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.

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.

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.

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.

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer-Current Treatment Options and Future Perspectives.

Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.

Cytomegalovirus pneumonia in an immunocompetent host with primary ciliary dyskinesia: A case report.

Primary ciliary dyskinesia (PCD) is an autosomal-recessive inherited disease caused by mutations in genes involved in ciliary structure and function leading to impaired mucociliary clearance and repeated or chronic, usually bacterial, infections of the upper and lower airways and decreased lung function and bronchiectasis. Cytomegalovirus (CMV) is a DNA virus that usually causes subclinical infection and in 10% of the patients causes a mononucleosis-like syndrome. CMV is a causative agent of serious illness in vulnerable immunocompromised groups such as transplant recipients, patients with immunodeficiency or malignancy and neonates. Life-threatening infection due to CMV, including CMV pneumonia, is not common in immunocompetent patients. In this report we describe a case of an otherwise immunocompetent woman, suffering from PCD, who developed severe CMV pneumonia.

Pulmonary adverse events due to immune checkpoint inhibitors: A literature review.

Cancer immunotherapy aims to stimulate the immune system to fight against tumors, utilizing the presentation of molecules on the surface of the malignant cells that can be recognized by the antibodies of the immune system. Immune checkpoint inhibitors, a type of cancer immunotherapy, are broadly used in different types of cancer, improving patients' survival and quality of life. However, treatment with these agents causes immune-related toxicities affecting many organs. The most frequent pulmonary adverse event is pneumonitis representing a non-infective inflammation localized to the interstitium and alveoli. Other lung toxicities include airway disease, pulmonary vasculitis, sarcoid-like reactions, infections, pleural effusions, pulmonary nodules, diaphragm myositis and allergic bronchopulmonary aspergillosis. This review aims to summarize these pulmonary adverse events, underlining the significance of an optimal expeditious diagnosis and management.

Red Blood Cell Alloantibody Titration - Does the Titration Method Matter?

BACKGROUND: Red blood cell (RBC) alloantibody titration is a quasi-quantitative method to assess antibody concentration and is considered a useful means of estimating maternal alloimmunization during pregnancy. Traditionally, titration is performed using conventional tube test (CTT). The gel microcolumn agglutination-based method (GMA) has been proven reliable for many immunohematology tests. Our study compared CTT with GMA of two different, commercially available GMA systems for RBC alloantibody titration. METHODS: Serum samples with significant RBC-alloantibodies were evaluated in our study. Each sample was titrated concurrently with CTT, with ID-DiaMed-GmbH, Cressier, Switzerland (GMA1), and with DG Gel Coombs Diagnostic Grifols, Passeig Fluvial, Spain (GMA2). RESULTS: One hundred thirty-seven titration tests including 50 anti-D, 25 anti-Kell, 10 anti-E, 9 anti-Jka, 8 anti-c, 5 anti-Cw, 5 anti-Fya, 7 anti-M, 6 anti-Kpa, 3 anti-Lua, 1 anti-e, 3 anti-G, and 2 anti-Cha were performed and evaluated. Samples tested by CTT versus GMA1 and GMA2 generated mostly equal or higher titers by GMAs. The results of both comparisons were in good agreement (W = 0.91, p < 0.0001, and W = 0.92, p < 0.0001, respectively). For all antibody specificities, the mean absolute difference in titers ranged from 1 - 3 for both GMA1 and GMA2 versus CTT. Samples tested by GMA1 vs. GMA2 were in almost perfect agreement (W = 0.95, p < 0.0001). CONCLUSIONS: Although both GMAs were found slightly more sensitive than CTT for alloantibody titration, the differences were not significant and the agreement between all methods was very good, possibly indicating GMA as a suitable alternative to CTT in RBC antibody titration.

Expression of S100B Protein in Ischemia/Reperfusion-Induced Brain Injury After Cyclosporine Therapy: A Biochemical Serum Marker with Prognostic Value?

BACKGROUND Accumulating evidence has indicated that S100B protein may be involved in the pathophysiology of ischemia-reperfusion brain injury. Cyclosporine has been shown to have neuroprotective functions. This study investigated the effect of cyclosporine on S100B serum levels and the severity of brain tissue damage in a rat model of cerebral ischemia-reperfusion (I/R). MATERIAL AND METHODS Twelve-week-old Wistar male rats were randomly divided into Control I/R and Cyclosporine I/R groups (n=10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral I/R, at a total volume of 15 mg/kg/day. The Control group received an equal volume of saline. Body weight was measured and all animals were subjected to 60-min focal ischemia by filament occlusion of the middle cerebral artery. ELISA was used to assess the concentrations of serum S100B and development of brain infarct size and neurological outcomes were determined at 2 and 24 h after occlusion withdrawal. RESULTS Cyclosporine improved the neurological deficit score and decreased the cerebral infarct size and body weight. S100B serum levels were significantly elevated in Cyclosporine-treated rats compared with untreated Control rats during the reperfusion phase. Total infarct size was positively associated with S100B serum levels in the Control I/R group, but no significant correlation was observed in the Cyclosporine I/R group. CONCLUSIONS Cyclosporine seems to affect both ischemia-reperfusion brain tissue damage and S100B protein serum levels. S100B serum level appears to be a state marker for the severity of the cerebral ischemia-reperfusion, rather than a trait marker for Cyclosporine responsiveness.

Pierre Franco (1505-1578): An Innovative Surgeon of the 16th Century in the Treatment of Hernia and Lithotomy.

Pierre Franco (1505-1578) was a brilliant surgeon of the Renaissance, a contemporary of Ambroise Paré. He made an impact on the history of surgery with his innovative approaches in the treatment of hernia, lithotomy, and the use of the suprapubic incision. The purpose of this study is to present a detailed account of his work, innovations, and achievements as well as the impact he made on the surgery of the Renaissance.

Antoine Ferrein (1693-1769)-His Life and Contribution to Anatomy and Physiology: The Description of the Vocal Chords and Their Function.

The purpose of this study is to summarize the life and work of the French anatomist and surgeon Antoine Ferrein (1693-1769). Ferrein made an impact in the history of anatomy and physiology through his work and especially with the description of phonation, renal anatomy, and liver and biliary structure. He also made an impact on ophthalmology with the description of the eyelid and its diseases. After a thorough review of the literature, we present in this review his life and his main discoveries with special emphasis on the anatomic description of the vocal chords resembling the chords of a violin tempered by the air exhaled from the lungs and how the physiology of phonation and the surgery of the larynx were revolutionized after that.

Anaplastic Thyroid Cancer: A Rare Entity Presented Clinically Only with Fever and Elevated CRP.

Anaplastic thyroid carcinoma (ATC) is a rare but almost invariably lethal disease. In this manuscript, we present a case where the dominant manifestation of ATC beside the goitre was elevated CRP values and a persistent low-grade fever. The patient underwent surgical removal of the tumour, chemotherapy and radiotherapy treatment. She is still alive and healthy 11 months after the surgery. We aim to demonstrate that ATC can be present with no specific symptoms or findings and to raise awareness towards an earlier diagnosis.

Karl Ludloff (1864-1945): An Inventive Orthopedic Surgeon, His Work and His Surgical Technique for the Correction of Hallux Valgus.

The purpose of this article is to summarize the work and pioneering achievements in the field of orthopedic surgery of the German orthopedic surgeon Karl Ludloff. Ludloff had an impact in the diagnostics, physical examination, orthopedic imaging, and orthopedic surgical technique of his era. He was a pioneer in the surgical treatment of dysplastic hip, anterior cruciate ligament reconstruction, and hallux valgus. His surgical technique for the correction of hallux valgus, initially stabilized with plaster of Paris, remained unpopular among other orthopedic surgeons for decades. In the 1990s, the advent and use of improved orthopedic materials for fixation attracted the interest of numerous orthopedic surgeons in the Ludloff osteotomy for its ability to correct the deformity in all 3 dimensions, its anatomic outcomes, and its low recurrence rate and patient satisfaction.

Primary Hepatic Leiomyosarcoma: a Case Report and Review of the Literature.

BACKGROUND/AIM: Primary hepatic leiomyosarcoma is an extremely rare type of liver sarcoma with relatively poor prognosis, with about 50 cases having been reported in the literature. Potential origins of this tumor in the liver are the smooth muscle cells in the round ligament, intrahepatic blood vessels and intrahepatic bile ducts. There is no apparent sex predilection and there is a wide age range. The clinical presentation is not specific and the diagnosis depends on the expression of markers such as smooth muscle actin, desmin and vimentin by tumor cells. PATIENTS AND METHODS: Herein, we present a case of a bulky primary hepatic leiomyosarcoma in a 68-year-old female patient. The patient underwent resection of the exophytic mass en block with the hepatic segments III and IVB. CONCLUSION: Surgical resection is the most effective among the treatment options.

Histone deacetylase inhibitors as a new anticancer option: How far can we go with expectations? delivery systems.

Histone modification that occurs through the process of acetylation plays a key role in the epigenetic regulation of gene expression. The balance between histone deacetylases (HDACs) and histone acetyltransferases controls this process. Histone deacetylase inhibitors (HDACIs) can induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Therefore, HDAIs represent a group of enzymes that can be used for the development of pharmaceutical agents against a variety of malignant diseases. The mechanisms of their anticancer effect depend on many factors. HDACIs vorinostat, romidepsin and belinostat have been approved for some T-cell lymphomas and panobinostat for multiple myeloma. Other HDACIs are tested in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed.

Preoperative bevacizumab and volumetric recovery after resection of colorectal liver metastases.

BACKGROUND AND OBJECTIVES: While preoperative treatment is frequently administered to CRLM patients, the impact of chemotherapy, with or without bevacizumab, on liver regeneration remains controversial. METHODS: The early and late regeneration indexes were defined as the relative increase in liver volume (RLV) within 2 and 9 months from surgery. Regeneration rates of the preoperative treatment groups were compared. RESULTS: Preoperative chemotherapy details and volumetric data were available for 185 patients; 78 (42.2%) received preoperative chemotherapy with bevacizumab (Bev+), 46 (24.8%) received chemotherapy only (Bev-), and 61 (33%) received no chemotherapy. Patients in the Bev+ and Bev- groups received similar chemotherapy cycles (4 [3-6] vs 4 [4-6]; P = 0.499). Despite the comparable clinicopathological characteristics and Resected Volume/Total Liver Volume (TLV) at surgery (P = 0.944) of both groups, Bev+ group had higher early and late regeneration (17.2% vs 4.3%; P = 0.035 and 14.0% vs 9.4%; P = 0.091, respectively). Of note, early and late regeneration rates (3.7% and 10.9% vs 6.6% and 5.5%, respectively) were comparable between the no chemotherapy and Bev- groups (all P > 0.05). In multivariable analysis -adjusted for gender, age, portal vein embolization, preoperative chemotherapy, resected liver volume, tumor number, postoperative chemotherapy, fibrosis, steatosis- bevacizumab independently predicted early liver regeneration (P = 0.019). CONCLUSION: Our findings suggest that preoperative bevacizumab administered along with chemotherapy was associated with enhanced volumetric restoration. Interestingly, this effect was more pronounced among patients who received oxaliplatin-based regimens and bevacizumab compared to those treated with irinotecan-based regimens and bevacizumab.

Orchitis reveals an extragonadal primary mediastinal thymic seminoma: a coincidence or not?

BACKGROUND: Mediastinal thymic seminomas are rare male germ cell tumors with extragonadal origin that appear predominately with a cystic appearance. CASE PRESENTATION: A 22-year-old male was referred to our department for further investigation of a mediastinal mass discovered incidentally during routine chest X-ray. The patient has denied any symptoms including dyspnea, chest pain, cough, fever, dysphagia, hemoptysis, weight loss, and weakness. His past medical history was remarkable for orchitis, for which he had undergone a bilateral testicular biopsy, without the latter however, indicating the presence of a germ cell tumor or a premalignant lesion. Contrast-enhanced chest computed tomography revealed a lobulated and well-marginated cystic lesion in the anterior mediastinum. Differential diagnosis included mostly a multilocular thymic cyst, a lymphoma, a seminoma, or a soft tissue tumor. Resection of the mass revealed a primary thymic seminoma. CONCLUSIONS: A surgical approach for the management of these tumors might be reasonable considering that an extensive sampling is mandatory to gain an appropriate biopsy preoperatively in order to securely confirm or refute the presence of a mediastinal extragonadal tumor. Orchitis might be a sign of a general disorder of the germ cells which might transform in time.

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

AIM: Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. METHODS: We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. RESULTS: No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. CONCLUSIONS: White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

Castleman's disease of the spleen.

INTRODUCTION: Castleman's disease (CD), also known as giant or angiofolicular lymphoid hyperplasia or lymphoid hamartoma, is a group of atypical lymphoproliferative disorders that share common lymph node histological features and may be localized either to a single lymph node (unicentric) or occur systemically (multicentric). PATIENT AND METHOD: Herein, we present a rare case of a of 75-year-old female patient who was referred to our department and after a thorough work-up, underwent splenectomy with synchronous resection of an accessory spleen, splenic artery lymph nodes, and splenic hilar lymph nodes due to splenic involvement in a multicentric CD. RESULTS: The pathology of the specimens led to the conclusion that it was a case of polycentric HHV-8-positive CD, affecting the spleen, the accessory spleen, and the lymph nodes. CONCLUSIONS: Incidence of this rare condition is believed to be approximately 0.001-0.05%. CD has been linked to the human immunodeficiency virus (HIV), human herpes virus 8 (HHV-8), and is associated with malignancies. The pathogenesis mechanism is considered to be a dysregulation and hypersecretion of cytokines, either idiopathic or secondary to a viral infection, with the latter considered the most frequent. Solid organ involvement is very rare as is splenic involvement.