Prolonged pemetrexed infusion plus gemcitabine in refractory metastatic colorectal cancer: Preclinical rationale and phase II study results

Background. We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine. This combination was then advanced to a phase II clinical trial. Methods. Patients with metastatic colorectal cancer in progression after standard treatment were included in the study. Adequate bonemarrow reserve, normal hepatic and renal function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were required. Treatment consisted of an 8-hour intravenous infusion of pemetrexed 150 mg/m 2 on day 1 and a 30-minute intravenous infusion of gemcitabine 1,000 mg/m 2 on day 3 of each cycle, repeated every 14 days. Results. Fourteen patients were enrolled onto the study (first step). No objective responses were seen, and evidence of stable disease was observed in only one of the 12 evaluable patients. The most important grade 3-4 side effects were hematological toxicity (neutropenia 64.2%, thrombocytopenia 71.4%, anemia 28.7%), fatigue (50.0%), and stomatitis (21.5%). Median overall survival and time to progression were 5.8 months (95% confidence interval [CI]: 3.9-7.1) and 2.1 months (95% CI: 1.7-2.8), respectively. Conclusion. The experimental pemetrexed-gemcitabine combination proved to be inactive and moderately toxic

Right- vs. left-sided metastatic colorectal cancer: Differences in tumor biology and bevacizumab efficacy

There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa)”, randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors

Prognostic role of a new inflammatory index with neutrophil-to-lymphocyte ratio and lactate dehydrogenase (CII: Colon Inflammatory Index) in patients with metastatic colorectal cancer: results from the randomized Italian Trial in Advanced Colorectal Cancer (ITACa) study

Aim: The aim of this study was to investigate the role of a new inflammatory index (Colon Inflammatory Index [CII]) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT)+ bevacizumab or CT alone. Patients and methods: Between November 14, 2007 and March 6, 2012, 276 patients diagnosed with CRC were available for baseline neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH). We divided the population into three groups on basis of the CII index. Results: At baseline in all populations, median PFS and OS was predictive of clinical outcome (p<0.0001). Following adjustment for clinical covariates, multivariate analysis confirmed CII index as an independent prognostic factor. The CII index was also predictive when we evaluated the two distinct arms with (p=0.0009) or without bevacizumab (p=0.0001). When we divided right side versus left side for treatment regimen (CT plus bevacizumab versus only bevacizumab), we found a benefit of bevacizumab versus only CT in the right side in patients treated with bevacizumab and not in patients treated with only chemotherapy. Conversely, we found no difference the left side, but we found a difference in the poor group of 4 months in favor to only chemotherapy. Conclusion: Our results indicate that the CII index is a good prognostic marker for mCRC patients in first line treatment with CT with or without bevacizumab

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

IntroductionThe European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.MethodsThe cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).ResultsImmuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.ConclusionApplication of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification

Decellularized human dermal matrix produced by a skin bank: A new treatment for abdominal wall defects

BACKGROUND; Interest is increasing for human decellularized scaffolds for their ability to favor healing and cell infiltration after transplantation, in the treatment of abdominal wall defects. The purpose of the present study is to show the clinical results obtained after the application of human decellularized dermal matrix (HDM) produced by RER Skin Bank, on patients suffering from different abdominal wall defects. METHODS: Between 2012 and 2014, 64 patients, average age 64 years, received HDM, to replace and cover the damage area during abdominal wall surgery. After surgical procedures, all patients were followed weekly for the first month and then monthly up to 6 months postoperative and any major problem or complication were recorded. Six months follow up included abdominal exams, serological tests and MRI analysis in order to evaluate integration of HDM with the patients surroundings tissues and eventual long-term complications. RESULTS: Incisional hernia was the most frequent clinical condition in which HDM was applied, requiring also the highest amount of human decellularized dermal matrix. One month after the surgical operation, 61 patients revealed a well tolerability of HDM and a normal wound healing was also identified in all the damage areas. Only 3 patients experienced postoperative infections. Moreover the follow up after 6 months reported no signs of dermis rejection and that none of the patients was positive to serological tests. CONCLUSIONS: Human decellularized dermal matrix can be considered a safe and useful bioproduct to treat large abdominal defects, characterized by minor complications and simplicity to be implanted

A Giant Lumbar Pseudomeningocele in a Patient with Neurofibromatosis Type 1: A Case Report

This is a rare case of giant lumbar pseudomeningocele with intra-abdominal extension in patient with neurofibromatosis type 1 (NF1). The patient's clinical course is retrospectively reviewed. A 34-year-old female affected by NF1 was referred to our institution for persistent low back pain and MRI diagnosis of pseudomeningocele located at L3 level with paravertebral extension. From the first surgical procedure by a posterior approach until the relapse of the pseudomeningocele documented by MRI, the patient underwent two subsequent posterior surgical procedures to repair the dural sac defect with fat graft and fibrin glue. One month after the third operation, the abdominal MRI showed a giant intra-abdominal pseudomeningocele causing compression of visceral structures. The patient was asymptomatic. The pseudomeningocele was treated with an anterior abdominal approach and the use of the acellular dermal matrix (ADM) sutured directly on the dural defect on the anterolateral wall of the spinal canal. After six months of follow-up the MRI showed no relapse of the pseudomeningocele. Our case highlights the possible use of ADM as an effective and safe alternative to the traditional fat graft to repair challenging and large dural defects

ROCK. Co-design workshops and self-built transformation of public space in Bologna with students and professionals. Urban regeneration of Piazza Rossini. Le Cinque Piazze experience

The dataset contains the presentation and preparatory materials presented within the co-design workshop and self-built transformation of public space “Le Cinque Piazze. Un workshop per prendersi cura della zona U” held in March 2019 in Bologna, and the project of urban regeneration of Piazza Rossini, co-developed by students and professionals during the Self-construction workshop workshop "Le Cinque Piazze" held in September 2019. The data represent the design proposals for temporary urban transformations, developed during the workshop Le Cinque Piazze, by the students of the Architecture and Advanced Design students of the University of Bologna. The 24 students involved worked together with the University of Bologna – Architecture Department researchers, the Municipality of Bologna staff, Foundation for Urban Innovation and Fondazione Rusconi staff. Data can be used by both university researchers (as methodology to be replicated in similar workshops) or by city staff to take inspiration for projects to be realized in similar parts of the city