Cemiplimab in Ultra-Octogenarian Patients with Cutaneous Squamous Cell Carcinoma: The Real-Life Experience of a Tertiary Referral Center.

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is provided for locally advanced cSCC. METHODS: We retrospectively revised all patients with locally advanced/metastatic cSCC treated with anti-PD1 antibody (Cemiplimab) at our Institution from January 2020 to March 2023 (minimum follow-up of 4 months on treatment). RESULTS: Overall, we consecutively treated 20 ultra-octogenarian patients, of whom 15 were males and 5 were females (median age: 86.9 years). Despite age, a median number of concomitant drugs, and comorbidities, efficacy, and safety were superimposable with the available literature. No patients reported treatment-related adverse events of grade 3 or higher. Grade 2 adverse events were reported in 25% of patients. Overall, the response rate was 65%, with 50% partial responses and 20% long-lasting stable disease. The median duration of response was 14 months. The G8 elderly score was assessed in all patients, and the median score was 12 (range 9-14). CONCLUSIONS: Among ultra-octogenarian patients, a clinical benefit from Cemiplimab was obtained in most, including tumor shrinkage and pain relief. Cemiplimab confirmed its effectiveness in elderly patients in a real-life setting, with no new safety concerns.

Necrosis of the nipple-areola complex in breast reduction. Our personal way to solve problem.

Necrosis of the NAC is a condition that penalizes patients who underwent breast reduction surgery or mastopexy. Breast reduction is a widely used technique for over-sized breasts. Breast hypertrophy, in fact, can cause the onset of many issues--both aesthetical and pathological--because of the excessive weight that the breasts exert on the patient's spine. Aim and objective of our study is to suggest a systematic use of diagnostic imaging composed of pre-operative and intraoperative ultrasound with color-Doppler and pre-operative MRI. Trying to solve this problem definitively, we relied on our notions of anatomy on ten fresh cadavers, on whose twenty breasts we could make very detailed dissections. The dissections led us to conclude that, albeit with their anatomic differences, each breast was characterized by a vascular-nervous pedicle coming out from the inter-costal spaces and aimed to the blood supply to the NAC. To overcome the anatomic variations between one subject and another--but also between one breast and the other from the same patient, we relied on diagnostic imaging, both in the pre-operative and in the intra-operative staging. This way we were able to intervene successfully with 15 patients, none of which has complained damages to the vascularity or innervation of the NAC so far. In conclusion we believe that pre and intra operative diagnostic imaging is the only way to completely eliminate any potential risk of NAC necrosis. Only by means of the systematic use of conventional imaging--especially during surgery--it is possible to constantly monitor the position of the NAC's pedicle in a breast that is being reduced in volume.

KOr.U Face Lift: Personal Technique.

AIM: Facial aging is the union of multiple effects such as exposure to the sun, ambiental stress, smog, tobacco. It reflects the dynamic, cumulative effects of time on the skin, soft tissues, and deep structural components of the face showing skin textural changes and loss of facial volume. There are a multitude of techniques currently used to perform face lifts, but the unique objective is to achieve a good and safe result. METHODS: This paper describes a new safe approach to midfacial rejuvenation that combines the elements of superficial musculoaponeurotic system (SMAS) plication, about four vectors, with a blepharoplasty to achieve long-lasting improvement of the aging midface and a more natural effect. Plication of the SMAS over the suture, provides three vectors of elevation beneath the skin in midface rhytidectomy linked to the Lorè's fascia and the third vector of elevation of platysma behind the ear. RESULTS: This new technique, called KOr.U technique, was used in 31 patients between October 2010 and October 2012, producing effective long-lasting results, returning a volume of midface with no injury. DISCUSSION: This simplified approach is safe and can be easily performed under local anesthesia as an isolated midface procedure, avoiding the facial nerve.

Oncoplastic reshaping in breast-conserving surgery in a peripheral hospital. The Novi Ligure "San Giacomo" hospital experience.

AIM: To confirm that oncoplastic approach to cancer is a fundamental part of modern breast conserving surgery also in a suburban hospital. MATERIAL OF STUDY: The Authors used oncoplastic techniques in 60 cases including 45 first level and 15 second level procedures: they show some cases of conservative surgery and breast reshaping with upper, medial and lower pedicle. DISCUSSION: Screening programs are able to identify early breast cancer; the breast conserving surgery with oncoplastic glandular reshaping should be an established custom to ensure oncological safety with the best cosmetic result. CONCLUSIONS: The oncoplastic approach to breast cancer should be the theoretical and practical knowledge of the breast surgeon. Today in fact the breast surgeon must be a "vertical surgeon" in order to treat cancer completely, interfaced with a multidisciplinary team to ensure a personalized treatment for each patient. In this presentation the Authors want to focus on oncoplastic surgery in a medium flow suburban hospital.

The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts.

The plant hormone abscisic acid (ABA) is released from glucose-challenged human pancreatic ß cells and stimulates insulin secretion. We investigated whether plasma ABA increased during oral and intravenous glucose tolerance tests (OGTTs and IVGTTs) in healthy human subjects. In all subjects undergoing OGTTs (n=8), plasma ABA increased over basal values (in a range from 2- to 9-fold). A positive correlation was found between the ABA area under the curve (AUC) and the glucose AUC. In 4 out of 6 IVGTTs, little or no increase of ABA levels was observed. In the remaining subjects, the ABA increase was similar to that recorded during OGTTs. GLP-1 stimulated ABA release from an insulinoma cell line and from human islets, by ∼10- and 2-fold in low and high glucose, respectively. Human adipose tissue also released ABA in response to high glucose. Nanomolar ABA stimulated glucose uptake, similarly to insulin, in rat L6 myoblasts and in murine 3T3-L1 cells differentiated to adipocytes, by increasing GLUT-4 translocation to the plasma membrane. Demonstration that a glucose load in humans is followed by a physiological rise of plasma ABA, which can enhance glucose uptake by adipose tissues and muscle cells, identifies ABA as a new mammalian hormone involved in glucose metabolism.

Prosthetic breast implant rupture: imaging--pictorial essay.

In recent years, requests for breast implant surgery have occurred for several reasons. First, the number of diagnosed breast cancer cases has increased, and the number of reconstructive surgeries consequently has multiplied. Second, the number of patients who constantly try to achieve a better physical shape, corresponding in Western countries to the common image of prosperous and tonic breasts, has proliferated. These circumstances have led to an increasingly frequent need for more accurate and sophisticated imaging methods to study prosthetic breast implants and their integrity. Diagnostic imaging for the study of patients with suspected breast implant ruptures uses different techniques of radiologic investigation such as mammography and ultrasonography, even if the current gold standard is magnetic resonance imaging (MRI). This study aimed to draw attention to the main MRI signs capable of highlighting contractures or ruptures of the implants that are not always clinically detectable and thus to provide plastic surgeons with an adequate instrument for discerning any possible alterations in prosthetic implants. Furthermore, it was necessary to stress the importance of teamwork. In fact, proper cooperation and coordination between radiologists and dedicated plastic surgeons are fundamental for the proper management of patients and the complications they may experience.

Immunocytochemical studies on the pituitary gland of Anguilla anguilla L., in relation to early growth stages and diet-induced sex differentiation.

Mammalian and teleost antisera against pituitary hormones were used to identify and localize pituitary cell types in the European eel (Anguilla anguilla L.). The investigation was conducted on unpigmented glass eels of 5.6-6.2 of total body length (L(T)) caught in river mouths, then on yellow eels reared from the pigmented glass eel (or elver) stage up to 12-14 cm of L(T), in an eel farm in warm freshwater. Treated elvers were fed with commercial paste food supplemented with mature carp ovaries, containing oestradiol, that induced an early ovarian differentiation and a higher growth rate. The antisera detected seven types of immunoreactive (ir) cells, six of which were already found in glass eel adenohypophysis, suggesting differentiation of these cell types during the leptocephalus stage. In 12-14 cm treated yellow eels with small ovaries, a seventh type (ir-GtH) was detected in the proximal pars distalis; in the same animals the ir-TSH cells increased in number and size. From unpigmented glass eels to 12-14 cm yellow eels, the whole pituitary volume of controls increased nearly four times, while that of treated ones increased nearly six times. The larger volume of pituitary in treated eels was mainly due to volume increase of proximal pars distalis and rostral pars distalis. The %GH, that is the potential index of GH production, was significantly higher in treated yellow eels with gonads differentiating into ovaries than in controls; no difference was detected in %PRL between treated and control eels. The above results strongly suggest that in eels the feminizing effects of oestrogen is first exerted on the pituitary, probably through the hypothalamus, and later on the gonads.

Development and early differentiation of gonad in the european eel (Anguilla anguilla [L.], Anguilliformes, Teleostei): A cytological and ultrastructural study.

The structure of the gonad of the European eel (Anguilla anguilla [L.]), an "undifferentiated" gonochoristic teleost, was investigated by transmission electron microscopy from 6-8 cm elvers to 22 cm yellow eels with juvenile hermaphroditic gonads. The pear-shaped gonads of 6-8 cm elvers assume, in 12-15 cm eels, a lamellar shape and enlarge by migration of germ cells, which we refer to as primary primordial germ cells. In the gonads of ∼ 16 cm eels, the primary primordial germ cells multiply, giving rise to clusters of germ cells that have ultrastructural characteristics of the primary primordial germ cells but show giant mitochondria, enlarged Golgi complexes, and round bodies not limited by membranes. We refer to these as secondary primordial germ cells. In 16-18 cm eels, syncytial clones of oogonia interconnected by cytoplasmic bridges are also observed. In 18-22-cm-long eels, the gonads contain primordial germ cells, oogonial clones, early oocyte cysts, single oocytes in early growth stages, and primary spermatogonia. Such germ cells are present in the same cross section where they are either intermingled or are in areas of predominantly female germ cells close to areas with predominantly male germ cells. These gonads are juvenile hermaphroditic and should be considered ambisexual because in larger eels they differentiate either into an ovary or into a testis. Somatic cells always envelop the germ cells following their migration into the gonad. These somatic cells first show similar ultrastructural features and then differentiate either into early Sertoli cells investing spermatogonia, or into early follicular (granulosa) cells investing the early previtellogenic oocytes. In eels ∼ 14 cm long, primitive steroid-producing cells also migrate into the gonad. In the ambisexual gonad they differentiate either into immature Leydig cells in the male areas, or into early special cells of the theca in the female areas. Nerve fibers are joined to the steroid-producing cells. Gonad development and differentiation are also associated with structural changes of the connective tissue characterized by the progressive appearance and deposition of collagen fibrils first in the mesogonadium, then in the gonad vascular region, and then in the germinal region. The collagen-rich areas are massive in the male areas and reduced in the female ones. J. Morphol. 231:195-216, 1997. © 1997 Wiley-Liss, Inc.