Search Results (92)

Background and Objectives: Squamous cell carcinoma (SCC) of the lip is a common malignancy of the oral and maxillofacial region. Medium-to-large post-excisional defects often require reconstructive techniques that preserve oral competence, function, and facial aesthetics. Despite its broad clinical use, the Karapandzic flap lacks comprehensive evidence describing its postoperative outcomes and associated complications. Materials and Methods: This retrospective cohort study evaluated all consecutive patients who underwent lip SCC excision followed by Karapandzic flap reconstruction at a tertiary oncologic center in Greece from 2000 to 2024. Demographic, clinical, pathological, and postoperative data were collected, and complications were categorized as early (wound dehiscence, surgical site infection, hematoma) or late (microstomia, excessive scarring). Statistical analyses included comparative tests and Firth’s logistic regression to explore potential predictors of morbidity. Results: A total of 102 patients met the inclusion criteria. Most were male (82.4%) with a median age of 68.8 years, and 94.1% had lower-lip tumors. Early complications occurred in 9.8% of patients and late complications in 17.7%, with microstomia being the most frequent late event (15.7%). Age was the only variable showing a borderline significant association with overall complications. No demographic, clinical, or pathological factor, including lesion morphology, cytological diagnosis, tumor location, or presence of metastasis, demonstrated a statistically significant association with early or late complications. Conclusions: Karapandzic flap reconstruction represents a reliable single-stage option for lip SCC defects, demonstrating relatively low complication frequencies and generally favorable functional outcomes. Further comparative studies are warranted to evaluate its performance relative to alternative reconstructive techniques. Full article

Background: Nasopharyngeal carcinoma (NPC) is an uncommon malignancy with a distinct geographical distribution. However, data from non-endemic areas are limited. This study aims to evaluate oncological outcomes and identify prognostic factors in a large cohort of non-metastatic NPC patients treated at a tertiary center in Israel. Methods: This single-institution, retrospective study included 181 patients diagnosed with non-metastatic NPC and treated with radiotherapy between 2005 and 2022. Data were collected from electronic medical records and included demographics, disease characteristics, treatment details, and outcomes. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Cox proportional hazards models were used to assess prognostic factors. Results: The median follow-up was 57 months. The cohort was predominantly male (82%), with a mean age of 51.7 years. Most patients had non-keratinizing histology, 75%presented with stage III–IV disease, and 86% received concurrent chemoradiotherapy. Induction chemotherapy was administered to 71%, though only 6.5% received the full three-cycle regimen. Nearly 90% were treated using modern radiotherapy techniques (VMAT), and 75% received concurrent chemotherapy. The 3-year RFS and OS were 82.6% and 91.2%, respectively; the 5-year RFS and OS were 77.7% and 84.7%. Age threshold analysis demonstrated that younger age predicted improved RFS (HR range, 3–5; p < 0.05). In the multivariate analysis, patients aged > 50 years had a significantly higher risk of recurrence (HR 6.02, 95% CI 1.30–27.85), while stage IV disease showed a borderline association with poorer RFS (HR 2.81, 95% CI 0.96–8.27), reaching statistical significance in the 30–50 years age group (HR = 7.06, 95% CI 1.14–43.76, p = 0.036). Smoking demonstrated a non-significant trend toward increased recurrence risk (HR 1.61, 95% CI 0.85–3.04). Similar patterns were seen for OS, with age >50 showing elevated but non-significant risk (HR 3.43, 95% CI 0.73–16.06), partly due to limited events. Bedouin ethnicity was associated with higher prevalence and a significantly younger age at diagnosis (39.4 ± 16.0 vs. 52.7 ± 16.9 years, p = 0.004), with a non-significantly better outcome. Conclusions: In this non-endemic cohort, favorable oncologic outcomes were observed. The age at diagnosis is a key prognostic factor. The higher incidence, younger age and better outcomes among the Bedouin ethnicity warrant further investigation calling for improved risk stratification and personalized treatment strategies. Full article

Background/Objectives: Optimal selection for perioperative therapy in urothelial carcinoma (UC) remains uncertain. We evaluated the efficacy of neoadjuvant and/or adjuvant chemotherapy (NAC/AC) for patients with bladder cancer (BC) and upper tract UC (UTUC), examined the role of lymphovascular invasion (LVI), and considered the implications for adjuvant nivolumab. Methods: We retrospectively analyzed consecutive patients who underwent radical cystectomy or radical nephroureterectomy at a single center (July 1998–April 2021; observation to 31 March 2025). After exclusions, 252 BC and 153 UTUC patients were included. Endpoints were cancer-specific survival, progression-free survival (PFS; BC), non-urinary-tract recurrence-free survival (NUTRFS; UTUC), and overall survival (OS). Survival was estimated by Kaplan–Meier analysis and compared by log-rank tests. Results: For BC, AC did not improve the PFS or OS in the overall pT ≥ 2 population, whereas node-positive (pN+) disease derived significant benefits in both endpoints among NAC-naïve patients (PFS and OS, p = 0.002 and p = 0.008). For UTUC, AC conferred no advantage in NUTRFS or OS for the overall pT ≥ 2 population. However, NUTRFS benefits emerged in the pN+ subset (p = 0.049), although the OS was not improved. Among NAC-treated BC, the outcomes were poorest for ≥ypT3 and ypN+, whereas ypT ≤ 2 fared better. LVI was associated with adverse outcomes and was borderline higher in pN+ versus pT ≥ 2/pN− for BC (p = 0.056) and significantly higher for UTUC (p = 0.012). Conclusions: In this retrospective, single-center cohort, our exploratory analyses suggest that perioperative benefit is largely node-dependent, supporting prioritizing systemic therapy for pN+ disease and cautioning against routine AC for pT2/ypT2 without nodal involvement. After NAC, adjuvant therapy appeared most justified for ≥ypT3/ypN+. Prospective biomarker-integrated validation is warranted and, given the small and underpowered subgroups and the potential for selection and immortal time biases, these observations should be interpreted as hypothesis-generating rather than causal. Full article

Background: Anal squamous cell carcinoma (ASCC) is a rare malignancy primarily treated with chemoradiotherapy (CRT). This study evaluated outcomes and the prognostic value of simple hematologic indices in patients receiving modern image-guided CRT. Methods: Fifty-five patients with non-metastatic ASCC treated between 2017 and 2025 were retrospectively analyzed. Survival was estimated by Kaplan–Meier methods, and prognostic factors were assessed by log-rank testing and Cox regression. Baseline neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios were analyzed individually and in combination with nodal status. Results: At a median follow-up of 53.1 months, overall survival reached 90% at 5 years, whereas disease-free survival declined to 51%. Nodal positivity showed a non-significant trend toward poorer DFS. Baseline PLR ≥ 150 was significantly associated with inferior DFS in univariable analysis (HR 5.28, 95% CI 1.12–24.97, p = 0.036), while NLR ≥ 3 showed a borderline effect (p = 0.108). In multivariable models, PLR retained borderline prognostic relevance (p = 0.083), whereas Kaplan–Meier curves indicated non-significant trends (p = 0.129 and 0.055). Integrated models combining nodal status with PLR ± NLR improved risk discrimination: Model A (N + PLR ≥ 150 ± NLR ≥ 3) showed a trend (p = 0.059), and Model B (N + PLR ≥ 150) reached significance (p = 0.021; C-index ≈ 0.68–0.69). Conclusions: Modern CRT achieved excellent OS with acceptable toxicity, though early recurrences limited DFS. Integrating hematologic indices with nodal status provides a pragmatic, cost-effective approach for individualized risk assessment and follow-up in ASCC. Full article

Background and Objectives: Breast lesions of uncertain malignant potential identified on biopsy, known as “B3 lesions,” constitute a significant portion of diagnoses in numerous published studies. These lesions are associated with a variable risk of coinciding malignant tumors, and current guidelines recommend complete excision, which can occasionally lead to an upgrade in the resection specimen. However, alternative, less invasive treatment strategies, such as clinical follow-up, may be considered. In this study, we retrospectively analyzed diagnostic biopsies from our institution to determine the upgrade rate of each B3 lesion subgroup to breast malignancy following complete excision. Materials and Methods: All breast biopsies conducted at our institution from 1 January 2018 to 30 November 2022 and classified as B3 lesions were included in this study. The lesions were categorized into groups and subgroups based on their growth pattern and histopathological features. To determine the upgrade rate to ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC) for each B3 lesion subgroup, we assessed the histological concordance between the biopsy and the resection specimen. Results: During the study period, 10,531 biopsies were performed, of which 1045 (9.93%) were classified as B3 lesions. Among these, 795 (76.08%) were subsequently resected, either through surgical procedures (98.32%) or using the Vacuum-Assisted Excision technique (1.68%). Histological examination revealed that 89 (11.19%) of the resected B3 lesions were upgraded to breast malignancy, with 59 cases (7.42%) progressing to DCIS, 22 cases (2.76%) to IBC, and 8 cases (1.01%) to borderline or malignant phyllodes tumor. The upgrade rate varied among histopathological subgroups, being lowest in complex sclerosing lesions without atypia (4.95%, 95% CI: 2.5–8.7%) and highest in intraductal papillomas with atypia (58.82%; 95% CI: 32.9–81.6%). Conclusions: Statistically significant differences were observed between B3 lesion subgroups, with a higher risk of upgrade in lesions exhibiting atypia. As our understanding of B3 lesions evolves, there is potential to implement therapeutic strategies tailored to the specific risk associated with each subgroup. This approach could allow for less invasive management options, such as clinical or radiological follow-up, thereby sparing patients from unnecessary invasive procedures when appropriate. Full article

Background: Endometrial proliferative lesions are common in the menopausal transition and carry a measurable risk of carcinoma. Early risk stratification may guide evaluation and follow-up. Methods: We performed a single-center retrospective study of 315 women aged 45–55 years (May 2021–May 2024) at a private clinic in Bucharest. Lesions were classified per WHO 2014 as hyperplasia without atypia, atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN), or adenocarcinoma; “advanced pathology” was defined as AH/EIN or adenocarcinoma. Clinical comorbidities and transvaginal ultrasound endometrial thickness were recorded. Associations were tested with χ²; odds were estimated with multivariable logistic regression (adjusted ORs), with a modified Poisson sensitivity analysis for adjusted relative risk. Thickness differences were compared by one-way ANOVA, and severity correlations by Spearman’s ρ. Internal validation used 1000-bootstrap resampling. Results: Hyperplasia without atypia comprised 74.6% of cases, AH/EIN 20.0%, and adenocarcinoma 5.4% (advanced pathology 25.4%). Diabetes was independently associated with advanced pathology (aOR 2.75; 95% CI 1.14–6.61; p = 0.0237), while a history of non-atypical hyperplasia was inversely associated (aOR 0.31; 95% CI 0.13–0.72; p = 0.0068). Obesity showed a borderline association (aOR 1.79; 95% CI 0.98–3.26; p = 0.058), and long-term oral contraceptive use also approached significance (aOR 0.42; 95% CI 0.18–1.00; p = 0.051). Endometrial thickness increased stepwise with histopathological severity (ANOVA p < 0.0001; η² = 0.44) and correlated with ordered severity (ρ = 0.634). The multivariable model showed moderate discrimination (AUC 0.68; optimism-corrected 0.66) with acceptable calibration (slope 0.92; Hosmer–Lemeshow p = 0.052) and overall accuracy (Brier 0.18). Conclusions: In perimenopausal abnormal bleeding, metabolic comorbidities—especially diabetes—together with increased endometrial thickness identify women at higher risk of AH/EIN or carcinoma. Histopathology remains the diagnostic reference. The model can aid clinical prioritization but requires external validation and should not be used as the sole basis for decisions. Full article

Hepatocellular carcinoma (HCC) management has evolved remarkably with the advent of diverse therapeutic options, particularly systemic and surgical treatments. Combination immunotherapy has redefined the treatment paradigm for advanced HCC and contributed to improved patient outcomes. However, this brings forth challenges such as immune-related adverse events that complicate decision-making. Surgical strategies have expanded with the emergence of conversion therapy and borderline resectability, offering curative potential for a broader patient population. However, robust evidence of their long-term efficacy is lacking. Therefore, decision-making biomarkers have gained prominence across treatment modalities. This review explores the current landscape of predictive, prognostic, and treatment-response biomarkers in HCC, from molecular and immune signatures to radiological and biochemical markers, highlighting their role in optimizing therapeutic strategies. By integrating recent advances in basic and translational research with clinical practice, we aim to outline a biomarker-driven framework for individualized care in HCC. Full article

Background: Adnexal masses are common in women across different age and hormonal states: pregnancy, premenopause, and postmenopause. Ovarian carcinoma, a malignancy arising in the adnexa, poses significant health risks. While malignancy risk increases with age and postmenopausal status, current methods for stratifying borderline cases remain inadequate, potentially leading to over- or undertreatment that may affect fertility or survival. Methods: This retrospective study was conducted with 318 adult women who were diagnosed with adnexal masses and underwent surgery at a university hospital between 2020 and November 2023. Patient data were retrieved from the hospital’s electronic medical record system. Routinely measured preoperative serologic parameters—carbohydrate antigen (CA)125, CA19-9, CA15-3, carcinoembryonic antigen (CEA), Alpha-fetoprotein (AFP), Lactate dehydrogenase (LDH), and fibrinogen-to-albumin ratio (FAR) levels—were analyzed alongside final histopathological results. No procedures outside routine clinical practice were performed. Diagnostic performance of each marker was evaluated using receiver operating curve (ROC) analysis. Results: A total of 318 patients with adnexal masses were analyzed. The FAR levels were significantly elevated in malignant compared to borderline and benign groups (p < 0.001), and FAR alone showed 47% sensitivity and 91% specificity for borderline tumors, whereas CA125 showed 70% sensitivity and 85% specificity. Multivariate models combining FAR, CA125, and CA15-3 achieved the highest diagnostic accuracy, with superior AUCs compared to single biomarkers. Conclusions: FAR is a simple, accessible inflammatory marker that complements CA125 by enhancing specificity. Combination of multiple markers with the highest sensitivity and specificity, together with FAR, may reduce the risk of both false negatives, offering a more balanced and accurate diagnostic tool for preoperative stratification of borderline tumor cases. Full article

Folate receptor alpha (FRα) is a high-affinity folate transporter overexpressed in various epithelial malignancies, particularly high-grade serous ovarian carcinoma. Given its restricted expression in normal tissues and accessibility in tumors, FRα is an emerging therapeutic target. Immunohistochemistry (IHC) is the standard method for FRα assessment; however, interpretation is semi-quantitative and prone to interobserver variability. This study aimed to evaluate interobserver agreement among 12 pathologists in the IHC assessment of FRα in ovarian cancer, focusing on internal control adequacy, staining intensity, and the percentage of FRα-positive tumor cells. Thirty-seven high-grade serous ovarian carcinoma cases were stained using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. A reference panel of four expert pathologists established consensus diagnoses. Twelve pathologists independently assessed the slides, recording internal control adequacy, staining intensity (positive vs. negative), and percentage of FRα-positive tumor cells. Interobserver agreement was measured using Fleiss’ kappa and intraclass correlation coefficient (ICC). Agreement on internal control adequacy was almost perfect (κ = 0.84). Substantial agreement was observed for staining intensity (κ = 0.76), while percentage estimation showed almost perfect concordance (ICC = 0.89). Discrepancies were primarily confined to borderline cases (65–85% positivity) and tumors with intermediate staining, reflecting interpretive challenges near clinical decision thresholds. Pathologists demonstrated high reproducibility in FRα IHC assessment, particularly in estimating percentage positivity and control adequacy. These findings support the clinical utility of FRα IHC but underscore the need for standardized scoring criteria and potential integration of digital tools to enhance consistency, especially in borderline cases. Full article

Mature teratomas account for approximately 20% of all ovarian tumors identified in pathological studies. Benign or malignant somatic neoplasms developing within teratomas can arise from any tissue in up to 2% of mature cystic teratomas, including low-grade malignant mucinous neoplasms. This report presents the case of a 34-year-old woman with no previous gynecological or general health issues, who was admitted to our Hospital after an asymptomatic pelvic mass was detected during a routine exam. A transvaginal ultrasound revealed a unilateral pelvic mass in the left adnexal region, measuring 8 cm. The CT scan showed a cystic-appearing formation measuring nearly 12 cm, which indented the bladder dome. Final diagnosis indicated a mucinous carcinoma arising from a mucinous borderline lesion within the context of a mature ovarian teratoma. No other involvement or lymphadenopathies were detected on 18FDG-PET CT scan, and the patient is now well and free of recurrences. Full article

Background/Objectives: Preoperative strategies for hepatocellular carcinoma (HCC) requiring major hepatectomy remain controversial, particularly in “borderline resectable” cases. This study aimed to evaluate the oncological benefit and perioperative safety of Yttrium-90 transarterial radioembolization (TARE) in patients undergoing right or extended right hepatectomy for HCC. Material and Methods: All consecutive patients who underwent right or extended right hepatectomy for HCC at a single tertiary center between January 2013 and December 2023 were retrospectively reviewed. Patients were grouped based on whether they received preoperative TARE or underwent upfront resection. Outcomes analyzed included perioperative morbidity and long-term oncological endpoints. Results: A total of 39 patients were included, of whom 18 received preoperative TARE and 21 underwent upfront surgery. Patients in the TARE group showed significantly greater tumor necrosis at pathology (70% vs. 10%, p = 0.002) and more frequent extended resections. Five-year cancer-specific survival (80.4% vs. 33.5%, p = 0.011), recurrence-free survival (33.8% vs. 14.0%, p = 0.047), and curative-intent disease-free survival (69.3% vs. 18.9%, p = 0.0037) were significantly higher in the TARE group. Overall survival showed a favorable trend. Intraoperative outcomes, postoperative morbidity, and 90-day mortality were comparable between groups. Conclusions: Preoperative TARE is a safe and effective neoadjuvant strategy in selected patients with HCC undergoing major hepatectomy. It may enhance long-term oncological outcomes without increasing surgical risk, supporting its potential role in the management of borderline resectable HCC. Full article

Background/Objectives: According to recent reports, the BRAF^V600E mutation in serous borderline tumors (SBTs) plays a protective role against progression to low-grade serous carcinoma through oncogene-induced senescence. One consequence of this is the appearance of eosinophilic cells (ECs). The aim of the current study was to determine the interobserver reproducibility of ECs and their predictive significance for the detection of the BRAF^V600E mutation in SBTs. Methods: The study was conducted using 63 cases of ovarian SBTs. Three gynecological pathologists, blinded to each tumor’s mutation status, assessed the presence of ECs. Immunohistochemical staining with p16 and Ki-67 was performed to validate ECs. Mutational analysis was carried out using targeted NGS. Results: Genetic analysis revealed 30 BRAF-mutated, 1 NRAS-mutated, and 9 KRAS-mutated SBTs. ECs were identified by the majority of pathologists (two or three) in 78% of the BRAF^V600E-mutated and 11% of the wild-type tumors with other mutations (p < 0.0001). The interobserver reproducibility of the presence of ECs was substantial (κ = 0.66). ECs validated with p16/Ki-67 were identified in 92.6% of the BRAF^V600E-mutated and in 13.8% of the wild-type tumors with other mutations (p < 0.0001). For the ECs identified by the majority of pathologists, the sensitivity and specificity when predicting the BRAF^V600E mutation were 77.8% and 88.9%, respectively. For the ECs validated with p16/Ki-67, the sensitivity and specificity when predicting the BRAF^V600E mutation were 95.3% and 90.5%, respectively. Conclusions: Overall, these results suggest that ECs in SBTs have potential association with the BRAF^V600E mutation. Full article

Background/objective: Mucinous borderline tumors of the ovary (MBOTs) are characterized by their unique histological features and intermediate malignant potential; however, the factors underlying their molecular carcinogenesis and tumor biology remain largely unknown. Developing cell lines from these tumors presents an ongoing challenge. The purpose of this study is to establish MBOT cell lines and characterize their biological features. Methods: Epithelial cells were collected and purified from surgically removed MBOT samples and then stably maintained with an extended life span by overexpressing CyclinD1/CDK4 in combination with human telomerase reverse transcriptase. The characterization of resulting cell lines was defined by morphology, growth kinetics, functional analysis, whole-exome sequencing, and tumorigenicity in mice. Results: Two independent cell lines, HMucBOT-1 and HMucBOT-2, were successfully established from the tissues of a patient with an MBOT, with the latter showing more aggressive growth capacity. In the patient-derived xenograft model, HMucBOT-1 cells retained the original morphological characteristics of the MBOT, whereas HMucBOT-2 cells displayed a transition to mucinous carcinoma accompanying undifferentiated carcinoma, suggestive of dedifferentiated carcinoma. Genetic analysis of the original tumor sample and HMucBOT-2 cells revealed shared oncogenic mutations. However, KRAS amplification and certain copy number alterations were uniquely observed in the HMucBOT-2 cells. Conclusions: The above results indicate that HMucBOT-1 can serve as a preclinical model for investigating the biological behavior of and potential targeted therapies for human MBOTs, with HMucBOT-2 serving as a valuable tool for studying the heterogeneity and genetic diversity of this tumor and explaining the potential causes of treatment failure or relapse. Full article

Background: Tumor recurrence significantly impacts the quality of life and fertility of patients with serous borderline ovarian tumors (SBOT) and early-stage low-grade serous ovarian carcinoma (LGSOC). This study aims to characterize recurrence patterns, identify independent risk factors for recurrence, and develop a nomogram to predict recurrence-free survival (RFS). Methods: We conducted a retrospective case-control study to investigate recurrence in patients undergoing fertility-sparing surgery (FSS) and radical surgery (RS). Logistic regression and Cox regression were used to identify risk factors. Kaplan–Meier analysis was applied to evaluate RFS. A nomogram was developed based on identified variables to predict RFS. Results: Tumor capsule disruption and micropapillary were associated with higher recurrence risk in the FSS group. Non-invasive implants were associated with higher recurrence risk in the RS group. The nomogram prediction model was developed based on identified risk factors. The area under the curve (AUC) for RFS predictions was 0.74 (95% CI: 0.62–0.85) at 3 years and 0.78 (95% CI: 0.67–0.89) at 5 years for the FSS group and 0.87 (95% CI: 0.76–0.98) at 3 years and 0.81 (95% CI: 0.65–0.97) at 5 years for the RS group. Conclusions: We identified the risk factors for recurrence of SBOT and early-stage LGSOC following FSS and RS procedures and developed a predictive model for forecasting RFS. This model provides valuable guidance for patients and clinicians in predicting recurrence risk for patients. Full article

Background and Objectives: This study aimed to evaluate the diagnostic potential of systemic inflammatory indices such as Systemic Inflammation Response Index (SIRI) and Systemic Inflammatory Response (SIR). These were assessed in combination with CA 125 to distinguish ovarian carcinoma (OC) from borderline ovarian tumors (BOT) in patients with suspicious adnexal masses. Materials and Methods: A retrospective multicenter observational study including patients undergoing surgery for suspected ovarian neoplasms was conducted. Inclusion criteria required preoperative blood sampling for inflammatory markers and CA 125. SIR-125 and SIRI-125 were developed by combining SIR and SIRI with CA 125 levels. Diagnostic performance was assessed using ROC curve analysis and linear regression models. Results: A total of 63 patients (42 BOT, 21 OC) were analyzed. OC patients exhibited significantly higher SIR-125 and SIRI-125 values (p < 0.001). ROC analysis demonstrated good diagnostic accuracy, with AUCs of 0.83 (SIR-125) and 0.82 (SIRI-125). SIR-125 showed higher specificity (0.83), while SIRI-125 had superior sensitivity (0.86). Conclusions: SIR-125 and SIRI-125 enhance diagnostic differentiation between OC and BOT, providing a simple, cost-effective preoperative tool. Future prospective studies are needed to validate these findings in broader patient populations. Full article