BLACREST

Bladder Cancer Research Team

About

BLAdder Cancer RESearch Team (BLACREST) is a special operations unit under Department of Clinical Medicine, Aarhus University Hospital.

Our goal is to cover all aspects of bladder cancer from the smallest non-invasive papillary tumors to locally advanced bladder cancer as well as from early detection over different treatment modalities to rehabilitation after major surgery. With this focus, we aim to be among the world leaders in bladder cancer research and set the tone for new treatment methods. 

As a general principle for patients with bladder tumors treated at the Department of Urology, they are offered participation in at least one research project in order to constantly develop the area for the benefit of the individual and future patients.

The Team

The BLACREST consists of a professor and secretary, project nurses, project bioanalysts and PhD students. All are listed below and you are welcome to get in touch.

Professor

Jørgen Bjerggaard Jensen

Professor, Chief of Operations

bjerggaard@clin.au.dk

PhD students

Linea S. Blichert-Refsgaard

PhD student, MD

lineblic@clin.au.dk

Maria Skydt Lindgren

PhD student, MD

msl@clin.au.dk

Maria Ordell Sundelin

PhD student, MD

marisund@clin.au.dk

Thomas Karmark Dreyer

PhD student, MD

thomas@clin.au.dk

Josephine Hyldgaard

PhD student, MD

josehyld@clin.au.dk

Simone B. Brandt

PhD student, MD

simbra@clin.au.dk

Stefanie K. Körner

PhD student, MD

stkoer@clin.au.dk

Erik Hansen

PhD student, MD

erik.hansen@clin.au.dk

Ninna Kjær Nielsen

PhD student, MD

ninna@clin.au.dk

Lene Munk

PhD student, MD

lenemu@rm.dk

Clinical trial coordinators

Anna Munk Nielsen

Clinical Trial Coordinator

annanils@rm.dk

Michael P. Hjørnholm

Clinical Trial Coordinator

micott@rm.dk

Medical laboratory technologists

Jameela Safi

Medical Laboratory Technologist

jamesafi@rm.dk

Birgitte Nielsen

Medical Laboratory Technologist

birgitte.nielsen@aarhus.rm.dk

Professor secretary

Lotte Bjerregaard Snabe

Professor Secretary

lottesnabe@clin.au.dk

Ongoing projects

Read more about our current projects down below or browse our full publication list here

non-muscle-invasive bladder cancer

Diagnosis

Kliniske og funktionelle konsekvenser af fotodynamisk diagnostik (PDD) og intravesical installationsterapi

Blærekræft rammer årligt cirka 2000 personer i Danmark. 75 % diagnosticeres på et tidligt stadie, hvor kræften endnu ikke er vokset ned i blærens muskulatur. Dette kaldes ikke-muskelinvasivblærecancer (NMIBC). Efter behandling opstarter patienterne kontrolforløb med gentagne kikkertundersøgelser af blæren. For nogle er disse kontrolforløb livslange. Den årlige risiko for tilbagefald ved NMIBC er 35 %.

Pga. de gentagne tilbagefald og kontroller er NMIBC en af de dyreste kræftformer fra diagnose til død.

 

I Danmark har de urologiske afdelinger haft forskellige behandlingsstrategier for NMIBC. Der er således forskel på anvendelsen af sporstof (photodynamic diagnosis, PDD) under kikkertoperation og på brugen af kemoterapi til blæreskyllebehandlinger.

 

Formålet med dette PhD-studie er at undersøge, om én behandlingsstrategi for NMIBC er de andre overlegen. Dette både i forhold til antallet af tilbagefald og udvikling i kræftstadiet over tid, men også i forhold til de blæresymptomer og påvirkning af blærefunktionen, som patienterne får pga. behandlingen. Hvis man kan finde en optimal behandlingsstrategi i fht. dette, vil det medføre forbedret patientforløb og dermed øget livskvalitet for denne store patientgruppe fremadrettet.

 

PhD-studiet vil blive udført som dels et registerbaseret nationalt kohorte studie og dels som et deskriptivt studie på en mindre patientgruppe. Patienterne identificeres ud fra nationale databaser, og de danske, urologiske afdelinger klassificeres i forhold til deres behandlingsstrategi ud fra spørgeskemaer. Brugen af blærerelateret medicin anvendes som et surrogat mål for blæresymptomer, mens blærefunktionen bestemmes ved hjælp af en detaljeret blæreundersøgelse (urodynamisk undersøgelse), som udføres af den PhD-studerende på udvalgte patienter.

 

Der er ikke tidligere lavet undersøgelser, som kobler NMIBC-behandling med de følgevirkninger, som patienterne får. Resultaterne af dette PhD-studie forventes derfor at blive essentielle for behandlingsstrategierne for NMIBC fremover.  Således forsøges at opveje fordele og ulemper ved forskellige behandlinger både i forhold til effekt mht tilbagefald, men også mht indflydelse på blærefunktion og dermed livskvalitet.

Contact:

Phd student: Linea Blichert-Refsgaard
Main supervisor: Jørgen Bjerggaard Jensen

Bladder cancer deep learning diagnostics project

Bladder cancer has a high recurrence and progression rate. In order to reduce recurrence rate, knowledge of the tumor grade is essential to perform resection to the correct depth of the layers in the urinary bladder during primary resection of the tumor.

However, visual estimation by the surgeon regarding tumor grade is very poorly correlated to the true tumor grade.
This is the main reason for the high recurrence rate and delay of relevant adjuvant treatment.
Using Deep-learning, we can predict tumor grade during the initial removal of the tumor, offering personalized treatment and thereby reduce recurrence rates.

The project is funded by The Innovation Fund Denmark under the Innoexplorer program. Based on our initial proof of concept CNN-model, the grant covers further development of a more complex CNN-model and the development of a prototype for clinical testing.

Read more https://bc-deeds.com/

Treatment

Neoadjuvant Short-term Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in NMIBC – NICSA

Background:

Bladder cancer is the 11th most common cancer in the world and one of the most costly cancers on a per patient basis, due to the cost of operative procedures, follow-up cystoscopies and instillation therapy. Furthermore there is a risk of progression to invasive and hence deadly cancer why efficient and immediate treatment is crucial. Treatment today consists of surgical removal of tumours (TURB) and adjuvant intravesical treatment. There is a chance; neoadjuvant intravesical treatment with chemotherapy can supersede surgical removal in chemo-sensitive tumours while however some tumours will not respond to intravesical chemotherapy. Currently it is not possible to predict which tumours are chemo-sensitive and which are not.

Objectives:

To assess the efficacy of neoadjuvant, short-term intensive chemoresection with Mitomycin C compared to standard treatment with TURB and adjuvant intravesical instillation therapy in patients with recurrent non-muscle invasive bladder cancer (NMIBC).

To investigate the ability to predict chemo-response in patients with recurrent non-muscle invasive bladder cancer (NMIBC).

Methods:

A randomised clinical controlled trial will include 120 patients with recurrent NMIBC.

The control group of 60 patients will receive standard care with TURB and adjuvant intravesical treatment. The intervention group of 60 patients will be submitted to neoadjuvant short-term intensive chemoresection with three instillations with Mitomycin C per week for two weeks. Remnant tumour tissue will be evaluated by flexible cystoscopy after four weeks.

To investigate the ability to predict chemo-response in patients with recurrent NMIBC, a connection between biomarkers of the initial tumour tissue and tumour response will be assessed.

Samples of the latest resected tumour prior to inclusion will be collected from all participants treated with neoadjuvant chemoresection and assessed against the tumour response seen in the trial.

Perspectives:

Validation of biomarkers to predict chemo-response will be an important step to integrate biomarkers in daily clinical practice and to individualize the treatment of NMIBC.

In some cases surgery could be avoided while ineffective chemotherapy could be avoided in others.

 

Contact:

Phd student: Maria Skydt Lindgren
Main supervisor: Jørgen Bjerggaard Jensen

Den optimale håndtering af T1 blærekræft. Den kliniske relevans for subklassifikation af T1 blærekræft

Baggrund:

Blærekræft er den 10. hyppigste kræftsygdom på verdensplan. I Danmark (DK) diagnosticeres ca. 2000 patienter med blærekræft årligt. Heraf er halvdelen overfladisk voksende polypper, 25% er bindevævs -nvaderende tumorer og 25% er muskel-invaderende tumorer. De overfladisk voksende polypper behandles med fjernelse af polyppen og minimum 5 års kontrol. De muskel-invaderende tumorer behandles med bortoperation af urinblæren (cystektomi) og anlæggelse af tør eller våd urinstomi eller kurativt intenderet strålebehandling. Behandlingen af de bindevævs-invaderende tumores, også kaldet T1 blærekræft (BK), er meget omdiskuteret på verdensplan.

Langt de fleste lande, bl.a. Sverige, behandler T1 BC med bortskrælning af blæretumoren TURB og efterfølgende ambulante blæreskylninger med Bacillus Calmette-Guérin (BCG) vaccine. Regimet for håndteringen af T1 BK i DK adskiller sig betydeligt fra andre landes regimer.

I DK underinddeles T1 BK i to understadier hhv T1a og T1b. T1a er overfladisk invaderende i bindevævet, imens T1b er dybt invaderende i bindevævet. Første gangs T1a BK behandles med TURB og BCG skylninger, imens  gentagende T1a og/eller T1a med samtidig carcinoma in situ behandles med cystektomi. T1b BK behandles med cystektomi. De danske guidelines hvori dette regime anbefales bygger på gamle studier, og underinddelingen i T1a og T1b er meget sparsomt defineret i den danske standard definition (SD). Under forberedelserne til denne Ph.d., blev en ny definition (ND) udviklet, hvori skellet imellem T1a og T1b er mere klart defineret.

Formål: For dette PhD projekt vil der være tre studier, med hver deres formål.

– Studie 1: At undersøge den prognostiske værdi af T1 BK subklassifikation anvendt i DK, samt at undersøge den prognostiske værdi for BCG-skylning hos patienter diagnosticeret med hhv T1a og T1b BK.

– Studie 2: At sammenligne prognosen for patienter diagnosticeret med T1 BK i hhv DK og Sverige.

– Studie 3: At klarlægge den kliniske relevans af ND, samt at undersøge reproducerbarheden af T1 stadiet ved ND.

Metode:

Studie 1: Alle T1 BK patienter i DK diagnosticeret i perioden 1. september 2012 til 31. august 2018 identificeres via Dansk Blære Cancer Database (DaBlaCa-data), sammen med information om subklassifikation, behandling, recidiv, progression og død. Data for T1a patienter vil blive sammenlignet med data for T1b patienter. Primært udfald vil være 1- og 5-års generel- (GO), recidivfri- (RFO) og progressionsfri overlevelse (PFO)

Studie 2: Alle T1 BK patienter fra DK og Sverige for samme periode som i studie 1 vil blive identificeret via hhv DaBlaCa-data og den svenske BladderBaSe sammen med information om behandling, redidiv, progression og død. Data for danske T1 BK patienter vil blive sammenlignet med data for svenske T1 BK patienter. Primært udfald vil være 1- og 5- års GO, RFO og PFO.

Studie 3: Alle patologipræparater diagnosticeret i samme periode som i studie 1, fra  2 store uro-patologiske afdelinger i DK identificeret via DaBlaCa-data. Præparaterne revideres af 2 højt dedikerede uro-patologer i henhold til den nye definition. Patienter der omklassificeres sammenlignes med patienter der opretholder samme subklassifikation.

Statistik:

I studie 1, 2 og 3 vil GO, RFO og PFO blive sammenlignet ved af udføre cox proportional hazard regressions analyser justeret for behandling, køn, alder og komorbiditet. I studie 3 vil interrater agreement blive udregnet vha. Cohen’s Kappa.

Perspektiv:

Studiet forventes at klarlægge hvorvidt T1 BK subklassifikation i T1a og T1b, samt ND, og det danske behandlingsregime skal anbefaler på internationalt niveau. Studiets resultater forventes som minimum af blive publiceret som 3 artikler i internationale peer-reviewed tidsskrifter.

Contact:

Phd student: Erik Hansen
Main supervisor: Jørgen Bjerggaard Jensen

En bloc transurethral resection of non-muscle invasive bladder cancer

Bladder cancer is the tenth most common cancer in the world, and approximately 75% present with non-muscle invasive bladder cancer (NMIBC). The cornerstone in diagnosis and removal of bladder tumours is transurethral resection (TURB) where the tumour is dissected in pieces, removed from the bladder, and then pathologically examined to identify potential detrusor muscle invasion. This method leads to two problems: first, incomplete resection of tumour and possible scattering of tumour cells may lead to recurrence. Second, pathological examination is impaired since tumour margins cannot be properly assessed. Thus, infiltration of suburothelial tissue or detrusor muscle may be underestimated or even missed.

En bloc resection (EBR), where the tumour is removed in total, is supposed to overcome the above mentioned flaws of conventional TURB.

We will conduct a randomised controlled multicentre trial comparing EBR to conventional TURB in patients with non-muscle invasive bladder cancer. We hypothesize EBR to be a superior operation technique to conventional TURB regarding both short-term outcomes, such as pathological assessment quality, as well as long-term outcomes. Primary endpoint will be recurrence free survival.

This study will provide insight whether EBR can improve surgical quality and reduce recurrence rates and thereby costs for patients and society.

Contact:

Phd student: Ninna Kjær Nielsen
Main supervisor: Jørgen Bjerggaard Jensen

Overfladiske blæretumorer er en hyppig blæresygdom, som ofte medfører mange tilbagefald med nye tumorer i blæren på trods af behandling. Derudover er der en risiko for udvikling af ondartet sygdom, hvorfor effektiv behandling er vigtig. Behandling af ikke invasive tumorer i urinblæren er som oftest en operation samt i visse situationer også kemoterapi i blæren. Kemoterapien kaldet Mitomycin gives som ugentlige blæreskylninger i seks på hinanden følgende uger.

Hos enkelte patienter, hvor kirurgi ikke er ønskværdigt, vælger man i stedet at behandle med primær blæreskyllebehandling med kemoterapi. Også her anvendes Mitomycin, som er en cellegift, der hæmmer delingen af celler i urinblæren, og medfører skade på tumorcellerne. Når Mitomycin bruges som primær behandling, administreres blæreskylningerne kortvarigt og intensivt, det vil sige tre gange ugentligt i to på hinanden følgende uger.

Et efterfølgende kontrolforløb for denne patientgruppe består af en kikkertundersøgelse af blæren i lokal bedøvelse enten hver fjerde måned i to år eller i tiltagende intervaller på fire til otte til 12 måneder afhængigt af aggressiviteten af tumoren. I tilfælde af aggressive tumorer udføres der desuden mikroskopi af patientens urinprøve med henblik på vurdering af synlige tumorceller.

For patienterne er behandling og kontrol forbundet med gener og risici, mens det indebærer store omkostninger for hospitalerne. 

Metode

Gennem de seneste år er der blevet udviklet forskellige urinundersøgelser, såkaldte molekylærdiagnostiske tests. Disse tests kan i tilfælde af tumorvæv i blæren finde små tumormolekyler i en urinprøve. Der er store forhåbninger om, at man på sigt kan bruge disse tests i stedet for en kikkertundersøgelse af blæren til at kontrollere for nye tumorer. På samme måde er forhåbningen i dette projekt, at en urintest kan overvåge behandlingseffekten både under og efter behandlingen med primær blæreskyllebehandling.

Rationalet er, at i tilfælde af tilbagefald med tumorer i blæren, vil afstødte celler eller molekyler fra tumoren være at finde i urinen.

Dette projekt har til formål at undersøge om urinundersøgelsesmetoden EpiCheck kan afspejle effekten af pågående behandling med primær kemoterapi i blæren.  

Der forventes at inkludere 22 forsøgsdeltagere i alt. I studiet bruges de urinprøver, som patienten afleverer i forbindelse med et behandlingsbesøg. I studiet vil vi indsamle og anvende disse til EpiCheck testen. Hvis EpiCheck testen er postitiv for en patient før behandlingens start, gentages testen fire gange i behandlingsforløbet. Hvis EpiCheck testen er negativ, foretages der ikke yderligere undersøgelser i studiet. 

Perspektiver

Hvis det viser sig, at testen kan bruges til at vurdere behandlingseffekten, vil der på sigt være mulighed for at undgå såvel kikkertundersøgelser som blæreskylninger. Sidstnævnte undgås, idet man kan afbryde behandlingen, når testen bliver negativ i stedet for at gennemføre den komplette serie. Mængden af og størrelsen på tumorer varierer fra patient til patient, og derfor vil det være en fordel at kunne tilpasse behandlingen til den enkelte. På den måde undgås enkelte behandlingsbesøg, som både kan være tidskrævende og ledsages af bivirkninger.

 

Approximately 8,000 patients are diagnosed with bladder cancer (BC) in the Nordic countries every year. The majority of BC patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). The majority of NMIBC are treated with Bacillus Calmette-Guérin vaccine (BCG) as adjuvant treatment but for carcinoma in situ it is the primary treatment. BCG is known to give a lot of side effects both local and systemic, the severity of these can lead to premature termination of the treatment.

The object of this PhD project is to investigate if reduced dwell time, the time the BCG is in the bladder, will decrease the severity of side effects due to BCG instillations.

This will be investigated in a Nordic setting and the project will be done as a two-armed randomized clinical trial. 

By decreasing the severity of side effects, we hypothesize the number of patients completing all planned instillations will increase and thereby decrease the risk of the BC evolving into a more aggressive type.

Contact:

Phd student: Lene Munk

Clinical trial coordinator: Michael P. Hjørnholm

Main supervisor: Jørgen Bjerggaard Jensen

Follow-up

Surveillance of High-grade Non-muscle Invasive Bladder Tumours Using the Xpert Bladder Cancer Monitor – SEALS Xpert

Epidemiology and treatment Bladder cancer is the 12th most diagnosed cancer worldwide with an incidence of approximately 550 000 new cases each year.1 A majority of the tumors are characterized as non-muscle invasive bladder cancer (NMIBC), meaning stage T1 according to the 2016 TNM-classification.2 Treatment of primary NMIBC is transurethral resection of the bladder (TUR-B) and treatment of recurring NMIBC is repeated TUR-B and often adjuvant instillation therapy with either Mitomycin C or Bacillus Calmette-Geerin (BCG) according to the histology of the tumor. NMIBC-tumors are graded into high grade (HG) and low grade (LG) according to the histological characteristics of their TUR-B specimen. Generally, intravesical Mitomycin C is recommended to treat LG tumors and intravesical BCG is recommended for treating HG tumors.3,4.

Follow-up schedules based on risk of recurrence. The histological grade, number of tumors, tumor size, T-stage, recurrence-rate and presence of carcinoma in situ (CIS) is used to estimate risk of recurrence according to the EORTC-scoring system. Based on the risk stratification, different follow-up schedules after initial TUR-B are planned. High risk tumors are followed-up with flexible cystoscopy and urinary cytology every four months until two recurrence-free years, whereas low and intermediate risk tumors are followed utilizing the 4-8-12 model where intervals between follow up are increased for patients without recurrence until 5 disease-free years.3 The evidence behind these follow-up schedules is not based on high level evidence and research but rather on tradition and ‘clinical experience’.

Clinical challenge of current follow-up schedules The majority of patients with HG tumors will have recurrence despite treatment, especially within the two first years after diagnosis. Moreover, many patients will receive lifelong follow-up cystoscopy and urinary cytology tests. Follow-up schedules are costly due to many visits at the hospital for flexible cystoscopy, urinary cytology, and treatment. A micro-costing analysis performed by the Urological Research Unit at Aarhus University Hospital prior to initiation of the current study, has shown that the total expense in relation to flexible cystoscopy in the outpatient clinic is approximately 315 EUR per examination (Appendix 1). Equally important to frequency and cost of follow-up, every follow-up visit is associated with patient discomfort, pain, risk of infections, and strictures of the urethra.6 Each cystoscopy carries a 15% risk of complications. Nearly 1,500 cystoscopies are carried out in HG patients in Central Denmark Region each year, resulting in approximately 240 complications each year, with cystitis being the most common complication. Furthermore, flexible cystoscopy is not always reliable in terms of diagnosing recurrences and CIS.7-9

Urinary biomarkers A proposed alternative to flexible cystoscopy in the detection of recurrent NMBIC is non-invasive molecular urinary markers that detect mRNA, protein or DNA from selected genes relevant for bladder cancer in urine samples. Several studies have been prospectively validated and shown high sensitivity and specificity for urinary markers.10,11 Recently, the Xpert Bladder Cancer Monitor test was shown by Valenberg et al.12 to have a sensitivity of 83% and specificity of 76% for HG disease and similarly D’Elia et al.13 showed a specificity of 77% and sensitivity of 46% for a cohort of mainly LG patients. However, studies have until now focused mainly on detection of NMIBC in patients with incident tumors, which are most often larger and more easily diagnosed with urinary biomarkers than recurrences.14 To our knowledge, no studies have so far substituted cystoscopies for urinary biomarkers in a randomized controlled setting. Thus, the need for high level evidence regarding the use of urinary biomarkers for surveillance of NMIBC is still there.

Contact:

Phd student: Thomas Karmark Dreyer

Clinical Trial Coordinator: Anna Munk

Main supervisor: Jørgen Bjerggaard Jensen

muscle-invasive bladder cancer

Diagnosis

Complete Local Response to Neoadjuvant Chemotherapy in Patients With Muscle Invasive Bladder Cancer Evaluated by 15O-H2O PET/MR – MAINTAIN

For patients with MIBC treated with NAC and radical cystectomy there is currently no good way of evaluating whether the patient is true T0 or has remnant tumor in need for consolidating radical treatment. Methods for better selection of patients that potentially can avoid cystectomy is therefore needed.

15O-labeled water (H2O) is the gold standard for PET quantification of regional tissue perfusion. 15O-H2O has been validated as a freely diffusible tracer for measuring perfusion in the myocardium and cerebral blood flow and 15O-H2O PET is the golden standard for noninvasive imaging to quantify tumor blood flow (TBF).

Method: Patients scheduled for NAC followed by radical cystectomy due to histologically documented MIBC stage cT2-4a in the urinary bladder will be included. A 15O-H2O PET/MR scan will be performed at time of inclusion (baseline) and again after NAC prior to cystectomy.

Hypothesis: We hypothesize that changes in tumor architecture and perfusion estimated with 15O-H2O PET/MR measurements and clinical evaluation during NAC can identify patients with complete local response to chemotherapy and therefore select patients to avoid radical cystectomy.

Perspectives: This study will be the first to use 15O-H2O as tracer in bladder cancer. If proven efficient, evaluation of patients undergoing NAC with 15O-H2O PET/MR could potentially safely select patients for a true bladder sparring approach and potentially give some patients the choice of chemotherapy monotherapy, or in combination with other systemic oncological treatments like immunotherapy. If successful, this should be followed by randomized studies to document the clinical benefit and potentially reduce cost and increase quality of life by safely selecting patients for bladder sparring treatment of bladder cancer.

Contact:

Phd student: Stefanie Korsgaard Körner
Main supervisor: Jørgen Bjerggaard Jensen

Treatment

Influence of Hormone Treatment in Radiation Therapy for Bladder Cancer

Bladder cancer (BC) is one of the most frequent cancers in the world and more common in men than female. Gender-related factors may be involved in the pathogenesis of BC.

Studies have suggested that androgen-receptors may be present in the bladder and potentially involved in BC aetiology, thus making BC susceptible for androgen deprivation therapy (ADT).

Currently treatment for BC includes surgery or radiation therapy. ADT include Degarelix, which besides decreasing testosterone, has been shown to reduce the occurrence of BC in rats and promote stem cell recovery following radiation therapy.

Hypothesis ADT will lower the incidence of BC, and the prognosis of BC will vary depending on the type of ADT used. Furthermore Degarelix administered during radiation therapy for BC will reduce the degree of fibrosis in the bladder thus decreasing adverse side effects.

Methods A cohort of patients treated with ADT for PC will be compared to two cohorts of age-matched men with and without PC both without ADT. The incidence of BC will be recorded for every group. Furthermore the cohort of patients with PC and ADT will be divided into subgroups, depending of the type of ADT they have received and the degree of deprivation. They will be compared in terms of incidence and prognosis of BC.

Finally, a small pilot study will be conducted to investigate the effect of Degarelix when administered during radiation therapy for BC.

Perspectives This will be one of the largest studies to investigate the potential influence of sex hormones in the development and prognosis of BC and potentially lead to new treatment options and possibly a new way of reducing radiation side effects.

Contact:

Phd student: Josephine Maria Hyldgaard
Main supervisor: Jørgen Bjerggaard Jensen

Modified Urinary Conduit to Lower Strictures After Radical Cystetomy – MOSAIC

Cystectomy is the chosen treatment of bladder cancer in 400 cases every year in DK. In replacement of the removed bladder, a urinary diversion is constructed using 15cm of terminal ilium (Ad Modum Bricker).

Ureteral strictures are diagnosed in 15% of the cystectomized patients, and these patients are at increased risk of infections, loss of renal function and repeated interventions. The left ureter is diagnosed with 70% of all strictures, presumably due to the construction of the urinary diversion.

A modified urinary diversion have been tested in two small studies. The modified diversion is prolonged with 5cm compared to the conventional urinary diversion. The prolongation permits the urinary diversion to reach both the left and the right side of the abdomen, resulting in greater resection of non-viably distal ureter and less mobilization of the left ureter, lowering the rates of strictures.

 

Contact:

Phd student: Simone Buchardt Brandt
Main supervisor: Jørgen Bjerggaard Jensen

Endo-GIA Versus Endowrist Stapler in Intracorporeal Urinary Diversion in Robotic Assisted Radical Cystectomy – EGIAES

Cystectomy with urinary diversion is the standard treatment of muscle invasive and high risk non-muscle invasive bladder cancer. During cystectomy, a urinary diversion is constructed from a bowel segment. Restoration of the intestinal continuity is therefore an obligate part of the procedure.

In Denmark, approximately 400 radical cystectomies are performed yearly with the majority of procedures performed as a laparoscopic robot assisted procedure. This includes urinary diversion by means of intracorporeal procedure.

During current standard intracorporeal urinary diversion, an Endo-GIA stapler is handled by the assisting surgeon and not by the main surgeon as the Endo-GIA stapler is not integrated into the robot.

The traditional Endo-GIA anastomosis is made as a side-by-side anastomosis with two 60 mm magazines: one for the side-to-side anastomosis and one for closing the end.

Any reduction in the lumen of the anastomosis will clinically affect post-operative bowel function. It is known that at all cystectomy patients have intestinal paralysis / lack of normal bowel function in the first days postoperatively. It is thus plausible that a wider anastomosis will be able to reduce the duration of this in favor of the patient’s post-operative nutrition, postoperative length of stay and convalescence.

A stapler integrated in the robot (Endowrist stapler from Intuitive) is available. This has several advantages: it is operated by the robotic surgeon and not by the assistant, it is more flexible, and faster mobility. These advantages provide the possibility of precisely removing a minimal intestinal segment by the final transverse stapling. The biggest disadvantage of the robot-operated Endowrist staple is that it is not available in a 60 mm version but only in 45 mm, thus giving only an anastomosis of approximately the same lumen as using a 60 mm Endo-GIA staple but not better.

An opportunity to make a more spacious anastomosis would be to “prolong” the longitudinal stapling as to the side-to-side anastomosis between the intestinal segments. This requires precise and coordinated handling of bowel graspers and staplers to make a complete elimination of the risk of anastomosis leakage, which in this respect is an advantage of robot-operated staples with the Endowrist stapler rather than an assistant handled stapler with Endo-GIA.

Both Endo-GIA and Endowrist stapler are approved for clinical use according to the procedures described.

 

Contact: 

Professor Jørgen Bjerggaard Jensen

Follow-up

Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy – TOMBOLA

Immunotherapy (checkpoint inhibitors) is approved as first and second line treatment to patients with metastatic bladder cancer. However, response rates are low and no biomarkers have yet shown strong predictive value for patient selection. Moreover, the term ‘metastatic’ is based on metastases visible on conventional CT scans and, thus, require a certain size of tumour load. Clinical trials are currently being conducted that investigate the use of adjuvant immunotherapy for this group of patients (treatment to all), which will result in massive over-treatment and huge costs to the healthcare system.

This project has the primary objective to identify new indications for initiating immunotherapy in patients with metastatic bladder cancer. Sensitive molecular techniques for detection of tumor DNA in the blood will be used to identify patients with early signs of metastatic disease. In addition, comprehensive biomarker analysis will be performed to identify predictors of treatment response.

Contact:

Professor Jørgen Bjerggaard Jensen and clinical trial coordinator Anna Munk

Klinisk relevante biomarkører til forudsigelse af sygdomsforløb og terapirespons hos patienter med blærekræft er stadig ikke blevet identificeret trods en intensiv forskningsindsats. Nye teknologiske fremskridt indenfor kortlægningen af vores arvemasse (genom) har gjort det muligt at identificere genomiske ændringer, som er specifikke for den enkelte patients tumor. Det er derfor nu muligt at bruge disse teknologiske fremskridt til bedre kontrol af den enkelte patients sygdom.

Dette projekts formål er vha. ”Next Generation Sequencing” (NGS) at identificere mutationer og genomiske ændringer i genomet i tumorer fra patienter med blærekræft. Ændringerne vil blive anvendt som patient-specifikke markører til at følge sygdomsudviklingen over tid. De specifikke formål med projektet er:

Identifikation af specifikke markører til test af urinprøver hos patienter med ikke muskelinvasiv blæretumor som følges med cystoskopiundersøgelser

Identifikation af specifikke markører til test af blodprøver hos patienter med muskelinvasiv blærekræft behandlet med neoadjuvant kemoterapi og efterfølgende cystektomi

Identifikation af specifikke markører til test af blodprøver hos patienter med avanceret muskelinvasiv blærekræft behandlet med kemoterapi 

Med dette projekt vil vi belyse, om det er muligt at identificere sygdomstilbagefald og sygdomsforværring på et tidligere tidspunkt vha. urin og blodprøver, og dermed forbedre overlevelsen for patienter med blærekræft. Yderligere vil vi undersøge om vi, vha. personlige biomarkører, kan undgå gentagne kikkertundersøgelser af blæren, og dermed spare patienterne for smerter og bivirkninger ved dette, samt spare store udgifter forbundet med de nuværende kontrolundersøgelser. Desuden vil vi med projektet belyse, om vi kan identificere spredning af sygdommen tidligere. Dermed vil man kunne igangsætte kemoterapi på et tidligere tidspunkt, hvilket ultimativt vil kunne forbedre patienternes overlevelse. Endelig vil måling af kemoterapi-effektivitet ultimativt sikre, at patienterne tilbydes den relevante behandling.  

Contact:

Professor Jørgen Bjerggaard Jensen and clinical trial coordinator Anna Munk

Nordic cystectomy biomarker validation study – NorCys

Muscle-invasive bladder cancer (BC) is an aggressive malignancy and radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the gold standard of therapy. In addition to surgery, neoadjuvant chemotherapy (NAC) is recommended for patients who are fit for cisplatin-based chemotherapy based on results from prospective trials. In the Nordic countries approximately 7.200 new BC cases are diagnosed annually and mortality is 2.100 cases per year. We estimate that about 1.200 RCs are performed due to MIBC in Nordic countries per year.

Currently the tools for estimating prognosis and risks are insufficient and improved ones are needed.

The rationale for the study is to gather, in a prospective, multi-institutional and international design, data of patients undergoing RC for MIBC in Nordic countries. The collected data will be used with the aim of validating existing prediction tools and discover novel tools for 1) prediction of morbidity related to RC, 2) prediction of oncological outcome after RC, and 3) prediction of response to NAC prior to RC. The hypothesis is that with this study we can meet the abovementioned aims and develop a well-documented model for prediction of individual patient outcome regarding RC. 

This study is in collaboration with all the Nordic countries, through the Nordic Urothelial Cancer Research Group, led by Peter Boström, Cheif at the Department of Urology at Turku University Hospital, Finland.

Read more: http://north-reg.nu/

Contact:

Professor Jørgen Bjerggaard Jensen, PhD student Simone Buchardt Brandt and clinical trial coordinator Anna Munk

 

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