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International Journal of Nephrology and... 2023Nephrogenic systemic fibrosis (NSF) is a rare disorder that occurs in association majorly with chronic kidney disease (CKD). The lack of collective quantitative data on... (Review)
Review
AIM
Nephrogenic systemic fibrosis (NSF) is a rare disorder that occurs in association majorly with chronic kidney disease (CKD). The lack of collective quantitative data on its clinical manifestations and the different treatment options' efficacy, call the need for our investigation.
METHODS
A systematic review was conducted covering a timeline from inception up to July 2022 without any restrictions. Article screening and data extraction were performed independently on PubMed, Google Scholar, ScienceDirect, and Cochrane Library. The keywords that we used were CKD, NSF, Gadolinium enduced fibrosis, etc; shortlisted articles were assessed for risk of bias. Data were presented as frequencies and percentages, with a confidence interval of 95%. A chi-square test was also done to find significant relationships, with a -value <0.05 considered significant.
RESULTS
We had 83 patients in this review consisting of 44 (55.7%) females with a mean age of 51.4±14.6 years. Sixty-nine (83.1%) patients had chronic kidney disease predisposition to NSF. Previous exposure to gadolinium-based contrast dyes was seen in 66 (79.5%) patients). The most common symptom in patients was cutaneous lesions in 69 (83.1%) patients. The most used treatments were ultraviolet therapy, renal transplant, and extracorporeal photopheresis; in 13.3% of the patients each. Condition in most patients either improved (67.1%) or remained stable (11.8%). Chi-square testing found that the treatments offered were also seen to be significantly related to outcome (p=0.015).
CONCLUSION
The findings in this study provide a quantitative measurement of NSF's presentations and treatment efficacies. This serves to make way for researchers to form comprehensive guidelines on the presentation-based treatment of NSF.
PubMed: 36660606
DOI: 10.2147/IJNRD.S392231 -
Medicine Jan 2023Chronic graft versus host disease (cGVHD) is a systemic immune-mediated complication that occurs in approximately half of patients undergoing allogeneic hematopoietic...
RATIONALE
Chronic graft versus host disease (cGVHD) is a systemic immune-mediated complication that occurs in approximately half of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT), and remains the leading cause of late morbidity and mortality. cGVHD involves a heterogeneous group of organic manifestations, many of which mimic autoimmune diseases such as scleroderma, primary biliary cholangitis, Sjögren syndrome and polymyositis.
PATIENT CONCERNS
A 60-years-old female with a history of allo-HCT developed de novo cGVHD 11 months after allo-HCT with isolated liver involvement. The patient presented with jaundice, cytolysis, cholestasis and concomitant acute digital ischemia. Liver biopsy and autoimmunity tests were performed and were found to be compatible with immune-mediated liver damage. Nailfold capillaroscopy revealed microangiopathy, characterized by avascular areas and some enlarged capillaries resembled an early systemic sclerosis pattern.
DIAGNOSIS
Biliary cholangitis-like and digital ischemia related to cGVHD.
INTERVENTIONS
The patient was treated with high-dose prednisone and ursodeoxycholic acid, and extracorporeal photopheresis. The patient required hospital admission for administration of intravenous prostacyclin due to refractory Raynaud syndrome.
OUTCOMES
After 6 to 8 weeks, the patient achieved a good response, with evident clinical improvement and progressive normalization of liver function.
LESSONS
cGVHD is a multiorgan pathological condition, and this case emphasizes that a multidisciplinary team, including rheumatologists, should be involved in the follow-up of allo-transplant patients to ensure that the clinical complications are adequately addressed. Early intervention is critical for improving patient' prognosis.In addition, we performed a systemic literature review based on published case articles on hepatic cGVHD and digital ischemia published up to August 2022. To the best of our knowledge, this is the first reported case of such an association.
Topics: Humans; Female; Middle Aged; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Cholangitis; Bronchiolitis Obliterans Syndrome; Scleroderma, Systemic; Ischemia; Chronic Disease
PubMed: 36637943
DOI: 10.1097/MD.0000000000032495 -
The Cochrane Database of Systematic... Sep 2022Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of... (Review)
Review
BACKGROUND
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.
MAIN RESULTS
We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.
Topics: Adolescent; Adrenal Cortex Hormones; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 36166494
DOI: 10.1002/14651858.CD009759.pub4 -
The Cochrane Database of Systematic... Jun 2022Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the... (Review)
Review
Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents.
BACKGROUND
Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the paediatric recipients. Currently, the therapeutic mainstay for cGvHD is treatment with corticosteroids, frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory cGvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and first updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of cGvHD in children and adolescents after haematopoietic stem cell transplantation.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL) (2021), MEDLINE (PubMed) and Embase databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We aimed to include randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in children and adolescents with cGvHD after haematopoietic stem cell transplantation.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author.
MAIN RESULTS
We found no studies meeting the criteria for inclusion in this 2021 review update.
AUTHORS' CONCLUSIONS
We could not evaluate the efficacy of ECP in the treatment of cGvHD in children and adolescents after haematopoietic stem cell transplantation since the second review update again found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this population will be challenging due to the limited number of eligible participants, variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, recipients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for children and adolescents treated with ECP.
Topics: Adolescent; Child; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 35679154
DOI: 10.1002/14651858.CD009898.pub4 -
Therapeutic Advances in Hematology 2020Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft--host disease (GvHD), a strong prognostic predictor of early... (Review)
Review
BACKGROUND
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft--host disease (GvHD), a strong prognostic predictor of early mortality within the first 2 years following allo-HSCT. The objective of this study was to describe the harm outcomes reported among patients receiving second- and third-line treatment as part of the management for GvHD a systematic literature review.
METHODS
A total of 34 studies met the systematic review inclusion criteria, reporting adverse events (AEs) across 12 different second- and third-line therapies.
RESULTS
A total of 14 studies reported AEs across nine different therapies used in the treatment of acute GvHD (aGvHD), 17 studies reported AEs of eight different treatments for chronic GvHD (cGvHD) and 3 reported a mixed population. Infections were the AE reported most widely, followed by haematologic events and laboratory abnormalities. Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab).
CONCLUSION
The reported incidence of infectious AEs in aGvHD and grade 3-5 AEs in cGvHD was lower on ECP compared with pharmaceutical management.
PubMed: 33343855
DOI: 10.1177/2040620720977039 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
The Cochrane Database of Systematic... Dec 2018Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers, which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Optical coherence tomography (OCT) is a microscopic imaging technique, which magnifies the surface of a skin lesion using near-infrared light. Used in conjunction with clinical or dermoscopic examination of suspected skin cancer, or both, OCT may offer additional diagnostic information compared to other technologies.
OBJECTIVES
To determine the diagnostic accuracy of OCT for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, basal cell carcinoma (BCC), or cutaneous squamous cell carcinoma (cSCC) in adults.
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles.
SELECTION CRITERIA
We included studies of any design evaluating OCT in adults with lesions suspicious for invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC, compared with a reference standard of histological confirmation or clinical follow-up.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standardised data extraction and quality assessment form (based on QUADAS-2). Our unit of analysis was lesions. Where possible, we estimated summary sensitivities and specificities using the bivariate hierarchical model.
MAIN RESULTS
We included five studies with 529 cutaneous lesions (282 malignant lesions) providing nine datasets for OCT, two for visual inspection alone, and two for visual inspection plus dermoscopy. Studies were of moderate to unclear quality, using data-driven thresholds for test positivity and giving poor accounts of reference standard interpretation and blinding. Studies may not have been representative of populations eligible for OCT in practice, for example due to high disease prevalence in study populations, and may not have reflected how OCT is used in practice, for example by using previously acquired OCT images.It was not possible to make summary statements regarding accuracy of detection of melanoma or of cSCC because of the paucity of studies, small sample sizes, and for melanoma differences in the OCT technologies used (high-definition versus conventional resolution OCT), and differences in the degree of testing performed prior to OCT (i.e. visual inspection alone or visual inspection plus dermoscopy).Pooled data from two studies using conventional swept-source OCT alongside visual inspection and dermoscopy for the detection of BCC estimated the sensitivity of OCT as 95% (95% confidence interval (CI) 91% to 97%) and specificity of 77% (95% CI 69% to 83%).When applied to a hypothetical population of 1000 lesions at the mean observed BCC prevalence of 60%, OCT would miss 31 BCCs (91 fewer than would be missed by visual inspection alone and 53 fewer than would be missed by visual inspection plus dermoscopy), and OCT would lead to 93 false-positive results for BCC (a reduction in unnecessary excisions of 159 compared to using visual inspection alone and of 87 compared to visual inspection plus dermoscopy).
AUTHORS' CONCLUSIONS
Insufficient data are available on the use of OCT for the detection of melanoma or cSCC. Initial data suggest conventional OCT may have a role for the diagnosis of BCC in clinically challenging lesions, with our meta-analysis showing a higher sensitivity and higher specificity when compared to visual inspection plus dermoscopy. However, the small number of studies and varying methodological quality means implications to guide practice cannot currently be drawn.Appropriately designed prospective comparative studies are required, given the paucity of data comparing OCT with dermoscopy and other similar diagnostic aids such as reflectance confocal microscopy.
Topics: Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Melanoma; Sensitivity and Specificity; Skin Neoplasms; Tomography, Optical Coherence; Melanoma, Cutaneous Malignant
PubMed: 30521690
DOI: 10.1002/14651858.CD013189 -
The Cochrane Database of Systematic... Dec 2018Early accurate detection of all skin cancer types is essential to guide appropriate management, reduce morbidity and improve survival. Basal cell carcinoma (BCC) is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early accurate detection of all skin cancer types is essential to guide appropriate management, reduce morbidity and improve survival. Basal cell carcinoma (BCC) is usually localised to the skin but has potential to infiltrate and damage surrounding tissue, while cutaneous squamous cell carcinoma (cSCC) and melanoma have a much higher potential to metastasise and ultimately lead to death. Exfoliative cytology is a non-invasive test that uses the Tzanck smear technique to identify disease by examining the structure of cells obtained from scraped samples. This simple procedure is a less invasive diagnostic test than a skin biopsy, and for BCC it has the potential to provide an immediate diagnosis that avoids an additional clinic visit to receive skin biopsy results. This may benefit patients scheduled for either Mohs micrographic surgery or non-surgical treatments such as radiotherapy. A cytology scrape can never give the same information as a skin biopsy, however, so it is important to better understand in which skin cancer situations it may be helpful.
OBJECTIVES
To determine the diagnostic accuracy of exfoliative cytology for detecting basal cell carcinoma (BCC) in adults, and to compare its accuracy with that of standard diagnostic practice (visual inspection with or without dermoscopy). Secondary objectives were: to determine the diagnostic accuracy of exfoliative cytology for detecting cSCC, invasive melanoma and atypical intraepidermal melanocytic variants, and any other skin cancer; and for each of these secondary conditions to compare the accuracy of exfoliative cytology with visual inspection with or without dermoscopy in direct test comparisons; and to determine the effect of observer experience.
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We also studied the reference lists of published systematic review articles.
SELECTION CRITERIA
Studies evaluating exfoliative cytology in adults with lesions suspicious for BCC, cSCC or melanoma, compared with a reference standard of histological confirmation.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Where possible we estimated summary sensitivities and specificities using the bivariate hierarchical model.
MAIN RESULTS
We synthesised the results of nine studies contributing a total of 1655 lesions to our analysis, including 1120 BCCs (14 datasets), 41 cSCCs (amongst 401 lesions in 2 datasets), and 10 melanomas (amongst 200 lesions in 1 dataset). Three of these datasets (one each for BCC, melanoma and any malignant condition) were derived from one study that also performed a direct comparison with dermoscopy. Studies were of moderate to poor quality, providing inadequate descriptions of participant selection, thresholds used to make cytological and histological diagnoses, and blinding. Reporting of participants' prior referral pathways was particularly poor, as were descriptions of the cytodiagnostic criteria used to make diagnoses. No studies evaluated the use of exfoliative cytology as a primary diagnostic test for detecting BCC or other skin cancers in lesions suspicious for skin cancer. Pooled data from seven studies using standard cytomorphological criteria (but various stain methods) to detect BCC in participants with a high clinical suspicion of BCC estimated the sensitivity and specificity of exfoliative cytology as 97.5% (95% CI 94.5% to 98.9%) and 90.1% (95% CI 81.1% to 95.1%). respectively. When applied to a hypothetical population of 1000 clinically suspected BCC lesions with a median observed BCC prevalence of 86%, exfoliative cytology would miss 21 BCCs and would lead to 14 false positive diagnoses of BCC. No false positive cases were histologically confirmed to be melanoma. Insufficient data are available to make summary statements regarding the accuracy of exfoliative cytology to detect melanoma or cSCC, or its accuracy compared to dermoscopy.
AUTHORS' CONCLUSIONS
The utility of exfoliative cytology for the primary diagnosis of skin cancer is unknown, as all included studies focused on the use of this technique for confirming strongly suspected clinical diagnoses. For the confirmation of BCC in lesions with a high clinical suspicion, there is evidence of high sensitivity and specificity. Since decisions to treat low-risk BCCs are unlikely in practice to require diagnostic confirmation given that clinical suspicion is already high, exfoliative cytology might be most useful for cases of BCC where the treatments being contemplated require a tissue diagnosis (e.g. radiotherapy). The small number of included studies, poor reporting and varying methodological quality prevent us from drawing strong conclusions to guide clinical practice. Despite insufficient data on the use of cytology for cSCC or melanoma, it is unlikely that cytology would be useful in these scenarios since preservation of the architecture of the whole lesion that would be available from a biopsy provides crucial diagnostic information. Given the paucity of good quality data, appropriately designed prospective comparative studies may be required to evaluate both the diagnostic value of exfoliative cytology by comparison to dermoscopy, and its confirmatory value in adequately reported populations with a high probability of BCC scheduled for further treatment requiring a tissue diagnosis.
Topics: Adult; Azure Stains; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Coloring Agents; Cytodiagnosis; Dermoscopy; Humans; Melanoma; Papanicolaou Test; Sensitivity and Specificity; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 30521689
DOI: 10.1002/14651858.CD013187 -
The Cochrane Database of Systematic... Dec 2018Early accurate detection of all skin cancer types is important to guide appropriate management and improve morbidity and survival. Basal cell carcinoma (BCC) is usually... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early accurate detection of all skin cancer types is important to guide appropriate management and improve morbidity and survival. Basal cell carcinoma (BCC) is usually a localised skin cancer but with potential to infiltrate and damage surrounding tissue, whereas cutaneous squamous cell carcinoma (cSCC) and melanoma are higher risk skin cancers with the potential to metastasise and ultimately lead to death. When used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may help to identify cancers eligible for non-surgical treatment without the need for a diagnostic biopsy, particularly in people with suspected BCC. Any potential benefit must be balanced against the risk of any misdiagnoses.
OBJECTIVES
To determine the diagnostic accuracy of RCM for the detection of BCC, cSCC, or any skin cancer in adults with any suspicious lesion and lesions that are difficult to diagnose (equivocal); and to compare its accuracy with that of usual practice (visual inspection or dermoscopy, or both).
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles.
SELECTION CRITERIA
Studies of any design that evaluated the accuracy of RCM alone, or RCM in comparison to visual inspection or dermoscopy, or both, in adults with lesions suspicious for skin cancer compared with a reference standard of either histological confirmation or clinical follow-up, or both.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities using the bivariate hierarchical model. For computation of likely numbers of true-positive, false-positive, false-negative, and true-negative findings in the 'Summary of findings' tables, we applied summary sensitivity and specificity estimates to lower quartile, median and upper quartiles of the prevalence observed in the study groups. We also investigated the impact of observer experience.
MAIN RESULTS
The review included 10 studies reporting on 11 study cohorts. All 11 cohorts reported data for the detection of BCC, including 2037 lesions (464 with BCC); and four cohorts reported data for the detection of cSCC, including 834 lesions (71 with cSCC). Only one study also reported data for the detection of BCC or cSCC using dermoscopy, limiting comparisons between RCM and dermoscopy. Studies were at high or unclear risk of bias across almost all methodological quality domains, and were of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, unclear blinding of the reference test, and exclusions due to image quality or technical difficulties were observed. It was unclear whether studies were representative of populations eligible for testing with RCM, and test interpretation was often undertaken using images, remotely from the participant and the interpreter blinded to clinical information that would normally be available in practice.Meta-analysis found RCM to be more sensitive but less specific for the detection of BCC in studies of participants with equivocal lesions (sensitivity 94%, 95% confidence interval (CI) 79% to 98%; specificity 85%, 95% CI 72% to 92%; 3 studies) compared to studies that included any suspicious lesion (sensitivity 76%, 95% CI 45% to 92%; specificity 95%, 95% CI 66% to 99%; 4 studies), although CIs were wide. At the median prevalence of disease of 12.5% observed in studies including any suspicious lesion, applying these results to a hypothetical population of 1000 lesions results in 30 BCCs missed with 44 false-positive results (lesions misdiagnosed as BCCs). At the median prevalence of disease of 15% observed in studies of equivocal lesions, nine BCCs would be missed with 128 false-positive results in a population of 1000 lesions. Across both sets of studies, up to 15% of these false-positive lesions were observed to be melanomas mistaken for BCCs. There was some suggestion of higher sensitivities in studies with more experienced observers. Summary sensitivity and specificity could not be estimated for the detection of cSCC due to paucity of data.
AUTHORS' CONCLUSIONS
There is insufficient evidence for the use of RCM for the diagnosis of BCC or cSCC in either population group. A possible role for RCM in clinical practice is as a tool to avoid diagnostic biopsies in lesions with a relatively high clinical suspicion of BCC. The potential for, and consequences of, misclassification of other skin cancers such as melanoma as BCCs requires further research. Importantly, data are lacking that compare RCM to standard clinical practice (with or without dermoscopy).
Topics: Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermoscopy; False Positive Reactions; Humans; Microscopy, Confocal; Physical Examination; Sensitivity and Specificity; Skin Neoplasms
PubMed: 30521687
DOI: 10.1002/14651858.CD013191 -
The Cochrane Database of Systematic... Dec 2018Melanoma accounts for a small proportion of all skin cancer cases but is responsible for most skin cancer-related deaths. Early detection and treatment can improve...
BACKGROUND
Melanoma accounts for a small proportion of all skin cancer cases but is responsible for most skin cancer-related deaths. Early detection and treatment can improve survival. Smartphone applications are readily accessible and potentially offer an instant risk assessment of the likelihood of malignancy so that the right people seek further medical attention from a clinician for more detailed assessment of the lesion. There is, however, a risk that melanomas will be missed and treatment delayed if the application reassures the user that their lesion is low risk.
OBJECTIVES
To assess the diagnostic accuracy of smartphone applications to rule out cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with concerns about suspicious skin lesions.
SEARCH METHODS
We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles.
SELECTION CRITERIA
Studies of any design evaluating smartphone applications intended for use by individuals in a community setting who have lesions that might be suspicious for melanoma or atypical intraepidermal melanocytic variants versus a reference standard of histological confirmation or clinical follow-up and expert opinion.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and poor quality of studies, we did not perform a meta-analysis for this review. For illustrative purposes, we plotted estimates of sensitivity and specificity on coupled forest plots for each application under consideration.
MAIN RESULTS
This review reports on two cohorts of lesions published in two studies. Both studies were at high risk of bias from selective participant recruitment and high rates of non-evaluable images. Concerns about applicability of findings were high due to inclusion only of lesions already selected for excision in a dermatology clinic setting, and image acquisition by clinicians rather than by smartphone app users.We report data for five mobile phone applications and 332 suspicious skin lesions with 86 melanomas across the two studies. Across the four artificial intelligence-based applications that classified lesion images (photographs) as melanomas (one application) or as high risk or 'problematic' lesions (three applications) using a pre-programmed algorithm, sensitivities ranged from 7% (95% CI 2% to 16%) to 73% (95% CI 52% to 88%) and specificities from 37% (95% CI 29% to 46%) to 94% (95% CI 87% to 97%). The single application using store-and-forward review of lesion images by a dermatologist had a sensitivity of 98% (95% CI 90% to 100%) and specificity of 30% (95% CI 22% to 40%).The number of test failures (lesion images analysed by the applications but classed as 'unevaluable' and excluded by the study authors) ranged from 3 to 31 (or 2% to 18% of lesions analysed). The store-and-forward application had one of the highest rates of test failure (15%). At least one melanoma was classed as unevaluable in three of the four application evaluations.
AUTHORS' CONCLUSIONS
Smartphone applications using artificial intelligence-based analysis have not yet demonstrated sufficient promise in terms of accuracy, and they are associated with a high likelihood of missing melanomas. Applications based on store-and-forward images could have a potential role in the timely presentation of people with potentially malignant lesions by facilitating active self-management health practices and early engagement of those with suspicious skin lesions; however, they may incur a significant increase in resource and workload. Given the paucity of evidence and low methodological quality of existing studies, it is not possible to draw any implications for practice. Nevertheless, this is a rapidly advancing field, and new and better applications with robust reporting of studies could change these conclusions substantially.
Topics: Adult; Algorithms; Diagnostic Errors; Early Detection of Cancer; Humans; Melanoma; Mobile Applications; Sensitivity and Specificity; Skin Neoplasms; Smartphone; Triage; Melanoma, Cutaneous Malignant
PubMed: 30521685
DOI: 10.1002/14651858.CD013192