Advanced Stage Research Articles

Platinum-based chemotherapy promotes antigen presenting potential in monocytes of patients with high-grade serous ovarian carcinoma

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. The major clinical challenge includes the asymptomatic state of the disease, making diagnosis possible only at advanced stages. Another OC complication is the high relapse rate and poor prognosis following the standard first-line treatment with platinum-based chemotherapy. At present, numerous clinical trials are being conducted focusing on immunotherapy in OC; nevertheless, there are still no FDA-approved indications. Personalized decision regarding the immunotherapy, including immune checkpoint blockade and immune cell–based immunotherapies, can depend on the effective antigen presentation required for the cytotoxic immune response. The major aim of our study was to uncover tumor-specific transcriptional and epigenetic changes in peripheral blood monocytes in patients with high-grade serous ovarian cancer (HGSOC). Another key point was to elucidate how chemotherapy can reprogram monocytes and how that relates to changes in other immune subpopulations in the blood. To this end, we performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with HGSOC who underwent neoadjuvant chemotherapeutic treatment (NACT) and in treatment-naïve patients. Monocyte cluster was significantly affected by tumor-derived factors as well as by chemotherapeutic treatment. Bioinformatical analysis revealed three distinct monocyte subpopulations within PBMCs based on feature gene expression – CD14.Mn.S100A8.9hi, CD14.Mn.MHC2hi and CD16.Mn subsets. The intriguing result was that NACT induced antigen presentation in monocytes by the transcriptional upregulation of MHC class II molecules, but not by epigenetic changes. Increased MHC class II gene expression was a feature observed across all three monocyte subpopulations after chemotherapy. Our data also demonstrated that chemotherapy inhibited interferon-dependent signaling pathways, but activated some TGFb-related genes. Our results can enable personalized decision regarding the necessity to systemically re-educate immune cells to prime ovarian cancer to respond to anti-cancer therapy or to improve personalized prescription of existing immunotherapy in either combination with chemotherapy or a monotherapy regimen.

Paclitaxel hyperthermia suppresses gastric cancer migration through MiR-183-5p/PPP2CA/AKT/GSK3β/β-catenin axis

BackgroundGastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it’s equivocal about the mechanism under HIPEC.MethodsMiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored.ResultsMiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression.ConclusionMiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.

EP484 - Triple negative male breast cancer: a case report

Abstract Background Male breast cancer (MBC) is a rare malignancy, may present at advanced disease stage. Triple negative breast cancer (TNBC) known to have the poorest prognosis of all other histological types of breast cancer. This paper presents a case of 71 years old gentleman diagnosed with TNBC. Materials and Methods A 71 years old male patient, presented with a right breast lump. Clinically he had a skin dent and a palpable 3cm lump underneath in the right breast axillary tail. Mammogram and breast US showed suspicious lesion in right breast axillary tail in addition to a suspicious lymph node in right axilla. Imaging guided core biopsies were taken from the breast and axillary abnormalities. The histology revealed grade1 invasive ductal carcinoma NST, ER 0, PR 0 and HER 2 negative. The Breast-Multidisciplinary Team meeting advised for mastectomy and axillary clearance, this has been performed. Result The postoperative Pathomorphology report revealed 23 mm triple negative invasive ductal carcinoma NST, grade 1with Ki67 10%, T2N1M0. The postoperative MDT recommended annual surveillance with mammogram for 5 years. Conclusions MBC is uncommon entity, accounting for < 1% of all breast cancer diagnosed in both genders and the MTNBC still is rarer, and mastectomy is the mainstay of surgical treatment in addition to chemotherapy and radiotherapy , however the later doesn’t affect the cause-specific survival rate.

FP2.2 - Does preoperative nutritional assessment correlate with postoperative outcomes of patients undergoing surgery due to colorectal cancer? A bicenter prospective observational study

Abstract Aims Preoperative nutritional status has been investigated as a risk factor for postoperative complications in patients undergoing surgery due to colorectal surgery. The aim of the present study was to investigate the predictive role of preoperative nutritional assessment in terms of morbidity and mortality in such patients. Methods Patients undergoing surgery due to colorectal cancer from March 2022 until March 2023 at two university surgical departments were included in the present study. Patients’ demographics and postoperative parameters, such as complications’ severity according to Clavien-Dindo classification and mortality, along with malignancy stage were reported. Preoperative nutritional assessment was conducted according to the Patient-Generated Subjective Global Assessment (PG-SGA) tool and the Geriatric Nutritional Risk Index (GNRI) tool. The present study was registered in ClinicalTrials.gov (NCT05795374). Results The present study included 159 patients with a mean age of 69 ± 12 years old. Severe malnutrition according to the PG-SGA tool was associated with advanced disease stage (66% vs 59%, p=0.006). In addition, the high risk of malnutrition according to the GNRI tool was correlated to major (Clavien-Dindo≥3) postoperative complications (19% vs 15%, p=0.026) and increased 30-day mortality (34% vs 9%, p=0.026). Conclusions Postoperative morbidity and mortality of patients undergoing surgery due to colorectal cancer seem to be associated with preoperative nutritional stratification, especially with the high malnutrition risk.

The Immunosuppressive Receptor CD32b Regulation of Macrophage Polarization and Its Implications in Tumor Progression.

Macrophages, pivotal components of the immune system, orchestrate host defense mechanisms in humans and mammals. Their polarization into classically activated macrophages (CAMs or M1) and alternatively activated macrophages (AAMs or M2) dictates distinct functional roles in immunity and tissue homeostasis. While the negative regulatory role of CD32b within the FC gamma receptor (FCγR) family is recognized across various immune cell types, its influence on macrophage polarization remains elusive. This study aimed to elucidate the regulatory role of CD32b in macrophage polarization and discern the differential expression markers between the M1 and M2 phenotypes following CD32b siRNA transfection. The results revealed a decrease in the CD32b levels in lipopolysaccharide (LPS)-treated M1 and an increase in interleukin-4 (IL-4)-treated M2 macrophages, as observed in macrophage Raw264.7 cells. Furthermore, CD32b siRNA transfection significantly downregulated the M2 markers (IL-10, VEGF, Arg-1, and STAT6), while upregulating the M1 markers (IL-6, NF-κB, NOS2, and STAT1) in the Raw264.7 cells. Similar findings were recapitulated in macrophage-rich adherent cells isolated from mouse spleens. Additionally, the cytopathological analysis of pleural effusions and ascitic fluids from patients with cancer revealed a positive correlation between advanced tumor stages, metastasis, and elevated CD32b levels. In conclusion, this study highlights the regulatory influence of CD32b in suppressing M1 expression and promoting M2 polarization. Moreover, heightened M2 activation and CD32b levels appear to correlate with tumor progression. A targeted CD32b blockade may serve as a novel therapeutic strategy to inhibit M2 macrophage polarization and is promising for anti-tumor intervention.

Durable remission of refractory and advanced stage mycosis fungoides/sezary syndrome utilizing an “outpatient” alemtuzumab, fludarabine-based reduced intensity allogeneic hematopoietic cell transplantation

Durable remission of refractory and advanced stage mycosis fungoides/sezary syndrome utilizing an “outpatient” alemtuzumab, fludarabine-based reduced intensity allogeneic hematopoietic cell transplantation

A new scoring system to predict survival in elderly advanced stage Hodgkin lymphoma patients

Predictive prognostic scoring (PS) systems are not primarily applicable to elderly patients with classical Hodgkin lymphoma (cHL). The objective of this study was to develop a PS system for these patients. The derivation cohort (DC) was utilized for model development, consisting of 97 variables. The resulting algorithm was named as Hodgkin’s Lymphoma Early Death in the Elderly within 12 months (HEDEL12). Internal and external validation cohorts (IVC and EVC) were employed for validation. A total of 286 patients were evaluated retrospectively. In DC 38 of 178 patients died within the first 12 months and overall survival (OS) at 12-month was 78.6%. Independent predictors of HEDEL12 were female sex, low albumin levels (<3.5 g/dL), and ECOG scores 2-4. According to HEDEL12 scores 0–1, OS at 12- months were 89.8% and 91.0% for IVC and EVC, respectively. The HEDEL12 scoring is useful in predicting the survival of advanced-stage cHL patients.

SP4.9 - Relationship Between Classifications for Cancer Cachexia and Overall Survival in Patients with Oesophagogastric Cancer

Abstract Aim Classifications for cancer cachexia remain heterogenous within the existing literature. The aim of this study is to compare prognostication using three established descriptors: the Fearon et al. consensus definition, Martin et al.’s weight loss grading system and the Global Leadership Initiative on Malnutrition (GLIM) criteria, in patients with oesophagogastric cancer. Methods Consecutive patients with newly diagnosed oesophagogastric cancer between 2019-2020 were identified from a prospectively maintained regional database. Data were retrieved regarding involuntary weight loss, body mass index, CT body composition analyses and neutrophil-lymphocyte-ratio at the time of clinical staging. This allowed comparison based on Fearon, Martin and GLIM classifications. The primary outcome of interest was overall survival. Results Overall, 465 patients (66.9% male, median 71 years) were diagnosed with oesophageal (72.0%) or gastric cancer (28.0%). Greater proportions of advanced stage disease were associated with Fearon (p=0.019), Martin (p=0.004) and GLIM (p&amp;lt;0.001) defined cachexia. Patients who met the GLIM criteria were also older and had poorer ECOG performance status (both p&amp;lt;0001). Each cachexia classifier was associated with worsened overall survival (all p&amp;lt;0.001). Following adjustment for clinicopathological confounders, Fearon (aHR: 1.54 (95%CI:1.24-1.92) and GLIM defined cachexia (aHR: 1.74 (95%CI:1.40-2.17) were both adversely associated with overall survival. Grade 4 weight-loss, as per Martin et al., had the greatest prognostic effect (aHR: 2.11 (95%CI:1.52-2.93). Conclusion Cancer cachexia is strongly associated with poorer survival in oesophagogastric cancer. The GLIM criteria and high Martin et al. weight loss grade appear to have the greatest prognostic value.

SP4.10 - Comparison of the Global Leadership Initiative on Malnutrition (GLIM) Phenotypic Criteria in Patients with Oesophagogastric Cancer

Abstract Aim The Global Leadership Initiative on Malnutrition (GLIM) consensus proposed that patients should meet one of three phenotypic criteria for a diagnosis of malnutrition. This study examined the association between these criteria and survival in oesophagogastric cancer. Methods Consecutive patients newly diagnosed with oesophagogastric cancer were identified from a prospectively maintained regional database between 2019-2020. Data were collected regarding the GLIM phenotypical criteria: involuntary weight loss (≥5% in 6 months or ≥10% in &amp;gt;6 months), body mass index (&amp;lt;20kg/m2 (&amp;lt;70 years) or &amp;lt;22kg/m2 (&amp;gt;70 years)) and reduced muscle mass via body composition analysis. Cross-sectional area of skeletal muscle was measured at mid-L3 on staging CT imaging. This was normalised for height to create skeletal muscle index (SMI), with low SMI being defined as per Martin et al. The outcome of interest was overall survival. Results Overall, 465 patients (median 71 years, n=311 males) were identified. Weight loss (p=0.022), BMI (p&amp;lt;0.001) and SMI (p=0.005) cut-offs were all associated with reduced ECOG performance status. BMI and SMI were also associated with increased age. A higher proportion of patients with advanced stage malignancy met the weight loss threshold (p=0.001). Each phenotypical criterion was associated with worsened overall survival (all p&amp;lt;0.001). While all three were prognostic, following adjustment for confounders, low SMI (aHR:1.76 (95%CI:1.39-2.22)) was more strongly associated with poor survival than low BMI (aHR:1.57 (95%CI:1.18-2.08)) or weight loss (aHR:1.46 (95%CI:1.17-1.81)). Conclusion While each of the GLIM phenotypical criteria are adversely prognostic in oesophagogastric cancer, low SMI is most strongly associated with poor survival.

FP4.16 - Impact of Clinician Factors and Judgement Biases on Delayed Referrals and Diagnosis of Colorectal Cancer (CRC)

Abstract Aim Colorectal cancer (CRC) is the 4th most common cancer in the U.K. contributing to 10% of cancer-related fatalities. Despite clear NICE referral guidelines, there are various patient-, clinician- and system-related delays in referrals to the lower gastrointestinal (LGI) services. Our article investigated clinician-associated biases that govern the timeliness of referral to the LGI services. Method Our article is a narrative review. We searched Embase and Ovid Medline databases using a range of terms. Results yielded 36 articles relevant to our topic. Results GP referrals make up 44%-69% of suspected CRC referrals. Yet, national data highlights that emergency presentations range from 14%-30% nationwide, indicating missed opportunity in the primary care setting. Cognitive bias was commonly seen and included GP’s poor familiarity with referral criteria and failure to recognise red flags. Patient cultural and demographical biases played a significant role in decision-making often leading to misappraisal, with the patient’s age being the most common factor. Younger patients were less commonly referred onto the 2-week-wait (2ww) pathway, and faced an average delay in diagnosis of a month with 1.4 times more visits to care providers. In addition, information and communication biases were a recurring theme in the literature which discussed the effects of inadequate histories and physical examinations on missed diagnosis and delayed referrals. Conclusions Unintentional bias delays CRC referrals resulting in a substantial proportion of patients presenting as an emergency with advanced stage cancer that has poorer outcome. We need to increase awareness of these biases and find ways to negate their effects in clinical decision-making.

EP502 - Outcome of 5 years of endoscopic oesophageal stenting: a retrospective analysis

Abstract Background Oesophageal endoscopic stenting has a wide range of indications however dysphagia and use in cancer of the oesophagus is by far the most common, being the 14th most common cancer in the UK, despite advances in diagnosis and therapy with patients often presenting at advanced stages of the disease. Greater than 50% of presentations are at an advanced stage of disease where resection is often not possible and palliation is required. Palliation often is a potential combination of palliative chemotherapy, radiotherapy and endoscopic stenting to control the disease burden and improve symptoms. One of the most limiting palliative symptoms is dysphagia for which oesophageal stenting has become the standard of treatment showing immediate results. However, intra/post procedural complication rates can be high leading to: oesophageal perforation, mediastinitis, aspiration pneumonia, failed stent insertion or slippage. Method A retrospective analysis of 97 patients who underwent oesophageal stenting, in a 5 year time period between 2018-2023 in the Dumfries Royal Infirmary, a large district general hospital. Patients electronic notes were retrospectively analysed for patient characteristics, indication for stenting, early complications, successful hospital discharge and mortality. Conclusion The retrospective study demonstrated oesophageal stenting is a relatively safe procedure with a low mortality and the majority of patients being discharged from hospital. However, complications are not uncommon and patients should be properly counselled; on the risks, benefits and also food habits to prevent bolus.

Clinicopathological factors predicting pathological complete response to neoadjuvant anti-HER2 therapy in HER2-positive breast cancer

Introduction Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor’s response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. Methods We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and pre-operative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. Results Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19–11.72, P = 0.02), preoperative-ER positivity (OR: 2.65, CI: 1.25–5.59, P = 0.01), PR negativity (OR: 3.92, CI: 1.82–8.45, P &amp;lt;0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23–6.42, P = 0.01) and strong preoperative-HER2 IHC 3+ staining (OR: 0.18, CI: 0.03–0.84, P = 0.04) were independent predictors of a higher pCR rate. Conclusions A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.

GALNT6 promotes bladder cancer malignancy and immune escape by epithelial-mesenchymal transition and CD8+ T cells

Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8+ T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC.

A case of diffused large B-cell lymphoma in an elderly patient successfully treated with R-mini-CHOP

Diffuse large B-cell lymphoma (DLBCL) is a diverse group of B-cell lymphomas that vary in their clinical characteristics. Usually manifesting as a rapidly progressing or advanced condition, it is often curable even at advanced stages. The illness originates in extranodal and extramedullary tissues in 40% of patients. Patients over the age of 80 who have comorbidities or fragile conditions may be eligible for Rituximab and Reduced Dose CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) (R-mini-CHOP) chemoimmunotherapy. We report a 75-year-old woman with a tumor on the right side of the nose that covers the eye, so it is easy to fall out. The diagnosis of DLBCL (sinonasal) was made on the basis of computed tomography (CT) scan of the paranasal sinuses with contrast and immunohistochemical examination. Due to the age of the patient, who was included in the very elderly category with moderate frailty based on instrumental activities of daily living (IADLs), the patient was given R-mini-CHOP chemoimmunotherapy for six cycles, followed by radiation as much as 20 × 18 Gray (Gy) where the patient in the final evaluation stated complete response.

Association of water stress and Fusarium solani exacerbated Dalbergia sissoo dieback disease.

Globally, there is a growing concern about tree mortality due to harsh climates and changes in pest and disease patterns. However, experimental studies on the interactions between biotic and abiotic stresses in plants are relatively scarce. In this study, we investigated the interaction between Fusarium solani and water-stressed Dalbergia sissoo saplings. We postulated that under drought conditions, sissoo plants would become more susceptible to dieback infestation. Five fungi, including Fusarium oxysporum, Curvularia lunata, Cladophialophora carrionii, Alternaria alternaria, and Fusarium solani, were isolated from an old shisham tree showing advanced symptoms of dieback infestation. These fungi were identified based on their ITS sequence homology and spore characteristics. Dieback development was more pronounced in plants experiencing water stress, regardless of their predisposition or whether it occurred simultaneously. Lesions were more noticeable and longer in predisposed saplings (3.8cm), followed by simultaneous (2.4cm) and much smaller lesions in seedlings that were inoculated and well-watered (0.24cm). Progressive browning of the upper leaves, which lowers sapling height in predisposed, simultaneous, and well-watered inoculated saplings to 8.09 inches, 5.93 inches, and 17.42 inches, are typical dieback symptoms. Water stress causes the loss of chlorophyll a, b, and carotenoids, which reduces stomatal conductance, transpiration rate, and photosynthetic activity, leading to poor development and mortality. Similarly, predisposed, simultaneous, and well-watered inoculated seedlings expressed increased activity of CAT (22.57, 18.148, and 9.714 U/mg) and POD (3.0, 4.848, 1.246 U/mg), to reduce the damage caused by elevated levels of H2O2 expression. It is concluded that water stress is the main cause of dieback in shisham saplings that subsequently disposed of infected seedlings to secondary agents such as fungi and insects in the advanced stages of the dieback with prolonged drought stress. The lack of dieback in native populations is attributed to the absence of several ecological stresses, including water stress, extended droughts, waterlogging, and salinity. This study emphasizes the need for additional research into the effects of abiotic factors linked with fungal diseases on the long-term production and management of D. sissoo in Pakistan.

The Role of RNA Splicing in Liver Function and Disease: A Focus on Metabolic Dysfunction-Associated Steatotic Liver Disease

RNA splicing is an essential post-transcriptional mechanism that facilitates the excision of introns and the connection of exons to produce mature mRNA, which is essential for gene expression and proteomic diversity. In the liver, precise splicing regulation is critical for maintaining metabolic balance, detoxification, and protein synthesis. This review explores the mechanisms of RNA splicing and the role of splicing factors, particularly in the context of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). This review also highlights how RNA splicing dysregulation can lead to aberrant splicing and impact the progression of liver diseases such as MASLD, with a particular focus on Metabolic Dysfunction-Associated Steatohepatitis (MASH), which represents the advanced stage of MASLD. Recent advances in the clinical application of antisense oligonucleotides (ASOs) to correct splicing errors offer promising therapeutic strategies for restoring normal liver function. Additionally, the dysregulation of splicing observed in liver diseases may serve as a potential diagnostic marker, offering new opportunities for early identification of individuals more susceptible to disease progression. This review provides insights into the molecular mechanisms that govern splicing regulation in the liver, with a particular emphasis on MASLD, and discusses potential therapeutic approaches targeting RNA splicing to treat MASLD and related metabolic disorders.

Prevention of cancer-Melanoma development and its diagnosis among Silesian Voivodeship residents: Preliminary results.

Melanoma is a malignant tumor with the highest growth rate in the incidence and is the leading cause of death due to skin cancers. In Poland, approximately 1500 cases of melanoma are detected annually in advanced or metastatic stages. Intensive preventive measures can contribute to its early-stage diagnosis, consequently reducing the number of fatalities. The aim of the study was to assess the occurrence of melanoma risk factors among the residents of Silesia region and their knowledge about the diagnosis and prevention of this cancer. An original questionnaire was used in the study, and its completion was anonymous. The study was conducted among the residents of the Silesian Voivodeship. A total of 400 (100%) individuals were examined. Among them were 243 women and 157 men. The participants' ages ranged from 16 to 84 years (mean age = 34.38 ± 18.39). The participants were burdened with melanoma development risk factors such as fair skin complexion (235; 58.75%), having more than 50 pigmented lesions (158; 39.50%) and sunburns (105; 26.25%). Over 40% (166; 41.50%) of the participants had never examined their pigmented lesions. A staggering 78% (311; 77.75%) of the respondents had never undergone dermatoscopic examination, and over 50% (215; 53.75%) did not know what this examination entailed. Just under 16% (63; 15.75%) of the participants stated that their family doctor had examined their pigmented lesions, and almost % (154; 97.47%) of those with numerous pigmented lesions had never been referred to a dermatologist for dermatoscopy. The surveyed residents of the Silesian Voivodeship were burdened with numerous risk factors for melanoma development, with the most common being fair skin complexion, having more than 50 pigmented lesions, and sunburns. The knowledge of the participants regarding the diagnosis and prevention of melanoma development was insufficient, thus highlighting the necessity for conducting systematic educational initiatives in the mentioned field. These initiatives should ultimately lead to the preservation of health and life, as well as the maintenance of its high quality.

Transition from opportunistic cytological to organized screening program with DNA-HPV testing detected prevalent cervical cancers 10 years in advance

Cervical cancer screening in Brazil is opportunistic, based on cytology and offered for women aged 25–64 years, with low coverage (30%) and 70% of cancer diagnoses done in advanced stages, without impact on mortality. The current study reports 5-year first-round results of a population-based DNA-HPV testing screening program in a Brazilian city, which intended to be a model for transition to a more efficient program. Program flowchart is simple and current, indicating repetition of a negative test after five years. The first-round (October 2017-September 2022) screened 20,551 women by DNA-HPV testing with 58.7% coverage and 99.4% compliance with the program's targeted age range. Coverage increases to 77.8% when excluding the ‘pandemic period’. The DNA-HPV testing was 87.2% negative with 6.2% colposcopy referrals and 84.8% colposcopies performed. A total of 258 high-grade precursor lesions and 29 cervical cancers (mean age = 41.4 years, 83% Stage I) were detected. As a reference, 41,387 cytology tests from the previous program (2012–2016) detected 36 cervical cancers (mean age = 52.0 years, p = 0.0005), with 67% in advanced stages (p < 0.0001). Organizing cervical cancer screening using DNA-HPV testing demonstrated good coverage, high age and colposcopy compliance, and detection of more precancerous lesions and cervical cancers 10 years in advance.

Multiplexed Spatial Imaging at the Single-Cell Level Reveals Mutually Exclusive Expression of B7 Family Proteins

Targeting novel inhibitory ligands beyond anti-PD-1 and PD-L1 and CTLA-4 therapies is essential for the next decade of the immunotherapy era. Agents for the B7 family molecules B7-H3, B7-H4, and B7-H5 are emerging in clinical trial phases; therefore, further accumulation of evidence from both clinical and basic aspects is vital. Here, we applied a 7-color multiplexed imaging technique to analyze the profile of B7 family B7-H3/B7-H4/B7-H5 expression, in addition to PD-L1, and the spatial characteristics of immune cell infiltrates in urothelial carcinoma (UC). The results revealed that B7-H3 and B7-H4 were mainly expressed on tumor cells and B7-H5 on immune cells in UC, and most of the B7-H3/B7-H4/B7-H5-positive cells were mutually exclusive with PD-L1-positive cells. Also, the expression of B7-H4 was elevated in patients with advanced pathologic stages, and high B7-H4 expression was a significant factor affecting overall mortality following surgery in UC. Furthermore, spatial analysis revealed that the distance from the B7-H4+ cells to the nearest CD8+ cells was markedly far compared with other B7 family-positive tumor cells. Interestingly, the distance from B7-H4+ cells to the nearest CD8+ cells was significantly farther in patients dying from cancer after surgery or immune checkpoint inhibitors compared with cancer survivors; thus, high B7-H4 expression in tumor cells may inhibit CD8 infiltration into the tumor space and that B7-H4-positive cells form a specific spatial niche. In summary, we performed a comprehensive evaluation of B7 family member expression and found that the spatial distribution of B7-H4 suggests the potentially useful role of combination blockade with both B7-H4 and the current anti-PD-1/PD-L1 axis in the treatment of UC.

Prognostic Implications of Selective Dissection of Left Lower Paratracheal Lymph Nodes in Patients with Left-Sided Non-Small Cell Lung Cancer.

This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages. We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND. The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both). OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.