Retrospective Evaluation of the Efficacy of Total Neoadjuvant Therapy and Chemoradiotherapy Neoadjuvant Treatment in Relation to Surgery in Patients with Rectal Cancer.

Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients.

Comprehensive preoperative psychological assessment of breast cancer patients.

In the context of the traumas suffered by patients following the oncological diagnosis and the expectation of the surgical intervention, it is important to unitary and multidimensional identify the psychological status, using a single interview structured to cover these psychological vulnerabilities. The overall psychological picture can help the psycho-oncologist to adapt his psychotherapeutic interventions to relieve the stress caused by the oncological diagnosis and specific treatment. 58 patients with a breast cancer diagnosis and 61 patients with breast lumps diagnosis who were waiting for the histopathological result, received several scales for assessing emotional distress, the level self-esteem, depression, anxiety and cognitive dysfunctions levels. The analysis of the answers led to the multidimensional identification of differences between the two categories of patients and establishing correlations between personality traits and the development of certain psychological changes. Statistically significant differences (p < 0.05) were observed between patients with breast cancer and those with breast lumps awaiting histopathological diagnosis, in the areas of self-esteem, depression and cognitive schemas. Diagnosed patients have predominantly dysfunctional attitudes such as negative emotions and cognitive schemas related to catastrophe and self-deprecation, while undiagnosed patients, have cognitive schemas related to low tolerance for frustration and absolutist requirements and lower dysfunctional attitudes. A global assessment with a single psychological tool can capture the overall picture of the cancer patient, including possible triggers and maintenance of symptoms, with the psychological consequences of the disease that are reflected somatically, as well as predisposing factors in the history that generates these feelings.

The Clinical, Biological, Psychological and Psychiatric Impact of the Diagnosis of Breast Cancer in Women.

OBJECTIVE: Psychosocial factors are correlated with the risk of breast cancer, by the lack of externalization of feelings and aggressive tendencies, or with a negative prognosis, by the presence of a high level of stress and reduced coping abilities. Impairment of psychological status should be assessed early to identify quantifiable psychooncological changes, such as depression, anxiety, and self-esteem. These indicators, measured in this study, may become psychometric markers for predicting the existence of the neoplastic process, prior to histopathological evaluations. METHODS: 58 patients diagnosed with breast cancer and in different stages of evolution and 61 breast lumps patients were evaluated for depression, anxiety and self-esteem. RESULTS: The correlation of depression and anxiety levels according to the evolutionary stage of the disease was as follows: in stage I cases of severe depression with significant anxiety predominate, in stage II mild depression predominates with insignificant anxiety, in stage III depression predominates moderate with significant anxiety, while in stage IV moderate depression with significant anxiety predominates. CONCLUSIONS: The presence of significant anxiety in the uncertainty phase and the anxious-depressive clinical picture can be an alarm signal for the initiation of specific psychotherapeutic strategies, to increase the adaptive potential and resilience to the disease to ensure a therapeutic collaboration of the patient by increasing adherence and compliance. the proposed therapeutic plan. Relatively sudden anxiety in a young woman, risk factors for breast cancer, and deficient cognitive impairment require intensified clinical and paraclinical investigations to confirm early oncological diagnosis.

Assessment of Epinephrine and Norepinephrine in Gastric Carcinoma.

The aim of our study was to assess the sympathetic nervous system's involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this system (epinephrine and norepinephrine), as well as by analyzing the histological expression of the norepinephrine transporter (NET). We conducted an observational study including 91 patients diagnosed with gastric carcinoma and an additional 200 patients without cancer between November 2017 and October 2018. We set the primary endpoint as mortality from any cause in the first two years after enrolment in the study. The patients were monitored by a 24-h Holter electrocardiogram (ECG) to assess sympathetic or parasympathetic predominance. Blood was also collected from the patients to measure plasma free metanephrine (Meta) and normetanephrine (N-Meta), and tumor histological samples were collected for the analysis of NET expression. All of this was performed prior to the application of any antineoplastic therapy. Each patient was monitored for two years. We found higher heart rates in patients with gastric carcinoma than those without cancer. Regarding Meta and N-Meta, elevated levels were recorded in the patients with gastric carcinoma, correlating with the degree of tumor differentiation and other negative prognostic factors such as tumor invasion, lymph node metastasis, and distant metastases. Elevated Meta and N-Meta was also associated with a poor survival rate. All these data suggest that the predominance of the sympathetic nervous system's activity predicts increased gastric carcinoma severity.

Impairment of the cardiac ejection fraction by blocking dopamine D2 receptors induced by long-acting injectable antipsychotic treatment.

INTRODUCTION: Atypical antipsychotics have numerous benefits compared to conventional ones in respect to the possible adverse effects. However, like the other ones, they may induce direct cardiovascular alterations, probably through the apoptotic effect of dopamine receptor D2 (DRD2) blockade. The main objective of the study was to assess the cardiac ejection fraction (EF) using transthoracic speckle tracking echocardiography (TSTE) in patients treated with long-acting injectable (LAI) atypical antipsychotics. PATIENTS, MATERIALS AND METHODS: This cross-sectional study was conducted on 123 patients with schizophrenia or schizoaffective disorder divided in four samples according to their treatment: Aripiprazole, Olanzapine, Paliperidone and Risperidone. We analyzed socio-demographic data, the intensity of psychiatric symptoms, the duration of psychosis and of LAI treatment, and the cardiac EF measured with TSTE. RESULTS: We found no statistically significant differences between the four antipsychotics regarding the values of the EF. Nevertheless, we observed a trend indicating that patients treated with an antipsychotic associated with a lower affinity for the DRD2, such as Olanzapine, have higher EF values than patients treated with antipsychotics with a stronger binding to the DRD2, such as Paliperidone and Risperidone. Patients receiving Aripiprazole, which has the strongest affinity for the DRD2 from all four antipsychotics but is also a partial DRD2 agonist, display higher EF values than those on Paliperidone and Risperidone. CONCLUSIONS: Antipsychotics with a lower affinity for the DRD2 or a partial agonism for it may be associated with higher EF. Cardiac monitoring should be performed periodically in patients on LAI antipsychotic therapy.

Neurobiological and pharmacological arguments for customization of cognitive behavioral psychotherapy in the treatment of major depressive disorder.

INTRODUCTION: Depression represents a public health issue because it significantly increases the risk of disabilities and premature mortality, decreases the quality of life, and increases the costs of care. The incomplete remissions favor the aggravation of neurobiological dysfunctions and pathogenesis of severe somatic comorbidities. The etiopathogenic mechanisms of depression are complex and involve multisystemic risk factors (genetic, neuroanatomic, neurobiochemical, neuroendocrine and psychosocial). Cognitive behavioral therapy (CBT) is used in all the stages of depression, as independent therapeutic method or as support of pharmacotherapy. PATIENTS, MATERIALS AND METHODS: This study has evaluated the therapeutic response of depression in M (medication) group with 136 patients under pharmacotherapy, compared with P (psychotherapy and medication) group with 137 patients treated simultaneously with medication and CBT, and the factors that can improve therapeutic management. RESULTS: Patients with depression had predominantly a reactive onset, recurrent evolution of at least four episodes, and frequent somatic comorbidities. After treatment, a significant improvement of depressive symptomatology was recorded especially in M group (72.06%), compared to P group (88.32%), p<0.01, as well as a significant difference in regaining functional skills (69.12% - M group, 93.43% - P group; p<0.001). The therapeutic response was significantly correlated with age (p<0.01), social-economical involvement and education level. CONCLUSIONS: CBT demonstrated efficiency in the treatment of major depressive disorder in association with pharmacotherapy. The therapeutic approach should rely on the pathogenic biological models that would highlight the prediction indicators for the therapeutic response and for the evolution of depression, as well as considering the psychological profile of each patient.

Expression of M3 muscarinic acetylcholine receptors in gastric cancer.

INTRODUCTION: Gastric cancer represents a real public health problem as far as incidence, aggressiveness and unfavorable prognosis are concerned. The autonomous nervous system might be one of the major factors involved in the onset, progression, and metastasis, both sympathetically and parasympathetically. The increased activation of the M3 muscarinic acetylcholine receptors (mAChRs) triggers pro-oncogenic mechanisms, especially at a gastric level, through the activation of the Hippo signaling pathway and the increase of the nerve growth factor. PATIENTS, MATERIALS AND METHODS: In this study, biopsy or postoperative gastric resection pieces have been evaluated by histopathological (HP) and immunohistochemical (IHC) examination in a group of 77 gastric patients and 23 patients without an oncological diagnosis. To quantify the IHC signal, also considering the HP aspect, light microscopy images were obtained. RESULTS: The M3 mAChR expression analysis has been correlated with the different gastric adenocarcinoma differentiation degrees (G1-G3). M3 mAChR presence has been observed also in the non-malignant gastric tissue, but it was significantly increased in the tumor tissue. The highest receptor expression was recorded in patients with a poorly-differentiated (G3) adenocarcinoma, these expressions decreasing with the increase of the differentiation degree towards moderately-differentiated (G2) and well-differentiated (G1). CONCLUSIONS: Surgical or pharmacological parasympathetic activity inhibition could decrease the development and progression of gastric tumors and could improve the gastric cancer patient's prognosis.

Mild TBI in the elderly - risk factor for rapid cognitive impairment in Alzheimer's disease.

In recent decades, traumatic brain injury (TBI) has become one of the most important health problems worldwide and is a major cause of morbidity, mortality and economic losses. Mild traumatic brain injury (mTBI) is less considered, with clinical underestimation leading to an epidemiological underevaluation of its incidence. Many of the signs and symptoms induced by mTBI are difficult to highlight clinically, especially those related to cognitive, behavioral, or emotional impairment. The complexity of the biological mechanisms induced by mTBI in the elderly determines synchronous pathogenic actions in which the vascular, inflammatory and neurodegenerative elements are intertwined. It is difficult to highlight a major pathogenic factor, since they act simultaneously, multimodally, in a real pathogenic cascade. The identification of mTBI and cerebral vascular changes by neuroimaging techniques, transcranial Doppler (TCD) or biological markers, suggests a potential prophylactic intervention by using neuroprotective factors as early as possible. Proper prophylaxis measures with neurotrophic treatment, rebalancing the gamma-aminobutyric acid (GABA)∕glutamate balance and combating the chronic inflammatory process, can become important pharmacological therapeutic targets.

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine.

Patients with serious mental illness are a high-risk category of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with schizophrenia are not participatory and have increased mortality and morbidity, patients with dementia cannot be cared for while depression, anxiety, bipolar tubing are associated with low immune status. Social stress is amplified by social isolation, amplifying depression and the mechanisms of decreased immunity. Hygiene measures and prophylactic behavior are impossible to put into practice in conditions of chronic mental illness. In coronavirus disease 2019 (COVID-19), the risk for severe development is associated with the presence of comorbidities and immune system deficiency. Prothrombotic status, cytokine storm and alveolar destruction are mechanisms that aggravate the evolution of patients, especially in the context in which they have dysfunction of the autonomic system. The activity of proinflammatory cytokines is accentuated by hyperglutamatergia, which potentiates oxidative stress and triggers the mechanisms of neural apoptosis by stimulating microglial activation. Activation of M1-type microglia has an important role in pathogenesis of major psychiatric disorders, such as major depression, schizophrenia or bipolar disorder, and may associate hippocampal atrophy and disconnection of cognitive structures. Memantine and Amantadine, N-methyl-D-aspartate (NMDA) glutamate receptor inhibitors, have demonstrated, through their pharmacological profile, psychotropic effects but also antiviral properties. In the conditions of the COVID-19 pandemic, based on these arguments, we suggest that they can be associated with the therapy with the basic psychotropics, Memantine or Amantadine, for the control of neuropsychiatric symptoms but also as adjuvants with antiviral action.

Depression and anxiety in recurrent giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a benign neoplasia more frequently encountered in young females. The pathogenic and evolutionary dynamics of the disease is strongly influenced by the presence of depression and cellular mechanisms, especially proinflammatory and immune. Although it is not a malignant tumor, it is often recurrent, which determines a high level of depression, anxiety, and fear of the patients. Cytokine mechanisms, especially through increased tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), as well as the involvement of the receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANK-L) system, can be correlated with the risk of malignancy. Unfavorable evolution is associated with persistent pain, difficulties of movement and body dysmorphic symptoms. The diagnosis is based mainly on histopathological (HP) assessment. The patients can be treated with pharmacological agents (Denosumab), surgery with tumor excision, reconstruction or osteosynthesis, and radiotherapy. Patients with GCTB require HP and imaging evaluations, especially of relapses, to detect the risk of metastasis or malignancy, simultaneously with psychological and psychiatric monitoring to detect depression, addictive behaviors, and suicide risk. It is necessary to evaluate in a multidisciplinary team to avoid unfavorable oncological and psychiatric developments. Through its clinical, HP, and therapeutic features, GCTB has multiple connections with the psychological and psychopathological dimension.

Cardiovascular anomalies and evolutionary risk factors in schizophrenia - multifactorial approach.

Schizophrenia is a functional psychosis with a multifactorial etiopathogeny involving genetic, endocrine and immunological risk factors. The main pathogenic hypothesis involves dopamine dysregulation, with hyperfunction in the limbic system and hypofunction in the prefrontal cortex. Normal dopamine activity is critical for cognitive and emotional processing, but also for autonomic and immune regulation. Co-morbidity between schizophrenia and cardiovascular anomalies is complex. Genetic factors influence the development of brain, cardiac and vascular structures, as well as the activity of enzymes involved in dopamine synaptic turnover. Autoimmunity triggered by infections or related to systemic diseases affects both brain and heart in a direct manner through autoantibodies and/or indirectly through microvascular injury. In most cases, the co-morbidity between schizophrenia and cardiac diseases is secondary to metabolic dysfunctions induced by psychotropic medication or psychosis itself. Because of their diverse pharmacodynamic profiles, antipsychotics differ in their propensity to facilitate the development of the metabolic syndrome. The distress associated with acute psychotic symptoms or a sedentary lifestyle due to negative symptoms may have a negative impact on the energetic metabolism or cardiac function. Conclusions: An interdisciplinary approach is required between neurosciences and cardiology not only at the research level, but also in the clinical practice. Cardiac co-morbidity in subjects with schizophrenia may critically affect the survival rates of these patients. Moreover, the nature of the cardiac co-morbidity may guide the clinician in better understanding and differentiating functional psychoses from organic ones. The multifactorial approach can identify cardiovascular risk factors based on clinical, biological and neuroimaging markers.

Adenocarcinoma versus pancreatic neuroendocrine tumor - case report.

Pancreatic cancer represents one of the most aggressive types of cancer, resulting in a late diagnosis and rapid death (poor overall survival). After adenocarcinoma (counting almost 80% of cases of pancreatic cancer), the second category, as frequency, is represented by the family of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Pancreatic cancer is characterized by genetic heterogeneity and may results in different evolution among metastases, which may acquire driver mutations with the ability to transform under the action of several cancer treatments. Here we report a case of a 64-year-old patient diagnosed with pancreatic tumor localized on the body and tail, invasive in the splenic and portal vein, pT3pN0M0 (adenocarcinoma pancreatic cancer), treated with a multimodal approach: surgery (splenectomy and distal pancreatectomy, with suture of the portal vein), chemotherapy, in 2010, that relapsed in 2015, with local recurrence that was resected and distant liver metastases. Immunohistochemistry of the recurrence tumor showed a neuroendocrine transformation of the tumor, with major implications in treatment and prognosis. Computed tomography examination, as well as histopathological and immunohistochemically testing, sustained positive and differential diagnosis.