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Background: Accumulation of malignant plasma cells in the bone marrow causes lytic bone lesions in 80% of multiple myeloma patients. Frequently fracturing, they are challenging to treat surgically. Myeloma cells surviving treatment in the presumably protective environment of bone lesions impede their healing by continued impact on bone turnover and can explain regular progression of patients without detectable minimal residual disease (MRD). Locally applicable biomaterials could stabilize and foster healing of bone defects, simultaneously delivering anti-cancer compounds at systemically intolerable concentrations, overcoming drug resistance. Methods: We developed silica-collagen xerogels (sicXer) and bortezomib-releasing silica-collagen xerogels (boXer) for local treatment of osteolytic bone disease and MRD. In vitro and in vivo (tissue sections) release of bortezomib was assessed by ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Material impact on bone formation was assessed in vitro regarding osteoclast/osteoblast numbers and activity. In vivo, drilling defects in a rat- and the 5T33-myeloma mouse model were treated by both materials and assessed by immunohistochemistry, UPLC-MS/MS, µCT, and ToF-SIMS. The material's anti-myeloma activity was assessed using ten human myeloma cell lines (HMCLs) and eight primary myeloma cell samples including four patients refractory to systemic bortezomib treatment. Results: sicXer and boXer show primary stability comparable to trabecular bone. Granule size and preparation method tailor degradation as indicated by release of the xerogel components (silica and collagen) and bortezomib into culture medium. In vitro, both materials reduce osteoclast activity and do not negatively interfere with osteoblast differentiation and function. The presumed resulting net bone formation with maintained basic remodeling properties was validated in vivo in a rat bone defect model, showing significantly enhanced bone formation for boXer compared to non-treated defects. Both materials induce myeloma cell apoptosis in all HMCLs and primary myeloma cell samples. In the 5T33-myeloma mouse model, both materials stabilized drilling defects and locally controlled malignant plasma cell growth. Conclusions: The combination of stabilization of fracture-prone lesions, stimulation of bone healing, and anti-tumor effect suggest clinical testing of sicXer and boXer as part of a combined systemic/local treatment strategy in multiple myeloma and non-malignant diseases. [ABSTRACT FROM AUTHOR]

Metastatic breast cancer (MBC) is still an incurable disease, which eventually develops resistance mechanisms against systemic therapies. While most patients experience widespread disease progression during systemic treatment (ST), in some cases, progression may occur at a limited number of metastatic sites. Evidence from other malignancies suggests that local treatment with stereotactic ablative radiotherapy (SABR) of oligoprogressive disease (OPD) may allow effective disease control without the need to modify ST. Available evidence regarding local treatment of oligoprogressive breast cancer is limited, mostly consisting of retrospective studies. The only randomized data come from the randomized CURB trial, which enrolled patients with oligoprogressive disease, including both small cell lung cancer and breast cancer patients, and did not show a survival benefit from local treatment in the latter group. However, local treatment of oligoprogressive MBC is still considered in clinical practice, especially to delay the switch to more toxic STs. This review aims to identify patients who may benefit from this approach based on the current available knowledge, focusing also on the potential risks associated with the combination of radiotherapy (RT) and ST, as well as on possible future scenarios. [ABSTRACT FROM AUTHOR]

Background: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy. Patients and Methods: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection. Results: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815–1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447–1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40). Conclusion: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the efficacy of local treatment (LT), including radiotherapy (RT) and cytoreductive prostatectomy (CRP), in improving outcomes for patients with oligometastatic prostate cancer (OmPCa). Methods: A systematic review and meta‐analysis of articles from PubMed, Embase, and Web of Science published between 2010 and November 2023 were conducted. The study included 11 articles, comprising three randomized controlled trials (RCTs) and eight retrospective analyses. The study assessed overall survival (OS), radiographic progression‐free survival (rPFS), prostate‐specific antigen (PSA) PFS, cancer‐specific survival (CSS), and complication rate (CR). Results: OS was significantly improved in the LT group, with both RCTs and non‐RCTs showing statistical significance [hazard ratios (HR) = 0.64; 95% confidence intervals (95% CIs), 0.51–0.80; p < 0.0001; HR = 0.55; 95% CIs, 0.40–0.77; p = 0.0004]. For rPFS, RCTs did not show statistically significant outcomes (HR = 0.60; 95% CIs, 0.34–1.07; p = 0.09), whereas non‐RCTs demonstrated significant results (HR = 0.42; 95% CIs, 0.24–0.72; p = 0.002). Both RCTs and non‐RCTs showed a significant improvement in PSA‐PFS (HR = 0.44; 95%CI, 0.29–0.67; p = 0.0001; HR = 0.51; 95% CIs, 0.32–0.81; p = 0.004). For CSS, RCTs demonstrated statistical differences (HR = 0.65; 95% CIs, 0.47–0.90; p = 0.009), whereas non‐RCTs did not (HR = 0.61; 95% CIs, 0.29–1.27; p = 0.19). Regarding CR, the risk difference was −0.22 (95% CIs, −0.32 to −0.12; p < 0.00001). Conclusion: LT significantly improved OS and PFS in patients with OmPCa. Further RCTs are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

The impact of local management of pulmonary metastases on the disease course of patients with metastatic colorectal cancer is poorly assessed. REPULCO database was a retrospective cohort on 18 years that included all patients treated for lung metastases from colorectal cancer who received local and/or systemic treatments. Primary objective was overall survival, secondary were progression-free survival and survival without chemotherapy. Three hundred and fifteen patients were analyzed, 157 with only systemic treatments, 78 with only local treatments, and 80 with local and systemic treatments. Overall survival at 5 years was 26.9% (IC95%: [17.7–36.9]) for systemic treatments only, 61.0% (IC95%: [40.8–76.1]) for local treatments only, and 77.8% (IC95%: [60.1–88.3]) for local and systemic treatments. Progression-free survival at 2 years was 4.8% (IC95%: [2.1–9.2]) for systemic treatment only, 28.3% (IC95%: [17.7–39.9]) for local treatments only, and 21.8% (IC95%: [13.1–31.9]) for local and systemic treatments. Median survival without chemotherapy was 2.99 months (IC95%: [2.33–3.68]) for systemic treatments, 33.97 months (IC95%: [19.06-NA]) for local treatments, and 12.85 months (IC95%: [8.18–21.06]) for local and systemic treatments. Local treatments of lung metastasis led to prolonged survival and allowed long periods of time without chemotherapy in this cohort. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLSs) are among the main disease-driving players in most cases of monoarthritis (MonoA), oligoarthritis, and polyarthritis. In this review, we look at the characteristics and therapeutic challenges at the onset of arthritis and during follow-up management. In some cases, these forms of arthritis develop into autoimmune polyarthritis, such as rheumatoid arthritis (RA), whereas local eradication of the RA synovium could still be combined with systemic treatment using immunosuppressive agents. Currently, the outcomes of local synovectomies are well studied; however, there is still a lack of a comprehensive analysis of current local intra-articular treatments highlighting their advantages and disadvantages. Therefore, the aim of this study is to review local intra-articular therapy strategies. According to publications from the last decade on clinical studies focused on intra-articular treatment with anti-inflammatory molecules, a range of novel slow-acting forms of steroidal drugs for the local treatment of synovitis have been investigated. As pain is an essential symptom, caused by both inflammation and cartilage damage, various molecules acting on pain receptors are being investigated in clinical trials as potential targets for local intra-articular treatment. We also overview the new targets for local treatment, including surface markers and intracellular proteins, non-coding ribonucleic acids (RNAs), etc. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present meta-analysis was to systematically determine the overall complication rate and incidence of cryoshock in patients undergoing cryoablation of the liver. Methods: A systematic review and meta-analysis adhering to the PRISMA guidelines and focusing on studies of cryotherapy for liver malignancies published after 2000 were conducted. PubMed, Web of Science, Embase, and Scopus were systematically searched for articles reporting incidences of adverse events associated with percutaneous cryoablation in patients with liver malignancies. Data extraction and screening were independently conducted by two reviewers, who resolved discrepancies through consensus. Statistical analysis was performed to assess heterogeneity and pooled complication rates and included a moderator analysis to explore factors influencing the occurrence of complications. Results: The initial search yielded 4,145 articles, of which 26 met our inclusion criteria. From these 26 articles, pooled data on 4,029 patients were extracted. Variance between studies reporting cryoshock was low (I2 = 13.15%), while variance among studies reporting major complications was high (I2 = 82.52%). The pooled weighted proportion of major complications was 4.71% while that of cryoshock was as low as 0.265%. Moderator analysis identified publication year as the only moderator for major complications and no moderator for the occurrence of cryoshock. Conclusion: Analysis of currently available evidence indicates that cryoablation has a relative safe profile with a pooled incidence of major complications below 5%. Cryoshock occurred in less than 0.3% of procedures and was not reported for liver lesions smaller than 3 cm. [ABSTRACT FROM AUTHOR]

Abstract Irreversible electroporation is a nonthermal ablation technique that uses a high-voltage electric current to create nanosized pores in the cell membrane of a malignant tumor, thus resulting in cell death. In recent years, an increasing number of clinical studies have shown that irreversible electroporation is a safe and effective treatment for prostate cancer. We describe the progress of irreversible electroporation in prostate cancer in recent years in terms of its mechanism of action, clinical studies, advantages and disadvantages and summarize the gaps in existing studies and directions for future research.

Abstract Background Immune checkpoint inhibitors (ICIs) have become the recommended first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, data on the failure patterns of first-line ICIs monotherapy is limited, and the optimal strategy for subsequent treatment remains controversial. Methods Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and October 2021 were identified. The progressive sites were recorded to analyze failure patterns. Post-progression survival (PPS) was compared between different treatment regimens. Results A total of 121 patients receiving first-line ICIs monotherapy were identified, with a median progression-free survival of 8.6 months. Sixty-five patients had available imaging at diagnosis as well as progressive disease, with 56.9% showing oligoprogression. For those with progression in existing lesions, the most common sites were the liver (77.8%) and lung parenchyma (62.5%), while progression with new lesions frequently occurred in the liver (32.0%). Fifty patients with recorded subsequent treatment were included in the analysis of subsequent treatment patterns. Patients treated with anti-angiogenesis therapy could get better PPS (HR: 0.275, P = 0.013). Isolated oligoprogression occurred most often in the lung parenchyma and intracranial lesions. More than half of these patients continued immunotherapy after local treatment, with a 2.5-year PPS rate of 51.4%. Conclusion The liver was the most common site of progression on first-line ICIs monotherapy. Anti-angiogenesis-based therapy might be an optimal regimen at the time of progression. Patients with isolated oligoprogressive could still benefit from immunotherapy after local treatment.

Background: Immune checkpoint inhibitors (ICIs) have become the recommended first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, data on the failure patterns of first-line ICIs monotherapy is limited, and the optimal strategy for subsequent treatment remains controversial. Methods: Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and October 2021 were identified. The progressive sites were recorded to analyze failure patterns. Post-progression survival (PPS) was compared between different treatment regimens. Results: A total of 121 patients receiving first-line ICIs monotherapy were identified, with a median progression-free survival of 8.6 months. Sixty-five patients had available imaging at diagnosis as well as progressive disease, with 56.9% showing oligoprogression. For those with progression in existing lesions, the most common sites were the liver (77.8%) and lung parenchyma (62.5%), while progression with new lesions frequently occurred in the liver (32.0%). Fifty patients with recorded subsequent treatment were included in the analysis of subsequent treatment patterns. Patients treated with anti-angiogenesis therapy could get better PPS (HR: 0.275, P = 0.013). Isolated oligoprogression occurred most often in the lung parenchyma and intracranial lesions. More than half of these patients continued immunotherapy after local treatment, with a 2.5-year PPS rate of 51.4%. Conclusion: The liver was the most common site of progression on first-line ICIs monotherapy. Anti-angiogenesis-based therapy might be an optimal regimen at the time of progression. Patients with isolated oligoprogressive could still benefit from immunotherapy after local treatment. [ABSTRACT FROM AUTHOR]

Background: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. Methods: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative‐intent local treatment. Hazard ratios were combined using a random‐effects model. Results: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta‐analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative‐intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24–0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative‐intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19–0.73). Conclusions: Curative‐intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing. [ABSTRACT FROM AUTHOR]

Background. The problem of purulent inflammatory diseases of the maxillofacial area remains one of the most pressing problems of modern dentistry and maxillofacial surgery. The aim of the study is to conduct a comparative evaluation of the effectiveness of a drug based on nanodispersed silica (NDS) with antimicrobial properties for the local treatment of purulent inflammatory diseases of the maxillofacial area. Materials and methods. A comparative assessment of the postoperative period was performed in 71 patients with maxillofacial phlegmon, who were divided into two representative groups: comparison (39 patients), in whose local treatment of purulent wounds was carried out by conventional methods, and the main group (32 patients), where the local treatment was carried out using a drug based on NDC. The level of endogenous intoxication was determined by the level of C-reactive protein (CRP), by the level of blood metabolites of average mass (MAM) and leukocyte intoxication index (LII) in the blood serum. The data obtained were statistically processed and compared. Results. During the study of the dynamics of СRР was found that starting from 3 days in the main group there was a tendency to its faster decrease and normalization before discharge, while in patients of the comparison group it was significantly higher (p < 0.05)., The level of MAM in patients of the comparison group remained significantly (p < 0.05) elevated throughout the treatment in the postoperative period, while in the main group it was on the verge of normal before discharge. Comparison group of patients had significantly higher LII during treatment and at the time of discharge from hospital (p < 0.05) than the main group. Conclusions: The treatment of maxillofacial phlegmon by the developed method provided a more favorable course of the postoperative period than in the comparison group, as evidenced by a significantly (p < 0.05) faster normalization of endogenous intoxication blood parameters.

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Abstract Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10–30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management. Graphical Abstract

Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10–30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management. [ABSTRACT FROM AUTHOR]

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood–brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton Beam Therapy (PBT) is an interesting therapeutic option for children and adolescents with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). In fact, if it is true that radiotherapy is a key part of the multi-modal treatment of NRSTS patients, it is also true that the risk of radiation-induced side effects represent an important limitation in its use. The unique characteristics of protons can be leveraged to minimize doses to healthy tissue, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. International cooperative efforts are required to better define the indications for PBT (based on the patient's age, estimated outcome, and tumor location), taking into account the currently limited number of available proton therapy facilities. This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking—partly due to the limited data available—PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications—based on the patient's age, estimated outcome, and tumor location—and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities. [ABSTRACT FROM AUTHOR]

A rise in the incidence of early rectal cancer consequent to bowel-screening programs around the world and an increase in the incidence in young adults has led to a growing interest in organ-sparing treatment options. The rectum, being the most distal portion of the large intestine, is a fertile ground for local excision techniques performed with endoscopic or surgical techniques. Moreover, the advancement in endoscopic optical evaluation and the better definition of imaging techniques allow for a more precise local staging of early rectal cancer. Although the local treatment of early rectal cancer seems promising, in clinical practice, a significant number of patients who could benefit from local excision techniques undergo total mesorectal excision (TME) as the first approach. All relevant prospective clinical trials were identified through a computer-assisted search of the PubMed, EMBASE, and Medline databases until January 2024. This review is dedicated to endoscopic and surgical local excision in the treatment of early rectal cancer and highlights its possible role in current and future clinical practice, taking into account surgical completion techniques and chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLSs) are among the main disease-driving players in most cases of monoarthritis (MonoA), oligoarthritis, and polyarthritis. In this review, we look at the characteristics and therapeutic challenges at the onset of arthritis and during follow-up management. In some cases, these forms of arthritis develop into autoimmune polyarthritis, such as rheumatoid arthritis (RA), whereas local eradication of the RA synovium could still be combined with systemic treatment using immunosuppressive agents. Currently, the outcomes of local synovectomies are well studied; however, there is still a lack of a comprehensive analysis of current local intra-articular treatments highlighting their advantages and disadvantages. Therefore, the aim of this study is to review local intra-articular therapy strategies. According to publications from the last decade on clinical studies focused on intra-articular treatment with anti-inflammatory molecules, a range of novel slow-acting forms of steroidal drugs for the local treatment of synovitis have been investigated. As pain is an essential symptom, caused by both inflammation and cartilage damage, various molecules acting on pain receptors are being investigated in clinical trials as potential targets for local intra-articular treatment. We also overview the new targets for local treatment, including surface markers and intracellular proteins, non-coding ribonucleic acids (RNAs), etc.

Simple Summary: For patients diagnosed with metastatic colorectal cancer, having colorectal liver metastases along with metastases in other organs may be deemed a contraindication for local treatment with curative intent. This observational study investigates whether administering local treatment to all metastatic sites could enhance overall survival rates. A total of 941 patients were included, among whom were 60 patients with metastases in both the liver and other organ(s). Our findings reveal that although patients with both liver and extrahepatic metastases exhibited lower survival rates compared to those with solely liver metastases, a survival plateau emerged after approximately 6.2 years. This implies that comprehensive local treatment of all metastatic sites might confer benefits for long-term survival. These insights could impact decision making regarding the scope of local treatment for patients with colorectal cancer that have metastases in multiple organs. Background: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites. Methods: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS). Results: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029–2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017–3.841, p = 0.041). Conclusions: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Sulfuryl fluoride (SF) is a fumigant used to eliminate drywood termites (DWT: Kalotermitidae; Froggatt) and other structural pests. Because of its global warming potential, it has been suggested that SF be restricted as a greenhouse gas (GHG). We present an economic model to assess the net social cost of restricting SF. We consider 3 approaches to address DWT control- no treatment, allowing SF fumigation and localized treatments, and only local treatment. Each approach generates private and public benefits and costs. We estimate that the annual damage and home equity loss by DWT in California is US$4.5–16.8 billion without treatment. If fumigation is used on 20% of the houses and local treatments on the others, the combined social cost of treatment, damage, and GHG emissions are between US$1–US$2 billion annually.The annual cost of local treatments only would be between US$3.2 and US$4.9 billion. If the application of SF is severely restricted or banned, the social costs will increase between US$1.43 and US$4.31 billion annually. The implied cost per ton of CO2 eliminated is between US$624 and US$1,465, much above the price range of CO2 in other applications. The restriction/ban has significant equity and environmental effects, impacting low-income individuals living in rented properties and replacing damaged wood in housing will increase GHG emissions. We further recommend the continued use of SF until a comparable whole-structure alternative is developed that fits the parameters of our model. [ABSTRACT FROM AUTHOR]

The prognosis for cancer of unknown primary site (CUP) is poor, and squamous cell carcinoma of the unknown primary site (SCCUP) is a rare histological type. CUP is often treated with aggressive multimodal treatments, while the treatment of single-area localized CUP remains controversial. We retrospectively reviewed the medical records of patients with CUP. SCCUP in women was classified according to several definitions. Based on the histologic type and site, they were classified into favorable and unfavorable subsets. We further divided SCCUP into two types (single and multiple areas) and reviewed treatment and efficacy. Among the 227 female CUP patients, 36 (15%) had SCCUP. The median age was 59.9 years (range, 31–90 years). Most patients (61.1%) had a good performance status. Of the SCCUP patients, 22 had cancer in a single area, and 14 in multiple areas. Single-area SCCUP was further divided into favorable (16 cases) and unfavorable subsets (6 cases). In the favorable subset, local treatment was predominant, and almost all cases had a good prognosis. Even in the unfavorable subset, local therapy was combined with systemic chemotherapy in only two cases, and four cases showed no recurrences. Local treatment may be effective for single-area SCCUP, even in the unfavorable subset.

Sabina Vennarini,1 Francesca Colombo,1,2 Alfredo Mirandola,3 Stefano Chiaravalli,4 Ester Orlandi,5 Maura Massimino,4 Michela Casanova,4 Andrea Ferrari4 1Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; 2Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy; 3Medical Physics Unit, Clinical Department, National Center for Oncological Hadrontherapy (CNAO), Pavia, Italy; 4Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy; 5Radiation Oncology Unit, Clinical Department, National Center for Oncological Hadrontherapy (CNAO), Pavia, ItalyCorrespondence: Andrea Ferrari, Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian, Milano, MI, 1 20133, Italy, Tel +39 02 23902588, Fax +39 02 23902648, Email andrea.ferrari@istitutotumori.mi.itAbstract: This paper offers an insight into the use of Proton Beam Therapy (PBT) in paediatric patients with rhabdomyosarcoma (RMS). This paper provides a comprehensive analysis of the literature, investigating comparative photon-proton dosimetry, outcome, and toxicity. In the complex and multimodal scenario of the treatment of RMS, clear evidence of the therapeutic superiority of PBT compared to other modern photon techniques has not yet been demonstrated; however, PBT can be considered an excellent treatment option, in particular for young children and patients with specific primary sites, such as the head and neck area (and especially the parameningeal regions), genito-urinary, pelvic, and paravertebral regions. The unique depth-dose characteristics of protons can be exploited to achieve significant reductions in normal tissue doses and may allow an escalation of tumour doses and greater sparing of normal tissues, thus potentially improving local control while at the same time reducing toxicity and improving quality of life. However, access of children with RMS (and more in general with solid tumors) to PBT remains a challenge, due to the limited number of available proton therapy installations.Keywords: rhabdomyosarcoma, pediatric, proton beam therapy, local treatment, radiotherapy

Yang Zhao,1– 3 Zhiyuan Li,2 Ying Chen,3– 5 Yushuang Li,3– 5 Jie Lu2– 5 1Department of Orthodontics, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Medical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 5Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Jie Lu, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Tel +86 17853297395, Fax +86 0532-82912019, Email 13127006046@163.comObjective: Gout is the most common inflammatory arthritis associated with interleukin-1β (IL-1β) accumulation during exacerbation. In this study, we aimed to clarify whether potassium channel antagonists attenuate local inflammation in mice with monosodium urate (MSU)-induced gout.Methods: We cultured human macrophage THP-1 cells and evaluated the molecular levels of both IL-1β and potassium channels stimulated with MSU and/or potassium channel antagonists. Acute gout models were generated in IL-1β luciferase transgenic male mice using synovium-like subcutaneous air pouches with MSU injection. Their luciferase activities were monitored following potassium channel blocker treatment using the IVIS Spectrum CT imaging system. The lavages and tissues were extracted from their air pouches, followed by cell counting and pathological analysis.Results: MSU stimulation increased the gene expression levels of pro-IL-1β, P2x7r and Kv1.3, whereas the expression of Kcnq1 was decreased in phorbol 12-myristate 13-acetate-induced THP-1 cells. Both high and low concentrations of the P2x7 receptor inhibitor adenosine 5′-triphosphate (ATP) derivative periodate oxidized ATP (oATP) decreased the production of IL-1β in the supernatant of THP-1 cells. The sixth hour was the peak time of IL-1β luciferase activity after MSU intervention in vivo. oATP ameliorated the synovial IL-1β luciferase activity, reduced inflammatory cell infiltration and alleviated the erosive damage in the cartilage.Conclusion: The anti-inflammatory properties of potassium channel inhibitors, especially of oATP, might point to new strategies for local anti-inflammatory therapy for acute gout.Keywords: acute gout, interleukin-1β, potassium channel, local treatment

Mouth ulcers, a highly prevalent ailment affecting the oral mucosa, leading to pain and discomfort, significantly impacting the patient’s daily life. The development of innovative approaches for oral ulcer treatment is of great importance. Moreover, a deeper and more comprehensive understanding of mouth ulcers will facilitate the development of innovative therapeutic strategies. The oral environment possesses distinct traits as it serves as the gateway to the digestive and respiratory systems. The permeability of various epithelial layers can influence drug absorption. Moreover, oral mucosal injuries exhibit distinct healing patterns compared to cutaneous lesions, influenced by various inherent and extrinsic factors. Furthermore, the moist and dynamic oral environment, influenced by saliva and daily physiological functions like chewing and speaking, presents additional challenges in local therapy. Also, suitable mucosal adhesion materials are crucial to alleviate pain and promote healing process. To this end, the review comprehensively examines the anatomical and structural aspects of the oral cavity, elucidates the healing mechanisms of oral ulcers, explores the factors contributing to scar-free healing in the oral mucosa, and investigates the application of mucosal adhesive materials as drug delivery systems. This endeavor seeks to offer novel insights and perspectives for the treatment of oral ulcers.

Insulin is a hormone whose efficacy in wound healing was recognised in the late 1920s. Intensive research is currently underway to develop materials that will allow the effective stabilisation of insulin and control of its diffusion rate. The aim of this review was to bring together research on the development of innovative wound care strategies based on insulin-enriched bioactive dressings. An analysis of the literature contained in bibliographic databases and published up to 30 June 2023 was performed. The results of the included basic and preclinical studies confirm that engineered polymeric matrices/scaffolds with insulin show high efficacy and good tolerability in topical wound treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the outcome of patients with cavitary chronic osteomyelitis undergoing adjuvant treatment with bioactive glass (BAG) S53P4 and identify the independent risk factors (RFs) for recurrence in 6- and 12-month patient follow-up. Methods: A retrospective, multicentre observational study conducted in tertiary specialised hospitals among patients undergoing the surgical treatment of chronic cavitary osteomyelitis using BAG-S53P4 in a granule and/or putty formulation to assess the clinical outcome and RFs for failure in 6- and 12-month patient follow-up. Results: Of the 92 and 78 patients with 6-month and 12-month follow-ups, infection was eradicated in 85.9% and 87.2%, respectively. In the 6-month follow-up, BAG-S53P4 in the granule formulation presented a greater risk of recurrence compared to the bioactive glass putty formulation or combined granules and putty (prevalence ratio (PR) = 3.04; confidence interval 95% [CI95%]: 1.13–10.52) and neoplasia (PR = 5.26; CI95%: 1.17–15.52). In the 12-month follow-up cohort of 78 patients, smoking (PR = 4.0; 95% CI: 1.03–15.52) and nonfermenting GNB infection (PR = 3.87; CI95%: 1.09–13.73) presented a greater risk of recurrence. Conclusions: BAG-S53P4 is a viable option for bone-void filling and the treatment of chronic cavitary osteomyelitis. Formulations of BAG with putty or in combination with granules showed better results. [ABSTRACT FROM AUTHOR]

Oligometastasis is defined as the presence of several limited metastatic lesions and is generally limited to three or fewer than five metastatic lesions. Previously, the treatment of metastatic cancer aimed to alleviate symptoms rather than cure them; however, the use of immunotherapy or targeted therapy has greatly improved patient life expectancy. Additionally, the effectiveness and safety of local treatment have recently been proven for oligometastatic cancers and have significantly improved patient survival and decreased recurrence rates. A few metastatic studies on lung cancer have demonstrated the usefulness of combining radiation therapy and immunotherapy. Recently, local and targeted therapy combinations have shown promising results in treating non-small cell lung cancer, predominantly caused by the epidermal growth factor receptor and anaplastic lymphoma kinase gene mutations, suggesting the potential of these new treatment strategies. It is well known that oligometastasis has better clinical results than polymetastasis; however, research on the biological profile of oligometastasis is still lacking. Studies using circulating tumor DNA and circulating tumor cells are at the initial stages of providing a better understanding of oligometastatic cancers, and the biological characteristics of these cancers may be revealed based on more diverse studies. With the development of these treatments, the prognosis for patients with oligometastatic cancers is steadily improving, and if the biological profile is revealed, customized treatment may be provided. [ABSTRACT FROM AUTHOR]

The prognosis for cancer of unknown primary site (CUP) is poor, and squamous cell carcinoma of the unknown primary site (SCCUP) is a rare histological type. CUP is often treated with aggressive multimodal treatments, while the treatment of single-area localized CUP remains controversial. We retrospectively reviewed the medical records of patients with CUP. SCCUP in women was classified according to several definitions. Based on the histologic type and site, they were classified into favorable and unfavorable subsets. We further divided SCCUP into two types (single and multiple areas) and reviewed treatment and efficacy. Among the 227 female CUP patients, 36 (15%) had SCCUP. The median age was 59.9 years (range, 31–90 years). Most patients (61.1%) had a good performance status. Of the SCCUP patients, 22 had cancer in a single area, and 14 in multiple areas. Single-area SCCUP was further divided into favorable (16 cases) and unfavorable subsets (6 cases). In the favorable subset, local treatment was predominant, and almost all cases had a good prognosis. Even in the unfavorable subset, local therapy was combined with systemic chemotherapy in only two cases, and four cases showed no recurrences. Local treatment may be effective for single-area SCCUP, even in the unfavorable subset. [ABSTRACT FROM AUTHOR]

Introduction. When purifying natural objects from heavy metals a decisive role is played by sorption technologies, for the development of which new kinds of sorbents are required. The aim of the study is to evaluate the sorption capacity of granulated foam glass in the treatment of surface wastewater (SW) from urbanized areas from heavy metals (on the example of Co, Cr, Cu, Fe, Ni, Pb and Zn).Materials and methods. Granulated foam glass was used as a sorbent. The sorbate was urban surface wastewater from the city of Chelyabinsk. The interaction in the sorbent-sorbate system was studied in laboratory conditions by the limited volume method of static sorption when the pollutants were in the liquid phase and brought into contact with a stationary sorbent. The contact time of the sorbent with the sorbate was varied from 3 to 168 hours and the ambient temperature from 0 to 20 °C. The structure and surface composition of the sorbents were studied using a JEOL JSM-6460LV scanning electron microscope with an attachment for micro X-ray spectral analysis. Changes in the sorbate composition during interaction with the sorbents were determined by atomic emission spectrometry on an OPTIMA 2100 DV spectrometer (Perkin Elmer). Hydrogen index was determined on a pH-meter microprocessor рН-150МИ.Results. The structure and surface composition of granulated cellular glass has been studied. The efficiency of sorption of granulated foam glass of heavy metals from urban surface wastewater has been revealed.Conclusions. The results show that the investigated granulated foam glass is an effective sorption material and allows the extraction of heavy metals (cobalt, chromium, copper, iron, nickel, lead, zinc) from urban surface wastewater.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood–brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

Background: Current guidelines recommend indefinite imatinib treatment for advanced gastrointestinal stromal tumor (GIST) patients. Imatinib-refractory progression-free survival (PFS) and overall survival were previously reported not to differ between GIST patients who interrupted imatinib and those who did not. Methods: Clinical outcomes of 77 consecutive patients with recurrent or metastatic GIST who interrupted imatinib treatment after maintaining years of imatinib treatment in the absence of gross tumor lesions were retrospectively analyzed. Associations between clinical factors and progression-free survival (PFS) following imatinib interruption were analyzed. Results: The median time from the absence of gross tumor lesions to imatinib interruption was 61.5 months. Since imatinib interruption, the median PFS was 19.6 months, and 4 patients (26.3%) remained progression-free for longer than 5 years. Among the patients who had progressive disease following the interruption, imatinib re-introduction led to an 88.6% objective response rate and a 100% disease control rate. Complete removal of the initial gross tumor lesion(s) and complete removal of the residual gross tumor lesion(s) by local treatment (vs. no local treatment or residual lesions after local treatment) were independently associated with favorable PFS. Conclusion: Interruption of imatinib following prolonged maintenance in the absence of gross tumor lesions led to disease progression in the majority of cases. However, re-introduction of imatinib resulted in effective tumor control. Unmaintained remission seems to be possible in some patients with metastatic or recurrent GIST after a prolonged remission with imatinib if there is complete removal of any gross tumor lesions. [ABSTRACT FROM AUTHOR]

There has been controversy over whether to radiologically follow up or use local treatment for asymptomatic small-sized brain metastases from primary lung cancer. For brain tumors without local treatment, we evaluated potential factors related to the brain progression and whether systemic therapy controlled the tumor. We analyzed 96 patients with asymptomatic small-sized metastatic brain tumors from lung cancer. These underwent a radiologic follow-up every 2 or 3 months without local treatment of brain metastases. The pathologies of the tumors were adenocarcinoma (n = 74), squamous cell carcinoma (n = 11), and small cell carcinoma (n = 11). The primary lung cancer was treated with cytotoxic chemotherapy (n = 57) and targeted therapy (n = 39). Patients who received targeted therapy were divided into first generation (n = 23) and second or third generation (n = 16). The progression-free survival (PFS) of brain metastases and the overall survival (OS) of patients were analyzed depending on the age, tumor pathology, number, and location of brain metastases, the extent of other organ metastases, and chemotherapy regimens. The median PFS of brain metastases was 7.4 months (range, 1.1–48.3). Targeted therapy showed statistically significant PFS improvement compared to cytotoxic chemotherapy (p = 0.020). Especially, on univariate and multivariate analyses, the PFS in the second or third generation targeted therapy was more significantly improved compared to cytotoxic chemotherapy (hazard ratio 0.229; 95% confidence interval, 0.082–0.640; p = 0.005). The median OS of patients was 13.7 months (range, 2.0–65.0). Univariate and multivariate analyses revealed that the OS of patients was related to other organ metastases except for the brain (p = 0.010 and 0.020, respectively). Three out of 52 patients with brain recurrence showed leptomeningeal dissemination, while the recurrence patterns of brain metastases were mostly local and/or distant metastases (94.2%). Of the 52 patients who relapsed, 25 patients received local brain treatment. There was brain-related mortality in two patients (2.0%). The intracranial anti-tumor effect was superior to cytotoxic chemotherapy in the treatment of asymptomatic small-sized brain metastases with targeted therapy. Consequently, it becomes possible to determine the optimal timing for local brain treatment while conducting radiological follow-up for these tumors, which do not appear to increase brain-related mortality. Furthermore, this approach has the potential to reduce the number of cases requiring brain local treatment. [ABSTRACT FROM AUTHOR]

Objective: To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis, received by patients in the Program for the Study and Control of Tropical Diseases- PECET-Medellín-Colombia. Methods: This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021. Relevant information regarding sociodemographic characteristics, history of leishmaniasis, characterization of current infection, treatment received, follow-up of therapeutic response and safety was collected from the medical records. Data were analyzed with Pearson's Chisquare association tests and Mann-Whitney U test using statistical software. Results: A total of 486 clinical records of patients were analyzed, and 356 received treatment. Eight different therapeutic alternatives (systemic, local and in combination) were analyzed. The therapeutic response of the different alternatives used (except thermotherapy) was higher than 50%. Most frequent adverse events were myalgias, arthralgias and headache, and vesicles for systemic and local treatment, respectively. Conclusions: Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a malignant disease that affects thousands of patients every year. Currently, we use surgical techniques for early-stage cancer and chemotherapy treatment combinations for advanced stage cancer. Several novel therapies are currently being investigated, with gene therapy and stem cell therapy being the corner stone of this investigation. We conducted a thorough search on PubMed and gathered up-to-date information regarding epithelial ovarian cancer therapies. We present, in the current review, all novel treatments that were investigated in this field over the past five years, with a particular focus on local treatment. [ABSTRACT FROM AUTHOR]

Nail psoriasis is a clinical manifestation of psoriasis involving the nails, with prevalence of 80%~90%. Changes in nail appearance and pain can negatively impact the quality of patients′ lives. The treatment regimens for nail psoriasis include local treatment, systemic treatment and physical therapy. Traditional therapy requires long-term treatment with uncertain outcomes. In recent years, the efficacy and the course of treatment have been improved by new regimens such as biologics and small molecule drugs. This article will review the treatment of nail psoriasis in order to facilitate the selection of most appropriate approach for the treatment of nail psoriasis.

Objective: To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis, received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia. Methods: This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021. Relevant information regarding sociodemographic characteristics, history of leishmaniasis, characterization of current infection, treatment received, follow-up of therapeutic response and safety was collected from the medical records. Data were analyzed with Pearson's Chi - square association tests and Mann-Whitney U test using statistical software. Results: A total of 486 clinical records of patients were analyzed, and 356 received treatment. Eight different therapeutic alternatives (systemic, local and in combination) were analyzed. The therapeutic response of the different alternatives used (except thermotherapy) was higher than 50%. Most frequent adverse events were myalgias, arthralgias and headache, and vesicles for systemic and local treatment, respectively. Conclusions: Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

At present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery; however, it is accompanied by off-target effects and server systemic toxicity. Herein, we proposed a biodegradable microdevice for local sustained drug delivery and postoperative pancreatic cancer treatment as an alternative and safe option. Biodegradable poly(l-lactic-co-glycolic acid) (P(L)LGA) was developed as the matrix material, gemcitabine hydrochloride (GEM·HCl) was chosen as the therapeutic drug and polyethylene glycol (PEG) was employed as the drug release-controlled regulator. Through adjusting the amount and molecular weight of PEG, the controllable degradation of matrix and the sustained release of GEM·HCl were obtained, thus overcoming the unstable drug release properties of traditional microdevices. The drug release mechanism of microdevice and the regulating action of PEG were studied in detail. More importantly, in the treatment of the postoperative recurrence model of subcutaneous pancreatic tumor in mice, the microdevice showed effective inhibition of postoperative in situ recurrences of pancreatic tumors with excellent biosafety and minimum systemic toxicity. The microdevice developed in this study provides an option for postoperative adjuvant pancreatic treatment, and greatly broadens the application prospects of traditional chemotherapy drugs.

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.

A 61-year-old man tested positive for occult urinary and fecal occult blood and was diagnosed with invasive prostate cancer extensively infiltrating the rectum. After scrutiny, he was diagnosed with cT4N1M0 prostate cancer, and androgen deprivation therapy (ADT) was initiated with a gonadotropin-releasing hormone antagonist. A prostatic rectal resection was performed 6 months after ADT began. The bladder and urethra were anastomosed, the anus was preserved intact, and the sigmoid colon was anastomosed to the anus. A temporary ileostomy was constructed to allow eating and to prevent fistula formation. The ileostomy was closed 5 months post-operation as the patient wanted to live without a stoma. Although the patient died of other disease factors, he remained untreated for 1 year and 7 months post-operation, and his symptoms and disease control were well supported. We report that we were able to perform stoma-free surgical treatment for prostate cancer extensively infiltrating rectum.

Papular dermatitis is a cutaneous manifestation of canine Leishmania infantum infection associated with mild disease. Although it is a typical presentation, nowadays, there is still no established treatment. This study evaluated the safety and clinical efficacy of local meglumine antimoniate, locally administered polyhexamethylene biguanide (PHMB) alone or PHMB in combination with a Toll-like receptor 4 agonist (TLR4a) for the treatment of papular dermatitis due to L. infantum and assessed parasitological and immunological markers in this disease. Twenty-eight dogs with papular dermatitis were divided randomly into four different groups; three of them were considered treatment groups: PHMB (n = 5), PHMB + TLR4a (n = 4), and meglumine antimoniate (n = 10)), and the remaining were considered the placebo group (n = 9), which was further subdivided into two sub-groups: diluent (n = 5) and TLR4a (n = 4). Dogs were treated locally every 12 h for four weeks. Compared to placebo, local administration of PHMB (alone or with TLR4a) showed a higher tendency towards resolution of papular dermatitis due to L. infantum infection at day 15 (χ2 = 5.78; df = 2, p = 0.06) and day 30 (χ2 = 4.; df = 2, p = 0.12), while local meglumine antimoniate administration demonstrated the fastest clinical resolution after 15 (χ2 = 12.58; df = 2, p = 0.002) and 30 days post-treatment (χ2 = 9.47; df = 2, p = 0.009). Meglumine antimoniate showed a higher tendency towards resolution at day 30 when compared with PHMB (alone or with TLR4a) (χ2 = 4.74; df = 2, p = 0.09). In conclusion, the local administration of meglumine antimoniate appears to be safe and clinically efficient for the treatment of canine papular dermatitis due to L. infantum infection. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy is more and more used for treatment of oligometastatic mediastinal lymph nodes. The objective of this single-centre study was to evaluate its efficacy in patients with either a locoregional recurrence of a pulmonary or oesophageal cancer or with distant metastases of extrathoracic tumours. Patients with oligometastatic mediastinal lymph nodes treated with CyberKnife from June 2010 to September 2020 were screened. The primary endpoint was to assess local progression free survival and induced toxicity. Secondary endpoints were overall survival and progression free survival. The delay before introduction of systemic treatment in the subgroup of patients who did not receive systemic therapy for previous progression was also evaluated. Fifty patients were included: 15 with a locoregional progression of a thoracic primary tumour (87% pulmonary) and 35 with mediastinal metastasis of especially renal tumour (29%). Median follow-up was 27 months (6–110 months). Local progression free survival at 6, 12 and 18 months was respectively 94, 88 and 72%. The rate of local progression was significantly lower in patients who received 36 Gy in six fractions (66% of the cohort) versus other treatment schemes. Two grade 1 acute oesophagitis and one late grade 2 pulmonary fibrosis were described. Overall survival at 12, 18 and 24 months was respectively 94, 85 and 82%. Median progression free survival was 13 months. Twenty-one patients were treated by stereotactic body irradiation alone without previous history of systemic treatment. Among this subgroup, 11 patients (52%) received a systemic treatment following stereotactic body radiotherapy with a median introduction time of 17 months (5–52 months) and 24% did not progress. Stereotactic body irradiation as treatment of oligometastatic mediastinal lymph nodes is a well-tolerated targeted irradiation that leads to a high control rate and delay the introduction of systemic therapy in selected patients. [ABSTRACT FROM AUTHOR]