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.

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UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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. 18F-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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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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.

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.

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.

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.

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.

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.
CONCLUSIONS: 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.