Immunoglobulin G4-related sclerosing mastitis: an unexpected diagnosis for a breast mass.

Immunoglobulin G4-related disease is an immune-mediated condition comprised of a number of various disorders sharing unique pathologic, serologic, and clinical features. Diagnosis of immunoglobulin G4-related sclerosing mastitis is challenging as the clinical and imaging findings mimic breast malignancies or other types of inflammatory mastitis. Herein, we describe a case of a female patient with a painless palpable mass in her right breast. An excisional core biopsy led to the rare diagnosis of immunoglobulin G4-related sclerosing mastitis, and the patient received steroid treatment for a month. To date, the patient has remained disease-free without any recurrence. As immunoglobulin G4-related sclerosing mastitis is a very rare disease, further studies are needed to reach conclusions about the pathogenesis, diagnosis, and treatment of this entity.

Giant Basal Cell Carcinoma in a Renal Transplant Recipient: A Case Report.

Basal cell carcinoma is a skin cancer with a more benign clinical course, compared to other skin cancers. However, when left neglected, it can cause serious morbidity and mortality. A basal cell carcinoma larger than 5 cm is defined as giant. Common causes of these carcinomas are negligence, immunosuppression, low socioeconomic status, physical or mental dysfunction, light exposure, exposure to radiation, existence of a previous lesion, recurrence after treatment, and aggressive histologic pattern. In some cases, giant basal cell carcinoma has been described to infiltrate multiple intracranial structures and to be associated with distant metastasis. Herein, we present a case of a giant basal cell carcinoma on the temporary scalp of a renal transplant recipient with depression.

The Role of Urothelial Cancer-Associated 1 in Gynecological Cancers.

Gynecological cancers (GC) represent some of the most frequently diagnosed malignancies in women worldwide. Long-non-coding RNAs (lncRNAs) are regulatory RNAs increasingly being recognized for their role in tumor progression and metastasis in various cancers. Urothelial cancer-associated 1 (UCA1) is a lncRNA, first found deregulated in bladder cancer, and many studies have exposed its oncogenic effects in more tumors since. However, the role of UCA1 in gynecological malignancies is still unclear. This review aims to analyze and define the role of UCA1 in GC, in order to identify its potential use as a diagnostic, prognostic, or therapeutic biomarker of GC. By employing the search terms "UCA1", "breast cancer", "endometrial cancer", "ovarian cancer", "cervical cancer", "vaginal cancer", and "vulvar cancer" in the PubMed database for the literature review, we identified a total of sixty-three relevant research articles published between 2014 and 2024. Although there were some opposing results, UCA1 was predominantly found to be upregulated in most of the breast, endometrial, ovarian, cervical, and vulvar cancer cells, tissue samples, and mouse xenograft models. UCA1 overexpression mainly accounts for enhanced tumor proliferation and increased drug resistance, while also being associated with some clinicopathological features, such as a high histological grade or poor prognosis. Nonetheless, no reviews were identified about the involvement of UCA1 in vaginal carcinogenesis. Therefore, further clinical trials are required to explore the role of UCA1 in these malignancies and, additionally, examine its possible application as a target for upcoming treatments, or as a novel biomarker for GC diagnosis and prognosis.

Evaluation of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

BACKGROUND/AIM: Triple negative breast cancer belongs to the most aggressive breast cancer forms. Histone deacetylases (HDACs) constitute a class of enzymes that exhibit a significant role in breast cancer genesis and progression. In this study, we aimed at assessing the clinical importance of HDAC-2 in triple negative breast cancer. MATERIALS AND METHODS: A total of 138 breast cancer specimens were examined on an immunohistochemical basis. A statistical analysis was performed in order to examine the association between HDAC-2 and the survival and clinicopathological features of the patients. RESULTS: Increased HDAC-2 expression was observed in every fourth case of triple negative breast cancer with positive HDAC-2 staining, whereas only 12 out of 98 non-triple negative breast cancer samples showed high HDAC-2 expression. HDAC-2 overexpression correlated with prolonged overall survival (OS) and disease-free survival (DFS) in triple negative breast cancer. CONCLUSIONS: High HDAC-2 levels in triple negative breast cancer seem to positively influence patient survival, disease stage and recurrence.

Synchronous Insulinoma and Glucagonoma: A Review of the Literature.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS: A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS: A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION: Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.

Ovarian Torsion in Polycystic Ovary Syndrome: A Potential Threat?

Polycystic ovary syndrome (PCOS) constitutes the most prevalent endocrine disorder in women of reproductive age worldwide. Given the increased risk of ovarian torsion in the presence of large ovarian cysts, polycystic ovarian syndrome could be regarded as one of the most significant risk factors for ovarian and/or adnexal torsion in cases of significantly enlarged ovaries. The aim of the present review is to investigate, for the first time, the association between polycystic ovarian syndrome and ovarian torsion. We performed a review of the literature using the MEDLINE and LIVIVO databases in order to find relevant studies. By using the search terms "polycystic ovarian syndrome" and "ovarian torsion", we were able to identify 14 studies published between 1995 and 2019. The present work constitutes the most up-to-date, comprehensive literature review focusing on the risk of ovarian/adnexal torsion in patients with polycystic ovaries. Ovarian/adnexal torsion seems to be a feared complication in patients with polycystic ovary syndrome. Acute lower abdominal pain in patients with known polycystic ovaries represents the most common symptom, while diagnostic assessment almost always incorporates transvaginal ultrasound and computer tomography or magnetic resonance tomography scans. In case of suspected torsion, emergency laparoscopy with ovarian or adnexal detorsion seems to be the standard therapeutic approach with a view to restitute the interrupted blood supply. In cases of repeated ovarian/adnexal torsions, ovariopexy or ovariectomy/adnexectomy had to be discussed with the patient in the context of risk recurrence minimization.

Liver Cancer and Pregnancy: A Review of the Literature.

BACKGROUND/AIM: Liver cancer constitutes one of the leading cancers globally. During pregnancy, however, liver cancer is an absolute rarity, with very few cases reported in the international literature. The aim of the present review was to provide a useful update and summarize all case studies of liver cancer in pregnancy published between 2012-2023. MATERIALS AND METHODS: A literature review was conducted using the MEDLINE, LIVIVO, and Google Scholar databases. Solely case reports and case studies written in the English language that explicitly reported on the presence of histologically confirmed HCC or intrahepatic cholangiocarcinoma during pregnancy were included in the data analysis. RESULTS: After detailed evaluation, a total of 35 reported cases of liver cancer during pregnancy were identified, hence bringing the total number of reported cases globally to 83. Oncological challenges during pregnancy call for an interdisciplinary approach. Although the desire to preserve the pregnancy should be taken into consideration, specialists need to evaluate maternal and fetal well-being and choose the optimal oncological treatment with the least dangers for both the maternal and fetal safety. CONCLUSION: The present review proves that, despite its scarcity, liver cancer may always occur during pregnancy and clinicians should, therefore, remain vigilant and endeavor to detect and evaluate any hepatic mass or symptoms of liver cancer promptly and exhaustively.

A Proposed Cytodiagnosistic Approach for Breast Lesions.

In clinical practice, the diagnosis of breast lesions is achieved by the triple approach of the specialized surgeon, radiologist and pathologist. The recommended approach to breast lesions should always include a detailed history, along with a thorough clinical examination, mammography and/or ultrasound, as well as preoperative cytodiagnosis. In this context, fine needle aspiration cytology and core needle biopsy are the methods of choice for histological diagnosis. Herein, we aim to explain why these procedures seem to be superior compared to open biopsy and we propose a cytodiagnostic algorithm for breast lesions.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy.

Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy.

Cervical carcinoma is one of the most common cancers among women globally. Histone deacetylase inhibitors (HDACIs) constitute anticancer drugs that, by increasing the histone acetylation level in various cell types, induce differentiation, cell cycle arrest, and apoptosis. The aim of the current review is to study the role of HDACIs in the treatment of cervical cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "histone deacetylase" and "cervical cancer", we managed to identify 95 studies published between 2001 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HDACIs as treatment agents for cervical cancer. Both well-established and novel HDACIs seem to represent modern, efficacious anticancer drugs, which, alone or in combination with other treatments, may successfully inhibit cervical cancer cell growth, induce cell cycle arrest, and provoke apoptosis. In summary, histone deacetylases seem to represent promising future treatment targets in cervical cancer.

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches.

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

Exploiting Autophagy-Dependent Neoantigen Presentation in Tumor Microenvironment.

Autophagy constitutes a well-known homeostatic and catabolic process that is responsible for degradation and recycling of cellular components. It is a key regulatory mechanism for several cellular functions, whereas its dysregulation is associated with tumorigenesis, tumor-stroma interactions and resistance to cancer therapy. A growing body of evidence has proven that autophagy affects the tumor microenvironment, while it is also considered a key factor for function of several immune cells, such as APCs, T-cells, and macrophages. Moreover, it is implicated in presentation of neo-antigens of tumor cells in both MHC-I and MHC-II in dendritic cells (DCs) in functional activity of immune cells by creating T-cell memory, as well as in cross-presentation of neo-antigens for MHC-I presentation and the internalization process. Currently, autophagy has a crucial role in immunotherapy. Emergence of cancer immunotherapy has already shown some remarkable results, having changed therapeutic strategy in clinical practice for several cancer types. Despite these promising long-term responses, several patients seem to lack the ability to respond to immune checkpoint inhibitors. Thus, autophagy through neo-antigen presentation is a potential target in order to strengthen or attenuate the effects of immunotherapy against different types of cancer. This review will shed light on the recent advances and future directions of autophagy-dependent neo-antigen presentation and consequently its role in immunotherapy for malignant tumors.

FDA-Approved Monoclonal Antibodies for Unresectable Hepatocellular Carcinoma: What Do We Know So Far?

Unresectable hepatocellular carcinoma (HCC) is an advanced primary liver malignancy with a poor prognosis. The Food and Drug Administration (FDA) has, to date, approved nivolumab, pembrolizumab, ramucirumab, nivolumab/ipilimumab, atezolizumab/bevacizumab, as well as tremelimumab/durvalumab, as first- or second-line monoclonal antibodies (mAbs) for unresectable HCC. The present review examines the current state of knowledge, and provides a useful update on the safety and efficacy of these therapeutic agents, thus attempting to define the suitability of each mAb for different patient subgroups.

Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Implication of gut microbiome in immunotherapy for colorectal cancer.

Colorectal cancer (CRC) constitutes the third most frequently reported malignancy in the male population and the second most common in women in the last two decades. Colon carcinogenesis is a complex, multifactorial event, resulting from genetic and epigenetic aberrations, the impact of environmental factors, as well as the disturbance of the gut microbial ecosystem. The relationship between the intestinal microbiome and carcinogenesis was relatively undervalued in the last decade. However, its remarkable effect on metabolic and immune functions on the host has been in the spotlight as of recent years. There is a strong relationship between gut microbiome dysbiosis, bowel pathogenicity and responsiveness to anti-cancer treatment; including immunotherapy. Modifications of bacteriome consistency are closely associated with the immunologic response to immunotherapeutic agents. This condition that implies the necessity of gut microbiome manipulation. Thus, creatingan optimal response for CRC patients to immunotherapeutic agents. In this paper, we will review the current literature observing how gut microbiota influence the response of immunotherapy on CRC patients.

Clinical Significance of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

BACKGROUND/AIM: There is a strong association between malignancy and histone deacetylases (HDACs). Histone deacetylase inhibitors (HDACIs) are now being tested as antitumor agents in various clinical trials. We aimed to assess the clinical importance of HDAC-2 in breast cancer (BC). MATERIALS AND METHODS: A total of 118 BC specimens were examined immunohistochemically. A statistical analysis was conducted in order to examine the relation between HDAC-2 and the clinicopathological features and survival of the patients. RESULTS: Higher HDAC-2 expression was related to lobular histological type of cancer, grade III, and stage III BC. In addition, the disease-free period and overall survival were curtailed and negatively related to the over-expression of HDAC-2. Other factors correlating with worse survival were histological types other than ductal or lobular, and the stage of the disease. CONCLUSIONS: This study showed a relationship between HDAC-2 and BC. Further studies are required in order to eventually potentiate the role of HDACIs as anticancer agents in BC.

The Emerging Role of MicroRNAs and Autophagy Mechanism in Pancreatic Cancer Progression: Future Therapeutic Approaches.

Pancreatic cancer constitutes the fourth most frequent cause of death due to malignancy in the US. Despite the new therapeutic modalities, the management of pancreatic ductal adenocarcinoma (PDAC) is considered a difficult task for clinicians due to the fact that is usually diagnosed in already advanced stages and it is relatively resistant to the current chemotherapeutic agents. The molecular background analysis of pancreatic malignant tumors, which includes various epigenetic and genetic alterations, opens new horizons for the development of novel diagnostic and therapeutic strategies. The interplay between miRNAs, autophagy pathway, and pancreatic carcinogenesis is in the spotlight of the current research. There is strong evidence that miRNAs take part in carcinogenesis either as tumor inhibitors that combat the oncogene expression or as promoters (oncomiRs) by acting as oncogenes by interfering with various cell functions such as proliferation, programmed cell death, and metabolic and signaling pathways. Deregulation of the expression levels of various miRNAs is closely associated with tumor growth, progression, and dissemination, as well as low sensitivity to chemotherapeutic agents. Similarly, autophagy despite constituting a pivotal homeostatic mechanism for cell survival has a binary role in PDAC, either as an inhibitor or promoter of carcinogenesis. The emerging role of miRNAs in autophagy gets a great deal of attention as it opens new opportunities for the development of novel therapeutic strategies for the management of this aggressive and chemoresistant malignancy. In this review, we will shed light on the interplay between miRNAs and the autophagy mechanism for pancreatic cancer development and progression.

Liver Transplantation and Budd-Chiari Syndrome: When the Cause Becomes the Solution.

Budd-Chiari syndrome consists a rare medical entity which has an estimated incidence of 0.1 to 10 people per million every year. It is defined by the obstruction of the flow in the inferior vena cava or the hepatic veins. Various classifications have been proposed. So, it can be acute or chronic and primary or secondary. Iatrogenic, a subtype of secondary Budd-Chiari syndrome, is caused by various medical interventions, including liver transplantation. On the other hand, liver transplantation is the ultimate therapeutic management of Budd-Chiari syndrome. Finally, a medical paradox and a vicious circle has been created. Liver transplantation can potentially be both the cause and treatment of Budd-Chiari syndrome. Budd-Chiari syndrome is simultaneously the cause and complication of liver transplantation. Our aim is to describe this double role of liver transplantation in Budd-Chiari syndrome and to acknowledge that a high degree of clinical suspicion is necessary for the proper recognition and management of this life-threatening condition.

COVID-19 and Acute Pancreatitis: A Systematic Review of Case Reports and Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents mainly with mild symptoms and involvement of the respiratory system. Acute pancreatitis has also been reported during the course of COVID-19. OBJECTIVE: Our aim is to review and analyze all reported cases of COVID-19 associated acute pancreatitis, reporting the demographics, clinical characteristics, laboratory and imaging findings, comorbidities and outcomes. DATA SOURCES: We conducted a systematic search of Pubmed/MEDLINE, SciELO and Google Scholar to identify case reports and case series, reporting COVID-19 associated acute pancreatitis in adults. STUDY SELECTION: There were no ethnicity, gender or language restrictions. The following terms were searched in combination:"COVID-19" OR "SARS-CoV-2" OR "Coronavirus 19" AND "Pancreatic Inflammation" OR "Pancreatitis" OR "Pancreatic Injury" OR "Pancreatic Disease" OR "Pancreatic Damage". Case reports and case series describing COVID-19 associated acute pancreatitis in adults were included. COVID-19 infection was established with testing of nasal and throat swabs using reverse transcription polymerase chain reaction. The diagnosis of acute pancreatitis was confirmed in accordance to the revised criteria of Atlanta classification of the Acute Pancreatitis Classification Working Group. Exclusion of other causes of acute pancreatitis was also required for the selection of the cases. DATA EXTRACTION: The following data were extracted from each report: the first author, year of publication, age of the patient, gender, gastrointestinal symptoms due to acute pancreatitis, respiratory-general symptoms, COVID-19 severity, underlying diseases, laboratory findings, imaging features and outcome. DATA SYNTHESIS: Finally, we identified and analyzed 31 articles (30 case reports and 1 case series of 2 cases), which included 32 cases of COVID-19 induced acute pancreatitis. CONCLUSION: COVID-19 associated acute pancreatitis affected mostly females. The median age of the patients was 53.5 years. Concerning laboratory findings, lipase and amylase were greater than three times the ULN while WBC counts and CRP were elevated in the most of the cases. The most frequent gastrointestinal, respiratory and general symptom was abdominal pain, dyspnea and fever, respectively. The most common imaging feature was acute interstitial edematous pancreatitis and the most frequent comorbidity was arterial hypertension while several patients had no medical history. The outcome was favorable despite the fact that most of the patients experienced severe and critical illness. LIMITATIONS: Our results are limited by the quality and extent of the data in the reports. More specifically, case series and case reports are unchecked, and while they can recommend hypotheses they are not able to confirm robust associations. CONFLICT OF INTEREST: None.