New Treatment Horizons in Uveal and Cutaneous Melanoma.

Melanoma is a complex and heterogeneous malignant tumor with distinct genetic characteristics and therapeutic challenges in both cutaneous melanoma (CM) and uveal melanoma (UM). This review explores the underlying molecular features and genetic alterations in these melanoma subtypes, highlighting the importance of employing specific model systems tailored to their unique profiles for the development of targeted therapies. Over the past decade, significant progress has been made in unraveling the molecular and genetic characteristics of CM and UM, leading to notable advancements in treatment options. Genetic mutations in the mitogen-activated protein kinase (MAPK) pathway drive CM, while UM is characterized by mutations in genes like GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. Chromosomal aberrations, including monosomy 3 in UM and monosomy 10 in CM, play significant roles in tumorigenesis. Immune cell infiltration differs between CM and UM, impacting prognosis. Therapeutic advancements targeting these genetic alterations, including oncolytic viruses and immunotherapies, have shown promise in preclinical and clinical studies. Oncolytic viruses selectively infect malignant cells, inducing oncolysis and activating antitumor immune responses. Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic virus for CM treatment, and other oncolytic viruses, such as coxsackieviruses and HF-10, are being investigated. Furthermore, combining oncolytic viruses with immunotherapies, such as CAR-T cell therapy, holds great potential. Understanding the intrinsic molecular features of melanoma and their role in shaping novel therapeutic approaches provides insights into targeted interventions and paves the way for more effective treatments for CM and UM.

The Skin and Natural Cannabinoids-Topical and Transdermal Applications.

The chemical constituents of the Cannabis plant known as cannabinoids have been extensively researched for their potential therapeutic benefits. The use of cannabinoids applied to the skin as a potential method for both skin-related benefits and systemic administration has attracted increasing interest in recent years. This review aims to present an overview of the most recent scientific research on cannabinoids used topically, including their potential advantages for treating a number of skin conditions like psoriasis, atopic dermatitis, and acne. Additionally, with a focus on the pharmacokinetics and security of this route of administration, we investigate the potential of the transdermal delivery of cannabinoids as a method of systemic administration. The review also discusses the restrictions and difficulties related to the application of cannabinoids on the skin, emphasizing the potential of topical cannabinoids as a promising route for both localized and systemic administration. More studies are required to fully comprehend the efficacy and safety of cannabinoids in various settings.

Differences and Similarities in Epidemiology and Risk Factors for Cutaneous and Uveal Melanoma.

Both cutaneous melanoma (CM) and uveal melanoma (UM) represent important causes of morbidity and mortality. In this review, we evaluate the available knowledge on the differences and similarities between cutaneous melanoma and uveal melanoma, focusing on the epidemiological aspects and risk factors. Uveal melanoma is a rare condition but is the most prevalent primary intra-ocular malignant tumor in adults. Cutaneous melanoma, on the other hand, is significantly more common. While the frequency of cutaneous melanoma has increased in the last decades worldwide, the incidence of uveal melanoma has remained stable. Although both tumors arise from melanocytes, they are very distinct entities biologically, with complex and varied etiologies. Both conditions are encountered more frequently by individuals with a fair phenotype. ultraviolet-radiation is an important, well-documented risk factor for the development of CM, but has shown not to be of specific risk in UM. Although cutaneous and ocular melanomas seem to be inherited independently, there are reported cases of concomitant primary tumors in the same patient.

Sentinel Lymph Node Biopsy in Cutaneous Melanoma, a Clinical Point of View.

Sentinel lymph node biopsy (SLNB) is a surgical procedure that has been used in patients with cutaneous melanoma for nearly 30 years. It is used for both staging and regional disease control with minimum morbidity, as proven by numerous worldwide prospective studies. It has been incorporated in the recommendations of national and professional guidelines. In this article, we provide a summary of the general information on SLNB in the clinical guidelines for the management of cutaneous malignant melanoma (American Association of Dermatology, European Society of Medical Oncology, National Comprehensive Cancer Network, and Cancer Council Australia) and review the most relevant literature to provide an update on the existing recommendations for SLNB.

Skin Dialogues in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic skin disorder associated with significant quality-of-life impairment and increased risk for allergic and non-allergic comorbidities. The aim of this review is to elucidate the connection between AD and most common comorbidities, as this requires a holistic and multidisciplinary approach. Advances in understanding these associations could lead to the development of highly effective and targeted treatments.

TECHNICAL DIFFICULTIES AND PROCEDURAL COMPLICATIONS IN CLOSING MALIGNANT ESOPHAGEAL-RESPIRATORY FISTULAS.

The aim of the study was to outline technical difficulties and procedural complications of using partially covered esophageal self-expandable metal stents (SEMSs) in malignant esophageal respiratory fistulas (ERFs) as a palliative treatment option. In this study, 150 patients with malignant dysphagia underwent treatment with SEMSs. A total of 36 ERFs were detected through endoscopic or clinical assessment. Complete fistula sealing with SEMSs was possible in 35 of the 36 patients. The majority of fistulas were diagnosed in male patients with advanced esophageal cancer. All of them presented with prolonged dysphagia and cachexia. Stent migration or tumoral overgrowth was identified in 6 cases with recurrent dysphagia, and required a second stent insertion. SEMSs were highly efficient in 98% of the patients studied with ERFs, with successfully sealed ERFs after the first attempt, with an overall median survival rate of 92 days. The technique of esophageal SEMS placement is simple and can be rapidly mastered. Patients with ERFs have a respiratory shunt that makes intubation difficult and is often avoided. Restoring oral feeding increased the patient quality of life. SEMS placement is generally safe, but has few associated postoperative complications.

Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

Design and Testing of an Experimental Steam-Induced Burn Model in Rats.

BACKGROUND: Most of the current models for experimental burns pose difficulties in ensuring consistency and standardization. AIM OF STUDY: We aimed to develop an automated, reproducible technique for experimental burns using steam-based heat transfer. METHODS: The system developed for steam exposure was based on a novel, integrated, computer-controlled design. Three groups of rats were exposed to steam for 1, 3, and 7 seconds. The lesions were evaluated after 20 minutes, 48 hours, and 72 hours after burn induction. RESULTS: One-second steam application produced a superficial second-degree burn; three-second application induced deep second-degree burn; and seven-second application led to a third-degree burn. CONCLUSION: The high level of automation of our integrated, computer-controlled system makes the difference between our system and other models, by ensuring the control of the duration of exposure, temperature, and pressure and eliminating as many potential human generated errors as possible. The automated system can accurately reproduce specific types of burns, according to histological assessment. This model could generate the reproducible data needed in the study of burn pathology and in order to assess new treatments.

New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

PURPOSE: Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. MATERIALS AND METHODS: A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected. RESULTS: In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40-42°C and 42-44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments. CONCLUSIONS: We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

EGIST of the greater omentum - case study and review of literature.

The development of immunohistochemical methods has outlined a particular group of tumors, with very specific features and treatment, originating in the Cajal cells of the muscularis propria or related stem cell-like precursors present in the wall of the digestive tract called gastrointestinal stromal tumors (GISTs). A sub-segment with similar features may develop outside the digestive tract, namely extra-gastrointestinal stromal tumors (EGISTs). From the small category of EGISTs, we report on a case of a primary epithelioid EGIST of the greater omentum, which is seldom reported in literature. The tumor was diagnosed in a man with non-specific symptoms who presented for abdominal enlargement. The tumor was characterized and there was a preoperative suspicion of a non-digestive tumor located in the greater omentum. The tumor was surgically removed showing no contact with adjacent organs. Immunohistochemical examination was consistent with a primary EGIST of the greater omentum. Treatment with Imatinib mesylate was started and at two-year follow-up, the patient is disease free. The case raises problems regarding pathogenesis, immunohistochemical features, behavior, evolution and prognosis of omental EGIST, for which no significant or conflicting data are available in the literature.

Hepatocellular carcinoma: insights in the biological treatment beyond sorafenib.

UNLABELLED: Hepatocellular carcinoma has an increasing incidence and an impressive mortality. At present, the only authorized systemic treatment is the multi-kinase inhibitor sorafenib. A multitude of clinical trials are aimed at improving outcomes, both in firstY- and in second-line therapy. In this multitude of clinical trials, the purpose of our article was to familiarize physicians with the mechanisms of action of new biological therapies and to offer an algorithm for optimal trial selection for each patient, based on clinical and biological indicators. The available data were structured as follows: antiangiogenic therapy, c -MET inhibitors, combinations of chemotherapy with sorafenib, immune response modulators, cellular metabolism modulators, mTOR inhibitors, other multi-kinase inhibitors. CONCLUSION: Treatment of advanced hepatocellular carcinoma remains a challenge for oncologists. Choosing the "right" trial may be the only chance of prolonging patient survival and improve his/her clinical status.

Laparoscopic-assisted percutaneous endoscopic transgastrostomy jejunostomy.

BACKGROUND AND OBJECTIVES: New therapeutic protocols for patients with end-stage Parkinson disease include a carbidopa/levodopa combination using continuous, modulated enteral administration via a portable pump. The typical approach involves a percutaneous endoscopic transgastrostomy jejunostomy (PEG-J), which requires a combination of procedures designed to ensure that no organ is interposed between the abdominal wall and the gastric surface. Lack of transillumination in maximal endoscopic light settings is a major contraindication for PEG-J, and we decided to use a different approach to establish enteric access for long-term medication delivery via pump, using a minimally invasive procedure. METHODS: In all patients, we performed a laparoscopic-assisted percutaneous transgastrostomy jejunostomy (LAPEG-J) after an unsuccessful endoscopic transillumination. RESULTS: Five patients with end-stage Parkinson disease were referred to our department after successful therapeutic testing with administration of levodopa/carbidopa via naso-jejunal tube. All patients failed the endoscopic transillumination during the endoscopic procedure and were considered for LAPEG-J. In all patients, the LAPEG-J procedure was uneventful. The most common reason identified for failed transillumination was a high position of the stomach, followed by interposition of the liver or colon between the stomach and anterior abdominal wall. There were no complications regarding the LAPEG-J procedure, and all patients were discharged during the second postprocedural day. CONCLUSIONS: LAPEG-J provides a simple and safe option for placing a jejunostomy after an unsuccessful PEG-J attempt.

Giant solitary gastric Peutz-Jeghers polyp mimicking a malignant gastric tumor: the largest described in literature.

A solitary Peutz-Jeghers polyp is defined as a unique polyp occurring without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers syndrome. Gastric solitary localization is a rare event, with only eight reported cases to date. We report herein the case of a 43-year old woman who presented with upper gastrointestinal bleeding, severe anemia, weight loss and asthenia. Endoscopy revealed a giant polypoid tumor with signs of neoplastic invasion of the cardia, with pathological aspect suggesting a Peutz-Jeghers hamartomatous polyp. Computed tomography suggested a malignant gastric tumor and a total gastrectomy was performed. The pathological specimen showed a giant 150/70/50 mm polypoid tumor and immunochemistry established the final diagnostic of a Peutz-Jegers type polyp. This is the largest solitary Peutz-Jeghers gastric polyp reported until now, and the second one mimicking a gastric malignancy with lymph node metastasis.