High mortality risk among women with acromegaly still persists.

Introduction: The mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly. Methods: This observational retrospective study included 399 consecutive patients with acromegaly between January 2001-December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality. Results: At the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95-1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975-2007 and 2008-2022 had SMR = 1.25 [95% CI 0.97-1.58] and SMR = 1.09 [95% CI 0.68-1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24-2.11]; 1.76 [95% CI 1.30-2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69-2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66-1.41]). Conclusion: Patients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women.

Therapies beyond Physiological Barriers and Drug Resistance: A Pilot Study and Review of the Literature Investigating If Intrathecal Trastuzumab and New Treatment Options Can Improve Oncologic Outcomes in Leptomeningeal Metastases from HER2-Positive Breast Cancer.

Leptomeningeal metastases (LM) are a rare but rapidly fatal complication defined by the spread of tumor cells within the leptomeninges and the subarachnoid space, found in approximately 10% of patients with HER2-positive breast cancers. This pilot study evaluated the efficacy of local treatment with intrathecal Trastuzumab (IT) added to systemic treatment. The oncologic outcome of 14 patients with HER2-positive LM is reported. Seven received IT, and seven received standard of care (SOC). The mean number of IT cycles administered was 12.14 ± 4.00. The response rate to CNS after IT treatment + SOC was 71.4%, and three patients (42.8%) obtained durable responses lasting more than 12 months. The median progression-free survival (mPFS) after LM diagnosis was six months, and the median overall survival (mOS) was ten months. The mean values of the PFS in favor of IT therapy (10.6 mo vs. 6.6 mo) and OS (13.7 vs. 9.3 mo) suggest a non-negligible investigation direction in the sense of exploiting intrathecal administration as a possible treatment modality in these patients. Adverse events reported were local pain related to intrathecal administration and one case of arachnoiditis, hematoma, and CSF fistulae. Intrathecal administration of Trastuzumab, alongside systemic treatment and radiotherapy, might improve oncologic outcomes in LM HER2-positive breast cancer with manageable toxicity.

The Female Reproductive Tract Microbiome and Cancerogenesis: A Review Story of Bacteria, Hormones, and Disease.

The microbiota is the complex community of microorganisms that populate a particular environment in the human body, whereas the microbiome is defined by the entire habitat-microorganisms and their environment. The most abundant and, therefore, the most studied microbiome is that of the gastrointestinal tract. However, the microbiome of the female reproductive tract is an interesting research avenue, and this article explores its role in disease development. The vagina is the reproductive organ that hosts the largest number of bacteria, with a healthy profile represented mainly by Lactobacillus spp. On the other hand, the female upper reproductive tract (uterus, Fallopian tubes, ovaries) contains only a very small number of bacteria. Previously considered sterile, recent studies have shown the presence of a small microbiota here, but there are still debates on whether this is a physiologic or pathologic occurrence. Of particular note is that estrogen levels significantly influence the composition of the microbiota of the female reproductive tract. More and more studies show a link between the microbiome of the female reproductive tract and the development of gynecological cancers. This article reviews some of these findings.

Validation of a New Prognostic Score in Patients with Ovarian Adenocarcinoma.

Background and Objectives: This study aimed to assess the impact of clinical prognostic factors and propose a prognostic score that aids the clinician's decision in estimating the risk for patients in clinical practice. Materials and Methods: The study included 195 patients diagnosed with ovarian adenocarcinoma. The therapeutic strategy involved multidisciplinary decisions: surgery followed by adjuvant chemotherapy (80%), neoadjuvant chemotherapy followed by surgery (16.4%), and only chemotherapy in selected cases (3.6%). Results: After a median follow-up of 68 months, in terms of progression-free survival (PFS) and overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status of 1 and 2 vs. 0 (hazard ratio-HR = 2.71, 95% confidence interval-CI, 1.96-3.73, p < 0.001 for PFS and HR = 3.19, 95%CI, 2.20-4.64, p < 0.001 for OS), menopausal vs. premenopausal status (HR = 2.02, 95%CI, 1.35-3,0 p < 0.001 and HR = 2.25, 95%CI = 1.41-3.59, p < 0.001), ascites (HR = 1.95, 95%CI 1.35-2.80, p = 0.03, HR = 2.31, 95%CI = 1.52-3.5, p < 0.007), residual disease (HR = 5.12, 95%CI 3.43-7.65, p < 0.0001 and HR = 4.07, 95%CI = 2.59-6.39, p < 0.0001), and thrombocytosis (HR = 2.48 95%CI = 1.72-3.58, p < 0.0001, HR = 3.33, 95%CI = 2.16-5.13, p < 0.0001) were associated with a poor prognosis. An original prognostic score including these characteristics was validated using receiver operating characteristic (ROC) curves (area under the curve-AUC = 0.799 for PFS and AUC = 0.726 for OS, p < 0.001). The median PFS for patients with none, one, two, three, or four (or more) prognostic factors was not reached, 70, 36, 20, and 12 months, respectively. The corresponding median overall survival (OS) was not reached, 108, 77, 60, and 34 months, respectively. Conclusions: Several negative prognostic factors were identified: ECOG performance status ≥ 1, the presence of ascites and residual disease after surgery, thrombocytosis, and menopausal status. These led to the development of an original prognostic score that can be helpful in clinical practice.

Prognostic Role of Vascular Endothelial Growth Factor and Correlation with Oxidative Stress Markers in Locally Advanced and Metastatic Ovarian Cancer Patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in tumor progression in ovarian cancer, but the complex mechanism and interaction with oxidative stress are not fully understood. METHODS: A prospective study included 52 patients with ovarian adenocarcinoma stage IIIA-IV. Serum VEGF and reactive oxygen species (ROS) such as malondialdehyde and ceruloplasmin were measured. RESULTS: VEGF levels were elevated (mean 1014.7 ± 165 pg/mL), especially in patients with macroscopic residual disease (1058 vs. 810 pg/mL, p = 0.0001). Median progression-free survival (PFS) and overall survival (OS) were 6 and 40 months in patients with a very high VEGF (over 1200 pg/mL), 11 and 48 months in patients with VEGF between 1000-1200 pg/mL, 18 and 84 months in patients with VEGF between 800-1000 pg/mL, and not reached in patients with normal VEGF. Increased VEGF values were associated with a 2.6-fold increased risk of disease progression (HR = 2.60, 95% CI 1.69-3.99), and a 1.4-fold increased risk of death (HR = 1.4, 95% CI 1.15-1.91, p = 0.002). Receiver operator characteristic (ROC) curves were used to validate VEGF as a prognostic factor and the area under the curve (AUC) was 0.814, p = 0.036 for PFS and 0.729, p = 0.043, for OS. There was a positive correlation between VEGF and malondialdehyde, Pearson coefficient of 0.35, p = 0.0001. CONCLUSIONS: VEGF and malondialdehyde are important prognostic markers in ovarian cancer, especially in macroscopic residual disease, and there is a positive correlation between angiogenesis and oxidative stress.

Upstaging and Downstaging in Gliomas-Clinical Implications for the Fifth Edition of the World Health Organization Classification of Tumors of the Central Nervous System.

In 2021, the 5th edition of the WHO Classification of Tumors of the Central Nervous System (WHO-CNS5) was published as the sixth volume of the international standard for brain and spinal cord tumor classification. The most remarkable practical change in the current classification involves grading gliomas according to molecular characterization. IDH mutant (10%) and IDH wild-type tumors (90%) are two different entities that possess unique biological features and various clinical outcomes regarding treatment response and overall survival. This article presents two comparative cases that highlight the clinical importance of these new classification standards. The first clinical case aimed to provide a comprehensive argument for determining the IDH status in tumors initially appearing as low-grade astrocytoma upon histologic examination, thus underlining the importance of the WHO-CNS5. The second case showed the implications of the histologic overdiagnosis of glioblastoma using the previous classification system with a treatment span of 7 years that proceeded through full-dose re-irradiation up to metronomic therapy. The new WHO-CNS5 classification significantly impacted complex neurooncological cases, thus changing the initial approach to a more precise therapeutic management.

Long-Term Outcome of Patients with Stage II and III Muscle-Invasive Urothelial Bladder Cancer after Multimodality Approach. Which Is the Best Option?

Background and Objectives: There is no consensus regarding the optimal therapy sequence in stage II and III bladder cancer. The study aimed to evaluate the long-term oncologic outcomes in patients with bladder cancer after a multimodality approach. Materials and methods: Medical files of 231 consecutive patients identified with stage II (46.8%), IIIA (30.3%), and IIIB (22.9%) transitional cell carcinoma of the bladder (BC) treated with a multimodality approach were retrospectively reviewed. The treatment consisted of transurethral resections or cystectomy, radiotherapy alone or concurrent chemoradiotherapy as definitive treatment, or neoadjuvant chemotherapy using platinum salt regimens. Results: Median age at diagnosis was 65 ± 10.98 years. Radical or partial cystectomy was performed in 88 patients (37.1%), and trans-urethral resection of bladder tumor (TURBT) alone was performed in 143 (61.9%) patients. Overall, 40 patients (17.3%) received neoadjuvant chemotherapy and 82 (35.5%) received definitive chemoradiotherapy. After a median follow-up of 30.6 months (range 3-146 months), the median disease-free survival (DFS) for an entire lot of patients was 32 months, and the percentage of patients without recurrence at 12, 24, and 36 months was 86%, 58%, and 45%, respectively. Patients receiving neoadjuvant chemotherapy had a better oncologic outcome compared to patients without neoadjuvant chemotherapy (median DFS not reached vs. 31 months, p = 0.038, HR = 0.55, 95% CI 0.310-0.951). There was a trend for better 3-year DFS with radical cystectomy vs. TURBT (60 months vs. 31 months, p = 0.064). Definitive chemoradiotherapy 3-year DFS was 58% compared to 44% in patients who received radiotherapy or chemotherapy alone. Conclusions: In patients with stages II and III, both neoadjuvant chemotherapy and concurrent radio-chemotherapy are valid options for treatment and must be part of a multidisciplinary approach.

Acromegaly treatment in Romania. How close are we to disease control?

INTRODUCTION: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. MATERIALS AND METHODS: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. RESULTS: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. CONCLUSIONS: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.