Tumescent local anesthesia in geriatric patients with head and neck skin cancer - a retrospective study of 782 patients.

BACKGROUND AND OBJECTIVES: Due to frailty, dermatosurgery in the elderly is preferably performed under tumescent local anesthesia, but data is limited. The aim was to evaluate tumescent local anesthesia for skin cancer surgery in the elderly with focus on clinical benefits (treatment processes, pain management) and local postoperative complication risk. PATIENTS AND METHODS: Investigation of patients ≥ 75 years with inpatient head and neck skin cancer surgery under tumescent local anesthesia. RESULTS: 2,940 procedures in 782 patients (mean age 83.3 years) were performed with the aim of complete tumor resection during the inpatient stay. 3.8 (range: 1-20) interventions were done over an average of 4.9 days (range: 1-28). 43.2% did not require any postoperative analgesia. 53.5% received NSAIDs, 3.3% opioids. Infection (13.6%) was the most common local postoperative complication. Surgical intervention due to bleeding was required in 2.8%. None was hemoglobin relevant or life-threatening. Suture dehiscence and necrosis were rare (0.6%). CONCLUSIONS: Tumescent local anesthesia is an effective method for skin cancer surgery in the elderly. By avoiding general anesthesia, treatment processes can be optimized and anesthesiologic risks minimized. Local postoperative complications are still low and well treatable. The long-lasting analgesia results in a reduced need for analgesics and drug interactions.

Sentinel lymph node biopsy for lentigo maligna melanoma under local anaesthesia.

BACKGROUND: Lentigo maligna melanoma is mainly localized in the head and neck region in elderly patients. Due to its slow horizontal growth, it has a good prognosis compared to other melanoma subtypes, but specific data are rare. OBJECTIVES: The aim of this study was to investigate sentinel lymph node biopsy in lentigo maligna melanoma under local anaesthesia and to discuss the benefit. METHODS: Investigation of patients with lentigo maligna melanoma and tumour thickness ≥1 mm treated at the Department of Dermatology, University Medical Centre Tuebingen, between January 2008 and October 2019. RESULTS: In total, 204 patients (126 SLNB, 78 non-SLNB) with a median age of 75.7 years (SLNB: 73.3 years, non-SLNB: 79.7 years) could be included. Sixteen of 126 (12.7%) sentinel lymph nodes were positive. Five-year overall survival was 87.9% (88.5% SLNB; 87.4% non-SLNB) and 5-year distant metastasis-free survival was 85.8% (85.4% SLNB; 86.7% non-SLNB). There was no significant difference for distant metastasis-free survival (p = 0.861) and overall survival (p = 0.247) between patients with and without sentinel lymph node biopsy. CONCLUSIONS: Sentinel lymph node biopsy in lentigo maligna melanoma under local anaesthesia is a safe and simple method, even in very old patients. However, LMM has a very good 5-year overall survival. In high-risk patients with high tumour thickness and/or ulceration, adjuvant immunotherapy can now be offered without the need to perform this procedure.

Risk analysis of systemic side effects of tumescent local anaesthesia in the surgical treatment of geriatric and multimorbid patients with skin cancer.

BACKGROUND: Due to demographic change and increased UV exposure, the number of dermatosurgical procedures in the elderly is increasing. Data on the occurrence of systemic side effects during and after treatment with tumescent local anaesthesia are limited and do not refer to details such as volume and composition of local anaesthetics or epinephrine additive. OBJECTIVES: The aim of this study was to investigate the risk of systemic side effects in elderly patients undergoing skin tumour surgery with tumescent local anaesthesia. METHODS: Investigation of systemic complications in patients (≥75 years) who underwent head and neck skin tumour surgery under tumescent local anaesthesia at the Department of Dermatology, University Medical Centre Tübingen, between October 2018 and March 2020. RESULTS: In total 782 patients (479 males, 303 females) with a mean age of 83.3 years (range: 75.1-102.2 years) could be included. A total of 2940 procedures were performed. Patients were assigned to two groups. The old-old group (≥75-84 years) included 491 patients and the oldest-old group (≥85 years) included 291 patients. The total inpatient stay and thus mean follow-up period was 4.9 days (range 1-28 days). 92.0% (719/782) suffered from pre-existing comorbidities. Systemic complications occurred in 10.2% (80/782; old-olds: 8.6%, oldest-olds: 13.1%). Hypertensive crisis (>180/120 mmHg) requiring intervention (6.7%) that occurred intraoperatively or during the inpatient stay was the most frequent systemic complication. Cardiac arrhythmias occurred postoperatively in 0.8% of cases. No life-threatening complications directly related to tumescent local anaesthesia were found. CONCLUSIONS: Skin tumour surgery in tumescent local anaesthesia for the elderly is safe, and complications caused by general anaesthesia can be avoided. Systemic complications can occur, but are usually mild, are caused by pre-existing diseases and perioperative excitement, and can be rapidly detected and well treated by monitoring. There is no direct correlation of complications to high-tumescent concentrations or volume quantities.

Modification of Skin Flaps for Single-Stage Reconstruction of the Nasal Ala Using All-Layer Suture: A Prospective Study.

BACKGROUND AND OBJECTIVES: After local flaps, it may be necessary to reconstruct the contour of the nasal ala. This is possible with a single-stage all-layer shaping suture. In the present study, the functional and aesthetic results after single-stage reconstruction of the nasal ala were prospectively evaluated. PATIENTS AND METHODS: Patients who underwent surgery for skin tumors of the nose between 06/2019 and 06/2020 who required reconstruction of the nasal ala as part of the defect closure and had an all-layer suture used were prospectively included in the study. A standardized evaluation of aesthetic and functional outcome was conducted by the patient and a physician at discharge as well as 4 weeks later. Patients additionally underwent a follow-up survey 6 months later. RESULTS: Thirty-seven patients were included in the study. Four weeks postoperatively, all flaps were found to be fully healed and vital. Aesthetic outcome at 4 weeks was rated as very good or good by physicians in 73% and by patients in 78.4%. Persistent complications due to reduced blood flow were not observed. CONCLUSION: The reshaping of the nasal ala as part of the defect reconstruction with an all-layer suture demonstrates very good aesthetic as well as functional results and can be performed in a single-stage procedure. .

Micrographic Surgery Allows Fascia Preservation in Dermatofibro-sarcoma Protuberans.

Removal of the deep fascia is recommended in therapy for dermatofibrosarcoma protuberans, but its necessity in the context of micrographic surgery is unclear. A retrospective clinicopathological analysis of 48 patients with dermatofibrosarcoma protuberans treated by micrographic surgery was performed, to determine in which tumours fascia preservation was feasible and safe. Histologically, 93% of tumours on the trunk and extremities and 14% of tumours in the head and neck region were fully located above the fascia. Localization on the head and neck was the only significant risk factor for tumour extension beyond the subcutis (p<0.001). Overall, 44% of tumours were completely excised above the fascia and 56% with deeper excisions. Two deeply infiltrating tumours (4%) on the head recurred, but in none of these lesions was the fascia spared. These results show that micrographic surgery allows fascia preservation in superficial tumours outside the head and neck region.

Stellenwert diagnostischer Verfahren und Risiko von Zweittumoren bei primär kutanen Lymphomen.

HINTERGRUND: Primär kutane Lymphome (PCL) unterscheiden sich oft stark im klinischen Verhalten und in der Prognose von systemischen Lymphomen des gleichen histopathologischen Typs. Ziel der Studie war es, die Verteilung der PCL-Subtypen, die Zeitspanne von der Krankheitsmanifestation bis zur Diagnosestellung, den Stellenwert diagnostischer Verfahren, das Auftreten von Zweittumoren und die verschiedenen Behandlungsmodalitäten im Rahmen des Krankheitsverlaufs zu untersuchen. PATIENTEN UND METHODIK: Retrospektive Analyse von 152 Patienten mit PCL, die von 2010-2012 an der Universitäts-Hautklinik Tübingen behandelt wurden. ERGEBNISSE: 105 Patienten mit primär kutanem T-Zell-Lymphom (CTCL) (69,1 %) und 47 Patienten mit primär kutanem B-Zell-Lymphom (CBCL) (30,9 %) wurden eingeschlossen. Die Zeitspanne von der Krankheitsmanifestation bis zur Diagnose betrug durchschnittlich vier Jahre. Mycosis fungoides (MF) (47,4 %) wurde am häufigsten diagnostiziert. Die First-Line-Therapien umfassten hier entweder eine alleinige Phototherapie (PUVA, n = 48; UVB 311 nm, n = 7) oder Kombinationstherapien (PUVA mit systemischen Retinoiden, n = 18). Häufigste Second-Line-Therapie war Interferon (INF)-α plus PUVA (n = 15). Der Behandlungsverlauf war insgesamt günstig (45,2 % Remission, 28,6 % stabile Erkrankung, 22,6 % Progress). Maligne Komorbiditäten wurden im Vergleich zu einer gesunden Vergleichsgruppe häufiger beobachtet. SCHLUSSFOLGERUNGEN: Bis zur Diagnosestellung der PCL dauert es oft mehrere Jahre. Der Wert der Staging-Verfahren ist gering. Die Behandlungsmodalitäten in früheren MF-Stadien basieren hauptsächlich auf der Phototherapie.

Importance of diagnostics and risk of secondary malignancies in primary cutaneous lymphomas.

BACKGROUND AND OBJECTIVES: Primary cutaneous lymphomas (PCL) often strongly differ in clinical behavior and prognosis from systemic lymphomas of the same histopathologic type. The aim of the study was to investigate the distribution of PCL subtypes, the average time from disease manifestation to diagnosis, the importance of diagnostic procedures, the occurrence of secondary malignancies and the different treatment modalities. PATIENTS AND METHODS: Retrospective analysis of 152 patients with PCL examined at the Department of Dermatology of the University Hospital Tübingen from 2010-2012. RESULTS: 105 patients with CTCL (69.1 %) and 47 patients with CBCL (30.9 %) were included. The average time from disease manifestation to diagnosis was four years. The most common diagnosed lymphoma was mycosis fungoides (MF) (47.4 %). First-line therapies here include phototherapy only (psoralen-UV-A [PUVA], n = 48; UVB 311 nm, n = 7) or combination therapies primarily phototherapy with systemic retinoids (n = 18). Most frequent second-line therapy was interferon (INF)-α plus PUVA (n = 15). The outcome was favorable (45.2 % remission, 28.6 % stable disease, 22.6 % progressive disease). Malignant comorbidities were observed more frequently compared to a healthy control group. CONCLUSIONS: The diagnosis of lymphoma often takes several years. The value of staging procedures is still low and the treatment modalities for MF in earlier stages are mainly based on phototherapy.

Post-operative follow-up of 150 patients with sentinel lymph node biopsy under tumescence local anesthesia.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. PATIENTS AND METHODS: We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. RESULTS: 32 % of the patients reported post-operative pain within the first 48 h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3 % of the patients. 98.7 % of the patients were satisfied with SLNB under TLA. CONCLUSIONS: SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

Use of local anesthetics with an epinephrine additive on fingers and penis - dogma and reality.

Epinephrine supplements in local anesthetics are regularly used for surgery in areas with terminal vessels. According to the pharmaceutical guidelines, the use of epinephrine as an additive to local anesthetics is contraindicated for these areas. This review provides an overview of the current scientific data as well as new clinical developments in various fields. It also reviews the current legal situation. A literature research was carried out to survey the current status of relevant data. Written inquiries to several German institutions (Institute for Quality and Efficiency in Health Care, National Association of Statutory Health Insurance Physicians, Center for Clinical Studies Tübingen, Federal Institute for Drugs and Medical Devices) were made to determine the legal situation. No evidence was found in the literature for a causal relationship between the use of epinephrine as a vasoconstrictor and necrosis of the finger or penis. Studies and reviews show that the use of local anesthetics with epinephrine on the fingers or penis is a safe procedure with many clinical and economic advantages. In routine clinical practice, the WALANT method (Wide Awake Local Anesthesia No Tourniquet) as well as the increasing incidence of skin tumors in acral areas has led to a tendency towards increasing use. However, its use is still legally contraindicated, and the pharmaceutical companies show no interest in supporting a drug study. Further clinical trials - regardless of the strength of the evidence - would not change the current legal contraindication.

Patientenzufriedenheit von 1827 Patienten nach verschiedenen Rekonstruktionsmethoden im Gesichtsbereich in Abhängigkeit von Alter, Defektgröße und Lokalisation.

HINTERGRUND: Nach Tumoroperationen erfolgt ein Defektverschluss mit den für den individuellen Fall optimalen chirurgischen Methoden. Besonders im Kopf-Hals--Bereich ist das Ergebnis sehr wichtig. Ziel der retrospektiven Studie war es, Rekonstruktionsmethoden von Defekten entsprechend Alter, Lokalisation und Größe nach funktionellen und ästhetischen Gesichtspunkten zu vergleichen. PATIENTEN UND METHODIK: Die betroffenen Patienten wurden mittels Fragebögen angeschrieben. 1827 Patienten (Alter von 18 bis 92 Jahren, Median: 56 Jahre) beurteilten postoperative Probleme, ästhetisches sowie funktionelles Ergebnis und das Gesamtresultat. Aus der Patientenakte wurden Größe und Lokalisation des Defektes sowie die Art des Verschlusses dokumentiert. ERGEBNISSE: Die Dehnungslappenplastik erhielt bezüglich des Gesamtresultats mit einer sehr guten oder guten Bewertung (86 %) das beste Ergebnis. Lappenplastiken und Hauttransplantate wurden schlechter beurteilt. Postoperative Beschwerden traten signifikant häufiger nach lokalen Lappenplastiken auf. Die Sichtbarkeit der Narbe wurde von älteren Patienten bei allen Defektgrößen (< 150 mm2 , 150-300 mm2 , > 300 mm2 ) geringer beurteilt als von jüngeren. Narben in der zentralen Gesichtspartie wurden als sichtbarer wahrgenommen. Geschlecht und Rauchen hatten keinen Einfluss. SCHLUSSFOLGERUNGEN: Narben in zentralen Gesichtsregionen werden stärker wahrgenommen. Ältere Patienten beurteilten die Narbenbildung insgesamt als unauffälliger. Dehnungslappenplastiken, auch unter Wundrandspannung, führen zu sehr guten Ergebnissen und einer hohen Patientenzufriedenheit.

Patient satisfaction in 1,827 patients following various methods of facial reconstruction based on age, defect size and site.

BACKGROUND: Defect coverage following tumor excision requires a case-by-case decision as regards the optimal reconstruction technique. In the head and neck region in particular, the cosmetic outcome is of major importance. The objective of the present study was to compare various reconstruction methods in terms of their functional and aesthetic outcome based on patient age, defect size and site. PATIENTS AND METHODS: Overall, 1,827 patients (age: 18-92 years, median age: 56 years) were contacted. Using a standardized questionnaire, they were asked to assess postoperative complications, cosmetic and functional outcome, and the overall result of the surgical procedure. In addition, patient records were used to collect data on defect size and site as well as the type of surgical procedure employed. RESULTS: Rated as very good or good (86 %), defect closure by advancement flaps received the highest scores in terms of overall result. Other flaps and skin grafts were rated less favorably. Postoperative complications were significantly more common after local flaps. Irrespective of defect size (< 150 mm2 , 150-300 mm2 , > 300 mm2 ), older patients considered the visibility of the scar to be less prominent than younger individuals. Scars in the central facial region were perceived to be more visible. Gender and smoking habits had no impact on the results of the survey. CONCLUSIONS: Scars in the central facial region were perceived to be more prominent. Overall, older individuals considered their scars to be less conspicuous. Even though they are initially associated with greater tension, advancement flaps resulted in very good aesthetic and functional results and a high level of patient satisfaction.

Safety of shortened infusion times for combined ipilimumab and nivolumab.

BACKGROUND: Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates. AIM: To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent. PATIENTS AND METHODS: We reviewed the rate of infusion-related reactions (IRRs) in the first 12 months of our single-institution experience using shortened infusion times for combined checkpoint inhibition with ipilimumab and nivolumab. RESULTS: Between May 24, 2016 and June 10, 2017, a total of 46 melanoma patients received 100 shortened cycles of combined 3 mg/kg ipilimumab and 1 mg/kg nivolumab. One patient (2.2%; 1/46) had a questionable reaction after administration of 1 mg/kg nivolumab over 30 min, but none of the other patients had a bona fide IRR. CONCLUSIONS: Shortened infusion times for combined ipilimumab and nivolumab treatment are safe, thereby facilitating a more efficient use of outpatient facilities and enhancing patient's convenience.

Intralesional anti-CD20 antibody for low-grade primary cutaneous B-cell lymphoma: Adverse reactions correlate with favorable clinical outcome.

BACKGROUND AND OBJECTIVES: Intralesional injection of anti-CD20 antibody (rituximab) has been described as effective therapeutic option for patients with indolent primary cutaneous B-cell lymphoma (PCBL). To date, no parameters that reproducibly predict favorable clinical outcome of this treatment have been identified. The study aims to evaluate the clinical response and adverse effects as well as patients' self-perception of intralesional injection of anti-CD20 antibody for treatment of indolent PCBL compared to other treatment modalities. PATIENTS AND METHODS: Eleven patients with PCBL, namely primary cutaneous follicle center lymphoma (n = 9) and primary cutaneous marginal zone lymphoma (n = 2), treated with intralesional anti-CD20 antibody were retrospectively evaluated for response rate and adverse events as well as their self-perception of anti-CD20 antibody therapy and other therapies of PCBL. RESULTS: Patients treated with intralesional anti-CD20 antibody for PCBL showed complete response or partial response in 45 % or 27 % of patients, respectively. Particularly, patients with marked flu-like symptoms after intralesional injection of rituximab responded very well to rituximab. The majority of patients considered rituximab as best therapy compared to other therapies such as excision or radiotherapy. CONCLUSIONS: Intralesional rituximab is an effective therapy with high patient satisfaction. Strong therapy induced side effects of fever, chills and headache after administration of rituximab might be used as indicator for favorable response.

Rapid generation of NY-ESO-1-specific CD4+ THELPER1 cells for adoptive T-cell therapy.

Tumor-associated antigens such as NY-ESO-1 are expressed in a variety of solid tumors but absent in mature healthy tissues with the exception of germline cells. The immune system anti-cancer attack is mediated by cell lysis or induction of growth arrest through paralysis of tumor cells, the latter of which can be achieved by tumor-specific CD4+, IFNγ-producing THelper type 1 (TH1) cells. Translation of these immune-mediated mechanisms into clinical application has been limited by availability of immune effectors, as well as the need for complex in vitro protocols and regulatory hurdles. Here, we report a procedure to generate cancer-testis antigen NY-ESO-1-targeting CD4+ TH1 cells in vitro for cancer immunotherapy in the clinic. After in vitro sensitization by stimulating T cells with protein-spanning, overlapping peptide pools of NY-ESO-1 in combination with IL-7 and low dose IL-2, antigen-specific T cells were isolated using IFNγ capture technique and subsequently expanded with IL-2, IL-7 and IL-15. Large numbers of NY-ESO-1-specific CD4+ T cells with a TH1 cytokine profile and lower numbers of cytokine-secreting CD8+ T cells could be generated from healthy donors with a high specificity and expansion potential. Manufactured CD4+ T cells showed strong specific TH1-responses with IFNγ+, TNFα+, IL-2+ and induced cell cycle arrest and apoptosis in tumor cells. The protocol is GMP-grade and approved by the regulatory authorities. The tumor-antigen specific CD4+ TH1 lymphocytes can be adoptively transferred as a T-cell therapy to boost anticancer immunity and this novel cancer treatment approach is applicable to both T cells from healthy allogeneic donors as well as to autologous T cells derived from cancer patients.