Search Results (694)

Background and Clinical Significance: Isoechoic renal tumors, defined as masses demonstrating echogenicity similar to normal renal parenchyma, represent a significant diagnostic challenge in contemporary ultrasonographic practice. These lesions, occurring in 5–12% of all renal masses, frequently escape detection on conventional ultrasound, leading to delayed diagnosis and potentially adverse oncological outcomes. Isoechoic renal tumors encompass both benign and malignant entities, with clear cell renal cell carcinoma representing 65–70% of malignant cases. Conventional ultrasound shows limited sensitivity (48–67%) for detecting isoechoic masses, while contrast-enhanced ultrasound achieves detection rates of 94–98%. Multiparametric MRI and dual-energy CT provide superior characterization, with accuracy rates of 85–92% for differentiating benign from malignant lesions. Case Presentation: We describe the case of an 80-year-old male in whom a 2.4 cm isoechoic renal mass was incidentally detected during abdominal ultrasound performed for chronic kidney disease monitoring. Contrast-enhanced CT confirmed a solid, hypervascular lesion with wash-out characteristics. Given the patient’s age, comorbidities, and tumor characteristics, multidisciplinary evaluation led to an active surveillance strategy. At 6-month follow-up, the lesion remained stable. Conclusions: Isoechoic renal tumors require multimodal diagnostic approaches and individualized management strategies. Emerging technologies, including artificial intelligence-enhanced ultrasound systems and radiomic-based decision support tools, are undergoing clinical validation and may improve detection and characterization. Investigational approaches such as liquid biopsy and novel PET tracers targeting carbonic anhydrase IX are in early development. Translation of these technologies into clinical practice will require prospective validation, standardization of protocols, and demonstration of cost-effectiveness. Full article

Background and Objectives: Adrenal gland tumors are frequently discovered incidentally. They remain challenging to evaluate because of their heterogeneous nature and overlapping imaging characteristics. Surgical resection continues to represent the primary treatment option for both benign and malignant lesions. This study aimed to characterize the clinical, demographic, and pathological features of adrenal tumors and to assess surgical management patterns in a tertiary referral center. Materials and Methods: A retrospective analysis was conducted on 112 patients who underwent adrenalectomy between 2015 and 2022. Demographic, clinical, radiological, and surgical data were reviewed. Histopathological findings were classified as benign tumors, primary adrenal malignancies, or adrenal metastases. Both laparoscopic adrenalectomy and open surgery were performed. The operative approach was determined by tumor characteristics and oncologic considerations. Results: Among the 112 patients, 48% had benign adrenal tumors, 32% had adrenal metastases, and 19.6% were diagnosed with primary adrenal malignancies. Most patients with adrenocortical carcinoma were women over 55 years of age. Benign lesions were predominantly managed with simple adrenalectomy and minimally invasive techniques, while malignant tumors frequently required complex oncologic resections and open surgical approaches. Distinct metastatic patterns were observed, with renal cell carcinoma representing the most common primary source of adrenal metastasis. Conclusions: Adrenal tumors demonstrate marked demographic and pathological variability. Surgical resection remains essential for definitive diagnosis and treatment, underscoring the importance of tailoring the operative approach. Minimally invasive surgery is appropriate for benign lesions, whereas open adrenalectomy is preferred for malignant or advanced tumors, where surgical expertise is critical to achieving optimal oncologic outcomes. Full article

Background: Haploidentical hematopoietic cell transplantations (haplo-HCTs) with post-transplant cyclophosphamide (PT-Cy) are standard practice, but complications causing morbidity and mortality are not well described. Methods: The aim of this prospective non-interventional multicenter study was to document frequency of potential non-infectious and infection-related complications and main transplant outcomes after the first unmanipulated haplo-HCT with PT-Cy between 2017 and 2019 in 129 adult patients with hematological malignancies. The median follow-up was 37.3 months [95% CI: 34.3–39.7]. Results: The cumulative incidence (CI) of acute graft versus host disease (aGvHD) at day +100 was 22.4% grade II-IV [95% CI: 15.5–30.1] and 8.8% grade III-IV [95% CI: 4.6–14.6], respectively. The cumulative incidence of chronic GvHD (cGvHD) at 24 months was 25.8% [95% CI: 18.5–33.6]; extensive cGvHD was 10.9% [95% CI: 6.3–17.1], respectively. The most frequent non-infectious complications for the whole study population were mucositis—37.5% (n = 48); renal insufficiency—18% (n = 23); and cardiovascular complications—10.9% (n = 14). The following infection-related complications were diagnosed: bacterial in 84 (65.1%), viral in 66 (51.6%), and fungal in 24 (18.6%) recipients. Two-year OS was 58.1% [95% CI: 50.2–67.3]; NRM—27.1% [95% CI: 19.7–35]; PFS—50.4% [95% CI: 42.5–59.8]; and GRFS—38.8% [95% CI: 31.2–48.1]. About 50% of all deaths were directly caused by infection or infection-related conditions. Conclusions: Disease remission status at transplant significantly affected PFS, chronic GvHD, and GRFS. Although clinical applications of haplo-HCT with PTCy are widespread, the study confirms the need to reduce infection-related mortality after this type of GvHD prophylaxis. Full article

Background/Objectives: The delta neutrophil index (DNI)—a hematology analyzer-derived measure of circulating immature granulocytes—may assist pre-biopsy decision-making, yet its behavior across tumor types is incompletely defined. We examined whether pre-biopsy DNI differs by pathology category, tumor class, and definitive histology, and evaluated diagnostic performance. Methods: In this retrospective, single-center cohort, consecutive inpatients with malignancy were screened (n = 2009). Exclusions included positive blood cultures, prior chemotherapy/radiotherapy before index labs, and lack of definitive pathology, yielding 1313 analyzable cases. All laboratories, including DNI, were obtained before diagnostic biopsy. DNI was assessed as a continuous variable and categorized (Zero = 0; High > 0.6). Groupwise differences used Kruskal–Wallis and χ² tests with FDR control; discrimination used ROC analyses (one-versus-rest/pairwise). Results: DNI distributions differed across pathology, tumor class, and definitive diagnoses (all p < 0.001). High DNI (>0.6) and Zero DNI (=0) proportions also varied significantly by grouping. Hematologic malignancies showed the highest DNI (median ~1.0) compared with sarcoma and carcinoma (medians ~0.4). Using DNI alone, one-versus-rest AUCs were 0.735 (hematologic), 0.692 (melanoma), 0.672 (sarcoma), and 0.652 (carcinoma); the strongest pairwise separation was hematologic versus sarcoma (AUC 0.780). For specific solid tumors, including breast and renal cell carcinoma, single-marker discrimination was modest; no clinically actionable RCC cutoff emerged. Sensitivity analyses restricted to culture-negative cases yielded consistent findings. Conclusions: Pre-biopsy DNI exhibits tumor-type-dependent variation and provides adjunct diagnostic signal—the strongest for hematologic malignancy—yet is insufficient alone for solid tumor subtyping. Integration with clinical assessment and routine biomarkers, and multi-center validation with device harmonization are warranted. Full article

Background: We investigated whether EphA2 inhibition can attenuate the progression of renal cell carcinoma (RCC) in an orthotopic mouse model of kidney tumor cells (Renca). Materials and Methods: 16 BALB/c mice were divided into two groups and implanted with either control or shRNA-mediated, EphA2-knockdown Renca–Luciferase cells via injection under the right renal capsule. Tumor progression was followed by in vivo bioluminescence imaging (BLI). Tumor growth was evaluated via ex vivo BLI and the wet weight of harvested orthotopic kidneys on day 18. Tumor apoptosis was evaluated using the TUNEL assay. Changes in FAK/RhoA signaling, a mediator of malignant cellular behavior, were determined using Western blotting and RT-PCR. Results: The TUNEL assay showed increased apoptosis of tumor cells in the EphA2-knockdown group compared to that in the control group (p = 0.021). Tumor wet weight (1569.9 ± 595.5 vs. 636.5 ± 288.9 mg, p = 0.009) and activation of RhoA and FAK were decreased in the EphA2-knockdown group (p < 0.05 for all). Tumor burden was reduced in the EphA2-knockdown group according to in vivo BLI on days 14 and 18 and an ex vivo test (p = 0.021, p = 0.043, p = 0.021). Conclusions: EphA2 knockdown significantly reduced the progression of RCC by inducing tumor apoptosis and suppressing FAK/RhoA signaling in an orthotopic mouse model. The EphA2/FAK/RhoA pathway might constitute a potential target to suppress the progression of RCC. Full article

Background: Urine cytology is a highly effective, straightforward, and cost-efficient diagnostic tool for identifying neoplastic and non-neoplastic changes in the bladder, ureter, and renal pelvis. The aim of this study is to demonstrate the high sensitivity and specificity of urine cytology in detecting a wide range of urothelial lesions, including metastatic involvement. Material and Methods: Urine cytology was performed on 9639 cases between 2000 and 2025. The samples, collected from patients, were processed at the Institute of Pathology. Cytological slides were prepared using cytocentrifugation and stained with May–Grünwald–Giemsa (MGG) and Papanicolaou stains. The cytological findings were classified according to WHO, 2004 compared with histological specimens. Additionally, selected cases underwent immunohistochemical and molecular analyses. All samples were anonymized and retrospectively analyzed following the guidelines and regulations of the local ethics committee. Results: Of the total cases, 7051 were classified as benign, 1269 as malignant, and 88 as normal findings. Insufficient material was obtained in 336 cases. No complications were reported during sample collection or processing. The concordance with histological findings for neoplastic lesions was over 96%, with a false-negative rate of 1.84%. The diagnostic methods demonstrated a sensitivity of 90.7% and a specificity of 96.64%. Among the 6956 cases analyzed, 3139 were women (45.13%) and 3817 were men (54.87%). Conclusions: The diagnostic value of urine cytology in representative material is relatively high in assessing both the presence or absence of malignancy and, when applicable, the tumor grade. This large 25-year single-center review demonstrates that urine cytology retains high sensitivity and specificity for the detection of urothelial malignancy, particularly high-grade disease. However, the atypical category remains a major diagnostic challenge and contributes substantially to false-positive results. Full article

Background: Triple primary malignant tumors (TPMTs) are extremely rare and represent a major diagnostic and therapeutic challenge. Their frequency has increased with advances in cancer detection and longer patient survival. Case presentation: We report the case of a 76-year-old male diagnosed with three synchronous primary malignancies involving the liver, left kidney, and right lung. Imaging revealed a hepatic mass with arterial enhancement and portal washout, a large left renal mass, and a cavitated pulmonary nodule. Histopathological and immunohistochemical evaluation confirmed three distinct tumors: well-differentiated hepatocellular carcinoma, chromophobe renal cell carcinoma, and invasive non-mucinous lung adenocarcinoma. A multidisciplinary oncology board recommended surgical resection of the liver and kidney lesions and stereotactic body radiotherapy for the lung tumor. The patient underwent hepatectomy and nephrectomy but experienced severe postoperative complications leading to multi-organ failure and death. Results of the systematic review: A systematic search identified 83 relevant cases of triple primary malignancies after full-text eligibility assessment. None of the 159 articles included after primary screening described a synchronous association of primary liver, kidney, and lung cancers. Conclusions: This case highlights the importance of thorough diagnostic assessment and individualized, multidisciplinary management in patients with multiple synchronous malignancies. To our knowledge, this is the first reported case of synchronous hepatocellular carcinoma, chromophobe renal cell carcinoma, and lung adenocarcinoma. Full article

Background/Objectives: Multiple primary malignancies (MPMs) are defined as the occurrence of two or more independent primary tumors in the same patient, histologically distinct and not of metastatic origin. Patients treated for Hodgkin’s lymphoma (HL) carry an increased risk of developing secondary malignancies, especially after chemotherapy and radiotherapy. The synchronous occurrence of breast and kidney carcinoma in this population is extremely rare. Methods: We present a 41-year-old female patient with a history of HL treated at the age of 23 with ABVD chemotherapy and supradiaphragmatic radiotherapy. Results: During staging for a newly diagnosed breast tumor (ER+/PR+/HER2+, pT1cN0), an incidental renal mass was identified and histologically confirmed as clear cell renal cell carcinoma (pT1aNxMx, G2). A multidisciplinary team performed simultaneous partial breast resection with sentinel lymph node biopsy and nephrectomy. The postoperative course was uneventful, and adjuvant systemic therapy was initiated according to oncological guidelines. Conclusions: Synchronous malignancies in HL survivors pose a clinical challenge, as they must be distinguished from metastatic disease and require coordinated therapeutic planning. Risk factors include prior radiotherapy, chemotherapy, genetic predisposition, and family history. This case highlights the importance of long-term surveillance of HL survivors, particularly young women, due to their elevated risk of secondary malignancies. Synchronous breast and kidney carcinomas after HL therapy are extremely rare and demand an integrated multidisciplinary approach. Early recognition and coordinated therapy are crucial for optimizing outcomes and contributing to a better understanding of the etiology and pathogenesis of multiple primary malignancies. Full article

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical. Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and III randomized controlled clinical trials assessing FDA-approved ICIs, including programmed cell death protein 1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, with emphasis on patient-reported HRQL. Validated HRQL instruments were summarized, and for pivotal trials, the positioning of HRQL outcomes as primary, secondary, or exploratory endpoints was taken from original protocols or primary manuscripts. Results: ICIs generally preserved or improved HRQL in patients with various malignancies compared with chemotherapy, targeted therapies, or observation. PD-1/PD-L1 inhibitors maintained global health and function and delayed symptom progression in patients with lung cancer, melanoma, and renal cell carcinoma. Regimens combining CTLA-4 blockade and PD-1/PD-L1 inhibition (e.g., nivolumab + ipilimumab, durvalumab + tremelimumab) are associated with HRQL outcomes similar or superior to those of targeted therapies. Overall, most immune-related adverse effects were short-term and did not diminish HRQL benefits. Conclusions: ICIs extend survival while preserving, and often enhancing, patient HRQL. These medications represent a shift in oncology, offering not just longer life but also better daily well-being. Continued long-term patient-reported outcome monitoring is essential to guide survivorship care in the immunotherapy era. Full article

Renal Cell Carcinoma (RCC) is a common malignancy, often diagnosed incidentally. In recent years, the prognosis of metastatic disease has been improved due to the development of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) as first-line treatments. However, when progression occurs, the therapeutic options are limited. Understanding crucial biological pathways could lead to a greater understanding of the natural history of the disease, which could help to overcome the mechanism of resistance and to develop new treatments. The clinical significance of homologous recombination deficiency (HRD) in RCC remains to be investigated. To improve the knowledge about this topic, we conducted a narrative review to summarize the current evidence on HRD-related variations and signatures in RCC, together with their prognostic and predictive implications. Preliminary evidence indicates that canonical HRD variants (BRCA1/2) are infrequent in RCC, while broader DNA damage response (DDR) alterations like BAP1, PBRM1, ATM, and SETD2 are more prevalent. Elevated HRD genomic scores in clear-cell RCC correlate with a worse prognosis and an immunologically exhausted microenvironment. From a therapeutic point of view, PARP inhibitor monotherapy has exhibited initial efficacy in small cohorts with high levels of DDR mutation, yet remains investigational for RCC. Full article

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy accounting for 3% of adult cancers globally. Despite advances in immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, durable disease control remains elusive for many patients. Increasing evidence implicates the acidic tumour microenvironment (TME) as a critical mediator of RCC progression, immune evasion, and therapeutic resistance. Solid tumours, including RCC, exhibit reversed pH gradients, characterised by acidic extracellular (pH 6.2–6.9) and alkaline intracellular conditions. This dysregulation arises from enhanced glycolysis, hypoxia-driven lactate accumulation, and the overexpression of pH-regulating enzymes such as carbonic anhydrase (CA9). Acidic TMEs impair cytotoxic T-cell and NK-cell activity, promote tumour-associated macrophage (TAM) polarisation towards an immunosuppressive phenotype, and upregulate alternative immune checkpoints. These mechanisms collectively undermine ICI efficacy and contribute to primary and secondary treatment resistance. Proton-sensing G-protein-coupled receptors (GPCRs), notably GPR65, have emerged as pivotal mediators linking extracellular acidosis to immune dysfunction. Preclinical studies demonstrate that GPR65 antagonists restore anti-tumour immune activity by reversing acidosis-driven immunosuppression and enhancing antigen processing. In RCC models, selective GPR65 inhibitors have shown the ability to reduce immunosuppressive cytokine IL-10 production, induce immunoproteasome activation, and synergise with anti-PD-1 therapy. The first-in-class GPR65 inhibitor, PTT-4256, is now under evaluation in the Phase I/II RAISIC-1 trial (NCT06634849) in solid tumours, including RCC. Targeting acid-sensing pathways represents a novel and promising therapeutic strategy in RCC, aiming to remodel the TME and overcome ICI resistance. Integrating GPR65 inhibition with existing immunotherapies may define the next era of RCC management, warranting continued translational and clinical investigation. Full article

Background: There is a great deal of knowledge regarding the development of polyomavirus-associated nephropathy and polyomavirus-associated hemorrhagic cystitis in transplant recipients with active BKPyV infection. However, recent studies have revealed a potential association between BKPyV reactivation and certain malignancies, including transitional cell carcinoma, malignant melanoma, colorectal cancer, and prostate cancer. This study aimed to identify a potential link between BKPyV infection and oncogenic transformation in kidney transplant recipients. Methods: Presentation of a case series of kidney transplant recipients diagnosed with polyomavirus-associated nephropathy who developed neoplasms after transplantation. Results: Positive immunohistochemical reactions confirmed the presence of polyomavirus large T antigen in tissue samples from all three patients’ cancers. Furthermore, a case of chromophobe renal cell carcinoma presenting BKPyV proteins in cancer cells was observed for the first time in the literature. Conclusions: BKPyV reactivation was found to be associated with the development of both urothelial cancer, which originates directly from the BKPyV-infected site, and colorectal cancer. Full article

Background/Objectives: Prevention and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major clinical issue in hospitalized patients. Some aspects of VTE management lack clarity due to differing physicians’ opinions and behaviors. Methods: A multidisciplinary steering committee identified two main areas of uncertainty: VTE prophylaxis and PE management in special settings. A multiple-choice questionnaire including 10 statements was circulated to 183 doctors trained in VTE management. The expected benefit-to-harm ratio was represented on a nine-point Likert scale, with consensus (≥75% agreement) on scores of 1–3 indicating inappropriate and 7–9 indicating appropriate care measures. Results: In online voting, a consensus was reached for 9/10 statements. Respondents considered the following to be appropriate: risk assessment of VTE (93.44%) and bleeding (91.6%) in hospitalized medical patients; low-molecular weight heparin (LMWH) prophylaxis for inpatients with pneumonia and malignancy (82.78%); therapeutic doses of LMWH/fondaparinux in patients with intermediate/high risk of PE with (80.9%) or without (77.97%) instability criteria; and echocardiography to manage patients with a post-PE syndrome (93.99%). Respondents considered the following to be inappropriate: use of 4000 IU LMWH in chronic renal failure (80.46%); use of 2000 IU LMWH in persons on dual antiplatelet therapy (77.01%); and use of low-dose apixaban (2.5 mg) in pregnancy (88.57%) or in subsegmental PE with hypoxemia (82.46%). No consensus was reached on the identification of PE cases eligible for outpatient treatment. Conclusions: Our findings show persistent gaps between guideline recommendations and clinical implementation despite improved awareness among physicians. Uncertainty persists regarding criteria for outpatient PE eligibility and/or for validation of bleeding-risk models. Full article

Surgical site infections (SSIs) are among the most frequent healthcare-associated infections, leading to prolonged hospitalization, increased costs, and impaired recovery. This retrospective cohort study aimed to identify the determinants and microbial patterns of SSIs following hepatobiliary and pancreatic (HPB) surgery to inform preventive strategies and optimize clinical outcomes. The patients undergoing hepatobiliary and pancreatic surgery from 2014 to 2024 in a tertiary university hospital are reviewed. SSI was defined according to Centers for Disease Control and Prevention (CDC) criteria, and microbiological isolates were identified through routine culture methods and susceptibility testing. Clinical, operative, and microbiological data of patients who underwent hepatobiliary and pancreatic surgery were extracted, including demographics, comorbidities, operative characteristics, and postoperative outcomes. Among 553 hepatobiliary and pancreatic surgery patients, SSI occurred in 48.6%. Gram-negative bacteria predominated, with E. coli as the leading pathogen. SSI was linked to open surgery, longer operative time, and higher ASA scores; malignancy, renal insufficiency, anemia, and COPD were independent risk factors. Age by itself was not a reliable predictor of infection, while operative duration demonstrated moderate predictive performance, with a sensitivity of 66%. These findings underscore the multifactorial pathogenesis of SSIs and emphasize the importance of refined perioperative strategies to mitigate postoperative infectious complications. Full article

Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting hypoxia-sensitive urinary tract tissues. This study aimed to assess the prevalence of different cancer types among patients with concurrent OSA and malignancy and to characterize the clinical profiles of those with urinary tract cancer. Methods: We retrospectively analyzed 50 patients with both OSA and cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. Results: Among the cohort (70% males) of OSA-cancer patients, urinary tract cancers were the most frequent (34%), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and other cancers (2%); 10% had multiple cancer sites. Patients with urinary tract cancer were mainly male (88%, p = 0.0043) and displayed better respiratory indices, frequent hypertension, and higher C-PAP adherence. Conclusions: These findings suggest a possible link between OSA-related hypoxia and carcinogenesis in urinary tract tissues and support increased clinical surveillance and further research to determine potential protective effects of C-PAP therapy. Full article