Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Patients in EUS-RFA group will undergo endoscopic ultrasound guided radiofrequency ablation(EUS-RFA ) and chemoradiotherapy

the control group will receive chemoradiotherapy only

Endoscopic ultrasound guided radiofrequency ablation （EUS-RFA） will be done in 3 different sessions with 2 weeks interval between each session on Day 1, Day 15 and Day 30. Each session will involve multiple applications of EUS-RFA (up to 10) with RF setting of 25 Watts over 90 seconds for each application.

Endoscopic ultrasound guided radiofrequency ablation

chemoradiotherapy

Xiaofeng Zhang

the study evaluate the efficacy and safety of EUS-RFA using Habib EUS-RFA catheter with a prospective randomised trial in patients with inoperable PDAC.

The five year survival for pancreatic ductal adenocarcinoma (PDAC) is less than 5% in spite of the advances in management of cancers in the last few decades. Endobiliary application of radiofrequency ablation (RFA) has been developed in our unit and used in patients with unresectable bile duct and pancreatic head adenocarcinomas presenting with biliary obstruction. Various techniques of EUS-guided tumour ablation have been described, including RF ablation, photodynamic therapy, laser ablation, and ethanol injection. Endoscopic ultrasound guided RFA (EUS-RFA) of the pancreatic head using Habib EUS-RFA catheter through a 19-gauge needle was well tolerated in 5 Yucatan pigs and with minimum amount of pancreatitis .

EUS-RFA for Unresectable Pancreatic Ductal Adenocarcinoma

Endoscopic Ultrasound Guided Radiofrequency Ablation (EUS-RFA) for Unresectable Pancreatic Adenocarcinoma - a Randomised Controlled Trial

The tumor size was compared before and after 60 days EUS-RFA

Serum levels of Ca 19-9 was compared before and after 60 days EUS-RFA

First People's Hospital of Hangzhou

Associate director of gastroenterology department

Gland and Hormone Related Diseases

Rare Diseases

Adenoma

Hyperaldosteronism

Adrenocortical Adenoma

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Endocrine System Diseases

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Adenoma of the Adrenal Gland

Hyperadrenalism

Vasoconstrictor Agents

Respiratory System Agents

All Drugs and Chemicals

Epinephrine

Racepinephrine

Epinephryl borate

All patients will undergo endoscopic US guided radiofrequency ablation, to assess safety and feasibility.

To establish if radiofreuqency ablation of aldosterone producing adrenal adenomas can be carried out via the endoscopic route and to assess safety of the procedure.

ultrasound

Stephen Pereira

High blood pressure (hypertension) causes strokes and heart attacks. While most patients need long-term treatment with pills, some have a cause which can be removed, curing the hypertension. The commonest curable cause is a benign nodule in one of the hormone glands, the adrenals. About one in 20 patients have such a nodule, but difficulties with diagnosis, and reluctance to proceed to surgery for a benign condition, limit the number having adrenal gland surgery to fewer than 300 per year in the UK. A potential, and exciting, solution to this dilemma is to use a momentary electric current to cauterise the nodule (radiofrequency ablation), without affecting the rest of the adrenal gland, and avoiding the need for surgery. Nodules in the left adrenal gland are easily reached under mild sedation using a similar procedure as is standard for investigating stomach ulcers (endoscopy). The study is designed to show that this approach (endoscopic ultrasound guided radiofrequency ablation) is very safe, and to provide initial evidence that the hormone abnormality is cured.

Primary hyperaldosteronism (PA) is one of the commonest causes of hypertension. It is estimated to be the root cause in 10% of all patients with hypertension and 20% of all patients with resistant hypertension. Conventionally, patients with PA are divided 50:50 into those with a curable, unilateral aldosterone-producing adenoma (APA), and those with bilateral idiopathic adrenal hyperplasia (IAH).

Individual clinicians may reasonably consider it unnecessary to diagnose a benign condition whose work-up for surgery can be arduous, and the benefits uncertain. Public health doctors could reasonably despair at a large increase in demand for scarce surgical resources, when long term comparison of medical and surgical approaches have not been undertaken. Yet PA is regarded as a high-risk subset of hypertension, with an estimated 4-12 fold excess rate of cardiovascular complications compared to otherwise comparable patients with Hypertension. The American Endocrine Society Guidance recommends that where resources permit, a unilateral APA should be removed in order to protect patients from the long-term consequences of excess aldosterone. At present, most APAs are removed by key-hole surgery, with a 2% conversion rate to open surgery.

While such surgery is justified by the serious cardiovascular risk of PA, the high level of proof (of unilateral disease) before surgical referral has the paradoxical outcome of reducing take-up of a procedure that can be life-prolonging. A further paradox is that the rigid division of PA into unilateral adenoma vs bilateral hyperplasia is probably incorrect and that an intervention which does not require the distinction may, in stages, come to be regarded as the more logical approach to cure of PA, with reduction/prevention of cardiovascular risk. The obvious alternative intervention is selective ablation of APA(s), sparing most of the adjacent adrenal gland. Several publications report anecdotal success using this technique. The eligibility criteria for ablation were variable, but generally the patients were medically unfit or declined to undergo surgery. Success rates, measured as reversal of the biochemical abnormalities of PA, and radiological resolution, were high. However, there were few major adverse events. Most patients were monitored in hospital after the procedures, with shorter stays than the 2-3 days typical of most centres following laparoscopic surgery.

The investigators wish to progress from the experience with percutaneous and retroperitoneoscopic ablation to an approach which should maximise the ease and applicability of ablation whilst reducing the risk of adverse events. The primary outcome of the study will be safety. However, by the end of the study the investigators also need to have sufficient evidence of efficacy to justify, and guide design of, a subsequent multi-centre comparison trial.

Population Patients over the age of 18 diagnosed with left adrenal aldosterone producing adenoma meeting criteria from Endocrine Society clinical practice guidelines for primary hyperaldosteronism. The intervention (ultrasound guided endoscopic radiofrequency ablation) will be offered to those unsuitable for left adrenalectomy, who do not want surgery, or those who meet the criteria for surgery but wish to consent to radiofrequency ablation.

Design of study and intervention FABULAS is a three-center study, modelled on phase 1b/2a trials of novel drugs. It aims to determine the safety and efficacy study of endoscopic ultrasound-guided ablation as a nonsurgical, adrenal-sparing treatment for aldosterone-producing adenomas. Thirty patients will be enrolled onto the study comprised of three cohorts of ten patients. The three cohorts will run sequentially with overlapping stages, and the safety of the first six patients in each cohort/group will be reviewed before the next group commences.

Potential patients will be identified by referrals to our specialist Endocrine or Hypertension clinics. Once identified patients will be recruited at St. Bartholomew's Hospital in a Screening Visit where they will be clinically assessed, bloods and baseline investigations such as urinalysis and ECGs will be performed and informed consent gained for official enrolment onto the study.

Diagnostic PET CT scans using a tracer 11-C-Metomidate (or an alternative tracer, when available) will be used for confirmation of a left Conn's adenoma(s). Some patients may have already had this investigation as part of their work up. If so the PET CT does not need to be repeated. Group 1's (please see eligibility section for details) endoscopies will be managed in the Research Endoscopy Suite within the Clinical Research Facility at UCLH. Assuming group 1 is non-problematic, Barts Hospital will initiate ablations in year 2. The two-site approach maximises safety, assures recruitment of 1-2 eligible patients per month, and provides some early insight to the generalisability of the innovation.

Outcomes and assessment

The Primary Outcome Measures The primary outcome is safety, whether the recorded patient safety outcome data establishes that perforation, haemorrhage and infarction of major organs does not occur. This will be assessed at 48 hours.

This will be achieved by:

* Accurate adverse event reporting;
* Clinical assessment (history and examination) looking for features of blood loss, perforation, or inflammation/infarction of peri-adrenal tissues;
* Blood tests for Hb, WBC, and Renal function, amylase, LFTs, CRP; and.
* Urinalysis for blood and protein.

The Secondary Outcome Measures

The difference from baseline measurements at 3 and 6 months following ablation will be measured using the following clinical, biochemical and radiological parameters:

* Plasma electrolytes;,
* Aldosterone and renin ratio at 3 and 6 months;
* PET CT 3 months post ablation for radiological disappearance, diameter size and SUV measurements;.
* The reduced use or cessation of supplementary potassium medication; and
* Home BP (measured 3 readings twice a day for 4 days preceding clinic visit).Reduction in/or no longer taking antihypertensive medication

Assessment of cure will be performed at the site not involved in patient care. This will be subject to ratification by the safety committee who are not involved in the study.

Sample size / recruitment size A sample size of 30 patients will be recruited to the clinical trial. These statistical analyses have been performed by Dr Stephen Morant, University of Dundee (statistician). Patients will be identified through specialist endocrine / hypertension clinics and recruitment will be at St Bartholomew's Hospital.

The Intervention

Initially the patient's imaging (PET CT) will be reviewed at a multidisciplinary meeting to confirm the diagnosis and suitability for treatment by radiofrequency ablation for a left aldosterone producing adenoma. Currently this technique can only be used for the left adrenal gland due to its position near to the stomach.

On the day of the procedure the patient will receive a general anaesthetic or conscious sedation for the treatment. An endoscope with an ultrasound probe in the tip will be passed in to the stomach or small bowel to identify the adrenal adenoma.. A fine needle is then inserted into the adenoma via the endoscope and its contents aspirated. Samples will be sent to the laboratory for routine analysis. Following aspiration of the adenoma, the patient will undergo Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) treatment. The radiofrequency probe will be placed into the adenoma via the needle. The needle will be withdrawn slightly so the probe lies within the adenoma. A low power current of 10 Watts for 90 seconds will then be applied to the lesion on up to 10 occasions to ablate the tumour. It is anticipated the treatment will cause destruction of the adenoma.

The 30 patients recruited to this study, will need to stay in hospital for approximately 48 hours following treatment. A CT scan will be performed 24-48 hours post ablation. Based on the experience so far, it is hoped that the side effects of radiofrequency ablation will be minor and that ultimately the treatment will be performed as a day-case procedure. If our initial experience confirms this, patients recruited to this study may be discharged on the same day as treatment, following review by the medical team. Patients will be followed up at one, three and six months in outpatients to recheck blood pressure and blood tests to check if the treatment has been successful, with a repeat PET CT scan prior to the appointment. Blood tests will also be performed on the day of the appointment, as part of standard care. If the adenoma has not been completely ablated at 3 months the patient may be offered a further EUS-RFA treatment.

Patients will be asked to measure their blood pressure at home 4 days before each study visit with a monitor loaned to them whilst on the clinical trial. In addition to formally checking for any adverse effects at each clinic visit, patients were also asked to report any side-effects encountered to the medical team.

Sample management Cytology from the fine needle aspiration will be sent for immunohistochemistry staining. RNA will be obtained to look expression of the enzymes that produce aldosterone.

All participants will undergo the intervention: endoscopic ultra-sound guided radiofrequency ablation of their left adrenal aldosterone producing adenoma. The primary outcome is safety and feasibility

Radiofrequency Endoscopic Ablation With Ultrasound Guidance: a Non-surgical Treatment for Aldosterone-producing Adenomas

Feasibility Study of RadioFrequency Endoscopic ABlation, With ULtrasound Guidance, as a Non-surgical, Adrenal Sparing Treatment for Aldosterone-producing Adenomas

The primary objective is to test the primary hypothesis which states that endoscopic ultrasound-guided radiofrequency ablation of aldosterone-producing adenomas of the adrenal gland is a safe method for achieving sustained reduction in plasma aldosterone.

Specifically this will be assess via number of patients in whom one of the following is reported:

1. Major haemorrhage (seen on 24-48 hour safety CT)
2. Fall in Hb
3. Evidence of infarction of peri-adrenal organs on blood tests and CT
4. Evidence of rupture of stomach on CT

Difference in measurement of plasma electrolytes, renin and aldosterone at baseline and 6 months following ablation looking for normalisation post procedure. Definition of biochemical success defined as per PASO consensus

Metomidate PET CT will be performed at 6 months after ablation and compared with baseline PET CT looking for 'radiological cure', ie successful ablation of previous 'hot' aldosterone producing adrenal adenoma.

Difference in Home BP measurements (3 readings morning and 3 in the evening for 4 days) before clinic visits at baseline and at 6 months. Definition of clinical success defined as per PASO consensus. If home BP is not available, clinic BPs will be used.

Queen Mary University of London

British Heart Foundation

University of Cambridge

Cambridge University Hospitals NHS Foundation Trust

Barts & The London NHS Trust

University College London Hospitals

University College, London

Digestive System Diseases

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Hematinics

Amino Acids

Liver Extracts

Tyrosine Kinase Inhibitors

Tyrosine

This group is comprised by patients with diagnosis of resectable GISTs with/without liver metastasis. The patients included are naïve (without previous treatment) or patients with stable/progressive disease following systemic therapy with tyrosine kinase inhibitors.

Patients will be first assessed by DFI-EUS and CE-EUS. Then. EUS guided RFA will be performed using the 19G electrode ablation needle connected to the Starmed radiofrequency generator (Taewong Medical, Seoul, South Korea). After EUS identification of the GIST, a place without interposing vessels will be found by the endosonographer. Puncture of the tumor will be performed directly with the ablation probe inserted through the working channel of the echoendoscope. Time - seconds will depend by the tumor dimension, localization, distance from vital structures (e.g., aorta) and EUS appearance (e.g., hyperechoic). Power will be set at no more than 30W. If the tumor is in contact with vital structures a 10mm safe margin will be kept from these to avoid thermal injury. Multiple applications can be performed in the same or separate session depending on the residual tumor tissue evaluated with DFI-EUSor CE-EUS immediately after procedure.

Carlos Robles-Medranda, MD FASGE

Hannah Pitanga-Lukashok, MD

Raquel Del Valle, MD

Daniela Tabacelia, MD

Maria Egas-Izquierdo, MD

Miguel Puga-Tejada, MD

Martha Arevalo-Mora, MD

Jorge Baquerizo-Burgos, MD

Juan Alcivar-Vasquez, MD

Nowadays, for the selection of the treatment for gastrointestinal stromal tumors (GISTs), tumor size, prognosis, resectability and stage should be considered. Due to mutations in KIT and platelet-derived growth factor alpha (PDGFRA) in 90% of patients with this mesenchymal tumor, many tyrosine kinase inhibitors are used. On the other hand, a resectable tumor is approached by surgery, endoscopic and ablation therapy.

Radiofrequency ablation (RFA) approach has been studied in hepatic GISTs, and hepatic metastases, but its evaluation in esophageal, gastric, and intestinal GISTs is scarce. This study aims to determine the feasibility, safety and efficacy of endoscopic ultrasound (EUS) guided RFA using the 19 G RFA probe developed by Taewong Medical for the treatment of GISTs.

Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal tumors of the gastrointestinal tract. GISTs usually appear like subepithelial lesions covered by normal mucosa, arising from the second of fourth layer of the gastrointestinal tract wall. They are variable in size and mostly asymptomatic, but they can present different clinical behavior as bleeding, pain, or obstruction. The tumor size, location and mitotic rate are important prognostic factors. For resectable tumors \>2 cm, surgery is the treatment of choice; the management of tumors \<2 cm remains debatable because they present unclear clinical significance and low risk of malignancy. Endoscopic treatment, when complete resection it's possible, could be an option to full thickness laparoscopic resection. Moreover, around 90% of GISTs harbour driver mutation in KIT and platelet-derived growth factor alpha (PDGFRA), making the treatment with tyrosine kinase inhibitors (i.e., imatinib, sunitinib and regorafenib) a suitable option for locally advanced and metastatic disease. Nevertheless, the role of local treatment in advanced and metastatic disease is limited, with few retrospective studies suggesting tumor ablation as a therapeutic approach.

According to literature, thermal ablation has been successfully used for local treatment of hepatic metastases from GISTs (as a curative treatment). However, its feasibility and technical success as a local treatment in esophageal, gastric or intestinal GISTs has not been evaluated.

The investigators aimed to determine the feasibility and efficacy of the RFA electrode developed by Taewong Medical for the treatment of resectable GISTs (esophageal, gastric and intestinal lesions) as well as its limited liver metastases in naïve patients or patients with stable disease following systemic therapy with tyrosine kinase inhibitors. The challenge is whether to introduce local ablative therapy as curative or as part of multimodal treatment in patients with GISTs to obtain a curable disease and an increase in overall survival for metastatic patients.

A non-blinded, single center, non-randomized prospective feasibility trial.

Endoscopic Ultrasound Radiofrequency Ablation for GISTs

Feasibility, Safety, and Efficacy of EUS-guided Thermal Radiofrequency Ablation in the Treatment of Gastrointestinal Stromal Tumors

Incidence of adverse events of EUS guided RFA for GISTs' lesions and metastasis. Data will be summarized as frequencies and relative frequencies.

The technical success will be assessed by completion of ablation on EUS by the time of the procedure, indicated by replacement of the lesion by structural/appearance changes on DFI and CE-EUS Data will be summarized as frequencies.

Will be assessed by measuring the proportion of patients demonstrating absence of residual tumor on follow-up. CT- scan and DFI at one, three and six months will be performed to evaluate tumor response to the treatment.

Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals.

Proportion of patients needing re-treatment for residual tumor in a one-month period after the intervention.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EUS-RFA for Unresectable Pancreatic Ductal Adenocarcinoma	NCT03772756	Pancreatic Aden...	Endoscopic ultr... chemoradiothera...	20 Years - 80 Years	First People's Hospital of Hangzhou
Radiofrequency Endoscopic Ablation With Ultrasound Guidance: a Non-surgical Treatment for Aldosterone-producing Adenomas	NCT03405025	Primary Hyperal... Primary Hyperal...	Endoscopic ultr... ultrasound	18 Years -	University College, London
Endoscopic Ultrasound Radiofrequency Ablation for GISTs	NCT05453292	Gastrointestina...	Endoscopic ultr...	18 Years - 89 Years	Instituto Ecuatoriano de Enfermedades Digestivas

Spots Global Cancer Trial Database for endoscopic ultrasound guided radiofrequency ablation