Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

Store-and-Forward Teledermatology for Assessing Skin Cancer in 2023: Literature Review

Background: The role of teledermatology for skin lesion assessment has been a recent development, particularly, since the COVID-19 pandemic has impacted the ability to assess patients in person. The growing number of studies relating to this area reflects the evolving interest. Objective: This literature review aims to analyze the available research on store-and-forward teledermatology for skin lesion assessment. Methods: MEDLINE was searched for papers from January 2010 to November 2021. Papers were searched for assessment of time management, effectiveness, and image quality. Results: The reported effectiveness of store-and-forward teledermatology for skin lesion assessment produces heterogeneous results likely due to significant procedure variations. Most studies show high accuracy and diagnostic concordance of teledermatology compared to in-person dermatologist assessment and histopathology. This is improved through the use of teledermoscopy. Most literature shows that teledermatology reduces time to advice and definitive treatment compared to outpatient clinic assessment. Conclusions: Overall, teledermatology offers a comparable standard of effectiveness to in-person assessment. It can save significant time in expediting advice and management. Image quality and inclusion of dermoscopy have a considerable bearing on the overall effectiveness. © Leah Kirsten Jones, Amanda Oakley.

Check Point SOS! A Case of Cemiplimab-Associated Sinusoidal Obstruction Syndrome

Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).

Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension

Background: The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Method(s): In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposureadjusted incidence rates per 100 patient-years (PY) were calculated. Result(s): The average age of TN OLE study participants was 41.7 years (+/-13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious;TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%;EAIR 0.1/100 PY;2 in TN and 1 in OLE;no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%;EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC < 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%];EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion(s): Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (>16,512 PY exposure). (Table Presented).

Reducing face-to-face visits for skin cancer assessment using patient-led teledermatology: a retrospective review of experience with the My Skin Selfie platform

Teledermatology has made massive progress throughout the COVID-19 pandemic, but significant debates are emerging about the correct way to use technology and deliver services in a nonpandemic future where all face-to-face (F2F) options will be available again. Some very fixed views are emerging, and it is important that future national guidelines are both evidence-based and pragmatic. Improvements in phone camera technology allow patients to take high-quality skin images. Adequate assessment of moles does require dermoscopy, but many other skin lesions can be accurately triaged without it, as was commonplace until relatively recently. There is now extensive literature confirming the ability to make safe and secure diagnoses of skin cancers using teledermatology. Debates around the optimal uses of teledermatology are now in progress. We report retrospective data from two pilot studies, for basal cell carcinoma (BCC) and 2-week wait (2WW), using patient-led skin images taken using the MySkinSelfie app and viewed on the MySkinSelfie web portal. The aim was to evaluate the number of F2F visits that had been prevented. In each pilot, patients were initially referred by their general practitioner in the usual way, without images. The BCC pilot was conducted prepandemic. Patients were sent a letter inviting them to submit images. Once images had been received, they were booked into a telephone clinic for assessment. In total, 288 patients were invited and 76 submitted images. Thirty-two (42%) needed further F2F review, 37 (49%) were booked for a surgical procedure, five (6%) were prescribed a cream and two (3%) lesions resolved. The 2WW pilot was conducted during the pandemic. Patients referred on a 2WW pathway were telephoned by administration staff and invited to submit images followed by a telephone consultation. In total, 1385 were invited and 704 submitted images. Two hundred and sixty-five (37 6%) needed further F2F review, 170 (24 1%) were booked for a surgical procedure, 219 (31 1%) were discharged and 50 (7 1%) received a cream. The agreement between diagnosis via digital images of nonpigmented skin lesions and a final diagnosis was 83%. Compared with a standard F2F model, 58% (BCC) and 62% (2WW) avoided a first F2F appointment, providing benefits for patients' travel time, infection risk and missed time at work for patients and carers. A larger prospective study is now needed to document image quality, diagnostic concordance and health economic effects with more precision.

Assessment of three different dermoscopy imaging systems during a fast-track skin cancer clinic

Dermoscopy is a noninvasive diagnostic investigation based on magnification, illumination and obliteration of light scatter on the skin surface allowing better visualization of structures beneath the stratum corneum. We aimed to assess image quality of lesions evaluated at a skin cancer clinic using three different handheld dermatoscopes;the Heine Delta 20T (contact) with an iPad;the MoleScope II (noncontact) with a Samsung 7 smartphone;and the Dino-Lite Edge with direct download to a MacBook laptop (noncontact). The Heine Delta 20T and iPad is the current standard used. The MoleScope is a mobile smartphone-attachable dermatoscope. The Dino-Lite is a handheld digital microscope that connects directly to the computer via a USB port. The cost of the Heine Delta 20T is roughly 1100, the MoleScope II 260 and the Dino-Lite 600. Twenty-three lesions were imaged with each device;15 were pigmented. A total of 69 images were downloaded and transferred to Microsoft PowerPoint for review in random order. The images were scored by four consultant dermatologists, one general practitioner with a special interest and one associate specialist, blinded to the diagnoses. A score of 1-5 (poor- excellent) was attributed to each category: (i) detail/dermoscopic features;(ii) colour discrimination;(iii) magnification. Each assessor recorded whether - based on the image alone - they could make a diagnosis. The lesions were basal cell carcinoma (n = 6), seborrhoeic keratosis (n = 4), lichenoid keratosis (n = 1), benign naevi (n = 4), dysplastic naevi (n = 2), melanoma (n = 1), blue naevus (n = 1), sebaceous gland hyperplasia (n = 1), ruptured cyst (n = 1), pyogenic granuloma (n = 1) and dermatofibroma (n = 1). The mean score for each device and category was calculated as follows. (i) Heine: detail = 3.2, colour = 3 3, magnification = 3 2 (overall score = 3 2);46 2% felt able to make a diagnosis. (ii) MoleScope: detail = 2 5, colour = 2 7, magnification 2 5 (overall score = 2 6);43 5% felt able to make a diagnosis. (iii) Dino-Lite: detail = 3 2, colour = 3 2, magnification = 3 6 (overall score = 3 3);57 2% felt able to make a diagnosis. Analysis on a PC screen allowed greater magnification than is generally employed in clinic, which may have affected assessors. The Heine is not primarily designed for digital dermoscopy. It requires two operators for image capture, whereas the other systems require only one. The MoleScope remains the most 'mobile', whereas the Dino-Lite is attached to a laptop/PC. Both the MoleScope and Dino-Lite can be used as noncontact dermatoscopes, avoiding contact medium use. Considering the current COVID-19 pandemic, these devices are less time consuming, more convenient and easier to clean. Overall, the Dino-Lite produced the best images. Despite the MoleScope scoring lower, it was comparable for diagnostic ability. It is proposed that the MoleScope and Dino-Lite systems may be optimal for use in teledermatology to facilitate virtual clinics.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report.

BACKGROUND: The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers. CASE PRESENTATION: A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient's inadequate compliance, and within 2 years, the patient's cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient's basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection. CONCLUSIONS: Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

The impact of COVID-19 on the progression and management of periocular basal cell carcinomas.

PURPOSE: To identify whether the delay caused by COVID-19 had an impact on the peroperative size of lesions and the choice of reconstruction performed in patients with periocular basal cell carcinomas (BCCs). METHODS: We undertook a retrospective study looking at whether the delay caused by COVID-19 had an impact on the lesion size at the time of surgery, and consequently, on the choice of surgical repair. Results were compared to an equivalent time period a year prior to the onset of COVID-19. Elective surgery was stepped down at our hospital between March and June 2020. We collected data on patients that underwent BCC excisions between July 2020 and April 2021 and for an equivalent time period from 2019 to 2020. Measurements at listing were compared with those preoperatively obtained and from histological specimen. RESULTS: Analysis using the paired T-test yielded a p-value 0.005 for the growth of the lesion between listing and surgery after the onset of the pandemic, while pre-COVID the p-value was 0.04. Most patients were able to undergo the same procedure as planned for despite the delay and statistically significant growth while awaiting surgery. CONCLUSION: Literature suggests that BCC operations can be safely delayed up to 3 months. Our longest wait post-COVID was 12 months with a mean wait of 5 months. Only two patients in this group had a more invasive surgery than planned. We conclude that the delay caused by the pandemic, even beyond 3 months, had a minimal impact on the surgical plan and outcomes for patients with BCCs.

BMLA 2022 Annual Conference

The proceedings contain 45 papers. The topics discussed include: developments in semi-permanent make up: tips and advice for laser removal;managing laser safety and COVID-19;a review of patients treated with ablative lasers for skin malignancies;rosacea: developments in recognizing and treating the sub-types of this progressive, inflammatory vascular disorder;laser hair removal for inflammatory medical conditions: pilonidal sinus disease;developing a predictive model to determine effectiveness of a laser using an artificial neural network;understanding the physical mechanisms involved in laser irradiation of tattoos;plume control in medical and cosmetic laser clinics: a practical guide;lasers in general dental practice - selection, safety and status;carbon dioxide laser and photodynamic therapy for the management of basal cell carcinomas;pulsed dye laser: a new case of successful treatment for reactive angioendotheliomatosis;and laser-assisted treatment in management of adult ankyloglossia.

The Impact of COVID-19 on Periocular NonMelanoma Skin Cancer in the Veteran Population

Purpose : Despite an increasing incidence of skin cancer over the last decade, studies have reported a decline in the diagnosis and treatment of skin cancer during the COVID19 pandemic. We performed a retrospective cohort study using a large population-based cohort from the Veterans Health Administration (VHA) to determine how the pandemic has affected tumor size and morbidity in veterans with periocular non-melanoma skin cancer. Methods : Electronic health records from all VHA sites were accessed through the VA Informatics and Computing Infrastructure (VINCI). Data were stored in the Observational Medical Outcomes Partnership (OMOP) model and queried via SQL Server. ICD-10 and current procedural terminology codes were used to identify patients who received Mohs surgery for periocular basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) between 08/01/2018 and 09/10/2021. A combination of structured algorithms and manual review were used to extract patient demographics, lesion characteristics, and surgical outcome at three time points, ie. pre-COVID, early, and late COVID. Unpaired t-tests were used to assess statistical significance. Results : Patient characteristics were similar between pre- and post-COVID cohorts in terms of gender, age, race, and tumor type. The average number of Mohs periocular surgeries performed per week were 23.1% (7.31 vs 5.62) and 13.1% (7.49 vs 6.51) lower in the early and later pandemic, respectively, compared to similar pre-COVID timeframes by month (Figure 1). Mean lesion size (maximum diameter) was 1.35 cm larger post-COVID compared to pre-COVID (95% CI 0.19 2.51, P=0.022);however, the defect size remained similar (Figure 2). Stratifying by tumor type, the same trends were noted in BCC, particularly early in the pandemic. However, mean SCC lesion and defect sizes did not vary over time. Conclusions : Periocular Mohs surgery rates declined in the COVID pandemic across VHA. Lesions were larger particularly in the earlier phase of the pandemic for BCC. Future analyses using this cohort will attempt to determine if telehealth and travel time were associated with distinct outcomes.

Participation in Clinical Trials Among Academic Dermatologists Affiliated With Veterans Affairs Hospitals: Survey Study.

Background: Clinical trials have led to the development of new and effective therapies for many dermatologic conditions. To our knowledge, there is no published study that has quantified and described the degree of involvement in clinical trials among academic dermatologists and their university affiliates. Objective: The purpose of this study was to characterize the involvement of academic dermatology departments in clinical trials research. Methods: An online survey was sent to 211 Veterans Affairs (VA)-employed dermatologists. It comprised 20 questions related to the number of clinical trials, support staff dedicated to clinical research, skin diseases studied, and the effect of the COVID-19 pandemic on conducting clinical research. Three rounds of survey invitations were sent over a 3-month period (March to May 2021). Data from all survey responses were reviewed for quantitative and descriptive analyses of the key outcome measures. Results: A total of 48 dermatologists completed the survey and provided their university affiliations and details of involvement in clinical trials research. Over half of participants (n=25, 58.1%) with a university affiliate reported that their affiliated dermatology department had a dedicated clinical trials unit. Basal cell carcinoma was the most frequently studied skin condition (n=9, 18.8%), followed by atopic dermatitis and psoriasis (n=4, 8.3% each); 66.7% of participants reported no current clinical trials participation. Of those conducting clinical trials, 87% (n=18) noted that COVID-19 was a barrier to conducting trials, with 52.2% (n=11) citing disrupted or decreased trials due to the pandemic. Conclusions: Although many dermatologists with university affiliations reported having a dedicated clinical trials unit at their institution, a majority of those surveyed reported not taking part in any active trials. Overall, the diseases investigated in academic clinical trials appear to follow national trends, though some of the top dermatological diseases are underrepresented in clinical trials research. A key limitation of our study was the low response rate (~23%) and that the survey responses from the sample of VA-based dermatologists may not be generalizable to all academic dermatology departments in the United States. The effect of the COVID-19 pandemic appeared to play a significant role in disrupting active trials.

Management of the Two-Week Wait Pathway for Skin Cancer Patients, before and during the Pandemic: Is Virtual Consultation an Option?

BACKGROUND: Although telemedicine emerged more than 100 years ago, the recent pandemic underlined the role of remote assessment of different diseases. The diagnoses of cutaneous conditions, especially malignant lesions, have placed significant stress on the fast-track pathway for general practitioners (GPs), dermatologists, and plastic surgeons. The aim of the study was to compare (pre- and during the pandemic) the ability of professionals to face the challenge. METHODS: The study was composed of 1943 consecutive patients (mean age 61.9 ± 18.3, 53.8% female) assessed by GPs, face-to-face (988 patients, 50.8%, between October 2019 and March 2020) and by virtual (video/photo) visits (955 patients, 49.2%, between March 2020 and October 2020) for skin lesions, and referred to secondary care via the two-week wait pathway for suspected skin malignancy. RESULTS: The two groups had similar primary skin malignancies identification rates (24.3% vs. 22.1%, p = 0.25). The virtual visits identified squamous cell carcinoma (SCC) better than face-to-face consultations (p = 0.04), but identified basal cell carcinoma less-well (BCC, p = 0.02), whereas malignant melanoma (MM) was equally identified in the two groups (p = 0.13). There was no difference in the median breach time (days) of the two-week wait pathway (12, IQR = 6 vs. 12, IQR = 5, p = 0.16) in the two groups. Virtual assessments (by GPs) of skin lesions suspected of malignancy, and referred via the two-week wait pathway, increased the probability of diagnosing SCC by 42.9% (p = 0.03), while for malignant melanomas, face-to-face and virtual consultations were alike (p = 0.12). CONCLUSIONS: The equivalent outcomes in the management of skin cancers (SCC, MM) via the two-week pathway through virtual consultations and face-to-face appointments underline the role of telemedicine as a reliable alternative to face-to-face assessments.

SAFETY PROFILE of JAK INHIBITORS in REAL WORLD from A SINGLE CENTER COHORT

Background: Recent published data have emerged some concerns about safety of Janus kinase (JAK) inhibitors and FDA have established prescribing restrictions. Objectives: The aim of this study was to analyze the safety profile of current approved JAK inhibitors in Europe with data from a Real World cohort. Methods: A single center observational study was performed including patients who had initiated treatment with Tofacitinib, Baricitinib or Upadacitinib from September, 2017 to January, 2022. Demographic, clinical, laboratory and safety variables were collected from baseline and at months 1, 3, 6 and every six months. Safety data was collected including any adverse event (AE) due to any cause. An AE was considered serious if it was life-threatening or result in hospitaliza-tion, disability or in death. All AE and SAE were expressed adjusted by exposure (E/100 PY). Results: A total of 194 patients were included whom baseline demographic and disease characteristics are exposed in Table 1. Drug exposure was 265.5 patient-years. Overall, 214 AE were detected being mild upper tract respiratory infection the most frequently registered (15.82 E/100PY) followed by Urinary tract Infection accounting 7.16 E/100PY. 10 Serious Infections were detected in 10 patients of which 5 were pneumonia (1.88 E/100PY), 1 cellulitis (0.38 E/100PY) and 2 COVID-19 (0.76 E/100PY). 12 herpetic infection were detected in 9 patients (4.52 E/100PY) of which 7 were caused by herpes zoster (2.64 E/100PY) and 5 by herpes simplex (1.88 E/100PY) 3 cases were mono-metameric and 4 multi-metameric. Moreover, 2 patient developed postherpetic neuralgia. A patient with RA developed Miliary Tuberculosis (0.38 E/100PY) with a negative IGRA test prior to the JAKi. A patient with RA suffered a Myocardial Infarction (0.38 E/100PY). 7 RA patients developed malignancy (2.64 E/100PY), one with oral squamous cell carcinoma, two Bowen carcinoma, one breast cancer, 2 basal cell carcinoma and a colorectal metastatic cancer. Not a single case of thromboembolic event nor Hepatitis B Virus reactivation were registered. 2 patients died, one with cancer and the other suffered a severe COVID-19 (unvaccinated). Conclusion: In this updated analysis of 194 patients treated with JAKi, the three approved JAKi showed a safety profile consistent with data from RCT. The patients under JAK therapy should be carefully evaluated on their follow-up.

Have Skin Biopsy Results in Adults Been Affected in the COVID-19 Pandemic?

The purpose of this study was to assess how skin biopsy results from adults, which occupy an important place in dermatological practice, have been affected by the COVID-19 pandemic. Adult patients aged over 18 presenting to the dermatology clinical of a tertiary hospital between March 12, 2019 and March 11, 2020, and between March 12, 2020 and March 11, 2021, from whom skin biopsies had been taken and who had undergone pathological examination were included in the study. Pre-COVID-19 pandemic data were compared with post-pandemic data. No significant difference was determined between the two periods in terms of age, sex, type of biopsy, preliminary diagnosis numbers, or clinicopathological correlation (P>0.05). The diseases most frequently diagnosed through biopsy before the pandemic were psoriasis (13.7%), pseudopelade of Brocq (6.8%), and fibroepithelial polyp (5.5%), compared with psoriasis (9.4%), basal cell carcinoma (BCC) (6.3%), lichen planus (6.3%), and urticarial vasculitis (6.3%) during the pandemic. Diagnoses of BCC and urticarial vasculitis were significantly elevated after the COVID-19 pandemic (P<0.05), while no periodic difference was observed in other diagnoses. A rise in the incidence of various diseases, such as urticarial vasculitis, may be indicative of a risk of asymptomatic COVID-19. Further polymerase chain reaction and/or antibody-based investigations should be carried out in order to establish whether dermatological diseases are associated with asymptomatic COVID-19 cases. Determining the clinical and histopathological aspects of COVID-19, which can progress with various cutaneous findings, will be useful in the early diagnosis and treatment of this novel and life-threatening disease.

Skin Biopsy Results of Geriatric Patients over a 5-year Period and the Frequency of Skin Diseases before and after COVID-19 Pandemic

Objective: The number of older adults has increased throughout the world. Aging affects all the organs and creates psychological, physiologic and anatomic changes. One of the most important organs of the human body is the skin, which shows the effects of aging the most. This study aims to determine whether age, gender, and season of biopsy play a significant role in skin biopsy results. Additionally, the study investigates whether the frequency of skin diseases differs before and after the coronavirus disease-2019 (COVID-19) pandemic. Methods: We conducted a retrospective study on the histopathology results of patients over 65 years old between June 2016 and September 2021. The histopathology results were obtained from the Acibadem Pathology Department. Results: Of the 677 patients, 310 (45.8%) were male and 367 (54.2%) were female. The most common disease in all patients were benign cutaneous neoplasms (23%), followed by eczematous disease (18.5%) and epithelial cutaneous cancers (16.8%). We divided the results into 12 groups: group 1: Urticaria, erythema and purpuras, group 2: Papulosquamous and eczematous diseases, group 3: Infectious diseases, group 4: Rheumatologic diseases and alopecia, group 5: Benign cutaneous neoplasms, group 6: Precancerous lesions, group 7: Basal cell carcinoma, squamous cell carcinoma, group 8: Cutaneous metastasis and other skin cancers, group 9: Pigmentation disorders, group 10: Pschycology related dermatological disorders, group 11: Granulomatous dermatitis, group 12: Bullous dermatitis. Before the COVID-19 pandemic, the most prevalent results were group 2 (21.3%), followed by group 5 (20.4%) and group 7 (16.7%) whereas, after the COVID-19 pandemic, the most frequent results were group 5 (28.4%) followed by group 7 (17.1%), and group 6 (14.9%). In terms of seasons, the most common diseases were group 5 (24.1%) in winter, group 2 (21.6%) in spring, group 5 (30.0%) in summer, and group 2 (18.9%) in autumn. Before the COVID-19 pandemic, the most common result was group 2 (21.3%), followed by group 5 (20.4%) and group 7 (16.7%), and during the COVID-19 pandemic, the most common result was group 5 (28.4%), followed by group 7 (17.1%), group 6 (14.9%). Conclusion: Many skin diseases affect the geriatric population. Geriatric patients face challenges such as multiple drug use, comorbidities, mobility problems and cognitive disorders. In our study, the most common diseases in all patients were benign cutaneous neoplasms (23%), followed by eczematous diseases (18.5%), and epithelial cutaneous cancers (16.8%). Knowing about the frequency of skin diseases is critical for the early detection of precancerous and cancerous lesions.

Multiple Basal Cell Carcinomas in Immunocompetent Patients.

BACKGROUND: The onset of multiple BCCs is a relatively common condition, not only among patients undergoing chronic treatment with immunosuppressant drugs, but also in the general population, although specific risk factors for immunocompetent patients have not been identified. A putative role of somatic mutations in the hedgehog pathway should be considered. METHODS: This study is a retrospective observation of all patients diagnosed and surgically treated for BCCs during 5 years at our Dermatological Division. For these patients, we evaluated clinical and histopathological characteristics and data about possible risk factors for BCC. RESULTS: Five-hundred and six patients affected by multiple BCCs, accounting for the 24.2% of the entire sample, have been identified. In these patients, the total number of BCCs was 1516, ranging from 2 to 11. Subjects affected by multiple BCCs were more frequently males, with an older age at diagnosis; multiple BCCs developed mainly on the trunk and were often represented by a nodular histotype. The multivariate analysis highlighted that male gender, older age, nodular BCC, or face involvement at the first diagnosis are risk factors for the development of multiple BCCs. CONCLUSIONS: The frequency of multiple BCCs even among the non-immunocompromised population underlines the need to subject patients to a close surveillance program, to allow early diagnosis and treatment of additional cancers.

THE ELDEST HEART TRANSPLANTED PATIENT IN EUROPE: 36 YEARS SURVIVAL AND STILL GOING ON

Development of endomyocardial biopsy for acute rejection monitoring in the early Seventies, and above all use of cyclosporine in the clinical practice starting from 1980, introduced the modern era of heart transplantation. Following the initial positive outcomes, the first Italian transplant was performed in Padua by V.Gallucci on November 15th 1985. This pioneering success was rapidly repeated in Pavia, where M.Viganò performed the second transplant on Novembre 17th. Recipient was 20 years old man, suffering from dilated cardiomyopathy, on urgent transplant list. Cardiac index was 1.38 l/min/m2 and pulmonary vascular resistance 1.6 WU. Donor was a 14 years old boy died of brain injury. Total ischemic time was 125 minutes. Induction immunosuppression consisted of horse anti-lymphocyte immunoglobulins, whereas maintenance therapy included cyclosporine, azathioprine and steroids. Postoperative course was complicated by pericardial effusion and cholestatic jaundice. Later pulmonary aspergillosis occurred and due to the profound immunodepression was complicated by fungal localization at L2 vertebral body. The infection was treated with surgical removal of the secondary localization and amphotericin B administration. On December 6th severe acute rejection was found at biopsy and treated with i.v. steroid pulse. Length of ICU and hospital stay was 28 and 72 days, respectively. In 1998 HCV infection was detected and eradicated in 2017 with elbasvir/grazoprevir therapy. Complications of long term immunosuppressive treatment included dyslipidemia, myeloma and basal cell carcinoma. Due to long-term calcineurin inhibitors therapy progressive chronic renal failure occurred, leading to replacement therapy in 2015 and kidney transplantation in 2016. In 2015 the patient underwent percutaneous coronary intervention with stents implantation in two marginal branches and in the anterior descending artery in 2021. Everolimus was introduced to slow down progression of cardiac allograft vasculopathy. In 2020 he suffered from Covid-19, but the course of infection was uneventful being cough the only symptom. We report the eldest survivor after heart transplant in Europe. Our case demonstrates that despite early and long-term complications of immunosuppressive therapy, a careful and patient tailored management allowed an amazing outcome. Nowadays heart transplant remains the best treatment for end stage heart failure and allows to resume a nearly normal quality of life.

Management of patients with giant basal cell carcinoma during SARS COV2 outbreak in Italy.

Basal cell carcinoma (BCC) is the most frequently occurring type of all cancers, and represents 80% of all skin cancer. The estimated lifetime risk for BCC in the white population is between 33% and 39% for men and 23% and 28% for women. Its incidence doubles every 25 years and is increasing in the young population. Death is uncommon and seems to decrease in the last years, probably due to early and better diagnosis. BCC arises from abnormal and uncontrolled growth of basal cells. It is a slow-growing tumor, therefore usually curable at an early stage with surgery or alternative treatment, such as cryotherapy, laser, photodynamic therapy, retinoids and topical agent like 5-Fluorouracil cream, imiquimod cream, and so forth. Topical treatment of superficial basocellular carcinoma is a viable option, when surgery is not an advisable treatment, especially in the case of giant basocellular carcinoma. In this subtype, imiquimod 5% cream can be a safe and effective treatment, but there are few reports in available literature. We present our case series of eight patients with superficial giant basocellular carcinoma successfully treated with imiquimod 5% cream, which showed clinical improvement after 8 weeks of treatment.