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International guidelines recommend local therapies (LTs) such as local thermal ablation (LTA; radiofrequency, microwave, cryoablation), transarterial (chemo)embolisation (TA(C)E), and transarterial radioembolisation (TARE) as therapeutic options for advanced adrenocortical carcinoma (ACC). However, the evidence for these recommendations is scarce. We retrospectively analysed patients receiving LTs for advanced ACC. Time to progression of the treated lesion (tTTP) was the primary endpoint. The secondary endpoints were best objective response, overall progression-free survival, overall survival, adverse events, and the establishment of predictive factors by multivariate Cox analyses. A total of 132 tumoural lesions in 66 patients were treated with LTA (n = 84), TA(C)E (n = 40), and TARE (n = 8). Complete response was achieved in 27 lesions (20.5%; all of them achieved by LTA), partial response in 27 (20.5%), and stable disease in 38 (28.8%). For the LTA group, the median tTTP was not reached, whereas it was reached 8.3 months after TA(C)E and 8.2 months after TARE ( p < 0.001). The median time interval from primary diagnosis to LT was >47 months. Fewer than four prior therapies and mitotane plasma levels of >14 mg/L positively influenced the tTTP. In summary, this is one of the largest studies on LTs in advanced ACC, and it demonstrates a very high local disease control rate. Thus, it clearly supports the guideline recommendations for LTs in these patients.

The liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well-established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM., (© 2023 American Cancer Society.)

Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Context: Unlike other cancers, the concept of oligometastatic disease (OMD) in bladder cancer (BC) has not been systematically investigated. There is therefore a need to develop universally accepted definitions and guidelines for the management of oligometastatic BC (OMBC)., Objective: To conduct a systematic review to assist a European consensus group in producing a definition of OMBC and to provide recommendations on staging and local therapies., Evidence Acquisition: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Abstracts for articles focused on BC that addressed the issue of OMBC and provided a definition of oligometastatic status were selected. We collected data on the number of metastases, the number of metastases per organ, the number of organs involved, and metastatic sites that were excluded., Evidence Synthesis: Sixteen eligible articles were retrieved (9 retrospective series involving 330 patients, 4 reviews, 1 consensus statement, 1 guideline paper, and 1 ongoing prospective phase 2 trial). A maximum of three to five metastatic lesions were compatible with the definition of OMBC. The number of organs involved and lesion size were not universally included in the OMBC definitions. OMD categories studied included synchronous OMBC, oligorecurrence, and oligoprogression. 18 F-Fluorodeoxyglucose positron emission tomography combined with computed tomography was used in addition to conventional imaging for OMD detection. Surgery and radiotherapy were both used. Systemic chemotherapy was also used in all studies., Conclusions: There is little information on OMBC in the literature. Our systematic review revealed that only three to five metastatic sites amenable to surgery or radiotherapy that respond to systemic therapy is the setting most frequently chosen for a combination of systemic treatment and metastases-directed therapy. This setting could represent a basis for future prospective studies on OMBC., Patient Summary: Oligometastatic bladder cancer is a disease state in which favorable outcomes can be expected after a treatment combination of systemic therapy, plus surgery and/or radiotherapy for sites of bladder cancer metastasis. Our systematic review showed a lack of meaningful evidence to define this disease state. There is an urgent need to develop organized research in this field., (© 2023 The Author(s).)

Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.

Background and objective Low back pain (LBP) and sciatica are major healthcare issues globally. Since patients may seek various ways to cure their ailments, these conditions are managed not just by physicians, but many other health-related professionals provide alternative treatment options for it as well. We conducted this study to examine a local subset of patients who used stabbing their back and legs as a treatment option for curing LBP and sciatica. Materials and methods This cross-sectional study was conducted in the outpatient clinic of the Neurosurgery unit of Government Naseer Ullah Babar Memorial Hospital, Peshawar, Pakistan, from July 2019 to March 2020. Patients who presented to the outpatient department (OPD) with complaints of LBP with or without sciatica, with a history of invasive therapy in the form of stabbing the back or leg, or drawing blood from the veins of the lower limbs, were included. All other patients with LBP seeking neurosurgical advice were excluded from the study. The study was approved by the management of the hospital and informed consent was obtained from the patients before interviewing them. Special permission was taken for publishing the photographs. The demographics and clinical information related to patients, such as age, gender, duration of symptoms, time since the local therapy, particulars of the treatment provider, any relief experienced by the patient, duration of relief, the patient beliefs/notions about the therapy and disease, and education level of the patients, were recorded on a predesigned form after taking informed consent. The study was done on purposive sampling. The data was presented in tables and charts and was analyzed using SPSS Statistics version 20 (IBM, Armonk, NY). Results During the study period, more than 8,000 patients visited the neurosurgical OPD, and the majority of them (>70%) sought treatment for LBP and sciatica. Of them, around 130 patients had a history of undergoing some alternative therapy that is not scientifically proven, and it was either in the form of stabbing the back or drawing blood from the veins in the lower limbs. Amongst these patients, almost 80% were males and 20% were females who had undergone this kind of treatment. The age range among the cohort was 25-68 years and the mean age was around 43 years. The duration of symptoms ranged from two months to nine years, and the time since the therapy and patient seeking medical advice ranged from three months to 4.5 years. The treatment had been provided by a local individual who did not hold any medical degree according to the patients in 100% (n=130) of the cases; 67% of patients felt they had experienced some relief from the therapy for a short period, which ranged from three days to one month. About the condition, none of the patients seeking the therapy knew it was nerve-related and were often confused about the term rugg (vessel in the native language) but could not differentiate it from the nerve. Of these patients, 76 required surgery while 54 were managed conservatively for LBP and sciatica. Conclusion A subset of the local population in our part of the world used stabbing the back and leg as a form of therapy for treating the problems of the lower back and sciatica. This has not been previously reported and has no scientific basis. Also, the majority of the patients were uneducated and had very little knowledge of the disease, and the treatment provider was a non-health-related professional., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Khan et al.)

Background: Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered., Methods: All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging., Results: We identified 59 patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32 patients (54%) and modified the lymph node stage in 8 of the 59 patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26 patients underwent complete tumor resection, 17 had R1 margins, and 5 were not operated due to early tumor progression. With a median follow-up of 82 months (range: 5-287), 18 relapses had occurred, at least locoregional in 12 cases. The 5‑year local and nodal control rates were 73% (63-86%) and 86% (77-95%), respectively. Five-year progression-free and overall survival were 57% (95%CI [45-72%]) and 70% (95%CI [58-84%]), respectively., Conclusion: The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Large-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options., Methods: We retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010., Results: 191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p<0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients' smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing., Conclusions: Highly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival., Competing Interests: FB reports research funding from BMS and travel grants from BMS and MSD. DK reports advisory board and speaker’s honoraria from AstraZeneca, BMS, Pfizer. JK reports research funding from AstraZeneca and Celgene. RS reports research funding from BMS and speaker’s honoraria from Roche. TM reports research funding from Roche and patents with Roche. AS reports advisory board honoraria from BMS, AstraZeneca, ThermoFisher, Novartis, speaker’s honoraria from BMS, Illumina, AstraZeneca, Novartis, ThermoFisher, MSD, Roche, and research funding from Chugai. PC reports research funding from AstraZeneca, Novartis, Roche, Takeda, and advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, Pfizer, Roche, Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fisch, Bozorgmehr, Kazdal, Kuon, Klotz, Shah, Eichhorn, Kriegsmann, Schneider, Muley, Stenzinger, Bischoff and Christopoulos.)

Locally advanced pancreatic cancer (LAPC) constitutes approximately one-third of all pancreatic cancer, with standard of care inconsistently defined and achieving modest outcomes at best. While resection after downstaging offers the chance for cure, only a fraction of patients with LAPC become candidates for resection. Chemotherapy remains the mainstay of treatment for the remainder. In these patients, ablative therapy may be given for local control of the tumor. Irreversible electroporation (IRE) is an attractive ablative technique. IRE changes the permeability of tumor cell membranes to induce apoptosis. Unlike other ablative therapies, IRE causes little thermal injury to the target area, making it ideal for LAPC involving major vessels. Compared to systemic chemotherapy alone, IRE seems to offer some survival benefit. Although early studies reported notable morbidity and mortality rates, IRE presents opportunities for those who cannot undergo resection and who otherwise have limited options. Another role of IRE is to extend the margins of resected tumors when there is a concern for R1 resection. Perhaps most exciting, IRE is thought to have effects beyond local ablation. IRE has immunomodulatory effects, which may induce in vivo vaccination and may potentially synergize with immunotherapy. Through electrochemotherapy, IRE may enhance drug delivery to residual tumor cells. Ultimately the role of IRE in the treatment of LAPC still needs to be validated through well designed randomized trials. Investigations of its future possibilities are in the early stages. IRE offers the potential to provide more options to LAPC patients., Competing Interests: Conflicts of interest The authors have no conflicts of interest, sources of financial support, corporate involvement or patent holdings to report., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Vaginal infections such as bacterial vaginosis (BV), chlamydia, gonorrhea, genital herpes, candidiasis, and trichomoniasis affect millions of women each year. They are caused by an overgrowth of microorganisms, generally sexually transmitted, which in turn can be favored by alterations in the vaginal flora. Conventional treatments of these infections consist in systemic or local antimicrobial therapies. However, in the attempt to reduce adverse effects and to contrast microbial resistance and infection recurrences, many efforts have been devoted to the development of vaginal systems for the local delivery of antimicrobials. Several topical dosage forms such as aerosols, lotions, suppositories, tablets, gels, and creams have been proposed, although they are sometimes ineffective due to their poor penetration and rapid removal from the vaginal canal. For these reasons, the development of innovative drug delivery systems, able to remain in situ and release active agents for a prolonged period, is becoming more and more important. Among all, nanosystems such as liposomes, nanoparticles (NPs), and micelles with tunable surface properties, but also thermogelling nanocomposites, could be exploited to improve local drug delivery, biodistribution, retention, and uptake in vulvovaginal tissues. The aim of this review is to provide a survey of the variety of nanoplatforms developed for the vaginal delivery of antimicrobial agents. A concise summary of the most common vaginal infections and of the conventional therapies is also provided.

Background/aim: Seizures impair patients' quality of life. The prognostic role of pre-treatment seizures in patients with 1-3 cerebral metastases receiving local therapies plus whole-brain radiotherapy (WBRT) was investigated., Patients and Methods: In 249 patients, prevalence, risk factors and associations of pre-treatment seizures with survival were retrospectively evaluated. Age, gender, performance score, tumor type, number of lesions, extra-cerebral metastases, and time from tumor diagnosis to treatment of cerebral metastasis were analyzed for associations with seizures. These characteristics and pre-treatment seizures were also analyzed for associations with survival., Results: The prevalence of pre-treatment seizures was 24.1%. Trends for associations were found between seizures and gender or performance score. On multivariate analysis, age (p=0.008), performance score (p=0.004), tumor type (p<0.001) and extra-cerebral metastasis (p<0.001) were significantly associated with survival., Conclusion: Seizures were comparably common prior to local therapies plus WBRT for cerebral metastases. No factor was found to be significantly associated with seizures, and seizures were not associated with survival., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Although omitting whole-brain radiotherapy (WBRT) during the treatment of few brain metastases more popular, many patients receive local therapies plus WBRT. WBRT may be less reasonable for patients with poor overall survival (OS), particularly if they are older. This study aimed to identify predictors of OS in these patients., Patients and Methods: One-hundred-and-two older patients receiving a local therapy (surgery, radiosurgery, simultaneous integrated boost) and WBRT for 1-3 brain metastases were evaluated. Type of local therapy, WBRT-regimen, age, gender, performance status, primary tumour type, number of brain metastases, extra-cerebral metastasis, and interval from tumour diagnosis to treatment of brain metastases were analysed for OS., Results: Absence of extra-cerebral metastasis was significantly associated with increased OS on univariate analysis (p=0.001) and Cox regression analysis (risk ratio=2.13, p=0.002)., Conclusion: Extra-cerebral metastasis is an independent predictor of OS and can be helpful when assigning a treatment to older patients with few brain metastases., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa., Methods: Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both., Results: Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p < 0.001). Completely resected disease had a five-year OS of 30.5%, incomplete resections 31.4% versus no surgery 6.0% (p < 0.001). Radiated patients had a five-year OS of 21.3% versus 14.2% without radiotherapy (p < 0.001). Patients who received radiotherapy without surgical interventions, had a marginally better five-year OS of 12.5% as opposed to 5.4% (p < 0.001). Patients who underwent surgery had a longer mean overall survival of 60.9 months, while patients, who were irradiated, had a longer mean overall survival of 7.9 months (p < 0.001). On multivariate analysis, complete metastatic remission (p < 0.001), surgical status (p = 0.027), and radiotherapy status (p = 0.040) were significant predictive factors in abdominal primaries., Conclusion: Surgery and radiotherapy significantly improve outcomes regardless of the primary tumor site, emphasizing the importance of local control in neuroblastoma.

Background/aim: Personalization of the treatment of brain metastases considering patient's overall survival (OS) prognosis is gaining importance. This study was conducted to develop an OS score particularly for patients receiving local therapies for single brain metastasis from gynecological malignancies., Patients and Methods: In 11 patients, the following factors were retrospectively analyzed for associations with OS: Age, Karnofsky performance score (KPS), tumor type, extra-cranial metastatic sites, and time from diagnosis of gynecological malignancy to treatment of brain metastasis. Factors showing at least a strong trend were used for the score., Results: A KPS of 80-90% resulted in a significantly better OS than a KPS of 50-70% (p=0.008). Absence of extra-cranial metastases showed a strong trend (p=0.052). For the score, the following points were used: KPS 50-70%=0, KPS 80-90%=1, presence of extra-cranial metastatic sites=0, absence=1. Patients' scores were 0, 1 or 2 points. OS rates at both 6 and 12 months were 0%, 67% and 100%, respectively (p=0.020)., Conclusion: This specific score can be used to estimate OS in patients receiving local therapies for single brain metastasis from gynecological malignancies and personalize their care., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease.

Due to the advances in screening of cirrhotic patients, hepatocellular carcinoma (HCC) is being diagnosed in earlier stages. For this reason the number of patients diagnosed of very early HCC (single tumors ≤ 2 cm) is continuously increasing. Once a patient has been diagnosed with this condition, treatment strategies include liver resection, local therapies or liver transplantation. The decision on which therapy should the patient undergo depends on the general patients performance status and liver disease. Anyway, even in patients with similar conditions, the best treatment offer is debatable. In this review we analyze the state of the art on the management of very early HCC on cirrhotic patients to address the best treatment strategy for this patient population.