Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients.

T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI+) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3+IFNγ+ cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI+ T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI+ patients compared to PreI- patients (not reached vs. 321 days, respectively; p = 0.014). PreI+ patients had significantly higher numbers of possible exhausted CD3+CD8+PD-1+ cells and lower percentages of immunosuppressive Tregs compared to PreI- patients. Additionally, patients with PreI+ and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens.

The Effects of Sarcopenia on Overall Survival and Postoperative Complications of Patients Undergoing Hepatic Resection for Primary or Metastatic Liver Cancer: A Systematic Review and Meta-Analysis.

Background: Colorectal cancer is the third most common cancer worldwide, and 20-30% of patients will develop liver metastases (CRLM) during their lifetime. Hepatocellular carcinoma (HCC) is also one of the most common cancers worldwide with increasing incidence. Hepatic resection represents the most effective treatment approach for both CRLM and HCC. Recently, sarcopenia has gained popularity as a prognostic index in order to assess the perioperative risk of hepatectomies. The aim of this study is to assess the effects of sarcopenia on the overall survival (OS), complication rates and mortality of patients undergoing liver resections for HCC or CRLM. Methods: A systematic literature search was performed for studies including patients undergoing hepatectomy for HCC or CRLM, and a meta-analysis of the data was performed. Results: Sarcopenic patients had a significantly lower 5-year OS compared to non-sarcopenic patients (43.8% vs. 63.6%, respectively; p < 0.01) and a significantly higher complication rate (35.4% vs. 23.1%, respectively; p = 0.002). Finally, no statistical correlation was found in mortality between sarcopenic and non-sarcopenic patients (p > 0.1). Conclusions: Sarcopenia was significantly associated with decreased 5-year OS and increased morbidity, but no difference was found with regard to postoperative mortality.

Large Language Models in Oncology: Revolution or Cause for Concern?

The technological capability of artificial intelligence (AI) continues to advance with great strength. Recently, the release of large language models has taken the world by storm with concurrent excitement and concern. As a consequence of their impressive ability and versatility, their provide a potential opportunity for implementation in oncology. Areas of possible application include supporting clinical decision making, education, and contributing to cancer research. Despite the promises that these novel systems can offer, several limitations and barriers challenge their implementation. It is imperative that concerns, such as accountability, data inaccuracy, and data protection, are addressed prior to their integration in oncology. As the progression of artificial intelligence systems continues, new ethical and practical dilemmas will also be approached; thus, the evaluation of these limitations and concerns will be dynamic in nature. This review offers a comprehensive overview of the potential application of large language models in oncology, as well as concerns surrounding their implementation in cancer care.

Pseudomyxoma Peritonei: A Challenging Clinical Diagnosis. Case Report and Review of the Literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical entity of subtle onset abdominal pain, ascites, and distention associated with characteristic imaging. In most cases, laparoscopic exploration will give the definitive diagnosis and histopathologic verification. However, usually there are difficulties in the diagnosis of this disease. Case Report: Herein, we present a case of a 51-year-old female who developed ascites over 5 months. An investigational laparotomy established the diagnosis of PMP, after the discovery of a mucinous, grey-brown tumor that was CK20 positive and CK7 negative. Subsequently, chemotherapy with oxaliplatin combined with 5-FU (FOLFOX4 regimen), was initiated and the patient survived for 30 months. We also present a comprehensive review of the English literature concerning the different symptoms and radiological findings of this rare entity. According to the literature review, 35 cases of PMP with different clinical and radiological findings have been described. In the majority of the cases, ultrasound, computed tomography or magnetic resonance imaging was orientating towards a proper diagnosis before a diagnostic laparotomy. Conclusion: The combination of a clinical picture with the characteristic imaging findings enables a prompt diagnosis of PMP, making prognosis more favorable.

Quality of life, distress and psychological adjustment in patients with colon cancer.

PURPOSE: The purpose of this study was to investigate the relationships between distress, psychological adjustment, and quality of life in patients with colon cancer. METHOD: This study employed a cross-sectional design and included 104 colon cancer patients treated at AHEPA Hospital, Thessaloniki, Greece. The assessment tools used encompassed the Distress Thermometer, MINI-MAC scale, and FACT-C to evaluate distress, psychological adjustment, and quality of life. Statistical analysis, conducted in SPSS software, encompassed correlation tests and linear regression to explore the interplay between these variables in colon cancer patients. RESULTS: Correlation tests revealed that patients' quality of life is positively correlated with a fighting spirit (r = 0.719, p < 0.001), cognitive avoidance (r = 0.634, p < 0.001), and fatalism (r = 0.518, p < 0.001), and negatively with helplessness and hopelessness (r = -0.756, p < 0.001), and anxious preoccupation (r = -0.679, p < 0.001). OLS regression findings verified these results partially for a significance level of 5% but indicated no statistically significant effect of cognitive avoidance and fatalism on quality of life, which was further found unaffected by total distress. CONCLUSIONS: The intricate links between quality of life, distress, and psychological adjustment in colon cancer patients call for deeper investigation. A personalized approach in psycho-oncology care is essential for comprehensive treatment. These findings highlight the significance of addressing the psychological and emotional needs of colon cancer patients, as observed in the study's results.

Renal Cell Cancer - Insights in Drug Resistance Mechanisms.

Renal cell carcinoma (RCC) is the prevalent form of kidney cancer in adults, with clear cell renal carcinoma (ccRCC) being the predominant subtype. While surgical resection remains the primary curative approach for localized RCC, a significant number of patients encounter disease relapse. The advent of targeted therapies, including tyrosine kinase inhibitors (TKI), mammalian target of rapamycin (mTOR) inhibitors, and immune checkpoint inhibitors, has revolutionized the treatment of metastatic RCC. However, despite therapeutic advancements, the emergence of resistance poses a significant challenge. Resistance mechanisms in RCC involve the disruption of hypoxia pathways, activation of the PI3K/AKT/mTOR pathway, and increased expression of alternate proangiogenic factors. Furthermore, the sequestration of TKI within lysosomes contributes to reduced drug effectiveness and development of resistance. Current research is focused on overcoming resistance by identifying predictive biomarkers for treatment efficacy, developing novel variations of existing therapies that target alternative signalling pathways, and exploring combination therapy approaches. The objective of this review article was to provide a comprehensive assessment of resistance mechanisms to systemic therapies and explore emerging treatment strategies for RCC.

Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A systematic review.

BACKGROUND: Gastric cancer (GC) is a major health concern worldwide. Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma, however, the optimal approach remains unclear and should be different in each individual. Chemotherapy can be administered both pre- and postoperatively, but a multidisciplinary approach is preferred when possible. This is particularly relevant for locally advanced GC (LAGC), as neoadjuvant chemotherapy (NAT) could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent. Even though the recent progress has been impressive, European and International guidelines are still controversial, thus attenuating the need for a more standardized approach in the management of locally advanced cancer. AIM: To investigate the effects of NAT on the overall survival (OS), the disease-free survival (DFS), the morbidity and the mortality of patients with LAGC in comparison to upfront surgery (US). METHODS: For this systematic review, a literature search was conducted between November and February 2023 in PubMed, Cochrane Library and clinicaltrials.gov for studies including patients with LAGC. Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews. RESULTS: Eighteen studies with 4839 patients with LAGC in total were included in our systematic review. Patients were separated into two groups; one receiving NAT before the gastrectomy (NAT group) and the other undergoing upfront surgery (US group). The OS ranged from 41.6% to 74.2% in the NAT group and from 30.9% to 74% in the US group. The DFS was also longer in the NAT group and reached up to 80% in certain patients. The complications related to the chemotherapy or the surgery ranged from 6.4% to 38.1% in the NAT group and from 5% to 40.5% in the US group. Even though in most of the studies the morbidity was lower in the NAT group, a general conclusion could not be drawn as it seems to depend on multiple factors. Finally, regarding the mortality, the reported rate was higher and up to 5.3% in the US group. CONCLUSION: NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates. However, patients with different clinicopathological features respond differently to chemotherapy, therefore currently the treatment plan should be individualized in order to achieve optimal results.

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.

Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC.

Gestational Renal Cell Cancer - An Update.

Gestational renal cell carcinoma (RCC) is an uncommon occurrence and presents a diagnostic and clinical challenge for healthcare providers. The manifestation of gestational RCC often lacks overt symptoms and can mimic physiological changes and disorders associated with pregnancy. Frequently, patients are asymptomatic, and the condition is detected during routine antenatal ultrasonography. However, the options for imaging modalities and treatment are limited due to the potential risks of harm to the developing fetus and interruption of pregnancy. Throughout the management of pregnant patients with RCC, both maternal and neonatal risks must be carefully considered, while respecting the patient's autonomy. Currently, there are no internationally or nationally recognized evidence-based guidelines for managing gestational RCC, highlighting the need for a multidisciplinary approach to treatment. Advances in surgical techniques have resulted in a shift from open surgeries to laparoscopic radical or partial nephrectomy procedures, with robotic-assisted approaches also gaining popularity. In cases of metastatic gestational RCC, termination of the pregnancy may be considered, and the appropriate treatment of RCC should be the priority. This article aims to provide a comprehensive review of the epidemiology, aetiology, clinical presentation, diagnosis, prognosis, and management of gestational RCC.

A Comprehensive Analysis on Nutritional and Antioxidant Characteristics of a Traditional Roasted Maize Flour (Furniko) of Pontic Greeks: Comparative Study to Related Flour Products.

Furniko flour (FF) is a traditional roasted flour derived from a maize landrace, commonly consumed by Greeks of Pontic origin in the northern regions of Greece. Despite its perceived nutritional benefits, there is a lack of scientific data to support and highlight its value. This study aimed to compare the nutritional, physicochemical, anti-nutritional, functional, and antioxidant characteristics of FF with those of traditional and non-traditional types of maize flour. Furniko flour (FF) presented the highest values for protein (10.86 ± 0.36 g/100 g), fat (5.05 ± 0.08 g/100 g), K (539.93 mg/100 g), Mg (126.38 mg/100 g), P (296.4 mg/100 g), Zn (2.44 mg/100 g), and total phenolic content (TPC) (156 mg GAE/100 g). However, FF exhibited lower levels of Fe (3.83 mg/100 g), carbohydrates (70.55 ± 0.24 g/100 g), and antioxidant activity (0.27 ± 0.02 µmol of TE/g) than other types of flour examined. Furniko's functional properties make it an excellent source for porridges, while its low content of antinutrients reduces the possibility of low bioavailability of Fe, Zn, Mg, and Ca. Due to its significant and functional characteristics, Furniko flour could be considered an important material in the food industry, especially in bakery goods and health-oriented foods like energy bars, breakfast cereals, and gluten-free pasta. More research is needed, however, to thoroughly investigate its dietary potential and compatibility with other components.

Median arcuate ligament syndrome often poses a diagnostic challenge: A literature review with a scope of our own experience.

The median arcuate ligament syndrome (MALS) is recognized as a rare clinical entity, characterized by chronic post-prandial abdominal pain, nausea, vomiting, and unintentional weight loss. Due to its vague symptomatology, it is mainly regarded as a diagnosis of exclusion. Patients can often be misdiagnosed for several years before a correct diagnosis is established, also due to a medical team's clinical suspicion. We present a case series of two patients who suffered from MALS and were treated successfully. The first patient is a 32-year-old woman, presenting with post-prandial abdominal pain and weight loss that have lasted for the past ten years. The second patient, a 50-year-old woman, presented with similar symptomatology, with the symptoms lasting for the last five years. Both cases were treated by laparoscopic division of the median arcuate ligament fibers, which alleviated extrinsic pressure from the celiac artery. Previous cases of MALS were retrieved from PubMed, to assemble a better diagnostic algorithm and propose a treatment method of choice. The literature review suggests an angiography with a respiratory variation protocol as the diagnostic modality of choice, along with the laparoscopic division of the median arcuate ligament fibers as the proposed treatment of choice.

Trocar-site hernia repair after laparoscopic surgery: a case report study.

Tracer site hernias (TSHs) are extremely uncommon. There have been only a few cases reported in the literature. Here we report a case of TSH after umbilicus laparoscopic hernia repair procedure. Diagnosis was based on patient symptoms and computed tomography. Patient underwent exploratory laparoscopy followed by laparoscopic hernia repair with mesh. We also provide a mini review of the literature in order to highlight that although rare, this pathology should be included in the differential diagnosis of acute abdomen.

Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.

Metachronous Single Pulmonary Metastasis of Prostate Cancer: Report of a Rare Case and Literature Review.

BACKGROUND: Prostate cancer recurrence after definitive local therapy usually involves the bone and regional lymph nodes. CASE REPORT: We present the case of a 72-year-old male patient with an isolated lung nodule, seven years after radical prostatectomy for prostate cancer, pT2bN0 and Gleason score 7(4+3), and prostatic-specific antigen (PSA) levels within normal limits. The nodule was considered as a primary lung cancer and the patient was subjected to lobectomy. The immunohistochemical staining showed that the tumor was PSA(+) and NKX3.1 (+), revealing that it was metastasis from prostatic cancer and that wedge resectomy was the proper procedure. Three years later the patient is disease-free, suggesting the importance of aggressive treatment of oligometastatic disease. CONCLUSION: Metastasis to the lung is present in more than 40% of men with metastatic prostate cancer; however, lung metastases without any bone or lymph node involvement are extremely rare and only a handful of cases are reported in the literature. Surgical excision of the metastatic lung site is the most common therapeutic approach associated with a good prognosis.

Inhibition of γδ-TcR or IL17a Reduces T-Cell and Neutrophil Infiltration after Ischemia/Reperfusion Injury in Mouse Liver.

Neutrophil and T-cell recruitment contribute to hepatic ischemia/reperfusion injury. The initial inflammatory response is orchestrated by Kupffer cells and liver sinusoid endothelial cells. However, other cell types, including γδ-Τ cells, seem to be key mediators in further inflammatory cell recruitment and proinflammatory cytokine release, including IL17a. In this study, we used an in vivo model of partial hepatic ischemia/reperfusion injury (IRI) to investigate the role of the γδ-Τ-cell receptor (γδTcR) and the role of IL17a in the pathogenesis of liver injury. Forty C57BL6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion (RN 6339/2/2016). Pretreatment with either anti-γδΤcR antibodies or anti-IL17a antibodies resulted in a reduction in histological and biochemical markers of liver injury as well as neutrophil and T-cell infiltration, inflammatory cytokine production and the downregulation of c-Jun and NF-κΒ. Overall, neutralizing either γδTcR or IL17a seems to have a protective role in liver IRI.

Case Report: Endoscopic radiofrequency ablation with radial-EBUS and ROSE.

Background: Single pulmonary nodules are a common issue in everyday clinical practice. Currently, there are navigation systems with radial-endobronchial ultrasound and electromagnetic navigation for obtaining biopsies. Moreover, rapid on-site evaluation can be used for a quick assessment. These small lesions, even when they do not have any clinically significant information with positron emission tomography, are important to investigate. Case description: Radiofrequency and microwave ablation have been evaluated as local treatment techniques. These techniques can be used as therapy for a patient population that cannot be operated on. Currently, one verified operating system is used for endoscopic radiofrequency ablation through the working channel of a bronchoscope. Conclusion: In our case, a new system was used to perform radiofrequency ablation with long-term follow-up.

Down-regulation of KLF2 in lung fibroblasts is linked with COVID-19 immunofibrosis and restored by combined inhibition of NETs, JAK-1/2 and IL-6 signaling.

Kruppel-like factor 2 (KLF2) has been linked with fibrosis and neutrophil-associated thromboinflammation; however, its role in COVID-19 remains elusive. We investigated the effect of disease microenvironment on the fibrotic potential of human lung fibroblasts (LFs) and its association with KLF2 expression. LFs stimulated with plasma from severe COVID-19 patients down-regulated KLF2 expression at mRNA/protein and functional level acquiring a pre-fibrotic phenotype, as indicated by increased CCN2/collagen levels. Pre-incubation with the COMBI-treatment-agents (DNase I and JAKs/IL-6 inhibitors baricitinib/tocilizumab) restored KLF2 levels of LFs to normal abolishing their fibrotic activity. LFs stimulated with plasma from COMBI-treated patients at day-7 expressed lower CCN2 and higher KLF2 levels, compared to plasma prior-to-treatment, an effect not observed in standard-of-care treatment. In line with this, COMBI-treated patients had better outcome than standard-of-care group. These data link fibroblast KLF2 with NETosis and JAK/IL-6 signaling, suggesting the potential of combined therapeutic strategies in immunofibrotic diseases, such as COVID-19.