Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 (p = 0.024, r = 0.49) and E-Cadherin (p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 (p = 0.107, r = −0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.
28 December 2022 in Journal of Patient-Reported Outcomes
Introduction: Acromegaly is a rare chronic endocrine disorder that can lead to significant quality of life (QoL) impairment and persistent symptomatology in both biochemically uncontrolled as well as in cured or controlled patients. We aimed to conduct an observational cross-sectional study investigating the associations between biochemical disease control, associated comorbidities, and symptoms severity on QoL in a cohort of acromegalic patients. Methods: Thirty-one patients with acromegaly were enrolled in our study. AcroQoL and PASQ (Pain assessed acromegaly symptoms questionnaire) questionnaires were applied to all patients. Information about disease status, associated comorbidities, and other relevant clinical and paraclinical data were gathered. Results: Patients with uncontrolled acromegaly presented worse QoL and symptoms scores than controlled patients, but the difference was not statistically significant (AcroQoL 57.22 vs 64.04, p > 0.05; PASQ 12 vs 16.47, p > 0.05). Worse symptoms were significantly associated with impaired QoL (overall symptoms score on PASQ was negatively correlated with AcroQoL total score, r = − 0.61, p < 0.05). Cardiovascular complications were associated with lower QoL scores, but not with worse symptoms (AcroQoL total score in patients with- versus patients without cardiovascular complications: 54.89 vs 70.14, p < 0.05). Conclusions: Achieving biochemical control of acromegaly might not be enough to reverse the QoL impairment and improve symptomatology in acromegalic patients. While symptoms severity and the presence of cardiovascular complications seem to play an important role in reducing patients QoL, the roles of disease control, diabetes, and pituitary insufficiency are less clear.
13 November 2021 in Journal of Critical Care Medicine
Diabetic individuals are considered a vulnerable population during the COVID-19 Pandemic, and several studies noted worse outcomes, including death, among those who get infected. Diabetic emergencies, such as ketoacidosis (DKA), are common and potentially life-threatening conditions in uncontrolled patients. While the pathophysiological background of the relationship between COVID-19 and DKA is not fully understood, early reports available so far indicate that patients with pre-existing diabetes who get infected with the SARS-CoV 2 virus are at higher risk of DKA. It was also suggested that DKA is a poor prognostic sign for infected patients, these being at higher risk of developing worse forms of COVID-19 disease and having high mortality. Therefore, healthcare personnel dealing with such patients face a considerable challenge, as the correct and safe emergency management of such cases is far from established. This article aimed to conduct a study that reviews the current published data available about patients with DKA and COVID-19.
Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. The study aimed to evaluate the prognostic significance of the PTEN and ERG biomarkers in predicting BCR and tumor progression in PCa patients who underwent radical prostatectomy. Methods: This study consisted of a cohort of 91 patients with localized PCa who underwent radical prostatectomy between 2016 and 2022. From this cohort, 77 patients were selected for final analysis. Tissue microarrays (TMAs) were constructed from paraffin blocks, and immunohistochemical (IHC) staining for PTEN and ERG was performed using specific antibodies on the Ventana BenchMark ULTRA system (Roche Diagnostics, Indianapolis, IN, USA). Stained sections were evaluated and correlated with clinical and pathological data. Results: PTEN expression showed a significant negative correlation with BCR (r = −0.301, p = 0.014), indicating that reduced PTEN expression is associated with increased recurrence risk. PTEN was not significantly linked to PSA levels, tumor stage, or lymph node involvement. ERG expression correlated positively with advanced pathological tumor stage (r = 0.315, p = 0.005) but was not associated with BCR or other clinical parameters. Conclusions: PTEN appears to be a valuable prognostic marker for recurrence in PCa, while ERG may indicate tumor progression. These findings support the potential integration of PTEN and ERG into clinical practice to enhance risk stratification and personalized treatment, warranting further validation in larger patient cohorts.
Cushing’s disease (CD) is a rare disorder caused by adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumors, which lead to chronic hypercortisolism and significant complications with increased mortality. These tumors are characterized by a substantial heterogeneity in their biological behavior, prognosis, and therapeutic response, making their management challenging. While transsphenoidal surgery remains the first-line treatment, recurrence rates remain high, and alternative therapeutic approaches, such as pharmacological therapy and radiotherapy, have a variable efficacy and are frequently limited due to side effects. Increasing evidence suggests that molecular biomarkers, both immunohistochemical and genetic, may play an important role in predicting a tumor’s aggressiveness, recurrence risk, and response to targeted therapies. The immunohistochemical evaluation of its granulation pattern, Ki-67 proliferation index, and E-cadherin expressions have been linked to a tumor’s invasiveness and surgical outcomes, while somatostatin and dopamine receptor expressions may influence its response to Pasireotide and cabergoline therapy. Genetic alterations such as USP8 mutations impact tumor growth and its response to targeted therapies, whereas CABLES1 and TP53 alterations may contribute to more aggressive tumor behavior. Despite these findings, the clinical applicability of many of these markers remains limited by inconsistent validation and lack of standardized cutoff values. This narrative review provides an update on the latest evidence regarding the roles of molecular biomarkers in corticotropinomas, emphasizing their role in prognosis, recurrence risk, and the response to different treatment options. A better understanding and integration of these biomarkers into clinical practice could lead to a better patient stratification, more efficient therapeutic strategies, and personalized treatment approaches for patients with CD.