For a list of institutions in Europe using this method, see below
Update Dec. 2005- References - Partial List of Published articles, see below

Local microwave-induced hyperthermia has a therapeutical potential for the treatment of many solid tumors. In bladder cancer it has shown itself to be especially useful when combined with intravesical chemotherapy for non-muscle-invasive tumors.. After extensive laboratory investigations, recent advances in miniaturized technology have led to the development of equipment which is specially designed for delivering thermo-chemotherapy (also known as thermal intravesical chemotherapy) to the human bladder.

Ongoing human and animal studies conducted in Europe and Israel dating back some 12 years or more have proven that microwave-induced hyperthermia combined with intravesical mitomycin C is a feasible, effective and safe conservative approach for those with [high risk] multiple and recurrent non-muscle-invasive bladder tumors when other treatment strategies have failed, and/or when cystectomy is contra-indicated or the patient refuses to undergo radical surgery.

Recent clinical experience has shown that treatments with Synergo® are highly efficient and give a lower recurrence rate than traditional methods. Synergo® technology has been approved by the European Standard Authorities (CE) and is now in the process of receiving FDA approval in the US.

In one randomized study, the patients having the new treatment showed a much lower recurrence rate (20%) than patients receiving conventional treatment (70%).

During the last decade this system was mainly used as an alternative to TURB. When clinically used for this indication, this system was shown to be effective, and safe. In a randomized trial it was more effective than intravesical chemotherapy alone.1

With the system now in clinical practice, a 915 MHz microwave applicator is inserted into the bladder via a special catheter. In addition, a set of thermocouples are inserted to control the tempature of the bladder wall layers which are heated to a temperature of 42 +/- 2 degree Celcius (approximately 104 degrees Farenheit +/- 1 degree). The drug is then pumped out and re-instilled, as a way of avoid overheating. Everything is monitored by a computerized unit with special software.

Each treatment lasts one hour, no major systemic side effects are observed, with local side effects being tolerable and temporary; no regional or general anesthetic is required, and patients can resume normal daily activities the same day.

All studies performed to date have shown the benefit of the Synergo® system over TUR or TUR+intravesical chemo with improved clinical results, lower recurrence rates and a reduced need for cystectomy. (see list below)

Synergo® treatments are performed in Germany, Israel and Italy, Holland, Switzerland, Austria, France and Belgium. For more info see article: New Technology For Superficial Bladder Cancer; http://www.medinews.com/GMEDTS32olcgi/ts.cgi?tsurl=0.55.1236.0.0 and manufacturer's website, Medical Enterprises

www.Medical-Enterprises.com Medical Enterprises Europe B.V.
Assumburg 152 B,1081GC Amsterdam, The Netherlands E-mail: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it MEL-Medical Enterprises Ltd.6 Odem st. P.O.B 7166, Kiryat MatalonPetah-Tikva, 49170, Israel E-mail: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

References - Partial List of Published articles-
To read all abstracts about thermo-chemotherapy at the National Library of Medicine click here

Thermo-Chemotherapy for intermediate or high-risk recurrent superficial bladder cancer patients. Ann Oncol.2005 Apr,16(40:585-9. Moskovitz B, Meyer G, Kravtzov A, Gross M, Kastin A, Biton K, Nativ O.

Effect of Hyperthermia on the Cytotoxicity of Four Chemotherapeutic Agents Currently Used for the Treatment of Transitional Cell Carcinoma of the Bladder - An in Vitro Study. Van der Heijden A.G, Verhaegh G, Cornelius F. J. J, Schalken J.A, Witjes J.A. J Urol Vol. 173, 1375-1380, 2005.

The Effect of Hyperthermia on Mitomycin-C Induced Cytotoxicity in Four Human Bladder Cancer Cell Lines. Van der Heijden A.G, Cornelius F. J. J, Verhaegh G, O'Donnell M.A, Schalken J.A, Witjes J.A. Eur Urol. 2004 Nov;46(5):670-674.

Preliminary European Results of Local Microwave Hyperthermia and Chemotherapy Treatment in Intermediate or High Risk Superficial Transitional Cell Carcinoma of the Bladder. Van der Heijden A.G, Kiemeney L.A, Gofrit O.N, Nativ O, Sidi A, Leib Z, Colombo R, Naspro R, Pavone M, Baniel J, Hasner F, Witjes J.A. Eur Urol 46:65-72;2004.

Combined Local Bladder Hyperthermia and Intravesical Chemotherapy for the Treatment of High Grade Superficial Bladder Cancer. Gofrit O.N, Shapiro A, Pode D, Sidi A, Nativ O, Leib Z, Witjes J.A, Van Der Heijden A.G, Naspro R, Colombo R.Urol 63(3):466-471;2004.

Multicentric Study Comparing Intravesical Chemotherapy Alone and With Local Microwave Hyperthermia for Prophylaxis of Recurrence of Superficial Transitional Cell Carcinoma. Colombo R, Da Pozzo L.F, Salonia A, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M. J Clin Oncol. 21:4270-4276;2003.

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Neoadjuvant combined microwave induced local hyperthermia and topical
chemotherapy versus chemotherapy alone for superficial bladder cancer.
J Urol 155:1227-1232;1996. Colombo R, Da Pozzo L.F, Lev A, Freschi M, Gallus G, Rigatti P.

Synergo for chemo-resection:
Thermo-chemotherapy and electromotive drug administration of mitomycin C in superficial bladder cancer eradication. Eur Urol 39:95-100;2001. Colombo R, Brausi M, Da Pozzo L.F, Salonia A, Montorsi F, Scattoni V, Roscigno M, Rigatti P
Medline Abstract, excerpt:
"A higher complete response rate on marker lesion was observed after thermo-chemotherapy compared to other administration methods. CONCLUSION: The intravesical administration of mitomycin C can be safely performed in the form of both thermo-chemotherapy and electromotive drug approach with an increased ablative success rate on small superficial tumor involving only minimal local side effects." .
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Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study.
Di Stasi SM, Giannantoni A, Stephen RL, Capelli G, Navarra P, Massoud R, Vespasiani G. Departments of Urology and Clinical Biochemistry, Tor Vergata University, Via Torrice n. 4, 00189 Rome, Italy; J Urol. 2003 Sep;170(3):777-82. PMID: 12913696
CONCLUSIONS: Intravesical electromotive administration increases bladder uptake of MMC, resulting in an improved response rate in cases of high risk superficial bladder cancer.Medline abstract
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Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors. Colombo R; Da Pozzo LF; Lev A; Salonia A; Rigatti P; Leib Z; Servadio C; Caldarera E; Pavone-Macaluso M
Department of Urology, Scientific Institute H. San Raffaele, Milan, Italy.
J Urol 1998 Mar;159(3):783-7 PMID: 9474148 UI: 98134423 CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed. Medline Abstract
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.Study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrences of superficial tumors of the bladder Mauroy B; Bonnal Jl; Prevost B; Chive M; Lhotellier V; Sozanski JP; Vanseymortier L; Stefaniak X Service Univeritaire d'Urologie, CHU de Lille-Roubaix, France Prog Urol 1999 Feb; 9(1):69-80 PMID: 10212955 UI:99229425 CONCLUSION: A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations. Medline Abstract_______________________________________________
Multicentric Study Comparing Intravesical Chemotherapy Alone and With
Local Microwave Hyperthermia for Prophylaxis of Recurrence of Superficial
Transitional Cell Carcinoma. J Clin Oncol. 21:4270-4276;2003. Colombo R, Da Pozzo L.F, Salonia A, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M. Medline Abstract, excerpt:
"Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. ..In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.
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Combined intravesical hyperthermia and mitomycin chemotherapy: a preliminary in vivo study.Rath-Wolfson L, Moskovitz B, Dekel Y, Kugel V, Koren R. Department of Pathology, Hasharon Hospital, Rabin Medical Centre, Petah-Tikva, Israel Int J Exp Pathol. 2003 Jun;84(3):145-52. PMID: 12974944
Conclusions: [in animal studies] the control group showed similar changes, some less pronounced. The combined treatment of hyperthermia with mitomycin C did not cause major damage to the urinary bladder or adjacent organs. All changes were superficial and reversible, and the control group showed similar changes, some less pronounced. Although this is an experimental model based on one single session treatment, rather than repeated treatments, it suggests that the approach may be useful in future studies both in models and man. Medine abstract
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Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma. Br J Clin Pharmacol 52:273–278;2001. Paroni R, Salonia A, Lev A, Da Pozzo L.F, Cighetti G, Montorsi F, Rigatti P, Colombo R.
Medline Abstract excerpt:
CONCLUSIONS: Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown to cause toxicity. ______________________________________________
Combination of intravesical chemotherapy and hyperthermia for the treatment of superficial bladder cancer: preliminary clinical experience. Crit Rev Oncol Hematol. 47(2):127-39;2003. Colombo R, Salonia A, Da Pozzo L.F, Naspro R, Freschi M, Paroni R, Pavone-Macaluso M, Rigatti P.
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Combined Local Bladder Hyperthermia and Intravesical Chemotherapy for the Treatment of High Grade Superficial Bladder Cancer. Accepted for publication in Urology: 2003. Gofrit O.N, Shapiro A, Pode D, Sidi A, Nativ O, Leib Z, Witjes J.A, Van Der Heijden A.G, Naspro R, Colombo R.
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Future strategies in the diagnosis, staging and treatment of bladder cancer.
Curr Opin Urol 13(5):389-95;2003. Van der Heijden A.G, Witjes J.A.
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Intravesical Chemotherapy: An Update – New Trends and Perspectives.
EAU Update Series 1 (2003) 71-79. Van der Heijden A.G, Witjes J.A.
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Locally induced hyperthermia in bladder cancer. Bladder Cancer: Biology,
Diagnosis and Management, Chapter 22, Oxford Medical Publication, Ed.
K.N. Syrigos & D.G. Skinner, 1999. Rigatti P, Lev A, Da Pozzo L.F, Salonia A, Colombo R.
______________________________________________
Local microwave hyperthermia and intravesical chemotherapy as bladder
sparing treatment for select multifocal and unresectable superficial bladder
tumors. J Urol 159:783-787;1998. Colombo R, Da Pozzo L.F, Lev A, Salonia A, Rigatti P, Leib Z, Servadio C, Caldarera E, Pavone-Macaluso M.
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Plasma mitomycin C concentrations determined by HPLC coupled to solid-
phase extraction. Clin Chem 43:615-618;1997. Paroni R, Arcelloni C, De Vecchi E, Fermo I, Mauri D, Colombo R.
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A new approach using local combined microwave hyperthermia and
chemotherapy in superficial transitional bladder carcinoma treatment.
J Urol 153:959-963;1995. Colombo R, Lev A, Da Pozzo L.F, Freschi M, Gallus G, Rigatti P.
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Combined intravesical chemotherapy with mitomycin C and local bladder
microwave-induced hyperthermia as a preoperative therapy for superficial
bladder tumors - A preliminary clinical study. Eur Urol 20:204-210;1991. Rigatti R, Lev A, Colombo R.
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List of Presentations and Book Chapters - (1991 - 2003)
.
Combined Local Bladder Hyperthermia and Intravesical Chemotherapy for the Treatment of High Grade Superficial Bladder Cancer. Gofrit O.N, Shapiro A, Pode D, Sidi A, Nativ O, Leib Z, Witjes J.A, Van Der Heijden A.G, Naspro R, Colombo R. Presented at the Israel Urology Association Conference, Eilat, 2003.
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Neo Adjuvant Treatment Modality in Intermediate- High Risk Superficial
Transitional Cell Carcinoma of the Bladder Facing Cystectomy:
A Multicenter Study. Presented at the A.U.A annual congress, Chicago, 2003.
Sidi A, Nativ O, Witjes J.A, Pavone-Macaluso M, Alken P, Shapiro A, Leib,
Z, Serretta V, Siegsmund M, Tarnopolsky A, Gofrit O, Van Der Heijden A.G,
Da Pozzo L.F, Salonia A, Wald M, Florio A, De Carolis D, Colombo R.
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Intravesical Chemotherapy alone versus Intravesical Thermo- Chemotherapy for Prophylaxis of Recurrence of Superficial Transitional Cell Carcinoma: A Multicenter Study. Presented at the A.U.A annual congress, Chicago, 2003. Colombo R, Da Pozzo L.F, Salonia A, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M.
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Neoadjuvant Combined Microwave Induced Local Hyperthermia and Topical
Chemotherapy in Superficial TCC of Bladder. Presented at the Israeli Urology Association Conference, Eilat, 2002. Tavdy E, Tarnopolsky A, Benjamin S, Mogutin B, Sidi A.
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Synergo – chemotherapy treatment in patients with refractory bladder TCC.
Presented at the Israel Urology Association Conference, Eilat, 2001. Gofrit O, Wald M, Sidi A, Nativ O, Pode D, Shapiro A.
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Pharmacokinetics of mitomycin C in patients treated with local microwave-
induced hyperthermia. Presented at the XIVthE.A.U. Congress, Stockholm, 1999. Salonia A, Colombo R, Lev A, Da Pozzo L.F, Montorsi F, Rigatti L, Bua L, Rigatti P, Paroni R.
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Adjuvant microwave hyperthermia and mitomycin C versus mitomycin C
alone for superficial bladder cancer. Presented at the XIVth E.A.U. Congress, Stockholm, 1999. (Eur Urol 35(2):39;1999). Colombo R, Da Pozzo L.F, Lev A, Gallus G, Salonia A, Freschi M, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M.
_________________________________________________________
Thermochemotherapy and electromotive drug administration of mitomycin C
in superficial bladder tumors eradication. A clinical trial on marker lesion.
Presented at the XIVth E.A.U. Congress, Stockholm 1999. (Eur Urol 35(2):25;1999). Colombo R, Brausi M, Da Pozzo L.F, Salonia A, Montorsi F, Scattoni V, Raber M, Rigatti P.
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Combined thermo-chemotherapy for recurrent superficial bladder tumors:
Results of a preliminary study using epirubicin. Presented at the XIIIth E.A.U. Congress, Barcelona, 1998. Da Pozzo L.F, Colombo R, Lev A, Salonia A, Rigatti P.
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Studio multicentrico randomizzato mitomicina C vs. mitomicina C + ipertermias endocavitaria nella profilassi delle neoplasie vescicali superficiali. Presented at the Società Italiana di Urologia (S.I.U) Congress, 1998. Da Pozzo L.F, Colombo R, Salonia A, Lev A, Grasso M, Montorsi F, Rigatti P, Gallus G, Leib Z, Baniel J, Caldarera E, Biancorosso M, Pavone-Macaluso M.
_________________________________________________________
Microwave hyperthermia + mitomycin C versus mitomycin C alone in the
prophylaxis of superficial transitional bladder cancer. Presented at the A.U.A. Congress, San Diego, CA, 1998. Da Pozzo L.F, Colombo R, Lev A, Gallus G, Salonia A, Rigatti P, Leib Z, Baniel J, Pavone-Macaluso M, Caldarera E.
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Quantificazione in HPLC della concentrazione plasmatica di mitomicina C in pazienti affetti da neoplasie vescicali superficiali sottoposti a termochemioterapia topica. Presented at the Società Italiana di Urologia (S.I.U) Congress, 1998. Salonia A, Colombo R, Lev A, Da Pozzo L.F, Rigatti D, Pompa P, Rigatti P, Paroni R, Arcelloni C, De Vecchi E, Fermo I.
_________________________________________________________
Bladder sparing treatment combining local microwave hyperthermia and
chemotherapy for multifocal unresectable superficial bladder tumors.
Presented at the A.U.A. Congress, New Orleans, 1997. Da Pozzo L.F, Colombo R, Lev A, Salonia A, Rigatti P, Caldarera E, Pavone-Macaluso M, Leib Z, Servadio C.
_________________________________________________________
Studio multicentrico randomizzato mitomicina C vs. mitomicina C +
ipertermia endocavitaria nella profilassi delle neoplasie vescicali superficiali. Presented at the Società Italiana di Urologia (S.I.U) Congress, 1997. Da Pozzo L.F, Colombo R, Salonia A, Lev A, Grasso M, Montorsi F, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M.
_________________________________________________________
Intravesical microwave-induced hyperthermia and mitomycin C for selected
multifocal unresectable superficial bladder tumors. Presented at the XIIthE.A.U Congress, Paris, 1996. Da Pozzo L.F, Colombo R, Lev A, Rigatti P, Leib Z, Servadio C, Caldarera E, Pavone-Macaluso M.
_________________________________________________________
Mitomycin C (MMC) vs. MMC combined with local microwave hyperthermia
(LMWH) as prophylaxis of recurrence of superficial transitional bladder
cancer: A preliminary report. Presented at the XIIthE.A.U Congress, Paris, 1996. Leib Z, Baniel J, Servadio C, Colombo R, Da Pozzo L.F, Lev A, Rigatti P,
Caldarera E, Pavone-Macaluso M.

Patients are being treated with Synergo at the following institutions:

AUSTRIA
Prof. Bartsch, TILAK Clinic Innsbruck
Prof. Bartsch, Clinic Innsbruck

BELGIUM
Prof. Schulman, Dr. Zlotta, Erasme Hospital, Brussels *
Prof. Schulman, Dr. Zlotta, Erasme Hospital, Brussels *

FRANCE
Prof. Martin, Prof. Colombel, Edouard Herriot Hospital, Lyon *
Prof. Gattegno, Tenon Hospital, Paris *
Prof. Hermanowicz, St Joseph Hospital, Marseille
Prof. Houlgatte, Hôpital d’instruction des armées du Val de Grâce, Paris
Prof. Teillac, Saint-Louis Hospital, Paris *

GERMANY
Prof. Alken, Klinikum Mannheim, Mannheim University Hospital
Prof. Chaussy, Krankenhaus Harlaching, Munich *
Prof. Muschter, Diakoniekrankenhaus Urologie, Rotenburg
Prof. Stenzl, Eberhard Karls University, Tuebingen
Prof. Tunn, City Hospital, Offenbach

ISRAEL
Prof. Baniel, Rabin Medical Center, Petah-Tikva
Dr. Leibovitch, Meir Medical Centre, Kefar-Saba
Prof. Kaneti, Soroka Medical Centre, Be'er-Sheva
Prof. Meretik, Rambam Medical Centre, Haifa
Prof. Nativ, Bnai-Zion Hospital, Haifa *
Prof. Pode, Hadassah University Hospital, Jerusalem *
Prof. Sidi, Wolfson Medical Center, Holon *
Prof. Stein, Carmel Medical Center, Haifa
Prof. Nativ, Bnai-Zion Hospital, Haifa *
Prof. Pode, Hadassah University Hospital, Jerusalem *
Prof. Sidi, Wolfson Hospital, Holon *

ITALY
Prof. Barbieri, Urology Dep., Ospedale C.G. Mazzoni, Ascoli Piceno
Prof. Bassi, Urology Dep., Sacro Cuore Catholic University Hospital "A. Gemelli", Rome
Prof. Conti, Urology Dep. Sant'Anna Hospital, Como
Prof. De Cobelli, Urology Dep. European Institute of Oncology, Milan *
Prof. Maffezzini, Urology Dep. Galliera Hospital, Genoa
Prof. Miano, Urology Dep. St. Andrea Hospital, Rome
Prof. Pavone, University Policlinic Hospital, Palermo *
Prof. Pino, Urology Dep, Treviglio Hosptial, Treviglio
Prof. Rigatti, Dr.Colombo, HSR Hospital, Milan*
Prof. Vavassori, Urology Dep. Humanitas Gavazzeni, Bergamo
Prof. Barbieri, Ospedale C.G. Mazzoni, Ascoli Piceno
Prof. Conti, Urology Dep. Sant'Anna Hospital, Como
Prof. De Cobelli, Urology Dep. European Institute of Oncology, Milan *
Prof. Pavone, University Policlinic Hospital, Palermo *
Prof. Pino, Azienda Ospedaliera, Ospedale di Treviglio
Prof. Rigatti, Dr.Colombo, HSR Hospital, Milan*
Prof. Rocco, Urology Dep. San Paolo Hospital, Milan

SWITZERLAND
Prof. Studer, Dr. Thalmann, Inselpital, Bern
Prof. Studer, Dr. Thalmann, Inselpital, Bern

THE NETHERLANDS
Dr. Oosterhof, Academic Hospital, Maastricht
Dr. van der Meijden, Jeroen Bosch hospital, Hertogenbosch
Prof. Witjes, University Hospital, Nijmegen *
Dr. van Moorselaar, Universitair Medisch Centrum (UMC), Utrecht
Dr. Oosterhof, Academic Hospital AZM, Maastricht

* Centers participating in the clinical study.
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