Photodynamic Diagnosis in Non–Muscle-Invasive Bladder Cancer: A Systematic Review and Cumulative Analysis of Prospective Studies

Context

The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially.

Objective

To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non–muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection.

Evidence acquisition

An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction.

Evidence synthesis

The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8–35) more tumour-positive patients were detected with PDD in all patients with non–muscle-invasive tumours and 39% (CI, 23–57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15–0.52; p < 0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002).

Conclusions

PDD detects more bladder tumour–positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

INTRODUCTION: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED. METHODS: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire. RESULTS: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity. CONCLUSIONS: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.     

The Prognostic Value of Prothrombin Time in Predicting Survival after Major Trauma: a Prospective Analysis of 1,351 Patients from the German Trauma Registry

Background: Early assessment of the individual trauma load in major trauma patients is difficult. A simple and reliable prognostic factor already available in the emergency room would help the emergency physician to make appropriate therapeutic decisions, e. g., when and how to operate on major fractures. The aim of the study was to evaluate the prognostic value of prothrombin time (PT). Patients and Methods: The German Trauma Registry is a prospective, standardized and anonymous documentation of severely injured patients. 3,814 patients were included in the registry. 1,351 patients with an Injury Severity Score (ISS) h 16 and complete data for specific variables (PT, Trauma Score + Injury Severity Score [TRISS], survival until discharge) were included in the study. The PT was measured on the patient's arrival in the emergeny room. Three different analyses were performed. 1. According to clinical judgment, three groups of patients were compared (PT S 60%, PT 40-59%, PT < 40%). A univariate analysis compared therapeutic interventions and outcome variables between the three groups. 2. A receiver-operator-characteristic (ROC) curve analysis compared the performance of PT with the prognostic standard TRISS. 3. A multivariate logistic regression was performed in order to evaluate PT as an independent prognostic variable. Results: PT values showed a good inverse correlation with the severity of injury and the level of therapeutic interventions. The ROC analysis as well as the regression revealed PT as a significant prognostic factor although it showed a slightly worse performance compared to TRISS. Conclusions: As PT, in contrast to TRISS, is readily available already in the emergency room, it can be used as a screening variable for the assessment of a patient's trauma load and thereby help in the decision-making for further operative treatment of major trauma patients.     

Incidence and Prognosis of Organ Failure in Severely Injured Children and Adult Patients

Abstract Background: Does there exist a difference in the outcome of severely injured children and severely injured healthy adults? Methods: The data of 1,566 severely injured patients, treated between May 1998 and December 2002 in our emergency department of the University Essen/Germany, were analyzed. Patients with an injury severity score (ISS) > 24 were included in the present study. Patients younger as 18 (17) years were located to the children group c. Patients aged 18 and up to the age of 54 were included in the adult group a. Results: Fifty-four children and 252 adults met the selection criteria. ISS and the Glasgow coma scale (GCS) before intubation were not statistically different in both groups. Seriously injured children stayed significantly shorter on the intensive care unit, required significantly less ventilator days. Furthermore, the incidence of single organ failure (SOF) and multiple organ failure (MOF) was significantly lower in the children group. Mortality in the children group (29.6%) was lower than that in the adult group (33.7%). There was no death due to MOF in the children group as compared to 2.4% (n = 6) in the adults. Conclusion: The incidence of SOF and MOF was significantly lower in the children group although there was no difference in ISS, GCS and injury patterns. The prognosis of severely injured children was found to be better than those of adults. Moreover, there was no death due to MOF in the children group.     

Experimental external irradiation of corneal neovascularization

The clinical effect of ionidizing radiation on ocular neovascularizations is controversial not only because of the variety of treatment modalities. The aim of our study was to investigate an experimental model which allows to evaluate radiation parameters and to study the mechanism of the inhibitory effect on neoangiogenesis. METHODS: Corneal angiogenesis was induced by use of a micropocket assay in NZW rabbits. Pellets with 500 ng bFGF in 2% methylecellulose were implanted into the stroma 2.0 mm from the limbus. Initiation of vessel growth occurred on day 3. At this time radiation was performed with different doses (single dose of 15 to 30 Gy or fractionated 5 x 5 Gy) using a 6 MeV linear accelerator. Vascular growth was quantified. RESULTS: Irradiation with a total dose of 25 Gy applied in a fractionated regimen or as single-dose irradiation on the day of surgery or on day 6 after surgery did not significantly reduce neovascular growth. In contrast, postoperative radiation therapy on day 3 was able to reduce the area of ingrowing vessels significantly (P < 0.01). In spite of the relatively high dose there were no significant side effects during the observation period of 8 weeks. CONCLUSION: Our results show that single-dose radiation (> or = 25 Gy) is sufficient to inhibit the growth of corneal neovascularizations. With this model it might be possible to investigate parameters for therapy of ocular neovascularizations as well as the underlying mechanisms.     

Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings

PURPOSE: To evaluate the safety and efficacy of gadoxetic acid disodium-enhanced magnetic resonance (MR) imaging for the detection of focal liver lesions, with results of histopathologic examination and/or intraoperative ultrasonography used as a standard of reference. MATERIALS AND METHODS: One hundred sixty-nine patients who were known to have or suspected of having focal liver lesions and were scheduled for liver surgery were included in this study. Results in 131 patients could be included in the efficacy analysis. MR imaging was performed before and immediately and 20 minutes after bolus injection of 0.025 mmol/kg of the liver-specific hepatobiliary contrast agent gadoxetic acid. T1-weighted gradient-echo (with and without fat saturation and including dynamic data sets) and T2-weighted fast spin-echo/turbo spin-echo sequences were performed. All images were evaluated on site and by three independent and blinded off-site reviewers. Lesion matching based on the standard-of-reference results was performed. Differences in lesion detection with precontrast and with postcontrast MR images were assessed with the two-sided Wilcoxon signed rank test. RESULTS: Gadoxetic acid was well tolerated. In the on-site review, the number of patients in whom all lesions were correctly matched increased from 89 of 129 patients at precontrast MR imaging to 103 of 129 patients at postcontrast MR imaging. In the off-site evaluation, the number of patients in whom all lesions were correctly matched and the corresponding sensitivity values increased from 72 (55.8%), 68 (52.7%), and 66 (51.2%) with the precontrast images to 88 (68.2%), 69 (53.5%), and 76 (58.9%) with the postcontrast images for readers 1, 2, and 3, respectively. Two of the three blinded readers showed a statistically significant difference in lesion detection between precontrast and postcontrast MR imaging (P <.001 and P =.008). A large number of additionally correctly detected and localized lesions were smaller than 1 cm. CONCLUSION: MR imaging with gadoxetic acid is safe and improves lesion detection and localization.     

Quality of life and comorbidity in localized malignant melanoma: results of a German population‐based cohort study

Background Incidences of malignant melanoma continue to increase in fair‐skinned populations. At least 80% of patients are diagnosed with localized disease and can expect a 5‐year relative survival rate of >90%. Given that the median age at diagnosis of malignant melanoma is 59 years, many patients already suffer chronic diseases when they are confronted with cancer. Objectives The aim of this study was to analyze the effect of additional chronic diseases on health‐related quality of life (QoL) in a population‐based cohort of melanoma patients two years after presumably curative treatment. Methods In 2003–2004, 1085 patients with localized malignant melanoma were recruited from the population‐based Munich Cancer Registry to answer validated QoL questionnaires. Information about comorbidities was also obtained. Factors predicting QoL were analyzed using multivariate logistic regression models. Results A total of 781 patients (72%) returned completed questionnaires, of which 664 (61%) could be included in the analyses. Quality of life scores and differences in subgroups (e.g. sex and age) were essentially similar to those in the general population. Age, number of comorbidities, and several chronic diseases (e.g. heart and kidney disease, diabetes, former depression) were the strongest predicting factors and influenced almost every aspect of QoL. Conclusions Localized malignant melanoma does not worsen QoL per se, compared with QoL in the general population. Comorbidities have similar effects on QoL in malignant melanoma patients as they do in the general population. Therefore, cohorts of patients with localized malignant melanoma can represent a basis for comparisons with other cohorts of cancer patients to determine the respective impacts of cancer‐related and non‐cancer‐related factors on QoL.