Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity.

OBJECTIVE: Recurrent gynecological tumors (e.g., endometrial, and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program. METHODS: From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study. RESULTS: Included patients had endometrial (17/36 [47%]), ovarian (10/36 [28%]), or other gynecological cancers (9/36 [25%]). Most patients had received 2-3 prior systemic treatments (endometrial, 47·2%; ovarian, 60%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively). CONCLUSION: Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.

Absence of blood donors' anti-SARS-CoV-2 antibodies in pre-storage leukoreduced red blood cell units indicates no role of passive immunity for blood recipients.

Transfer of vaccine antibodies (Ab) from donors to recipients after transfusion of packed red blood cells (RBC) is supposed, thus affecting the recipients' response to vaccinations. In this prospective study, SARS-CoV-2 IgG level in donors' serum and RBC supernatant samples was assessed. Among 346 subjects, 280 were referred for hyperimmune plasma donation and 30 for whole blood donations. All units underwent pre-storage filtration, and residual plasma volume was 18±18 mL. The mean total IgG and IgM levels were 171.43 ± 48.79 and 11.43 ± 10.69 mg/dL respectively, with significant reduction after plasma depletion and filtration (IgG 5.86 ± 5.2 and IgM 1.43 ± 3.78, p < 0.05). Anti-COVID-19 Ab were identified in serum of 28/30 (93.5%) blood donors but were absent in all blood units. The mean value of anti-SARS-CoV-2 IgG level in donors' serum samples and in RBC units was 8.80 S/C (range 0.01-23.4) and 0.11 (range 0.01-0.37) S/C, respectively (p<0.05). This study shows deplasmation and leukodepletion of RBC units ensured removal of IgG content and no red blood cell unit was reactive for anti-COVID-19 antibodies even from donors with high serum titre. These findings demonstrate that deplasmated and leukodepleted RBCs are not to be considered blood products containing substantial amounts of immune globulin, and differently from other blood derived-products containing Ab, transfusions with deplasmated and leukodepleted RBCs do not require delayed vaccinations and a revision of current recommendations is requested.

Natural history of malignant bone disease in gastric cancer: final results of a multicenter bone metastasis survey.

BACKGROUND: Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. PATIENTS AND METHODS: Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. RESULTS: Median time to bone metastasis was 8 months (CI 95%, 6.125-9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). CONCLUSIONS: To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients.

[Anatomy and variants of the cerebral venous system--fact or defect?]. / Anatomia e variantes do sistema venoso cerebral--defeito ou feitio?

UNLABELLED: The anatomy of the cerebral venous system (CVS) is based on a known variable three-dimensional structure. For a correct recognition and characterization of its elements, a detailed knowledge of its anatomy and potential variants is essential. However, this structural changes, commonly named as variants, may appear in asymptomatic situations as well as associated to certain pathological syndromes with diagnostic and therapeutic consequences. PURPOSE: The authors present a brief summary of the CVS anatomy, highlight the potential structural changes and discuss their ethiology as constitutional or pathological. METHOD AND RESULTS: Based on clinical cases, the most frequent anatomical modifications will be presented and their ethiology discussed,whether constitutional or pathological. CONCLUSION: The CVS is characterized by its various presentations. These changes are classically named as anatomic variants. However,they may appear associated to certain pathological situations. Only a profound recognition of the normal CVS anatomy allows a correct definition of the ethiology of the structural change as constitutional or pathologic.

[The development of the cerebral venous system--from the embryo to the adult definitive structure]. / O desenvolvimento do sistema venoso cerebral--do embrião à estrutura definitiva no adulto.

INTRODUCTION: The human development consists of a continuous process where an uninterrupted pattern of extremely complex repetitive cycles of growth, modulation and modification take place. Despite this extreme complexity, the normal development is ordered by an impressive regularity, namely, in chronological, anatomical, topographic and physiological trends. In some organic systems, this development will not be totally ended by the time of birth. In this situation, further changes will have to take place until the adult definitive pattern is achieved. The cerebral venous system (CVS) is such a paradigm. PURPOSE: The authors pretend to present a synopsis of the specific organogenesis of the cerebral venous system in order to allow a correct interpretation of the vascular structures, recognise the anatomical variations and better comprehend the topographic correlations between neighbouring structures. METHOD AND RESULTS: Following a structured and synthetic order, the main guiding lines of the principal evolutional steps will be presented from the first embryological stages until the final and definitive adult pattern. CONCLUSION: The detailed study of the continuous development stages of the CVS constitutes a fundamental tool for the whole recognition of the anatomical structures, their correct interpretation and detection of possible variants as well as a better comprehension of topographic relationship between neighbouring structures. In other words and following KL Moore, Embryology illuminates anatomy.

[Mesial-temporal lesions in patients with neurosyphilis]. / Alterações mesiotemporais em doentes com neurossífilis.

BACKGROUND AND PURPOSE: Evaluate and describe clinical and imaging findings in two patients with mesial-temporal changes in a context of Neurosyphilis. METHODS: The clinical files of two patients with mesial-temporal lesions in the context of Neurosyphilis were reviewed, gathering information about sex, age, clinical presentation, laboratory and EEG changes, treatment and clinical outcome. An emphasis was placed in the initial and follow-up MR studies. RESULTS: Two male caucasian patients, aged 43 and 45, with a normal immunological status, with no prior known history of syphilis. Both presented a history of behavioral changes, disorientation and mnesic changes. Laboratorial results were compatible with neurosyphilis(TPHA and VDRL were detected in blood and LCR) and the HSV serology was negative. MR studies revealed changes of signal indicating lesions in the temporal white matter, amygdala, hippocampus, gyri parahipocampi and insulas. CONCLUSIONS: Neurosyphilis is a challenging diagnosis due to the variability of clinical and imaging findings. Precocious therapy significantly improves prognosis and outcome, stressing the need for an early diagnosis. In imaging studies Neurosyphilis should be considered as a differential diagnosis when mesial-temporal lesions are detected, prompting adequate laboratorial investigation.

[Pemetrexed monotherapy in previously treated patients with advanced non small cell lung cancer; differences by histology. Our experience]. / Monoterapia con pemetrexed in pazienti pretrattati affetti da carcinoma polmonare non a piccole cellule in fase avanzata: impatto dell'istologia. Nostra esperienza.

Emerging data suggest pemetrexed is active in patients with adenocarcinoma of lung compared to those with squamous cell carcinoma. We retrospectively reviewed advanced non small cell lung cancer (NSCLC) patients previously treated, analysing efficacy on histologic characteristics. From January 2007 to December 2010, 25 patients with stage IIIB or IV NSCLC (17 with adenocarcinoma and 8 with squamous cell carcinoma), who had previously failed on platinum-based chemotherapy, received pemetrexed 500 mg/mq every 3 weeks until disease progression or unacceptable toxicities. Analysing the histologic subgroups we observed 1 (5.9%) complete response, partial response in 5 patients (29.4%), stable disease in 6 (35.3%), progression disease in 5 (29.4%) in adenocarcinoma group compared to 4 (50%) stable disease and 4 (50%) progression disease in squamous cell carcinoma group. Median progression free survival was 8 months (range 3-22) for adenocarcinoma patients and 4 months (range 2-6) for squamous cell patients. According to data of the literature, also our small retrospective study conducted on unselected patients confirms the difference of pemetrexed efficacy by histology type, with better results in patients with adenocarcinoma lung cancer.

The outcome of elderly patients with cognitive complaints but normal neuropsychological tests.

Elderly patients may present with prominent cognitive complaints and have performances in neuropsychological tests within the normal range for the age and education, and thus do not fulfill the criteria for mild cognitive impairment (MCI). There is insufficient evidence to support the clinical decision in these cases ("pre-MCI"). Forty-three subjects, 11 controls, 15 "pre-MCI," and 17 MCI, were followed for about three and half years with neuropsychological testing and magnetic resonance imaging including volumetric measurements of the hippocampus and amygdala. Two of the "pre-MCI" subjects suffered cognitive and functional deterioration and were diagnosed with dementia. Although the "pre-MCI" subjects as a group had no significant deterioration in neuropsychological tests, they suffered a decline in the total hippocampal volume (P=0.04) along the follow-up time. In contrast, all control subjects remained stable and had no volumetric decreases. As expected, MCI patients underwent significant deterioration in several neuropsychological tests, often progressed to Alzheimer's disease, and showed decreases both in total hippocampal and amygdalar volumes. Elderly people presenting with cognitive complaints may be in an initial phase of a degenerative disorder and should be followed clinically, even if they have normal neuropsychological tests.

[Evaluation of cerebral glioma with advanced magnetic resonance techniques]. / Avaliação dos gliomas cerebrais. Por técnicas avançadas de Ressonância Magnética.

Magnetic Resonance Imaging (MRI) is the technique of choice for the radiological evaluation of cerebral gliomas. Determination of its malignant grade is important for therapeutic approach and prognosis. The authors focus on the utility of MRI advanced techniques, namely proton magnetic resonance spectroscopy, perfusion and diffusion. These techniques are complementary to conventional MRI and allow improved non-invasive early evaluation of malignant grade of gliomas. Moreover, these techniques are useful in the determination of the most malignant areas of the tumours, which are potential targets for stereotaxic biopsy and therapy. They also have particular utility on the distinction between residual tumor, recurrence and radiation necrosis.

[Angio-CT in atheromatous carotid disease]. / Angio-TC da doença carotídea ateromatosa.

CT angiography is a diagnostic tool, which is rapidly becoming an important modality for non-invasive evaluation of the neurovasculature. The aim of this article is to review this method, including acquisition and image processing protocols and its application for the evaluation of atherosclerotic stenosis of the carotid artery. Illustrative cases are shown and a revision of the literature is also made.

Weekly low-dose docetaxel in advanced hormone-resistant prostate cancer patients previously exposed to chemotherapy.

OBJECTIVE: The aim of this study was to evaluate the activity and tolerability of docetaxel in patients with hormone-resistant prostate cancer previously exposed to chemotherapy. METHODS: We enrolled 27 patients with hormone-resistant prostatic cancer that had progressed during first-line chemotherapy. The primary end-point was palliative response defined as a 2-point reduction in the 6-point present pain intensity scale, and an improvement in Karnofsky performance status of one 10-point category. The treatment consisted of weekly docetaxel 25 mg/m(2) body surface area administered by means of a 1-hour intravenous infusion with corticosteroid premedication. RESULTS: The primary criterion of palliative response was met in 13 patients (48%) after eight treatment cycles; its median duration was 6 months (range 1-8). Mean global quality of life improved in 8 and 10 patients after respectively four and eight treatment cycles. After a median follow-up of 8 months, 21 patients had died: the median survival was 9+ months (range 2-18). Weekly docetaxel was very well tolerated: grade 3 neutropenia occurred in 1 patient and grade 3 anemia in 2. CONCLUSIONS: Weekly low-dose docetaxel is an effective and well-tolerated treatment for patients with hormone-resistant prostate cancer previously exposed to chemotherapy.