Low expression of exosomal miR-150 predicts poor prognosis in colorectal cancer patients after surgical resections.

Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change [FC] = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.

Management of retroperitoneal sarcoma involving the iliac artery: Single-center surgical experience.

BACKGROUND: Management of retroperitoneal sarcoma (RPS) involving the iliac artery is challenging and requires the concerted efforts of multidisciplinary team (MDT) members during surgical treatment. AIM: To summarize the clinicopathologic features of RPS involving the iliac artery and our retroperitoneal soft tissue tumor MDT surgical experience. METHODS: In this retrospective study, 15 patients with RPS involving the iliac artery who underwent surgery at our retroperitoneal soft tissue tumor center from July 2004 to June 2020 were analyzed. Statistical analyses were performed by Student's t-test with SPSS 16.0. RESULTS: Complete tumor resection (R0/R1) and iliac artery reconstruction were achieved in all 15 patients. All the operations were successful, with no serious complications or perioperative death. Resection with bilateral iliac artery reconstruction required a higher intraoperative blood transfusion volume than resection with unilateral iliac artery reconstruction. Recurrent cases were more likely to bleed and required a higher blood transfusion volume than primary cases. As of January 2021, 11 patients were alive, and 4 had died. Local recurrence occurred in two patients, one of whom developed liver metastasis. CONCLUSION: Resection of RPS involving iliac vessels is feasible and effective when performed by MDT members. Iliac artery oncovascular resection and reconstruction are key to a successful operation. Adequate blood preparation is important for successful completion of surgery.

Efficacy and safety of anlotinib, a multikinase angiogenesis inhibitor, in combination with epirubicin in preclinical models of soft tissue sarcoma.

BACKGROUND: Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient-derived xenografts (PDX) model. METHODS: We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty-six PDX models were divided into six groups and treated with anlotinib alone (low-dose, 1.5 or high-dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150-200 mm3 . After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki-67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively. RESULTS: After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high-dose anlotinib group was significantly smaller than the low-dose anlotinib group (P < .001). Combined high-dose anlotinib and epirubicin treatment resulted in the most pronounced tumor inhibition. In the groups treated with the anlotinib-containing regimen, the expression levels of CD31, EGFR, MVD, and Ki-67 were significantly low. The weight in each group had no statistical differences; the same applied to the hepatic function, cardiac function, and toxicity. CONCLUSIONS: High-dose anlotinib combined with epirubicin was an effective and safe therapy for STS.

Identification of EML4-ALK as an alternative fusion gene in epithelioid inflammatory myofibroblastic sarcoma.

BACKGROUND: Known as solid tumors of intermediate malignant potential, most inflammatory myofibroblastic tumors (IMTs) are treatable as long as the tumor is en-bloc resected. However, in some cases, the tumors have recurred and grown rapidly after successful surgery. Some of these tumors were classified as an epithelioid inflammatory myofibroblastic sarcoma (EIMS). Most previously reported EIMSs have been caused by RANBP2-ALK fusion gene. We herein report an EIMS case caused by an EML4-ALK fusion gene. METHODS: RNAseq was conducted to find out the new ALK fusion gene which could not be detected following previously reported RT-PCR methods for EIMS cases with RANBP2-ALK fusion gene. After that, RT-PCR was also conducted to further prove the newly found fusion gene. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) test were applied to find out the unique morphological characters compared with the previous reported EIMS cases. RESULTS: We found an EIMS case who was suffering from a rapid recurrence after cytoreducyive surgery was done to relieve the exacerbating symptoms. The patient finally died for tumor lysis syndrome after the application of crizotinib. Distinctive ALK staining under the membrane and relatively weak ALK staining in the cytoplasm could also be observed. RNAseq and RT-PCR further revealed that the tumor harbored an EML4-ALK fusion gene. CONCLUSION: In conclusion, this is the first EIMS demonstrated to have been caused by the formation of an EML4-ALK fusion gene. This enriches the spectrum of EIMS and enlarges the horizon for the study of EIMS. The experience we shared in managing this kind of disease by discussing aspects of its success and failure could be of great value for surgeons and pathologists.

Successful establishment of patient-derived tumor xenografts from gastrointestinal stromal tumor-a single center experience.

Patient-derived tumor xenografts (PDTX) generally represent a kind of more reliable model of human disease, by which a potential drugs' preclinical efficacy could be evaluated. To date, no stable gastrointestinal stromal tumor (GIST) PDTX models have been reported. In this study, we aimed to establish stable GIST PDTX models and to evaluate whether these models accurately reflected the histological feature of the corresponding patient tumors and create a reliable GIST PDTX models for our future experiment. By engrafting fresh patient GIST tissues into immune-compromised mice (BALB/c athymic mice), 4 PDTX models were established. Histological features were assessed by a qualified pathologist based on H&E staining, CD117 and DOG-1. We also conduct whole exome sequencing(WES) for the 4 established GIST PDTX models to test if the model still harbored the same mutation detected in corresponding patient tumors and get a more intensive vision for the genetic profile of the models we have established, which will help a lot for our future experiment. To explore the tumorigenesis mechanism for GIST, we also have a statistical analysis for the genes detected as nonsynchronous-mutated simultaneously in 4 samples. All 4 GIST PDTX models retained the histological features of the corresponding human tumors, with original morphology type and positive stains for CD117 and DOG-1. Between the GIST PDTX models and their parental tumors, a same mutation site was detected, which confirmed the genetic consistency. The stability of molecular profiles observed within the GIST PDTX models provides confidence in the utility and translational significance of these models for in vivo testing of personalized therapies. To date, we conducted the first study to successfully establish a GIST PDTX model whose genetic profiles were revealed by whole exome sequencing. Our experience could be of great use.

Giant retroperitoneal bronchogenic cyst mimicking a cystic teratoma: A case report.

Retroperitoneal bronchogenic cysts (RBCs) are regarded as a rare type of congenital dysplasia disease that stems from the primitive foregut. Thus far, the exact pathogenesis of RBCs remains unknown. Due to an atypical clinical manifestation, RBCs are often incidentally detected and diagnosed by imaging modalities, such as computed tomography and magnetic resonance imaging. However, they are easily misdiagnosed due to their non-specific imaging features. Additionally, the most appropriate treatment strategy for an RBC is considered to be surgical resection. The present study reports the rare case of a 36-year-old female with a large RBC containing fatty fluid that was previously misdiagnosed as liposarcoma or cystic teratoma. Following a complex surgical resection, pathological findings confirmed a diagnosis of RBC. The follow-up examination showed that the patient was in good health at 16 months post-surgery, with no evidence of recurrence. Although rare, bronchogenic cysts must be considered in the differential diagnosis of retroperitoneal teratoma, and surgical resection should be pursued for symptom resolution and to establish a definitive histology.

Expression profile of microRNAs in gastrointestinal stromal tumors revealed by high throughput quantitative RT-PCR microarray.

AIM: To investigate the microRNA (miRNA) expression profile in gastrointestinal stromal tumor (GIST) tissues that could serve as a novel diagnostic biomarker for GIST detection. METHODS: We performed a quantitative real-time quantitative reverse transcriptase polymerase chain reaction assay to analyze the expression of 1888 miRNAs in a sample set that included 54 GIST tissue samples. RESULTS: We found that dysregulation of several miRNAs may be related to the malignant potential of GISTs. Six of these miRNAs, hsa-let-7c, miR-218, miR-488#, miR-4683, miR-34c-5p and miR-4773, were selected as the final list of biomarkers to separate the malignant GISTs (M group) from the benign GISTs (B group). In addition, MiR-29b-2#, hsa-let-7c, miR-891b, miR-218, miR-204, miR-204-3p, miR-628-5p, miR-744, miR-29c#, miR-625 and miR-196a were used to distinguish between the borderline (BO group) and M groups. There were 11 common miRNAs selected to separate the benign and borderline (BB) group from the M group, including hsa-let-7c, miR-218, miR-628-5p, miR-204-3p, miR-204, miR-891b, miR-488#, miR-145, miR-891a, miR-34c-5p and miR-196a. CONCLUSION: The identified miRNAs appear to be novel biomarkers to distinguish malignant from benign GISTs, which may be helpful to understand the mechanisms of GIST oncogenesis and progression, and to further elucidate the characteristics of GIST subtypes.

A novel germline mutation in SDHA identified in a rare case of gastrointestinal stromal tumor complicated with renal cell carcinoma.

Succinate dehydrogenase (SDH), which is located on the mitochondrial inner membrane, is essential to the Krebs cycle. Mutations of the SDH gene are associated with many tumors, such as renal cell carcinoma, wild type gastrointestinal stromal tumors (WT GISTs) and hereditary paragangliomas/pheochromocytomas. Herein we present a rare case diagnosed as a WT GIST complicated with a renal chromophobe cell tumor and detected a novel germline heterozygous mutation (c.2T>C: p.M1T) in the initiation codon of the SDHA gene. We also conduct a preliminary exploration for the mechanism of reduced expression of SDHB without mutation of SDHB gene. Our case enriches the mutation spectrum of the SDH gene. After reviewing previous studies, we found it to be the first case diagnosed as a WT GIST complicated with a synchronous renal chromophobe cell tumor and identified a novel germline heterozygous mutation. It was also the second reported case of a renal cell carcinoma associated with an SDHA mutation.

Long-term survival following total pancreatectomy and superior mesenteric-portal vein resection for pancreatic ductal adenocarcinoma: A case report.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with few therapeutic options. At present, surgical resection remains the only potential curative treatment for PDAC. However, only 15-20% of patients with PDAC are eligible for lesion resection. Total pancreatectomy (TP) and superior mesenteric-portal vein resection (SMPVR) may increase the rate of resection of PDCA, but the effect of this approach on improving long-term patient outcomes remains controversial. The present study investigated a case of PDAC in the pancreatic neck of a male patient. The patient underwent a TP, combined with SMPVR, for a margin-negative resection. Following an uneventful post-operative recovery, the patient received adjuvant chemoradiotherapy. The patient is currently alive at six years post-surgery, with a high quality of life. Given the clinical outcome of this patient, TP combined with SMPVR may provide PDAC patients with an opportunity for long-term survival. Therefore, patients with PDAC that is believed to be unresectable based on pre-operative assessment, may benefit from TP and SMPVR.

Recurrent abdominal liposarcoma: analysis of 19 cases and prognostic factors.

AIM: To evaluate the clinical outcome of re-operation for recurrent abdominal liposarcoma following multidisciplinary team cooperation. METHODS: Nineteen consecutive patients who had recurrent abdominal liposarcoma underwent re-operation by the retroperitoneal sarcoma team at our institution from May 2009 to January 2012. Patient demographic and clinical data were reviewed retrospectively. Multidisciplinary team discussions were held prior to treatment, and re-operation was deemed the best treatment. The categories of the extent of resection were as follows: gross total resection (GTR), palliative resection and partial resection. Surgical techniques were divided into discrete lesion resection and combined contiguous multivisceral resection (CMR). Tumor size was determined as the largest diameter of the specimen. Patients were followed up at approximately 3-monthly intervals. For survival analysis, a univariate analysis was performed using the Kaplan-Meier method, and a multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Nineteen patients with recurrent abdominal liposarcoma (RAL) underwent 32 re-operations at our institute. A total of 51 operations were reviewed with a total follow-up time ranging from 4 to 120 (47.4 ± 34.2) mo. The GTR rate in the CMR group was higher than that in the non-CMR group (P = 0.034). CMR was positively correlated with intra-operative bleeding (correlation coefficient = 0.514, P = 0.010). Six cases with severe postoperative complications were recorded. Patients with tumor sizes greater than 20 cm carried a significant risk of profuse intra-operative bleeding (P = 0.009). The ratio of a highly malignant subtype (dedifferentiated or pleomorphic) in recurrent cases was higher compared to primary cases (P = 0.027). Both single-factor survival using the Kaplan-Meier model and multivariate analysis using the Cox proportional hazards model showed that overall survival was correlated with resection extent and pathological subtype (P < 0.001 and P = 0.02), however, relapse-free interval (RFI) was only correlated with resection extent (P = 0.002). CONCLUSION: Close follow-up should be conducted in patients with RAL. Early re-operation for relapse is preferred and gross resection most likely prolongs the RFI.