Case Report: Low-Dose Apatinib in the Treatment of Intrahepatic Biliary Cystadenoma With Recurrence and Malignant Transformation.
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SUBMITTER: Yang Y
PROVIDER: S-EPMC8273731 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBiliary cystadenoma is a rare cystic neoplasm of the liver. The clinical signs and symptoms are nonspecific, and treatment strategy is variable.Case presentationIn this study, we presented a case of a 32-year-old female with multilocular biliary cystadenoma. The patient underwent partial removal of the hepatic cyst two times in two different hospitals for two years and that the histopathological results were biliary cystic adenoma but was successfully treated by radical resection after the second recurrence. The patient underwent a J-shaped laparotomy. The giant cystic mass measuring 20 cm × 15 cm was below the position of the right anterior segment. This lesion pushed the liver parenchyma to both sides and compressed the hepatic hilum, causing dilatation of the intrahepatic bile ducts. The patient underwent complete resection of cystic mass. During the dissection, a 0.5mm-diameter fistula of left hepatic duct with the cyst was found. It was sutured using absorbable polydioxanone (PDS 6.0) and the cystic duct tube (C tube) (6 Fr) was inserted via the cystic duct into the left hepatic duct due to drain the bile fluid.DiscussionA biliary cystadenoma (BCA) primary origin is occasionally rare. Although imaging modalities such as ultrasound, computed tomography and magnetic resonance imaging could be suggestive, however, the definitive diagnosis is depended on the histological examination. Despite of being a benign tumor, it has a high risk of recurrence after conservative treatment. The potential risk for malignant is also present. Therefore, complete resection of the tumors is the treatment of choice.ConclusionWe herein present a report of a rare case with had a giant biliary cystadenoma (BCA) primary origin. This report aims to improve the understanding of the diagnosis and management of this uncommon disease.
| S-EPMC9207045 | biostudies-literature
Project description:Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.
| S-EPMC4871351 | biostudies-literature
Project description:Biliary enteric anastomosis for relief of biliary obstruction caused by malignancy at the confluence of the bile ducts can be difficult due to non availability of an adequate length of duct for anastomosis. This paper describes an approach to the left hepatic duct to decompress the biliary tree and its successful application in 11 of 12 patients who presented with malignant hilar obstruction.
| S-EPMC5531209 | biostudies-other
Project description:BackgroundClonorchis sinensis granulin (CsGRN), a component of the excretory/secretory products of this species, is a multifunctional growth factor that can promote the metastasis of cholangiocarcinoma cells. However, the effect of CsGRN on human intrahepatic biliary epithelial cells (HIBECs) is unclear. Here, we investigated the effect of CsGRN on the malignant transformation of HIBECs and its possible underlying mechanism.MethodsThe malignant transformation phenotypes of HIBECs after CsGRN treatment were estimated by EdU-488 incorporation assay, colony formation assay, wound-healing assay, Transwell assay and western blot. The biliary damage of CsGRN-treated mice was detected by western blot, immunohistochemical staining and hematoxylin and eosin staining. The phenotypes of the macrophages [human monocytic leukemia cell line (THP-1)] were analyzed by flow cytometry, immunofluorescence and immunohistochemistry, both in vitro and in vivo. A co-culture system was developed to explore the interaction between THP-1 and HIBECs in CsGRN-containing medium. Enzyme-linked immunosorbent assay and western blot were used to detected the activation of interleukin 6 (IL-6), phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. An inhibitor of the MEK/ERK pathway, PD98059, was used to determine whether this pathway is involved in CsGRN-mediated cell interactions as well as in STAT3 phosphorylation and malignant transformation of HIBECs.ResultsExcessive hyperplasia and abnormal proliferation of HIBECs, enhanced secretion of hepatic pro-inflammatory cytokines and chemokines, as well as biliary damage, were observed in vitro and in vivo after treatment with CsGRN. The expression of the markers of M2 macrophages significantly increased in CsGRN-treated THP-1 cells and biliary duct tissues compared with the controls. Moreover, following treatment with CsGRN, the HIBECs underwent malignant transformation in the THP-1-HIBECs co-culture group. In addition, high expression of IL-6 was observed in the CsGRN-treated co-culture media, which activated the phosphorylation of STAT3, JAK2, MEK and ERK. However, treatment with an inhibitor of the MEK/ERK pathway, PD98059, decreased expression of p-STAT3 in CsGRN-treated HIBECs and further repressed the malignant transformation of HIBECs.ConclusionsOur results demonstrated that, by inducing the M2-type polarization of macrophages and activating the IL-6/JAK2/STAT3 and MEK/ERK pathways in HIBECs, CsGRN promoted the malignant transformation of the latter.
| S-EPMC10124682 | biostudies-literature
Project description:BackgroundFraser syndrome or "cryptophthalmos syndrome" is a rare autosomal recessive disease. It is characterized by a group of congenital malformations such as: crytophthalmos, syndactyly, abnormal genitalia, and malformations of the nose, ears, and larynx. Although cryptophthalmos is considered as a main feature of Fraser syndrome, its absence does not exclude the diagnosis. Clinical diagnosis can be made by Thomas Criteria. Here we present the first documented case of Fraser Syndrome in Aleppo, Syria that is characterized by bilateral anophthalmia and intrahepatic biliary atresia.Case presentationDuring pregnancy, several ultrasound scans revealed hyperechoic lungs, ascites, and unremarkable right kidney at the 19th-week visit; bilateral syndactyly on both hands and feet at the 32nd-week visit. On the 39th week of gestation, the stillborn was delivered by cesarean section due to cephalopelvic disproportion. Gross examination showed bilateral anophthalmia, bilateral syndactyly on hands and feet, low set ears, and ambiguous genitalia. Microscopic examination of the lung, spleen, liver, ovary, and kidneys revealed abnormalities in these organs.ConclusionThe diagnosis of Fraser syndrome can be made prenatally and postnatally; prenatally by ultrasound at 18 weeks of gestation and postnatally by clinical examination using Thomas criteria. Moreover, intrahepatic biliary atresia was not described previously with Fraser syndrome; this recommends a more detailed pathologic study for Fraser syndrome cases.
| S-EPMC7288532 | biostudies-literature
Project description:Tumor cells co-express vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) that interact each other to support a self-sustainable cell growth. So far, this autocrine VEGF loop is not reported in human intrahepatic cholangiocarcinoma (ICC). Apatinib is a highly selective VEGFR2 inhibitor, but its effects on ICC have not been investigated. In this study, we reported that VEGF and phosphorylated VEGFR2 were expressed at a significantly high level in ICC patient tissues (P<0.05). In vitro, treating ICC cell lines RBE and SSP25 with recombinant human VEGF (rhVEGF) induced phosphorylation of VEGFR1 (pVEGFR1) and VEGFR2 (pVEGFR2); however, only the VEGFR2 played a role in the anti-apoptotic cell growth through activating a PI3K-AKT-mTOR anti-apoptotic signaling pathway which generated more VEGF to enter this autocrine loop. Apatinib inhibited the anti-apoptosis induced by VEGF signaling, and promoted cell death in vitro. In addition, Apatinib treatment delayed xenograft tumor growth in vivo. In conclusion, the autocrine VEGF/VEGFR2 signaling promotes ICC cell survival. Apatinib inhibits anti-apoptotic cell growth through suppressing the autocrine VEGF signaling, supporting a potential role for using Apatinib in the treatment of ICC.
| S-EPMC4941382 | biostudies-literature
Project description:BackgroundExtrapelvic endometriosis is defined as the presence of ectopic endometrial tissue in structures outside the pelvis. Although extra-pelvic endometriosis is generally considered benign conditions, malignant potential within endometriotic foci occurs even after definitive surgery. Malignant transformation of hepatic endometriosis is extremely rare. Preoperative diagnosis of this cancer is difficult, and no guidelines on the optimal management currently exist. Here, we present a case report of malignant transformation of hepatic endometriosis and a brief literature review to highlight the current knowledge of the prevalence, clinical features, diagnosis, and management of this condition.Case presentationA 50-year-old woman with a 2-year duration of progressive right upper quadrant abdominal pain was admitted to the hospital. She underwent hysterectomy and bilateral salpingo-oophorectomy for benign conditions 4 years prior. Tumor markers demonstrated elevated carbohydrate antigen (CA)-199 112U/mL (normal range: 0-35U/mL) only. Radiological imaging suggested the presence of a 10.7 × 7.7-cm mass in the right lobe of the liver extending to the diaphragm. The intraoperative frozen sections suggested malignant tumor. Right hepatectomy with infiltrating diaphragm resection was performed. The final pathology with immunohistochemistry staining confirmed endometrioid adenocarcinoma in the liver originating from preexisting hepatic endometriosis. After the multidisciplinary team meeting, the consensus was surgery followed by adjuvant chemotherapy. To our knowledge, this is the first case of Chinese woman of a malignant liver tumor originating from endometriosis ever reported by reviewing the current English medical literature.ConclusionThough rare, extrapelvic endometriosis-associated cancers should be considered as differentiated diagnosis even after hysterectomy and bilateral salpingo-oophorectomy. This case highlights the importance of collaborative efforts across multiple disciplines for accurate diagnosis and appropriate treatment of malignant transformation of hepatic endometriosis.
| S-EPMC8218461 | biostudies-literature
Project description:BackgroundOral potentially malignant disorders (OPMDs) represent a heterogeneous set of different histological lesions, characterized by the capacity to transform in oral squamous cell carcinoma (OSCC). Despite optimal surgical treatment, approximately 20%-30% of OPMDs may evolve into OSCC. No clear clinical/histological factors are able to identify OPMDs at higher risk of malignant transformation.Materials and methodsWe considered surgically treated patients with a diagnosis of OPMDs, enrolled from 1996 to 2019 at ASST Spedali Civili of Brescia without a diagnosis of OSCC within the previous 2 years. Clinical and histological characteristics were recorded. Outcomes of interest were recurrence-free survival (RFS), defined as the time from surgery for primary OPMD to any relapse of OPMD or malignant transformation, whichever occurred first, and carcinoma-free survival (CFS), defined as the time from surgery for OPMD to malignant transformation.ResultsWe retrospectively reviewed 106 OPMDs cases. Median age at first diagnosis was 64 years old (IQR = 18.75); female patients comprise 51.9% of the cases. During a median follow-up of 30.5 months (IQR = 44), in 23.5% of patients, malignant transformation occurred. RFS at 1, 5, and 10 years was 92.4%, 60.9%, and 43.2%, respectively. Female sex and history of previous OSCC were independent risk factors for RFS. CFS at 1, 5, and 10 years of follow-up was 97.1%, 75.9%, and 64.4%, respectively. Previous OSCC was an independent risk factor for CFS.ConclusionsIn this large series of OPMDs, only previous diagnosis of OSCC was a prognostic factor for further OSCC occurrence. Given the lack of additional clinical/pathological prognostic factors, we advocate further studies into molecular characterization of OPMDs to better stratify the risk of malignant transformation.
| S-EPMC9069132 | biostudies-literature
Project description:Purpose: There is limited standard treatment for patients with advanced cholangiocarcinoma after refractory of chemotherapy. Apatinib is a tyrosine kinase inhibitor targeting VEGFR-2, which exhibited broad-spectrum antitumor activities in previous studies. We aim to evaluate the efficacy and safety of apatinib as non-first-line treatment in patients with advanced cholangiocarcinoma. Methods: This was a prospective open-label phase II trial (NCT03251443). Patients with pathology-confirmed cholangiocarcinoma after prior systemic therapy were enrolled. Participants were treated with apatinib 500 mg orally once daily. The primary end point was overall response rate (ORR). Results: Between August 8, 2017 and November 13, 2018, 30 patients participated in this study, and 26 patients received apatinib treatment except 4 patients withdrew consent before the first dosage. For full analysis set, the ORR was 11.5% and the disease control rate was 50.0%. 3 patients (11.5%) achieved partial response and no patients achieved complete response. The median progression free time was 2.0 (95% CI: 0.7-3.3) months and median overall survival was 9. 0 (95% CI: 4.6-13.4) months. The most common adverse events of any grade were fatigue (80.8%), hypertension (73.1%) and decreased appetite (38.5%). Grade 3 adverse events occurred in 23.1% patients and no grade 4 adverse events occurred. The most common grade 3 adverse events were hypertension (23.1%) and elevated transaminase (11.5%). Conclusion: Apatinib as non-first-line monotherapy has potential therapeutic efficacy in patients with advanced cholangiocarcinoma.
| S-EPMC7847639 | biostudies-literature
Project description:Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low-dose apatinib for the treatment of gastric cancer in real-world practice. We performed a prospective, multicenter observation study in a real-world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low-dose apatinib (500 mg or 250mg per day) therapy. The median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47-6.28), and mOS was 7.5 months (95% CI 6.74-8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand-foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand-foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3-4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment-related death was observed during the treatment of apatinib. The prospective study suggested that low-dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world. Trial registration: NCT03333967.
| S-EPMC7367613 | biostudies-literature