Background Colorectal cancer is a successful model of genetic biomarker development in oncology. Currently, several predictive or prognostic genetic alterations have been identified and are used in clinical practice. The RAS gene family, which includes KRAS and NRAS act as predictors for anti-epithelial growth factor receptor treatment (anti-EGFR), and it has been suggested that NRAS mutations also play a role in prognosis: patients harboring NRAS alterations have a significantly shorter survival compared to those with wild type tumours. BRAF V600E mutations are rare and occur mostly in tumors located in the ascending colon in elderly female patients. BRAF is instrumental in establishing prognosis: survival is shorter by 10–16 months in BRAF-mutant patients, and BRAF may be a negative prognostic factor for patients who undergo hepatic or pulmonary metastasectomy. Moreover, this mutation is used as a negative predictive factor for anti-EGFR therapies. Two new biomarkers have recently been added to the metastatic colorectal cancer panel: HER2 and microsatellite instability. While HER2 is still being investigated in different prospective studies in order to validate its prognostic role, microsatellite instability already guides clinical decisions in substituted with advanced colorectal cancer. Conclusions There are current evidences that support using above mentioned genetic biomarkers to better identify the right medicine that is supposed to be used in the right patient. This approach contributes to a more individualized patient-oriented treatment in daily clinical practice.

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Background and Aims: The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case presentation, this review aims to examine the prevalence, clinical, histopathological and molecular features of tumors with concomitant mutations. Methods: Case report and systematic review. We performed a systematic literature search in PubMed and EMBASE using the following MeSH terms: “coexistence” OR “concomitant” AND “RAS” AND “BRAF” AND “colorectal cancer” from the inception of the databases onwards. Results: We present the case of a 53-year-old man diagnosed with metastatic rectal adenocarcinoma with both a KRAS and a BRAF mutation. The review included eleven papers reporting on a total of 30 mCRC cases with concomitant RAS and BRAF mutations. The male/female ratio was 11/5. The average age was 58.5 years. The tumor was located in nine cases on the right colon and in two cases in the left colon. 43.3% of subjects had liver metastases, and 6.6% had lung metastases. Next-generation sequencing (NGS) was used in 36.6% of cases and polymerase chain reaction (PCR) in 16.6% of cases. KRAS mutations were present in 83.3% of patients and NRAS mutations in 16.6% of patients. Survival could be assessed in 10 patients and the median was 21.1 months (about 30% lower than the survival in the general mCRC population). Conclusion: The results of this systematic review suggest the need to design a cohort study (either prospective or retrospective) to better characterize the patients with concomitant RAS and BRAF mutations and to establish the optimal treatment for this rare situation.

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Rationale:Male adenomyoepithelioma of the breast with malignant features is a rare tumor with only one previous case reported in the literature over 25 years ago.Patient concerns:We report the case of a 63-year-old man admitted to our Oncology Institute with a painless tumor mass of 6 cm in the left breast with no additional regional lymph nodes. Ultrasound revealed a complex cystic tumor mass of 60 mm in the left breast, with both anechoic (cystic) and echogenic (solid) components, with ill-defined margin.Diagnoses:Extemporaneous assessment showed a solid (invasive) papillary intracystic carcinoma. Definitive pathology examination revealed the presence of a breast malignant adenomyoepithelioma.Interventions:Based on the extemporaneous assessment, wide tumor excision was performed. The tumor board decided to continue treatment with adjuvant anthracycline-based chemotherapy.Outcomes:After 6 years of follow-up, the patient is cancer-free. No chronic side effects were noted.Lessons:Because this pathology is extremely rare, no guidelines are available for its therapeutic approach. All decisions regarding patient management should be made by a multi-disciplinary team and can only be based on clinical experience and the few cases reported in female patients.

Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography–mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.

Rationale: Acrometastases of the hand are an unusual sign of lung cancer onset and may often be mistaken for other benign disorders, thus delaying diagnosis and treatment. Patient concerns: A 58-year-old man presented at the Rheumatology Clinic with a lump in the distal phalanx of the right index finger associated with intense pain, swelling, rib pain, and hemoptysis. Diagnoses: Given the clinical manifestations, an x-ray of the right hand was performed, and it revealed an osteolytic lesion in the distal phalanx of the right index finger. The subsequent CT of the thorax and abdomen showed a lung tumor, osteolytic lesions in the ribs, sternum, and the thoracic spine. Interventions: Amputation of the phalanx was decided on account of intense pain refractory to NSAIDs and opioids. Pathology assessment established the diagnosis of bone metastases secondary to lung adenocarcinoma. The patient underwent 6 cycles of first-line palliative chemotherapy with cisplatin and gemcitabine with partial response according to the RECIST 1.1. criteria. EGFR and ALK testing were not available at the time. A year later, the patient presented with progressive disease, which lead to 6 more cycles of chemotherapy with docetaxel. The disease progressed during chemotherapy and the patient was switched to erlotinib. Outcomes: After 7 months of anti-EGFR treatment, the patient passed away due to disease progression, thus having an overall survival of 25 months. Lessons: On rare occasions, acrometastases of the hand may be the first manifestation of a lung cancer and, as such, they must be taken into consideration in the differential diagnosis of rheumatologic disorders. They are a poor prognosis marker, but some cases like this one can have a better survival than reported in the literature, most likely due to that particular cancer's biology.

Systemic sclerosis (SSc) is a rare and complex autoimmune disease associated with poor vital and functional outcomes. The functional hindrance in patients derives from various disease-specific manifestations, including Raynaud's phenomenon and digital ulcers (DUs). Bosentan is an endothelin receptor antagonist capable of preventing the appearance of new DUs in patients with scleroderma. The present study aimed to evaluate the effects of Bosentan on the severity of Raynaud's phenomenon, DU-related symptoms and functional impairment during the first year of treatment. A prospective study that included adult patients with SSc admitted to the Rheumatology Department between January 2016 and January 2017 that were candidates for Bosentan therapy, was performed. All patients were asked to evaluate the burden of symptoms secondary to Raynaud's and DUs using a visual analogue scale (VAS), whereas functional hindrance was assessed via Health Assessment Questionnaire Disability Index (HAQ-DI). The outcomes were assessed at baseline and every 3 months during 1 year of therapy. Among the 41 patients included initially, 2 participants discontinued the treatment after 1 month due to adverse events (elevation of liver enzymes). The study cohort exhibited a significant improvement in HAQ-DI, VAS-R and VAS-DU scores in response to Bosentan therapy over the 1-year follow-up period. Higher scores at baseline predicted a weaker treatment-related improvement, with the risk of a poor outcome being increased by 220% for VAS-R, 116% for VAS-DU, whereas no increase was observed for HAQ-DI. The post-treatment improvement in VAS-DU levels was associated with a better outcome for HAQ-DI (R=0.44; P=0.005). This association was not identified for VAS-R (R=0.24; P=0.137). Throughout the follow-up period, patients with dyspnea presented with significantly higher HAQ-DI scores compared with non-dyspneic patients. Bosentan therapy may indirectly influence functionality and quality of life in patients with scleroderma by reducing the burden of Raynaud's and DU-related symptoms. Nonetheless, patients with SSc with a decreased symptom burden at baseline exhibited improved outcomes.