A Vismodegib Experience in Elderly Patients with Basal Cell Carcinoma: Case Reports and Review of the Literature.

Cutaneous basal cell carcinoma (BCC) is the most common type of human tumor, and its incidence rate is increasing worldwide. Up until a few years ago, therapeutic options have been limited for patients with advanced BCC (including metastatic and locally-advanced BCC). Over the last few years, promising systemic therapies have been investigated for the treatment of advanced BCC. In particular, the Hedgehog signaling inhibition has shown remarkable results for this population. Hedgehog inhibitors, represented by vismodegib and sonidegib, have been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of both locally advanced and metastatic BCC, with, generally, a good safety profile. Notwithstanding the late onset of BCC in the global population, associated with life expectancy increase, only a few clinical trials have evaluated the efficacy and safety profile of Hedgehog inhibitors in this complex and neglected population. Herein, we review the major mechanisms implicated in the pathogenesis of BCC focusing on the Hedgehog signaling pathway and its therapeutic role in the elderly population. Finally, we report two case reports of BCC elderly patients in order to demonstrate both efficacy and safety of the Hedgehog inhibitors.

Primary Leiomyosarcoma of the Great Saphenous Vein: Case Report and Review of the Literature.

Soft tissue sarcomas are very rare tumors, representing less than 1% of all cancers. Leiomyosarcomas are a rare group of them representing about 6% of soft tissue sarcomas and they involve smooth muscles. Less than 2% of all leiomyosarcomas involves large blood vessels. Leiomyosarcomas of vein tunica media are very rare (1/100,000 malignant cancers) and only 10% of these originate from the great saphenous vein. In this article, we report a clinical case that occurred in our institution and review all the literature available at now.

Electrochemotherapy in Kaposi's Sarcoma Patients: From the Gold Standard Strategy to Locally Advanced Cutaneous and Subcutaneous Lesions.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as a medical procedure for skin neoplasms' treatment, especially for classic Kaposi's sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and the local control of CKS disease. The primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions' treatment. In total, 19 CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt; meanwhile, 3 and 4 out of 19 patients obtained a partial response (PR), so they underwent a second and third ECT treatment, respectively. Clinical response was evaluated during the entire timeframe of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. The control of CKS skin lesions still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors' recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi's sarcoma locally advanced lesions.

Facial artery flaps in facial oncoplastic reconstruction.

The face is one of the common sites for cutaneous cancer localization. It is well known that the face is the localization of more than 50% of skin cancers. Nowadays, the principles of modern "oncoplasty" recommend the complete excision of the cancer and the reconstruction with respect to cosmetic features of the face in terms of good color, good softness, and good texture of the flaps, utilized in cancer repair. The oncological and cosmetic results of facial reconstruction are strictly linked and the modern plastic and reconstructive surgeon must respect both oncological and cosmetic aspects. For that reason the best solution in facial cancer repair is the utilization of locoregional flaps based on the tributary vessels of the facial artery. In consideration of the dimension of recipient area to repair, the retroangular flap (RAF) or the submental flap could be used. This article is voted to illustrate a very large and long-term casuistry dedicated to these flaps.

Indications for and Limitations of Reconstruction of Auricular Defects with the "Mid-moon Flap" and Evaluation of Outcome by the Aesthetic Numeric Analogue Score.

A variety of skin grafting techniques and local flaps have been described for medium-sized auricular defect reconstruction. Despite this, the reconstruction of a medium-sized auricular defect starting from the opposite surface is not yet reported in the literature. In the present article, the authors describe a novel surgical approach, the "mid-moon flap" technique, used for 87 patients in that kind of reconstruction. Eighty-seven patients presenting tumors located on the pinnal surface were enrolled in this study. The patient distribution included 68 men and 19 women, aged from 52 to 94 years, with a median age of 77.4 years. For all the patients, a customized cutaneous flap, named the mid-moon flap, was performed for auricular defect reconstruction. Histopathology reports confirmed the diagnosis of malignant tumors, with complete excision of the lesions in all cases. Follow-ups ranged from 6 to 36 months, with a mean of 18 months. There were no recurrences of the malignancy during the study, and the aesthetic outcome was globally considered good. The authors reported that the mid-moon flap technique is most appropriate for medium-sized auricular defects for two principal reasons: it covers the recipient area very well and, at the same time, leaves almost imperceptible relics on the donor area without causing any morphofunctional alteration of the ear.

Gonadal vein leiomyosarcoma, from clinical practice to a literature review: surgical, oncological and histopathologic correlation.

BACKGROUND AND AIM: Vascular leiomyosarcomas are rare and generally originate from the muscular wall of the inferior vena cava. Leiomyosarcomas originating from the wall of the gonadal veins are rare and just about ten cases are described in literature. In the present paper, we have described a case of a LMS originating from the left gonadal vein. METHODS: A 44-year-old woman presented in March 2020 pain symptoms at the level of the left renal lodge. The subsequent CT and the biopsy confirmed the diagnosis of G2 grade LMS. The mass was then removed en bloc from the posterior and inferior pancreatic plane, from the aortic plane and from the retroperitoneal plane, post chemoteraphy. RESULTS: Pathologic report revealed a typical leiomyosarcoma, moderately differentiated G2 with minor dedifferentiated areas of pleomorphic leiomyosarcoma. CONCLUSIONS: The LMSs originating from gonadal veins represent an uncommon oncologic challenge. The radical en bloc excision represents the therapeutic gold standard.

Natural Products for the Prevention, Treatment and Progression of Breast Cancer.

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.

Efficacy of Electrochemotherapy in Breast Cancer Patients of Different Receptor Status: The INSPECT Experience.

Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ (p = 0.0297) and HR+ (p = 0.0094), while overall survival was affected by time to local progression in all groups (p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions.

INDICATIONS FOR LIMITATIONS OF THE OMENTAL PEDICLE FLAP IN IMMEDIATE BREAST RECONSTRUCTION - SURGICAL RESULTS EVALUATION AND BREAST-Q© 2.0 SURVEY.

BACKGROUND AND AIM: Immediate reconstruction with an omental flap is a recognized suitable method for a full-thickness breast reconstruction or implant coverage for well-selected cases of nipple or skin-sparing mastectomies as well as cases of skin-reducing mastectomies. The authors' aim is the evaluation of indications and limitations of this technique with an original approach and also based on the analysis of patients' global satisfaction using the BREAST-Q 2.0© survey. MATERIALS AND METHODS: From January 2014 to March 2018, 12 women aged between 29 to 67 years old (mean age: 49 years) underwent immediate breast reconstruction alone or with a definitive implant covered by a pedicled omental flap. All of them were asked to fill out the BREAST-Q© 2.0 survey. CONCLUSIONS: The careful analysis of the cases shows that the indications for the immediate breast reconstruction based on the omental flap with a minimal resulting donor-site morbidity are strictly linked to its limitations, which are correctly reported in the study, but in the same way, it suggests that patients who underwent implant-based immediate breast reconstruction with omental flap reported significant improvements in satisfaction and health-related quality of their life.

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience.

BACKGROUND: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). METHODS: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. RESULTS: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). CONCLUSIONS: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

Neoadjuvant treatment by ECT in cutaneous malignant neoplastic lesions.

Electrochemotherapy (ECT) is a local treatment and its use has been standardised for cutaneous nodules of any histological origin. In this study, we use ECT as a neoadjuvant therapy to reduce the size of neoplastic lesions to obtain an ideal cleavage plane where vital or very important vascular and/or nervous structures are separated from the tumour, thus allowing a radical surgical excision, which is otherwise unfeasible. In their retrospective study, the authors identified 41 patients who were treated at our institution with neoadjuvant intent. ECT was performed under general (30 patients, 73%), regional (9 patients, 22%) or local anaesthesia with sedation (2 patients, 5%). At a median time of 2 months (range, 0.3-9) after neoadjuvant ECT, all patients underwent surgical intervention to resect the residual tumour. Median reduction of tumour volume after ECT was 55% (range, 10%-65%). After ECT plus surgery, 25 patients (61%) had complete response (CR), 16 patients (39%) partial response (PR). The percentage of CR in patients with larger lesions (>100 mm) was 27%, in patients with smaller lesions (≤100 mm) was 73% (p = 0.0119). Major side effects after ECT were: bleeding and/or ulceration (54%) and pain (59%) naturally resolved within 1-2 months. Side effects observed after surgery were: necrosis of the flap (N = 3), a case of diastasis of the donor site. Median survival time in CR patients was 53 months (range, 4-108), whereas in PR survival was 23 months (range, 5-126), p = 0.0400. ECT represents a safe and effective therapeutic approach that could be effectively used for neoadjuvant purposes.

Treatment patterns and outcomes for patients with locally advanced basal cell carcinoma before availability of Hedgehog pathway inhibitors: a retrospective chart review.

Understanding the molecular basis of basal cell carcinoma (BCC) has led to development of Hedgehog pathway inhibitors (HPIs) for patients with advanced forms of BCC (aBCC). A practical definition of aBCC as a distinct disease entity is unavailable, and epidemiological information is limited. To conduct the RONNIE study to describe characteristics, treatment patterns, and outcomes of patients with aBCC during the period preceding HPI introduction, as well as results from patients with locally advanced BCC (laBCC). A retrospective chart review was conducted using data from adult patients with a new diagnosis of laBCC between 1st January 2005 and 31st December 2010. The study period was 1st January 2005 to 31st December 2011 to allow for inclusion of at least 12 months of follow-up information for all patients. RESULTS: Treatment data were available for 106/117 patients. Radiation and excisional surgery were the most common first-line treatment options (43.4% and 23.5% of patients, respectively). Patients typically received multiple subsequent treatments; no apparent trend or pattern was observed. Complete visual response, partial visual response, and stable disease were obtained in 51.9%, 25.9%, and 11.1% of patients, respectively, after first-line surgery, and in 53.7%, 22.0%, and 9.8%, respectively, after first-line radiation. Median progression-free survival after first-line treatment was 32.1 months. Median overall survival was 78.8 months. These data represent a baseline for laBCC before HPIs became part of the treatment algorithm. The observed heterogeneity of treatment patterns highlights the lack of an established standard treatment for laBCC before HPIs were available.

Evaluation of Social Support, Quality of Life, and Body Image in Women with Breast Cancer.

BACKGROUND: This study was aimed at comparing the quality of life, body image, and perceived social support in women with breast cancer surgery. PATIENTS AND METHODS: Patients receiving breast-conserving surgery (BCS) (n = 72), mastectomy alone (n = 44), and mastectomy with breast reconstruction (n = 41) were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Breast Cancer Module (QLQ-BR23), the Body Image Scale (BIS) and the Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: The results indicated that the BCS group had a better body image compared with the other 2 groups and better role functioning compared with the mastectomy-alone group. In the reconstruction group, body image correlated with perceived social support, especially from family and significant others. CONCLUSION: These results suggest that a positive perception of a supportive social network can help women with breast reconstruction to better cope with the psychological effects of surgery on their body image.