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OBJECTIVE: This study evaluated single intra-articular injections of Hymovis MO.RE., a hyaluronic acid hexadecyl derivative (HYADD4-G), to manage post-traumatic or degenerative knee or ankle chondropathy in professional soccer players. PATIENTS AND METHODS: Twenty-five players affected by knee (n = 12) or ankle (n = 13) chondropathy were prospectively enrolled and treated by two single Hymovis MO.RE. (32 mg/4 ml) injections at the beginning of the football season (V0, baseline) and at mid-season (V1, 19-20 weeks thereafter), and were followed-up until the end of the season (V2, after further 19-20 weeks). Knee cases were evaluated using the 2000 IKDC knee subjective examination form and the modified Lysholm scoring system. Ankle cases were evaluated using the American Orthopaedic Foot Ankle Society (AOFAS) ankle-hindfoot score. Patients were also evaluated using a VAS Likert scale and a four-category scale recording both the patient's and the doctor's assessment on joint mobility in degrees and overall treatment efficacy. Adverse events, patient withdrawals and local reaction to injections were also assessed. RESULTS: In knee patients, the 2000 IKDC subjective score improved from 46.8 ± 11.4 at V0 to 83.1 ± 12.5 at V2. Their modified Lysholm score improved from 58.8 ± 8.9 at V0 to 90.6 ± 8.3 at V2. In the ankle patients, the AOFAS score improved from 52.2 ± 5.6 at V0 to 96.4 ± 4.5 at V2. VAS Likert values and subjective evaluations improved at V1 and were maintained at V2. No side effects were recorded. CONCLUSIONS: A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection, repeated after 19-20 weeks, may be a viable option to improve symptoms and function in professional soccer players suffering from knee and ankle chondropathy. [ABSTRACT FROM AUTHOR]

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC. [ABSTRACT FROM AUTHOR]

Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures from 25/27 human BC samples, in which the ability of growth in vitro replicates the clinical and biological aggressiveness of the original tumors. According to the results of next generation sequencing analysis, a direct correlation was found between PI3KA mutations and the sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents. Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS and BRAF, were found in resistant samples, suggesting their potential role as negative predictive factors of response to these agents. Thus, we demonstrated that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug screening for chemotherapies and targeted agents in genetically selected patients and represent an innovative model to identify new biomarkers of drug resistance. [ABSTRACT FROM AUTHOR]

Frailty is a condition of increased vulnerability to cope with stressors, predisposing to the development of disability in basic and instrumental activities of daily living, falling, institutionalization and finally death. It is characterized by the loss of functional reserve in multiple domains resulting in a reduced tolerance to common external stresses. The pathogenetic steps conducting to frailty are not completely clear, but there is increasing evidence of a crucial role of insulin resistance and systemic inflammation in the development of frailty, disability, and related medical conditions. These two conditions may act directly, through a negative impact on homeostatic regulation and cross-systems compensation, or indirectly, by the effect of several diseases strongly related to frailty. Therefore, counteracting insulin resistance and systemic inflammation could be a powerful way to prevent the development of frailty and/or of its adverse outcomes. In this framework, diet and physical exercise may represent two important weapons in the prevention of frailty; indeed, current literature supports the effectiveness of a correct lifestyle based on a healthy diet (Mediterranean type diet) and regular physical exercise on frailty primary prevention. Studies on secondary prevention of frailty suggest that multi-component and resistance training, together with adequate energy and protein intake, might be helpful although data are still lacking. The efficacy of dietary supplementation in secondary prevention of frailty, albeit promising, remains to be confirmed in large clinical trials. [ABSTRACT FROM AUTHOR]

Pancreatoduodenectomy is the gold standard operation for malignant and benign diseases of the pancreas and periampullary region. Even if improvements in intensive care management and surgical technique have dramatically reduced postoperative mortality after pancreatic surgery, morbidity remains high (30–50%), also in specialized pancreatic units. In order to reduce postoperative complications, particularly pancreatic fistula, different surgical techniques and their modifications have been proposed. In order to determine the better management of the pancreatic stump after pancreatoduodenectomy, the Authors analysed and compared derivative – pancreaticojejunal, pancreaticogastrostomy – vs no-derivative technique – pancreatic stump closure (duct ligation or mechanical suture, duct occlusion by fibrin glue or cyanoacrylate). A systematic research of the English literature, including major meta-analysis articles, clinical randomized trials, retrospective studies and systematic reviews was performed, analysing the risk factors and the incidence of short-medium term postoperative complications. Up to now, even if derivative procedures are preferred as gold standard the best method to deal a pancreatic stump is still controversial and remains matter of research. Pancreatic surgeons must have more than one technique for managing the pancreatic remnant. [ABSTRACT FROM AUTHOR]

SUMMARY: Capecitabine is an orally administered fluoropyrimidine carbamate which has been developed as a prodrug of 5-FU with the goal to improve its tolerability and intratumoral drug concentration. The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profile, dosage and administration of this drug, alone or in combination with conventional chemotherapeutics and/or new target-oriented drugs, in the management of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

SUMMARY: In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50–60%, 9–11 and 20–24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic “treatment until progression”. [ABSTRACT FROM AUTHOR]

SUMMARY: Surgery is the only curative therapy for gastric cancer. In the metastatic setting the objective of treatment is to manage symptoms, improve quality of life and prolong survival, but current treatment options have limited efficacy and some of them exhibit unfavourable toxicity profiles. Fluoropyrimidine, taxanes and platinum-based regimens are used most frequently and offer a response rate of 30–50% with a median overall survival of =1 year. These discouraging data support the need for new therapeutic strategies based on targeted drugs. Trastuzumab, a monoclonal antibody against HER2, has shown survival benefits when given with chemotherapy in all setting of HER2-positive breast cancer patients. The ToGA trial, the first study evaluating the efficacy and safety of adding trastuzumab to chemotherapy in HER-2 positive advanced gastric cancer, showed a significant superiority of combination over chemotherapy alone. Based on these results trastuzumab combined with a cisplatin and fluoropyrimidine regimen appear the new reference treatment for HER-2 positive metastatic gastric cancer. [ABSTRACT FROM AUTHOR]