Search Results (61)

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Background and Objectives: Although cyanoacrylate–polylactic acid (CA + PLA) patches shorten the time to hemostasis after partial hepatectomy, their long-term biocompatibility remains uncertain. We compared the 5-month histopathological footprint of a novel CA + PLA patch (Study group) with a licensed fibrinogen/thrombin matrix (TachoSil^® group) and electrocautery (Control group). Methods: Thirty-three male Wistar rats underwent a 3 × 1.5 cm hepatic segment resection and were randomized to the Control (n = 5), Study (n = 14), or TachoSil^® (n = 14) group. The animals were sacrificed on postoperative day (POD) 50, 100, or 150. Blinded semiquantitative scoring (0–3) was used to capture inflammation intensity, and the number of neutrophils (PMNs), lymphocytes (Ly’s), isolated histiocytes, and foreign-body giant cells (FBGCs). Results: The proportions of animals in each group across the different sacrifice time points were homogeneous (χ² = 4.34, p = 0.36). The median inflammation remained mild (2 [IQR 1–2]) in the Control and Study groups but lower in the TachoSil^® group (1 [1–2], p = 0.47). The FBGC scores differed markedly (score ≥ 2: 64% in Study, 0% in Control, 14% in TachoSil^®; p < 0.001). Fibrosis occurred almost exclusively in the Study group (79% vs. 0%; χ² = 22.4, p < 0.001). Mature vessels were most frequently observed in the TachoSil^® group (50%, aOR = 5.1 vs. Study, p = 0.04). Abscesses only developed in the Study group (29%, p = 0.046). Within the TachoSil^® group, inflammation (ρ = −0.62, p = 0.019) and Ly infiltration (ρ = −0.76, p = 0.002) declined with time; no significant temporal trends emerged in the Study group. Conclusions: At the five-month follow-up, there was an exuberant foreign-body reaction, dense collagen deposition, and a higher abscess rate around the CA + PLA patch compared with both TachoSil^® and cautery. Conversely, TachoSil^® evolved toward a mature, well-vascularized scar with waning inflammation. These findings underscore the importance of chronic-phase evaluation before clinical adoption of new hemostatic biomaterials. Full article

Colorectal surgery has undergone significant advances over the past few decades, driven by the evolution of minimally invasive techniques, particularly laparoscopy and robotics. While laparoscopy is widely recognized for its short-term benefits and oncological safety, the increasing adoption of robot-assisted surgery (RAS) has generated considerable debate regarding its clinical benefits, economic implications, and overall impact on patient outcomes. This narrative review synthesizes the existing evidence, highlighting the clinical and economic aspects of RAS in colorectal surgery, while exploring areas for future research. The findings suggest that RAS offers potential technical advantages, including increased precision, three-dimensional visualization, and improved ergonomics, particularly in anatomically complex scenarios such as low rectal resections. Still, its superiority over laparoscopy remains inconclusive and current evidence is mixed. For colon cancer, meta-analyses and analyses of large cohorts suggest lower conversion rates and faster recovery with RAS, although data are mostly retrospective and lack long-term oncological endpoints. In rectal cancer, emerging evidence from randomized controlled trials demonstrates improved short-term outcomes. Additionally, the recently published three-year results of the REAL trial are the first to demonstrate enhanced oncological outcomes following RAS. However, findings remain inconsistent due to methodological heterogeneity, the absence of patient stratification, and limited data on long-term survival and cost-effectiveness. The available evidence indicates that RAS may offer advantages in selected patient populations, particularly for anatomically complex procedures. Yet, its overall utility remains uncertain. Future studies should emphasize high-quality randomized trials, stratified subgroup analyses, and standardized economic evaluations to better define the role of RAS in colorectal surgery. Full article

Background and Clinical Significance: Neurofibromatosis type 1 (NF1) predisposes individuals to various peripheral nerve sheath tumors (PNSTs), including benign neurofibromas, malignant peripheral nerve sheath tumors (MPNSTs), and intermediate lesions known as atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), previously often termed atypical neurofibroma. These atypical lesions are considered premalignant precursors to MPNST. Case Presentation: We present the case of a 33-year-old male with NF1 who developed a rapidly growing, painful mass in his right calf. Clinical examination revealed signs consistent with NF1. Magnetic resonance imaging showed a large, heterogeneous mass in the lateral compartment. Biopsy revealed a neurofibroma with hypercellularity, moderate atypia, scarce S100 positivity, focal CD34 positivity, and an elevated Ki-67 proliferation index of 10–12%, consistent with ANNUBP. The patient underwent wide surgical resection, including the fibula and peroneal muscles. At the 30-month follow-up, there was no local recurrence, though the patient had a mild residual limp. Discussion: This case highlights the clinical presentation, diagnostic features, and management considerations for ANNUBP in NF1, emphasizing the importance of recognizing warning signs and the role of pathology in guiding treatment for these high-risk precursor lesions. Full article

Background/Objectives: Patients with advanced ovarian cancer face a high risk of venous thromboembolism (VTE). This study evaluates the incidence and risk factors for pulmonary thromboembolism (PE) in patients with advanced high-grade serous ovarian carcinoma (HGSOC) undergoing primary treatment, with a focus on personalized risk stratification. Methods: A retrospective analysis was conducted on women with FIGO stage IIIA-IVB HGSOC treated at the University Hospital of Parma between January 2012 and May 2023. All patients underwent CT-based staging prior to primary treatment. When resectability was uncertain, diagnostic laparoscopy and the Fagotti score were performed. Based on cytoreductive potential, patients received either primary debulking surgery (PDS) followed by adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and AC. The Khorana score, a thromboembolic risk model, was calculated prior to chemotherapy. Logistic regression was used to assess the association between baseline characteristics and PE. Results: Among 167 HGSOC patients analyzed, 13 (7.8%) experienced PE. Among the 115 patients undergoing diagnostic laparoscopy, each 2-point increase in the Fagotti score above 8 raised PE risk by 76% (OR 1.76, p = 0.006, 95% CI: 1.17–2.63). Patients undergoing NACT-IDS had a significantly higher risk of PE (OR 4.04, 95% CI: 1.19–13.74, p = 0.02) than patients who underwent PDS. A Khorana score of 3 was an independent predictor of PE (OR 37.66, 95% CI: 2.43–582.36, p = 0.009). Conclusions: Based on our results, NACT followed by IDS or a Fagotti score greater than 8 were associated with increased PE risk in HGSOC patients. Khorana score was the strongest predictor of PE in HGSOC patients. Full article

Primary hepatic gastrointestinal stromal tumours (PHGISTs) are rare and frequently misdiagnosed due to their atypical presentation and uncertain origin. The purpose of this article is to present the case of a 79-year-old female patient with a gigantic PHGIST characterized by a predominantly cystic nature—an extremely rare presentation, as most cases of PHGIST are solid. Despite extensive imaging and exploratory laparotomy, the primary origin remained uncertain, leading to questioning about whether it was a true primary hepatic GIST or an atypical metastatic lesion. The initial therapeutic approach involved a surgical procedure aimed to confirm the diagnosis and achieve reductive tumourectomy. Following the surgery, the patient was administered imatinib with a favourable clinical response for four and a half years—an atypical pattern of resistance, as most patients typically develop therapeutic resistance within two to three years. A second surgical intervention was performed to address a cystic lesion localized in the left hepatic lobe, followed by an atypical segment III hepatectomy to achieve macroscopic resection. Subsequently, the patient received sunitinib for two and a half years, which resulted in temporary disease stabilization. However, the sunitinib treatment was associated with hypertension and leukopenia. The patient’s overall survival was 8 years, suggesting that individualized therapeutic strategies and close monitoring might be the key in such cases. Furthermore, this case confirms the role of surgical intervention even in advanced disease stages, with multiple major resections contributing significantly to prolonged survival. The interplay between surgical and oncologic therapies remains essential to guiding clinical decisions. Given the unusual cystic presentation, this case highlights the necessity to expand the pathological and molecular profiling of PHGISTs. Furthermore, the atypical timeline of resistance development and treatment-related toxicity emphasizes the importance of further research into the genetic and pharmacological determinants of PHGISTs. These findings advocate for the refinement of diagnostic, therapeutic, and surveillance protocols tailored to rare GIST subtypes. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

Background: The impact of adjuvant chemotherapy (AC) on outcomes in real-world patients with locally advanced rectal cancer (LARC) remains uncertain. Methods: Consecutive patients with LARC (stage II/III) undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were identified in the Canadian Health Outcomes Research Database. The impact of AC on clinical outcomes, including disease-free survival (DFS) and overall survival (OS), was evaluated using the Kaplan–Meier method and Cox proportional hazards modeling. Results: A total of 1448 patients had sufficient data available to be included for analysis with 1085 (74.9%) receiving AC. Of AC patients, 40.5% received oxaliplatin-based treatments. With a median follow-up of 66.43 months, the 5-year DFS rate was 67.7% (95% CI: 64.5–70.1%) vs. 58.7% (95% CI: 52.8–64.2%) in the AC group and non-AC group, respectively (p < 0.001). The 5-year OS rate of the whole cohort was 74.3% (95% CI: 71.5–76.85%) while the 5-year OS rate of the AC group was 77.8% (95% CI: 74.7–80.6%) compared with 63.8% (95% CI: 57.9–69.2%) for the non-AC group (p < 0.001). On multivariate analysis, patients who received AC had improved DFS (HR 0.6, 95% CI: 0.49–0.73, p < 0.001) and OS (HR 0.46, 95% CI: 0.36–0.58, p < 0.001). Conclusions: This large multi-institutional database analysis supports the use of AC in real-world LARC patients treated with nCRT followed by surgical resection. Full article

Background/Objectives: Phyllodes tumors (PTs) are rare fibroepithelial breast neoplasms with a high propensity for local recurrence, particularly in borderline and malignant forms. Although wide local excision with negative margins is standard, the role of full-thickness chest wall resection (FTCWR) for PTs invading the chest wall remains unclear. This systematic review evaluated the outcomes of FTCWR in such cases, focusing on oncologic effectiveness and reconstruction. Methods: A comprehensive literature search of PubMed, Embase, Scopus databases, and Google Scholar (up to the end of November 2024) identified 18 case reports describing 18 patients (mean age of 42.9 years) with locally invasive PTs. Results: Most patients presented with large (>5 cm), recurrent malignant tumors fixed to the chest wall, with the largest measuring 38 cm. Median disease-free survival was 12 months (range: 1–60), with local recurrence in 5.6% and distant metastases in 22.2% of cases. Common complications included respiratory and wound-related issues. Despite the radical surgery, all patients achieved satisfactory cosmetic results. Conclusions: While FTCWR appears feasible and provides symptom relief and short-term disease control in select patients, the evidence remains limited to case reports. Its long-term oncologic benefit is still uncertain, and further research, including prospective studies and multi-center registries, is needed to elucidate its role in clinical practice. Full article

Lung cancer is the leading cause of cancer-related mortality among both men and women worldwide, underscoring the need for an effective treatment strategy. For early-stage non-small cell lung cancer [NSCLC], surgical resection is the standard treatment. Robotic-assisted thoracic surgery [RATS] and video-assisted thoracic surgery [VATS] are better than open thoracotomy because they are less invasive. Recent lung cancer screening programs are detecting NSCLC at earlier stages, which is expected to result in an increase in the number of NSCLC surgeries as early-stage cases are diagnosed. A limited number of randomized controlled trials have compared RATS and VATS in operable NSCLC. We conducted a literature review to summarize the available evidence on these two surgical techniques. The purpose of this study is to compare the intraoperative and postoperative outcomes of RATS and VATS in early-stage NSCLC patients. RATS shows lower conversion rates to thoracotomy (6.3% vs. 13.1% p < 0.01) and more thorough lymph node dissection than VATS (e.g., 7.5 vs. 5.6 stations, p < 0.001). However, RATS is linked to considerably higher costs (USD 22,582 vs. USD 17,874, p < 0.05) and longer operative times (median 241.7 vs. 214.4 min, p = 0.06). The two techniques exhibited minimal differences in postoperative complications and pain, while RATS patients experienced shortened hospital stays (4–5 vs. 5–6 days, p < 0.006). While the accuracy of staging and treatment planning is improved by the improved lymph node retrieval in RATS, the long-term survival rate is still uncertain. Full article

Objectives: The distinction of clinically uncertain, poorly differentiated liver masses into primary liver cancer (PLC) of cholangiocytic origin (intrahepatic cholangiocarcinoma; CCA) or hepatocellular origin (hepatocellular carcinoma; HCC) vs. metastasis is highly relevant to guiding patient treatment. Protocols differ in terms of resection, local ablation, liver transplantation, or systemic therapies with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Methods: This retrospective case series exemplifies a multidisciplinary, practical guide to clinically uncertain liver masses using imaging, histomorphology, immune phenotyping, and mutational testing of telomerase promoter (TERT) combined with a literature review. Results: In 2/3 patients with uncertain liver masses and inconclusive immunohistochemistry profiles, TERT testing supported the diagnosis of poorly differentiated hepatocellular carcinoma. The third case with a history of sclerosing cholangitis and vague adenoid morphology yielded mutations in ARID1a and TP53 and was identified as primary liver cancer, consistent with poorly differentiated intrahepatic cholangiocarcinoma or mixed hepatocellular cholangiocarcinoma (cHCC/CCA). Conclusions: Finding HCC-typical TERT promoter mutations is a useful diagnostic tool in poorly differentiated primary liver cancer. Full article

Objective: We explored the impact of uncertain resection in lung cancer on overall survival and disease-free survival. Methods: We performed an exhaustive literature review of all studies comparing prognosis after resection according to the IASLC classification, from the PubMed, Cochrane, MEDLINE, and Google Scholar databases. Results: Overall, 68 original studies were included, of which 67 were retrospective and 1 was prospective, with 81 785 patients included over 46 years. R(un) reclassification was mostly caused by a lack of hilar or mediastinal node dissection, or because of metastasis in the highest node. R(un) is a strong factor for higher recurrence and mortality, while its effects seem limited in early stages. Carcinoma in situ at bronchial margin resection (CIS BRM) does not show an effect on survival, while positive pleural cytology (Cy+) and positive highest mediastinal lymph node (HMLN+) appear to be highly predictive of recurrence and death. Discussion: The R(un) classification of the IASLC appears highly relevant, especially in locally advanced stages IIb-IIIA, and helps to discriminate patients with poor prognosis despite being classified as R0 in the UICC classification. Conclusions: The use of this more precise classification would allow for better stratification of recurrence risk and more effective use of adjuvant therapies. Cy+ patients should receive adjuvant chemotherapy, while CIS BRM patients could likely benefit from endoscopic surveillance to detect local recurrences. HMLN+ patients should be considered at high risk of recurrence, and adjuvant radio-chemotherapy should be considered. Full article

Background: The Gollop–Wolfgang complex is a rare congenital limb deformity characterized by a bifid femur, tibial hemimelia, and ectrodactyly of the hand. First described in 1980, fewer than 200 cases have been reported globally, with an estimated incidence of 1:1,000,000 live births. Case Presentation: We report a 2-month-old female infant with classic features of the Gollop–Wolfgang complex, including a left bifid femur, complete absence of the left tibia, and contralateral tetradactyly. A clinical examination revealed significant limb length discrepancy, knee instability, equinovarus foot deformity, and skeletal abnormalities confirmed by imaging studies. Extensive investigations, including echocardiography and genetic testing, excluded systemic anomalies and identified non-pathogenic variants in the Collagen Type XI Alpha 2 (COL11A2) and EVC2 genes. A surgical resection of the bifid femur was performed. Results: This case highlights the importance of early diagnosis and a multidisciplinary approach in managing the Gollop–Wolfgang complex. While our case presented with typical features, subtle variations highlight the phenotypic spectrum of the condition. The combination of tibial hemimelia and bifid femur frequently necessitates knee disarticulation due to the absence of a viable tibial anlage, while limb salvage techniques remain challenging. A genetic evaluation identified variants of uncertain significance in the COL11A2 and EVC2 genes, indicating that the genetic basis of the condition is not fully understood. Conclusions: These findings emphasize the need for continued genetic research to clarify the etiology of the Gollop–Wolfgang complex and to improve treatment strategies, particularly in refining surgical approaches and exploring new therapeutic options. Full article

Background: Neoadjuvant imatinib therapy plays a crucial role in the management of gastrointestinal stromal tumors (GISTs), but its impact across various mutational profiles remains uncertain. Objective: The aim of this study is to describe the clinicopathological features and to assess the response and surgical outcomes of neoadjuvant imatinib in GIST patients exhibiting diverse mutational profiles. Methods: We conducted a retrospective study, extracting data from the Dutch GIST Registry, including patients treated with neoadjuvant imatinib. Response rate was the primary outcome, and secondary outcomes were the time on neoadjuvant treatment and resection margins (R0 vs. R1/R2), respectively. Results: Between 2009 and 2021, 326 patients were treated with neoadjuvant imatinib, of which 264 (80.9%) underwent resection. A total of 197 (74.6%) of them had a KIT-exon 11 mutation, 19 (7.3%) had other KIT mutations, 10 (3.8%) had PDGFRA D842 mutations, 21 (6.8%) had other PDGFRA mutations, 2 (0.7%) had NTRK mutation, 1 (0.4%) had an SDH mutation, and 17 (6.4%) had WT GISTs. Patients with KIT-exon 11 mutations demonstrated a higher rate of partial response to imatinib (60.5% vs. 33.3%; p = 0.00). A positive resection margin (R1 or R2) was observed in 14 (21.2%) patients with a non-KIT exon 11 mutations and in 11 (5.5%) patients with a KIT-exon 11 mutation (p = 0.00). Moreover, non-KIT exon 11 mutation patients had a shorter median duration of neoadjuvant therapy (5.3 months, range 0.5–21.0) compared to patients with a KIT exon 11 mutation (8.8 months, range 0.2–31.3; p < 0.001). Conclusions: Our study highlights the variability in treatment response associated with different GIST mutational profiles. Patients with a KIT-exon-11 mutation tended to respond more favorably to neoadjuvant imatinib in terms of partial response and surgical outcomes. Full article

Background: Individually personalized reconstructive microsurgery is more and more universally recognized and applied as a one-time, part of a few, or even the only highly effective treatment of patients with locally advanced midface cancer. Among the increasing number of publications focused on this field, most present different reconstructive techniques used for a single patient (case reports), and fewer papers evaluate a group including more than 100 patients. Methods: A dataset of 119 locally advanced midface cancers in stage T₃ or T₄ was used to analyze whether there is any correlation between clinical factors, resection defect parameters, and the free flaps chosen for reconstruction. Results: In general, the 5-year OS was 95% and 77% for the DFS, which inversely correlated with the increasing Cordeiro’s type of resective defects. Local recurrence occurred in 23% of cases. Taxonomic dendrograms allow the selection of four (A–D) different case clusters. Cluster B, which characterizes a tumor size of 8–18 cm², Cordeiro type IIIA, and an uncertain radicalism of resection, has the worst prognosis with a very high (89%) risk of local recurrence. On the contrary, the most favorable was found in cluster C, characterized by Cordeiro type IIA, a tumor size of 8 cm², and negative resective margins, because it has a very low (6%) risk of local recurrence. Conclusions: The results of the present analysis have led to design algorithms for midface resection and reconstruction. However, these should not be considered obligatory but rather as a useful general guideline. Full article