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.

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.

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.