Hexaminolevulinate Articles

Articles

  • [Cost-effectiveness analysis of blue light cystoscopy with hexylaminolevulinate in transurethral resection of the bladder].

    Photodynamic diagnosis using the optical imaging agent hexaminolevulinate (HAL, Hexvix®, Ipsen Pharma GmbH, Ettlingen, Germany) as an adjunct to white light cystoscopy (WLC) during the initial transurethral resection of bladder tumours (TURB) improves the detection rate of bladder cancer and leads to fewer recurrences.

    Published April 27, 2018
  • Bladder Cancer Diagnosis & Detection

     Non–muscle invasive bladder cancer (Ta, T1, and CIS), describes malignant urothelial tumors that have not invaded the detrusor.  

    • Approximately 70% of malignant bladder tumors are non–muscle invasive at presentation. (70% present as stage Ta, 20% as T1, and 10% as CIS).

    Signs and Symptoms Bladder Tumors

    • The common symptoms of localized disease (hematuria, dysuria).
    • Microscopic hematuria is associated with a 0.5% to 10.5% rate of bladder cancer.
    • Patients with macroscopic (gross) hematuria have reported rates of bladder cancer of 13% to 34.5%. 
    • The presence of irritative voiding symptoms may double the risk, especially for CIS (5% vs. 10.5%).
    • About 15% of patients are asymptomatic at presentation and are diagnosed when an incidental lesion is found on radiologic evaluation. 
    • Cystoscopy and upper tract imaging are indicated in patients with hematuria and/or unexplained irritative symptoms.
    • Low-grade Ta lesions are low risk, whereas all high-grade lesions (including CIS) have a high risk of progressing.
    • Patients may also present with symptoms of advanced disease, including flank or abdominal mass, weight loss, anorexia, and bone pain. 

    Consideration in the Diagnosis of Bladder Cancer

    • Recurrence is common in all patients with non–muscle-invasive urothelial cancer but can often be controlled successfully with transurethral surgery, intravesical therapy, or a combination. 
    • In contrast to recurrence, patients can be divided into low or high risk for progression, which is the true concern. 
    • Low-grade Ta lesions are low risk, whereas all high-grade lesions (including CIS) have a high risk of progressing.
    • Low-grade Ta lesions recur at a rate of 50% to 70% and progress in approximately 5% of cases. 
    • In contrast, high-grade T1 lesions recur in more than 80% of cases and progress in 50% of patients within 3 years. 
    • This behavior is primarily grade, rather than stage, dependent, because patients with high-grade tumors progressed with similar frequency regardless of whether they were invasive (T1) or noninvasive (Ta).
    • Prognosis also correlates with tumor size, multiplicity, papillary versus sessile configuration, presence or absence of lymphovascular invasion, and status of the remaining urothelium.
    • The variance in biologic behavior for low-grade versus high-grade lesions correlates with the known dual molecular lines of genetic development for these two pathways and supports the concept that high-grade and low-grade cancers may be considered as essentially different diseases.
    • Chromosomal alterations caused by oxidative DNA damage create two separate genetic pathways to the development of UC.
    • The first and more common (low grade) leads to noninvasive, papillary tumors. 
    • These usually follow an indolent course unless they convert to or are associated with a tumor of the second pathway.
    • The second pathway leads to the development of high-grade cancer including CIS, T1, and, ultimately, muscle-invasive carcinoma.
    • High-grade tumors tend to have numerous and greatly variable chromosomal gains and losses. 
    • In addition to their relatively predictable aneuploidy, high-grade tumors can also lose all or part of chromosome 9.
    • Because of these differing genetic imprints, it has been suggested that papillary pTa tumors could almost be considered benign and might be a completely separate disease entity in contrast to high-grade tumors.
    • High-grade and low-grade lesions are known to coexist. 
    • UC is traditionally considered a field change disease, with tumors arising at different times and sites. 
    • Rarely, patients who initially have low-grade tumors will subsequently develop high-grade tumor. 
    • Long-term surveillance is usually reasonable.

    Detection of Urothelial Bladder Tumors

    • Painless gross hematuria occurs in 85% of patients with bladder cancer and requires a complete evaluation that includes cystoscopy, urine cytology, CT scan, and a PSA blood test.
    • Patients with microscopic hematuria require a full evaluation, but low-risk patients do not require repeat evaluations. High-risk individuals primarily are those with a smoking history and should be evaluated every 6 months.
    • White light cystoscopy with random bladder biopsies is the gold standard for tumor detection. 
    • White light cystoscopy has an excellent sensitivity and specificity for papillary tumors but is relatively poor for CIS. 
    • Cystoscopy with blue light may be more sensitive in the detection of CIS.  
    • Porphyrin-induced fluorescence cystoscopy uses photoactive porphyrins, such as hexaminolevulinate, that accumulate preferentially in neoplastic tissue and emit red fluorescence under blue-wavelength light. 
    • This may improve the detection of small papillary lesions and CIS.
    • There are various urine markers that evaluate secreted proteins or shed cells in the hope of noninvasively detecting bladder cancer. 
    • None of these markers to date have a high enough sensitivity or specificity to replace office cystoscopy.  
    • NMP-22 is commonly used along with cystoscopy in approximately 10% of patients.

    References

    • Epstein JI, Amin MB, Reuter VR, Mostofi FK: The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol  1998; 22:1435-1448.
    • Golin AL, Howard RS: Asymptomatic microscopic hematuria. J Urol  1980; 124:389-391.
    • Grossfeld GD, Wolf Jr JS, Litwan MS, et al: Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. Am Fam Physician  2001; 63:1145-1154.
    • Grossman HB, Soloway M, Messing E, et al: Surveillance for recurrent bladder cancer using a point-of-care proteomic assay. JAMA  2006; 295(3):299-305.
    • Harnden P: A critical appraisal of the classification of urothelial tumours: time for a review of the evidence and a radical change?. BJU Int  2007; 99(4):723-725.
    • Herr HW: Tumor progression and survival of patients with high grade, noninvasive papillary (TaG3) bladder tumors: 15-year outcome. J Urol  2000; 163:60-61.discussion 61–62.
    • Herr HW, Donat SM: A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences. BJU Int  2008; 102(9):1111-1114.
    • Khadra MH, Pickard RS, Charlton M, et al: A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol  2000; 163:524-527.
    • Kiemeney LA, Witjes JA, Verbeek AL, et al: The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group. Br J Cancer  1993; 67:806-812.
    • Kunju LP, You L, Zhang Y, et al: Lymphovascular invasion of urothelial cancer in matched transurethral bladder tumor resection and radical cystectomy specimens. J Urol  2008; 180(5):1928-1932.
    • Lee LW, Davis Jr E: Gross urinary hemorrhage: a symptom, not a disease. JAMA  1953; 153:782-784.
    • Lotan Y, Gupta A, Shariat SF, et al: Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol  2005; 23:6533-6539.
    • Mohr DN, Offord KP, Owen RA, et al: Asymptomatic microhematuria and urologic disease: a population-based study. JAMA  1986; 256:224-229.
    • Murphy WM, Crabtree WN, Jukkola AF, Soloway MS: The diagnostic value of urine versus bladder washing in patients with bladder cancer. J Urol  1981; 126(3):320-322.
    • Richter J, Jiang F, Gorog JP, et al: Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization. Cancer Res  1997; 57:2860-2864.
    • Ro JY, Staerkel GA, Ayala AG: Cytologic and histologic features of superficial bladder cancer. Urol Clin North Am  1992; 19:435-453.
    • Sauter G, Mihatsch MJ: Pussycats and baby tigers: non-invasive (pTa) and minimally invasive (pT1) bladder carcinomas are not the same!. J Pathol  1998; 185:339-341.
    • Smith Jr JA, Labasky RF, Cockett AT, et al: Bladder cancer clinical guidelines panel summary report on the management of non–muscle-invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association. J Urol  1999; 162:1697-1701.
    • Soloway MS, Briggman V, Carpinito GA, et al: Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J Urol  1996; 156:363-367.
    • Sultana SR, Goodman CM, Byrne DJ, et al: Microscopic hematuria: urological investigation using a standard protocol. Br J Urol  1996; 78:691-698.
    • Tissot WD, Diokno AC, Peters KM: A referral center's experience with transitional cell carcinoma misdiagnosed as interstitial cystitis. J Urol  2004; 172:478-480.
    • Varkarakis MJ, Gaeta J, Moore RH, et al: Superficial bladder tumor: aspects of clinical progression. Urology  1974; 4:414-420.
    Published April 10, 2012
  • Hexaminolevulinate hydrochloride blue-light flexible cystoscopy in the detection and follow-up of nonmuscle-invasive bladder cancer: cost consequences during outpatient surveillance in Sweden.

    AIM - This study explored the cost consequences of introducing hexaminolevulinate hydrochloride-guided blue-light flexible cystoscopy (HAL BLFC) as an adjunct to white-light flexible cystoscopy compared with white-light flexible cystoscopy alone, for the detection and management of nonmuscle invasive bladder cancer in Sweden.

    Published April 4, 2016
  • Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder.

    Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment.

    Published April 17, 2016
  • Impact of photodynamic diagnosis-assisted transurethral resection of bladder tumors on the prognostic outcome after radical cystectomy: results from PROMETRICS 2011.

    Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC).

    Published June 22, 2016
  • Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect.

    The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance.

    Published August 15, 2017
  • Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine.

    To evaluate the feasibility of hexaminolevulinate (HAL) for the photodynamic detection of cancer cells in voided urine.

    This study included 50 patients with bladder cancer that was confirmed histologically after transurethral resection (bladder cancer group) and 50 outpatients without a history of urothelial carcinoma or cancer-related findings (no malignancy group).

    Published July 24, 2017
  • Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non-Muscle Invasive Bladder Cancer.

    Introduction: Although there is evidence that hexaminolevulinate (HAL)-based transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non-muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is uncertainty about its beneficial effects on progression.

    Published May 1, 2019
  • The Impact of Blue Light Cystoscopy on the Diagnosis and Treatment of Bladder Cancer.

    Photodynamic diagnostic technique with blue light cystoscopy (BLC) takes advantage of the preferential uptake and accumulation of protoporphyrins in neoplastic tissue which emit a red fluorescence when illuminated with blue light (360-450 nm wavelengths).

    Published March 29, 2017
  • The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis.

    Background: The International Bladder Cancer Group (IBCG) recently proposed a new definition of disease progression in non-muscle invasive bladder cancer (NMIBC), including change in T-stage, change to T2 or higher or change from low to high grade.

    Published May 1, 2019
  • The prognostic impact of hexaminolevulinate-based bladder tumor resection in patients with primary non-muscle invasive bladder cancer treated with radical cystectomy.

    To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC).

    Published May 22, 2019
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