Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.

Image-Guided Local Treatment for Unresectable Intrahepatic Cholangiocarcinoma—Role of Interventional Radiology

Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.

Cytoreductive Surgery for Peritoneal Carcinomatosis from Gastric Cancer: Technical Details

Due to limited systemic treatment options, peritoneal carcinomatosis of gastric origin is still associated with a dismal outcome and is claimed a terminal disease. In the past, surgery had not been considered as a potential treatment option. However, there is emerging evidence that in selected patients, locoregional treatment modalities including cytoreductive surgery of peritoneal carcinomatosis can improve survival in patients with gastric cancer. These operative procedures are complex and challenging, and a high surgical expertise of the treating physician is necessary to prevent major postoperative morbidity and mortality with a delay of further systemic therapy. This review summarizes our current knowledge and personal experience regarding the techniques of cytoreductive surgery for peritoneal metastasis of gastric origin.

Photodynamic Therapy Targeting Macrophages Using IRDye700DX-Liposomes Decreases Experimental Arthritis Development

Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system’s first responders, it is inadvisable to systemically deplete these cells. By loading the liposomes with the photosensitizer IRDye700DX, we have developed and tested a novel way to perform photodynamic therapy (PDT) on macrophages in inflamed joints. PEGylated liposomes were created using the film method and post-inserted with micelles containing IRDye700DX. For radiolabeling, a chelator was also incorporated. RAW 264.7 cells were incubated with liposomes with or without IRDye700DX and exposed to 689 nm light. Viability was determined using CellTiterGlo. Subsequently, biodistribution and PDT studies were performed on mice with collagen-induced arthritis (CIA). PDT using IRDye700DX-loaded liposomes efficiently induced cell death in vitro, whilst no cell death was observed using the control liposomes. Biodistribution of the two compounds in CIA mice was comparable with excellent correlation of the uptake with macroscopic and microscopic arthritis scores. Treatment with 700DX-loaded liposomes significantly delayed arthritis development. Here we have shown the proof-of-principle of performing PDT in arthritic joints using IRDye700DX-loaded liposomes, allowing locoregional treatment of arthritis.

Diagnosis Issues and Management of Nasopharyngeal Non-Hodgkin Lymphomas

Background: Non-Hodgkin lymphomas (NHL) comprise a variety of lymphoproliferative malignancies with certain differences related to the morphological, clinical, immunohistochemical and hematological patterns, as well as the results of treatment. The patients with generalized and relapsed nasopharyngeal NHL experience marked disease burden and unfavorable impact on their life quality and working capacity. Objective: The aim of the study was to characterize the diagnosis issues of NHL with primary involvement of the nasopharynx and evaluate the short- and long-term results of management options. Materials and methods: This analytical and cohort study included 66 patients with different stages of nasopharyngeal NHL, who were managed at the Institute of Oncology from Moldova between 2014-2021. The diagnosis was confirmed by cytological, histopathological and immunohistochemical examinations. The histological types of NHL were verified and distinguished according to the 2017 Revision of WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. The patients treatment, follow-up and researches were realized at the comprehensive cancer center. The study was related to the hospitalized care. The patients age ranged between 19-85 years (average age - 58.4±2,14 years). Males were 28 (42%), females - 38 (58%). Stage I NHL was diagnosed in 10 (15.2%) cases, stage II - in 36 (54.5%), stage III - in 8 (12.1%) and stage IV - in 12 (18.2%). The eligible NHL patients underwent combined chemotherapy (CChT) regimens (CVChlP, R-CVChlP, CHOP and R-CHOP), associated with radiotherapy locoregional treatment in cases of bulky disease or residual tumor masses. The ECOG-WHO score and complete response (CR) rate assessed the short-term results. The long-term results were asserted by the overall one- and 5-year survival. Results: Primary nasopharyngeal NHL occurred commonly in females (58%) and in patients over 60 years (42.4%). The ECOG-WHO score accounted 1-3 at diagnosis. The aggressive NHL were diagnosed mostly (76.1%) in stage I and II due to the earlier developed disease burden. The primary tumor site was localized in the palatine tonsils in 22 (33.3%) patients, in 33 (50%) patients in the pharyngeal tonsil, in 2 (3%) patients in the lingual tonsil. The palatine and pharyngeal tonsils were concomitantly involved in 9 (13.7%) patients. Palatine tonsil involvement occurred mostly in patients over 60 years old, and pharyngeal tonsil involvement - in patients of 40-59 years. CR was achieved in 10 (100%) cases with stage I after combined chemotherapy (CChT) and radiotherapy locoregional treatment. CR occurred in 21 (67.7%), partial response (PR) - in 7 (22.6%) and response failure (RF) - in 3 (9.7%) in stage II NHL after CChT and radiotherapy locoregional treatment. In stage II NHL treated with CChT along, CR was achieved in 1 (25%), PR - in 2 (50%) and RF in 1 (25%). In stage III treated with CChT and radiotherapy locoregional treatment, CR was registered in 1 (20%), PR - in 2 (40%) and RF - in 2 (40%). PR occurred in 2 (66.7%), RF - in 1 (33.3%) in stage III managed with CChT alone. In stage IV NHL, CR was obtained 1 (11.1%) case, PR - in 5 (55.6%), RF - in 3 (33.3%) after CChT and radiotherapy locoregional treatment. PR occurred in 1 (33.3%), RF - in 2 (66.7%) cases in stage IV patients managed with CChT alone. No significant differences of CR rate were found in stage III (12,5%) and stage IV (8.3%) NHL (P>0.05). Irrespective of the stage, the highest CR rate was registered after CChT and radiotherapy locoregional treatment (97.1% of all cases), as compared to CChT alone (2.9% of all cases). The ECOG-WHO score reached 0-1 under the management with CChT and radiotherapy locoregional treatment in all cases with CR and PR. The overall survival was 79.9% at one year and 34.5% at 5 years. One- and 5-year survival proved to be significantly higher în stage I and II NHL - 96.1% and 64.2% respectively. One- and 5-year survival was 79.9% and 34.5% in stage III and IV NHL. Conclusions: Primary nasopharyngeal NHL were outlined by the predominant involvement of females, patients over 60 years and frequent site in the pharyngeal tonsil. The aggressive NHL were revealed commonly in stage I and II due to the progressive disease burden. The rates of the indolent and aggressive NHL turned out to be statistically equal in stage III and IV. The response and overall survival rates proved to be superior after R-CHOP regimen followed by the radiotherapy locoregional treatment. Disclosures No relevant conflicts of interest to declare.

Value of Plasma Squamous Cell Carcinoma Antigen-IgM Immune Complexes (SCCA-IgM IC) as a Novel Biomarker for Monitoring Hepatocellular Carcinoma Treatment Outcome

Background Assessment of the levels of Squamous Cell Carcinoma Antigen-IgM Immune Complexes (SCCA-IgM IC) as a serum biomarker to assess the prognosis and treatment outcome of HCC after locoregional treatment Aim of the work Evaluation of plasma squamous cell carcinoma antigen-IgM immune complex (SCCA-IgM IC) level as a biomarker to predict response to treatment with radiofrequency ablation (RF) and/or trance arterial chemoembolization (TACE) in HCC patients. Patients and Methods This study was conducted at the Internal Medicine department, Faculty of Medicine, Ain Shams University, during the period from July 2016 to November 2018 on 60 sequentially recruited patients with HCC undergoing locoregional treatment (RF and/or TACE). Patients were divided into two groups, Group A: 40 patients underwent TACE, Group B: 20 patients Underwent RF, all patients were followed up at 3 and 6 months post treatment. Patients who were excluded, those with HCC with late stage of the BCLC (Barcelona clinic liver cancer) staging system, patients with decompensated liver disease (Child-Pugh C), Hepato-renal syndrome or renal insufficiency, patients who had history of organ transplant or previously treated HCC. Results SCCA IgM IC serum level was significantly lower in patients without recurrence post TACE than patients with HCC recurrence at 3 and 6 months post treatment. SCCA IgM IC showed promising results especially when combining with AFP in diagnosis and monitoring of treatment response of HCC Conclusion the use of SCCA IgM IC in combination with AFP serum level may prove to be useful in assessing prognosis of HCC locoregional treatment

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.