Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

The field of transplantation, including the specialized area of vascularized composite allotransplantation (VCA), has been transformed since the first hand transplant in 1998. The major challenge in VCA comes from the need for life-long immunosuppressive therapy due to its non-vital nature and a high rate of systemic complications. Ongoing research is focused on immunosuppressive therapeutic strategies to avoid toxicity and promote donor-specific tolerance. This includes studying the balance between tolerance and effector mechanisms in immune modulation, particularly the role of costimulatory signals in T lymphocyte activation. Costimulatory signals during T cell activation can have either stimulatory or inhibitory effects. Interfering with T cell activation through costimulation blockade strategies shows potential in avoiding rejection and prolonging the survival of transplanted organs. This review paper aims to summarize current data on the immunologic role of costimulatory blockade in the field of transplantation. It focuses on strategies that can be applied in vascularized composite allotransplantation, offering insights into novel methods for enhancing the success and safety of these procedures.

The Complexity of Treatments and the Multidisciplinary Team-A Rare Case of Long-Term Progression-Free Survival in Prostate Cancer until Development of Liver and Brain Metastases.

INTRODUCTION: Prostate cancer has no initial clinical manifestation in the case of brain metastases since they are asymptomatic at first. This is why there is a high risk for clinicians to overlook these lesions, and they are often confused with other diseases. With all the improvements in diagnostic technological methods, which allow the early detection of lesions, and the progress in terms of systemic therapy associated with increased survival, an increase in incidence has also been noticed. MATERIALS AND METHODS: We report the case of a 64-year-old patient who presented himself to the Oncology Department of "St. Luca" Chronic Disease Hospital in Bucharest in November 2011 and received the following diagnosis: biopsied prostate neoplasm, local-regionally advanced, pelvic lymph node metastases. RESULTS: After receiving complex oncological treatment, this patient represents a rare case of long-term progression-free survival (15 years). DISCUSSIONS: This case has some particularities. According to the literature data, survival with metastatic prostate cancer is approximately 21 months, and cerebral metastases are found in only 2% of prostate cancer cases. This case is one of the few cases in the specialty literature that benefited from all therapeutic sequences; namely, total androgenic blockade, docetaxel, abiraterone, enzalutamide, and cabazitaxel. CONCLUSIONS: Brain metastases are an unfavorable prognostic factor in prostate cancer. The therapeutic options developed in recent years allow the improvement of survival.

The Efficacy of Immunotherapy in Long-Term Survival in Non-Small Cell Lung Cancer (NSCLC) Associated with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).

INTRODUCTION: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in cancer patients, occurring most frequently in patients with small cell lung cancer. However, this syndrome occurs extremely rarely in patients with non-small cell lung cancer. The results of the clinical trials have revealed that immuno-oncological therapies are effective for long periods of time, providing hope for long survival and with a good quality of life. CASE PRESENTATION: We present the case of a female patient who was 62 years old at the time of diagnosis in 2016 who underwent surgery for a right pulmonary tumor (pulmonary adenocarcinoma) and subsequently underwent adjuvant chemotherapy. The patient had a left inoperable mediastinohilar relapse in 2018, which was treated using polychemotherapy The patient also had an occurrence of progressive metastasis and a syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 2019 for which immunotherapy was initiated. The patient has continued with immunotherapy until the time this study began to be written (April 2023), the results being the remission of hyponatremia, the clinical benefits and long-term survival. DISCUSSION: The main therapeutic option for SIADH in cancer patients is the treatment of the underlying disease, and its correction depends almost exclusively on a good response to oncological therapy. The initiation of immunotherapy at the time of severe hyponatremia occurrence led to its remission as well as the remission of the other two episodes of hyponatremia, which the patient presented throughout the evolution of the disease, demonstrating an obvious causal relationship between SIADH and the favorable response to immunotherapy. CONCLUSIONS: Each patient must be approached individually, taking into account the various particular aspects. Immunotherapy proves to be the innovative treatment that contributes to increasing the survival of patients with metastatic non-small cell lung cancer and to increasing their quality of life.

The Benefits and Challenges of the Multimodal Treatment in Advanced/Metastatic Malignant Melanoma.

Currently, the treatment of malignant melanoma offers the longest and the most studied experience of innovative treatments in malignant pathology. The algorithm of the therapeutic decision in advanced or metastatic melanoma must comprise: the timing of the therapeutic initiation, the sequencing of the specific oncological treatment (radiotherapy and chemotherapy still being therapeutic alternatives in selected cases), the diagnosis and the management of adverse reactions. We present the case of a patient diagnosed with metastatic malignant melanoma in November 2019, who progressed successively under new systemic treatment throughout the 3 years of treatment and experienced skin reactions of various degrees of severity. The comprehensive response to secondary hilar pulmonary lymphatic determinations under subsequent chemotherapy was specific to the presented case. The occurrence of vitiligo secondary to immunotherapy is a favorable prognostic factor, but the occurrence of secondary cerebral determinations is an extremely severe prognostic factor in malignant melanoma and a challenge in making the therapeutic decision. Previous treatment with immune checkpoint inhibitors may trigger a favorable response to systemic chemotherapy. The early and accurate diagnosis of the adverse events of the new therapies requires a multidisciplinary approach, because it can radically change the therapeutic decision.

Particular aspects of treating rectal cancer: The watch and wait approach.

Background: Rectal cancer is one of the most common malignant pathologies worldwide. Currently, the standard treatment of this pathology consists of radio-chemotherapy followed by low anterior resection with total mesorectal excision or abdominoperineal proctectomy for medium/low rectal cancer. Objectives: In recent years, another treatment strategy has been proposed, stemming from the finding that up to 40% of patients receiving neoadjuvant treatment had a complete pathological response. This method, also referred to as the watch and wait approach, implies delaying surgery and following a rigorous protocol for patients who have developed a complete response to neoadjuvant treatment with a good oncologic outcome. The objective of this study was to highlight the merits of this approach in selected patients. Case Reports: In this study, we present two patients with low-rectal tumors who developed complete response post neoadjuvant therapy and for whom the watch and wait protocol has been applied over the past 4 years. Conclusion: Although the watch and wait protocol appears to be a feasible option in the management of patients with a complete clinical and pathological response post neoadjuvant therapy, more prospective studies and randomized trials comparing this approach with standard surgical treatment are required before establishing it as the standard of care for distal rectal cancer. Therefore, establishing universal criteria for the selection and assessment of the patients with a complete clinical response following neoadjuvant treatment is required.