Commentary on "a case of paratesticular leiomyosarcoma successfully treated with orchiectomy and chemotherapy"

We have read with great interest the article written by Ko and colleagues on a particularly rare type of malignant mesenchymal tumor that is paratesticular leiomyosarcoma and we did appreciate the argumentation on the utility of adjuvant chemotherapy as treatment of stage III disease. As for our experience, we would like to shed light on a very rare and little-known aspect surrounding this neoplasm, which is the capability of dedifferentiation exerted in order to recur or metastasize

The Italian Business Cycle; Coincident and Leading Indicators and Some Stylized Facts

This paper analyses the business cycle properties of 183 time series relevant to the Italian economy, including real, monetary and international variables. We propose new monthly coincident and leading composite indicators for the Italian business cycle; the leading indicator anticipates the turning points of the coincident indicator on average by six months. On the methodological side, the study provides a scheme for constructing cyclical indicators on a sound statistical basis through iterative steps, combining the use of traditional NBER methods with that of more recent techniques of cyclical analysis. A number of stylized facts of the Italian business cycle emerge. Among them, money and financial variables are found to lead the cycle, chronologically, by an average of between one year and sixteen months. There is also strong evidence of synchronization of international cycles, with the US and UK cycles leading the Italian cycle by two to three quarters. The main linking channel seems to be trade, with Italian exports to EU countries leading the cycle by six months on average.business cycles, cyclical indicators, leading indicators, Italian stylized fact

Anti epidermal growth factor receptor therapy in small bowel adenocarcinoma

Rationale:Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal cancer, thus limited data about treatment for advanced disease are available. The lack of specific guidelines has justified the use of therapeutic protocols usually applied in advanced colorectal cancer. Few and preliminary data have suggested possible clinical benefit from the use of target therapy such as bevacizumab and cetuximab.Patient concerns:We present the case of a young woman who was admitted to the emergency department for acute abdominal pain, nausea, and vomiting related to a jejunal stenosis.Diagnoses:An enteroscopy with jejunal biopsy showed poorly differentiated cancerous cells suggestive for primary intestinal cancer. There were no signs of metastatic disease at radiological evaluation. A jejunal resection was subsequently carried out and the diagnosis of mucinous adenocarcinoma of the jejunum was confirmed.Interventions:The computed tomography scan performed 1 month after surgery showed metastatic disease. Therefore, the patient received combined protocols of chemotherapy and either bevacizumab or the anti-epidermal growth factor receptor (EGFR) panitumumab.Outcomes:A partial response (PR) was achieved with Folfox plus panitumumab and a maintenance therapy with panitumumab is being conducted with a mild toxicity and a progression free survival of 19 months since the beginning of panitumumab.Lessons:This is, to the best of our knowledge, the first report in the literature of a patient with SBA who has benefitted from panitumumab with an overall survival of 83 months

The microbiota impact. bacteria shaping immunity, disease and response to therapy

N

Ion channel expression in human melanoma samples. in silico identification and experimental validation of molecular targets

Expression of 328 ion channel genes was investigated, by in silico analysis, in 170 human melanoma samples and controls. Ninety-one members of this gene-family (i.e., about 28%) show a significant (p 0.90 and p 90% in most cases). Such five genes (namely, SCNN1A, GJB3, KCNK7, GJB1, KCNN2) are novel potential melanoma markers or molecular targets, never previously related to melanoma. The “druggable genome” analysis was then carried out. Miconazole, an antifungal drug commonly used in clinics, is known to target KCNN2, the best candidate among the five identified genes. Miconazole was then tested in vitro in proliferation assays; it dose-dependently inhibited proliferation up to 90% and potently induced cell-death in A-375 and SKMEL-28 melanoma cells, while it showed no effect in control cells. Moreover, specific silencing of KCNN2 ion channel was achieved by siRNA transfection; under such condition miconazole strongly increases its anti-proliferative effect. In conclusion, the present study identified five ion channels that can potentially serve as sensitive and specific markers in human melanoma specimens and demonstrates that the antifungal drug miconazole, known to target one of the five identified ion channels, exerts strong and specific anti-melanoma effects in vitro

adding pertuzumab to adjuvant therapy for high risk her2 positive early breast cancer in aphinity a grade analysis

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population

Could time detect a faking-good attitude? A study with the MMPI-2-RF

Background and Purpose: Research on the relationship between response latency (RL) and faking in self-administered testing scenarios have generated contradictory findings. We explored this relationship further, aiming to add further insight into the reliability of self-report measures. We compared RLs and T-scores on the MMPI-2-RF (validity and restructured clinical [RC] scales) in four experimental groups. Our hypotheses were that: the Fake-Good Speeded group would obtain a different completion time; show higher RLs than the Honesty Speeded Group in the validity scales; show higher T-Scores in the L-r and K-r scales and lower T-scores in the F-r and RC scales; and show higher levels of tension and fatigue. Finally, the impact of the speeded condition in malingering was assessed. Materials and Methods: The sample was comprised of 135 subjects (M = 26.64; SD = 1.88 years old), all of whom were graduates (having completed at least 17 years of instruction), male, and Caucasian. Subjects were randomly assigned to four groups: Honesty Speeded, Fake-Good Speeded, Honesty Un-Speeded, and Fake-Good Un-Speeded. A software version of the MMPI-2-RF and Visual Analog Scale (VAS) were administered. To test the hypotheses, MANOVAs and binomial logistic regressions were run. Results: Significant differences were found between the four groups, and particularly between the Honest and Fake-Good groups in terms of test completion time and the L-r and K-r scales. The speeded condition increased T-scores in the L-r and K-r scales but decreased T-scores in some of the RC scales. The Fake groups also scored higher on the VAS Tension subscale. Completion times for the first and second parts of the MMPI-2-RF and T-scores for the K-r scale seemed to predict malingering. Conclusion: The speeded condition seemed to bring out the malingerers. Limitations include the sample size and gender bias

Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis

Background: Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy. Materials and methods: We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results: A total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407-2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719-0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763-0.997; P = 0.045)

The role of stereotactic body radiation therapy in oligometastatic colorectal cancer

Rationale: Regorafenib is the new standard third-line therapy in metastatic colorectal cancer (mCRC). However, the reported 1-year overall survival rate does not exceed 25%. Patient concerns: A 55-year-old man affected by mCRC, treated with regorafenib combined with stereotactic body radiotherapy (SBRT), showing a durable response. Interventions: After 6 months of regorafenib, a PET/CT scan revealed a focal uptake in a solid lung nodule which was treated with SBRT, whereas continuing regorafenib administration. Fourteen months later, the patient had further progression in a parasternal lymph node, but treatment with regorafenib was continued. The regorafenib-associated side effects, such us the hand-foot syndrome, were favorable managed by reducing the dose from 160 to 120 mg/day. Outcomes: Patient-reported outcome was characterized by a progression-free survival of approximately 3 years. Lessons: in presence of oligometastatic progression, a local SBRT while retaining the same systemic therapy may be a better multidisciplinary approach. Moreover, disease progression is no longer an absolute contraindication for continuing the regorafenib treatment

Observations on the Enamel of Odontomas

The morphological study of odontomas provides an alternative model for observing the formation of dental tissues, since different maturing stages are present simultaneously. Investigations were performed on decalcified samples (using light microscopy and transmission electron microscopy) and on undecalcified samples of complex odontoma enamel (using transmission electron microscopy). Simultaneous presence of prismatic enamel at various maturing stages with different structural characteristics was observed. Such enamel was sometimes associated with layers of ameloblastic cells with characteristics of cells in functional activity. In other sites, the enamel did not present a prismatic structure but it appeared as unstructured material clusters with abundant organic component. It was concluded that the theory according to which an ecto-mesenchymal inductive failure occurs in odontomas is not confirmed. The defect seen at the beginning of the differentiated and anomalous tissue maturation may be related to latest events in the development of the enamel organ. In this regard, it was concluded that such events involve the efficiency of the ameloblasts and the possible alterations in the organic matrix