Search

Leptomeningeal carcinomatosis (LMC) is exceedingly rare in gastric cancer. It is most commonly seen in breast, lung cancer and melanoma, and is associated with an extremely poor prognosis. If untreated, median overall survival is four to six weeks. No standard treatment for LMC exists and published data are scarce. We present two cases of gastric carcinoma diagnosed with LMC that exemplify how aggressive this condition is and how short the time lapse is to perform any targeted therapy. This report aims to raise awareness of this rare metastatic possibility in gastric cancer and its diagnostic and therapeutic challenges.

Cancer-associated-cachexia represents a systemic syndrome of unintended weight-loss (WL) and systemic inflammation, affecting80% patients with pancreatic adenocarcinoma (PA). We aimed to evaluate the association of weight change (WC) with survival of patients treated with chemotherapy (ChT) for PA and the influence of disease staging. We also studied the prognostic and predictive value of inflammation-based scores.Observational, retrospective cohort study. Individuals were divided into two cohorts, according to WC (WL ≥5% vs. non-WL5%) after ChT. Main endpoints were weight change and survival time. Statistical analysis was performed using Stata software.Sixty-five patients were included (median age 69; 48% female), 60% with advanced disease. At 3 months after ChT start, 54% experienced WL. Advanced disease independently predicted WL (OR 2.10; 95% CI, 1.11-19.6;WL was an independent prognostic factor for survival. Particularly in early stage disease, interventions targeting this modifiable factor may translate into better outcomes for PA patients. NLR may be a surrogate marker of systemic inflammatory status in this setting.

Background: Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. They decrease bone mineral density, accelerate osteoporosis and lead to increased risk of fractures, thus impairing quality of life. Identification of patients at higher risk would be helpful for best treatment decisions. Recommendations have been published for bone health preservation but real-world data regarding implementation and adherence to these recommendations is scarce. This work aimed to assess bone loss, fracture incidence and risk factors associated with these events, as well as the prognostic influence of fractures in women undertaking adjuvant AI. Materials and Methods: In this retrospective cohort study, we have evaluated women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. A minimum of 3 months under AI and 3 years of follow-up after AI start were necessary for inclusion. Statistical analysis of collected data was performed using R 3.5.2, R-Studio 1.1.456 and Stata 15.1 software. Results: 451 eligible women were reviewed (median age 68 years, 30-98 min-max). Median time under AI was 40 months (3-114). Baseline bone densitometry, carried out in only 69% patients, showed abnormal results in 75%, but only 69% and 16% started calcium/vitD supplementation and bisphosphonates therapy, respectively. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in women with higher age (p=0.006). This group also showed lower T-scores at lumbar spine and femoral neck (p=0.067). On multivariate analysis, age (OR 1.04, 95% CI 1.01-1.07, p=0.016) and time under AI (OR 1.02, 95% CI 1.00-1.03, p=0.045) were independent predictors of fracture events, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups disfavouring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6-92.4 vs. 95.6%, 95% CI, 91.2-97.8, p=0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted-HR of 3.17, 95% CI 1.10-9.11; p=0.032). Conclusion: Bone health is often forgotten, despite its great impact in survivorship. Our results suggest a pathophysiologic link between EBC and bone metabolism, potentially estrogen-mediated, which translates into EBC recurrence. Further research in this area may help refining these findings. Moreover, early identification of women at higher risk with individualized treatment plans comprising shorter duration of AI is warranted. Poor adherence to existing guidelines is a crucial barrier to effective approaches to bone health. Citation Format: Leonor Vasconcelos Matos, Maria Teresa Neves, Fatima Alves, Mafalda Baleiras, André Ferreira, Pedro Cotovio, Tiago Dias Domingues, Mariana Malheiro, Joana Graça, Leonor Fernandes, Ana Plácido, Helena Miranda, Ana Martins. From theory to practice: Impact of aromatase inhibitors in the bone health of women with early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-27.

Syphilis is potentially a multisystem chronic infection caused by Treponema pallidum. Late symptomatic neurosyphilis has been less reported in developed countries, most often seen in untreated patients or in patients with HIV coinfection. We present a case of complicated neurosyphilis with widespread neurological involvement (dementia paralytica, tabes dorsalis, leptomeningitis and left oculomotor nerve involvement) presenting in the 21st century in an urban area of a well-developed European country in an HIV-negative patient.

Extramammary Paget Disease (EMPD) is an often-misdiagnosed rare disorder, whose cause remains unknown. Diagnosis is confirmed by skin biopsy. Primary treatment for EMPD is surgery. Recurrence is common in the first two years and prognosis is good if the disease is localized and there is no underlying associated cancer. Patients with invasive and metastatic EMPD are uncommon and exhibit a poor prognosis, even when there is good response to a first chemotherapy line. Multiple chemotherapeutic regimens, with varying levels of success, have been attempted, but standard of care is not established. The central nervous system seems to be a common metastatic site with better survival than visceral metastasis.We report a case of metastatic EMPD that addresses the difficulties associated with the treatment of this rare disease, that has no current guidelines.

Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas. Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma. Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL ( Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.

A minority of lesions found in the sellar region are non-adenomatous neoplastic, inflammatory, or cystic masses. Our study aims to describe the prevalence and characteristics of these lesions in a multidisciplinary pituitary outpatient clinic. We conducted an observational study which included 36 patients (15.9% of those followed up in this outpatient clinic between 2006 and 2016 who had pituitary surgery) submitted to pituitary surgery with histological results showing a non-adenomatous sellar lesion. We evaluated clinical, radiological, and biochemical (pituitary function) characteristics during the pre-operative and post-operative period. Thirty-six patients (50% female) with a mean age of 41.3 ± 21.9 years and a mean follow-up duration of 8.0 ± 9.0 years were included. Histologic diagnoses were divided into benign neoplasms (80.6%), malignant neoplasms (11.1%), inflammatory lesions (5.6%), and cystic masses (2.8%). The most common clinical presentation was headache (66.7%) and visual defects (61.1%). Forty-seven percent of patients had at least one pituitary axis insufficiency at the time of diagnosis. In the majority of cases (58.3%), a transsphenoidal approach was used for the initial pituitary surgery. Thirteen patients had more than one pituitary surgery and eight also had radiotherapy. At the time of data retrieval, five patients had no pituitary hormonal insufficiency and 13 patients had some visual defect improvement. Although rare, non-adenomatous sellar lesions may be associated with significant causes of morbidity, such as hypopituitarism and visual defects, per se or due to the various treatment modalities employed. Moreover, since the lesions are difficult to distinguish from adenomas, these patients require a careful multidisciplinary approach.

Introduction Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. Objective The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. Methods We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. Results From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern. Conclusion After 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

Purpose Epilepsy is a common neurologic disorder requiring continued treatment during pregnancy. Treatment with antiepileptic drugs (AEDs) is needed for seizure control, but the risk of adverse events has to be minimized for both mother and foetus. Available data on pregnancy and foetal/postnatal outcomes following eslicarbazepine acetate (ESL) exposure via parent is herein presented for the first time. Methods ESL's global safety database was reviewed to identify pregnancy cases with exposure to ESL reported up to October 21st, 2017. The EMBASE™ and MEDLINE ® databases were searched to identify literature reports of such cases published between May 1st, 2009 and October 21st, 2017. Results Overall, 91 notifications of pregnancy were identified, of which 79 involved ESL exposure: 28 during clinical trials and 51 from 8-years of post-marketing surveillance. Thirty pregnancies resulted in live birth without congenital anomalies; in 25 pregnancies the outcome was ongoing and 3 was unknown; 18 cases resulted in abortion (10 spontaneous and 8 induced) and congenital anomalies were identified in 5 cases (no clear relationship with ESL was established). ESL was used concomitantly to other AEDs in 11 of the 15 pregnancies for which the outcome was spontaneous abortion and congenital anomaly. Literature review did not yield additional information. Conclusions Available data are insufficient to draw conclusions regarding ESL use during pregnancy. Although no particular safety problem was identified, ESL exposure during pregnancy will continue to be monitored and evaluated.

Background Cachexia affects 70-80% patients with pancreatic adenocarcinoma (PA). Systemic inflammation is a key feature of this multifactorial syndrome of unintended weight loss (WL). Despite being often described, cancer-associated cachexia (CAC) remains poorly understood and rarely recognized in clinical settings, therefore an unmet need. This study aims to acknowledge the effect of CAC in PA patients and to study the impact of WL, body mass index (BMI) and other available biomarkers (BM) on survival. Methods Retrospective analysis of PA patients treated in our institution between 2013 - 2018. Patients were categorized at baseline as having CAC if 1 of 2 criteria were met: WL > 5% from previous stable weight; BMI 2%. Serum hemoglobin, c-reactive protein (CRP), albumin, inflammation-based score (Glasgow Prognostic Score mGPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and cancer specific antigen CA 19-9 were assessed at baseline and at 3-month. Data analysis with descriptive statistics, t-test, chi-square test, cox regression and log-rank test were performed with StataIC. Results 95 eligible patients (median age 72 [46;98], 60% female) were reviewed. At baseline, cachectic patients (CP) (74%), when compared to non-CP, had higher CA 19-9 (p = 0,047), more advanced disease (p = 0,001) lower BMI (p = 0,016), worse performance status (p = 0,016) and mean WL of 13,8 ± 6,7 (%) (p = 0,001). Also, NLR>3,5 (p = 0,001), PLR>150 (p = 0,018) and hypoalbuminemia (p = 0,004) were all statistically associated to CP. Median overall survival (OS) of non-CP was 19,13 months versus 5,03 months in CP (HR 2,69 95% CI 1,58-4,59, p = 0,001). In the latter, at baseline, higher CA 19.9 (HR 1,0 95% CI 1,01-1,021, p = 0,015), higher CRP (HR 1,21 95% CI 1,06-1,39, p = 0,006) and PLR>150 (HR 2,45; 95% CI 1,09-5,54, p = 0,031) were independent predictors of worst OS. In non-CP, normal baseline albumin (HR 0,04 95 CI 0,02-0,72, p = 0,029) was an independent predictor of better OS. Conclusions A better understanding of CAC in PA might improve outcomes for PA patients. Our study suggests that a prompt identification of prognostic BM may lead to a better standardized management of CAC and that nutritional parameters can be optimized, with impact on prognosis. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

We report a case of a 90-year-old man with hypereosinophilia, lymphadenopathies and skin lesions, namely lichenification and pruritus. An aetiological investigation was performed, and a bone marrow (BM) biopsy and aspirate showed a hypercellular marrow with hypereosinophilia without dysmorphia or abnormal elements, and the BM and inguinal node’s immunophenotyping denied any presence of abnormal lymphoid cell population. The inguinal node biopsy revealed a multinodular proliferation of large cells S100 and CD1a(+), and a diagnosis of Langerhans cell histiocytosis was made. The hypereosinophilia and skin lesions were managed with corticotherapy with substantial improvement of cutaneous lesions and lymphadenopathies and normalisation of eosinophil count. Finally, to define if it is a single or multisystem disease, a skin biopsy will be necessary.

Spontaneous transsphenoidal meningoencephalcele is a rare entity, even rarer through the Sternberg’s canal, a congenital defect on the lateral wall of the sphenoid sinus. We report such a case in an obese 52-year-old female with spontaneous cerebrospinal fluid (CSF) rhinorrhoea and recurrent meningitis. Brain CT, MRI and CT cisternography were performed. Surgical correction and short-term follow-up were recorded. CT scan showed a defect on the lateral wall of the right sphenoid sinus filled with a soft tissue mass extending to the nasal cavity. MRI scan revealed brain parenchyma from the right temporal lobe herniated through the sphenoid bone defect. CT cisternography showed 270 mmH2O opening pressure and confirmed the CSF leakage. Surgical correction was performed with resolution of the symptoms. MRI and CT are complementary modalities for evaluating this entity, the first being the method of choice for meningoencephalcele diagnosis although bone defects are best depicted on CT scan. CT cisternography identifies the specific site of leak and confirms benign intracranial hypertension, consistently reported in meningoencephaloceles. Obesity and benign intracranial hypertension have been reported as a combined mechanism allegedly contributing to meningoencephaloceles through congenital skull base defects, by increasing intraabdominal pressure thus decreasing venous return, with augmented intracranial pressure and subsequent reduced absorption of the CSF.

imicrobial residue deposition can change the physico-chemical properties of bacteria and surfaces and thus promote or impair bacterial adhesion. This study focuses on benzalkonium chloride (BC) deposition on polystyrene (PS) surfaces and the influence of this conditioning film on the physico-chemical properties of PS and on early adhesion and biofilm formation by Pseudomonas aeruginosa wild-type and its laboratory BC-adapted strain. The latter readily acquired the ability to grow in BC, and also exhibited physico-chemical surface changes. The existence of residues on PS surfaces altered their hydrophobicity and favoured adhesion as determined by the free energy and early adhesion characterization. Adapted bacteria revealed a higher ability to adhere to surfaces and to develop biofilms, especially on BC-conditioned surfaces, which thereby could enhance resistance to sanitation attempts. These findings highlight the importance of investigations concerning the antimicrobial deposition effect after cleaning procedures, which may encourage bacterial adhesion, especially of bacteria that have been previously exposed to chemical stresses., Financial support from IBB-CEB and Fundacao para a Ciencia e Tecnologia (FCT) and the European Community fund FEDER, through the Program COMPETE, in the ambit of Project PTDC/SAUESA/64609/2006 /FCOMP-01-0124-FEDER-00702, Idalina Machado's PhD Grant (SFRH/BD/31065/2006) and Susana Lopes' PhD Grant SFRH/BD/47613/2008) are gratefully acknowledged.

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.

This work aims at characterizing endoscope biofilm-isolated (PAI) and reference strain P. aeruginosa (PA) adhesion, biofilm formation and sensitivity to antibiotics. The recovery ability of the biofilm-growing bacteria subjected to intermittent antibiotic pressure (ciprofloxacin (CIP) and gentamicin (GM)), as well as the development of resistance towards antibiotics and benzalkonium chloride (BC), were also determined. The capacity of both strains to develop biofilms was greatly impaired in the presence of CIP and GM. Sanitization was not complete allowing biofilm recovery after the intermittent cycles of antibiotic pressure. The environmental pressure exerted by CIP and GM did not develop P. aeruginosa resistance to antibiotics nor cross-resistance towards BC. However, data highlighted that none of the antimicrobials led to complete biofilm eradication, allowing the recovery of the remaining adhered population possibly due to the selection of persister cells. This feature may lead to biofilm recalcitrance, reinforcement of bacterial attachment, and recolonization of other sites.