Surgery vs non-surgery in cutaneous melanoma based on SEER database: A cross-sectional study.

ABSTRACT: This study was to assess the survival outcome of cutaneous melanoma (CM) patients with surgery vs non-surgery through inverse probability of treatment weighting (IPTW) using the propensity score. Patients diagnosed as CM were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. The survival outcome was estimated and compared by IPTW using the propensity score. Totally 2203 CM patients were identified, in which 1921 cases received surgical treatment (surgery group), while 282 cases didn't (non-surgery group). The median survival time of surgery and non-surgery groups was respectively 150 months and 15 months (unmatched cohort), 70 months and 40 months (matched cohort) and 130 months vs. 75 months (IPTW-weighted cohort). Compared with the non-surgery group, the surgery group had a lower risk of death in unmatched [hazard ratio (HR): 0.647, 95% confidence interval (CI): 0.509-0.821, P < .001] and matched (HR: 0.636, 95%CI: 0.459-0.882, P < .01) cohorts. In multivariate Cox model of IPTW-weighted cohort, the risk of death in the surgery group decreased notably than the non-surgery group (HR: 0.423, 95%CI: 0.383-0.468, P < .001). In conclusion, CM patients receiving surgical treatment are associated with a better survival outcome compared with those without surgical treatment through IPTW using the propensity score.

The Effect of Organ System Surgery on Intensive Care Unit Mortality in a Cohort of Critically Ill Surgical Patients.

BACKGROUND: The critical illness burden in the United States is growing with an aging population obtaining surgical intervention despite age-related comorbidities. The effect of organ system surgical intervention on intensive care units (ICUs) mortality is unknown. METHODS: We performed an 8-year retrospective analysis of surgical ICU patients. Poisson regression analysis was performed assessing the relative risk of in-hospital mortality based on surgical intervention. RESULTS: Of 468 000 ICU patients included, 97 968 (20.9%) were surgical admissions and 97 859 (99.9%) had complete outcomes data. Nonsurvivors were older (68.8 ± 15.4 vs. 62.7 ± 15.8 years, P < .001) with higher Acute Physiology, Age, Chronic Health Evaluation (APACHE) III Scores (81.4 ± 33.6 vs. 46.7 ± 20.1, P < .001. Patients with gastrointestinal (GI) (n = 1,558, 7.8%), musculoskeletal (n = 277, 5.5%), and neurological (n = 884, 4.6%) system operations had the highest mortality. Upon Poisson regression model, patients undergoing emergent operative interventions on the neurologic system (RR 1.86, 95% CI 1.67-2.07, P < .001) had increased relative risk of mortality when compared to emergent operative interventions on the cardiovascular system after controlling for pertinent covariates. Elective operative interventions on the respiratory (RR 2.39, 95% CI 2.03-2.80, P < .001), GI (RR 2.34, 95% CI 2.10-2.61, P < .001), and skin and soft tissue (RR 2.26, 95% CI 1.77-2.89, P < .001) systems had increased risk of mortality when compared to elective cardiovascular system surgery after controlling for pertinent covariates. CONCLUSION: We found significant differences in the risk of mortality based on organ system of operative intervention. The prognostication of critically ill patients undergoing surgical intervention is currently not accounted for in prognostic scoring systems.

Mini-Skin Incision for Carotid Endarterectomy: Neurological Morbidity and Health-related Quality of Life.

BACKGROUND: Cranial and cervical nerve (CCN) injury is recognized as a possible complication after carotid endarterectomy (CEA), which may result in minor local neurologic deficiencies and significant discomfort for the patient. The aim of this study is to investigate the effect of a mini-skin incision (<5 cm) on the CCN injury after CEA in comparison to standard longitudinal incision of 12-15 cm in a high volume center, and to evaluate health-related quality of life (HRQOL) outcomes in those patients who had undergone both types of the skin incision. METHODS: From January 2013 to December 2019, 446 CEAs (47.3%) were performed through a standard neck incision of 12-15 cm (group A), while 496 (52.7%) were performed through a mini-skin incision (<5 cm) (group B). Sixty-two patients underwent standard neck incision on one side and mini-skin incision on the other side (subgroup B). The main outcome measures were stroke, death, CCN injuries, cervical hematoma rates, and reinterventions. The HRQOL was assessed at baseline and after 30 days using Medical Outcomes Study Short-Form 36 and 6 disease-specific modified Likert scales. RESULTS: The stroke and death rate at 30 days was 1.12% in group A and 1% in group B (P = 1). The incidence of CCN deficits was significantly lower in group B (5.1%) in comparison to group A (13.4%) (P < 0.001). The cervical hematoma was more common after standard incision (4.9% vs. 1.2%, P = 0.02). HRQOL at 1 month showed that the outcomes after mini-skin incision were significantly better for less difficulty with eating/swallowing and neck pain (P < 0.01). CONCLUSIONS: CEA through a small incision (<5 cm) may reduce CCN complications without additional perioperative neurologic risks. As validated by patients with bilateral disease who experienced both surgical techniques, mini-skin incision is also associated with better HRQOL at 1 month, particularly with regard to eating/swallowing and neck pain.

Cutaneous Melanoma - A Review of Systemic Therapies.

This decade has brought significantly improved outcomes for patients with advanced melanoma with immunotherapies and targeted treatments offering utility in a variety of settings. In 2020, we can hope for durable long-term responses, and complete remission in a subset of patients with metastatic disease. In the adjuvant setting, approximately 50% improvements in recurrence-free survival are seen both with targeted and immunotherapies. Early data from neoadjuvant immunotherapy clinical trials are very promising. However, responses to treatment are heterogeneous and not always durable; further advances are required, and several emerging strategies are of particular interest. We review the systemic treatment of melanoma, discussing the treatment of unresectable stage III-IV and recurrent disease, outlining curative treatment of cutaneous melanoma in the adjuvant setting and briefly discussing neoadjuvant systemic therapies for advanced melanoma.

Dermatofibrosarcoma protuberans: surgical management of a challenging mesenchymal tumor.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade malignant mesenchymal tumor of the soft tissue, characterized by slow infiltrative growth and common local recurrence, with rare distant metastases. PATIENTS AND METHODS: We present a retrospective study of nineteen patients who were diagnosed with DFSP and operated at our institution in > 10-year period. We examined the clinicopathological parameters with special emphasis on the margin status regarding the clinical outcome and the follow-up. RESULTS: A total of eight cases underwent re-excision at our institution following primary excision or incisional biopsy performed at a different institution. Seven cases received excision after incisional biopsy at our institution. Four patients developed recurrent disease following primary excision with histological R0 margins at other institutions and received re-excision at our institution. All excisions at our institution resulted in R0 margins with no recurrence recorded at last follow-up (6 to 175; mean 84 months). The mean margin for those who received resection at our institution was 1.67 cm. Negative margins upon primary excision were achieved using a mean margin width of 2.04 cm. Most common tumor localization was the trunk (10 cases). CONCLUSION: Awareness of this rare entity is important for a prompt diagnosis and a proper management of the disease. The greatest clinical challenge in the management of DFSP is achieving local control. Complete excision of the tumor with surgical margin widths of at least 2 cm is recommended.

Patient-reported outcomes in patients with resected, high-risk melanoma with BRAFV600E or BRAFV600K mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: In the phase 3 COMBI-AD study, patients with resected, stage III melanoma with BRAFV600E or BRAFV600K mutations received adjuvant dabrafenib plus trametinib or placebo. The primary analysis showed that dabrafenib plus trametinib significantly improved relapse-free survival at 3 years. These results led to US Food and Drug Administration approval of dabrafenib plus trametinib as adjuvant treatment for patients with resected stage III melanoma with BRAFV600E or BRAFV600K mutations. Here, we report the patient-reported outcomes from COMBI-AD. METHODS: COMBI-AD was a randomised, double-blind, placebo-controlled, phase 3 study done at 169 sites in 25 countries. Study participants were aged 18 years or older and had complete resection of stage IIIA (lymph node metastases >1 mm), IIIB, or IIIC cutaneous melanoma as per American Joint Committee on Cancer 7th edition criteria, with BRAFV600E or BRAFV600K mutations, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system, stratified by mutation type and disease stage, to receive oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) or matching placebos for 12 months. Patients, physicians, and the investigators who analysed the data were masked to treatment allocation. The primary endpoint was relapse-free survival, reported elsewhere. Health-related quality of life, reported here, was a prespecified exploratory endpoint, and was assessed with the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in the intention-to-treat population. We used a mixed-model repeated-measures analysis to assess differences in health-related quality of life between groups. This study is registered with ClinicalTrials.gov, number NCT01682083. The trial is ongoing, but is no longer recruiting participants. FINDINGS: Between Jan 31, 2013, and Dec 11, 2014, 870 patients were enrolled and randomly assigned to receive dabrafenib plus trametinib (n=438) or matching placebos (n=432). Data were collected until the data cutoff for analyses of the primary endpoint (June 30, 2017). The median follow-up was 34 months (IQR 28-39) in the dabrafenib plus trametinib group and 33 months (20·5-39) in the placebo group. During the 12-month treatment phase, there were no significant or clinically meaningful changes from baseline between groups in EQ-5D-3L visual analogue scale (EQ-VAS) or utility scores. During treatment, there were no clinically meaningful differences in VAS scores or utility scores in the dabrafenib plus trametinib group between patients who did and did not experience the most common adverse events. During long-term follow-up (range 15-48 months), VAS and utility scores were similar between groups and did not differ from baseline scores. At recurrence, there were significant decreases in VAS scores in both the dabrafenib plus trametinib group (mean change -6·02, SD 20·57; p=0·0032) and the placebo group (-6·84, 20·86; p<0·0001); the mean change in utility score also differed significantly at recurrence for both groups (dabrafenib plus trametinib -0·0626, 0·1911, p<0·0001; placebo -0·0748, 0·2182, p<0·0001). INTERPRETATION: These findings show that dabrafenib plus trametinib did not affect patient-reported outcome scores during or after adjuvant treatment, and suggest that preventing or delaying relapse with adjuvant therapy could be beneficial in this setting. FUNDING: Novartis.

Reconstruction of the Forehead and Scalp.

Tissue inelasticity and the hair-bearing nature of the scalp and forehead pose unique challenges during reconstruction. A thorough understanding of the surgical anatomy of the scalp and forehead is paramount for optimal reconstructive outcomes. Primary wound closure is usually preferred over secondary intention healing and skin grafting. Use of dermal alternatives and tissue expansion are adjunctive therapies to facilitate scalp wound closure. Local skin and soft tissue flaps are commonly used for most small to medium defects; however, microsurgical free tissue transfer can be considered for large full-thickness skin defects of the forehead and scalp.

Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell Carcinoma.

In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I and II. We performed a monocentric retrospective study of 37 consecutive cases with Merkel cell carcinoma stage I to III treated with a combination of surgery and adjuvant radiation to evaluate progression-free and overall survival. The median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary tumours, of which 13 had negative sentinel lymph node biopsy (IA n = 10 and IIA n = 3) and 18 no sentinel lymph node biopsy (IB n = 15 and IIB n = 3), 2 tumours with positive sentinel lymph node biopsy (IIIA) and 4 with local macrometastasis (IIIB). The median age was 71 years and the median follow-up was 60.4 months. The 5-year progression-free survival was 83.8% and 5-year disease-specific survival was 95.7% (overall survival 93.0%). So far, our results show a high survival rate with combined treatment of surgery and adjuvant radiotherapy in early tumour stages of Merkel cell carcinoma.

The long-term results and prognostic significance of cutaneous melanoma surgery using sentinel node biopsy with triple technique.

BACKGROUND: The sentinel lymph node biopsy (SLN) is a basic staging method in all primary cutaneous melanomas ≥pT1b. The standard technique is a triple technique consisting of preoperative lymphoscintigraphy, intraoperative blue-dye lymphography, and gamma-probe assessment. We performed the analysis of long-term results in a very large one-institution series of cutaneous melanoma patients. METHODS: We have analyzed treatment results of a group of 1764 consecutive patients with cutaneous melanoma, who underwent SLN biopsy between 1997 and 2008 in one tertiary center. Additionally, we have analyzed the outcomes of a group of 473 patients with positive SLN biopsy undergoing completion lymph node dissection (CLND). Median follow-up time was 5.3 years. RESULTS: Metastases to SLN (SLN+) were found in 19.9%. Eight-year overall survival (OS) rate in the entire group was 73.5%, 80% without SLN metastases (SLN-) and 50% in group with SLN+ (p < 0.001). Independent prognostic factors for OS were as follows: presence of metastases to SLN, primary tumor ulceration, and higher mitotic index (>5/mm(2)) of primary tumor. The nodal recurrences in the biopsied lymphatic basin were 5.4%. The metastases to non-sentinel lymph nodes (NSLN found in 27% of patients with SLN+) correlated (on multivariable logistic regression analysis) with primary tumor thickness >4 mm, SLN metastatic deposit size >1 mm, and extracapsular involvement of SLN. In an additionally analyzed SLN+ group, the NSLN involvement was related to poorer prognosis (8-year OS rate NSLN- vs NSLN+: 59.6 vs. 34.7%, respectively). The independent prognostic factors for OS in the SLN+ group were a higher Breslow thickness and ulceration of primary tumor, metastases to more than 1 lymph nodes. CONCLUSIONS: The long-term results confirm crucial prognostic significance of SLN biopsy in cutaneous melanoma. We identified factors related to NSLN involvement, which in the future may limit indications for CLND.

A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm.

BACKGROUND: Most guidelines recommend at least 2-cm excision margin for melanomas thicker than 2 mm. OBJECTIVE: We evaluated whether 1- or 2-cm excision margins for melanoma (>2 mm) result in different outcomes. METHODS: This is a retrospective cohort study on patients with melanomas (>2 mm) who underwent tumor excision with 1-cm (228 patients) or 2-cm (97 patients) margins to investigate presence of local recurrences, locoregional and distant metastases, and disease-free and overall survival. RESULTS: In all, 325 patients with mean age of 61.84 years and Breslow thickness of 4.36 mm were considered for the study with a median follow-up of 1852 days (1995-2012). There was no significant difference in the frequency of locoregional and distant metastasis between the 2 groups (P = .311 and .571). The survival analysis showed no differences for disease-free (P = .800; hazard ratio 0.948; 95% confidence interval 0.627-1.433) and overall (P = .951; hazard ratio 1.018; 95% confidence interval 0.575-1.803) survival. LIMITATIONS: The study was not prospectively randomized. CONCLUSIONS: Our study did not show any significant differences in important outcome parameters such as local or distant metastases and overall survival. A prospective study testing 1- versus 2-cm excision margin is warranted.

Comparison of acute skin reaction following morning versus late afternoon radiotherapy in patients with breast cancer who have undergone curative surgical resection.

We investigated the relationship between the time of radiotherapy (RT) and treatment outcomes in breast cancer. Patients with pathologic T1-2N0-1 breast cancer who received adjuvant RT in the morning (before 10:00 AM) or late afternoon (after 3:00 PM) were eligible for inclusion in this study. We retrospectively compared the clinicopathologic characteristics, acute skin reaction, and survival outcomes according to the time of RT. The median follow-up duration was 83 months (range, 10-131 months). From the 395 eligible patients, 190 (48.1%) and 205 (51.9%) patients were classified into the morning RT group and the afternoon RT group, respectively. The clinicopathologic characteristics were relatively well balanced between the treatment groups, except for pathologic N-stage (P = 0.0409). Grade 2 or higher acute skin reaction according to the Radiation Therapy Oncology Group criteria was observed in 39 (9.9%) patients, with a higher frequency in the afternoon RT group than the morning RT group (13.7% vs 5.8%, respectively; P = 0.0088). There was no difference in the failure patterns or survival outcomes between the treatment groups. RT in late afternoon was associated with increased Grade 2 or more skin reaction after RT for breast cancer patients, but treatment outcomes did not differ according to the time of RT. Individualized considerations for treatment should be taken into account to reduce the risk of skin reactions.

[Platelet inhibitors and anticoagulants: managing blood thinners in dermatosurgery]. / Thrombozytenaggregationshemmer und Antikoagulanzien : Umgang mit Blutverdünnern in der Dermatochirurgie.

Many patients requiring dermatologic surgery are taking anticoagulants or antiplatelet agents. The perioperative management of these drugs is not standardized and affected by fear of bleeding complications. Studies show only moderate increase in bleeding complications while taking these drugs. Our clinical experience shows no significant peri- or postoperative bleeding. As part of a risk assessment, thromboembolic complications outweigh any bleeding risk of surgery. Therefore, in the experience of the authors, blood thinning drugs should be continued before and during dermatosurgical procedures. General assessment of laboratory parameters concerning coagulation or platelet function is not necessary and can be restricted to selected subgroups of patients.

Perioperative haemostatic management of haemophilic mice using normal mouse plasma.

Intense haemostatic interventions are required to avoid bleeding complications when surgical procedures are performed on haemophilia patients. The objective of this study was to establish an appropriate protocol for perioperative haemostatic management of haemophilic mice. We assessed the prophylactic haemostatic effects of normal mouse plasma (NMP) on haemophilia B (HB) mice for both a skin flap procedure and a laparotomy. When 500 µL of NMP was administered to the mice, plasma factor IX (FIX:C) levels peaked at 15.1% immediately after intravenous (IV) administration, at 6.1% 2 h after intraperitoneal (IP) administration and at 2.7% 6 h after subcutaneous administration. Administering 500 µL of NMP via IP or IV 30 min in advance enabled the skin flap procedure to be performed safely without any complications. After the laparotomy procedure, several mice in the IP administration group exhibited lethal bleeding, but all mice survived in the IV administration group. Anti-mouse FIX inhibitors did not develop, even after repetitive administrations of NMP. However, human FIX concentrates, especially plasma-derived concentrates, elicited the anti-human FIX inhibitors. The results show that administering 500 µL of NMP via IV or IP 30 min in advance enables surgical procedures to be safely performed on HB mice, and that IV administration is more desirable than IP if the procedure requires opening of the abdominal wall.