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Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS). Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes. Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival. Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

Background ASCO and ESMO guidelines have identified inadequate sampling of lymph nodes, pT4 primary tumors, obstruction or perforation, lymphovascular and perineural invasion, and poorly differentiated tumors as negative prognostic factors supporting the clinicians in treating their patients with stage II colon cancer (CC). However, the influence of histological subtypes on the risk of death or disease recurrence remains controversial. Methods The phase III, multicenter, randomized TOSCA trial compared 3 vs. 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. Objective of this sub-study was to investigate the role of the histological subtype [(mucinous adenocarcinoma (MUC) or non-mucinous adenocarcinoma (NMUC)] on the impact of the treatment duration in terms of relapse-free survival (RFS) and overall survival (OS) in the subgroup of patients with high-risk stage II, grade 3 CC. Results Out of 3,614 patients from 130 centres enrolled in the per-protocol population defined in the TOSCA trial, 85 MUC and 389 NMUC patients were included in this analysis. No statistical differences were found between 3 vs. 6 months groups in both histological subgroups in terms of baseline characteristics, except for tumor side. The proportion of patients with right-sided cancer was higher for patients with MUC than NMUC. A significant interaction between treatment duration and histology was observed on both RFS (p = 0.027) and OS (p = 0.017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03–15.17; p = 0.045) and OS (HR, 9.56; 95% CI, 1.14–79.98; p = 0.037) were detected for patients treated in the 3 months arm. No statistically significant differences were detected in the subgroup of patients with NMUC. Conclusions Both MUC and poorly differentiated subtypes have unfavorable clinical characteristics. Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to clarify the possible negative effect of the histological subtype to improve the prognosis of these patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background: Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. Patients and methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m 2 day 1, LV 100 mg/m 2 as 2 h infusion and 5-FU 400 mg/m 2 as bolus, days 1 and 2 followed by 600 mg/m 2 /day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m 2 day 1, cisplatin 75 mg/m 2 day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). Results: From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85–1.17; P= 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82–1.18; P= 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. Conclusions: A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy. Clinical trial registration: ClinicalTrials.gov Identifier: NCT01640782.

Premessa: Nonostante una generale giustificabilità sul piano etico, la sedazione palliativa (SP) presenta ancora numerosi aspetti controversi che richiedono un ulteriore dibattito e chiarificazione. Dal punto di vista pratico, inoltre, si osserva una notevole variabilità per quanto riguarda la procedura clinica della SP e un confine tra la SP alla fine della vita e l’eutanasia involontaria sempre più sottile e incerto. Questa situazione rende particolarmente necessaria l’elaborazione di percorsi decisionali trasparenti, anche nella forma di linee-guida locali, che chiariscano le procedure e le implicazioni etiche della sedazione palliativa. Obiettivi: Lo scopo di questo lavoro è di presentare le principali caratteristiche del percorso decisionale e assistenziale per la SP elaborato presso il Policlinico Universitario “Campus Bio-Medico” di Roma. Metodi: L’elaborazione della proposta presentata è stata preceduta da uno studio, attraverso la somministrazione di questionari semistrutturati, sulle conoscenze del personale medico e infermieristico in merito alla SP e da uno studio retrospettivo sulle cartelle cliniche, per verificare le modalità di utilizzo della SP all’interno dell’ospedale. Risultati: Il percorso decisionale ed assistenziale elaborato considera non solo gli aspetti farmacologici, ma affronta con chiarezza anche le implicazioni etiche e legali della procedura di SP, e in particolare la comunicazione, la cura dei familiari e degli operatori sanitari, la possibilità di avvalersi della consulenza di etica clinica nei casi più complessi o nei quali è difficile raggiungere una decisione condivisa. Si sottolinea, inoltre, come l’applicazione di un percorso decisionale e assistenziale per la SP debba essere supportata da momenti formativi e di confronto attivo tra gli operatori sanitari, per favorire l’adeguata comprensione e il corretto utilizzo di tali strumenti operativi, ma anche per assicurare il rispetto della coscienza degli operatori sanitari coinvolti. Conclusioni: È raccomandabile che tutte le istituzioni sanitarie producano percorsi decisionali ed assistenziali per la SP, attenti non solo agli standard scientifici, ma anche alla sensibilità etica e culturale del contesto in cui verranno utilizzate. Percorsi decisionali ed assistenziali così strutturati forniscono non solo un orientamento operativo e formativo per l’agire clinico, ma costituiscono anche un doveroso strumento di trasparenza nei confronti dei pazienti, dei loro familiari, della stessa struttura sanitaria e di tutta la società. ---------- Background: Despite a general ethical basis for justification, palliative sedation (PS) still has many controversial aspects that require further discussion and clarification. From a practical standpoint, moreover, there is considerable variability in the clinical procedure and an increasingly uncertain boundary between PS and involuntary euthanasia. This situation makes it necessary to develop local guidelines to clarify the procedures and the ethical implications of PS. Purpose: The aim of this paper is to present the main features of the ethical and clinical decision-making process for PS developed at the University Hospital “Campus Bio-Medico”, in Rome. Methods: The development of the present proposal was preceded by a survey, through a questionnaire, on the knowledge of medical and nursing staff on PS, and a retrospective study on medical records, to see how PS is used inside the hospital. Results: The benefit of this decision-making process is that it considers the pharmacological aspects, but also clearly addresses the ethical and legal procedure of PS, communication, the care for family members and health workers, the possibility of taking advantage of a clinical ethics consultation in complex cases or where it is difficult to reach a joint decision. We also emphasize that the application of the decision-making process must be supported by training sessions and active confrontation, to promote proper understanding and correct use of the guidelines themselves, but also to ensure respect for the conscience of health care professionals who are involved in the procedures of PS. Conclusions: It is recommended that all health care institutions produce local guidelines for PS, attentive to scientific standards, but also sensitive to the ethical and cultural context in which they are used. Ethical and clinical guidelines provide not only a well-structured operational guidance and training for clinical work, but are also a necessary tool for transparency with regard to all society.

Il presente lavoro ha l’obiettivo di condividere con la comunità scientifica, le riflessioni sorte all’interno di un Gruppo di Lavoro sul tema delle Cure Palliative costituito nell’Ospedale S. Giovanni Calibita dell’Isola Tiberina di Roma. Ci si è chiesti: come si muore in Ospedale? Che attenzione c’è nei confronti del paziente non guarito e destinato al trapasso in termini medio brevi? Le cure palliative possono essere di ausilio in questa fase di assistenza? Come modificare le abitudini consacrate di un ospedale per acuti e come indirizzare le stesse verso una maggior attenzione al problema delle cure di fine vita? E poi: il supporto palliativo deve restare destinato a coprire solo le ultime fasi della vita o intervenire anche prima? Lo stato dell’arte dimostra quanto ancora sia lontano lo sviluppo di una corretta mentalità di approccio al tema in discussione in ambiente ospedaliero e, fatto salve alcune virtuose eccezioni, ancora tende a distinguersi la fase puramente interventistica dell’azione sulla malattia da quella più attenta al controllo dei sintomi posticipata ad un momento successivo e distinto dall’intervento causale. Molto resta da fare in ambito ospedaliero ed il pensiero comune tra i componenti del gruppo è che solo attraverso una adeguata formazione, si può orientare la preparazione del personale verso una cultura diversa che permetta di guardare al paziente nella sua interezza ampliando la prospettiva che fa sì che ci si occupi solo della sua malattia. L’articolo riporta le riflessioni dei componenti del gruppo di lavoro rappresentanti di diverse unità operative e di vari servizi trasversali i quali, con oggettività e trasparenza, propongono una lettura critica dell’attenzione al tema delle cure palliative nelle unità operative di appartenenza. ---------- This work aims to share with the scientific community, the reflections arising within a Working Group on Palliative Care in Tiber Island Hospital – S. John Calibita – in Rome. The questions were: How people die in the hospital? What’s the approach to the patient not healed but nearly to die? Can palliative care be an aid in this fase of assistance? How can we change legitimate routines and modifying them to the issue of end of life care in acute-care hospitals? Can palliative support be intended only in the last stages of life or intervene before? The state of the art is far away from the development of a correct approach regarding palliative care in hospitals and except for a certain exceptions, it still tends to stand out on the stage of the disease interventional purely than the most careful control of symptoms. From the point of view of the group much remains to be done in the hospital especially aiming, with proper training, a different culture that allows to look at the patient as a whole and not just the disease. The article reflects the opinion of the working group who represents the different Operative Units and Cross-Services in our hospital. They propose a critical “reading” about palliative care according to their personal experience.