simultaneous knockdown of GDF15. Mechanistically, the repressive effect of YAP on GDF15 requires its transcriptional factor TEAD (TEA domain family). In addition, YAP recruits polycomb repressive complex 2 (PRC2) to tri-methylate histone H3 lysine 27 in the promoter region of GDF15. Co-immunoprecipitation experiments demonstrated that YAP and enhancer of zeste 2 PRC2 subunit (EZH2) physically interact with each other. In conclusion, our data reveal that YAP promotes metastasis of breast cancer cells by repressing GDF15 transcription and present a novel molecular mechanism underlying the pro-metastasis function of YAP oncoprotein, with the implication of a therapeutic avenue for breast cancer treatment.

Iridoid glycosides from Callicarpa nudiflora Hook.

Four new iridoid glycoside derivatives (1-4), along with ten known iridoid glycosides (5-14), were isolated from Callicarpa nudiflora Hook et Arn. The structure of the new iridoid glycosides was elucidated as 5″-methoxy-ampicoside (1), 6″-O-trans-caffeoylcatalpol (2), 6″-O-trans-feruloylcatalpol (3) and 3″-methoxy-agnucastoside C (4) on the basis of spectroscopic analysis. Compounds 1-11 were reported from this plant for the first time. The cytotoxic activity of the isolated compounds against human cervical carcinoma Hela cells and ovarian carcinoma HeyA8 cells was evaluated using the microculture tetrazolium assay. Compounds 4, 5, 8, 12 and 13 showed cytotoxic activity against the Hela cell line with IC50 values of 25.3, 48.1, 17.3, 38.3 and 28.2 µM, respectively. While only compound 8 showed cytotoxicity against the HeyA8 cell line, with an IC50 of 35.5 µM.

[Diagnosis and treatment for complicated gastrointestinal stromal tumors].

Tyrosine kinase inhibitor(TKI) combined with surgical treatment is the optimal strategy for gastrointestinal stromal tumors(GIST). However, there is no systemic report about the complicated GIST(recurrence or metastasis, peritoneal dissemination, combined resection of multiple organs), except the cases review and experimental studies. Tyrosine kinase inhibitor combined with surgery may increase the overall survival of complicated GIST. This article will describe the definition, clinical features, surgical and drug therapy, and prognosis, in order to provide reliable theoretical basis and experience for clinical doctors, prolong patient survival and improve the quality of survival.

[Chemical constituents from Callicarpa nudiflora and their cytotoxic activities].

The chemical consitituents from cytotoxic fraction of the Callicarpa nudiflora extract were isolated and purified by a combination of HP-20 macroporous resin, silica gel and Sephadex LH-20 column chromatographies. The structures were elucidated on the basis of the spectroscopic data and comparison of their spectroscopic data with reported data. The cytotoxicity was evaluated by the MTT assay. The 50% and 70% EtOH elutions of EtOH-extract showed significant cytotoxic activities, leading to the isolation of twelve compounds, which were identified as luteoloside(1), lutedin-4'-O-ß-D-glucoside(2), 6-hydroxyluteolin-7-O-ß-glucoside(3), lutedin-7-O-neohesperidoside(4), rhoifolin (5), luteolin-7, 4'-di-O-glucoside (6), forsythoside B (7), acteoside (8), alyssonoside (9), catalpol(10), nudifloside(11), and leonuride(12). Compounds 3-6, 10 and 12 were isolated from this genus for the first time, and compound 9 was isolated from this plant for the first time. The cytotoxicity assay demonstrated that flavonoids 1-6, in various concentrations, showed monolithic proliferation inhibitory activities against Hela, A549 and MCF-7 cell lines. Compounds 3, 5 and iridoid glycoside 11 possessed higher cytotoxicacivities. In short, flavonoids are the main components of cytotoxic extract from C. nudiflora, while phenylethanoid glycosides are the predominant ingredient but inactive to cancer cell lines. In addition, the minor iridoid glycoside expressed weak cytotoxic activity.

[Efficacy and prognosis of different treatments on 63 patients with small intestinal gastrointestinal stromal tumors].

OBJECTIVE: To analyze the efficacy and prognosis of different treatments on small intestinal gastrointestinal stromal tumors(SIGIST). METHODS: Clinical data of 63 patients with SIGIST who were admitted to the Chinese PLA General Hospital from January 2004 to December 2013 were analyzed retrospectively. According to resection procedure and postoperative use of imatinib, patients were divided into R0 resection plus imatinib group (13 cases), R0 resection without imatinib group (42 cases), non-R0 resection plus imatinib group (7 cases), non-R0 resection without imatinib group (1 case). Survival was compared among groups. Result All the patients were followed up with a median length of 24 months(3 to 120 months), and the over survival (OS) rates at 1-year, 3-year, 5-year were 97%, 94% and 80%. In R0 resection plus imatinib group, R0 resection without imatinib group, and non-R0 resection plus imatinib group, the progression free survival(PFS) time was 24, 24 and 23 months; the 1-year PFS were 100%, 97% and 83%; the 3-year PFS were 100%, 45% and 83%; the 5-year PFS were 100%, 28% and 42%. R0 resection plus imatinib group had significantly higher PFS(all P<0.05). The case of non-R0 resection without imatinib died 6 months after operation. Among 55 patients undergoing R0 resection, recurrence was found in 16 patients, whose recurrence rates of 1-year, 3-yeart and 5-year were 2%,43% and 58%. Local recurrence was found in 8 cases, hepatic recurrence in 3 cases and widespread recurrence in 5 cases, who received simple imatinib, operation plus imatinib and imatinib intervention, with median survival time of 66.5 months, 92.5 months and 48 months respectively. One patient initiatively abandoned treatment and died 17 months later. CONCLUSION: The total resection and postoperative imatinib administration can improve the prognosis and raise the progression free survival of patients with small intestinal stromal tumors.

CD133 and Ki-67 expression is associated with gastrointestinal stromal tumor prognosis.

CD133+ tumor cells have a greater potential ability for tumorigenesis, proliferation, invasion and metastasis compared with CD133- tumor cells. Ki-67 is associated with cell proliferation in various tumors and has a markedly positive correlation with the prognosis of patients. However, there are a limited number of studies that have investigated the association between the prognosis of gastrointestinal stromal tumors (GISTs) and the two markers. The present study aimed to investigate CD133 and Ki-67 expression in GISTs and to explore their clinicopathological significance in the prognosis of patients with GISTs. A total of 111 GIST patients from the Chinese People's Liberation Army (PLA) General Hospital were retrospectively followed up and immunohistochemistry was used to detect CD133, Ki-67 and CD117 expression in the tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. The log-rank test, χ2 test and Cox's proportional hazards model were used to determine the association between CD133, Ki-67, CD117 expression and the prognosis of GIST. The 1-, 3- and 5-year survival rates were 93.0, 89.0 and 82.0%, respectively, in all the patients. However, in the patients with CD133+ or Ki-67+, the 1-, 3- and 5-year survival rates were 81.0, 61.5 and 50.0% and 83.0, 66.6 and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were statistically lower (CD133 log-rank, P=0.028; Ki-67 log-rank, P=0.002). The multivariate Cox analysis revealed that CD133 and Ki-67 expression were considerable factors in the prognosis of GIST patients (CD117, P=0.495; CD133, P=0.036; Ki-67, P=0.003). In conclusion, the positive expression of CD133 and Ki-67 was associated with a poor prognosis of GIST.

Overexpression of carbonic anhydrase II and Ki-67 proteins in prognosis of gastrointestinal stromal tumors.

AIM: To investigate the expression and prognostic value of carbonic anhydrase II (CA II) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People's Liberation Army General Hospital from January 2004 to December 2010 were retrospectively followed up, and immunohistochemistry was used to detect CA II, Ki-67 and CD117 expression in tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. Log-rank test, χ² test and Cox proportional hazards model were used to determine the relationships between CA II, Ki-67 and CD117 expression and prognostic value in GISTs. RESULTS: The survival rates at 1, 3 and 5 years were 90.0%, 82.0% and 72.0% in all patients. However, in patients with positive CA II or Ki-67, the survival rates were 92.0%, 83.0% and 77.0% or 83.0%, 66.6% and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were significantly lower (CA II log-rank P = 0.000; Ki-67 log-rank P = 0.004). Multivariate Cox analysis revealed that CA II, CD117 and Ki-67 were considerable immune factors in prognosis of GIST patients (CA II P = 0.043; CD117 P = 0.042; Ki-67 P = 0.007). Besides, tumor diameter, mitotic rate, tumor site, depth of invasion, complete resection, intraoperative rupture, and adjuvant therapy were important prognosis predictive factors. Our study indicated that CA II had strong expression in GISTs and the prognosis of GISTs with high CA II expression was better than that of GISTs with low or no expression, suggesting that CA II is both a diagnostic and prognostic biomarker for GIST. CONCLUSION: CA II and Ki-67 are significant prognostic factors for GISTs. CA II associated with neovascular endothelia could serve as a potential target for cancer therapy.

[Prognosis analysis of 216 cases of gastrointestinal stromal tumor].

OBJECTIVE: To analyze the impact of location of gastrointestinal stromal tumor(GIST) on the survival, and the influence of surgical treatment and imatinib therapy on survival. METHODS: The clinical data of 216 patients with GIST who were admitted to the People's Liberation Army Hospital from January 2004 to December 2010 were analyzed retrospectively. RESULTS: All the patients were followed up with a median time of 22 months(1 to 83 months). The 1-, 3-, and 5-year survival rates were 93%, 75% and 30%. The survival rates of 5-year with GIST located in the stomach (103 cases), the small intestine (45 cases) and gastrointestinal outside(41 cases) were 93%, 75%, and 30%, respectively, and the differences were statistically significant(P<0.05). There were no deaths in patients with GIST located in duodenum(18 cases) and rectum(9 cases). The 5-years survival rates of GIST in the groups of complete excision combined with imatinib, complete resection without imatinib, incomplete resection combined with imatinib, incomplete resection without imatinib were 100%, 98%, 49% and 14%, respectively, and the differences were statistically significant(P<0.05). CONCLUSIONS: GISTs in different parts of gastrointestinal tract have different survival rates. Radical resection and imatinib can improve the survival rates of patients with GIST.

Parenteral nutrition impairs lymphotoxin ß receptor signaling via NF-κB.

OBJECTIVE: To determine effects of (1) parenteral nutrition (PN), (2) exogenous Lymphotoxin ß receptor (LTßR) stimulation in PN animals, and (3) exogenous LTßR blockade in chow animals on NF-κB activation pathways and products: MAdCAM-1, chemokine (C-C motif) Ligand (CCL) 19, CCL20, CCL25, interleukin (IL)-4, and IL-10. BACKGROUND: LT stimulates LTßR in Peyer's patches (PP) to activate NF-κB via the noncanonical pathway. The p100/RelB precursor yields p52/RelB producing MAdCAM-1, cytokines, and chemokines important in cell trafficking. TNFα, IL-1ß, and bacterial products stimulate the inflammatory canonical NF-κB pathway producing p65/p50 and c-Rel/p50. PN decreases LTßR, MAdCAM-1, and chemokines in PP and lowers small intestinal IgA compared with chow. METHODS: Canonical (p50 and p65) and noncanonical (p52 and Rel B) NF-κB proteins in PP were analyzed by TransAM NF-κB kit after 5 days of chow or PN, 2 days of LTßR stimulation or 3 days of LTßR blockade. MAdCAM-1, chemokines, and cytokines in PP were measured by ELISA after LTßR stimulation or blockade. RESULTS: PN significantly reduced all NF-κB proteins in PP compared with chow. Exogenous LTßR stimulation during PN increased p50, p52, Rel B, MAdCAM-1, IL-4, and IL-10 in PP, but not p65, CCL19, CCL20, or CCL25 compared with PN. LTßR blockade reduced noncanonical products (p52 and Rel B), MAdCAM-1, CCL19, CCL20, CCL25, IL-4, and IL-10 but had no effect on the inflammatory pathway (p50 and p65) compared with chow. CONCLUSION: Lack of enteral stimulation during PN decreases both canonical and noncanonical NF-κB pathways in PP. LTßR stimulation during PN feeding completely restores PP noncanonical NF-κB activity, MAdCAM-1, IL-4, IL-10, and partly the canonical pathway. LTßR blockade decreases the noncanonical NF-κB activity, MAdCAM-1, chemokines, and cytokines without effect on the canonical NF-κB activity in PP.