ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS (AME) AND INTERNATIONAL CHAPTER OF CLINICAL ENDOCRINOLOGY (ICCE). POSITION STATEMENT FOR CLINICAL PRACTICE: PROLACTIN-SECRETING TUMORS

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century prolactinomas represented the paradigm of pituitary tumors for whom the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Need for a Tailored Approach to a Rare Entity

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively new entity that has gained increased attention because of its unique features – presence of different subtypes with different malignant potential, biological behavior, and prognosis, higher rates of recurrences and concomitant or metachronous pancreatic duct cancer. It is rare with an incidence of 4 to 5 cases per 100 000. The relative lack of experience significantly hampers decision making for surgery (pancreatic head resection, distal pancreatectomy or enucleation) or follow-up. Herein we present two cases managed by diametrically different tactic according to the risk stratification – distal pancreatectomy with splenectomy and observation, respectively. An up-to-date literature review on the key points in diagnostics, indications for surgery, the extent of surgery, follow-up, and prognosis is provided. The tailored approach based on risk stratification is the cornerstone of management. Absolute indications for surgery are the lesions with high-risk stigmata, whereas the worrisome features should be evaluated by endoscopic ultrasound and fine-needle aspiration. Main duct and mixed type are usually referred to surgery, whereas the management of a branch type is more conservative due to the lower rate of invasive cancer. Strict postoperative follow-up is mandatory even in negative resection margins due to a high risk for recurrences and metachronous lesions. Despite the guidelines, the intraductal papillary mucinous neoplasm remains a major challenge for clinicians and surgeons in the balance the risk/benefit of observation versus resection. Risk stratification plays a key role in decision-making. Future trials need to determine the optimal period of surveillance and the most reliable predictive factors for concomitant pancreatic duct cancer.

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Exemplifying the long-pursued thyroid hormones (TH)–cancer association, the TH–lung cancer association is a compelling, yet elusive, issue. The present narrative review provides background knowledge on the molecular aspects of TH actions, with focus on the contribution of TH to hallmarks of cancer. Then, it provides a comprehensive overview of data pertinent to the TH–lung cancer association garnered over the last three decades and identifies obstacles that need to be overcome to enable harnessing this association in the clinical setting. TH contribute to all hallmarks of cancer through integration of diverse actions, currently classified according to molecular background. Despite the increasingly recognized implication of TH in lung cancer, three pending queries need to be resolved to empower a tailored approach: (1) How to stratify patients with TH-sensitive lung tumors? (2) How is determined whether TH promote or inhibit lung cancer progression? (3) How to mimic the antitumor and/or abrogate the tumor-promoting TH actions in lung cancer? To address these queries, research should prioritize the elucidation of the crosstalk between TH signaling and oncogenic signaling implicated in lung cancer initiation and progression, and the development of efficient, safe, and feasible strategies leveraging this crosstalk in therapeutics.

The primary lumbar hernia with multiple defects: a rare case

Lumbar hernia is a rare entity of abdominal wall hernia. Due to varied presentation it poses a challenge in diagnosis and management to attending surgeon. The requirement of preoperative imaging and clinical examination has indispensable role in the diagnosis and surgical (open or laparoscopic) approach is the only treatment option. We are presenting a case of 44 year old male, diagnosed as lumbar hernia with multiple defects and successfully managed by laparoscopic mesh hernioplasty. The primary lumbar hernia is a rare entity that a surgeon may encounter once in his lifetime making it an interesting surgical challenge. The adequate knowledge of preoperative imaging and anatomy are indispensable. With advances in minimally invasive surgery, it can be applied to patients with lumbar hernia and management requires a more tailored approach. This condition can be managed by laparoscopic approach successfully.

Toward Overcoming Treatment Failure in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune cytokines, signaling pathways and effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) are commonly used in RA treatment and classified into different categories. Nevertheless, RA treatment is based on a “trial-and-error” approach, and a substantial proportion of patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome treatment failure, including identification of biomarkers, exploration of the reasons for loss of efficacy, development of sequential or combinational DMARDs strategies and approval of new DMARDs. Here, we summarize these efforts, which would provide valuable insights for accurate RA clinical medication. While gratifying, researchers realize that these efforts are still far from enough to recommend specific DMARDs for individual patients. Precision medicine is an emerging medical model that proposes a highly individualized and tailored approach for disease management. In this review, we also discuss the potential of precision medicine for overcoming RA treatment failure, with the introduction of various cutting-edge technologies and big data.

How do we optimally utilize factor concentrates in persons with hemophilia?

The current mainstay of therapy for hemophilia is to replace the deficient clotting factor with the intravenous administration of exogenous clotting factor concentrates. Prophylaxis factor replacement therapy is now considered the standard of care in both pediatric and adult patients with hemophilia with a severe phenotype to protect musculoskeletal health and improve quality of life. Heterogeneity in bleeding presentation among patients with hemophilia due to genetic, environmental, and treatment-related factors has been well described. Accordingly, the World Federation of Hemophilia recommends an individualized prophylaxis regimen that considers the factors mentioned above to meet the clinical needs of the patient, which can vary over time. This review focuses on the practical points of choosing the type of factor concentrate, dose, and interval while evaluating appropriate target trough factor levels and bleeding triggers such as level of physical activity and joint status. We also discuss the use of a pharmacokinetics assessment and its incorporation in the clinic for a tailored approach toward individualized management. Overall, adopting an individualized prophylaxis regimen leads to an optimal utilization of factor concentrates with maximum efficacy and minimum waste.

Gender Differences in the Relationship Between Coping Style and Attitudes Towards Palliative Care

Palliative care (PC) is becoming more widely available and its benefits, including improved quality of life for patients, have been demonstrated. Studies on patient-level barriers to PC access focus on knowledge and misperceptions. This study aimed to explore, among a community sample, whether more approach-focused coping styles may be associated with more positive attitudes towards PC and whether more avoidant coping styles are associated with more negative attitudes towards PC. Two linear regression analyses (an approach model and an avoidance model) were conducted to determine predictors of attitudes towards PC, controlling for potential confounds. The sample consisted of 87 community-dwelling adults ages 65+ (mean age=72.72 (5.88); 56.32% = women; 86.21% = White). In both models, more knowledge of PC was associated with more positive attitudes towards PC (β = .71, p<.01). Coping by engaging more social support was significantly associated with more positive attitudes towards PC (β = .54, p<.05). Results demonstrated a significant interaction (β = -1.24, p<.01) such that women who endorsed high levels of disengaged coping reported more favorable attitudes towards PC than men who endorsed high levels of disengaged coping. Results indicate the need for a tailored approach to PC education for patients and families. Men who often cope with a stressor via distraction, self-blame, denial, or giving up may be less receptive to acceptance of PC. Future research on educational interventions tailored for individuals with distinct coping styles may be beneficial, particularly for men who frequently rely on disengaged coping styles.