Search Results (325)

Introduction: Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer-related death worldwide. CRC is characterized by morphologic and biological heterogeneity, and molecular profiling is required to select appropriate treatment in the metastatic setting. Mutations in KRAS are detected in approximately 40% of CRCs, with prognostic and predictive value, and with the most frequent being p.G12D. Nonetheless, there are few data on the morphologic features in KRAS-mutated CRCs. Materials and Methods: We retrospectively collected clinicopathological features and molecular profiles of CRCs in a multicenter cohort. Results: A total of 2816 patients from 12 centers were included. KRAS mutation was found in 47.4% of cases; Gly12Asp was detected in 23.9%, with different mutation frequencies between centers. Clinicohistological features associated with Gly12Asp mutation included younger patient age (≤70 years of age), higher prevalence in males (58.6%), NOS histotype (87.1%), low pathologic grade (73.9%), high grade budding—Bd3 (43.8%), and tumoral lympho-vascular invasion (68.9%). Conclusions: Recent data have pinpointed the prognostic and predictive value of Gly12Asp mutation, and our results contribute to understanding its biology, with particular focus on peculiar clinicopathological features. Moreover, we found significant differences in pathology reports and assays for molecular profiling in different centers, which can affect a standardized therapeutic approach in CRC. Full article

Background: Re-excision after breast-conserving surgery (BCS) is routinely recommended when positive margins are found. However, secondary surgery often reveals no residual disease, exposing patients to unnecessary interventions that compromise cosmetic outcomes, increase costs, and reduce quality of life. This study investigates clinicopathological predictors of a residual tumour to identify low-risk patients who may safely avoid re-excision. Methods: We conducted a retrospective cohort study of 135 patients who underwent reoperation for positive margins following BCS at the Breast Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, between 2019 and 2024. Data on patient demographics, tumour characteristics, and histopathological findings were analyzed using univariate and multivariate models to identify predictors of residual disease. Results: A residual tumour was detected in 66 of 135 patients (48.9%). In the remaining 69 cases (51.1%), no residual disease was found, indicating that re-excision may have been unnecessary. Multifocality (p < 0.01), lymphovascular invasion (LVI) (p < 0.05), and involvement of ≥2 margins (p < 0.05) were independently associated with the residual tumour. Patients with unifocal disease, absence of LVI, and a single positive margin had a significantly lower risk of residual disease. Conclusions: Over half of re-excisions performed for positive margins may be avoidable. A risk-adapted approach incorporating tumour focality, LVI status, and margin involvement can help identify patients for whom secondary surgery may offer limited benefits. These findings support a more individualized strategy to margin management in BCS aimed at reducing overtreatment without compromising oncologic safety. Full article

Background: Perioperative factors significantly impact oncologic outcomes after radical cystectomy (RC) for bladder cancer. This study aimed to identify key perioperative predictors for overall (OS) and progression-free survival (PFS) and to develop a prognostic nomogram for the identification of high-risk patients adapted to the clinical routines and standard of care of our country. Methods: We retrospectively analyzed 121 patients undergoing RC (2014–2024). Data on patient demographics, comorbidities, tumor pathology, neoadjuvant treatments, extensive intraoperative factors, and postoperative events were assessed using COX models. A prognostic nomogram for 3-year OS was constructed. Results: Median follow-up was 44.33 months. Significant predictors for worse OS included lymphovascular invasion (LVI) (HR 2.22), higher T stage (HR 8.75), N+ status (HR 1.10), and intraoperative complications (HR 3.04). Similar predictors were noted for PFS. The developed nomogram incorporated T-, N-stages, sex, grade, intraoperative complications and early (12 months) recurrence, and was able to significantly identify patients with a higher mortality risk (p < 0.001) with a C-index of 0.74. Conclusions: Our nomogram for mortality prediction of BC patients offers a promising tool for individualized risk stratification. Further studies are required for its external validation. Full article

The optimal sequencing of chemotherapy in locally advanced gastric cancer (LAGC) remains controversial. This study aimed to compare survival outcomes between adjuvant (ACT) and neoadjuvant (NACT) chemotherapy and to identify clinicopathological factors associated with progression-free survival (PFS) and overall survival (OS) in a real-world setting. Methods: We retrospectively analyzed 103 patients with non-metastatic gastric cancer treated between 2014 and 2024. Patients were categorized into ACT (n = 56) and NACT (n = 47) groups. Kaplan–Meier and Cox regression analyses were used to assess survival outcomes and prognostic factors. Results: The NACT group was younger and had more proximal tumors. Median OS was 48.7 months in the ACT group versus 17.7 months in the NACT group (p = 0.048). Median PFS was not reached in the ACT group and was 15.6 months in the NACT group (p = 0.008). Negative surgical margin status was independently associated with improved survival, whereas age was an independent negative prognostic factor for OS. No significant associations were found between OS or PFS and histologic subtype, lymphovascular invasion, perineural invasion, gender, D2 dissection, or type of surgery. Notably, 21% of NACT patients did not proceed to surgery due to progression, treatment intolerance, or refusal. Conclusion: Although ACT was associated with longer PFS and OS in this cohort, these differences are most likely explained by baseline imbalances, patient selection factors, and survivorship bias rather than the timing of chemotherapy itself. These findings highlight the importance of careful patient selection for NACT and underscore the need for prospective, randomized studies to define optimal sequencing strategies in LAGC. Our study contributes descriptive, real-world data rather than definitive evidence of treatment superiority. Full article

Background/Objectives: Endometrial cancer (EC) is the most common gynecological tumor in developed countries, and presents a wide variety of histological and molecular characteristics that make its treatment increasingly complex. In recent years, advances in molecular imaging, particularly with [¹⁸F]FDG-PET/CT and PET/MRI, have changed clinicians’ management of diagnosis, treatment planning, and prognosis of EC. Methods: In this narrative review, a search was conducted for current evidence on the role of [¹⁸F]FDG-PET/CT and PET/MRI throughout the treatment of EC, focusing on their diagnostic performance, clinical relevance, and prognostic implications. Their use in areas such as initial staging, treatment monitoring, recurrence detection, and individualized risk assessment was also discussed. Results: [¹⁸F]FDG-PET/CT is effective in detecting lymph node and distant metastases, while [¹⁸F]FDG-PET/MRI offers greater accuracy for T and N staging. In addition, [¹⁸F]FDG-PET/CT provides early metabolic indicators of therapeutic response and facilitates differentiation between viable tumors and post-treatment changes. Radiomics-derived parameters have shown promising associations with tumor aggressiveness and lymphovascular invasion and survival, supporting their role as prognostic imaging biomarkers. In addition, the use of non-FDG radiotracers, as well as predictive models based on machine learning, can further refine preoperative stratification and treatment planning in certain subtypes of EC. Conclusions: Molecular imaging enhances the accuracy of TNM staging in EC. The incorporation of molecular imaging biomarkers into daily clinical practice could significantly improve personalized decision-making in EC. However, large prospective studies are needed to confirm their efficacy. Full article

Adenocarcinoma of the gastroesophageal junction (AEG) is an aggressive cancer with rising incidence and poor long-term survival despite multimodal treatment. Reliable preoperative prognostic markers are lacking. Methods: The study is based on data from a prospectively maintained institutional database, which was retrospectively analyzed. In total, 211 patients were analyzed who underwent curative resection for AEG to evaluate the association of SII and LVI and their combined prognostic value. Results: LVI was present in 45% of patients and was significantly associated with higher median SII values compared to patients without LVI (943 vs. 652; p < 0.001). Both high SII and the presence of LVI were independently associated with worse overall survival (p < 0.001 for both). In patients treated with primary surgery (65%), the combined presence of high SII and LVI identified a subgroup with particularly poor prognosis (pseudo-R² increased from 0.451 to 0.524; likelihood-ratio test p < 0.001). Among patients who received neoadjuvant therapy (NT) (35%), SII remained a strong prognostic factor (pseudo-R² = 0.432), while LVI alone was not statistically significant (p = 0.135), and its addition to the SII model did not improve prognostic performance (p = 0.377). Conclusions: The combined assessment of SII and LVI may improve prognostic stratification in AEG, especially in patients undergoing upfront surgery. These findings suggest that combined assessment of SII and LVI enhances prognostic stratification, particularly in patients treated with upfront surgery, and may aid personalized treatment and follow-up planning in AEG. To the best of our knowledge, this is the first study investigating the association of SII and LVI in AEG. Full article

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Background/Objectives: The COVID-19 pandemic disrupted global cancer care. This study compared gastric cancer surgical outcomes before and during the pandemic in Turkey. We also aimed to analyze the impact of the pandemic and factors on survival and mortality in gastric cancer patients. Materials and Methods: This retrospective, multicenter cohort study included 324 patients from three tertiary centers in Turkey who underwent gastric cancer surgery between January 2018 and December 2022. Patients were stratified into Pre-COVID-19 (n = 150) and COVID-19 Era (n = 174) groups. Comprehensive demographic, surgical, pathological, and survival data were analyzed. To identify factors independently associated with postoperative mortality, a multivariable logistic regression model was applied. For evaluating predictors of long-term survival, multivariable Cox proportional hazards regression analysis was conducted. Results: The median time from diagnosis to surgery was comparable between groups, while the time from surgery to pathology report was significantly prolonged during the pandemic (p = 0.012). Laparoscopic surgery (p = 0.040) and near-total gastrectomy (p = 0.025) were more frequently performed in the Pre-COVID-19 group. Although survival rates between groups were similar (p = 0.964), follow-up duration was significantly shorter in the COVID-19 Era (p < 0.001). Comparison between survivor and non-survivor groups showed that several variables were significantly associated with mortality, including larger tumor size (p < 0.001), greater number of metastatic lymph nodes (p < 0.001), elevated preoperative CEA (p = 0.001), CA 19-9 (p < 0.001), poor tumor differentiation (p = 0.002), signet ring cell histology (p = 0.003), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001). Multivariable logistic regression identified total gastrectomy (OR: 2.14), T4 tumor stage (OR: 2.93), N3 nodal status (OR: 2.87), and lymphovascular invasion (OR: 2.87) as independent predictors of postoperative mortality. Cox regression analysis revealed that combined tumor location (HR: 1.73), total gastrectomy (HR: 1.56), lymphovascular invasion (HR: 2.63), T4 tumor stage (HR: 1.93), N3 nodal status (HR: 1.71), and distant metastasis (HR: 1.74) were independently associated with decreased overall survival. Conclusions: Although gastric cancer surgery continued during the COVID-19 pandemic, some delays in pathology reporting were observed; however, these did not significantly affect the timing of adjuvant therapy or patient outcomes. Importantly, pandemic timing was not identified as an independent risk factor for mortality in multivariable logistic regression analysis, nor for survival in multivariable Cox regression analysis. Instead, tumor burden and aggressiveness—specifically advanced stage, lymphovascular invasion, and total gastrectomy—remained the primary independent determinants of poor prognosis. While pandemic-related workflow delays occurred, institutional adaptability preserved oncologic outcomes. Full article

Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article

Colorectal cancer (CRC) diagnosed in an advanced stage has an increased predisposition for invasion and metastasis, requiring upgraded prognostic markers. CDH17, a liver-intestine cadherin, is an adhesion molecule implicated in tumor progression. This retrospective study assessed the immunohistochemical expression of CDH17 in 84 CRC cases with lymphovascular invasion (LVI), analyzing its correlation with clinicopathological features and survival outcomes. CDH17 expression was evaluated in the tumor core, invasive front, tumor emboli, and lymph node metastases. Statistical analyses showed significant associations between high CDH17 expression and favorable histological types, as well as low-grade differentiation. However, high CDH17 levels in tumor emboli correlated with advanced T stage and poorer overall survival. Multivariable Cox regression confirmed CDH17 expression in tumor emboli as an independent prognostic factor, indicating an approximately twofold risk of death. These findings suggest that CDH17 may have a dual role—maintaining adhesion in low-grade tumors while facilitating tumor emboli-related dissemination. CDH17 expression, particularly in the tumor emboli, could serve as a valuable prognostic biomarker in CRC with LVI. Full article

Background/Objectives: Lymphovascular invasion (LVI) has been consistently linked to poor outcomes in patients with bladder cancer (BC), yet its independent prognostic value, especially after adjusting for established pathological features, remains debated. This study aimed to evaluate the prognostic value of LVI in the context of other pathological features of patients undergoing radical cystectomy. Methods: We conducted a retrospective cohort study including 200 patients treated at the Municipal Clinical Hospital in Cluj-Napoca, Romania. Associations between LVI and overall survival (OS) were assessed using univariable and multivariable Cox proportional hazards models, with Kaplan–Meier curves used for visualizing survival distributions. Results: In univariable analysis, increasing age, presence of LVI, advanced pathological tumor stage (pT ≥ 2), and nodal involvement (pN ≥ 1) were significantly associated with worse OS. LVI was a strong predictor of poor survival (HR 3.13; 95% CI: 2.09; 4.69; p < 0.001). However, in multivariable analysis, only tumor stage (HR 4.85; 95% CI: 2.19; 10.77; p < 0.001) and nodal involvement (HR 1.87; 95% CI: 1.13; 3.09; p = 0.015) remained independently associated with OS. In patients with incomplete nodal staging (Nx), LVI was significantly associated with OS (p = 0.028). Conclusions: Our findings reinforce the prognostic relevance of LVI in bladder cancer and support its role as a marker of aggressive tumor biology, highlighting its value in clinical risk assessment, especially in patients with incomplete nodal staging. Routine reporting of LVI in pathology and consideration in treatment planning are warranted. Full article

Background/Objectives: The aim of this study was to investigate the relationship between the PRIMARY score derived from [⁶⁸Ga]Ga-PSMA PET/CT and key clinical and pathological parameters of prostate cancer aggressiveness, including the PSA level, ISUP Grade Group, and D’Amico risk classification, in patients with biopsy-proven prostate cancer. A secondary aim was to evaluate the interobserver agreement of the PRIMARY score in routine clinical practice. Methods: This retrospective analysis included 51 patients with histopathologically confirmed prostate adenocarcinoma who underwent [⁶⁸Ga]Ga-PSMA PET/CT imaging for staging. PRIMARY scores were determined based on the intraprostatic uptake pattern, intensity, and zonal localization. These scores were compared with PSA levels, ISUP GG, D’Amico risk classification, and histopathological features such as the cribriform pattern, intraductal carcinoma, perineural invasion, extraprostatic extension, and lymphovascular invasion. The PRIMARY scores were independently assigned by a total of three nuclear medicine physicians, and interobserver agreement was calculated using Fleiss’ kappa analysis. Results: Significant associations were found between the PRIMARY scores and the PSA level, ISUP Grade Group, and D’Amico risk classification. The most prevalent score was PRIMARY 5 (54.9%), which was significantly associated with ISUP GG 5 and the high-risk category in D’Amico classification. Among patients with PRIMARY Score 2, a substantial proportion (64.7%) had ISUP GG ≥ 3, and 58.8% were in the high-risk group, highlighting the limitations of binary PRIMARY classification. No statistically significant correlations were found between the PRIMARY scores and specific histopathologic features. Interobserver agreement was excellent (κ = 0.833). Conclusions: The PRIMARY score demonstrates high reproducibility and clinical relevance in stratifying prostate cancer aggressiveness. However, the findings challenge the reliability of binary classifications, particularly for patients with Score 2, who may still harbor high-grade disease. Integrating imaging-based scores with clinical and histopathological data is essential, particularly for accurate staging and decision-making regarding active surveillance. Full article

Background/Objectives: Given the increasing interest in the predictive role of inflammation in oncology, we aimed to assess the association between inflammatory factors (IFs) and the histopathological characteristics of bladder cancer (BC). Our objective was to correlate some of these IFs with BC progression and recurrence, identifying possible new diagnostic tools. Methods: We retrospectively analyzed 285 patients (79.8% male, 20.4% female; median age 73) who underwent transurethral resection of the bladder (TURB) between January 2016 and January 2022. The preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), and standard clinical variables were collected one month before TURB and evaluated as predictors of recurrence and progression. Patients were stratified using the Youden Index and ROC analysis. Cox regression models were applied to identify independent predictors. Results: High-grade tumors were present in 74.6% of cases, and 34% were recurrent. Carcinoma in situ was found in 5%. After 72 months, 53% underwent radical cystectomy, and 13.7% died within 5 years. The optimal cutoffs were PLR 139, SIRI 1.12, PIV 248.49, NLR 2, SII 327. Smoking, primary MIBC, age, and lymph node status were significantly associated with recurrence. Elevated PLR correlated with recurrence and T2 progression (p = 0.004). Higher SIRI, PIV, and PLR levels were significantly associated with lymphovascular invasion and nodal metastasis (p < 0.05). PLR was linked to recurrence in tumors ≥ 3 cm post-BCG (p = 0.004); high SIRI predicted recurrence within 48 months (p = 0.05). Conclusions: High PLR and SIRI levels were associated with recurrence. Our findings support the emerging role of IFs in predicting BC outcomes and suggest their potential inclusion in future prognostic models. Full article

Background/Objectives: With evolving guidelines favoring de-escalation in the management of papillary thyroid microcarcinoma (PTMC), options such as active surveillance and minimally invasive procedures are now considered for patients with low-risk disease. However, a subset of PTMCs—particularly non-incidental cases—may exhibit aggressive behavior. This study compares disease characteristics and outcomes between incidental and non-incidental PTMCs over a 10-year period. Methods: This is a single-center retrospective comparative analysis utilizing a prospectively collected database of patients referred for thyroid surgery. Results: Papillary thyroid carcinoma accounted for 86.7% of thyroid malignancies, with PTMC comprising 36.2% (137 patients). Incidental PTMC represented 109 out of 1012 patients undergoing surgery for benign thyroid disease (10.8%). Non-incidental PTMC (NIPTMC), diagnosed preoperatively and presenting clinically without coexisting thyroid disease, was identified in 28 patients (20.4%). NIPTMCs were more frequently associated with high-risk features (75% vs. 10.1%, p = 0.004), including extrathyroidal extension (21.43% vs. 7.3% p = 0.0015), positive central lymph nodes (21.43% vs. 2.8%, p = 0.0291), positive lateral lymph nodes (28.6% vs. 0% p = 0.012), and lymphovascular invasion (3.6% vs. 0%). Multifocal PTMC was seen in 37 patients (27%), of which 27 had bilobar disease. Multifocal tumors had a higher likelihood of high-risk features (48.6% vs. 14%, p = 0.007). NIPTMC was a significant predictor of multifocality (p = 0.0098). All patients underwent surgery, none opted for active surveillance. Conclusions: NIPTMC is more often associated with high-risk features and multifocality, necessitating more extensive surgery. These findings emphasize the need for careful preoperative risk stratification to guide individualized management. Full article

Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment involvement, has been observed in PTC with a wide range of reported frequencies. The identification of risk factors for SM is crucial for preoperative evaluation and surgical planning. This research aims to explore the clinicopathological features and potential risk factors linked to SM in patients with PTC, while also offering valuable insights for preoperative risk evaluation. Methods: A retrospective cohort study was conducted on 81 PTC patients who underwent central and lateral cervical lymph node dissection (LND) in our center. Clinical, demographic, and pathological data, including age, sex, tumor size, location, subtype, extrathyroidal extension, lymphovascular invasion, and the number of lymph node metastases were analyzed. Clinicopathological characteristics were analyzed between SM-positive and SM-negative patient groups using suitable statistical methods. Additionally, a regression analysis was performed to identify the risk factors for SM. Results: Of the 81 patients, 17.3% (n = 14) were diagnosed with skip metastasis (SM). The SM-positive group had a significantly higher age (p = 0.006), smaller tumor size (p < 0.001), and higher rates of extrathyroidal extension (p = 0.006). The proportion of female patients was elevated in the SM-positive group, but this observation did not achieve statistical significance (p = 0.128). Tumors located in the upper pole were more common in the SM-positive group (p = 0.016). Multivariate analysis revealed that female sex, older age, and tumor location in the upper pole were significant risk factors for SM (p = 0.031, p = 0.004, and p = 0.017, respectively), while a lower number of lateral lymph node metastases was significantly associated with SM (p = 0.010). Additionally, an age over 43.5 years predicted SM with a sensitivity of 78.6% and a specificity of 72.7%. Conclusions: Skip metastasis is not uncommon in PTC and may be associated with older age, female sex, upper pole tumor location, and fewer lateral lymph node metastases. Recognizing these factors during preoperative assessment may aid in anticipating atypical lymphatic spread patterns and optimizing surgical strategies. Full article