An unusual cause of gastric extraluminal compression: fibrolamellar hepatocellular carcinoma

Abstract Fibrolamellar hepatocellular carcinoma (FLH) is a rare variant of hepatocellular carcinoma that typically occurs in adolescents or young subjects in an otherwise normal liver. Correct recognition of FLH is extremely important, because a complete resection of the tumor can confer an excellent prognosis. FLHs can become large, exerting mass effects on adjacent organs before diagnosis. Unfortunately, there are very few imaging reports describing external compression of the stomach caused by a FLH. We report the case of a young female suffering from dyspepsia and abdominal pain caused by stomach compression resulting from a large FLH

Immunotherapy for advanced urothelial carcinoma (UC): rational and current evidence.

Combination platinum-based chemotherapy has been the standard of care for several decades in first-line treatment of advanced urothelial carcinoma (UC) patients. UC is often chemosensitive, though durable responses are quite rare and the development of chemoresistance still leads to poor clinical outcomes. Up until a few years ago, UC patients could not benefit from any valuable alternatives to cytotoxic chemotherapy, but the scenario has been recently transformed by the advent of immunotherapy. Molecular biology of UC is characterised by a relatively high prevalence of alterations in DNA damage response pathway, genomic instability, high tumour burden, and elevated programmed cell death ligand 1 (PD-L1) protein expression, which are established factors predicting favourable response to immune checkpoint inhibitors (ICIs) in several tumour types. To date, various ICIs have been approved as systemic anti-cancer therapy for advanced UC in multiple settings, including first-line, maintenance, and second-line therapy. ICIs are also in development either as monotherapy or in combination with chemotherapy or other targeted agents. Moreover, a number of alternative ICIs, interleukins, and novel immune molecules have been identified as promising agents in advanced UC. Herein, we review rational and current literature evidence supporting the clinical development and current indications of immunotherapy, particularly focusing on ICIs

Diagnostic biomarkers in ovarian cancer: advances beyond CA125 and HE4

Ovarian cancer (OC) is the most lethal gynaecologic malignancy, attributed to its insidious growth, non-specific symptoms and late presentation. Unfortunately, current screening modalities are inadequate at detecting OC and many lack the appropriate specificity and sensitivity that is desired from a screening test. Nearly 70% of cases are diagnosed at stage III or IV with poor 5-year overall survival. Therefore, the development of a sensitive and specific biomarker for early diagnosis and screening for OC is of utmost importance. Currently, diagnosis is guided by CA125, the patient’s menopausal status and imaging features on ultrasound scan. However, emerging evidence suggests that a combination of CA125 and HE4 (another serum biomarker) and patient characteristics in a multivariate index assay may provide a higher specificity and sensitivity than either CA125 and HE4 alone in the early detection of OC. Other attempts at combining various serum biomarkers into one multivariate index assay such as OVA1, ROMA and Overa have all shown promise. However, significant barriers exist before these biomarkers can be implemented in clinical practice. This article aims to provide an up-to-date review of potential biomarkers for screening and early diagnosis of OC which may have the potential to transform its diagnostic landscape

Diagnostic biomarkers in ovarian cancer: advances beyond CA125 and HE4.

Ovarian cancer (OC) is the most lethal gynaecologic malignancy, attributed to its insidious growth, non-specific symptoms and late presentation. Unfortunately, current screening modalities are inadequate at detecting OC and many lack the appropriate specificity and sensitivity that is desired from a screening test. Nearly 70% of cases are diagnosed at stage III or IV with poor 5-year overall survival. Therefore, the development of a sensitive and specific biomarker for early diagnosis and screening for OC is of utmost importance. Currently, diagnosis is guided by CA125, the patient's menopausal status and imaging features on ultrasound scan. However, emerging evidence suggests that a combination of CA125 and HE4 (another serum biomarker) and patient characteristics in a multivariate index assay may provide a higher specificity and sensitivity than either CA125 and HE4 alone in the early detection of OC. Other attempts at combining various serum biomarkers into one multivariate index assay such as OVA1, ROMA and Overa have all shown promise. However, significant barriers exist before these biomarkers can be implemented in clinical practice. This article aims to provide an up-to-date review of potential biomarkers for screening and early diagnosis of OC which may have the potential to transform its diagnostic landscape

Systemic anti-cancer treatment in malignant ovarian germ cell tumours (MOGCTs): current management and promising approaches

Malignant ovarian germ cell tumours (MOGCTs) are rare. Unlike epithelial ovarian cancer, MOGCTs typically occur in girls and young women. Fertility-sparing surgery and platinum-based chemotherapy remain the standard of care, providing high chance of cure at all stages. Given the lack of high-quality studies in this field, current practice guidelines recommend chemotherapy regimens adopted in testicular germ cell tumours. However, platinum-resistant/refractory MOGCTs retain a worse prognosis in comparison with their male counterpart. Herein, we focus on current systemic anti-cancer treatment options in MOGCTs and promising approaches. Future studies enrolling exclusively female participants or germ cell tumour trials allowing participation of MOGCT patients are strongly recommended in order to improve evidence on existing management and develop novel strategies

Neoadjuvant treatment for newly diagnosed advanced ovarian cancer: where do we stand and where are we going?

Newly diagnosed high grade serous epithelial ovarian cancer (EOC) patients are treated with radical surgery followed by adjuvant platinum and taxane combination chemotherapy. In EOC patients where upfront surgery is contraindicated for medical reasons (e.g., comorbidities or poor performance status), or where complete cytoreduction cannot be achieved, neoadjuvant chemotherapy (NACT) prior to interval debulking surgery (IDS), and adjuvant chemotherapy is an alternative therapeutic option. There is currently a lack of consensus about who are the best candidates to receive NACT, and some authors have even suggested that this approach could be harmful in a subset of patients via promotion of early chemoresistance. Standard and novel imaging techniques together with a better molecular characterization of the disease have the potential to improve selection of patients, but ultimately well designed randomised clinical trials are needed to guide treatment decisions in this setting. The advent of new and effective treatment options (antiangiogenics and PARP inhibitors), now approved for use in the first line and relapse settings has opened the way to clinical trials aiming to investigate these agents as substitute or in addition to chemotherapy in the neoadjuvant setting in molecularly selected EOC patients. Here, we will review the evidence supporting the use of NACT in newly diagnosed EOCs, data highlighting the importance of its use in selected patients, new imaging methodologies and biomarkers that can guide patient selection

Serum bone sialoprotein levels and bone metastases

The skeleton is the most common site of tumor metastasis. The detection of metastatic bone disease is critical for primary cancer staging because it will condition the therapeutic decision and the prognosis. For the diagnosis of bone metastases, imaging techniques are usually employed, even if these techniques have some limitations in terms of accuracy and costs. An innovative, cheaper method for the screening of skeletal metastases could be the measurement of bone turnover markers. This article is aimed at providing a literature review on the clinical significance of increased serum levels of bone sialoprotein (BSP) observed in patients suffering from metastatic bone lesions. In addition, we have briefly summarized recent studies reporting the biological and pathological roles of BSP in bone remodeling and bone metastasis. Some studies have demonstrated that serum BSP can be considered as an early marker and a prognostic factor for the development of bone metastases. BSP may help in assessing osteolytic bone disease, in evaluating additional prognostic information and in monitoring treatment modalities

Immunotherapy for advanced urothelial carcinoma (UC): rational and current evidence

Combination platinum-based chemotherapy has been the standard of care for several decades in first-line treatment of advanced urothelial carcinoma (UC) patients. UC is often chemosensitive, though durable responses are quite rare and the development of chemoresistance still leads to poor clinical outcomes. Up until a few years ago, UC patients could not benefit from any valuable alternatives to cytotoxic chemotherapy, but the scenario has been recently transformed by the advent of immunotherapy. Molecular biology of UC is characterised by a relatively high prevalence of alterations in DNA damage response pathway, genomic instability, high tumour burden, and elevated programmed cell death ligand 1 (PD-L1) protein expression, which are established factors predicting favourable response to immune checkpoint inhibitors (ICIs) in several tumour types. To date, various ICIs have been approved as systemic anti-cancer therapy for advanced UC in multiple settings, including first-line, maintenance, and second-line therapy. ICIs are also in development either as monotherapy or in combination with chemotherapy or other targeted agents. Moreover, a number of alternative ICIs, interleukins, and novel immune molecules have been identified as promising agents in advanced UC. Herein, we review rational and current literature evidence supporting the clinical development and current indications of immunotherapy, particularly focusing on ICIs

Serum bone sialoprotein levels and bone metastases

The skeleton is the most common site of tumor metastasis. The detection of metastatic bone disease is critical for primary cancer staging because it will condition the therapeutic decision and the prognosis. For the diagnosis of bone metastases, imaging techniques are usually employed, even if these techniques have some limitations in terms of accuracy and costs. An innovative, cheaper method for the screening of skeletal metastases could be the measurement of bone turnover markers. This article is aimed at providing a literature review on the clinical significance of increased serum levels of bone sialoprotein (BSP) observed in patients suffering from metastatic bone lesions. In addition, we have briefly summarized recent studies reporting the biological and pathological roles of BSP in bone remodeling and bone metastasis. Some studies have demonstrated that serum BSP can be considered as an early marker and a prognostic factor for the development of bone metastases. BSP may help in assessing osteolytic bone disease, in evaluating additional prognostic information and in monitoring treatment modalities

Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets—a narrative review

Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future