Thursday 12 November 2020

Radiofrequency treatment alters cancer cell phenotype

We are at the doorstep of an exciting era in which the due importance of Radiofrequency treatment for cancer (and possibly many other ailments) is being finally and gradually revealed.

Multiple studies are being conducted into this exciting field and plausible explanations of pathways are being suggested. Field in which these selective non-thermal effects have been shown include, and are not limited to treatment of Non-Small Cell Lung Cell Carcinoma, Glioblastoma, Bladder Cancer and Pancreatic Cancer.

Synergo incorporates a 915MHz generator, responsible for delivering microwave (the high end of the RF frequencies) in the treatment of bladder cancer. This RF is regulated in real-time by the operator (up to 36W).

One of the questions that is often raised is what effect the RF has on the cancer cells.

In vitro studies have demonstrated that tumor-specific frequencies identified in patients with various forms of cancer are capable of blocking the growth of tumor cells in a tissue- and tumor-specific fashion. Current experimental evidence suggests that tumor-specific modulation frequencies regulate the expression of genes involved in migration and invasion and disrupt the mitotic spindle.

2 independent studies present explanations to these effects and how RF operates.

An article published in 2015 by Ware et al. demonstrates that RF radiation creates micropores selectively on cancer cells and disconnects the adhesion between cancer cells. The writers conclude that there are clear phenotypical differences observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. They also reported, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. They provided evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

Another article published by Curley et al. in 2014 compared how RF and hyperthermia (HT) treatments change the proliferation rate, oxygen consumption and autophagy in malignant and nonmalignant cells and their results were clear.

Their conclusion: “The results obtained in the current study, along with our previous reports, indicate the ability of RF treatment to provide a tumor-specific cytotoxic effect by inhibiting the proliferation and mitochondrial activity of tumor cells and the stimulation of autophagy. These effects exceed the hyperthermic property of the RF field. All of this assures further investigation of the biological effects of RF treatment to stimulate the development of novel, non-invasive approaches for cancer treatment using electromagnetic fields.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199010/

https://pubmed.ncbi.nlm.nih.gov/26165830/

Monday 26 October 2020

Synergo for High-risk NMIBC

Urology Cancer specialists,

We are proud and honoured to share an article published in October 2020, by Denosshan Sri et al. St Georges Urology Centre (London) on Urologic Oncology. 

https://doi.org/10.1016/j.urolonc.2020.09.016

Cystectomy outcomes in patients who have failed Radiofrequency-induced Thermo-chemotherapeutic Effect Mitomycin-C (RITE-MMC) treatment for high-risk non-muscle invasive bladder cancer (HRNMIBC) -Does it complicate surgery and adversely impact oncological outcome?

Denosshan SriHack Jae LeeSarah El-GemmalChris BackhouseAndrea TayBabbin JohnMatthew J PerryBenjamin E AyresRami Issa St. George's Hospital, London, UK

Highlights for Review

Radiofrequency-Induced Thermo-chemotherapeutic Effect Mitomycin (RITE-MMC) can be an alternative in BCG failure.

RITE-MMC treatment does not result in a technically more challenging cystectomy.

RITE-MMC treatment does not compromise oncological outcome compared to those patients undergoing cystectomy immediately post BCG failure.

The article presents a retrospective study of a prospective cystectomy database. Inclusion criteria were HRNMIBC with BCG failure undergoing cystectomy.

Thirty-six patients who received RITE-MMC underwent cystectomy, compared to 102 that did not. Median ages were comparable at 72 and 69 years, respectively. Patients were followed up for a median of 24 months across the 2 groups. The commonest histological stage in both groups was CIS. There were no significant differences in intraoperative blood loss, length of stay and 90-day readmission between the 2 groups. There were proportionally fewer recurrences in the RITE-MMC group (16% vs. 19%) and median time to recurrence was longer in the RITE-MMC group (37 months vs. 24 months). Multivariate analysis did not reveal a significant correlation between pre-op RITE-MMC and post-operative readmission (P = 0.606). Survival curves show no significant difference in time to recurrence across both groups (P = 0.513), and no overall (P = 0.069) or cancer specific mortality (P = 0.129) dis-advantage was noted in the RITE-MMC group.

Conclusion
We have found that RITE-MMC treatment does not result in a technically more challenging cystectomy and does not compromise oncological outcome compared to those patients undergoing cystectomy immediately post-BCG failure. We feel RITE-MMC remains a useful tool in a carefully selected group of patients who may not be willing to accept the morbidity of a cystectomy at the time, without significantly compromising their long-term outcome.


 

Medical Enterprises’s commentary:

St Georges University Hospital Urological centre is one of the leading Referral Centres of Synergo worldwide and its dedicated team accumulated a vast experience over the past 16 years with Synergo Radiofrequency-Induced ThermoChemotherapy (RITE).

One may note that, as such, the referrals to the hospital for cystectomy constitutes a very high number, and seeing the relatively few cystectomies carried out on patients whom previously received radiofrequency treatment in the bladder prompts hope for many patients who opt to preserve their bladders despite the indication for a radical surgery.

This researcher’s group has presented their bladder preservation study in over 10 years follow-up (Link to the study), and this new article sheds light on the possibility of administering RITE as a last step before radical cystectomy (as recurrence and progression rates are oncologically similar), while in the relatively low percentage of patients who would fail this modality over time, a surgery would not impose a greater risk of complications than in an early cystectomy.

Tuesday 15 September 2020

A history note: 1995 post R&D

25 years ago!

Synergo at the very outset. The year is 1995. A group of urologists and scientists at HSR publishes its first article and presents a new device based on a microwave source delivering local bladder hyperthermia together with intravesical chemotherapy.



44 patients treated. Overall response rate in 90.8%: 70.4% complete and 20.4% partial.




Positive, repetitive results have led to the development of the “Synergo®”.

Synergo® RITE technology was specifically developed and designed to deliver local microwave hyperthermia (radiofrequency) in combination with chemo to treat Non Muscle invasive Bladder Cancer. All administered via Synergo transurethral RF applicator.

Starting as early as 1992 and continuously to date clinical trials have been conducted to study the benefits of combined treatment of Synergo® over chemotherapy and immunotherapy alone for people who suffer from NMIBC and other tumors in the bladder. The treatment has become a common practice in leading centres both as a prophylactic treatment (after TUR) and ablative treatment (for tumour eradication).

Photo below: pre-Synergo: transurethral microwave bladder with chemo instillation. A lamp was used to hold the embedded antenna within the silicone catheter.


Photo: 25 years ago! Synergo at the very outset. A designed device. Arm replaces the lamp. 




Monday 27 July 2020

Radiofrequency impairs viability of bladder cancer cells and has an additive effect when combined with chemotherapeutics in vitro

Presented by I.S.G. Brummelhuis et al. ESUR, Porto

A study comparing the effects of two techniques combined with chemotherapy on cell viability of bladder cancer cells in vitro.

 

MMC and epirubicin showed the greatest impact on the cell viability of all cell lines. RF-induced HT inhibited cell viability of T24, J82 and RT4 cancer cell lines. In combination with MMC and epirubicin this effect was additive. The majority of the effects of RF-induced HT were not attributable to the effect of HT, implying that the effect of RF adds independently to the effects of HT and chemotherapy. The cell viability of benign hbSMC was not affected by RF. 


European Urology Supplements 18(8):e3152-e3153 · October 2019
 

Monday 18 May 2020

"Tough times never last, but tough people do."—Robert H. Schuller

Together, we are facing a truly unprecedented situation. The global coronavirus pandemic is affecting all of our families, our businesses, our communities, and our way of life.
We are truly inspired by the selfless healthcare workers around the world who are on the front lines working tirelessly to care for people in need.

We wish you and your families stay safe & healthy, gradual and phased return, as we continue to work together as a collective community to support business continuity and each other.

Sincerely, 

Medical Enterprises Team

Wednesday 12 September 2018

Synergo presented at the SWDGU (Südwestdeutsche Gesellschaft für Urologie e.V.), Offenburg 2018


45-year-old patient suffering from a multifocal, recurrent non-muscle invasive transitional cell carcinoma of the urinary bladder since 2012.The patient had multiple transurethral resections of the bladder (max. Tumor Stage pTA, high-grade).

The patient received instillations therapy with Mitomycin (8x), 2013 followed BCG instillations, which was aborted due to BCGitis with pulmonary and hepatic infection.
In 2015, following repeated recurrences of tumors, the patient was recommended cystectomy which the patient rejected.
Synergo® treatment was performed at the patient's request. A total of 8 induction cycles (11/2015 -01/2016, 2x40 mg Mitomycin weekly) and 6 maintenance cycles (04 – 12/2016, 2x20 mg Mitomycin 6-weekly) were given.

Since 03/17 the patient receives a maintenance therapy (2x20 mg Mitomycin, once every 3 months) and has been remaining free of tumour for 2 years.
With overall good therapy compatibility, a unique Intradetrusorale Botox injection was required to treat the increasingly pronounced urge symptoms.

RF-Induced hyperthermia and chemotherapy after failure of previous instillation therapies with Mitomycin and BCG can be an effective therapy option in individual cases before offering cystectomy.

Hyperthermiegestützte Mitomycininstillation nach Versagen der herkömmlichen Instillationstherapien bei rezidivierendem, nicht muskelinvasivem Harnblasenkarzinom als Alternative zur Zystektomie 

Presentation given by Maxim KocherginUlrich Witzsch; Joseph Bcheraoui; Stefan Tietz; Eduard Walter Becht from Krankenhaus Nordwest

Saturday 25 August 2018

"Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder
instillation is a key to understand the safety profile and clinical activity of chemotherapy."

Intravesical Chemotherapy and Chemohypherthermia in Non-Muscle-Invasive Bladder
Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics
Campodonico F, Di Stasi S, Lev GM, Terrone C, Bongiovanni L, Mattioli F, Pagliarulo V and Introini C
Current Drug Metabolism, 2017

https://doi.org/10.2174/1389200218666170427092421

Despite the widely adopted international guidelines’ recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical
administration. This paper gives a comprehensive review covering various aspects of different treatments with intravesical drugs.
Device-assisted therapies have set a goal to potentiate the drug’s effect and efficacy. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy.

This new published study examined whether RF-CHT (using Synergo system) results in higher MMC drug tissue concentrations as compared to cold MMC instillation.

Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue,
F. Johannes P. van Valenberg, Antoine G. van der Heijden, Rianne J. M. Lammers, Johannes Falke, Tom J. H. Arends, Egbert Oosterwijk & J. Alfred Witjes
International Journal of Hyperthermia


Patients received either (1) cold drug instillation (Mitomycin) or (2) RF-CHT (Synergo) before a planned transurethral resection operation. After instillation, three biopsy tests were taken of both normal and tumour tissue. The results showed that the median drug concentration in tumour tissue was higher in the RF-CHT (Synergo) group (median 665.00ng/g vs. 63.75ng/g, U¼51.0, p¼0.018). Moreover, in both techniques the MMC concentration was lower in normal tissue compared to tumour tissue. They concluded that Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.



virtual London (EAU 2017)
Enjoyed meeting all urology specialists at the last EAU conference!