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Sarcomas comprise over 100 mesenchymal malignancies characterised by extreme genomic heterogeneity, ranging from fusion-driven paediatric tumours to highly unstable adult leiomyosarcomas. This genetic complexity shapes tumour behaviour, influences growth and metastasis, and determines how patients respond to therapy. Accurate animal models must reflect not only the molecular characteristics of these tumours, but also their microenvironment and dynamic interaction with the host immune system. The diversity of this group of cancers presents different challenges for animal model selection, particularly as sarcoma-specific resources are very limited. Therefore, we have reviewed in detail several types of models, including: syngeneic (e.g., MCA205 and KRIMS series), chemically induced (e.g., MCA, DMBA), cell-derived xenografts (CDX; e.g., KCS8 and KCS9 osteosarcoma lines), patient-derived xenograft (PDX; e.g., pleomorphic leiomyosarcoma and GIST models), including humanised PDX (huPDX; e.g. HuNOG-EXL ), and zebrafish (e.g. tp53M214K PNST and EWS-FLI1 transgenics) - to illustrate their sarcoma-specific use cases and discuss their advantages and limitations. Genetically engineered models and their development are not a subject of this review, as they represent a very broad subject independently and are discussed elsewhere. Graphical abstract

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC.

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1 , TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.

Background Medical education in Poland consists of a six-year course, a 13-month postgraduate internship, and a Final Medical Examination. The possible further career path is to specialise in a particular field of medicine, and the choice of speciality is one of the most important decisions made by young doctors. Therefore, the decision-making process creates challenges. We conducted this study to determine the factors considered during the process of choosing a medical speciality and to investigate the influence of student performance in the Final Medical Examination on this choice. Methods A descriptive cross-sectional survey was conducted between 4 January and 7 February 2024. The data were collected via an online survey in Polish. The survey was disseminated to doctors engaged in postgraduate internships via social networks. The Chi-square test (χ 2 ) was used to analyse the significance of differences. Results The survey included 336 postgraduate trainees. Internal medicine subspecialties, surgical specialities, and paediatrics were of most interest to the respondents. The average age of respondents was 26 years. In the multiple-choice question, most people (86.6%) marked their individual interests as a key factor influencing their choice of specialisation, followed by earning opportunities in the private sector (58%) and work-life balance (54.2%). The Final Medical Examination score is a significant factor in the selection of a speciality, as indicated by 68% of respondents. Conclusions The process of selecting a medical speciality involves overcoming numerous limitations. The outcome of the Final Medical Examination is a significant factor influencing the choice of future specialisation. Furthermore, the decision-making process is affected by several different factors and the distinctive complexities of practising a specific speciality within the Polish healthcare system.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available “-omics” approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

Introduction: Soft tissue sarcomas (STS) exhibit profound molecular heterogeneity. While recurrent gene fusions hold significant diagnostic and therapeutic value—guiding treatment selection and identifying novel molecular targets—our understanding of their broader clinical implications remains limited. Materials and Methods: We performed next-generation sequencing (NGS; FusionPlex Sarcoma v2, Archer™) and bioinformatic analysis (STAR v.2.7, Arriba) on formalin-fixed paraffin-embedded (FFPE) core needle biopsy specimens. The cohort consisted of patients enrolled in a phase II clinical trial (NCT03651375) who received preoperative chemoradiotherapy according to the UNRESARC protocol. Results: The analysed cohort comprised nine adult patients (median age 66 years; range 44–73) diagnosed with undifferentiated pleomorphic sarcoma (UPS; n = 3), malignant peripheral nerve sheath tumour (MPNST; n = 3), myxofibrosarcoma (MFS; n = 2), and leiomyosarcoma (LMS; n = 1), predominantly high-grade (G3; 5/9) and extremity-localised (6/9). Gene fusions were detected in one-third of patients (3/9), exclusively in G3 tumours. Specifically, we identified an SGSH-PRKCA fusion in MFS (thigh), a LINC01133-OGA fusion in MPNST (thorax), and a concurrent JAZF1-MYH7B (chr7:27995037 intronic-chr20:33563203 exon/splice-site, out-of-frame but preserving myosin domains) with a PRKCA-associated intergenic rearrangement (chr1, retaining C1/kinase domains) in UPS (upper back). Notably, the SGSH-PRKCA and JAZF1-MYH7B pairs have not been previously described in the literature for these STS subtypes. Fusion-positive (F1) cases showed stable radiological disease (RECIST 1.1 SD) and EORTC C/D pathological responses with 5–20% residual viable tumour, whereas fusion-negative (F0) cases showed a wider range of radiological and pathological outcomes, including partial response, progression, and stable disease. Conclusions: Our analysis suggests that broad genomic profiling may provide complementary molecular information in diagnostically challenging cases managed at specialised sarcoma centres, particularly when morphology and immunohistochemistry are insufficient. In the present series, however, the detected rearrangements did not alter systemic treatment, and the data do not support claims of prognostic, predictive, or therapeutic actionability.

PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total of 20 patients were diagnosed with PEComa following histopathological examination. The age of the patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization have been described. Liver resection was the treatment of choice. There was only one postoperative complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high arterial vascularization are observed. Liver resection is the treatment of choice.

Background Iatrogenic bile duct injuries (BDIs) are mostly associated with laparoscopic cholecystectomy but may also occur following gastroduodenal surgery or liver resection. Delayed diagnosis of type of injury with an ongoing biliary leak as well as the management in a non-specialized general surgical units are still the main factors affecting the outcome. Case presentation Herein we present three types of BDIs (Bismuth type I, IV and V) following three different types of upper abdominal surgery, ie. Billroth II gastric resection, laparoscopic cholecystectomy and left hepatectomy. All of them were complex injuries with complete bile duct transections necessitating surgical treatment. All were also very difficult to treat mainly because of a delayed diagnosis of type of injury, associated biliary leak and as a consequence severe inflammatory changes within the liver hilum. The treatment was carried out in our specialist hepatobiliary unit and first focused on infection and inflammation control with adequate biliary drainage. This was followed by a delayed surgical repair with the technique which had to be tailored to the type of injury in each case. Conclusion We emphasize that staged and individualized treatment strategy is often necessary in case of a delayed diagnosis of complex BDIs presenting with a biliary leak, inflammatory intraabdominal changes and infection. Referral of such patients to expert hepatobiliary centres is crucial for the outcome.

IntroductionRoux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are the two most frequently performed bariatric operations. These two types of metabolic surgery alter the anatomy and function of digestive tract producing significant weight loss in morbidly obese patients but may lead to malnutrition.AimAnalysis of incidence and severity of malnutrition after bariatric surgery in patients submitted to RYGB or LSG during 12 months of follow-up.Material and MethodsRetrospective study of 98 patients after RYGB (n = 47) or LSG (n = 51) assessed for nutritional deficiencies during 12 months after surgery was conducted. The differences in body mass index (BMI) and blood tests including erythrocytes, haemoglobin, total protein, albumin, iron, ferritin, transferrin, vitamin B12, folic acid, calcium and phosphorus concentrations were compared between groups before the operations and at 1 and 12 months.ResultsNutritional deficiencies were common before surgery with prevalence up to 19.6% for albumin in the LSG group. Median preoperative BMI levels and albumin concentrations were higher in the RYGB group compared to the LSG group, but there was no difference in percent excess weight loss (%EWL) at 1 and 12 months between LSG and RYGB. One month after LSG erythrocyte count, haemoglobin, iron, ferritin and transferrin levels were significantly higher than in the RYGB group. These differences subsided at 12 months. At 12 months, only the prevalence of vitamin B12 deficiency was significantly higher in the RYGB group.ConclusionBoth RYGB and LSG lead to nutritional deficiencies despite different properties of operations and similar %EWL during follow-up.

Purpose of Review The review compares the effectiveness of neoadjuvant(pre-operative, NAC) and adjuvant(post-operative, AC) in Soft Tissue Sarcomas as this topic is controvesial and multiple new studies have been over the years. Recent Findings Sarculator and other nomograms assess patients with a predicted 10-year OS below 60% who will benefit from perioperative chemotherapy. Further research supports perioperative chemotherapy’s role. European guidelines do not recommend anthracycline and ifosfamide (AI) perioperative chemotherapy as a standard treatment for STS of the extremities and trunk. However, some studies show that AI chemotherapy can improve recurrence-free survival (RFS). The EORTC 62,771 trial found that the CYVADIC regimen (doxorubicin, dacarbazine, cyclophosphamide, vincristine) reduced RFS without affecting OS. Meanwhile, the EORTC 62,931 trial showed no effect of AI chemotherapy on RFS or OS, but a pooled analysis suggested an OS benefit for patients with R1 (microscopically positive) resections. The AI regimen shows further support from Sarculator-based data, with EORTC 62,931 analysis indicating an improvement in disease-free survival and OS in patients with low expected OS. Similar outcomes were seen in the ISG-STS 1001 study. Recently, PERSARC analysis revealed that AI chemotherapy significantly improves OS in high-grade STS patients with a low 5-year OS prediction (< 33%). Summary NAC improves the chances of complete tumour removal, especially in large, high-grade tumours. It often reduces the need for more aggressive surgeries by shrinking tumours before surgery, leading to higher rates of successful resections with clear margins (R0). Sarculator and other nomograms assess patients with a predicted 10-year OS below 60% who will benefit from perioperative chemotherapy. Further research supports perioperative chemotherapy’s role.