PD-1/PD-L1 axis: implications in immune regulation, cancer progression, and translational applications.

The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management.

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer.

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan-Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC's pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

Elevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients.

Pancreatic cancer is a highly lethal malignancy with a growing incidence reported worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, which is often diagnosed at advanced stages, making its prognosis and medical management difficult. The identification of histopathological biomarkers has allowed a more precise stratification of pancreatic cancer patients, providing additional information about their prognosis and offering possible therapeutic targets to be explored. The prognostic value of the receptor activator of nuclear factor-kappa B (RANK) and its ligand (RANKL) has been evaluated in breast and prostate tumors, however, their usefulness has not been assessed in pancreatic cancer. In the present work, we analyzed the relationship between the protein expression of RANK and RANKL with the survival of 41 patients with pancreatic cancer followed for 60 months, by performing immunohistochemistry and Kaplan-Meier curves. Our results demonstrate a direct association of high expression levels of RANK and RANKL with poorer survival of pancreatic cancer patients in comparison to those with low/medium and null expression levels of both markers. Further studies should be conducted to explore the carcinogenic role of both components in this type of tumor, as well as additional promising translational uses.

Exploring Biomarkers in Breast Cancer: Hallmarks of Diagnosis, Treatment, and Follow-Up in Clinical Practice.

Breast cancer is a prevalent malignancy in the present day, particularly affecting women as one of the most common forms of cancer. A significant portion of patients initially present with localized disease, for which curative treatments are pursued. Conversely, another substantial segment is diagnosed with metastatic disease, which has a worse prognosis. Recent years have witnessed a profound transformation in the prognosis for this latter group, primarily due to the discovery of various biomarkers and the emergence of targeted therapies. These biomarkers, encompassing serological, histological, and genetic indicators, have demonstrated their value across multiple aspects of breast cancer management. They play crucial roles in initial diagnosis, aiding in the detection of relapses during follow-up, guiding the application of targeted treatments, and offering valuable insights for prognostic stratification, especially for highly aggressive tumor types. Molecular markers have now become the keystone of metastatic breast cancer diagnosis, given the diverse array of chemotherapy options and treatment modalities available. These markers signify a transformative shift in the arsenal of therapeutic options against breast cancer. Their diagnostic precision enables the categorization of tumors with elevated risks of recurrence, increased aggressiveness, and heightened mortality. Furthermore, the existence of therapies tailored to target specific molecular anomalies triggers a cascade of changes in tumor behavior. Therefore, the primary objective of this article is to offer a comprehensive review of the clinical, diagnostic, prognostic, and therapeutic utility of the principal biomarkers currently in use, as well as of their clinical impact on metastatic breast cancer. In doing so, our goal is to contribute to a more profound comprehension of this complex disease and, ultimately, to enhance patient outcomes through more precise and effective treatment strategies.

The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer.

The RANK-RANKL-OPG system is a complex signaling pathway that plays a critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL is a ligand that binds to RANK, a receptor expressed on osteoclasts, dendritic cells, T cells, and other cells. RANKL signaling promotes osteoclast differentiation and activation, which leads to bone resorption. OPG is a decoy receptor that binds to RANKL and inhibits its signaling. In cancer cells, RANKL expression is often increased, which can lead to increased bone resorption and the development of bone metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown to be effective in the treatment of skeletal-related events, including osteoporosis or bone metastases, and cancer. This review will provide a comprehensive overview of the functions of the RANK-RANKL-OPG system in bone metabolism, mammary epithelial cells, immune function, and cancer, together with the potential therapeutic implications of the RANK-RANKL pathway for cancer management.

Uterine carcinosarcoma with intestinal involvement: A case report and literature review.

Uterine carcinosarcoma (UCS) is a high-grade endometrial cancer characterized by two components: Carcinomatous (epithelial) and sarcomatous (stromal tissue) elements. The present study describes a clinical case of this type of UCS and also provides a brief literature review of this type of tumor. A 72-year-old female visited the emergency department of the authors' hospital with pain in the hypogastric region, intestinal dysrhythmia since 3 months prior, fever and a palpable abdominal mass. Laboratory test results revealed sepsis and mild anemia and an imaging test revealed a large uterine tumor with wide areas of necrosis and adenopathies. As determined by the multidisciplinary committee, surgery was considered the main treatment option and this was performed with no incidences. Carcinosarcoma is a rare tumor, which most frequently occurs in older women. The diagnosis is based on symptoms and imaging tests, such as ecography and scans. The gold standard of treatment is surgery, although it is possible that other types of therapies, such as chemotherapy and radiotherapy may also be effective, depending on the tumor stage. On the whole, the prognosis of patients with this type of tumor is poor, with a low survival rate, even in earlier stages due to its malignant component and the possibility for metastasis. Surgery is the optimal treatment for this type of tumor, if this is possible, always individualizing patients.

Rotura espontánea de quiste hepático simple: éxito del tratamiento conservador / Spontaneous rupture of a simple liver cyst: success of a conservative approach

RESUMEN Los quistes hepáticos simples (QHS) son las lesiones hepáticas más frecuentes. Cursan habitualmente asintomáticas, aunque cuando alcanzan gran tamaño pueden causar síntomas. El objetivo del presente artículo es presentar una complicación excepcional de los QHS. Presentamos a una mujer de 61 años con historia de QHS múltiples que acude a Urgencias por dolor abdominal brusco sin antecedente traumático. Ante la sospecha de rotura quística espontánea, se realiza tomografía computarizada (TC) abdominal que confirma el diagnóstico. Se decide tratamiento conservador con buena evolución. Tras el episodio agudo es intervenida quirúrgicamente realizándose destechamiento de los quistes. a rotura de los QHS es una complicación excepcional que habitualmente cursa con dolor abdominal. Debido a su baja frecuencia no existe un tratamiento estándar. Se acepta que el tratamiento conservador es una buena opción en pacientes sin signos de peritonitis, mientras que la cirugía urgente está indicada en pacientes con abdomen agudo.

ABSTRACT Simple liver cysts (SLC) are the most common liver tumors. They are usually asymptomatic but large cysts may produce symptoms. The aim of this article is to report a rare complication of SLC. We report the case of a 61-year-old woman with a history of multiple SLCs who sought medical care due to sudden abdominal pain not associated with trauma. A probable diagnosis of spontaneous rupture was made, and the patient underwent computed tomography (CT) scan of the abdomen which confirmed the suspicion. Conservative treatment was decided, with favorable outcome. After the acute episode the patient underwent surgery and the cysts were unroofed. Rupture of SLC is a rare complication that usually presents with abdominal pain. There is no standard of care due to the low incidence of this complication. The conservative approach is a good option in patients without signs of peritonitis, while emergency surgery is indicated in patients with acute abdomen.

Clostridium perfringens necrotizing pancreatitis: an unusual pathogen in pancreatic necrosis infection.

Pancreatic necrosis infection (PNI) accounts for about 20-40 % of severe acute pancreatitis. PNI caused by anaerobic bacteria is unusual but when they present, Clostridium perfringens is the microorganism most commonly involved. We present a 60-year-old patient with a previous history of SARS-CoV-2, diagnosed with acute pancreatitis. During the hospitalisation he developed Clostridium perfringens bacteraemia. A CT-scan showed pancreatic gas gangrene and a surgical necrosectomy was performed. Clostridium perfringens was isolated in cultures of the pancreatic tissue and collections. The patient's clinical status improved after surgery and the appropriate medical therapy. He was discharged 76 days after admission. Nowadays, the 'step-up approach' is an accepted therapeutic tool in treatment of pancreatic necrosis and peripancreatic fluid collections. However, most authors suggest that Clostridum perfringens infection requires a more aggressive approach due to the high mortality associated to clostridial infection.

Prognostic factors of survival in stage IV colorectal cancer with synchronous liver metastasis: Negative effect of the KRAS mutation.

The aim of the present study was to identify predictive parameters of survival in patients affected by stage IV colorectal cancer with synchronous and bilateral liver metastases. A retrospective cohort study was performed. Patients diagnosed between January 2013 and December 2018 were included in the present study. Data on the histopathological, clinical and treatment factors (chemotherapy as the first measure or resection of the primary tumor) were collected. The effect of each variable on survival was evaluated using Cox regression analysis. A total of 104 patients were included [43 women (41.3%) and 61 men (58.7%); mean age, 63 years]. The long-term survival rate at 36 months was 29% (median, 25 months). Kaplan-Meier analysis was used to estimate that survival was higher in patients with wild-type KRAS tumors (42%) than in patients with mutated KRAS tumors (9%; P=0.001). In the multivariate analysis, KRAS mutation (HR, 2.484; 95% CI, 1.472-4.192), T4 tumors (HR, 1.795; 95% CI, 1.045-3.084), resection/local treatment of hepatic metastases (HR, 0.447; 95% CI, 0.222-0.901), Eastern Cooperative Oncology Group performance status (HR, 1.632; 95% CI, 1.182-2.254), were revealed to have independent predictive value. The type of treatment (chemotherapy or resection of the primary tumor) did not influence the survival. The results indicated that mutation of the KRAS gene was an important prognostic factor and associated with survival.

Colon adenocarcinoma first presenting as shoulder pain. Case report.

Bone metastases of colorectal cancer (CRC) are uncommon and usually occur in the context of a widespread disease. A 77-year-old woman presented with increasing pain in the right shoulder which had started 5 months earlier. On examination, a hard mass arising from the right scapula was found. There were no other abnormal findings on body Computerized Tomography (CT). A biopsy confirmed a metastatic adenocarcinoma. Further colonoscopy revealed a colonic obstructive tumour. Both solitary metastasis and the primary tumour were treated, and patient maintains a progression-free status. This is an unusual form of presentation for a colon cancer. With this report we aimed to discuss the unique clinical and pathological features of this colonic cancer and call attention of the physicians' community for this atypical presentation. Isolated bone metastasis in CRC is a rare entity and there are only a few similar cases reported in the literature.

Primary Hyperparathyroidism due to Parathyroid Adenoma Originated from Supernumerary Gland.

INTRODUCTION: The variability of the location of the parathyroid glands is directly related to the events that occur during embryonic development. The impact that an individual submits more than four parathyroid glands is close to 13%. However the presentation of a parathyroid adenoma in a supernumerary gland is an uncommon event. CASE REPORT: A 30-year-old man diagnosed with primary hyperparathyroidism with matching findings on ultrasonography and scintigraphy for parathyroid adenoma localization lower left regarding the thyroid gland. A cervicotomy explorer showed four orthotopic parathyroid glands. The biopsy of the inferior left gland was normal. No signs of adenoma were seen in the biopsy. Following mobilization of the ipsilateral thyroid lobe, fifth parathyroid gland was found increased significantly in size than proceeded to remove, confirming the diagnosis of adenoma. After the excision, the levels of serum calcium and parathyroid hormone were normalized. CONCLUSIONS: The presentation of a parathyroid adenoma in a supernumerary gland is a challenge for the surgeon. The high sensitivity having different imaging techniques has been a key to locate preoperatively the pathological parathyroid gland. Analytical or clinical persistence of primary hyperparathyroidism after parathyroid surgery can occur if the location of the adenoma is a supernumerary or ectopic gland location.