Optimizing the Diagnosis and Biomarker Testing for Patients with Intrahepatic Cholangiocarcinoma: A Multidisciplinary Approach.
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ABSTRACT:
SUBMITTER: Cho MT
PROVIDER: S-EPMC8773504 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches. Liver resection represents the therapeutic backbone and only curative treatment option, with the functional residual capacity of the liver and oncologic radicality being deciding factors for postoperative and long-term oncological outcome. Furthermore, in selected cases and depending on national guidelines, liver transplantation may be a therapeutic option. Given the often advanced tumor stage at diagnosis or the potential for postoperative recurrence, locoregional therapies have become increasingly important. These strategies range from radiofrequency ablation to transarterial chemoembolization to selective internal radiation therapy and can be used in combination with liver resection. In addition, adjuvant and neoadjuvant chemotherapies as well as targeted therapies and immunotherapies based on molecular profiles can be applied. This review discusses multimodal treatment strategies for iCC and their differential use.
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Project description:PurposeThe oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib.MethodsClinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs.ResultsThe most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs-in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment.ConclusionOverall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach.
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Project description:Medulloblastoma is a malignant tumor of the cerebellum and the most frequent malignant brain tumor in children. The standard of care consists of maximal resection surgery, followed by craniospinal irradiation and chemotherapy. Such treatment allows long-term survival rates of nearly 70%; however, there are wide disparities among patient outcomes, and in any case, major long-term morbidity is observed with conventional treatment. In the last two decades, the molecular understanding of medulloblastoma has improved drastically, allowing us to revolutionize our understanding of medulloblastoma pathophysiological mechanisms. These advances led to an international consensus in 2010 that defined four prognostic molecular subgroups named after their affected signaling pathways, that is, WNT, SHH, Group 3 and Group 4. The molecular understanding of medulloblastoma is starting to translate through to clinical settings due to the development of targeted therapies. Moreover, recent improvements in radiotherapy modalities and the reconsideration of craniospinal irradiation according to the molecular status hold promise for survival preservation and the reduction of radiation-induced morbidity. This review is an overview of the current knowledge of medulloblastoma through a molecular approach, and therapeutic prospects currently being developed in surgery, radiotherapy and targeted therapies to optimize the treatment of medulloblastoma with a multidisciplinary approach will also be discussed.
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Project description:Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disease grouping five genetic disorders, four of them occurring in humans and one known to date only in a mouse model. In every subtype of MPS III (designed A, B, C, D or E), a lack or drastically decreased activity of an enzyme involved in the degradation of heparan sulfate (HS) (a compound from the group of glycosaminoglycans (GAGs)) arises from a genetic defect. This leads to primary accumulation of HS, and secondary storage of other compounds, combined with changes in expressions of hundreds of genes and many defects in organelles and various biochemical processes in the cell. As a result, dysfunctions of tissues and organs occur, leading to severe symptoms in patients. Although changes in somatic organs are considerable, the central nervous system is especially severely affected, and neurological, cognitive and behavioral disorders are the most significant changes, making the disease enormously burdensome for patients and their families. In the light of the current lack of any registered therapy for Sanfilippo syndrome (despite various attempts of many research groups to develop effective treatment, still no specific drug or procedure is available for MPS III), optimizing care with a multidisciplinary approach is crucial for managing this disease and making quality of patients' life passable. This includes efforts to make/organize (i) accurate diagnosis as early as possible (which is not easy due to various possible misdiagnosis events caused by similarity of MPS III symptoms to those of other diseases and variability of patients), (ii) optimized symptomatic treatment (which is challenging because of complexity of symptoms and often untypical responses of MPS III patients to various drugs), and (iii) psychological care (for both patients and family members and/or caregivers). In this review article, we focus on these approaches, summarizing and discussing them.
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Project description:Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains unclear, however. The data of ICC and healthy individuals were downloaded from the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases. Meanwhile, a cutting-edge ICC high-resolution spatial transcriptome was also acquired before these data were comprehensively analysed using bioinformatics approaches. Moreover, 95 individuals with ICC who had undergone resection surgery were enrolled in this study to investigate the relationship between HEV and tumour microenvironment (TME) applying immunohistochemistry and multiple immunofluorescence techniques. The high-HEV subtype contains rich immune infiltrates including tertiary lymphoid structure (TLS), CD8+ T cells, and CD20+ B cells. Furthermore, HEV and TLS exhibited a strong relationship of spatial colocalization. Correlated with improved prognostic outcomes in ICC, the high-HEV subtype could be an independent prognostic indicator for individuals with ICC. This study revealed the association of HEV with immune function and observed a strong spatial colocalization correlation between HEV and TLS. Moreover, correlated with immunotherapeutic response, HEV could improve prognostic outcomes, which may be a potential indicator of immunotherapy pathology in ICC.
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Project description:Combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC-CC who underwent resection in order to elucidate whether the classification of ICC and cHCC-CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC-CC who underwent liver resection from 2001 to 2017. Clinic-pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence-free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut-off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC-CC, tumor cut-off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC-CC was 0.9 years (95% confidence interval: 0.3-1.6), which was poorer than that of patients with ICC (1.3 years, 0.5-2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC-CC into different categories because of a significant difference in RFS between the two.
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Project description:PurposeMutations in the IDH1 and IDH2 (IDH1/2) genes occur in approximately 20% of intrahepatic cholangiocarcinoma and lead to accumulation of 2-hydroxyglutarate (2HG) in the tumor tissue. However, it remains unknown whether IDH1/2 mutations can lead to high levels of 2HG circulating in the blood and whether serum 2HG can be used as a biomarker for IDH1/2 mutational status and tumor burden in intrahepatic cholangiocarcinoma.Experimental designWe initially measured serum 2HG concentration in blood samples collected from 31 patients with intrahepatic cholangiocarcinoma in a screening cohort. Findings were validated across 38 resected patients with intrahepatic cholangiocarcinoma from a second cohort with tumor volume measures. Circulating levels of 2HG were evaluated relative to IDH1/2 mutational status, tumor burden, and a number of clinical variables.ResultsCirculating levels of 2HG in the screening cohort were significantly elevated in patients with IDH1/2-mutant (median, 478 ng/mL) versus IDH1/2-wild-type (median, 118 ng/mL) tumors (P < 0.001). This significance was maintained in the validation cohort (343 ng/mL vs. 55 ng/mL, P < 0.0001) and levels of 2HG directly correlated with tumor burden in IDH1/2-mutant cases (P < 0.05). Serum 2HG levels ≥170 ng/mL could predict the presence of an IDH1/2 mutation with a sensitivity of 83% and a specificity of 90%. No differences were noted between the allelic variants IDH1 or IDH2 in regard to the levels of circulating 2HG.ConclusionsThis study indicates that circulating 2HG may be a surrogate biomarker of IDH1 or IDH2 mutation status in intrahepatic cholangiocarcinoma and that circulating 2HG levels may correlate directly with tumor burden. Clin Cancer Res; 20(7); 1884-90. ©2014 AACR.
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Project description:CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital hypoplasia, Ear anomalies including hearing loss) syndrome is a rare syndrome with an incidence of approximately 1:15,000 newborns. It is caused by pathogenic variants in the CHD7 gene and clinically characterized by a wide range of anomalies with variable expression. Growth retardation affects 60-72% of children with CHARGE syndrome, making it one of the most prominent medical issues in the syndrome. Growth retardation in CHARGE syndrome is thought to be multifactorial and can be influenced by almost all co-morbidities, requiring a multidisciplinary approach to the different medical problems. In this systematic review, we describe what is currently known about growth in CHARGE syndrome and how it is influenced by commonly seen clinical problems including feeding difficulties, hypogonadotropic hypogonadism and growth hormone deficiency. Furthermore, we provide recommendations for a multidisciplinary approach.
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Project description:Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis and can be present in over 50% of adults with the disease. CFRD is associated with poorer clinical outcomes, including accelerated pulmonary function decline and excess morbidity. The management of CFRD is complex and differs from that of type 1 and type 2 diabetes mellitus such that clinicians responsible for the care of people with CFRD must work closely with colleagues across a number of different specialities and disciplines. This review aims to discuss why a multi-disciplinary approach is important and how it can be harnessed to optimize the care of people with CFRD.
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Project description:The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.
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