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2.
Anal Chem ; 2024 May 29.
Article En | MEDLINE | ID: mdl-38810149

The retroperitoneal liposarcoma (RLPS) is a rare malignancy whose only curative therapy is surgical resection. However, well-differentiated liposarcomas (WDLPSs), one of its most common types, can hardly be distinguished from normal fat during operation without an effective margin assessment method, jeopardizing the prognosis severely with a high recurrence risk. Here, we combined dual label-free nonlinear optical modalities, stimulated Raman scattering (SRS) microscopy and second harmonic generation (SHG) microscopy, to image two predominant tissue biomolecules, lipids and collagen fibers, in 35 RLPSs and 34 normal fat samples collected from 35 patients. The produced dual-modal tissue images were used for RLPS diagnosis based on deep learning. Dramatically decreasing lipids and increasing collagen fibers during tumor progression were reflected. A ResNeXt101-based model achieved 94.7% overall accuracy and 0.987 mean area under the ROC curve (AUC) in differentiating among normal fat, WDLPSs, and dedifferentiated liposarcomas (DDLPSs). In particular, WDLPSs were detected with 94.1% precision and 84.6% sensitivity superior to existing methods. The ablation experiment showed that such performance was attributed to both SRS and SHG microscopies, which increased the sensitivity of recognizing WDLPS by 16.0 and 3.6%, respectively. Furthermore, we utilized this model on RLPS margins to identify the tumor infiltration. Our method holds great potential for accurate intraoperative liposarcoma detection.

3.
Abdom Radiol (NY) ; 49(3): 958-963, 2024 Mar.
Article En | MEDLINE | ID: mdl-38245900

PURPOSE: Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. METHODS: The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. RESULTS: The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). CONCLUSION: Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.


Fibromatosis, Aggressive , Fluorodeoxyglucose F18 , Humans , Positron Emission Tomography Computed Tomography , Fibromatosis, Aggressive/diagnostic imaging , Fibromatosis, Aggressive/therapy , Watchful Waiting , Neoplasm Recurrence, Local/diagnostic imaging , Prognosis , Tumor Burden , Retrospective Studies , Radiopharmaceuticals
4.
BMC Med Imaging ; 23(1): 215, 2023 12 18.
Article En | MEDLINE | ID: mdl-38110909

PURPOSE: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. METHODS: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. RESULTS: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). CONCLUSIONS: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.


Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Humans , Retrospective Studies , Prognosis , Tumor Burden , Radiopharmaceuticals
5.
Ann Med ; 55(2): 2242247, 2023.
Article En | MEDLINE | ID: mdl-37544888

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant solid tumours, and abnormal metabolic reprogramming in the tumour microenvironment is regarded as an important contributor to its pathogenesis. OBJECTIVES: As there is an urgency to identify new targets based on the metabolic features that are highly refractory to PDAC treatment, this study aimed to identify suitable therapeutic targets for PDAC. METHODS: In this study, gene set enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were performed on 163 PDAC tissue samples and 165 normal pancreatic tissue samples from The Cancer Genome Atlas and Genotype-Tissue Expression databases to identify alterations in critical metabolites that may contribute to PDAC pathogenesis. Furthermore, ultra-performance liquid chromatography-tandem mass spectrometry was performed to identify significant metabolic pathways between 24 pairs of tumour and adjacent non-tumour tissues and between serum samples from PDAC patients and healthy donors. RESULTS: Fifty-one tissue metabolites and 26 serum metabolites were altered in PDAC. Among them, those in the γ-glutamyl cycle were the most substantially changed, and 5-oxoproline was the biomarker of PDAC with the most significantly decreased levels. CONCLUSIONS: The γ-glutamyl cycle and 5-oxoproline might be potential biomarkers and therapeutic targets to improve the diagnosis, therapy, and prognosis of PDAC.


Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pyrrolidonecarboxylic Acid , Biomarkers, Tumor , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Tumor Microenvironment , Pancreatic Neoplasms
6.
BMC Surg ; 23(1): 189, 2023 Jul 04.
Article En | MEDLINE | ID: mdl-37403109

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Distant metastasis has been detected in approximately 50% of GIST patients at the first diagnosis. The surgical strategy for metastatic GIST with generalized progression (GP) after imatinib therapy remains unclear. METHODS: We recruited 15 patients with imatinib-resistant metastatic GIST. They received cytoreductive surgery (CRS) for tumor rupture, intestinal obstruction and gastrointestinal bleeding. We collected clinical, pathological and prognostic data for analyses. RESULTS: OS and PFS after R0/1 CRS were 56.88 ± 3.47 and 26.7 ± 4.12 months, respectively, when compared with 26 ± 5.35 and 5 ± 2.78 months after R2 CRS (P = 0.002 and P < 0.001, respectively). The OS of patients from the initiation of imatinib in the R0/1 group was 133.90 ± 15.40 months when compared with 59.80 ± 10.98 months in the R2 CRS group. There were two significant grade III complications after 15 operations (13.3%). No patient underwent reoperation. In addition, no perioperative death occurred. CONCLUSIONS: R0/1 CRS is highly probable to provide prognostic benefits for patients with metastatic GIST who experience GP following imatinib treatment. An aggressive surgical strategy for achieving R0/1 CRS can be deemed safe. If applicable, R0/1 CRS should be carefully considered in imatinib-treated patients with GP metastatic GIST.


Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Humans , Imatinib Mesylate/therapeutic use , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Prognosis , Retrospective Studies , Antineoplastic Agents/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/surgery , Gastrointestinal Neoplasms/diagnosis , Cytoreduction Surgical Procedures
7.
Ann Transl Med ; 11(5): 212, 2023 Mar 15.
Article En | MEDLINE | ID: mdl-37007540

Background: Conventional chemotherapy has limited therapeutic effects in retroperitoneal soft tissue sarcomas (RSTs), while anlotinib emerged as a novel multi-target tyrosine kinase inhibitor (TKI) for sarcomas. TKIs in combination with immunotherapy have demonstrated clinical activity in a variety of solid tumors. This study retrospectively analyzed the efficacy and safety of anlotinib plus camrelizumab for the treatment of RSTs. Methods: Patients with RSTs who received anlotinib plus camrelizumab at Peking University Cancer Hospital Sarcoma Center were enrolled. Response assessment was conducted every 3 cycles of treatment according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Treatment-related adverse events (TRAEs) were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patients who had at least 1 response evaluation were analyzed. Results: In all, 57 RSTs cases including 35 males and 22 females were analyzed, with a median age of 55 years. The pathological subtypes included 38 cases of L-sarcoma (liposarcoma and leiomyosarcoma), and 19 cases of non-L-sarcoma. Two patients (3.5%) had complete response (CR) and 13 patients (22.8%) had partial response (PR), with an objective response rate (ORR) of 26.3%. There were 31 (54.4%) and 11 (19.3%) patients with stable and progressive disease, respectively, with a disease control rate of 80.7%. Patients with non-L-sarcoma had a significantly better response rate than those with L-sarcoma (ORR: 52.6% vs. 13.2%; P=0.0031). After a median follow-up of 15.8 months, the median progression-free survival (PFS) was 9.1 months, with 3- and 6-month PFS rates of 83.6% and 60.8%, respectively. Patients with non-L-sarcoma had a significantly longer median PFS than did those with L-sarcoma (median PFS: 11.1 vs. 6.3 months; P=0.0256). TRAEs occurred in 28 (49.1%) patients, and 13 (22.8%) patients had grade 3-4 TRAEs. Hypertension (24.6%), hypothyroidism (19.3%), and palmar-plantar erythrodysesthesia syndrome (12.3%) were the most common TRAEs. Conclusions: The combination of anlotinib and camrelizumab demonstrated possible therapeutic efficacy and safety in the treatment of RSTs, especially for non-L-sarcomas.

8.
J Surg Oncol ; 127(4): 633-644, 2023 Mar.
Article En | MEDLINE | ID: mdl-36444482

BACKGROUND AND OBJECTIVES: Resection of retroperitoneal sarcoma (RPS) en bloc with pancreas is challenging and controversial. This single-center retrospective study aimed to analyze the impact of pancreatic resection (PR) and its different types on short- and long-term outcomes in patients with RPS. METHODS: Data from 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were analyzed. Out of these, 90 patients underwent PR, including pancreaticoduodenectomy (PD) in 31 and distal pancreatectomy (DP) in 59. RESULTS: Patients in the PR group had a higher major morbidity (37.8% vs. 14.5%) and mortality (8.9% vs. 1.3%) than those in the non-PR group, with a similar 5-year overall survival (OS) rate (46.9% vs. 53.6%). Patients in the PD and DP groups had a slight difference in major morbidity (48.4% vs. 32.2%), mortality (6.4% vs. 10.2%), and 5-year OS rates (43.3% vs. 49.3%). The PR type was not an independent risk factor for major morbidity or OS. CONCLUSIONS: PR in RPS resection was associated with increased morbidity and mortality with minimal influence on survival. Patients with RPS undergoing PD and DP showed slight differences in terms of safety and OS.


Pancreatic Neoplasms , Retroperitoneal Neoplasms , Sarcoma , Humans , Pancreatectomy , Retrospective Studies , Sarcoma/surgery , Retroperitoneal Neoplasms/surgery , Treatment Outcome , Pancreatic Neoplasms/surgery
9.
Int J Med Sci ; 19(13): 1977-1988, 2022.
Article En | MEDLINE | ID: mdl-36438917

Purpose: Retroperitoneal liposarcoma (RLPS) is a rare malignancy without effective treatment. Since current treatment for unresectable RLPS is unsatisfactory, immunotherapy and targeted therapy are urgently needed. Siglec-15 is a transmembrane protein highly homologous to PD-L1 and is involved in tumor immune escape. The biological function of Siglec-15 in RLPS, its prognostic relevance and its relationship with PD-L1 need to be further clarified. In this study, we aimed to explore the biological function of Siglec-15 in sarcomas through bioinformatics analysis, and we also evaluated Siglec-15 and PD-L1 expression in RLPS samples. The relationship between the expression of Siglec-15 and PD-L1 and their clinicopathological relevance and prognostic value were also investigated in clinical RLPS patients. Methods: The RNA sequencing data of 259 sarcoma cases and 48 RLPS cases from TCGA were used to analyze the Siglec-15 expression and the differentially expressed genes (DEG) related with Siglec-15 expression. In addition, DEGs were subsequently analyzed through the gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. Tumor specimens were obtained from 91 RLPS patients of our sarcoma center, and Siglec-15 and PD-L1 expression were evaluated using immunohistochemistry. The correlation between the expression level of these two markers as well as their correlation with clinicopathological factors and prognosis of RLPS patients was also assessed. Results: GEPIA analysis showed that the high expression of Siglec-15 was associated with poor sarcoma OS (P=0.034). A total of 682 differential genes were identified between the high and low expression groups of Siglec-15 in RLPS. Enrichment analysis of the KEGG pathway showed that Siglec-15 was related to the Hippo signaling pathway and the neuroactive ligand-receptor interaction. GO annotation analysis showed that the expression of Siglec-15 may thus be able to affect serine hydrolase activity, alongside signal receptor activator activity. The top 5 genes with the largest number of connection points are APOA1, F2, AHSG, AMBP, SERPINC1. In subsequent studies, we used 91 liposarcoma samples from our center for verification. Siglec-15 was expressed in 84.6% of RLPS cases, whereas PD-L1 was expressed in 17.6% of RLPS cases. A negative correlation was observed between Siglec-15 and PD-L1 expression (P=0.020). In this group of RLPS patients, high Siglec-15 expression was correlated with poorer disease-free survival (DFS) (P=0.021), and it was an independent predictor of DFS (hazard ratio: 2.298; 95% confidence interval: 1.154-4.576; P=0.018). However, we did not find a correlation between PD-L1 expression and overall survival or DFS in RLPS patients. Conclusion: The DEG and signaling pathways identified in the study could provide a preliminary understanding of the underlying molecular mechanisms of Siglec-15 in the development and progression of RLPS. High expression of Siglec-15 was a negative independent predictive factor for DFS of RLPS. The negative relationship between Siglec-15 and PD-L1 expression suggested that the Siglec-15 pathway might be an important supplement to PD-L1 treatment.


Liposarcoma , Retroperitoneal Neoplasms , Sialic Acid Binding Immunoglobulin-like Lectins , Humans , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Computational Biology , Liposarcoma/genetics , Liposarcoma/metabolism , Sarcoma/genetics , Sarcoma/metabolism , Sialic Acid Binding Immunoglobulin-like Lectins/genetics , Sialic Acid Binding Immunoglobulin-like Lectins/metabolism , Retroperitoneal Neoplasms/genetics , Retroperitoneal Neoplasms/metabolism
10.
Int J Med Sci ; 19(8): 1241-1253, 2022.
Article En | MEDLINE | ID: mdl-35928724

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas. It is characterized by poor sensitivity to radiotherapy and chemotherapy and a low success rate of complete surgical resection. However, there are few reliable preclinical RLPS models for target discovery and therapy research. In this study, we aimed to establish RLPS patient-derived xenograft (PDX) models that are useful for biological research and preclinical drug trials. A total of 56 freshly resected RLPS tissues were subcutaneously transplanted into non-obese diabetic-severe combined immune deficient (NOD-SCID) mice, with subsequent xenotransplantation into second-generation mice. The tumor engraftment rate of first generation PDXs was 44.64%, and higher success rates were obtained from implantations of dedifferentiated, myxous, pleomorphic, high-grade liposarcomas and those with retroperitoneal organ infiltration. The first- and second- generation PDX models preserved the histopathological morphology, gene mutation profiles and MDM2 amplification of the primary tissues. PDX models can also provide the benefit of retaining original tumor biology and microenvironment characteristics, such as abnormal adipose differentiation, elevated Ki67 levels, high microvessel density, cancer-associated fibroblast presence, and tumor-associated macrophage infiltration. Overall survival (OS) and disease-free survival (DFS) of patients with successful first-generation PDX engraftment were significantly poorer than those with failed engraftment. Treatment with MDM2 inhibitor RG7112 significantly suppressed tumor growth of DDLPS PDX in mice. In conclusion, we successfully established RLPS PDX models that were histologically, genetically, and molecularly consistent with the original tissues. These models might provide opportunities for advancing RLPS tumor biology research, facilitating the development of novel drugs, particularly those targeting MDM2 amplification, adipose differentiation process, angiogenesis, cancer-associated fibroblasts, and so on.


Liposarcoma , Animals , Disease Models, Animal , Heterografts , Humans , Liposarcoma/genetics , Mice , Mice, Inbred NOD , Mice, SCID , Retroperitoneal Neoplasms , Tumor Microenvironment , Xenograft Model Antitumor Assays
11.
Int J Biol Sci ; 18(13): 5038-5055, 2022.
Article En | MEDLINE | ID: mdl-35982904

Retroperitoneal liposarcoma (RLPS) is the most common subtype of retroperitoneal soft tissue sarcoma, characterized by a high recurrence rate and insensitivity to radiotherapy and chemotherapy. The function of tumor microenvironmental components, especially tumor-associated fibroblasts (TAFs), remains unclear in RLPS. The crosstalk between tumor cells and stromal cells should be clarified for therapy target discovery in RLPS. In this study, we demonstrated that TAFs from dedifferentiated liposarcoma (DDLPS) could attract LPS cells and promote their proliferation and migration. However, although α-SMA is positively expressed in RLPS, its expression does not indicate prognosis. By screening differentially expressed genes, performing Oncomine visualization, TCGA gene expression correlation analysis and qPCR verification, we determined that thrombospondin-2 (THBS2) gene expression was related to TAFs. The expression of Tsp2 protein, which was encoded by THBS2, was correlated with α-SMA expression, and it was an independent predictive factor for disease-free survival and recurrence-free survival in patients with RLPS. In vitro, Tsp2 facilitated the transformation of bone marrow-derived fibroblasts (BMFs) to TAFs and promoted the malignant biological behaviors of LPS cells by activating the MAPK/MEK/ERK pathway. Therefore, suppression of Tsp2 is expected to be a promising treatment method for RLPS patients.


Cancer-Associated Fibroblasts , Liposarcoma , Thrombospondins , Cancer-Associated Fibroblasts/pathology , Humans , Liposarcoma/genetics , Liposarcoma/pathology , Retroperitoneal Neoplasms , Thrombospondins/genetics
12.
Pancreatology ; 22(1): 112-122, 2022 Jan.
Article En | MEDLINE | ID: mdl-34764022

BACKGROUND: Whether coeliac axis resection (CAR) results from tumour topography or a prognostic factor for distal pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to compare the clinicopathological data between distal pancreatectomy with en bloc CAR (DP-CAR) and distal pancreatectomy plus splenectomy (DP-S) and analyse the prognostic factors. METHODS: We retrospectively analysed clinicopathological data from 102 patients who underwent distal pancreatectomy for PDAC and the factors affecting disease-free survival (DFS) and overall survival (OS). Of these patients, 45 and 57 underwent DP-CAR and DP-S, respectively. RESULTS: DP-CAR was associated with more operative challenges than DP-S: more portomesenteric vein resections (48.9% vs. 14.0%), longer operations (320 vs. 242 min), and greater estimated blood loss (EBL) (600 vs. 200 ml). DP-CAR had larger tumours (5 vs. 4 cm), more perineural invasion (91.1% vs. 73.7%), and more microscopically positive surgical margins (20% vs. 3.5%), compared to DP-S. The major complication was clinically relevant postoperative pancreatic fistula (20.6%). The median DFS was 15.8 months and the median OS was 20.1 months. CAR was not associated with DFS or OS. EBL>700 ml, lymphovascular invasion (LVI), and adjuvant chemotherapy independently affected DFS and OS. CONCLUSION: DP-CAR was associated with larger tumours and more surgical challenges but not with poorer DFS and OS than DP-S. CAR was more likely to result from tumour topography rather than from an adverse prognostic factor for resected distal PDAC. EBL>700 ml, LVI, and adjuvant chemotherapy were independent factors affecting the survival of patients with distal PDAC who underwent surgical resection.


Carcinoma, Pancreatic Ductal/surgery , Celiac Artery/surgery , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Splenectomy , Aged , Carcinoma, Pancreatic Ductal/pathology , Celiac Artery/pathology , Chemotherapy, Adjuvant , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Postoperative Complications , Prognosis , Retrospective Studies , Pancreatic Neoplasms
13.
Front Oncol ; 12: 1040833, 2022.
Article En | MEDLINE | ID: mdl-36620578

Background: Retroperitoneal sarcomas (RPSs) located in the lower abdominal quadrants involving iliac vessels are difficult to manage. This study introduced a 5-step method for en bloc resection with graft interposition using the abdominoinguinal approach and evaluated its efficacy and safety. Methods: Data of 24 consecutive patients who met the inclusion criteria from 272 patients with RPS who underwent surgical treatment between April 2015 and April 2022 were retrospectively collected and analyzed. Results: The patients underwent left- or right-sided abdominoinguinal incision. In all patients, the abdominoinguinal approach provided good exposure, and complete resection was achieved. Iliac artery+vein, vein, and artery resection and replacement by graft were performed in 70.8%, 25.0%, and 4.2% of patients, respectively. Additional resected organs mainly included the colon, ureter, bladder, kidney, and abdominal wall. The median number of organs resected was 5. In 37.5% of patients, reconstruction of the lower abdominal wall and inguinal ligament was performed using a mesh. Venous graft thrombosis occurred in 21.7% of patients, while no patient had pulmonary embolism or arterial occlusion. Major complications occurred in 20.8% of patients, and no 30-day mortality was observed. The estimated 5-year local recurrence and distant metastasis rates were 54.4% and 22.1%, respectively, with a median recurrence-free survival of 27 months. Conclusions: En bloc resection of RPS involving iliac vessels with graft interposition using the abdominoinguinal approach is feasible and advantageous. Good complete resection rate and safety can be achieved. The long-term survival benefit of this surgical approach should be verified by further large-scale prospective controlled studies.

14.
Front Oncol ; 11: 739139, 2021.
Article En | MEDLINE | ID: mdl-34868934

BACKGROUND: Primary retroperitoneal liposarcomas (RLPSs) are rare heterogeneous tumors for which there are few effective therapies. Certain anti-angiogenic tyrosine kinase inhibitors have demonstrated efficacy against various solid tumors. The aims of this study were to investigate the effect of Apatinib against retroperitoneal liposarcoma cells and its underlying mechanism and to explore the anti-tumor efficacy of a combination of Apatinib and Epirubicin. METHODS: CD34 immunohistochemical staining was used to measure microvessel density (MVD) in 89 retroperitoneal liposarcoma tissues. We used CCK-8 cell proliferation, clone formation, Transwell migration, invasion assays and flow cytometry to evaluate the effects of Apatinib alone and the combination of Apatinib and Epirubicin on liposarcoma cells. High-throughput RNA sequencing and western-blotting was used to identify key differentially expressed genes (DEGs) in SW872 cell line after application of Apatinib. Murine patient-derived tumor xenograft (PDX) was established to assess the efficacy and safety of Apatinib monotherapy and the combination of Apatinib and Epirubicin in RLPS. RESULTS: The microvessel density (MVD) varied widely among retroperitoneal liposarcoma tissues. Compared with the low-MVD group, the high-MVD group had poorer overall survival. Apatinib inhibited the liposarcoma cell proliferation, invasion and migration, increased the proportion of apoptosis, and induced G1 phase arrest. In addition, the combination of Apatinib and Epirubicin enhanced the foregoing inhibitory effects. High-throughput RNA sequencing showed that Apatinib downregulated the expression of TYMS and RRM2. Western blotting verified that Apatinib downregulated the TYMS/STAT3/PD-L1 pathway and inhibited liposarcoma proliferation by suppressing the RRM2/PI3K/AKT/mTOR pathway. In the murine PDX model of retroperitoneal liposarcoma, Apatinib and its combination with Epirubicin significantly inhibited microvessel formation and repressed tumor growth safely and effectively. CONCLUSIONS: Apatinib and its combination with Epirubicin showed strong efficacy against liposarcoma both in vitro and in vivo. Apatinib might inhibit liposarcoma cell proliferation through the RRM2/PI3K/AKT/mTOR signaling pathway and downregulate PD-L1 via the TYMS/STAT3 signaling pathway.

15.
Contrast Media Mol Imaging ; 2021: 7191363, 2021.
Article En | MEDLINE | ID: mdl-33505228

This study aimed to evaluate the usefulness of maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) in differentiating the subtypes and tumor grades of retroperitoneal liposarcoma (RPLS). The data of RPLS patients who underwent surgical resection from November 2013 to December 2019 at the sarcoma center of our institute were reviewed. The demographics, clinical features, and SUVmax of 84 patients who underwent preoperative 18F-FDG PET/CT scans were analyzed. Of these, 19 patients (22.6%) were with well-differentiated liposarcoma (WDLPS), 60 patients (71.4%) were with dedifferentiated liposarcoma (DDLPS), and 5 patients (6.0%) were with pleomorphic liposarcoma (PMLPS). The median SUVmax of WDLPS, DDLPS, and PMLPS groups was 2.8 (IQR: 1.9-3.2), 6.2 (IQR: 4.1-11.3), and 4.5 (IQR: 4.0-7.4). The ROC curve suggested 3.8 as an approximate cutoff value of SUVmax for distinguishing WDLPS and non-WDLPS (sensitivity = 0.769; specificity = 0.895). The median SUVmax for FNCLCC Grades 1, 2, and 3 of RPLS was 2.5 (IQR: 1.9-3.2), 4.5 (IQR: 3.2-6.7), and 9.0 (IQR: 6.0-13.3). The ROC curves suggest that SUVmax of ≤3.8 and >5.3 can be used for predicting FNCLCC Grades 1 and 3, respectively. The result showed that 18F-FDG PET/CT exhibited high sensitivity and specificity for identifying the subtypes and FNCLCC grades of RPLS. Additionally, 18F-FDG PET/CT might be a useful complementary imaging modality for guiding suitable biopsy location of RPLS.


Liposarcoma/diagnostic imaging , Positron Emission Tomography Computed Tomography , Retroperitoneal Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Fluorodeoxyglucose F18/administration & dosage , Humans , Liposarcoma/diagnosis , Liposarcoma/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Radiopharmaceuticals/administration & dosage , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/pathology
16.
Front Oncol ; 10: 548789, 2020.
Article En | MEDLINE | ID: mdl-33072576

BACKGROUND: En bloc resection of retroperitoneal sarcoma (RPS) with adjacent organs such as pancreatic head and duodenum is challenging for surgeons. This mono-institutional study aims to evaluate the feasibility, safety, and outcome of performing pancreaticoduodenectomy (PD) during RPS resection. METHODS: The clinical data of RPS patients who underwent PD at the Sarcoma Center of Peking University Cancer Hospital from January 2011 to December 2019 was collected and analyzed. RESULTS: Twenty-seven patients out of a total of 264 surgically treated RPS underwent PD. The main pathological subtype was liposarcoma. All patients received concomitant resection of a median of three additional organs (range: 1-5), including 11 patients (40.7%) who underwent inferior vena cava resection and one patient who underwent segmental superior mesenteric-portal vein resection. Microscopic tumor infiltration to the duodenum or pancreas was observed in 81.5% of patients. Major complications occurred in 40.7% of patients; the reoperation rate was 22.2%. One patient (3.7%) died from liver abscess postoperatively. During a median follow-up of 18.9 months, 15 patients (55.6%) developed locally recurrent disease; two patients (7.4%) also had pulmonary metastases additionally. Twelve patients (44.4%) died from local relapse eventually. CONCLUSION: PD during RPS resection is feasible, and it may be necessary to achieve complete resection. However, considering the complexity and risk, it should be performed by an experienced surgical team. The long-term survival benefit of this procedure should be verified by further large-scale multi-institutional studies.

17.
Contrast Media Mol Imaging ; 2018: 2601281, 2018.
Article En | MEDLINE | ID: mdl-30065620

Rationale: To assess the diagnostic value of 18F-FDG-PET/CT for different retroperitoneal soft tissue sarcomas (STS) and other similar tumors. To analyze the predictive value of 18F-FDG-PET/CT for histological grade and main prognostic factors. Methods: 195 patients with 44 different diseases have been included. Relationship between SUVmax, Clinical, pathological, and prognostic information has been analyzed. Results: Malignant tumors do not show higher SUVmax than benign ones (P=0.443). We divided all 44 different diseases into two groups; SUVmax of group 1 is significantly higher than group 2 (P ≤ 0.001). The ROC curve suggests 4.35 is the cutoff value to distinguish groups 1 and 2 (sensitivity = 0.789; specificity = 0.736). SUVmax correlates with Ki-67 index, mitotic count, vascular resection, histological grade, and recurrent STS without considering pathological diagnosis (P=0.001, P=0.012, P=0.002, P ≤ 0.001, and P=0.037, resp.). Conclusion: 18F-FDG-PET/CT cannot simply distinguish malignant and benign tumors in retroperitoneal/intra-abdominal cavity; however, the SUVmax of malignant tumors, inflammatory pseudotumor, and PPGL group is higher than the SUVmax of benign tumors, lymph node metastasis, hematoma, and low malignant STS group. Guidance of "SUVmax location" may be helpful for biopsy and pathology dissection.


Abdominal Cavity/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Retroperitoneal Neoplasms/diagnostic imaging , Sarcoma/diagnostic imaging , Abdominal Cavity/pathology , Diagnosis, Differential , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Ki-67 Antigen/analysis , Prognosis , Sensitivity and Specificity
18.
Oncotarget ; 8(5): 7766-7776, 2017 Jan 31.
Article En | MEDLINE | ID: mdl-27999192

The aim of this study is trying to describe more details of superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, to evaluate biological and prognostic implications of tumor budding in this margin, and to provide more evidence for evaluation of R0 surgery in pancreaticoduodenectomy. 46 patients in 5-years period are included in this study. Immunochemistry and immunofluorescence are used to analyze tumor budding and epithelial-mesenchymal transition. Superior mesenteric artery margin might be described from four aspects including location, gross appearance, microscopic appearance and tumor budding. We find that 1mm rule for R1 surgery is more appropriate to predict prognosis (P = 0.009) than 0mm rule (P = 0.141). Expression of cytokeratin in tumor budding is significantly lower than primary tumor (P = 0.001), and it suggests that tumor budding may participate the procedure of epithelial-mesenchymal transition. High-grade tumor budding and decreasing cytokeratin of tumor budding correlate with distant metastasis and has negative influence on prognosis. So superior mesenteric artery margin might be not only an area that tumor cells may invade, but also a pathway for distant metastasis. It is necessary to evaluate superior mesenteric artery margin in pancreaticoduodenectomy for pancreatic cancer.


Carcinoma, Pancreatic Ductal/surgery , Mesenteric Artery, Superior/surgery , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Aged , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/secondary , Cell Movement , Disease Progression , Disease-Free Survival , Epithelial-Mesenchymal Transition , Female , Humans , Kaplan-Meier Estimate , Male , Margins of Excision , Mesenteric Artery, Superior/pathology , Middle Aged , Neoplasm Invasiveness , Neoplasm, Residual , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/mortality , Risk Factors , Time Factors , Treatment Outcome
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