Background: Platinum-resistant ovarian cancer with peritoneal metastases remains a therapeutic frontier marked by limited systemic efficacy and a persistent unmet clinical need for effective locoregional strategies. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel minimally invasive platform designed to enhance intraperitoneal drug distribution and overcome biological barriers to chemotherapy delivery. Methods: We performed a PRISMA-compliant systematic review and meta-analysis evaluating clinical outcomes of PIPAC in platinum-resistant ovarian cancer. Primary endpoints included histologic regression (PRGS ≤ 2), severe toxicity, and 12-month overall survival, complemented by exploratory analyses of treatment feasibility, disease burden dynamics, and bidirectional therapy strategies. Results: PIPAC demonstrated a consistent signal of biologic activity, with pooled histologic response rates indicating meaningful tumor regression despite advanced disease. Severe toxicity remained low across studies, supporting the favorable tolerability of repeated intraperitoneal treatment. Survival outcomes were clinically relevant for a heavily pretreated population, while feasibility analyses suggested that PIPAC may facilitate downstream surgical opportunities in selected patients. Exploratory findings further supported the concept of intraperitoneal disease modulation, reflected by reductions in peritoneal cancer index and integration within multimodal treatment pathways. Conclusions: Beyond a purely palliative intervention, PIPAC may represent a biologically active component of personalized treatment strategies for platinum-resistant ovarian cancer. These findings redefine the therapeutic narrative from symptom control toward disease modulation and treatment escalation, underscoring the need for prospective trials to refine patient selection and optimize multimodal sequencing.

Background: The benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery (CRS) in ovarian cancer with peritoneal metastasis remains debated outside selected indications. We performed a systematic review and meta-analysis to quantify survival, perioperative morbidity, and completeness of cytoreduction using study-level data. Methods: PubMed/MEDLINE, Embase, and Web of Science were searched. Eligible English-language studies included ovarian cancer patients undergoing CRS plus HIPEC and reported at least one of the following: overall survival (OS), progression-free survival (PFS), Grade III–IV complications, or CC-0 rate. Random-effects meta-analyses were conducted using inverse-variance pooling. For HR outcomes, DerSimonian–Laird τ² with Hartung–Knapp confidence intervals was applied. Proportions were pooled using logit transformation (PLOGIT) with random-effects models. Results: Twelve studies (n = 567) were included. Only two studies provided extractable HRs for OS and PFS (n = 217). CRS plus HIPEC was associated with improved OS (HR 0.68, 95% CI 0.52–0.90, p = 0.0023; I² = 0%; prediction interval 0.14–3.34) and improved PFS (HR 0.70, 95% CI 0.31–1.57, p = 0.0007; I² = 0%; prediction interval 0.18–2.66). Across 12 studies (n = 563), the pooled Grade III–IV complication rate was 0.18 (95% CI 0.14–0.22; I² = 16.3%; prediction interval 0.12–0.26). In 10 studies (n = 385), the pooled CC-0 rate was 0.87 (95% CI 0.79–0.92; I² = 46.7%; prediction interval 0.66–0.96). Conclusions: CRS plus HIPEC shows a favorable signal for OS and PFS in the limited HR-eligible evidence and appears feasible, with a pooled severe complication rate of ~18% and high CC-0 rates. Current data support HIPEC primarily as a targeted intensification strategy in carefully selected patients, while broader adoption requires additional randomized, context-specific evidence.

Background: Colorectal cancer (CRC) prognosis, particularly in liver metastasis (CRLM), is influenced by histopathological and molecular factors. Methods: A narrative analysis of the specialized literature was conducted using databases such as PubMed, MEDLINE, Scopus, and Embase. The review focused on original articles published between 2005 and 2025. Results: Lymph node involvement is a critical prognostic factor, with lymph node-positive CRC correlating with increased risk of liver metastasis and significantly reduced survival rates. Poorly differentiated tumors (G3) exhibit a higher likelihood of metastasis, including liver involvement, and are associated with worse clinical outcomes. Vascular emboli and perineural invasion are indicative of hematogenous spread and higher metastatic potential, leading to poorer survival outcomes. Genetic mutations, such as KRAS, NRAS, and BRAF, are associated with therapy resistance, complicating treatment and highlighting the importance of personalized approaches. MSI-H and HER2 amplification further affect treatment response, with MSI-H tumors showing a favorable response to immunotherapy, while HER2-positive CRCs may benefit from targeted therapies. Tumor budding, high levels of which predict poor survival, is another key histopathological feature associated with aggressive metastatic behavior. Systemic inflammatory markers, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and C-Reactive Protein-to-Albumin Ratio (CAR), offer prognostic insights into CRLM patient survival. Conclusions: Histopathological features, molecular alterations, and immune microenvironment factors significantly impact the prognosis of CRC with liver metastasis. The integration of molecular profiling, immunotherapy, and targeted therapies offers promise for improving treatment outcomes. Personalized treatment strategies, incorporating these factors, are essential for overcoming therapy resistance and improving survival in CRLM patients.

Background: The choice between mitomycin C (MMC) and oxaliplatin (OX) for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery for appendiceal neoplasms remains unresolved. Methods: PubMed/MEDLINE, Europe PMC, Scopus, Web of Science and ClinicalTrials.gov were searched to 1 October 2026 for studies comparing OX- and MMC-based HIPEC with outcomes in appendiceal neoplasms (PRISMA 2020; the protocol was not prospectively registered). Hazard ratios (HRs; OX vs. MMC, HR > 1 favours MMC) not reported by the studies were estimated from reconstructed individual patient data. Random-effects meta-analyses were performed; risk of bias was assessed with RoB 2 and ROBINS-I, and certainty with GRADE. Results: Ten studies (12 reports), including one randomised trial (n = 121), were included. In the randomised trial, HRs reconstructed from published Kaplan–Meier curves were 1.02 (95% CI 0.61–1.72) for disease-free survival and 1.05 (95% CI 0.59–1.85) for overall survival. In exploratory pooled analyses that also included observational cohorts, the HR for disease-free survival (4 studies, 343 patients) (OX vs. MMC) was 1.12 (95% CI 0.55–2.29; I² = 60%), and 0.89 (95% CI 0.57–1.40) after exclusion of the only study reporting a significant difference. For overall survival (2 studies, 157 patients), the pooled HR was 0.97 (95% CI 0.56–1.69). Major morbidity did not differ (risk ratio 0.98, 95% CI 0.64–1.50). Leukopenia was more frequent with MMC, and health-related quality of life favoured OX in exploratory analyses of the randomised trial. Certainty of evidence was low to very low. Conclusions: Current evidence shows no survival difference between OX- and MMC-based HIPEC for appendiceal neoplasms, but it is sparse and imprecise. Regimen choice may reasonably be guided by toxicity, perfusion protocol and patient factors until adequately powered trials are available.

Background: Radical cystectomy (RC) remains associated with substantial perioperative morbidity despite advances in minimally invasive surgery and reconstructive techniques. Comparisons between intracorporeal reconstruction, robotic-assisted approaches, and urinary diversion strategies are frequently confounded by clinical heterogeneity and patient selection. This study aimed to perform a stratified surgical systematic review evaluating perioperative outcomes across distinct reconstructive pathways following RC. Methods: A PRISMA-guided systematic review identified comparative studies evaluating intracorporeal versus extracorporeal/open orthotopic neobladder reconstruction, robotic-assisted versus open radical cystectomy in frail patients undergoing ureterocutaneostomy, and ileal conduit versus orthotopic urinary diversion. Analyses were performed within predefined clinical modules to preserve surgical context. Outcomes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs), complemented by rare-event sensitivity analyses and exploratory absolute risk metrics, including number needed to treat or harm (NNT/NNH). Continuous outcomes such as estimated blood loss and length of hospital stay were assessed descriptively. Results: Three comparative observational cohorts met inclusion criteria. Intracorporeal neobladder reconstruction and robotic-assisted cystectomy demonstrated consistent reductions in transfusion rates and favourable trends in perioperative morbidity. In frail patient populations, robotic surgery showed reduced intraoperative burden without increased readmission or mortality. Ileal conduit diversion was associated with increased wound-related complications and infectious outcomes; however, these findings likely reflect baseline differences in patient frailty and selection. Rare-event sensitivity analyses confirmed directional consistency of treatment effects despite wide confidence intervals. Integration of absolute risk differences and NNT/NNH metrics provided clinically interpretable context for stratified outcomes. Conclusions: Minimally invasive and intracorporeal strategies following radical cystectomy may reduce perioperative burden, whereas diversion type primarily influences complication patterns rather than overall morbidity. A stratified analytical framework integrating relative and absolute effect measures may offer a more clinically meaningful approach to evaluating reconstructive strategies in heterogeneous surgical populations.

Background: Medullary thyroid carcinoma (MTC) is a rare but aggressive neuroendocrine thyroid malignancy in which early diagnosis is essential for improving clinical outcomes. Although calcitonin (CT) remains the standard diagnostic biomarker, its interpretation may be limited by false-positive elevations, assay variability, and indeterminate cut-off values. Consequently, alternative biomarkers such as procalcitonin (PCT), circulating microRNA-375 (miR-375), and fine-needle aspiration washout calcitonin (FNA-CT) have gained increasing interest. Methods: A systematic review and diagnostic meta-analysis were conducted to evaluate the diagnostic performance of circulating and tissue-related biomarkers for MTC. Eligible studies reporting sufficient diagnostic accuracy data were included. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves were calculated using a bivariate random-effects model. Methodological quality was assessed using the QUADAS-2 tool. Results: Five diagnostic datasets were included in the quantitative synthesis. The pooled sensitivity and specificity were 0.90 (95% CI: 0.84–0.94) and 0.99 (95% CI: 0.97–0.997), respectively. The pooled LR+ was 84.78, while the pooled LR− was 0.10. The pooled diagnostic odds ratio was 857.30, indicating excellent discriminatory diagnostic performance. SROC analysis demonstrated near-perfect overall diagnostic accuracy with an area under the curve (AUC) of 0.986. Procalcitonin-based approaches showed the most consistent diagnostic performance across studies, while combined CT + PCT strategies achieved the highest overall diagnostic accuracy. Emerging biomarkers such as miR-375 and FNA-CT also demonstrated promising results, although evidence remains limited. Conclusions: Biomarker-based diagnostic strategies demonstrate excellent diagnostic accuracy for medullary thyroid carcinoma. Among the evaluated biomarkers, procalcitonin-based approaches, particularly combined CT + PCT strategies, showed the most robust and clinically relevant diagnostic performance. These findings support the potential integration of procalcitonin into future diagnostic algorithms for MTC. Further large-scale prospective studies are required to validate diagnostic thresholds and standardize biomarker assessment protocols.