International consensus recommendations on face transplantation: A 2-step Delphi study.

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.

Defining a Safe Corridor of Cervical Branch Preservation in Lateral Platysmaplasty Surgery During Facial Rejuvenation Surgery.

BACKGROUND: During rhytidectomies, the cervical branch of the facial nerve (CBFN) can easily be encountered, and potentially injured, when releasing the cervical retaining ligaments in the lateral neck. This nerve has been shown to occasionally co-innervate the depressor anguli oris muscle, and damage to it can thus potentially compromise outcomes with a postoperative palsy. OBJECTIVES: The authors sought to examine the lateral cervical anatomy specific to the CBFN to ascertain if the position of the nerve can be predicted, thereby enhancing safety of the platysmal flap separation and dissection from this lateral zone of adhesion. METHODS: Eleven cadaveric hemifaces were dissected, and the distance between the medial border of sternocleidomastoid muscle (SCM) and the CBFN was measured at 3 key points: (1) superior: the distance between the SCM and the nerve at the level of the angle of the mandible in neutral; (2) narrowest: the narrowest distance measurable between the superior and inferior points as the CBFN descends into the neck medial to the SCM; and (3) inferior: the distance at the most distal part of the cervical nerve identified before its final intramuscular course. RESULTS: The average distances (in mms) were as follows: superior = 12.1 (range, 10.1-15.4), narrowest = 8.8 (range, 5.6-12.2), and inferior = 10.9 (range, 7.9-16.7). CONCLUSIONS: There is a narrow range between the nerve and the anterior border of SCM. We thus propose a safe corridor where lateral deep-plane dissection can be performed to offer cervical retaining ligament release, with reduced risk of endangering the CBFN.

Intraoperative Near-infrared Fluorescence (NIR) Imaging With Indocyanine Green (ICG) Can Identify Bone and Soft Tissue Sarcomas Which May Provide Guidance for Oncological Resection.

BACKGROUND: Complete excision of sarcomas to maximize function without compromising the oncological outcome can be challenging. The aim of this study was to investigate the feasibility and potential drawbacks of near-infrared (NIR) fluorescence imaging with indocyanine green during resection of bone and soft tissue sarcomas. METHODS: Eleven patients with high-grade sarcomas were enrolled in the study. All patients received intravenous indocyanine green (75 mg) between 16 and 24 hours before the resection. Sarcomas were resected under NIR guidance and specimens were sent for routine histopathological analysis. RESULTS: Majority of treatment naive tumors demonstrated fluorescence. There were no adverse events from the indocyanine green administration. In 3 cases, the fluorescence was reported by the surgeon to have been of definite guidance leading to further tissue resection to improve the margin. CONCLUSION: This is the first report of NIR fluorescence guidance in the setting of open sarcoma surgery. The technique is acceptable to patients and surgeons and was able to guide resection. Multicenter studies are required to assess the utility of this technique in a large cohort of patients with regards to quantification of fluorescence, resection guidance, and longer follow-up period.

Reflectance confocal microscopy for diagnosing cutaneous melanoma in adults.

BACKGROUND: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Early detection and treatment is key to improving survival; however, anxiety around missing early cases needs to be balanced against appropriate levels of referral and excision of benign lesions. Used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may reduce unnecessary excisions without missing melanoma cases. OBJECTIVES: To determine the diagnostic accuracy of reflectance confocal microscopy for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with any lesion suspicious for melanoma and lesions that are difficult to diagnose, and to compare its accuracy with that of dermoscopy. 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; and seven other databases. We studied reference lists and published systematic review articles. SELECTION CRITERIA: Studies of any design that evaluated RCM alone, or RCM in comparison to dermoscopy, in adults with lesions suspicious for melanoma or atypical intraepidermal melanocytic variants, compared with a reference standard of either histological confirmation or clinical follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all 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 per algorithm and threshold using the bivariate hierarchical model. To compare RCM with dermoscopy, we grouped studies by population (defined by difficulty of lesion diagnosis) and combined data using hierarchical summary receiver operating characteristic (SROC) methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of specificity at the point on the SROC curve with 90% sensitivity as this value lies within the estimates for the majority of analyses. We investigated the impact of using a purposely developed RCM algorithm and in-person test interpretation. MAIN RESULTS: The search identified 18 publications reporting on 19 study cohorts with 2838 lesions (including 658 with melanoma), which provided 67 datasets for RCM and seven for dermoscopy. Studies were generally at high or unclear risk of bias across almost all domains and of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, lack of blinding of the reference test to the RCM result, and differential verification were particularly problematic. Studies may not be representative of populations eligible for RCM, and test interpretation was often undertaken remotely from the patient and blinded to clinical information.Meta-analysis found RCM to be more accurate than dermoscopy in studies of participants with any lesion suspicious for melanoma and in participants with lesions that were more difficult to diagnose (equivocal lesion populations). Assuming a fixed sensitivity of 90% for both tests, specificities were 82% for RCM and 42% for dermoscopy for any lesion suspicious for melanoma (9 RCM datasets; 1452 lesions and 370 melanomas). For a hypothetical population of 1000 lesions at the median observed melanoma prevalence of 30%, this equated to a reduction in unnecessary excisions with RCM of 280 compared to dermoscopy, with 30 melanomas missed by both tests. For studies in equivocal lesions, specificities of 86% would be observed for RCM and 49% for dermoscopy (7 RCM datasets; 1177 lesions and 180 melanomas). At the median observed melanoma prevalence of 20%, this reduced unnecessary excisions by 296 with RCM compared with dermoscopy, with 20 melanomas missed by both tests. Across all populations, algorithms and thresholds assessed, the sensitivity and specificity of the Pellacani RCM score at a threshold of three or greater were estimated at 92% (95% confidence interval (CI) 87 to 95) for RCM and 72% (95% CI 62 to 81) for dermoscopy. AUTHORS' CONCLUSIONS: RCM may have a potential role in clinical practice, particularly for the assessment of lesions that are difficult to diagnose using visual inspection and dermoscopy alone, where the evidence suggests that RCM may be both more sensitive and specific in comparison to dermoscopy. Given the paucity of data to allow comparison with dermoscopy, the results presented require further confirmation in prospective studies comparing RCM with dermoscopy in a real-world setting in a representative population.

Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults.

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).

Neighborhood Stress, Depressive Symptoms, and Asthma Morbidity in Youth.

OBJECTIVE: Living in a dangerous and disadvantaged neighborhood is consistently linked with poor health outcomes; however, few studies have investigated psychosocial mechanisms of this relationship. We hypothesized that a specific facet of depression-anhedonia-would partially explain the relationship between stressful neighborhoods and poor health in youth with asthma. METHOD: 156 youths provided reports on their depressive symptoms, daily asthma symptoms, and peak expiratory flow rate (PEFR). Caregivers provided reports on neighborhood characteristics. RESULTS: Youth residing in more at-risk neighborhoods experienced more symptoms of depression, greater asthma symptoms (both during the day and night), and marginally lower PEFR. Indirect effect analyses revealed that the relationship between neighborhood stress and youth asthma symptoms was partially explained by a key symptom of depression, anhedonia. CONCLUSIONS: These findings suggest that the neighborhood-health link is partially explained by symptoms of depression tapping into difficulties experiencing pleasure and motivation.

An Anatomic Appraisal of Biplanar Muscle-Splitting Breast Augmentation.

BACKGROUND: Biplanar muscle-splitting (BMS) breast augmentation is a relatively new technique for which the safe regions of dissection have not been delineated. OBJECTIVES: The authors performed cadaver dissections to elucidate the surgical anatomy of the BMS pocket and to infer the safety of this method. METHODS: The breasts and chest regions of 5 female cadavers were dissected to identify anatomic landmarks and to ascertain the optimal split site in the pectoralis major. CS was defined as the lateral junction of the middle and caudal one-third of the sternum, and the sternal index was defined as the ratio of the length of the sternum to the distance from CS to the most medial major nerve branch. RESULTS: Initiating the muscle split at CS is likely to avoid nerve injury. The mean distance from CS to the most medial nerve branch was 15.36 cm. The sternal index is a reproducible marker of the extension of the nerve branches in relation to chest size. The sternal length and the cranio-caudal length of the pectoralis major were similar, enabling reliable planning of the muscle split site. CONCLUSIONS: If dissection is limited to the safe regions delineated herein, BMS breast augmentation is likely to be a safe procedure for most patients. By maintaining the connections between the pectoralis major and its origins, a breast deformity associated with muscle contraction may be avoidable.

Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life.

OBJECTIVES: Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. METHODS: Forty-three youths with asthma (26 boys; aged 10-17 years) wore the Electronically Activated Recorder for 4 days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated Electronically Activated Recorder sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin (IL)-5, IL-13, and interferon-γ. RESULTS: Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = -0.38, p = .012) and IL-13 (r = -0.33, p = .031). Greater total positive affect in youth was linked to decreased stimulated production of IL-5 (r = -0.46, p = .002) and IL-13 (r = -0.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% confidence interval = -3.41 to -0.03) and IL-13 (95% confidence interval = -2.34 to -0.01) when adjusting for caregiver-youth conflict and negative affect among youth. CONCLUSIONS: These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youth with asthma.

Effects of socioeconomic status on maternal and child positive behaviors in daily life among youth with asthma.

OBJECTIVE: Socioeconomic disadvantage is associated with poorer behavioral and emotional outcomes in children with asthma. This study investigated the associations between maternal income and education and naturalistically observed behaviors and affect during everyday parent-child interactions. METHODS: 53 predominantly low-income youth with asthma, aged 10-17 years, wore a naturalistic event-sampling device, the Electronically Activated Recorder, for 4 days to assess mother and child positive behaviors and affect in daily life. RESULTS: Maternal education, but not income, was positively associated with child positive behaviors, displays of mother and child positive affect, and increased maternal responsiveness. Maternal positive affect and maternal responsiveness mediated the effect of maternal education on child positive affect. CONCLUSIONS: Our findings suggest that maternal education has an important influence on the socioemotional adjustment of youth with asthma and point to the importance of investigating the independent influence of socioeconomic status components on everyday parent-child interactions.

The partial myocutaneous gluteal flap reconstruction of extralevator abdominoperineal defects in irradiated patients.

Reconstruction of the irradiated perineum has posed a consistent reconstructive challenge historically. The evolution of reconstructive techniques must mirror advances in neoadjuvant treatment and surgery for low rectal cancer. The purpose of this study was to evaluate the perineal healing in a cohort of patients, of whom a majority had laparoscopic tumor excision and partial myocutaneous gluteal flap reconstruction. There were 11 patients in this cohort; 8 primary reconstructions and 3 salvage cases. Complete healing was measured as the cessation of all dressings. There were no returns to theater for flap-related surgery. Mean postreconstruction inpatient stay was 16.5 days. All patients healed completely. Mean time to healing was 42 days. This method has been successful for primary and salvage reconstruction in patients having laparoscopic or open surgery; thus, averting the major morbidity associated with failed reconstruction as reported for most of other reconstructive modalities in these patients.

'Thou shalt not throw away a living thing': A single-centre 10-year experience using the spare parts principle for complex sarcoma reconstruction.

INTRODUCTION: For aggressive limb sarcomas beyond reconstructive reach, an amputation may be the only alternative to achieve a complete tumour resection. However, very proximal amputations result in greater loss of function and quality-of-life impact. The spare parts principle advocates utilising tissues distal to the amputation site, for reconstructing complex defects and preserving the function. We aim to present our 10-year experience utilising this principle in complex sarcoma surgery. METHODS: A retrospective review of our prospective sarcoma database was conducted for sarcoma patients treated with an amputation between 2012 and 2022. Cases in which distal segments were used for the reconstruction were identified. Demographic data, tumour characteristics, and surgical and non-surgical treatment, along with oncological outcomes and complications, were recorded and analysed. RESULTS: Fourteen patients were eligible for inclusion. The median age was 54 years at presentation (8-80 years) with 43% being females. Nine had a primary sarcoma resection, two were treated for recurrent tumours, two presented intractable osteomyelitis following sarcoma treatment and one had an amputation as a palliative procedure. The latter was the only oncological case in which tumour clearance was not achieved. Three patients developed metastasis and subsequently died during follow-up. DISCUSSION: Careful balancing of oncological goals and preservation of function is required for proximal limb-threatening sarcomas. When an amputation is required, tissues distal to the cancer site provide a safe reconstructive alternative, optimising patient recovery and preserving function. Our experience is limited by the small number of cases presenting with these rare and aggressive tumours.

An anatomical appraisal of dynamic muscle transfer of the orbicularis oculi muscle.

Facial nerve palsy can cause significant distress for patients. We investigated the innervation of the orbicularis oculi muscle (OOM) and assessed the viability of unipedicle contralateral muscle transfer to restore symmetrical and spontaneous blinking. Cadaveric dissection and measurements were performed on lite fixed cadavers (n = 15). Medial innervation of the OOM was identified prior to raising and transposing a flap to the contralateral eyelid. Measurements were performed in-situ and following transposition. A medial ascending branch of the buccal nerve innervating the OOM was identified bilaterally in all cadavers. The average length of flap raised was 59.85 mm (± 4.69 mm) with no difference between the left and right. Flaps with pedicles not dissected off the bone covered 48% of the ciliary margin length (CM) and 62% of the palpebral length (PL). Flaps dissected off the bone covered 72% of the CM and 92% of the PL. The results demonstrate that a flap can theoretically transpose to >50% of the contralateral eyelid length. Increased coverage of the eyelid was achieved by releasing the pedicle from the underlying bone. Little attention was focused on buccal innervation of the eyelids, and this consistent medial pattern may allow an innervated flap transfer to restore symmetrical blinking, something that eludes modern paralysis surgery in a single-stage procedure.

Postoperative radiotherapy delay in head and neck cancer patients undergoing major resection and free flap reconstruction.

BACKGROUND: Delays to postoperative radiotherapy (PORT) are frequent and associated with poorer oncologic outcomes in head and neck cancer (HNC) patients. Free flap patients have been suggested as the most at-risk group. Thus, PORT delivery experienced by HNC patients who required a free flap reconstruction was analysed, identifying reasons for the delays if any. METHODS: A retrospective analysis of a single tertiary unit's PORT delivery to HNC patients undergoing major resection followed by free flap reconstruction between 2017 and 2020. RESULTS: Eighty-seven patients were identified. Thirty-two patients received PORT within 6 weeks of their surgery date. Reasons for the delays could be categorised into surgery-derived, system-derived and patient-derived reasons. Five patients (5.74%) received PORT >6 weeks after their surgery due to surgical complications. No patients experienced surgical complications during their PORT. CONCLUSION: In our experience, surgical aspects of free flap reconstructions do not appear to overtly delay or interrupt PORT.

Autologous fat grafting in the face and neck: Multinational trends and knowledge of the safety, applications, and indications considering oncologic risk potential.

BACKGROUND: Autologous fat grafting (AFG) is evolving in both aesthetic and reconstructive applications, since the body of evidence for its use has expanded. The earliest controversies were evident in lipofilling for oncological breast reconstruction, and to this day, some countries do not allow it for fear of inducing tumourigenesis in an oncologically ablated field. METHODS: We sought to review contemporary harvesting and processing techniques for AFG in the craniofacial region, therefore distributed a survey to evaluate the clinical impact of oncological risk across four European countries. RESULTS: We found no significant geographical differences between the German-speaking and the English groups concerning their harvesting and processing technique. Half of our respondents discuss the possibility of pro-oncologic behavior of AFG. CONCLUSION: AFG harvesting and processing techniques do not considerably vary by geography. Further studies should evaluate oncologic risk potential of AFG in head and neck tumor sites, especially because there is no excellent article regarding this phenomenon.Level of Evidence: V.

Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) for the Resection of Sarcomas May Reduce the Positive Margin Rate: An Extended Case Series.

BACKGROUND: Sarcomas are rare, aggressive cancers which can occur in any region of the body. Surgery is usually the cornerstone of curative treatment, with negative surgical margins associated with decreased local recurrence and improved overall survival. Indocyanine green (ICG) is a fluorescent dye which accumulates in sarcoma tissue and can be imaged intraoperatively using handheld near-infrared (NIR) cameras, theoretically helping guide the surgeon's resection margins. METHODS: Patients operated on between 20 February 2019 and 20 October 2021 for intermediate to high grade sarcomas at our centres received either conventional surgery, or were administered ICG pre-operatively followed by intra-operative NIR fluorescence guidance during the procedure. Differences between the unexpected positive margin rates were compared. RESULTS: 115 suitable patients were identified, of which 39 received ICG + NIR fluorescence guided surgery, and 76 received conventional surgery. Of the patients given ICG, 37/39 tumours fluoresced, and surgeons felt the procedure was guided by the intra-operative images in 11 cases. Patients receiving ICG had a lower unexpected positive margin rate (5.1% vs. 25.0%, p = 0.01). CONCLUSIONS: The use of NIR fluorescence cameras in combination with ICG may reduce the unexpected positive margin rate for high grade sarcomas. A prospective, multi-centre randomised control trial is now needed to validate these results.

Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: three systematic reviews and an economic model.

BACKGROUND: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. OBJECTIVES: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. REVIEW METHODS: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration's Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel's c-statistic), calibration (e.g. the Hosmer-Lemeshow 'goodness-of-fit' test) or overall performance (e.g. Brier score, R2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. RESULTS: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. LIMITATIONS: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. CONCLUSIONS: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018086784. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 25, No. 64. See the NIHR Journals Library website for further project information.

Malignant melanoma is the deadliest of skin cancers; in the UK, > 2500 people die from it every year. Initially, the cancer is removed surgically, which cures it for most people, but, for some, the cancer returns. For this reason, after a melanoma is removed, patients are followed up to see if the melanoma reoccurs or if new melanomas have developed. It is felt that early cancer detection improves the chance of future treatment working. A key question is how best to follow up patients after initial melanoma surgery. This study concentrates on the earliest stage of melanoma (American Joint Committee on Cancer stage I), which accounts for more than 7 out of 10 of all melanoma diagnoses. The study also investigates if new ways of follow-up could be at least as good as current practice and a better use of NHS money. We systematically reviewed studies comparing different ways of organising follow-up, and then methods to identify those patients at high risk of developing a further melanoma and how good different tests are at detecting this cancer. We then compared different possible follow-up strategies. For each strategy, we considered its impact on quality and length of life, and how well it used NHS resources. We found little evidence to support a change in how follow-up should be organised currently. There were some ways of organising follow-up that might be better than current care, but further research is needed. We found that new research on whether or not follow-up should be performed by a cancer nurse specialist, rather than a dermatologist or surgeon, would be worthwhile. We also found that more research could be worthwhile on how frequently melanoma recurs and spreads, as well as how accurately a diagnosis of further cancer is made and how to identify those most at risk of further melanoma spread.