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European Urology Focus Jul 2021The main challenge in radical prostatectomy is complete excision of malignant tissue, while preserving continence and erectile function. Positive surgical margins (PSMs)... (Review)
Review
CONTEXT
The main challenge in radical prostatectomy is complete excision of malignant tissue, while preserving continence and erectile function. Positive surgical margins (PSMs) occur in up to 38% of cases, are associated with tumour recurrences, and may result in debilitating additional therapies. Despite surgical developments for prostate cancer (PCa), no technology is yet implemented to assess surgical margins of the entire prostatic surface intraoperatively.
OBJECTIVE
The aim of this systematic review is to provide an overview of novel imaging methods developed for intraoperative margin assessment in PCa surgery, which are compared with standard postoperative histopathology.
EVIDENCE ACQUISITION
A literature search of the last 10 yr was conducted in the Scopus, PubMed, and Embase (Ovid) databases. Eligible articles had to report the PSM rate according to their intraoperative margin assessment technology in comparison with standard histopathology.
EVIDENCE SYNTHESIS
The search resulted in 616 original articles, of which 11 were included for full-text review. The main technical developments in PCa margin assessment included optical coherence tomography, photodynamic diagnosis with 5-aminolevulinic acid, spectroscopy, and enhanced microscopy. These techniques are described and their main advantages, limitations, and applications in the clinical setting are discussed.
CONCLUSIONS
Several imaging methods are suggested in literature for the detection of positive margins during PCa surgery. Despite promising qualifications of the mentioned technologies, many struggle to find implementation in the clinic. Surgical conditions hampering the signal, long imaging times, and comparison with histopathology are mutual challenges. The next step towards reduction of PSMs in PCa surgery includes evaluation of these technologies in large clinical trials.
PATIENT SUMMARY
In this review, new technologies are reported that can assist the surgeon by detecting insufficient removal of all tumorous tissue during surgery, instead of the standard postoperative histopathological assessment. Currently, it is not clear whether these technologies improve the patient outcome directly; however, the review shows potential future implementations.
Topics: Humans; Male; Margins of Excision; Neoplasm Recurrence, Local; Prostate; Prostatectomy; Technology
PubMed: 32088139
DOI: 10.1016/j.euf.2020.02.004 -
Photodiagnosis and Photodynamic Therapy Mar 2020Basal cell carcinoma (BCC) is the most common type of non-melanoma skin cancer worldwide. Methyl-5-aminolevulinate (MAL) photodynamic therapy (PDT) is an effective and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Basal cell carcinoma (BCC) is the most common type of non-melanoma skin cancer worldwide. Methyl-5-aminolevulinate (MAL) photodynamic therapy (PDT) is an effective and acceptable treatment for BCC. The purpose of this analysis was to compare the benefit and tolerability of MAL-PDT with other modalities for the treatment of BCC.
METHODS
PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched from inception until 5 August 2019. Eligible studies were prospective and retrospective clinical trials of MAL-PDT for superficial and nodular BCC. At least one of the following outcomes were reported: complete response (CR) at 3 months and sustained at 12 months; recurrence at 12 months and sustained at 5 years; cosmetic outcome at ≥ 3 months; adverse events.
RESULTS
From 427 search results, 11 articles including seven randomized controlled trials (1339 patients; 1568 lesions) and one retrospective study (108 lesions) were eligible. CR was inferior with MAL-PDT versus surgery (3 months: Risk Ratio [RR]: 0.93, 95 % confidence interval [CI] 0.89-0.97, p = 0.002; 12 months: RR: 0.90, 95 % CI 0.85-0.95, p = 0.0002). Moreover, MAL-PDT had higher 12 months recurrence rate (RR: 10.43, 95 % CI 1.98-55.03, p = 0.006) and more toxicities (RR: 2.12, 95 % CI 1.46-3.09, p < 0.0001) in comparison with surgery. However, MAL-PDT cosmesis was superior to excisional surgery (RR: 1.99, 95 % CI 1.50-2.63, p < 0.00001). Additionally, MAL-PDT was associated with similar CR in comparison with 5-aminolaevulinic acid (ALA)-PDT and ALA nanoemulsion (BF-200 ALA)-PDT, but had higher recurrence rate at 12 months and worse cosmesis compared with BF-200 ALA-PDT, even though the differences were not statistically significant.
CONCLUSION
MAL-PDT might not be the best first-line treatment option for BCC, although cosmetic outcome could be good-to-excellent.
Topics: Aminolevulinic Acid; Carcinoma, Basal Cell; Humans; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms
PubMed: 31978564
DOI: 10.1016/j.pdpdt.2020.101667 -
Operative Neurosurgery (Hagerstown, Md.) Jul 2020For optimizing high-grade glioma resection, 5-aminolevulinic acid is a reliable tool. However, its efficacy in low-grade glioma resection remains unclear.
BACKGROUND
For optimizing high-grade glioma resection, 5-aminolevulinic acid is a reliable tool. However, its efficacy in low-grade glioma resection remains unclear.
OBJECTIVE
To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and the effect on the extent of resection.
METHODS
A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. The quality index of the selected papers was provided. No patient information was used, so Institutional Review Board approval and patient consent were not required.
RESULTS
A total of 12 articles met the selection criteria with 244 histologically confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n = 60/244; 24.5%) demonstrated visual intraoperative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies; however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10-17), which correlated with an overall good quality.
CONCLUSION
There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.
Topics: Aminolevulinic Acid; Brain Neoplasms; Glioma; Humans; Reproducibility of Results; Surgery, Computer-Assisted
PubMed: 31828346
DOI: 10.1093/ons/opz336 -
Journal of Minimally Invasive Gynecology Feb 2020To evaluate the diagnostic accuracy of intraoperative laparoscopic imaging tools in reference to that of histopathology for detecting endometriotic lesions and to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the diagnostic accuracy of intraoperative laparoscopic imaging tools in reference to that of histopathology for detecting endometriotic lesions and to compare them with conventional white-light inspection by performing a systematic review with meta-analysis.
DATA SOURCES
We searched the MEDLINE, EMBASE, and CENTRAL databases in addition to citations and reference lists until the end of February 2019.
METHODS OF STUDY SELECTION
Two authors screened 1038 citations for eligibility. We included randomized controlled trials or prospective cohort studies published in English, assessing the accuracy of intraoperative imaging tools for diagnosing endometriosis during laparoscopy. We considered studies using histopathologic evaluation as a standard criterion.
TABULATION, INTEGRATION, AND RESULTS
Seven studies were eligible, including 472 women and 1717 histopathologic specimens, and they involved study of the use of narrow-band imaging (2 studies), 5-aminolevulinic acid-induced fluorescence (2 studies), autofluorescence imaging (1 study), indocyanine green (1 study), and a 3-dimensional robotic laparoscopy (1 study). Two authors extracted data and assessed the validity of the included studies. Bivariate random-effects models and McNemar's test were used to compare the tests and evaluate sources of heterogeneity. Four studies were attributed a high risk of bias, and biopsies of normal-looking peritoneum were not performed to verify the results in 3 studies; both factors were identified as significant sources of heterogeneity, leading to the overestimation of the sensitivity and underestimation of the specificity of imaging tools. In all studies, additional endometriotic lesions were diagnosed with the enhanced imaging tool compared with white-light inspection alone. In the 4 studies that appropriately performed control biopsies (171 women, 448 specimens), enhanced imaging techniques were associated with a higher sensitivity and specificity compared with white-light inspection (0.84 and 0.89 compared with 0.75 and 0.76, respectively, p ≤.001). Adverse events were uncommon (n = 5) and reported only with the use of exogeneous photosensitizers. There were no reports of long-term changes in patient-reported outcomes arising from better detection of endometriosis lesions.
CONCLUSION
Studies report that enhanced imaging allows for the detection of additional endometriotic lesions missed by conventional white-light laparoscopy. The benefits of finding these additional lesions using enhanced imaging compared with white-light inspection alone on long-term postoperative outcomes have not been determined, and these tools should be considered only in a research context at this time.
Topics: Biopsy; Diagnostic Imaging; Diagnostic Techniques, Obstetrical and Gynecological; Endometriosis; Female; Humans; Image Enhancement; Image-Guided Biopsy; Intraoperative Period; Laparoscopy; Narrow Band Imaging; Optical Imaging; Peritoneal Diseases; Physical Examination; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity
PubMed: 31760118
DOI: 10.1016/j.jmig.2019.11.010 -
Acta Neurochirurgica Feb 2020Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas...
BACKGROUND
Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas infiltrate the ventricles. However, the underlying pathophysiology and clinical importance are largely unknown but may play a role in deciding whether to continue resection into the ventricles or not. Here, we systematically review available data regarding ependymal fluorescence in FGR using five aminolevulinic acid (5-ALA) and sodium fluorescein (SF).
METHODS
A literature search on MEDLINE, EMBASE, and WEB OF SCIENCE was performed using the following headings and search operators: ependy* fluorescence AND (5-ALA OR five aminolevulinic acid), ventric* wall fluorescence AND (5-ALA OR five aminolevulinic acid), ependy* fluorescence AND fluorescein, and ventric* wall fluorescence AND fluorescein. Both authors analyzed abstracts independently. Included articles were further reviewed for prevalence of ependymal fluorescence, patterns of fluorescence, and histopathological characteristics of sampled tissues as well as radiological signs of ependymal fluorescence. Results are reported according to the PRISMA statement.
RESULTS
Of 202 records identified, 6 studies were included compiling a total number of 198 patients treated with FGR using 5-ALA. No study on ependymal fluorescence after administration of SF was found. Overall prevalence of ependymal fluorescence was 61.4%. A total of 54.5% of cases were found to be positive for tumor cells. A total of 25.5% of patients with ependymal fluorescence were related to contrast enhancement in ventricular walls.
CONCLUSIONS
The phenomenon of ventricular wall fluorescence in 5-ALA-derived fluorescence-guided resection of malignant glioma is poorly understood and not always may fluorescence represent tumor infiltration. A larger scale prospective sampling study with molecular analyses is currently ongoing and will hopefully provide further insight into pathophysiology and clinical implications of ependymal fluorescence.
Topics: Aminolevulinic Acid; Brain Neoplasms; Ependyma; Fluorescein; Fluorescence; Fluorescent Dyes; Glioma; Humans; Photosensitizing Agents; Surgery, Computer-Assisted
PubMed: 31754847
DOI: 10.1007/s00701-019-04144-4 -
Photodiagnosis and Photodynamic Therapy Mar 2020We conducted a systematic review to evaluate the efficacy of PDT in the management of recurrent herpes labialis (RHL).
OBJECTIVE
We conducted a systematic review to evaluate the efficacy of PDT in the management of recurrent herpes labialis (RHL).
STUDY DESIGN
systematic review.
METHODS
This study was reported according to the PRISMA checklist and we performed a literature search on five databases.
RESULTS
The search revealed that there are no published clinical trials addressing PDT on RHL, therefore we conducted a review of case reports and five studies were included for qualitative review. The number of treated patients varied from 2 to 6 in each article. Most studies used methylene blue as a photosensitizer, while one used 5-aminolevulinic acid. For light irradiation, most studies used laser and one used a red light from halogen lamp. Patients' follow-up varied from 24 h to 12 months. All articles reported good outcomes with resolution of disease and no recurrences. Only one study reported adverse effects during treatment (burning and pain).
CONCLUSION
The results of this review suggest that PDT could be an effective treatment for herpes labialis. However, due to very few case reports and heterogeneity among protocols, there is a call for well-designed randomized clinical trials to confirm the efficacy of this therapy and to establish standardized protocols. The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD CRD42018108973.
Topics: Herpes Labialis; Humans; Low-Level Light Therapy; Patient Satisfaction; Photochemotherapy; Photosensitizing Agents; Recurrence
PubMed: 31648056
DOI: 10.1016/j.pdpdt.2019.08.018 -
BMJ Open Oct 2019To explore the diagnostic performance of image technique based transurethral resection for bladder cancer, with white light-guided cystoscopy (WLC) as the reference... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the diagnostic performance of image technique based transurethral resection for bladder cancer, with white light-guided cystoscopy (WLC) as the reference standard.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed/MEDLINE, Web of Science, the Cochrane Library, Central Register of Controlled Trials and Embase from inception to 31 March 2018.
METHODS
Included studies reported the diagnostic performance of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA), PDD with hexaminolevulinic acid (HAL) or narrow band imaging (NBI), with WLC as the reference standard at the patient or lesion level. The studies' risk of bias (RoB) was assessed using Quality Assessment of Diagnostic Studies-2. Data were pooled using a random effect diagnostic meta-analysis, and subgroup analyses were performed.
RESULTS
Twenty-six studies comprising a total of 3979 patients were included in this diagnostic meta-analysis. Pooled sensitivity (SSY), specificity (SPY), diagnostic OR (DOR) and area under the receiver operating characteristic curve (AUROC) values were calculated per group for NBI, HAL and 5-ALA at the lesion or patient level. NBI showed significant diagnostic superiority compared with WLC at the lesion level (SSY 0.94, 95% CI 0.82 to 0.98; SPY 0.79, 95% CI 0.73 to 0.85; DOR 40.09, 95% CI 20.08 to 80.01; AUROC 0.88, 95% CI 0.85 to 0.91). NBI presented the highest DOR (358.71, 95% CI 44.50 to 2891.71) in the patient level. Subgroup analyses were performed on studies with low to moderate RoB and at least 100 patients at the lesion level. These results were consistent with those of the overall analysis.
CONCLUSIONS
Pooled data indicated that image technique based transurethral resection (NBI, HAL and 5-ALA) showed diagnostic superiority compared with WLC. Moreover, NBI is potentially the most promising diagnostic intervention, showing the best diagnostic performance outcomes. Further prognostic outcomes of novel imaging technologies compared with those WLC should be explored in addition to current diagnostic performance analysis.
Topics: Aminolevulinic Acid; Cystoscopy; Humans; Image Interpretation, Computer-Assisted; Narrow Band Imaging; Photosensitizing Agents; Urinary Bladder Neoplasms
PubMed: 31628123
DOI: 10.1136/bmjopen-2018-028173 -
Journal of the American Academy of... Sep 2020No large studies have defined the best treatment of actinic cheilitis.
BACKGROUND
No large studies have defined the best treatment of actinic cheilitis.
METHODS
We conducted a systematic review to define the best therapies for actinic cheilitis in clinical response and recurrences.
RESULTS
We first identified 444 papers, and 49 were finally considered, including 789 patients and 843 treated areas. The following therapies were recorded in order of frequency: laser therapy, photodynamic therapy (PDT), 3% diclofenac in 2.5% hyaluronic acid, PDT + 5% imiquimod, aminolevulinic acid-laser or methyl-aminolevulinic acid-laser, 5% imiquimod, fluorouracil, partial surgery, 0.015% ingenol mebutate, 50% trichloroacetic acid, and laser + PDT. Concerning the primary outcome, complete clinical response was achieved in 76.5% of patients, and 10.2% had clinical recurrences. Partial surgery and laser therapy showed the highest complete response rates (14 of 14 [100%] and 244 of 260 [93.8%], respectively) with low recurrences. Only a limited number of patients were treated with other therapies, with the exception of PDT, with 68.9% complete responses and 12.6% of recurrences. Interestingly, when combined with 5% imiquimod, the efficacy of PDT was significantly enhanced.
LIMITATIONS
Heterogeneity across studies.
CONCLUSION
Laser therapy appears the best option among nonsurgical approaches for actinic cheilitis, and PDT showed higher efficacy when sequentially combined with 5% imiquimod. Larger studies are needed to confirm these data.
Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Cheilitis; Combined Modality Therapy; Dermabrasion; Diclofenac; Disease Progression; Fluorouracil; Humans; Imiquimod; Laser Therapy; Lip Neoplasms; Photochemotherapy; Precancerous Conditions; Treatment Outcome
PubMed: 31400450
DOI: 10.1016/j.jaad.2019.07.106 -
Frontiers in Oncology 2019High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and...
High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. 5-aminolevulinic acid (5-ALA) is the only US Food and Drug Administration-approved intraoperative optical agent used for fluorescence-guided surgical resection of gliomas. Despite several studies on the impact of intra-operative 5-ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable. A systematic review was conducted of all relevant studies assessing the GTR rate and survival outcomes [overall survival (OS) and progression-free survival (PFS)] in HGG. A meta-analysis of eligible studies was performed to assess the influence of 5-ALA-guided resection on improving GTR, OS, and PFS. GTR was defined as >95% resection. Of 23 eligible studies, 19 reporting GTR rates were included in the meta-analysis. The pooled cohort had 998 patients with HGG, including 796 with newly diagnosed cases. The pooled GTR rate among patients with 5-ALA-guided resection was 76.8% (95% confidence interval, 69.1-82.9%). A comparative subgroup analysis of 5-ALA-guided vs. conventional surgery (controlling for within-study covariates) showed a 26% higher GTR rate in the 5-ALA subgroup (odds ratio, 3.8; < 0.001). There were 11 studies eligible for survival outcome analysis, 4 of which reported PFS. The pooled mean difference in OS and PFS was 3 and 1 months, respectively, favoring 5-ALA vs. control ( < 0.001). This meta-analysis shows a significant increase in GTR rate with 5-ALA-guided surgical resection, with a higher weighted GTR rate (~76%) than the pivotal phase III study (~65%). Pooled analysis showed a small yet significant increase in survival measures associated with the use of 5-ALA. Despite the statistically significant results, the low level of evidence and heterogeneity across these studies make it difficult to conclusively report an independent association between 5-ALA use and survival outcomes in HGG. Additional randomized control studies are required to delineate the role of 5-ALA in survival outcomes in HGG.
PubMed: 31380272
DOI: 10.3389/fonc.2019.00620 -
Acta Neurochirurgica Jun 20195-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of...
BACKGROUND
5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of resection, and improves patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial and the role of 5-ALA-guided resection of these tumors is not clear, we sought to perform a comprehensive literature review on this topic.
METHODS
A systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 19 eligible publications encompassing 175 5-ALA-guided operations on pediatric brain tumors. To prevent bias, publications were revised independently by two authors.
RESULTS
We found that 5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. One important finding is that when 5-ALA-guided resections were considered helpful, the degree of resection was higher than is cases where it was not helpful. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae.
CONCLUSION
5-ALA could play a role in resection of pediatric brain tumors. However, further prospective clinical trials are needed.
Topics: Aminolevulinic Acid; Brain Neoplasms; Child; Female; Glioma; Humans; Male; Photosensitizing Agents; Postoperative Complications; Surgery, Computer-Assisted
PubMed: 30989383
DOI: 10.1007/s00701-019-03898-1