Search Results (521)

Background: This study aimed to evaluate the impact of surgical margin status, tumor size, and adjuvant radiotherapy on local control, overall survival, and postoperative complications in patients undergoing surgery for sacral chordoma. Methods: This retrospective analysis included 18 patients who underwent surgical treatment for primary sacral chordoma between 2002 and 2019. The variables assessed included patient demographics, tumor size and volume, surgical margin status, adjuvant radiotherapy, local recurrence, overall survival, and postoperative complications. Survival analysis was performed using the Kaplan–Meier method, and appropriate parametric or non-parametric tests were used for group comparisons. Results: The cohort’s mean age was 62.6 ± 7.9 years, with a mean follow-up of 8.8 ± 4.1 years and an average tumor volume of 235 cm³. Negative surgical margins (R0) were achieved in 44% of patients. Local recurrence occurred in 50% of R0 cases and 83% of R2 cases. Negative surgical margins (R0) were associated with significantly lower local recurrence rates compared to R1 and R2 resections (Fisher’s exact test, p = 0.043), and showed a trend toward improved overall survival (p = 0.077). Overall survival was significantly lower in patients with tumors measuring ≥ 5 cm (p = 0.031). Adjuvant radiotherapy did not significantly reduce local recurrence (p = 0.245); however, an increase in complication rates was observed, although this association did not reach statistical significance (p = 0.108). Bladder dysfunction was significantly more frequent in patients undergoing S1–S2 resections (p = 0.036). Conclusions: Achieving negative surgical margins improves local control and may prolong survival. Larger tumors (≥5 cm) were associated with worse prognosis. While adjuvant RT may be considered in selected high-risk cases, its efficacy in preventing recurrence is unclear and may increase complication rates. Full article

Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article

Background/Objectives: Neo-adjuvant chemotherapy (NACT) is increasingly utilized in Western countries for the treatment of gastric cancer (GC). While its oncologic benefits are well established, its impact on surgical safety and long-term outcomes remain a matter of debate. This study evaluates the real-world effect of NACT on perioperative and oncologic outcomes in a high-volume Western center. Methods: Data from 254 patients who underwent gastrectomy with D2 lymphadenectomy for GC between March 2016 and January 2024 were prospectively collected and retrospectively analyzed. Patients were categorized into an upfront surgery group (n = 144, 56.7%) and a NACT group (n = 110, 43.3%). The primary outcome was to compare the two study groups in terms of perioperative outcomes, as well as overall (OS) and disease-free survival (DFS). Multivariate analyses were conducted to identify factors associated with perioperative complications and long-term survival. Results: Patients in the NACT group were younger (median age 65 vs. 72 years; p = 0.001) and had fewer comorbidities. NACT was associated with a higher incidence of proximal tumors (54–49.1% vs. 37–25.7%; p = 0.001), diffuse-type tumors (27–45.8% vs. 39–31.7%; p = 0.03), and lymph-node metastases (82–74.1% vs. 84–58%; p = 0.007). No significant differences were observed in median hospital stay (9 (7–16) and 10 (8–22) days for the upfront and NACT groups, respectively; p = 0.26), post-operative mortality (11–7.6% and 5–4.5% for the upfront and NACT groups, respectively; p = 0.32), and major complications (30–20.8% and 23–20.9% for the upfront and NACT groups, respectively; p = 0.99). Among patients receiving NACT, the FLOT regimen was associated with a lower rate of complications (12–16.2% vs. 11–30.5% in the non-FLOT cohort; p = 0.05) and reoperations (4–5.4% vs. 8–22.2% in the non-FLOT group; p = 0.008). Tumor location was identified as an independent predictor of perioperative complications (OR 4.7, 95% C.I.: 1.56–14.18; p = 0.006), while non-FLOT regimens were independently associated with higher reoperation rates (OR 0.22, 95% C.I.: 0.06–0.86; p = 0.003). Five-year OS was comparable between the two groups (44.6% in the NACT group vs. 47.7% in the upfront surgery group; p = 0.96). N+ status (OR 2.5, 95% C.I. 1.42–4.40; p = 0.001) and R+ margins (OR 1.89, 95% C.I. 0.98–3.65; p = 0.006) were negative independent prognostic factors for DFS. Conclusions: Although several selection biases limit the generalizability of our findings, our results suggest that NACT prior to gastrectomy for GC does not increase postoperative morbidity and mortality in appropriately selected patients. However, its use in elderly and polymorbid patients should be carefully considered to determine the safest and most effective therapeutic approach, particularly in selecting the appropriate chemotherapy regimen, to minimize the risk of postoperative complications requiring surgical reintervention. Full article

Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs. Methods: We conducted a retrospective multicenter study analyzing patients diagnosed with intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA) or gallbladder cancer (GBC) who underwent curative-intent surgical resection between 1999 and 2023. Demographic, clinicopathological, and treatment data were collected from institutional databases. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified through Cox proportional hazards regression. Results: A total of 155 patients were included, with a median follow-up of 84.6 months. The cohort comprised 38.7% iCCA, 31.6% eCCA, and 29.7% GBC. R0 resection was achieved in 77.4% of cases, while lymph node involvement was present in 39.4%. Median overall survival (OS) significantly varied by stage (p < 0.001), ranging from >60 months for stage I to ~12 months for stage IVA. Eastern Cooperative Oncology Group (ECOG) performance status (PS) emerged as the strongest independent prognostic factor for OS (p < 0.001). Adjuvant chemotherapy, administered to 49.0% of patients, did not significantly improve OS in the overall cohort (p = 0.899). However, subgroup analyses suggested potential benefits in iCCA and eCCA but not in GBC. High CA19-9 levels and vascular invasion were associated with poorer survival outcomes. Conclusions: This study highlights the prognostic significance of ECOG PS, resection margin status, lymph node involvement, and CA19-9 levels in resected BTCs. The lack of a clear survival benefit from adjuvant chemotherapy underscores the need for improved therapeutic strategies. Future research should focus on refining risk stratification models and identifying more effective adjuvant treatments to enhance long-term survival outcomes in patients with BTC. Full article

Purpose: Pellucid Marginal Degeneration (PMD) is a rare ectatic corneal disorder characterized by inferior peripheral thinning and significant irregular astigmatism. Despite its clinical similarities to keratoconus, PMD presents unique diagnostic and therapeutic challenges. This review aims to provide a comprehensive update on the pathophysiology, clinical features, diagnostic approaches, and management strategies for PMD, emphasizing the latest advancements in treatment options. Methods: A systematic literature search was performed in MEDLINE (via PubMed), Google Scholar, and Scopus up to February 2025 using the terms: “pellucid marginal degeneration,” “PMD,” “ectatic corneal disorders,” “keratoplasty in PMD,” “corneal cross-linking in PMD,” “ICRS in PMD,” “toric IOL PMD” and their Boolean combinations (AND/OR). The search was restricted to English-language studies involving human subjects, including case reports, case series, retrospective studies, clinical trials, and systematic reviews. A total of 76 studies met the inclusion criteria addressing treatment outcomes in PMD. Results: PMD is characterized by a crescent-shaped band of inferior corneal thinning, leading to high irregular astigmatism and reduced visual acuity. Diagnosis relies on advanced imaging techniques such as Scheimpflug-based corneal tomography, which reveals the characteristic “crab-claw” pattern. Conservative management includes rigid gas-permeable (RGP) lenses and scleral lenses, which provide effective visual rehabilitation in mild to moderate cases. Surgical options, such as CXL, ICRS, and toric IOLs, are reserved for advanced cases, with varying degrees of success. Newer techniques such as CAIRS, employing donor tissue instead of synthetic rings, show promising outcomes in corneal remodeling with potentially improved biocompatibility. Penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) remain definitive treatments for severe PMD, though they are associated with significant risks, including graft rejection and postoperative astigmatism. Conclusions: PMD is a complex and progressive corneal disorder that requires a tailored approach to management. Early diagnosis and intervention are critical to optimizing visual outcomes. While conservative measures are effective in mild cases, surgical interventions offer promising results for advanced disease. Further research is needed to refine treatment protocols and improve long-term outcomes for patients with PMD. Full article

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are a deadly subtype of soft tissue sarcoma for which effective therapeutic options are lacking. Currently, the best treatment for MPNSTs is complete surgical resection with wide negative margins, but this is often complicated by the tumor size and location and/or the presence of metastases. Radiation or chemotherapy may be combined with surgery, but patient responses are poor. Targeted treatments, including small-molecule inhibitors of oncogenic proteins such as mitogen-activated protein kinase kinase (MEK), cyclin-dependent kinases 4 and 6 (CDK4/6), and Src-homology 2 domain-containing phosphatase 2 (SHP2), are promising therapeutics for MPNSTs, especially when combined together, but they have yet to gain approval. Immunotherapeutic approaches have been revolutionary for the treatment of some other cancers, but their utility as single agents in sarcoma is limited and not approved for MPNSTs. The immunosuppressive niche of MPNSTs is thought to confer inherent treatment resistance, particularly to immunotherapies. Remodeling an inherently “cold” tumor microenvironment into a “hot” immune milieu to bolster the anti-tumor activity of immunotherapies is of great interest throughout the cancer community. This review focuses on novel therapeutics that target dysregulated factors and pathways in MPNSTs, as well as different types of immunotherapies currently under investigation for this disease. We also consider how certain therapeutics may be combined to remodel the MPNST immune microenvironment and thereby generate a durable anti-tumor immune response to immunotherapy. Full article

Colorectal cancer (CRC) is characterized by complex interactions between inflammation, oxidative stress, and extracellular matrix remodeling. Recent studies have highlighted the significance of the reactive oxygen species (ROS)–nuclear factor kappa B (NF-κB)–matrix metalloproteinase-9 (MMP-9) axis in promoting tumor invasion and metastasis in CRC, linking oxidative stress with inflammatory signaling and extracellular matrix degradation. In this study, we analyzed the concentration of advanced oxidation protein products (AOPPs), expression of NF-κB, and the activity of MMP-9 in tumor tissue, adjacent tissue, and healthy control colon tissue. Tissue specimens were collected from 50 patients with primary CRC following surgical resection. The analyses were performed using appropriate and validated biochemical methods, including ELISA, spectrophotometry, and indirect immunofluorescence. Significantly higher levels of all three markers were observed in tumor tissue compared to controls. Additionally, adjacent tissue exhibited elevated NF-κB expression and MMP-9 activity when compared to healthy colon tissue. AOPP levels correlated strongly with MMP-9 activity, highlighting the role of oxidative stress in the activation of MMP-9. MMP-9 demonstrated the highest predictive value for CRC, emphasizing its potential as a diagnostic and theranostic marker. Our findings support the hypothesis that the ROS–NF-κB–MMP-9 axis plays an important role in CRC progression, particularly during stages T2 and T3. Targeting this pathway may offer new therapeutic strategies for limiting tumor invasion and recurrence. Moreover, ensuring adequate surgical resection margins is crucial to optimizing treatment outcomes. Full article

Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist^® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation. Full article

Peri-implantitis (PI) presents a growing challenge in implant dentistry, with regenerative surgical approaches often incorporating barrier membranes despite the uncertainty of their clinical value. This systematic review and meta-analysis of in vivo studies aimed to evaluate the efficacy of barrier membranes in the reconstructive surgical treatment of PI. A comprehensive electronic search was performed in PubMed, Scopus, Google Scholar, and the Cochrane Library, covering studies published from 1990 to 2024. The protocol followed PRISMA guidelines and was registered in PROSPERO (CRD42025625417). Eligible studies included in vivo investigations comparing regenerative procedures with and without membrane use, with a minimum follow-up of 6 months and at least 10 implants per study. Risk of bias (RoB) was assessed using the Cochrane RoB tool. The meta-analysis was conducted using a random-effects model and included 15 studies comprising 560 patients. Although not consistently statistically significant, the findings suggested that membrane use may offer enhanced outcomes in terms of probing pocket depth (PPD) reduction and marginal bone level (MLB) gain. The evidence was limited by high clinical heterogeneity, variability in outcome definitions, and short follow-up durations. While membranes are commonly utilized, current evidence does not justify their routine use. Further well-designed, long-term clinical trials are needed to establish specific indications and optimize treatment strategies. Full article

The incidence of pancreatic ductal adenocarcinoma (PDAC) is continuing to rise globally, while overall survival continues to be poor. Margin-negative (R0) surgical resection is essential to improve patient outcomes. With increasing understanding of the importance of anatomy and biology to establishing the resectability of PDAC, neoadjuvant therapy (NAT) has emerged as an important strategy to achieve an R0 resection, particularly for those with borderline resectable (BR-PDAC) and locally advanced disease (LA-PDAC). However, despite the multiple randomised controlled trials (RCTs) published in recent years, the optimum regime has yet to be fully established. The role of neoadjuvant chemoradiation therapy (CRT) remains controversial, possibly allowing for improved local disease control at a potential cost of interrupting systemic treatment. The emergence of stereotactic ablative radiotherapy (SABR), in place of conventional radiation therapy, improves patient tolerance of NAT and may improve local tumour control for patients with PDAC during limited fractions, minimising systemic therapy interruption. A particular niche for SABR may be as part of NAT for LA-PDAC, potentially converting a minority of patients with favourable biology to allow for resection. While pancreaticoduodenectomy can be technically challenging following NAT, there is no difference in the rate of major morbidity or mortality post operatively. Indeed, post-operative pancreatic fistula (POPF) rates may be lower following NAT. Overall, however, evidence for SABR in a neoadjuvant setting for BR- and LA-PDAC remains sparse. Full article

Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant ADT may be associated with reduced surgical complexity, pathologic downstaging, decreased positive margins, and decreased rates of nodal positivity, although they have not shown benefits for cancer progression and survival. Accordingly, neoadjuvant ADT is currently not recommended for surgical patients. Conversely, ADT is a mainstay of treatment in metastatic disease, and interest remains in expanding its use towards patients with clinically localized disease. There are several ongoing trials of second-generation androgen blockers such as enzalutamide, darolutamide, radiopharmaceuticals, and poly (ADP-ribose) polymerase (PARP) inhibitors to explore long-term cancer-specific survival benefits with neoadjuvant use. In this narrative review, we provide a comprehensive overview of the recent literature and ongoing efforts to incorporate neoadjuvant therapy for clinically localized prostate cancer patients who are at high-risk of recurrence after prostatectomy. Full article

Since its development in 1904, radical prostatectomy (RP) has remained a fundamental surgical option in the management of localised prostate cancer. Over time, continuous advancements in surgical techniques have improved oncological outcomes while reducing functional complications. This narrative review explores the evolution of RP, depicting its progression from the traditional open approach to minimally invasive laparoscopic and robotic-assisted techniques. Key developments in RP techniques, including nerve-sparing, bladder neck-sparing and Retzius-sparing techniques as well as enhanced perioperative management, have contributed to reduced postoperative complications, namely incontinence and erectile dysfunction. Additionally, technological innovations such as augmented reality, utilising indocyanine green for improved visualisation of prostatic boundaries and illuminare-1 to easily identify nerves intraoperatively, artificial intelligence, and novel molecular imaging technologies such as PSMA PETs for improved margin assessment are shaping the future of RPs. Despite these advancements, challenges persist, including a steep learning curve associated with newer techniques, disparities in access due to cost considerations, and a lack of standardised outcome measures across different surgical approaches. This review provides insight into current trends, ongoing challenges, and future directions that may further refine surgical precision, enhance patient safety, and improve long-term treatment success in prostate cancer management. Full article

Background: Gastric neoplasms remain pathologies of the malignant spectrum with high incidence and prevalence, with their management requiring a precise histopathological characterization for optimal treatment planning. Methods: The present study is a retrospective analysis that included 67 histopathologically confirmed gastric neoplasia subjects and was performed at a single surgical center from January 2020 to December 2021. Demographics, tumor characteristics, surgical procedures, and oncologic outcomes were included, filtered, and subsequently analyzed using SPSS Statistics 29.0. Results: This study involved 67 patients (mean age 65.7 years, 56.7% men), with adenocarcinoma being the most common histologic type (91.0%) and most tumors being diagnosed directly as Stage III (40.3%). Lauren classification revealed the intestinal type as the most common (49.2%), followed by diffuse (36.1%) and mixed (14.8%). Poorly differentiated tumors (G3) accounted for 53.7% of cases. The surgical team performed curative resection in 75% (n = 50) of patients, achieving R0 margins in 88% of these cases. Subtotal gastrectomy with D2 lymphadenectomy yielded the highest curative success rate with 96.6% R0 resection. Statistically, we identified two significant correlations between age and tumor grade (rho = 0.28; p = 0.021) and between the number of lymph nodes examined and the number of lymph nodes invaded (rho = 0.65, p < 0.001). This study again revealed that adenocarcinomas showed higher rates of lymph node invasion than other tumor types (p = 0.017). Conclusions: The analysis of patients with gastric neoplasms is vital for appropriate therapeutic management. Even though the study period included a pandemic, the analysis remained a complex one with high-quality surgical outcomes, confirming the importance of maintaining oncologic standards during medical crises. Full article

Background and Aim: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with poor prognosis despite maximal surgical resection, radiotherapy (RT), and temozolomide (TMZ) per the Stupp protocol. IDH-wild-type GBM, the predominant molecular subtype, frequently harbors EGFR amplification and is resistant to therapy, while MGMT promoter methylation predicts improved TMZ response. This study aimed to assess the prognostic impact of EGFR and MGMT status on survival and recurrence patterns in IDH-wild-type GBM. Materials and Methods: We retrospectively analyzed 218 patients with IDH-wild-type GBM treated at the Azienda Ospedaliero-Universitaria Senese (2016–2024). All patients underwent maximal safe surgical resection whenever feasible. The cohort includes patients who received gross total resection (GTR), subtotal resection (STR), or biopsy only, depending on tumor location and clinical condition, followed by intensity-modulated RT (59.4–60 Gy) with concurrent and adjuvant TMZ. EGFR amplification was assessed via FISH/NGS and immunohistochemistry; MGMT promoter methylation was determined using methylation-specific PCR. Progression-free survival (PFS), overall survival (OS), and recurrence patterns (in-field, marginal, out-field) were evaluated using Kaplan–Meier, Cox regression, and logistic regression analyses. Results: Among patients (64.7% male; mean age 61.8), 58.7% had EGFR amplification and 49.1% showed MGMT methylation. Median OS and PFS were 14 and 8 months, respectively. EGFR non-amplified/MGMT methylated tumors had the best outcomes (OS: 22.0 months, PFS: 10.5 months), while EGFR-amplified/MGMT unmethylated tumors fared worst (OS: 10.0 months, PFS: 5.0 months; p < 0.001). MGMT methylation was an independent positive prognostic factor (HR: 0.48, p < 0.001), while EGFR amplification predicted worse survival (HR: 1.57, p = 0.02) and higher marginal recurrence (OR: 2.42, p = 0.01). Conclusions: EGFR amplification and MGMT methylation significantly influence survival and recurrence dynamics in IDH-wild-type GBM. Incorporating these biomarkers into treatment planning may enable tailored therapeutic strategies, potentially improving outcomes in this challenging disease. Prospective studies are needed to validate biomolecularly guided management approaches. Full article

Background: Primary vaginal cancer is a rare gynecological condition. We present a case of complete utero-vaginal prolapse complicated by primary invasive vaginal carcinoma. To our knowledge, only a few similar cases have been reported in our region. Case Report: A 77-year-old woman, gravida two and para two, was admitted for treatment of pelvic organ prolapse. The patient reported an eight-year history of uterine bulging but had not used a pessary. The gynecological examination revealed a complete manually irreducible utero-vaginal prolapse with an ulcerative lesion on the right posterolateral vaginal wall. The histological examination diagnosed an HPV-independent keratinizing squamous cell carcinoma, grade I. Comprehensive imaging showed no evidence of metastasis. The patient underwent radical hysterectomy, bilateral adnexectomy, complete resection of the vaginal mass, and pelvic lymphadenectomy. The histopathological examination confirmed clear surgical margins. According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, the disease was classified as stage I vaginal cancer. Postoperatively, the patient received radiotherapy (45 Gy) and high-dose-rate brachytherapy (14 Gy). Conclusions: The co-occurrence of vaginal cancer and utero-vaginal prolapse is exceedingly rare. Surgical intervention followed by radiotherapy is the most common treatment approach. Given the aggressive nature of the disease, comprehensive follow-up is essential. Further research is needed to determine whether long-term genital prolapse increases the risk of vaginal carcinoma. Full article