"Poker" association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study

<p>Abstract</p> <p>Background</p> <p>This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC).</p> <p>Methods</p> <p>Simon two-step design: delta 20% (p₀50%, p₁70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m², days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m²plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m², days 8, 22; every 4 weeks.</p> <p>Results</p> <p>Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m². ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%.</p> <p>Conclusion</p> <p>Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered.</p> <p>Trial registration</p> <p>Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34</p

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Histiocitose de células de Langerhans como causa de mielopatia: Relato de caso e revisão da literatura

ResumoHistiocitose de células de Langerhans é uma doença uni ou multifocal que acomete osso, tecido mole ou ambos. Relativamente incomum, abrange entidades clínicas anteriormente conhecidas como doença de Hand-Schüller-Christian, Abt-Letterer-Siwe, Hashimoto-Pritzker, granuloma eosinofílico e histiocitose X. Responsável por menos de 1% dos tumores ósseos, muito raramente leva a acometimento neurológico. Sua etiologia é desconhecida e seu tratamento, controverso. A ocorrência de um caso com comprometimento neurológico nos motivou a este relato. Paciente do sexo feminino, 4 anos de idade, com processo expansivo de C7 a T3 e paraparesia crural; após a cirurgia apresentou melhora importante já no segundo pós-operatório. Encontra-se em terapia complementar com corticoide e quimioterapia estando no nono mês de tratamento. Na revisão da literatura foram encontrados poucos relatos de manejo cirúrgico desse tipo de lesão, em razão de sua característica de doença autolimitada. O tratamento adequado pode variar dependendo das características do paciente e de seu comprometimento neurológico.</jats:p

Split and whole liver transplantation outcomes : a comparative cohort study

A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323 cases, respectively. SLTs were performed in situ as 147 left lateral segments (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers (MSL), used for couples of adult recipients. After a median posttransplant follow-up of 22 months, SLTs achieved a 3-yr patient and graft survival not significantly different from the entire series of transplants (79.4 and 72.2% vs. 80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed significantly better outcomes than patients receiving RTL and MSL (P 60 yr, RTL transplant, 7 hours, and retransplantation were factors independently related to graft failure and to significantly worst patient survival. Right grafts procured from RTL and either split procured as MSL had a similar outcome of marginal whole livers. In conclusion, in 5 yr, the increased number of pediatric transplants due to split liver donation reduced to 3% the in-list children mortality, and a decrease in the adult patient dropout rate from 27.2 to 16.2% was observed. Such results justify a more widespread adoption of SLT protocols, organizational difficulties not being a limit for the application of such technique