Laparoscopy in liver transplantation: The future has arrived

In the last two decades, laparoscopy has revolutionized the field of surgery. Many procedures previously performed with an open access are now routinely carried out with the laparoscopic approach. Several advantages are associated with laparoscopic surgery compared to open procedures: reduced pain due to smaller incisions and hemorrhaging, shorter hospital length of stay, and a lower incidence of wound infections. Liver transplantation (LT) brought a radical change in life expectancy of patients with hepatic endstage disease. Today, LT represents the standard of care for more than fifty hepatic pathologies, with excellent results in terms of survival. Surely, with laparoscopy and LT being one of the most continuously evolving challenges in medicine, their recent combination has represented an astonishing scientific progress. The intent of the present paper is to underline the current role of diagnostic and therapeutic laparoscopy in patients waiting for LT, in the living donor LT and in LT recipients

Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer

Colorectal cancer; Metastasis; Targeted therapiesCáncer colorrectal; Metástasis; Terapias dirigidasCàncer de colorectal; Metàstasi; Teràpies dirigidesDESTINY-CRC01 (NCT03384940) was a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC) that progressed after ≥2 prior regimens; results of the primary analysis are published. Patients received T-DXd 6.4 mg/kg every 3 weeks and were assigned to either: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), cohort B (IHC 2+/ISH−), or cohort C (IHC 1+). Primary endpoint was objective response rate (ORR) by independent central review in cohort A. Secondary endpoints included ORR (cohorts B and C), duration of response, disease control rate, progression-free survival, overall survival, pharmacokinetics, and safety of T-DXd. 86 patients were enrolled (53 in cohort A, 15 in cohort B, and 18 in cohort C). Results of the primary analysis are published, reporting an ORR of 45.3% in cohort A. Here, we report the final results. No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively. Overall serum exposure (cycle 1) of T-DXd, total anti-HER2 antibody, and DXd were similar regardless of HER2 status. Most common grade ≥3 treatment-emergent adverse events were decreased neutrophil count and anemia. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 patients (9.3%). These findings support the continued exploration of T-DXd in HER2-positive mCRC.This study was sponsored by Daiichi Sankyo and funded by both Daiichi Sankyo and AstraZeneca. The sponsor was involved in data collection, analysis, interpretation, and preparation of the manuscript. We thank the patients who participated in this study, as well as their families and caregivers. We also thank the staff and investigators at all the study sites. We thank Masato Fukae, PhD, and Emi Kamiyama, PhD, for the analysis of the pharmacokinetic parameters, both of whom are employed by Daiichi Sankyo. Under the guidance of the authors, assistance in medical writing and editorial support was provided by Cindy M. Rigby, PhD, and Marianna B. Johnson, PhD, of ApotheCom, and was funded by Daiichi Sankyo

A Case Report of a Solitary Fibrous Tumor of the Maxillary Sinus

A solitary fibrous tumor (SFT) is a benign neoplasm, firstly described as a mesenchymal tumor of the pleura. Its incidence range in the head and neck region is about 5\u201327%, but only rarely does it affect paranasal sinuses. The differential diagnosis is challenging, owing to its erosive growth pattern and immuno-histochemical features. SFTs have an aggressive behavior and an important recurrence potential. Therefore, a radical surgical excision is the gold standard therapeutic procedure. A rare SFT originating from the right maxillary sinus is reported here. The 37-year-old patient presented to the outpatient clinic with a painful expansive lesion in the whole right maxillary region. The overlying skin was inflamed and the patient had no epistaxis episodes. The 1.5 dentary element tested negative for vitality; however, a puncture of the lesion led to a hematic spill and no purulent discharge. An endoscopic-guided biopsy was suggestive either of SFT or hemangioperictoma, excluding a malignant neoplasm. A multi-equipe surgical team was activated. The lesion was embolized in order to achieve a good hemostatic control and, after 48 h, the neoplasm was radically excised with a combined open and endoscopic approach. The patient was disease-free at 12-month radiological and clinical follow-up. Given the rarity of this lesion and the delicacy required in addressing head and neck neoplasms, we believe that the present case report might be of help in further understanding how to approach cranio-facial SFTs

Side-gate leakage and field emission in all-graphene field effect transistors on SiO2/Si substrate

We fabricate planar all-graphene field-effect transistors with self-aligned side-gates at 100 nm from the main graphene conductive channel, using a single lithographic step. We demonstrate side-gating below 1V with conductance modulation of 35% and transconductance up to 0.5 mS/mm at 10 mV drain bias. We measure the planar leakage along the SiO2/vacuum gate dielectric over a wide voltage range, reporting rapidly growing current above 15 V. We unveil the microscopic mechanisms driving the leakage, as Frenkel-Poole transport through SiO2 up to the activation of Fowler-Nordheim tunneling in vacuum, which becomes dominant at high voltages. We report a field-emission current density as high as 1uA/um between graphene flakes. These findings are essential for the miniaturization of atomically thin devices

Side-gate leakage and field emission in all-graphene field effect transistors on SiO2/Si substrate

We fabricate planar all-graphene field-effect transistors with self-aligned side-gates at 100 nm from the main graphene conductive channel, using a single lithographic step. We demonstrate side-gating below 1V with conductance modulation of 35% and transconductance up to 0.5 mS/mm at 10 mV drain bias. We measure the planar leakage along the SiO2/vacuum gate dielectric over a wide voltage range, reporting rapidly growing current above 15 V. We unveil the microscopic mechanisms driving the leakage, as Frenkel-Poole transport through SiO2 up to the activation of Fowler-Nordheim tunneling in vacuum, which becomes dominant at high voltages. We report a field-emission current density as high as 1uA/um between graphene flakes. These findings are essential for the miniaturization of atomically thin devices.Comment: Research article, 8 pages, 5 figure

Activation of mammalian target of rapamycin (mTOR) in triple negative feline mammary carcinomas

BACKGROUND: Triple negative breast cancer (TNBC) in humans is defined by the absence of oestrogen receptor (ER), progesterone receptor (PR) and HER2 overexpression. Mammalian target of rapamycin (mTOR) is overexpressed in TNBC and it represents a potential target for the treatment of this aggressive tumour. Feline mammary carcinoma (FMC) is considered to be a model for hormone-independent human breast cancer. This study investigated mTOR and p-mTOR expression in FMC in relation to triple negative (TN) phenotype. RESULTS: The expression of mTOR, p-mTOR, ERα, PR and HER2 was evaluated in 58 FMCs by immunohistochemistry and in six FMC cell lines by Western blot analysis. 53.5% of FMC analyzed were ER, PR, HER2 negative (TN-FMC) while 56.9% and 55.2% of cases expressed mTOR and p-mTOR respectively. In this study we found that m-TOR and p-mTOR were more frequently detected in TN-FMC and in HER2 negative samples. CONCLUSIONS: In this study, we demonstrate that there is also a FMC subset defined as TN FMC, which is characterised by a statistically significant association with m-TOR and p-mTOR expression as demonstrated in human breast cancer

Il trattamento di prima e seconda linea nel carcinoma gastrico

Despite the progressive decline of its incidence and mortality over the past decades, gastric cancer remains the forth most common cause of cancer-related death in Europe. While historically gastric adenocarcinoma has been classifed according to the Lauren classifcation in intestinal and diffuse subtype, the knowledge of the complex molecular mechanisms underlying its carcinogenesis has led to new molecular classifcations which can represent the starting point for the development of a personalized approach also in this disease. From a clinical point of view, while the addition of trastuzumab in the therapeutic armamentarium paved the way for the introduction of targeted therapy in the frst-line treatment, only recently the confrmation of the role of second-line therapy along with the approval of ramucirumab as a standard of care in this setting led to a new concept of continuum of care in gastric cancer. Furthermore, also the pivotal role of nutritional counseling and support both in early- and advanced-stage disease has been recently confrmed in many retrospective and prospective series

Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study

Abstract Background Aflibercept combined with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) as second-line treatment of metastatic colorectal cancer (mCRC) significantly improved survival compared with FOLFIRI alone in the pivotal VELOUR (aflibercept vs. placebo in combination with irinotecan and 5-fluorouracil in the treatment of patients with metastatic colorectal cancer after failure of an oxaliplatin-based regimen) trial. No quality-of-life assessment was performed in VELOUR; therefore, the ASQoP (Aflibercept Safety and Quality-of-Life Program) trial was designed to capture the safety and health-related quality of life (HRQL). Patients and Methods ASQoP was an international, open-label, single-arm trial evaluating the safety and HRQL of aflibercept combined with FOLFIRI administered in a real-life setting to 781 patients with mCRC, pretreated with an oxaliplatin-based regimen with or without bevacizumab. The Italian subset of ASQoP enrolled 200 patients from 28 institutions. The primary endpoint was safety; HRQL was a secondary endpoint, assessed by validated questionnaires (European quality of life 5-dimension instrument 3-level; European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30, version 3; and EORTC-CR29) at baseline, during treatment, and at the end of treatment. Results The median age of the Italian ASQoP population was 63 years; the median number of aflibercept and FOLFIRI cycles was 7. Treatment-emergent adverse events were reported in 97.5% of patients. Hypertension (28.5%), neutropenia (27.5%; from laboratory data), asthenic conditions (20.0%), diarrhea (17.0%), and stomatitis (13.0%) were the most frequent (incidence, ≥ 5%) grade 3/4 toxicities. One toxic death occurred during the study period due to sepsis, without neutropenic complications. No significant worsening of HRQL was shown during treatment. Conclusion Aflibercept combined with FOLFIRI was well tolerated when administered as second-line treatment for patients with mCRC in a real-life setting. It did not affect HRQL and showed similar rates of treatment-emergent adverse events as those observed in the VELOUR trial. No new safety signals were identified

Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults

BACKGROUND: Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.METHODS: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.RESULTS: Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1 plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).CONCLUSIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.)