Search Results (43,538)

Objectives: This study aimed to assess the performance of the LI-RADS tumor response algorithm in analyzing inter-reader agreement in patients with hepatocellular carcinoma (HCC) treated with Microwave Ablation (MWA) and Transarterial Embolization (TAE) and the relationship between inter-reader agreement and Neutrophils to Lymphocytes ratio dynamic variations at different time points to explore how inflammation influences tumor response and its interpretation on imaging. Methods: A retrospective analysis was conducted on 78 HCC patients treated with MWA or TAE. Two independent radiologists evaluated pre- and post-treatment imaging and assigned categories according to the LR-TRA. Inter-reader agreement was assessed with a focus on subgroup analysis considering the different locoregional treatments. NLR values, measured at baseline (T0), 72 h (T1), and 30 days post-procedure (T2), were compared with patients with concordant and discordant LR-TRA assessments. This analysis aimed to identify any association between NLR dynamics and inter-reader agreement on treatment response. Results: The inter-reader agreement in the LR-TRA application was “substantial” in the cases of MWA treatment evaluation (κ = 0.65), and “moderate” in the cases of TAE treatment evaluation (κ = 0.51). The differences in inter-reader agreement were found to be expressions of different levels of NLR mean values in the different time frames evaluated. Three days after treatment, NLR increased significantly in TAE groups. At 30 days, NLR had returned close to baseline levels but with NLR persisting higher in the TAE group. There was a statistically significant difference in NLR between the “mismatch” group (those with discrepant LR-TRA readings) and the “match” group at 3 days (p = 0.004) and late evaluation (30+ days). Conclusions: This study has shown that NLR levels can predict inter-reader discrepancies in LR-TRA assessment and may be translated into different levels of difficult imaging interpretation. Combining LR-TRA and NLR is promising for a more comprehensive assessment of tumor response and inflammatory dynamics. Full article

The mitochondrial serine β-lactamase-like protein LACTB has emerged as a critical regulator in cancer biology, distinguished by its unique structural and functional attributes. Defined by its conserved penicillin-binding proteins and β-lactamases (PBP-βLs) domain and SXXK catalytic motif, LACTB demonstrates properties distinct from its prokaryotic homologs, including the ability to polymerize into filaments. These structural characteristics enable LACTB to modulate mitochondrial organization and enzymatic activity, influencing lipid metabolism and indirectly affecting cellular proliferation. Importantly, the expression and functional roles of LACTB exhibit cancer-type-specific variation, underscoring its dual function as both a tumor suppressor and an oncogene. Decreased LACTB expression is associated with poor clinical outcomes in cancers such as breast cancer, lung cancer, and colorectal cancer, while specific mutations and regulatory mechanisms have been linked to its oncogenic activity in osteosarcoma and pancreatic adenocarcinoma. Mechanistically, LACTB regulates key processes in cancer progression, including mitochondrial dynamics, epithelial–mesenchymal transition (EMT), and cell death pathways. This duality highlights LACTB as a promising therapeutic target and underscores its relevance in advancing precision oncology strategies. This review provides a comprehensive analysis of expression level, structure–function relationships, and the diverse roles of LACTB in oncogenesis, underscoring its promise as a focal point for precision cancer therapies. Full article

Background: Cutaneous melanoma (CM) is a malignant tumor originating from melanocytes. Despite improvements in prevention, Central and Eastern European countries continue to report higher rates of advanced-stage melanoma and lower survival rates. This study aims to characterize CM and the associated risk factors in Northwestern Romania. Methods: This cross-sectional cohort study was conducted in Cluj and Bihor counties. Between January 2023 and May 2024, 172 patients with histopathologically confirmed melanoma completed a standardized questionnaire addressing demographics, sun exposure history, nevi count, and melanoma-specific characteristics. Results: The median age at diagnosis of participants was 44 years. The median Breslow index (BI) was 1.5 mm, and 39% of cases presented with a BI > 2 mm. Superficial spreading melanoma (SSM) was the most common subtype, predominantly affecting women, while nodular melanoma (NM) was more frequent in men. Higher BI was associated with NM and acral lentiginous melanoma (ALM). Limbs were women’s most frequent tumor site, whereas the trunk was predominant in men. Significant associations were observed between younger age at diagnosis and factors such as high nevus count, indoor activity, and smoking status. Rural residents reported a higher history of sunburns compared to urban residents. Conclusions: Our findings underscore the importance of targeted public health interventions to promote early detection and primary prevention of melanoma. Establishing a national melanoma registry is crucial to improving epidemiological surveillance and reducing the burden of melanoma in Romania. Full article

Background/Objectives: Current evidence suggests that patients with unresectable non-small cell lung cancer (NSCLC) whose tumours harbour driver mutations do not benefit from immune checkpoint inhibition. Kirsten rat sarcoma virus mutations (KRASmts), however, seem to be the exceptions to the rule. To this end, we compared KRASmt patients who were treated with immunotherapy to those without. Methods: ALLSTAR is a nationwide registry for patients with histologically verified non-operable NSCLC aged 18 or older having a curative treatment option. This report presents a subcohort of KRASmt patients who were recruited between 2020/03 and 2023/04. The diagnostic work-up included ¹⁸F-FDG-PET-CT scan and contrast-enhanced cranial CT or—preferably—MRI. Patients were treated with chemoradiotherapy (CRT) either followed by immune checkpoint inhibition (ICI) or not. Results: Thirty-two KRASmt patients with a median follow-up of 25.9 months were included in this analysis. After CRT, 27/32 (84%) patients received ICI. The 2-year overall survival rate in KRASmt patients who received immunotherapy was significantly better compared to those without ICI (N = 32; 84% versus 20%; p < 0.001). Likewise, the 2-year progression-free-survival with immunotherapy was also significantly better than in those without ICI (N = 32; 75% versus 20%; p < 0.001). Of the 12/32 patients (38%) who had received radiation doses > 66 Gy, none had a locoregional relapse, whereas in the other 20 patients, 5 (25%) events occurred (p-value = 0.116). Conclusions: Since KRASmt patients could benefit from ICI treatment, immunotherapy should be offered to these patients, similar to those without actionable genetic drivers. Additionally, radiation dose escalation > 66 Gy may also improve locoregional control in this subset of patients. Full article

Introduction: Patients with transplant-ineligible (TIE) multiple myeloma (MM) have high rates of symptom burden. The aim of this study was to develop and validate a prognostic model to predict symptoms in patients with TIE MM. Methods: In this population-based, retrospective cohort study, using multiple administrative health care databases linked using a unique encrypted patient identifier in Ontario, Canada, symptoms were identified using the patient self-reported Edmonton Symptom Assessment System (ESAS) at each clinic visit. The primary outcome was the presence of moderate-to-severe (ESAS score 4–10) symptoms (specifically symptoms of pain, tiredness, depression, and impaired well-being) within one year from the index date. Using the entire cohort, a multivariable logistic regression model with baseline covariates was developed to predict the risk of experiencing each of the above symptoms, categorized as moderate to severe within 1 year post-index date. Internal validation of the model was assessed via bootstrap validation methods. Results: A total of 1535 TIE adults with MM met the inclusion criteria. The median age was 75, with 25.2% of patients aged 80 years or older. In the multivariate analysis, baseline symptoms continued to be most associated with future symptom burden. Baseline severe pain (OR 9.84, 95% CI 6.29–15.7) was most associated with patients experiencing moderate–severe pain one year post-index date. Similarly, baseline severe tiredness (OR 17.34, 95% CI 9.00–33.42), baseline severe depression (OR 28.07, 95% CI 15.96–49.38), and baseline severely impaired well-being (OR 4.12, 95% CI 2.30–7.37) were the biggest predictors of patients experiencing moderate–severe tiredness, depression, and impaired well-being, respectively, at one year after the index date. Conclusions: Patients with MM experience persisting symptoms of pain, tiredness, depression, and impaired well-being, with baseline symptoms being the biggest predictor of future symptom burden. Full article

Background: Hematological indices such as the neutrophil-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), and systemic immune inflammation index (SII) have been proposed as markers of inflammatory disease and prognostic indicators in some tumors, but their role remains controversial. This study aims to evaluate the relationship between these indices and postoperative complications in patients undergoing robotic-assisted anatomic lung resection for oncological purposes. Methods: This retrospective, single-center study included patients who underwent anatomical lung resection from January 2022 to June 2023 using robotic-assisted surgery. The data collected included hematological variables, demographic information, body mass index (BMI) data, information about pulmonary function, medical history, postoperative outcomes, and survival data. Results: A total of 96 patients were included, with a median BMI of 26.10. The data distribution across demographic and clinical variables was homogeneous. Univariate and multivariate analyses revealed no significant association between preoperative or postoperative inflammatory indices and postoperative complications, persistent air leak (PAL), or 1-year mortality. Conclusions: This small, retrospective study with short-term follow-up found no significant relationship between inflammatory indices and postoperative outcomes. These findings suggest that SII and similar indices are not reliable predictors of complications, PAL, or mortality in patients undergoing robotic-assisted anatomic lung resection. Full article

Background: Psychrobacter species are aerobic, Gram-negative, spherical-to-rod-shaped, psychrophilic bacteria that belong to the Moraxellaceae family. In spite of their uncommon manifestation in the general population, infections due to Psychrobacter spp. are increasingly identified especially in immunocompromised individuals or patients with severe comorbidities. Objectives: This review aims to analyze all reported instances of Psychrobacter spp. infections in humans, with an emphasis on data pertaining to epidemiology, microbiology, antimicrobial resistance, treatment strategies, and mortality outcomes. Methods: A narrative review was performed through a literature search of PubMed/MedLine and Scopus databases. Results: In total, 12 articles offered data on 12 patients infected with Psychrobacter spp. Their mean age was 33.41 years, while 63.64% of them were male. Immunosuppression was the predominant risk factor (33.3%). Bacteremia was the most commonly observed type of infection (41.6%), followed by meningitis, skin infection, and conjunctivitis. Psychrobacter immobilis was the most usually identified species (33.3%). The pathogen exhibited sensitivity to most antimicrobials. The most widely administered antimicrobials included cephalosporins (70%), followed by aminopenicillins and vancomycin (40%, respectively). The clinical outcome depended primarily on the infection site; mortality rate was high (44.4%), especially in cases of bacteremia (50%). Conclusion: Due to the potential of Psychrobacter spp. to cause serious infection, clinicians and laboratory professionals should consider it in the differential diagnosis in patients with infections by Gram-negative spherical bacteria, particularly in patients with significant comorbidities and immunodeficiency, in order to accurately establish the diagnosis and proceed to the right treatment. Full article

Background/Objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan–Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55–15.26), involved margins (HR = 3.94, 95% CI = 1.68–9.25), uncertain margins (HR = 4.42, 95% CI = 1.55–12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19–7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial. Full article

Background: The prognostic impact of internal carotid artery (ICA) invasion in nasopharyngeal cancer (NPC) patients is not well established. Thus, we conducted a retrospective study to analyze the prognostic factors for ICA invasion by NPC. Methods: This retrospective study included consecutive biopsy-proven NPC patients who received CCRT from November 2015 to December 2022 at E-Da Hospital. Patients were then classified into two groups according to ICA invasion by tumor or not. Survival was estimated by the Kaplan–Meier method with a five-year overall survival (OS) rate and five-year disease specific survival (DSS) rate. Results: A total of 191 patients with pathologically confirmed NPC were included in this study, with 54 patients in the ICA invasion group and 137 patients in the no ICA invasion group. The ICA invasion group showed a worse prognosis compared to the no ICA invasion group (p < 0.001 in OS and DSS). Patients were stratified into a poor response group and good response group. OS and DSS in the poor response group had a significant difference compared to the good response group (both p < 0.001). In multivariate analysis, NLR was an independently prognostic factor for OS (HR 2.430, 95% CI 1.040–5.678, p = 0.040 and HR 0.412, 95% CI 0.176–0.962, p = 0.040, respectively) and for DSS (HR 2.430, 95% CI 1.040–5.678, p = 0.040 and HR 0.412, 95% CI 0.176–0.962, p = 0.040, respectively). Conclusions: Locally advanced NPC patients with ICA invasion have a miserable outcome and NLR represents a significant prognostic factor that impacts treatment decisions and survival. Full article

AI applications are increasingly prevalent in radiotherapy, including commercial software solutions for automatic segmentation of anatomical structures for 3D CT. However, their use in intraoperative electron radiotherapy (IOERT) remains limited. In particular, no AI solution is available for contouring cone beam CT (CBCT) images acquired with a mobile CBCT device. The U-Net convolutional neural network architecture has gained huge success for medical image segmentation but still has difficulties capturing the global context. To increase the accuracy in CBCT segmentation for IOERT, three different AI architectures were trained and evaluated. The features of the natural language processing models Transformer and xLSTM were added to the popular U-Net architecture and compared with the standard U-Net and manual segmentation performance. These networks were trained and tested using 55 CBCT scans obtained from breast cancer patients undergoing IOERT in the department of radiotherapy and radiation oncology in Salzburg, and each architecture’s segmentation performance was assessed using the dice coefficient (DSC) as a similarity measure. The average DSC values were 0.83 for the standard U-Net, 0.88 for the U-Net with transformer features, and 0.66 for the U-Net with xLSTM. The hybrid U-Net architecture, including Transformer features, achieved the best segmentation accuracy, demonstrating an improvement of 5% on average over the standard U-Net, while the U-Net with xLSTM showed inferior performance compared to the standard U-Net. With the help of automatic contouring, synthetic CT images can be generated, and IOERT challenges related to the time-consuming nature of 3D image-based treatment planning can be addressed. Full article

Introduction: Peritoneal carcinomatosis presents significant treatment challenges. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers a promising therapeutic approach. Patient selection remains critical, and the role of age as an exclusion criterion requires further investigation. This study evaluates whether age influences postoperative outcomes in CRS-HIPEC patients. Methods: A retrospective review of a prospective comprehensive database of 271 CRS-HIPEC procedures performed between 2018 and 2023 was conducted. Logistic regression assessed the relationship between age and postoperative outcomes. Age groups (18–44, 45–69, ≥70 years) were compared based on demographic data, primary tumor site, Peritoneal Cancer Index scores, and key outcome measures. Results: Across the different age groups, there were no significant differences in PCI scores, recurrence, disease-free survival, 30-day morbidity, or mortality. Length of stay was longer in older patients (p = 0.009). Patients aged ≥70 had higher readmission rates (p = 0.041) and were more often discharged to transitional care facilities (p = 0.001). Older patients were also more likely to experience Clavien–Dindo grade III or higher complications (p = 0.008). Logistic regression confirmed these findings. Continuous age analysis yielded similar results and revealed significant differences in race and primary organ involvement. Conclusions: Age is not a significant predictor of 30-day morbidity, mortality, or survival outcomes in patients undergoing CRS-HIPEC. However, older patients require closer attention to discharge planning and readmission risk management. This study highlights the importance of comprehensive patient assessment beyond age and underscores the need for further research to better understand factors influencing outcomes in this population. Full article

The human microbiome, which encompasses microbial communities and their genetic material, significantly influences health and disease, including cancer. The urogenital microbiota, naturally present in the urinary and genital tracts, interact with factors such as age, lifestyle, and health conditions to affect homeostasis and carcinogenesis. Studies suggest that alterations in this microbiota contribute to the development and progression of genitourinary cancers, emphasizing the concept of oncobiome, which refers to microbial genetic contributions to cancer. Similarly, gut microbiota can influence hormone levels and systemic inflammation, impacting cancers such as cervical and prostate cancer. Advanced studies indicate that microbial communities in genitourinary cancers have distinct profiles that may serve as diagnostic biomarkers or therapeutic targets. Dysbiosis of the urinary microbiota correlates with bladder and kidney cancer. Additionally, gut microbiota influence the effectiveness of cancer treatments. However, further research is necessary to clarify causality, the role of microbial metabolites, and hormonal regulation. The aim of this review is to understand that these dynamics present opportunities for innovative cancer diagnostics and therapies, highlighting the need for integration of microbiology, oncology, and genomics to explore the role of microbiota in genitourinary cancers. For this, a comprehensive search of relevant databases was conducted, applying specific inclusion and exclusion criteria to identify studies examining the association between microbiota and urogenital cancers. Research into the mechanisms by which microbiota influence urogenital cancers may pave the way for new diagnostic and therapeutic approaches, ultimately improving patient outcomes. Full article

Background and Objectives: Robotic-assisted laparoscopy (RS) has been widely adopted for the management of endometrial cancer (EC) due to favorable perioperative outcomes, especially in the context of obesity, which is an established risk factor for EC. This study retrospectively evaluated the perioperative outcomes of RS versus conventional laparoscopy (LS) in treating EC and atypical endometrial hyperplasia (AH). Methods: Between November 2021 and October 2023, 138 patients with AH or EC underwent surgery at the Clinic of Obstetric and Gynecological—Azienda Sanitaria Universitaria Friuli Centrale, Udine. All patients had total hysterectomy with bilateral salpingo-oophorectomy, with or without lymphadenectomy or sentinel lymph node biopsy. The study included 62 patients treated with LS and 62 with RS. Results: The median BMI was higher in the RS group (35.5 vs. 24 kg/m², p = 0.001). There was no significant difference in operative time between the laparoscopic group and the robotic console time (median 130 vs. 130 min, p = 0.131). No significant differences were found in terms of blood loss, conversion to laparotomy, intraoperative complications, hospital stay, or early postoperative complications between the two groups. Conclusions: Our data confirm the feasibility of robotic surgery in obese patients, allowing surgical results comparable to those of laparoscopy in normal-weight patients. Full article

Malignant pleural mesothelioma (MPM) still represents a complex diagnostic challenge for pathologists in routine practice. This diagnosis requires a multidisciplinary approach, and pathological evaluation is mandatory. The histopathological diagnosis is stepwise and should be based on morphological and immunohistochemical assessment, sometimes associated with molecular tests, and supported by clinical and radiological findings. A correct morphological approach aims to exclude pleural metastasis or benign mesothelial proliferations, which are the main differential diagnoses. While certain histological features are diagnostic of MPM, others are highly suggestive but not definitive. Immunohistochemistry plays a pivotal role, with a panel of both traditional and newer markers being used to assess mesothelial differentiation and to differentiate malignant from benign proliferations. In more challenging cases, molecular tests, such as fluorescent in situ hybridization (FISH) to detect CDKN2A deletion, can be helpful in distinguishing malignant from benign pleural lesions. This review summarizes the key morphological, immunohistochemical, and molecular features that should be considered when pleural biopsy samples are examined, with the aim of improving diagnostic accuracy in this complex area. Full article

Background: Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy. While its role is well established in lung cancer and melanoma, its predictive value for breast and prostate cancers remains unclear. Objective: This systematic review aimed to assess the predictive value of TMB for ICI therapy across four major cancer types—lung, melanoma, breast, and prostate—and to explore factors contributing to the variability in its effectiveness as a biomarker. Methods: A systematic search and a review of the literature were conducted in accordance with PRISMA guidelines. Studies examining the relationship between TMB levels and clinical outcomes following ICI therapy in the specified cancers were analyzed. The data were synthesized to evaluate TMB’s predictive value and identify gaps in the current research. Results: High TMB consistently correlated with improved outcomes in lung cancer and melanoma, confirming its predictive utility in these cancers. Conversely, the findings for breast and prostate cancers were inconclusive. The variability in TMB’s predictive value for these cancers suggests the need for complementary biomarkers or refined criteria to enhance its reliability. Methodological inconsistencies in TMB evaluation were also noted as a significant limitation. Conclusions: TMB serves as a robust biomarker for predicting ICI response in lung cancer and melanoma, but demonstrates limited predictive utility in breast and prostate cancers. Future research should prioritize standardizing TMB assessment protocols and investigating additional biomarkers to improve treatment personalization for these cancer types. Full article