Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is associated with lack of expression of estrogen and progesterone receptors and HER2 and is the subgroup of breast cancers with the worst prognosis. Osteopontin is a phosphorylated glycoprotein whose overexpression may occur in pathological states such as cancers. The main purpose of our study was to evaluate the immunohistochemical expression of osteopontin in connection with the analysis of recognized clinical and pathological prognostic factors in primary sites of TNBC with and without lymph node metastases. Material and methods: The immunohistochemical evaluation of osteopontin expression in 35 women with TNBC, chosen from a group of 726 patients, was performed. The material came from the excisional biopsies of primary breast cancers and total mastectomies. Results: All patients showed expression of osteopontin, in most cases the expression of osteopontin rated at [+] (57.1%) and [++] (42.9%). Our study analyzed the relationship between the expression of osteopontin and traditional prognostic markers, such as the tumor grade, size, and lymph node involvement. We found a strong relationship only between the expression of osteopontin and the presence of lymph node metastases (p ≤ 0.0001). 93% of patients for whom the expression of osteopontin was determined at [++] had metastasis to lymph nodes and, for comparison, only 15% of women for whom the expression of osteopontin was rated at [+] showed the presence of metastases in the lymphatic nodes. Conclusions: There is a correlation between osteopontin expression and the presence of lymph node metastases in TNBC, suggesting that osteopontin plays an important role in the invasiveness of TNBC.

How A Patient with Resectable or Borderline Resectable Pancreatic Cancer should Be Treated-A Comprehensive Review.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.

Evaluation of Nutritional Status and the Impact of Nutritional Treatment in Patients with Pancreatic Cancer.

Patients with pancreatic cancer who develop irreversible cancer cachexia have a life expectancy of less than 3 months. Therefore, it is extremely important to evaluate the patient's nutritional status as early as possible and to implement an appropriate nutritional intervention in order to reduce the risk of further weight loss and/or muscle loss, which affect the outcomes of cancer treatment and the correct nutritional treatment in patients with pancreatic cancer. A literature review was performed by using the PubMed and Cochrane quick search methodology. The main purpose of this review was to present the current approach to nutritional treatment in pancreatic cancer. The review included publications, most of which concerned clinical nutrition as part of the phase of treatment of patients with pancreatic cancer, nutritional and metabolic disorders in pancreatic cancer, and the period after pancreatic resection. Some of the publications concerned various nutritional interventions in patients with pancreatic cancer undergoing chemotherapy or surgical treatment (nutritional support before surgery, after surgery, or during palliative treatment). There is an unmet need for integrated nutritional therapy as a key part of the comprehensive care process for PC patients. Nutritional counseling is the first line of nutritional treatment for malnourished cancer patients, but pancreatic enzyme replacement therapy also constitutes the cornerstone of nutritional treatment for relieving symptoms of indigestion and maintaining or improving nutritional status.

Rare Non-Neuroendocrine Pancreatic Tumours.

The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms.

New Treatment Options in Metastatic Pancreatic Cancer.

Pancreatic cancer (PC) is the seventh leading cause of cancer death across the world. Poor prognosis of PC is associated with several factors, such as diagnosis at an advanced stage, early distant metastases, and remarkable resistance to most conventional treatment options. The pathogenesis of PC seems to be significantly more complicated than originally assumed, and findings in other solid tumours cannot be extrapolated to this malignancy. To develop effective treatment schemes prolonging patient survival, a multidirectional approach encompassing different aspects of the cancer is needed. Particular directions have been established; however, further studies bringing them all together and connecting the strengths of each therapy are needed. This review summarises the current literature and provides an overview of new or emerging therapeutic strategies for the more effective management of metastatic PC.

Quality of Life in Patients with Pancreatic Cancer-A Literature Review.

Pancreatic cancer is the malignant disease with the highest mortality rate, and it ranks third in the world after lung and colon cancer. Identified factors that increase the risk of developing pancreatic cancer include chronic pancreatitis, radiation therapy to the pancreatic area due to another cancer, diabetes mellitus, obesity, smoking, and age. The objective of this study was to present the current state of knowledge on the quality of life of patients diagnosed with pancreatic cancer, factors that determine QoL, and ways of coping with the disease. The low curability and low survival rates of pancreatic cancer significantly affect the quality of life of patients, often in the form of significant deterioration, especially in terms of mental changes, cognitive functions, and coping with the disease. Cognitive decline with comorbid depression is also typical for patients with this type of cancer. Research has shown that the health-related quality of life of patients with pancreatic cancer is low, so further research is needed to improve the situation in this area.

Cancer-associated inflammation: pathophysiology and clinical significance.

PURPOSE: Cancer cells, despite stemming from the own cells of their host, usually elicit an immune response. This response usually enables elimination of cancer at its earliest stages. However, some tumors develop mechanisms of escaping immune destruction and even profiting from tumor-derived inflammation. METHODS: We summarized the roles of different immune cell populations in various processes associated with cancer progression and possible methods of reshaping tumor-associated inflammation to increase the efficacy of cancer therapy. RESULTS: Changes in various signaling pathways result in attraction of immunosuppressive, pro-tumorigenic cells, such as myeloid-derived suppressor cells, tumor-associated macrophages, and neutrophils, while at the same time suppressing the activity of lymphocytes, which have the potential of destroying cancer cells. These changes promote tumor progression by increasing angiogenesis and growth, accelerating metastasis, and impairing drug delivery to the tumor site. CONCLUSION: Due to its multi-faceted role in cancer, tumor-associated inflammation can serve as a valuable therapy target. By increasing it, whether through decreasing overall immunosuppression with immune checkpoint inhibitor therapy or through more specific methods, such as cancer vaccines, oncolytic viruses, or chimeric antigen receptor T cells, cancer-derived immunosuppression can be overcome, resulting in immune system destroying cancer cells. Even changes occurring in the microbiota can influence the shape of antitumor response, which could provide new attractive diagnostic or therapeutic methods. Interestingly, also decreasing the distorted tumor-associated inflammation with non-steroidal anti-inflammatory drugs can lead to positive outcomes.

Civil Lawsuits as an Indicator of Adverse Outcomes in Healthcare.

The financial burden of adverse healthcare outcomes in Poland still remains unknown. The objective of the study was to estimate the cost of adverse healthcare outcomes in the Polish healthcare system. Cost calculation was performed on the basis of civil cases completed in Polish courts against doctors and healthcare entities. The research material consisted of 183 civil cases completed by a final judgment in 2011-2013. The case study was conducted in five out of forty-five district courts across the country. Out of 183 reviewed cases, 73 complaints ended up with favorable judgments (39.9%). The average value of the subject matter of the dispute was USD 78,675. The total expected value of lawsuits in the 183 reviewed cases was USD 11,299,020. The total amount awarded in 73 judgments from medical facilities to injured patients was USD 2,653,595, which on average means USD 36,351 per case. The average amount of awarded compensation was USD 33,317 per case. The average compensation amount in the analyzed cases was USD 11,724. The average one-time annuity for a patient was USD 11,788. The estimated costs of negative healthcare outcomes amounted to USD 8,000,000 per year.

Diabetes Mellitus and Pancreatic Ductal Adenocarcinoma-Prevalence, Clinicopathological Variables, and Clinical Outcomes.

BACKGROUND: pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths with increasing incidence and link to the onset of diabetes mellitus (DM). The aim of this study is to describe the prevalence of DM among patients with the diagnosis of PDAC, analyse the association between the occurrence of DM and clinicopathological factors, and detect variables influencing overall survival. METHODS: a retrospective analysis of medical records was performed. The patients were divided into non-DM (n = 101) and DM (n = 74) groups. Statistical analysis with the usage of appropriate tests was conducted. RESULTS: Patients in the groups of DM and NODM had significantly longer median OS than the non-DM group. Nodal involvement, tumour location, level of CEA, CRP and CRP/lymphocytes ratio were significantly associated with OS among patients with any type of DM. Neutropenia was less frequently observed in the DM group. CONCLUSIONS: DM is prevalent among patients with pancreatic cancer. In our study, patients with DM receiving palliative chemotherapy had significantly higher median OS than those without DM. The increased comprehension of the mechanisms of the relationship between DM and pancreatic cancer needs further research, which might provide avenues for the development of novel preventive and therapeutic strategies.

Current State of Knowledge on the Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer Treatment: Approaches, Efficacy, and Challenges.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options. Recently, there has been a growing interest in immunotherapy with immune checkpoint inhibitors (ICIs) in TNBC, leading to extensive preclinical and clinical research. This review summarizes the current state of knowledge on ICIs efficacy and their predictive markers in TNBC and highlights the areas where the data are still limited. Currently, the only approved ICI-based regimen for TNBC is pembrolizumab with chemotherapy. Its advantage over chemotherapy alone was confirmed for non-metastatic TNBC regardless of programmed death-ligand 1 (PD-L1) expression (KEYNOTE-522) and for metastatic, PD-L1-positive TNBC (KEYNOTE-355). Pembrolizumab's efficacy was also evaluated in monotherapy, or in combination with niraparib and radiation therapy, showing potential efficacy and acceptable safety profile in phase 2 clinical trials. Atezolizumab + nab-paclitaxel increased the overall survival (OS) over placebo + nab-paclitaxel in early TNBC, regardless of PD-L1 status (IMpassion031). In IMpassion130 (untreated, advanced TNBC), the OS improvement was not statistically significant in the intention-to-treat population but clinically meaningful in the PD-L1 positive cohort. The durvalumab-anthracycline combination showed an increased response durability over placebo anthracycline in early TNBC (GeparNuevo). Several phase 1 clinical trials also showed a potential efficacy of atezolizumab and avelumab monotherapy in metastatic TNBC. ICIs appear to be applicable in both neoadjuvant and adjuvant settings, and are both pretreated and previously untreated patients. Further research is necessary to determine the most beneficial drug combinations and optimize patient selection. It is essential to identify the predictive markers for ICIs and factors affecting their expression.

Medullary breast cancer is a predominantly triple-negative breast cancer - histopathological analysis and comparison with invasive ductal breast cancer.

Introduction: Medullary breast cancer (MdBC) is an uncommon type of breast cancer representing 1-7% of all cases. It is characterized by the occurrence of many histopathological features associated with a high grade of malignancy. Material and methods: Twelve MdBCs chosen from a group of 1,122 women suffering from invasive breast cancer were analyzed. Histopathological examination and analysis of a basic molecular profile, i.e. estrogen (ER), progesterone (PR) and HER2 receptor expression, and their comparison with invasive ductal breast cancer (IDC), were performed. Results: MdBC accounted for 1.07% of all analyzed invasive breast cancer patients. All patients were female, with an average age of 58.54 years. The MdBC group exhibited a larger median tumor diameter (2.05 vs. 1.89 cm), although ≥ T2 tumors comprised 42% vs. 51% for IDCs. Women without regional lymph node involvement (pN0) (83%) formed the largest group. There was a statistically significant difference in the presence of nodal involvement between the studied groups (p < 0.001). Based on the histological grade of malignancy, the majority of MdBC comprised grade II tumors (G2) (93%). In general, MdBC showed statistically higher histologic grade (G1-G3) than IDC (p = 0.003). The 5-year overall survival rate of MdBC patients was 91%. Most MdBCs (92%) were triple-negative, whereas the remaining 8% were HER2 positive. Conclusions: MdBC presented at a younger age than IDC, had a higher histological grade, larger median size and less frequent regional lymph node involvement. Most MdBCs were triple-negative, whereas IDCs were predominantly luminal. Despite numerous aggressive pathological features of MdBC, its clinical outcome and overall prognosis are favorable.

Pulmonary blastoma in a pregnant woman: a case report and brief review of the literature.

BACKGROUND: Pulmonary blastoma (PB) comprises a rare heterogeneous group of lung tumours typically containing immature epithelial and mesenchymal structures that imitate the embryonic lung tissue and extremely rarely occurs during pregnancy. Although cough and haemoptysis are the most common PB symptoms, they usually indicate other serious pregnancy-related complications. CASE PRESENTATION: The article presents the unusual case of a 22-year-old pregnant woman diagnosed with PB during pregnancy. CONCLUSIONS: PB is characterized by poor prognosis and patients' outcome relies on a rapid diagnosis. Surgery remains the most common and effective treatment. Due to the extreme rarity, the literature contains only single mentions of PB in pregnancy, thus its impact on the course of pregnancy and the developing fetus remains unknown.

Can we minimize carbon footprint by using "greener" inhalers and improve clinical outcome at the same time in asthma therapy?

The treatment of patients with obstructive airway diseases is based on the use of inhalation preparations. Some of them, mainly including pressurized metered dose inhalers (pMDIs), contain compressed gases - hydrofluoroalkanes, which generate carbon dioxide emissions, creating the so-called carbon footprint. AIM: The aim of the study was to evaluate the consumption of individual active substances, the types of inhalers used and calculation of the carbon footprint of therapies in patients with asthma in 2018 and 2019 in Poland. MATERIALS AND METHODS: The ratio of pMDI vs DPI (dry powder inhaler) data and the data on using in patients with asthma long-acting ß2-agonists (LABAs), short-acting ß2-agonists antagonists (SABAs), long-acting muscarinic antagonists (LAMAs), LAMA+LABAs, LAMA+LABA+ICSs (inhaled corticosteroids) on Polish market during 2018 and 2019 were analyzed. The carbon footprint of such therapies was counted. Then, we studied the reduction of the carbon footprint for scenario A (reducing pMDI by 50%) and scenario B (reducing pMDI by 80%) in the following steps of analysis. RESULTS: The general structure of pMDI/DPI in Poland in asthma patients was not changed in 2019 vs 2018. The carbon footprint is primarily created by pMDI SABAs. In 2019 in Poland pMDI SABAs were 1.9 mio units (the same as in 2018), which generated 36.8 kt CO2e annually. Scenario A gives us a benefit of 17.4 kt CO2e reduction and scenario B brings us a benefit of 28.0 kt CO2e reduction of emissions. CONCLUSIONS: Despite Poland's ratification the Kigali amendment did not affect pMDI consumption by asthma patients and did not reduce the carbon footprint. The lower carbon footprint of DPIs should be considered alongside other factors when choosing inhalation devices.

Improved understanding of gastrointestinal stromal tumors biology as a step for developing new diagnostic and therapeutic schemes.

A gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract, with an estimated incidence of 10-15 per 1 million per year. While preparing holistic care for patients with GIST diagnosis, scientists might face several difficulties - insufficient risk stratification, acquired or secondary resistance to imatinib, or the need for an exceptional therapy method associated with wild-type tumors. This review summarizes recent advances associated with GIST biology that might enhance diagnostic and therapeutic strategies. New molecules might be incorporated into risk stratification schemes due to their proven association with outcomes; however, further research is required. Therapies based on the significant role of angiogenesis, immunology, and neural origin in the GIST biology could become a valuable enhancement of currently implemented treatment schemes. Generating miRNA networks that would predict miRNA regulatory functions is a promising approach that might help in better selection of potential biomarkers and therapeutical targets in cancer, including GISTs.

The complexity of tumour angiogenesis based on recently described molecules.

Tumour angiogenesis is a crucial factor associated with tumour growth, progression, and metastasis. The whole process is the result of an interaction between a wide range of different molecules, influencing each other. Herein we summarize novel discoveries related to the less known angiogenic molecules such as galectins, pentraxin-3, Ral-interacting protein of 76 kDa (RLIP76), long non-coding RNAs (lncRNAs), B7-H3, and delta-like ligand-4 (DLL-4) and their role in the process of tumour angiogenesis. These molecules influence the most important molecular pathways involved in the formation of blood vessels in cancer, including the vascular endothelial growth factor (VEGF)-vascular endothelial growth factor receptor interaction (VEGFR), HIF1-a activation, or PI3K/Akt/mTOR and JAK-STAT signalling pathways. Increased expression of galectins, RLIP76, and B7H3 has been proven in several malignancies. Pentraxin-3, which appears to inhibit tumour angiogenesis, shows reduced expression in tumour tissues. Anti-angiogenic treatment based mainly on VEGF inhibition has proved to be of limited effectiveness, leading to the development of drug resistance. The newly discovered molecules are of great interest as a potential source of new anti-cancer therapies. Their role as targets for new drugs and as prognostic markers in neoplasms is discussed in this review.

Histopathological analysis of mucinous breast cancer subtypes and comparison with invasive carcinoma of no special type.

Mucinous breast cancer (MBC) is a rare histological type of breast cancer characterized primarily by mucin's production and extracellular presence. MBC is usually associated with a better prognosis than other invasive breast neoplasms. Because of the low prevalence, MBC biology is not well understood. The aim of the present study was to introduce the last 2-year experience regarding MBC pathological diagnostics in our clinical center and comparison of the obtained data with invasive breast carcinoma of no special type (NST) comprising the most common invasive breast cancer. We identified 24 MBC cases representing 3.09% of all 766 invasive breast cancers, including 15 cases of pure type and 9 mixed MBCs. The median MBC patients' age at presentation was 65.5 years. Compared to NST, MBC presented a higher T stage with a statistically larger tumor median size, although lower regional lymph node involvement, tumor histological grade and TNM stage. MBC is a rare type of breast cancer, accounting for about 4% of all diagnosed breast cancers. Our findings are consistent with those published in recent years and show significant differences between MBC and NST cancer patients and also highlight differences between pure and mixed MBC, emphasizing the essence of their differentiation. MBC is associated with a better long-term prognosis than NST and is characterized by the less aggressive biological behavior expressed through favorable clinicopathologic features in terms of tumor grade, regional lymph node involvement and hormone receptor status.

What is new about ovarian malignancies?

Ovarian cancer is one of the most prevalent pathologies in gynaecology. This malignancy can be divided into 2 large groups: epithelial and non-epithelial. Because epithelial ovarian cancers (EOC) are the most commonly diagnosed, this paper focuses on the latest therapies associated with this disease. Due to the difficult diagnosis, EOC is frequently detected in the advanced stage. The treatment is usually complex and requires specialist knowledge. Advances and new ideas, such as identification of various genes and molecules that can serve as prognostic factors, might increase patients' chances of survival; they may contribute to optimization of patients' treatment, deciding whether to use aggressive treatment strategies, and predicting chemoresistance. Moreover, new strategies might also improve the quality of life of patients. The study aimed to analyse and discuss the latest reports on new methods of managing EOC.

Incorporating immunohistochemical markers into screening methods for BRCA1-mutated breast cancer.

BRCA1-mutated breast cancer (BC) is responsible for approximately 25% of hereditary breast cancer cases. BRCA1 is a tumor suppressor protein regulating the cell cycle and DNA repair; therefore its dysfunctions play a significant role in carcinogenesis. BRCA1-mutated BC is associated with basal-like phenotype, lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in addition to frequent TP53 mutations and poor prognosis. Currently used criteria for genetic evaluation of BC for the risk of hereditary mutations are based on patients' age and family history, and therefore are prone to be imprecise or incomplete. This review discusses recently developed sets of immunohistochemical markers, promising independent markers (nestin, ALDH1, FOXO3, claudins, topoisomerase 1, EGFR) and their potential to be incorporated into clinical practice as a support tool in oncological counseling. This approach could be applied as a screening method for cost-effective selection of cases requiring genetic testing or adapted in pathology laboratories with limited access to molecular techniques. Although not all of the described predictor models have been validated yet, they could further improve the performance of BRCA1 screening methods in BC in the near future via increasing the accuracy of criteria for further genetic evaluation.

αB-crystallin as a promising target in pathological conditions - A review.

INTRODUCTION AND OBJECTIVE: αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. STATE OF KNOWLEDGE: α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. CONCLUSIONS: Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.