Hot dots - which nodes should be removed in sentinel lymph node biopsy for melanoma?

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. METHODS: The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. RESULTS: Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. CONCLUSIONS: By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye.

Eccrine Porocarcinoma: Clinical and Histopathological Study of 14 Patients with Special Emphasis on Sentinel Lymph Node Biopsy.

Eccrine porocarcinoma is a rare skin adnexal tumour that affects elderly people. Most eccrine porocarcinomas are stage I or II according to the American Joint Committee on Cancer. The prognosis is good in early stages, but worsens when advanced. Since information on the use of sentinel lymph node biopsy in these patients is scarce, this study examined the records of all patients with eccrine porocarcinoma treated at Helsinki University Hospital during a 17-year period and focused on sentinel lymph node biopsy patients. The study identified 14 patients (9 male, 5 female). There were 2 metastases to the lymph nodes and 2 recurrences at initial referral to our institution. All primary tumours had wide local excision and 6 patients also had sentinel lymph node biopsy, of whom none had positive lymph nodes. There were no new metastases or recurrences during follow-up. Three patients died of causes other than eccrine porocarcinoma. When comparing the wide local excision only and wide local excision with sentinel lymph node biopsy groups, no parameters reached statistical significance. The decision process of the multidisciplinary tumour board meeting on whether to perform sentinel lymph node biopsy was not clear, perhaps due to the limited knowledge of eccrine porocarcinoma. Further studies and international collaboration are warranted.

Kajava Classification: The Person and the Research.

The Kajava classification for ectopic breast tissue is still widely used, although it was published in 1915 in Finnish. This historical note sheds light on the person and research behind the classification. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Neurocan expression associates with better survival and viral positivity in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that is frequently divided into Merkel cell polyomavirus negative and positive tumors due their distinct genomic and transcriptomic profiles, and disease outcomes. Although some prognostic factors in MCC are known, tumorigenic pathways, which that explain outcome differences in MCC are not fully understood. We investigated transcriptomes of 110 tissue samples of a formalin-fixed, paraffin-embedded MCC series by RNA sequencing to identify genes showing a bimodal expression pattern and predicting outcome in cancer and that potentially could play a role in tumorigenesis. We discovered 19 genes among which IGHM, IGKC, NCAN, OTOF, and USH2A were associated also with overall survival (all p-values < 0.05). From these genes, NCAN (neurocan) expression was detected in all 144 MCC samples by immunohistochemistry. Increased NCAN expression was associated with presence of Merkel cell polyomavirus DNA (p = 0.001) and viral large T antigen expression in tumor tissue (p = 0.004) and with improved MCC-specific survival (p = 0.027) and overall survival (p = 0.034). We conclude that NCAN expression is common in MCC, and further studies are warranted to investigate its role in MCC tumorigenesis.

What could we make of AI in plastic surgery education.

To explore the possibilities of artificial intelligence (AI) text-to-picture system, DALL·E 2 was used to generated clinical photographs for medical and plastic surgery education. Generic English text was used to guide AI in three categories: subcutaneous tumor, wound and skin tumor. The most clinically accurate images were chosen for the article or for further editing. AI-generated images with variating clinical accuracy in different categories. The most accurate images were the soft-tissue tumors and the least accurate wounds. This study showed that AI text-to-picture system might be worthy tool for medical education.

Sauna contact burns in adults in the Helsinki Burn Centre during 2006-2018.

INTRODUCTION: Within Finish culture is a strong tradition of sauna bathing. This special environment predisposes the persons refreshing in the sauna to different kind of burns with varying etiologies. Despite the high prevalence of sauna related burns in Finland, there is paucity on the sauna related burns literature. METHODS: In this 13-year retrospective study, all sauna-related contact burns in the adult population treated at the Helsinki Burn Centre were analyzed. Altogether 216 patients were included in this study. RESULTS: The incidence of sauna-related contact burns was significantly higher in males; they accounted for 71.8% of patients. In addition to male gender, another risk factor was high age, with the elderly also being more prone to have a longer length of stay in hospital and more often receiving operative treatment. Despite most burns being relatively small, they were deep and more than one-third (36.6%) of patients underwent surgery. A strong seasonal variation in the injuries was recorded; over 40% of the burns took place during the summer months. CONCLUSION: Sauna contact burns are common, and despite their small size, they frequently cause deep injuries indicating operative treatment. There is a clear male predominance in the patient population. Most probably the cultural aspects of sauna bathing at summer cottages explain the strong seasonal variation in the incidence of these burns. The long latency between initial injury and presentation at the Helsinki Burn Centre should be highlighted to health care centres and central hospitals.

Bumping to a rollator walker: How pretibial hematomas create more costs than pretibial lacerations.

Pretibial lacerations (PL) and pretibial hematomas (PH) are debilitating traumas among the elderly and infirm. The injuries are frequently grouped together despite differences in treatment and symptoms. Patients are known to have multiple contacts in health care, perhaps because of inadequate treatment. Despite the burden, financial costs have not been assessed. Calculate and compare the treatment costs of PLs and PHs for differences and provide economic incentives to treat and diagnose patients optimally. From linkage to ICD10 diagnoses, we analysed NordDRG product invoices generated by the treatment of the patients. We calculated and compared the costs of treatment in both cohorts from the invoices. This method has not been previously used for analysing wound care costs. Mean treatment costs were 1800€ (PL) and 3300€ (PH). The total costs, emergency room, surgical treatment, and inpatient care of PHs were higher than PLs (P = .0486, P = .0002, P = .0058, P = .6526). PLs generate more costs from the outpatient clinic but were not statistically significant (P = .6533). PHs cause a higher economic burden than PLs. Costs arise from repeat ER visits and the need for surgeries because of delayed treatment. PLs have multiple contacts in the wound clinic. Improvement in the diagnosis and treatment of both injuries is needed.

Transcriptomic analyses reveal three distinct molecular subgroups of Merkel cell carcinoma with differing prognoses.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a poor prognosis and an unknown cell of origin. Proffered cells of origin include epithelial stem cells of the hair follicle or interfollicular epidermis, dermal stem cells and pro/pre- or pre-B cells. MCC has also been proposed to have more than one cell of origin and indeed to represent more than one type of carcinoma, currently grouped together due to phenotypic similarities. We explored the heterogeneous nature of MCC by studying the most variably expressed genes with the goal of identifying gene expression patterns that are either clinically relevant or have implications regarding the cell(s) of origin. We performed RNA sequencing on primary tumor samples from 102 patients and identified the top 200 most variably expressed genes. These genes and the tumor samples were hierarchically clustered based on their expression. The functions of three gene clusters exhibiting clearly divergent expression between samples were studied by cross-referencing the lists of genes with online databases. High expression of a gene cluster related to embryonic developmental processes and low expression of a gene cluster related to neuroendocrine processes distinguished Merkel cell polyomavirus (MCPyV)-negative tumors from MCPyV-positive tumors. Furthermore, two prognostically relevant subgroups of MCPyV-positive MCC were identified based on dichotomic expression of genes related to epidermal structures and processes. We identified three distinct molecular subgroups of MCC with prognostic relevance. We propose that the dichotomic expression of epidermis-related genes might reflect both an epidermal and a nonepidermal origin for MCPyV-positive MCC.

Activation of Oncogenic and Immune-Response Pathways Is Linked to Disease-Specific Survival in Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes. METHODS: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC. RESULTS: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response. CONCLUSION: This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes.

Lessons learned from COVID-19 pandemic in undergraduate surgical education.

In this editorial, we review our experience on distance teaching and based on our experiences suggest modifications to undergraduate surgical education.

UV-induced local immunosuppression in the tumour microenvironment of eccrine porocarcinoma and poroma.

Eccrine porocarcinoma (EPC) is a rare malignant adnexal tumour of the skin. Part of EPCs develop from their benign counterpart, poroma (EP), with chronic light exposure and immunosuppression hypothesized to play a role in the malignant transformation. However, the impact of chronic light exposure on the microenvironment of EPCs and EPs has not been investigated yet. Although the clinical relevance of tumour infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) has been established in various tumours, their distribution and significance in EPCs and EPs is still poorly understood. We characterized the distribution of TILs and TLSs using CD3, CD4, CD8, CD20 immunohistochemistry in a cohort of 10 EPCs and 49 EPs. We then classified our samples using solar-elastosis grading, analyzing the influence of ultraviolet (UV) damage on TIL density. A negative correlation between UV damage and TIL density was observed (CD4 r = -0.286, p = 0.04. CD8 r = -0.305, p = 0.033). No significant difference in TIL density was found between EPCs and EPs. TLS was scarse with the presence rate 10% in EPCs and 8.3% in EPs. The results suggest that UV has an immunosuppressive effect on the microenvironment of EPCs and EPs.

The Merkel Cell Polyomavirus T-Antigens and IL-33/ST2-IL1RAcP Axis: Possible Role in Merkel Cell Carcinoma.

Merkel cell polyomavirus (MCPyV) is a causal factor in Merkel cell carcinoma (MCC). The oncogenic potential is mediated through its viral oncoproteins large T-antigen (LT) and small T-antigen (sT). Cytokines produced by tumor cells play an important role in cancer pathogenesis, and viruses affect their expression. Therefore, we compared human cytokine and receptor transcript levels in virus positive (V+) and virus negative (V-) MCC cell lines. Increased expression of IL-33, a potent modulator of tumor microenvironment, was observed in V+ MCC cell lines when compared to V- MCC-13 cells. Transient transfection studies with luciferase reporter plasmids demonstrated that LT and sT stimulated IL-33, ST2/IL1RL1 and IL1RAcP promoter activity. The induction of IL-33 expression was confirmed by transfecting MCC-13 cells with MCPyV LT. Furthermore, recombinant human cytokine domain IL-33 induced activation of MAP kinase and NF-κB pathways, which could be blocked by a ST2 receptor antibody. Immunohistochemical analysis demonstrated a significantly stronger IL-33, ST2, and IL1RAcP expression in MCC tissues compared to normal skin. Of interest, significantly higher IL-33 and IL1RAcP protein levels were observed in MCC patient plasma compared to plasma from healthy controls. Previous studies have demonstrated the implication of the IL-33/STL2 pathway in cancer. Because our results revealed a T-antigens-dependent induction of the IL-33/ST2 axis, IL-33/ST2 may play a role in the tumorigenesis of MCPyV-positive MCC. Therefore, neutralizing the IL-33/ST2 axis may present a novel therapeutic approach for MCC patients.

Skin Graft Donor Site Healing among Elderly Patients with Dermatoporosis - A Case Series.

We reviewed donor site wound healing among morbid ≥65-year-old patients after split-thickness skin graft (STSG) harvesting. Patients were treated for a pretibial laceration or hematoma in Kymenlaakso Central Hospital, Finland, between 2015 and 2019. Twelve morbid patients with a mean Charlson Comorbidity Index of 7.1 (range 4-12) and a mean age of 80.6 years (range 69-91) were studied. Nine patients were female. Eight had a chronic cutaneous fragility syndrome, eg, dermatoporosis. All donor site areas were located on the thigh and were less than 2% TBSA. One donor site infection occurred. STSG integration on the pretibial wound bed was successful with all patients, and none of the patients needed further operative treatment. Graft thickness varied between 0.010 to 0.014 inches. STSG donor sites healed within the normal range of 21 days in 50% of patients. Among two patients, healing took 25 days, and among four, 37 to 97 days. All donor sites healed via local wound care without the need for regrafting. 4Our study indicates that harvesting STSG from elderly and morbid patients with poor skin condition is safe and does not result in significant complications. Prolonged donor site healing can occur, which can be managed with regular local wound care.

Actualized lower body contouring surgery after bariatric surgery - a nationwide register-based study.

Massive weight loss might lead to excess skin folds causing functional, physical, and psychosocial discomfort. Following bariatric procedures, an increasing number of patients are seeking lower body contouring surgery (LBCS). The proportion of bariatric patients who undergo LBCS is largely unknown. The aim of this current study was to analyse the incidence and realization of LBCS in bariatric patients in Finland.National retrospective register linkage study including all adult patients who received bariatric surgery in Finland during 1998-2016. The data were obtained from the Finnish national health registers maintained by the Finnish Institute for Health and Welfare. Altogether 1089 (14.1%) of 7703 bariatric patients underwent LBCS during the study period. The majority of the LBCS procedures were abdominoplasty (89%). Median latency between bariatric surgery and LBCS was 31 months. The patients with LBCS were younger (p < 0.001) and received sleeve gastrectomy (p < 0.001). We revealed an annual correlation between LBCS and bariatric procedures (r = 0.683). With a two-year latency between the bariatric and post-bariatric operations, the correlation co-efficiency was strong (r = 0.927). LBCS operations ranged from 5 to 215 per hospital district. Most LBCSs (97.3%) were performed in public hospitals, and some (41%) were performed in university hospitals. This study shows that only 14.1% of bariatric patients undergo LBCS. There is a correlation between bariatric procedures and succeeding plastic surgical reconstructive procedures.

Sentinel lymph node biopsy in high-risk cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) shows malignant behaviour in 3-4% of patients with locoregional metastases and a poor prognosis, metastases that are difficult to predict clinically. Therefore, sentinel lymph node biopsy (SLNB) has been assessed, with contradictory findings thus far. We aimed to clarify the prognostic value of SLNB in high-risk cSCC patients. PATIENTS AND METHODS: We completed a retrospective clinical study amongst 63 patients, preoperatively classified as N0 with a high-risk primary cSCC of the head and neck who underwent SLNB between 2001 and 2014 at Helsinki University Hospital (Finland). Considered high risk, the inclusion criteria comprised at least two of the following characteristics: tumour diameter ≥10 mm and/or thickness ≥4 mm and a specific tumour location, such as the lips, ear, scalp and central face. Patients were followed-up postoperatively for a median of 4.1 years (0.2-13.8 years). RESULTS: Only four (6.3%) patients had positive sentinel nodes. One of these patients died of cSCC, while the other three ultimately survived their disease. Five (7.9%) patients showed a negative SLNB, but developed recurrence within one year postoperatively. Recurrence appeared in the neck lymph nodes concurrently with locoregional soft-tissue invasion in all patients. Amongst these patients, three died for cSCC and the remaining two from other causes. Comparing the SLNB-positive and SLNB-negative groups with recurrence, we identified no significant differences in terms of patient or tumour characteristics. CONCLUSIONS: SLNB appears to carry no prognostic value for identifying recurrent disease amongst high-risk cSCC in the head and neck area.

Merkel cell polyomavirus is a passenger virus in both poroma and porocarcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) has been studied in several malignant and nonmalignant tissues. However, only in Merkel cell carcinoma (MCC) has the connection to tumorigenesis been established. Previously, eccrine porocarcinoma samples were shown to express MCPyV in the majority of samples. We aimed to examine MCPyV in porocarcinoma and poroma samples using MCC as the reference material. METHODS: We analyzed 17 porocarcinoma and 50 poroma samples for the presence of MCPyV using LT antigen immunostaining and DNA detection methods. In addition, 180 MCC samples served as controls. RESULTS: MCPyV LT antigen immunostaining was detected in 10% of poroma and 18% of porocarcinoma samples; on the other hand, it was present in 65% of MCC samples. MCPyV DNA was detected in only 10% of poroma and porocarcinoma samples compared with 96% of MCC samples. The viral DNA copy number in all MCPyV DNA-positive MCCs was at least 25 times higher than that in porocarcinoma or poroma samples with the highest MCPyV DNA-to-PTPRG ratio. CONCLUSIONS: The low number of viral DNA copies in poroma and porocarcinoma samples, together with the negative LT expression of MCPyV DNA-positive tumors, indicates that MCPyV is simply a passenger virus rather than an oncogenic driver of porocarcinoma.