Search Results (148)

Objective: Accurate diagnosis of sentinel lymph node (SLN) status after neoadjuvant therapy (NAT) for breast cancer is crucial for guiding axillary management. This study aimed to evaluate novel contrast-enhanced ultrasound (CEUS) patterns for assessing SLNs following NAT. Methods: We retrospectively analyzed clinical and imaging data from 279 breast cancer patients who completed NAT and underwent surgery between June 2019 and December 2024. Preoperative SLN evaluations included percutaneous CEUS (PCEUS), intravenous CEUS (IVCEUS), and conventional ultrasound (CUS). Intraoperative SLN biopsy was performed using methylene blue tracer, with pathological results serving as the gold standard. Diagnostic efficacy was compared among CUS, previously used PCEUS patterns, newly proposed PCEUS, IVCEUS, and combined CEUS. Results: The newly proposed PCEUS classified SLNs into six types, while IVCEUS categorized enhancement into three sequences and four patterns. Among the 347 SLNs detected via PCEUS, 292 (84.15%) were benign and 55 (15.85%) were malignant. The newly proposed PCEUS demonstrated higher diagnostic efficacy compared to CUS, prior PCEUS patterns, IVCEUS, and combined CEUS, with sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve of 49.1% (27/55), 86.3% (252/292), 40.3% (27/67), 90.0% (252/280), 80.4% (279/347), and 0.677 (95% CI: 0.625–0.726), respectively. However, DeLong tests revealed no statistically significant differences between the methods (all p > 0.05). Conclusions: The novel CEUS classification improved diagnostic accuracy for SLNs after NAT, though accuracy remains relatively low. Future integration of artificial intelligence may further enhance diagnostic efficacy. Full article

Background/Objectives: Squamous cell carcinoma of the nail unit (SCCNU) is a rare yet often underrecognized malignancy that can lead to delayed diagnosis and significant functional morbidity. This review aims to comprehensively summarize the current understanding of SCCNU, focusing on its clinical, dermoscopic, and molecular features, diagnostic approaches, and evolving management strategies, including the role of emerging technologies and immunotherapy. Methods: A detailed literature review was conducted using peer-reviewed publications, case series, and institutional guidelines related to SCCNU. Emphasis was placed on studies addressing clinical presentation, dermoscopic patterns, molecular pathology, histologic subtypes, imaging, biopsy techniques, staging systems, and both conventional and novel therapeutic approaches. Comparative analyses of histopathological variants and diagnostic algorithms were included. Results: SCCNU presents in patients with diverse clinical manifestations, often mimicking benign nail disorders, leading to diagnostic delays. Dermoscopy improves lesion visualization, revealing features such as vascular changes and onycholysis. Histologically, SCCNU exhibits two main subtypes: basaloid (HPV-related) and keratinizing (HPV-negative) types. Molecular analyses have identified TP53 as the most frequently mutated gene, with additional alterations in HRAS, BRAF, and TERT. Imaging modalities such as MRI and LC-OCT aid in staging and surgical planning. Management is centered on complete excision—often via Mohs micrographic surgery—while topical, intralesional, and HPV-directed therapies are under investigation. Immunohistochemical markers (p16, Ki-67, AE1/AE3) and neoadjuvant immunotherapy represent promising adjuncts. Conclusions: Early diagnosis through non-invasive imaging, improved molecular characterization, and personalized treatment strategies are essential to advancing care in SCCNU. Future directions include clinical trials evaluating immunotherapy, vaccine strategies, and precision-guided surgical approaches to preserve function and minimize recurrence. Full article

Background/Objectives: Management of cancer treatment-induced bone loss (CTIBL) is essential for preserving quality of life among breast cancer (BC) patients receiving endocrine therapy. However, bone-modifying agents (BMAs) remain underused and delayed. In 2014, IRST launched the first bone health outpatient service in Romagna (the eastern area of the Emilia-Romagna region). A multi-centre, retrospective observational study with propensity score matching (PSM) was conducted to evaluate the impact of the IRST organisational model on bone health. Methods: The PSM matched the Emilia-Romagna patients who underwent BC surgery between 2014 and 2022 and were in follow-up in the Romagna area. Patients were grouped as follows: (1) IRST and (2) other Romagna hospitals (without bone health service, i.e., the control group). The matching was based on age, in situ/invasive cancer, and type of early-stage treatment (hormone treatment vs. chemotherapy). Logistic regression and Cox proportional-hazard models assessed factors associated with bone care treatment initiation and timings, respectively. Results: After PSM, we matched 3112 of the 8021 eligible patients into the two cohorts. IRST patients were 39% more likely to receive BMAs (OR: 1.393; 95% CI: 1.236–1.571) and initiated treatment approximately 12 months earlier. We observed that patients with invasive tumours were 77% more likely to initiate bone therapy than those with in situ tumours (OR: 1.766; 95% CI: 1.237–2.585). The early initiation of bone health therapy was influenced by age (p < 0.001) and neoadjuvant chemotherapy treatment (p < 0.001). Conclusions: The IRST model demonstrates responsiveness to bone health needs in BC patients and may be implemented elsewhere to support integrated CTIBL care. Full article

Skin cancer is the most common cancer form worldwide, and it is primarily divided into melanoma and non-melanoma types, with non-melanoma being the most prevalent condition. Cutaneous squamous cell carcinoma (cSCC) accounts for 50% of primary skin cancers and is characterized by uncontrolled keratinocyte proliferation. cSCC’s current standard treatment is surgical resection and chemotherapy. Unfortunately, these methods often lead to disfigurement, functional morbiditly, and compromised function. In contrast to immunotherapy, emerging scenarios have shown promising results, especially in neoadjuvant settings. Cemiplimab (Libtayo^®; Regeneron, Tarrytown, NY, USA), a PD-1 monoclonal antibody, has shown efficacy in treating advanced or metastatic cSCC, and its use as a neoadjuvant therapy has been recently explored. This review aims to evaluate Cemiplimab in the neoadjuvant setting for cSCC treatment. The Methodology followed PRISMA guidelines, this review analyzed studies on Cemiplimab as a neoadjuvant therapy for cSCC that were sourced from PubMed, Web of Science, and Scopus. Only controlled trials, cohort studies, case series, and systematic reviews were included. From 341 records, 21 studies were included, and six clinical trials provided key data about neoadjuvant Cemiplimab’s response rates, efficacy, adverse effects, and safety considerations. The targeted data revealed a neoadjuvant Cemiplimab mean pathologic response rate of 72%, with a 62% objective response rate. Treatment-related adverse events (TRAEs) affect 66% of patients, though most cases are not severe. The most common include fatigue, maculopapular rash, and diarrhea. The studies showed high rates of complete pathological responses (cPRs) and major pathological responses (mPRs), suggesting a strong therapeutic potential. Neoadjuvant Cemiplimab for cSCC therapy shows high response rates, low recurrence, improved survival, and manageable side effects. The current literature indicates that Cemiplimab may also be effective when used in immunosuppressed patients. Despite more research still being needed to confirm its long-term benefits and the effects of the drug’s use outside of clinical trials, there is strong evidence to consider neoadjuvant Cemiplimab as a promising and efficient treatment. Full article

Background/Objectives: Chemotherapy is an aggressive form of oncological treatment often accompanied by numerous adverse effects. A patient’s baseline status significantly influences the course of therapy, its efficacy, quality of life, and overall survival. This review aims to analyze the published peer-reviewed studies in this area and to assess whether they permit the formulation of preliminary recommendations for future prehabilitation protocols. Methods: An integrative review was conducted due to the limited number of relevant studies. Four databases—MEDLINE/PubMed (Medical Literature Analysis and Retrieval System Online/National Library of Medicine), Scopus, Cochrane, and Web of Science—were systematically searched for English-language articles published between 2010 and 13 January 2025, using the terms “prehabilitation,” “chemotherapy,” “drug therapy,” and “neoadjuvant.” A total of 162 records were retrieved. After duplicate removal, titles and abstracts were screened. The remaining papers were subjected to detailed analysis, resulting in ten studies with diverse methodologies being included. Results: We reviewed ten (n = 10) studies, most of which were reviews focused on breast cancer, indicating variation in the state of knowledge across different cancer types. A protein intake of 1.4 g/kg body mass helps preserve fat-free mass, with whey being more effective than casein. Supplementing EPA at a dose of 2.2 g/day may help prevent chemotherapy-related neurotoxicity and support appetite and weight maintenance. Physical activity, especially when it includes strength training, improves VO₂max, preserves fat-free mass, and may reduce stress and anxiety. We identified one randomized controlled trial in which a single exercise session before the first dose of doxorubicin resulted in a smaller reduction in cardiac function. Continuous psychological support should be available. A combined behavioural and pharmacological approach appears to be the most effective strategy for smoking cessation. Conclusions: No official guidelines exist for prehabilitation before chemotherapy, and the availability of studies on this topic is very limited. The pre-treatment period represents a critical window for interventions. Further research is needed to evaluate the effectiveness and applicability of particularly single-component interventions. Full article

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients. Full article

Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This retrospective monocentric study included 235 women (mean age 46 ± 11 years) with non-metastatic breast cancer treated with NAST. We developed various machine learning models using clinical features (age, genetic mutations, TNM stage, hormonal receptor expression, HER2 status, and histological grade), along with morphological features (size, T2 signal, and surrounding edema) and radiomics data extracted from pre-treatment MRI. Patients were divided into training and test groups with different MRI models. A customized machine learning pipeline was implemented to handle these diverse data types, consisting of feature selection and classification components. Results: The models demonstrated superior prediction ability using radiomics features, with the best model achieving an AUC of 0.72. Subgroup analysis revealed optimal performance in triple-negative breast cancer (AUC of 0.80) and HER2-positive subgroups (AUC of 0.65). Conclusion: Machine learning models incorporating clinical, qualitative, and radiomics data from pre-treatment MRI can effectively predict pCR in breast cancer patients receiving NAST, particularly among triple-negative and HER2-positive breast cancer subgroups. Full article

Triple-negative breast cancer (TNBC) is a heterogenous group of breast tumors. This type of breast tumor is relatively difficult to manage, due to the lack of expression of Hormone Receptors (HR) and human epidermal growth factor receptor (HER2). Efforts have been made to understand the factors involved in determining how a triple-negative breast tumor responds to therapy. The standard of treatment in most cases today is a combined modality of immune checkpoint inhibitors (ICIs) and chemotherapy with agents such as anti-mitotic (taxanes) or DNA-damaging agents (alkylating agents, cyclophosphamides, platin salts). In this study, we investigated the predictive and prognostic factors for TNBC, in the neoadjuvant setting; understanding each patient’s response before treatment initiation is crucial to guiding the subsequent approach and finally improving patient outcomes. We focused on tumor-infiltrating lymphocytes at the site of the primary tumor (TILs), circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), the mutational status of protein 53 (p53), and Ki-67, investigating the potential roles of these factors in predicting responses to anti-cancer agents. Full article

Objectives: Inflammation plays an important role in cancer development, and various inflammation parameters are used as potential prognostic markers. This study aimed to evaluate the effectiveness of the combined use of HALP and H index in predicting pathological response to neoadjuvant therapy in patients with HER2-positive early-stage breast cancer. Method: This retrospective cohort study was conducted on 146 HER2-positive breast cancer patients treated in two centers. To stratify patients by their predicted probability of pathological response, HALP and H index values were combined into a composite biomarker score called the combined response score (CRS). Patients were classified into three groups based on biomarker levels: 0 = low CRS (low predictive score), 1 = intermediate CRS, and 2 = high CRS (high predictive score). These groups reflect predicted response likelihood and do not represent actual pathological outcomes. Pathological response results were evaluated according to the combined response score. Pathological complete response (pCR) was defined as residual cancer burden (RCB) 0, indicating no residual invasive tumor in breast or lymph nodes. Results: The mean age of 146 early-stage breast cancer patients included in our study was 52.3 ± 11.3 (min: 29-max: 83). In the ROC analysis, the optimum cut-off value for the HALP score in pathological response classification was found to be 36 (AUC = 0.608, sensitivity = 76.29%, specificity = 44.9%, PPV = 73%, NPV = 47.89%) and 2.3 for the H index (AUC = 0.641, sensitivity = 65.98%, specificity = 51.02%, PPV = 72.73%, NPV = 43.1%). While the pathological complete response rate was 66.4% in all patients, it was 81.8% in those with a combined score of 2, 51% in those with a score of 1, and 58.6% in those with a score of 0 (p < 0.001). In the logistic regression analysis, the probability of pathological response in patients in the combined score = 2 group is 3.77 times higher than in group 0. In the Fagan nomogram, the pretest probability of pathological response is 66%, while the post-test probability for combined response score group 2 is 81.5%, and for the low-H index < 2.3 and the high-HALP ≥ 36 patient group, our estimate for pathological complete response increases to 82%. Conclusions: The HALP-H index combined score is an important predictor of pathological response in early-stage HER2-positive breast cancer patients, independent of histological type and stage. This new score may enable personalized approaches in treatment planning. Full article

Background: The role of neoadjuvant endocrine therapy (NET) in patients with luminal tumors is still not well defined in everyday clinical practice. To assess the efficacy of combination NET, we analyzed the outcomes of fulvestrant and aromatase inhibitors (AI) in combination in a real-world population. Methods: This was a single-arm, retrospective longitudinal study of the total population of patients diagnosed with locoregionally advanced, clinical stage II-III, HR+ HER2-, luminal-type eBC, who were treated with the neoadjuvant combination of fulvestrant and AI between 2019 and 2024 at the Clinical University Hospital of Split, Croatia. Results: We enrolled 44 patients in the intention-to-treat (ITT) population, while 34 completed NET and surgery (per-protocol population; PPP). The median duration of NET was 11 months (interquartile range [IQR] of 9–16 months). The best radiological objective response rate (partial or complete response) was achieved by 30 (68.2%) in ITT, and 26 (76.5%) in PPP, defined by radiological examination, breast ultrasound, or MR. In the PPP, the minimal or moderate pathological response according to residual cancer burden (I or II) was observed in 29 (85.3%) patients. The median of absolute changes in Ki-67 was −5 (95% CI: −9 to 0), and the median of relative Ki67 changes was −40% (95% CI: −72% to 0%). Post-surgical Ki-67 was significantly predicted by initial Ki-67, positive lymph nodes, and time from diagnosis to the initiation of NET. Treatment was well tolerated, with no therapy discontinuation or dose reductions needed due to toxicity. The most commonly reported side effects included musculoskeletal pain (45.5%), asthenia (34.1%), and hot flashes (29.5%). Conclusions: Dual hormonal therapy with fulvestrant and AI is an active, easily given, non-toxic, promising neoadjuvant treatment in real-world patients with locally advanced luminal-type eBC who are not candidates for chemotherapy. Full article

Objectives: Esophagectomy is a central component of surgical treatment for esophageal cancer, with both one- and two-stage procedures frequently employed. However, these procedures are associated with a high rate of postoperative complications. This study aimed to assess the rates and types of complications following one- and two-stage esophagectomies, and to identify predictors of adverse outcomes in patients with esophageal cancer. Methods: We analyzed clinical data from patients undergoing one-stage (Ivor Lewis) or two-stage esophagectomies. Postoperative complications were defined as events occurring within 30 days after surgery. Variables such as patient demographics, clinical staging, histological tumor grade, and neoadjuvant chemoradiotherapy were assessed for their association with complications. Statistical analyses included logistic regression and chi-squared tests. Results: Among 61 patients, postoperative complications occurred in 24.6% of cases. The most frequent were pneumonia (22.2%), anastomotic leakage (22.2%), and hemothorax (27.8%). Significant predictors of complications included intraoperative disease staging, histological tumor grade, and the use of neoadjuvant chemoradiotherapy. The odds ratio for complications following neoadjuvant chemoradiotherapy was 8.75. The frequency of anastomotic leakage was similar in one- and two-stage procedures (30.8% vs. 26.3%, respectively). Conclusions: Postoperative complications remain a significant challenge in esophageal cancer surgery, particularly in the context of advanced disease or neoadjuvant chemoradiotherapy. These findings underscore the necessity for precise surgical planning and comprehensive postoperative care to mitigate risks and optimize patient outcomes. While postoperative risk is high, it is primarily driven by tumor characteristics and preoperative therapy. Full article

Background/Objectives: The real impact of prehabilitation in the healthcare setting is controversial due to the efficacy–effectiveness gap. The effectiveness of prehabilitation in real-world scenarios has been associated with program attrition and adherence. This study aimed to identify factors influencing adherence to a multimodal prehabilitation program for patients undergoing major surgery. Methods: This is a analysis of a prospective trial conceived to explore the implementation of prehabilitation in a real-life setting. Participants were patients enrolled in our multimodal prehabilitation program, candidates for major surgery, and at high risk for postoperative complications. Sociodemographic and clinical variables were studied, with adherence to the program as the primary outcome. Descriptive analyses were conducted to examine associations between adherence and the study variables. A binary logistic regression model was applied to identify predictors of adherence. Results: Among the 559 patients included in the study, 356 (63.7%) were labelled as adherent. The analysis revealed significant associations between adherence and working status, type of exercise program prescribed (p < 0.001), smoking status (p = 0.023), age (t = −3.00, p = 0.003), comorbidities (t = −2.19, p = 0.029), and self-reported physical activity (t = −2.45, p = 0.015). The logistic regression identified as independent factors the type of exercise prescription, smoking status, residential area, working status, and neoadjuvant therapy. The predictive model demonstrated good specificity (86.1%) but lower sensitivity (50.6%), suggesting its utility in identifying patients at risk of non-adherence. Conclusions: Multiple factors influence adherence in prehabilitation programs. Our model exhibited good accuracy and specificity, but poor sensitivity. Full article

Objectives: The objective of this study was to assess the relationship of VEGF-C and LVD with pathoclinical factors of potential prognostic value and with the survival time of gastric cancer patients. Materials and methods: A total of 103 radically operated patients for gastric cancer who did not undergo neoadjuvant therapy were included in this study. The minimum follow-up period after surgery was 61 months. VEGF-C and lymphatic vessels were immunohistochemically determined using antibodies, including VEGF-C (c-20) sc 1881-Goat Polyclonal IgG (Santa Cruz Biotechnology) and Podoplanin D2-40 Mouse Monoclonal Antibody (ROCHE). The relationship between VEGF-C expression in gastric adenocarcinoma cells and the density of lymphatic vessels at the periphery of the primary tumor was assessed, along with the relationships of VEGF-C and LVD with selected pathoclinical parameters of gastric cancer and prognosis. Results: VEGF-C overexpression was associated with increased LVD (Mann–Whitney U test, p = 0.03) and the Lauren intestinal type of cancer (Pearson’s chi-square test, p < 0.001). Increased LVD was more often associated with cancers located beyond the cardia (Mann–Whitney U test, p = 0.04). We did not demonstrate an association of VEGF-C or LVD with OS or with prognostic features, such as pT, pN, or pTNM staging. However, in the Lauren intestinal type of cancer, VEGF-C overexpression correlated with shorter OS (log-rank, p = 0.01) and, at the level of p = 0.05 in multivariate analysis, it had an independent negative prognostic value. Conclusions: Peritumoral overexpression of VEGF-C in primary gastric cancer tumors is associated with increased LVD. The Lauren intestinal type of cancer is associated with VEGF-C overexpression. The overexpression of VEGF-C in intestinal-type gastric cancer is associated with worse prognosis. Full article

Background/Objectives: The improved long-term survival of rectal cancer patients has led to a major increase in the prevalence of functional complications. Understanding which patients are prone to develop major LARS is important for their preoperative counselling and follow-up. Herein, we aimed to assess the risk factors for LARS. Methods: This is a retrospective cohort study on rectal cancer patients. All patient and tumour variables, management plan, type of neoadjuvant therapy, radiation dose to anal sphincter, and perioperative outcomes were collected from the hospital electronic databases. We quantified LARS and compared the score before and after surgery (mean follow-up of 42.2 ± 32 months). Results: A total of 182 patients were included for the final analysis. LARS was present in 43.4% (n = 79) of patients, with 14.8% (n = 27) having minor LARS and 28.5% (n = 52) having major LARS. Age (p = 0.03), male gender (p < 0.00001), smoking (p = 0.04), neoadjuvant radiotherapy (p = 0.02), rectal stump length (p = 0.008), end-to-end anastomosis (p = 0.008), and ileostomy (p = 0.002) were found to significantly increase the rate of LARS. A logistic regression model based on the above variables was able to predict major LARS with good predictive value (AUC 0.700). Conclusions: LARS is highly common after sphincter-preserving surgery, and it is significantly more common in young, male patients with a history of smoking, having mid-lower rectal cancers with neoadjuvant radiotherapy, and undergoing TME surgery with end-to-end low anastomosis and ileostomy. Full article