Search Results (200)

Background/Objectives: Busulfan is a key component of myeloablative conditioning regimens in hematopoietic stem cell transplantation (HSCT) for pediatric patients with acute myeloid leukemia, solid tumors, and certain non-malignant diseases. This study compares the clinical outcomes of once-daily (BU1) versus four-times-daily (BU4) busulfan dosing regimens in pediatric HSCT recipients. Methods: A retrospective analysis was conducted on 70 pediatric patients who underwent HSCT at Hadassah Medical Center between June 2018 and October 2023. Thirty-five patients received the BU4 regimen, and 35 received BU1. The primary endpoint was 100-day event-free survival (EFS). Results: There was no statistically significant difference in 100-day event-free survival between the BU1 group (88.6%) and the BU4 group (85.7%; p = 0.768). Similarly, no significant differences were found in time to neutrophil engraftment (p = 0.251) or platelet engraftment (p = 0.688). Sinusoidal obstruction syndrome (SOS) occurred in 17.1% of patients in each group. No significant differences were observed in the increase in liver enzyme levels (p = 1.0). The incidence of acute graft-versus-host disease was comparable between the groups (41.9% for BU1 vs. 40.0% for BU4; p = 0.878). Conclusions: Once-daily and four-times-daily busulfan regimens demonstrated comparable clinical outcomes in terms of efficacy and adverse events. Further prospective studies are needed to validate these findings. Full article

Background: Invasive BC patients are at risk of loco-regional recurrence, distant MTS, and the development of second primary tumors. SPMs comprise the sixth most common group of malignancies. Material and methods: The records of 125 consecutive patients with primary invasive TCC of the bladder seen in the Oncology Department of Soroka University Medical Center were reviewed between January 2016 and December 2023. We recorded demographic details, the type of primary treatment, tumor site, time to diagnosis of MTS, and occurrence of SPMs. Results: The primary treatments included RC in 58 patients (median age 66 years, range 43–86), PC in 9 patients (median age 64 years, range 22–73), and XRT in 23 patients (median age 74 years, range 22–87). Five patients from the PC group were also treated by XRT. A total of 90 (72%) patients developed MTS or SPMs, with 66 of these developing MTS and 24 developing SPMs. The median age was 70 years (range 22–87). The most frequent site of MTS was in the pelvic LNs (34 patients), followed by bone (18 patients), liver (8 patients), and lung (6 patients), with 4 patients developing synchronous MTS in the pelvic LNs and liver. The median time from diagnosis to MTS was 14.3 months. The distribution of MTS varied according to primary treatment. After RC, 17 patients developed LN MTS, 7 liver, 6 bone, and 3 lung MTS. The average times for developing MTS were as follows: LNs, 14.8 months, liver, 59.7 months, bone, 6.8 months, and lung, 16 months. Following XRT, LN MTS developed in 17 patients: 12 bone, 3 lung, and 1 liver. The most frequent SPMs were prostate cancer with 11 patients and lung cancer with 6 patients, with the median time from TCC diagnosis of 54 months. Conclusion: A regular extended follow-up for invasive BC patients is vital to ensure the early detection of frequently occurring MTS and SPMs. Through the early diagnosis of local recurrences, MTS, and SPMs, treatment results and patient prognosis can be significantly improved. Full article

Background/Objectives: Tumor-associated inflammation plays a crucial role in supporting tumorigenesis and the progression of oncological diseases. This study aimed to evaluate whether systemic inflammatory indices are associated with overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing surgery. Methods: A retrospective cohort study was conducted on consecutive patients with HCC who underwent hepatic resection. Data were prospectively collected and retrospectively reviewed. The 5-year OS rate was used as the primary endpoint to stratify the values of inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), aspartate aminotransferase-to-neutrophil ratio index (ANRI), fibrinogen-to-albumin ratio (Fib-Alb), the systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and aspartate aminotransferase-to-platelet ratio index (APRI), through receiver operating characteristic (ROC) curve analysis. The optimal albumin–bilirubin (ALBI) and platelet–ALBI (PALBI) cut-off points from the literature were also applied. Results: Patients included in the study were 153. The 1-, 3-, and 5-year OS rates were 81.7%, 65.2%, and 40.7%, respectively. Univariate Cox proportional hazards analysis showed that, in addition to several patient- and tumor-related characteristics and postoperative complications, elevated values of PLR, ANRI, Fib-Alb, SII, APRI, ALBI, and PALBI, as well as low PNI, were significantly associated with poorer overall survival (OS). Among these, only APRI and PNI emerged as independent prognostic factors in the multivariate analysis. Conclusions: PNI and APRI could serve as valuable inflammatory indices for predicting OS, helping to identify HCC patients who might benefit from hepatic resection. However, further prospective studies with larger cohorts are needed to validate the prognostic role of PNI and APRI. Full article

Background and Clinical Significance: Combined hepatocellular–cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy exhibiting both hepatocellular and cholangiocellular features. Due to overlapping clinical, imaging, and pathological characteristics with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCC), diagnosis remains challenging. Early and accurate differentiation is critical for optimal treatment planning. Case Presentation: We report three histologically confirmed cases of cHCC-CC with different imaging features, biomarker profiles, treatment strategies, and clinical outcomes. Patient 1, a 69-year-old female, presented with a large centrally located liver mass exhibiting iCC-like imaging features and mildly elevated AFP and CA 19-9 levels. Biopsy confirmed poorly differentiated cHCC-CC. Treatment involved palliative chemotherapy, with a survival of 16 months following diagnosis. Patient 2, an 80-year-old female with a small lesion in a cirrhotic liver, demonstrated an HCC-like enhancement pattern but normal AFP levels. Surgical resection was performed, and histology confirmed cHCC-CC with a dual phenotype. Despite initial remission, intrahepatic recurrence developed, treated with TACE and systemic therapy. The patient later transitioned to palliative care due to progression and survived 36 months. Patient 3, a 67-year-old male with chronic hepatitis C, presented with an HCC-like lesion and elevated AFP. Due to comorbidities, surgical resection was not feasible, and the patient was treated with percutaneous microwave ablation as a safer alternative. Biopsy during ablation confirmed cHCC-CC; follow-up was ongoing at submission. Conclusions: These cases highlight the diagnostic complexity and clinical variability of cHCC-CC. Imaging may be misleading, and tumor markers do not reliably predict subtype or prognosis. Histological confirmation is essential, particularly in patients with atypical imaging or discordant biomarker profiles. Individualized management, informed by tumor biology and patient condition, remains critical. Further research is needed to refine diagnostic criteria and develop tailored therapeutic strategies for this challenging tumor entity. Full article

Liver transplantation (LT) for hepatic malignancies is becoming increasingly common, largely because it offers superior survival relative to other treatment approaches. LT is well-accepted for primary liver cancers such as hepatocellular carcinoma and perihilar cholangiocarcinoma and is being increasingly accepted for intrahepatic cholangiocarcinoma and metastases of colorectal cancer or neuroendocrine tumors to the liver. Over time, indications for transplant oncology have broadened, as has the acceptable disease burden for transplantation, particularly with the advent of new neoadjuvant therapies. Other current frontiers in the field include expanding the donor pool through living donors, extended criteria donors, machine perfusion and increasing access to LT for people from disadvantaged socioeconomic backgrounds. Expanding access to LT can offer renewed hope for long-term survival to patients with primary and secondary liver cancer. Full article

Uveal melanoma (UM), the most common primary intraocular malignancy in adults, poses a unique clinical challenge due to its high propensity for liver metastasis and poor responsiveness to conventional therapies. Despite the expanding landscape of immunotherapy in oncology, progress in managing metastatic uveal melanoma (mUM) remains limited, and no universally accepted standard of care has been established. In this review, we examine the current state and evolving strategies in immunotherapy for mUM, focusing on immune checkpoint inhibitors (ICIs), T cell receptor (TCR)-engineered therapies, and tumor-targeted vaccines. We also present a meta-analytical comparison of clinical outcomes between ICI monotherapy and combination regimens, alongside the recently FDA-approved T cell engager tebentafusp. Our analysis indicates that the triple combination of Ipilimumab, anti-PD-1 agents, and tebentafusp significantly enhances objective response rates, disease control rates, 1-year overall survival rates, and median overall survival (mOS) compared to ICI monotherapy alone. However, this enhanced efficacy is accompanied by increased toxicity due to broader immune activation. In contrast, tebentafusp offers superior tumor specificity and a more favorable safety profile in HLA-A*02:01-positive patients, positioning it as a preferred therapeutic option for this genetically defined subset of UM. Additionally, early-phase studies involving dendritic cell-based immunotherapies and peptide vaccines has shown encouraging signs of tumor-specific immune activation, along with improved tolerability. Collectively, this review underscores the urgent need for more precise and effective immunotherapeutic approaches tailored to the unique biology of mUM. Full article

Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic procedures. The aim of this narrative review is to depict the common appearance of liver metastases, as well as to depict atypical imaging patterns. Moreover, this review will cover the differential diagnosis between liver metastases from neuroendocrine tumors and other primary and secondary malignant liver lesions, as well as benign liver lesions. Full article

Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal neoplasms with distinctive histological and immunohistochemical features. This systematic review aims to characterize the clinical presentation, diagnostic approach, treatment, and outcomes of adult patients with hepatic PEComa. Methods: We performed a systematic literature search for English-language articles regarding hepatic PEComas using the terms (perivascular epithelioid cell tumor) OR (PEComa) AND (liver) OR (hepatic), up to 25 May 2025. Results: A total of 145 studies encompassing 281 patients were included in the analysis. Most studies originated from Asia. The mean age at diagnosis was 46 years (IQR: 35.25–53.75) with a female predominance. The underlying comorbidities were uncommon among the reported cases, and more than half were asymptomatic at presentation. The tumor presented as a single liver lesion in almost 9 out of 10 patients. Surgical excision was the primary treatment, and diagnosis in 74% of patients was made with positive immunohistochemistry for markers such as HMB-45 and smooth muscle actin. A malignant phenotype was reported in 30 cases. The median follow-up duration was 24 months (IQR: 12–48); recurrence occurred in 17 patients, and disease-related mortality occurred in 8 patients. Conclusions: Primary hepatic PEComa is a rare liver tumor with mostly benign clinical behavior and non-specific presentation. Future studies are needed to support clinician decisions regarding this entity and improve patient care. Full article

Background/Objectives: Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models. Methods: In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by injecting pancreatic cancer cells interperitoneally. Once the tumors were established, anti-MUC4-IR800 was administered to the mice by tail vein injection. Laparotomy was performed and tumors were imaged under white-light and near-infrared (NIR) fluorescence with the Pearl Small Animal Imaging System. Results: NIR imaging after 72 h shows the bright targeting of pancreatic cancer metastasis in both mouse models with high tumor-to-background ratios. Conclusions: Anti-MUC4-IR800 was able to successfully target and brightly label metastatic pancreatic cancer as small as 1 mm. Future clinical applications of the results of the present study are discussed. Full article

Hepatocellular carcinoma (HCC) constitutes more than 90% of the primary tumor of the liver. Metabolic reprogramming is decisive in promoting HCC development. The new metabolic program drives the surrounding immune cells to an immune suppressive commitment, enabling tumor survival. The enhanced metabolic activity of cancer cells leads to competition for essential nutrients, depriving non-malignant cells of critical resources. Simultaneously, the accumulation of metabolic byproducts within the tumor microenvironment (TME) selectively favors innate immune responses while impairing adaptive immunity. Recent advances in cancer immunotherapy underscore the importance of targeting both immune cell function and metabolic pathways. In this context, reprogramming the metabolism of effector and regulatory immune cells represents a promising therapeutic avenue. This review focuses on a relatively underexplored aspect of liver cancer immunology, the immunosuppressive role of tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) driven by metabolic alterations and how these mechanisms contribute to the suppression of effective anti-tumor immune responses. Full article

Transplant oncology is a rapidly evolving discipline that incorporates oncology, transplant medicine, and surgery. As the field continues to grow, there remains an opportunity to enhance patient selection, detect recurrence after liver transplantation, and optimize treatment after recurrence. Liquid biopsies are an emerging resource to improve patient care. In this review, we evaluate the most recent available data on circulating tumor DNA and how it pertains to primary and metastatic hepatobiliary malignancies. We discuss the opportunities and current limitations to clinical practice, especially in relation to total hepatectomy and liver transplantation. We conclude that as both transplant oncology and our understanding of circulating tumor DNA continue to evolve, rigorous, prospective study is required to integrate this technology into a clinical paradigm. Full article

Background: Uveal melanoma (UM) is a relatively rare malignancy, yet it remains the most common primary intraocular cancer in adults. Several risk factors have been identified, including light iris color, fair skin tone, and cutaneous freckles. Methods: The aim of this article was an overview of the treatment methods for uveal melanoma, with a particular focus on emerging therapies such as tebentafusp and da-rovasertib. The research method was a review of the latest literature. Results: Genetic studies have uncovered key mutations in GNAQ and GNA11, which significantly contribute to UM pathogenesis. Treatment selection depends on tumor location and disease stage. In localized disease, radiotherapy—especially brachytherapy—is commonly used and generally effective. However, the prognosis worsens significantly once distant metastases, most often to the liver, develop, as no standard systemic therapy has demonstrated high efficacy in this setting. Recent years have seen the emergence of promising therapies, including tebentafusp, which stimulates immune responses against gp100-expressing melanoma cells, and darovasertib, a potent PKC inhibitor that targets MAPK pathway activation driven by GNAQ/GNA11 mutations. Both agents have shown encouraging tolerability; tebentafusp has demonstrated clinical benefit in Phase II and III trials, while darovasertib is still under investigation. Additionally, melphalan-based liver-directed therapy, particularly via hepatic arterial infusion (approved by the FDA), has shown potential in controlling liver-dominant disease in metastatic UM. This localized approach may provide significant benefit for patients with limited extrahepatic spread. Conclusions: Future research should focus on optimizing these novel strategies—tebentafusp, darovasertib, melphalan, and combination therapies—and on expanding our understanding of UM’s molecular drivers to enable the development of more effective, personalized treatments. Full article

Hepatocellular carcinoma (HCC) is a malignant form of primary liver cancer. Intricate networks linked to the host immune system may be associated with the pathogenesis of HCC. A huge amount of interdisciplinary medical information for the treatment of HCC has been accumulated over recent years. For example, advances in new immunotherapy have improved the results of treatment for HCC. This approach can be advantageously combined with standard conventional treatments such as surgical resection to improve the therapeutic effect. However, several toxic effects of treatments may pose a significant threat to human health. Now, a shift in mindset is important for achieving superior cancer therapy, where probiotic therapy may be considered, at least within the bounds of safety. The interplay between the gut microbiota and immune system could affect the efficacy of several anticancer treatments, including of immune checkpoint therapy via the alteration of Th17 cell function against various malignant tumors. Here, some recent anticancer techniques are discussed, whereby the growth of HCC may be effectively and safely repressed by probiotic therapy. Full article

CCA is a highly desmoplastic malignant cancer and is the second most common primary liver malignancy after hepatocellular carcinoma (HCC), accounting for approximately 15% of all primary liver tumors. CCA has a poor prognosis, with an average five-year survival rate of 9%, which is lower than that of pancreatic cancer. Although considerable efforts have been invested into the genomics, epigenetics, and risk factors, very little is known about what might have been the key causes for the high malignancy level of CCA. In this review, we analyze the incidence and mortality of CCA in different regions based on data from 1994 to 2022 obtained from the International Agency for Research on Cancer (IARC), discuss the current status of treatment of the disease, and focus on what might be the main factors contributing to the high malignancy level of CCA: alkalosis caused by the Fenton reaction, hypoxia, and the TIME. The review includes studies published from 1979 to 2024, aiming to provide an updated synthesis of basic early classical theoretical knowledge and current knowledge about CCA. By revealing the epidemiological characteristics of CCA, the potential mechanisms of high malignancy, and the current challenges of treatment, this review aims to provide new directions for future cancer research, promote the development of personalized treatment strategies, and facilitate a deeper understanding and the more effective management of CCA worldwide. Full article

 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan–Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs. Full article