Imatinib as adjuvant therapy for high risk GIST: a case report

We here report a case of 42 years old man who experienced sudden abdominal cramps and then underwent explorative laparotomy because of the CT-finding of a 23 cm abdominal mass at the stomach. Frozen specimen analysis indicated a probable gastrointestinal stromal tumor (GIST). Radical excision was performed. Definitive pathological analysis revealed a CD34 and CD 117(c-KIT) positive GIST with a mitotic count of 15/50 HPF. These features indicate a disease with an high risk of recurrence within few years. Molecular analysis found a WK557-558 deletion of c-KIT exon 11, that indicates a poor prognosis in patients with completely resected GIST. In april 2010 he started adjuvant therapy with imatinib at standard dose of 400 mg/day that was well tolerated: he reported only G1 periocular edema and conjunctivitis. Considering the risk of disease recurrence he continued adjuvant therapy beyond the first year

Different quality of treatment in retroperitoneal sarcomas (RPS) according to hospital-case volume and surgeon-case volume: a retrospective regional analysis in Italy

Abstract Background Retroperitoneal sarcomas (RPS) should be surgically managed in specialized sarcoma centers. However, it is not clearly demonstrated if clinical outcome is more influenced by Center Case Volume (CCV) or by Surgeon Case Volume (SCV). The aim of this study is to retrospectively explore the relationship between CCV and SCV and the quality of surgery in a wide region of Northern Italy. Methods We retrospectively collected data about patients M0 surgically treated for RPSs in 22 different hospitals from 2006 to 2011, dividing them in two hospital groups according to sarcoma clinical activity volume (HCV, high case volume or LCV, low case volume hospitals). The HCV group (> 100 sarcomas observed per year) included a Comprehensive Cancer Center (HVCCC) with a high sarcoma SCV (> 20 cases/year), and a Tertiary Academic Hospital (HVTCA) with multiple surgeon teams and a low sarcoma SCV (≤ 5 cases/year for each involved surgeon). All other hospitals were included in the LCV group (< 100 sarcomas observed per year). Results Data regarding 138 patients were collected. Patients coming from LCV hospitals (66) were excluded from the analysis as prognostic data were frequently not available. Among the 72 remaining cases of HCV hospitals 60% of cases had R0/R1 margins, with a more favorable distribution of R0/R1 versus R2 in HVCCC compared to HVTCA. Conclusions In HCV hospitals, sarcoma SCV may significantly influence RPS treatment quality. In low-volume centers surgical reports can often miss important prognostic issues and surgical quality is generally poor

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients

Colorectal cancers (CRCs) evolve by a reiterative process of genetic diversification and clonal evolution. The molecular profile of CRC is routinely assessed in surgical or bioptic samples. Genotyping of CRC tissue has inherent limitations; a tissue sample represents a single snapshot in time, and it is subjected to spatial selection bias owing to tumor heterogeneity. Repeated tissue samples are difficult to obtain and cannot be used for dynamic monitoring of disease progression and response to therapy. We exploited circulating tumor DNA (ctDNA) to genotype colorectal tumors and track clonal evolution during treatment with the epidermal growth factor receptor (EGFR)-specific antibodies cetuximab or panitumumab. We identified alterations in ctDNA of patients with primary or acquired resistance to EGFR blockade in the following genes: KRAS, NRAS, MET, ERBB2, FLT3, EGFR and MAP2K1. Mutated KRAS clones, which emerge in blood during EGFR blockade, decline upon withdrawal of EGFR-specific antibodies, indicating that clonal evolution continues beyond clinical progression. Pharmacogenomic analysis of CRC cells that had acquired resistance to cetuximab reveals that upon antibody withdrawal KRAS clones decay, whereas the population regains drug sensitivity. ctDNA profiles of individuals who benefit from multiple challenges with anti-EGFR antibodies exhibit pulsatile levels of mutant KRAS. These results indicate that the CRC genome adapts dynamically to intermittent drug schedules and provide a molecular explanation for the efficacy of rechallenge therapies based on EGFR blockade

The representation of the onset of the Covid-19 pandemic and the consequent lockdown in Italy: A psychosocial research by SPS, Studio di Psicosociologia of Rome

A fine febbraio 2020, in SPS4ci siamo chiesti quali fossero i vissuti evocati dalla pandemia Covid-19 in esordio, e quali fatti “derivassero” da tali vissuti. A tal fine abbiamo interpellato 419 persone, tra l’1 marzo e il 5 maggio 2020. Il corpus raccolto è stato analizzato con l’Analisi Emozionale del Testo (AET). Si ipotizzava che la pandemia avesse destrutturato le modalità abituali di rapporto, e pensavamo stessero emergendo dimensioni relazionali inedite. I nostri dati dicono che l’individualismo abituale, di avida competitività, è in crisi. In risposta alla destrutturazione dello schema relazionale amico/nemico, alla base della socialità, è emerso un nuovo individualismo. La rappresentazione del pericolo insito nel contagio pandemico ci ha reso, tutti, potenzialmente nemici gli uni degli altri. Tutti siamo vissuti come potenzialmente nemici di tutti, a meno di non essere dichiaratamente malati. I malati, di contro, non sono vissuti come nemici: sono un’alterità scissa, relegata in un altrove lontano da chi è “sano”. Le cure, nel lockdown, erano confinate nell’ospedale, caratterizzate dall’isolamento, dall’emergenza, dalla morte esperita nel peggiore dei modi. L’altrove è stato reificato in un ospedale diventato sintomatico del fallimento del sistema sanitario. Si è costituito un “noi” qui insieme, sani e maniacalmente felici, e un “loro”contagiati, dannati, isolati e “altrove”. Internet, consentendo vicinanza senza contatto, è diventata un nuovo contesto di socialità. Ha permesso di ridiventare umani, ovvero amici, a meno che non si dimostri il contrario. Ma la nuova amicalità è fondata sulla scissione dall’altro dannato: la coppia malato/curante, e tutti gli esclusi, per diverse motivazioni, dalla protezione del lockdown. Dalla nuova socialità è escluso anche il vissuto dello stare chiusi in casa con gli abituali conviventi, dove emerge la violenza delle relazioni familiari obbligate. Si evidenziano altri esclusi dal noi maniacalmente amicale: gli anziani che non usano internet e che più di tutti rischiano di morire. C’è poi una cultura che, entro il fallimento delle relazioni sociali abituali, sottolinea l’impotenza delle istituzioni (politiche, sanitarie, mediatiche etc.) nella contingenza pandemica. Infine, c’è una cultura pre-lockdown, fatta della paura che porterà a scegliere l’isolamento. Manca, nei dati, il mondo produttivo, che non ha ritrovato, per gli interpellati dalla ricerca –nel periodo di tempo da noi considerato –un codice emozionale condiviso che potesse raccogliersi in un cluster. La ricerca aveva anche un obiettivo di intervento: quello di creare un contesto in cui l’evento pandemia potesse essere interpretato, entro un setting di partecipazione. Oltre a effettuare una pubblicazione rapida dei dati, intendiamo promuovere gruppi di discussione su internet con i partecipanti. La creazione di un contesto di condivisione è anche un motivo dell’alto numero di Autori.At the end of February 2020, in SPS2we asked ourselves what were the experiences evoked by the Covid-19 pandemic in its debut, and what facts “derived”from these experiences. To this end, we interviewed 419 people, between 1 March and 5 May 2020. The collected corpus was analyzed through the Emotional Text Analysis (AET). It was assumed that the pandemic had deconstructed the usual ways of relating, and we thought that new relational dimensions were emerging. Our data show that habitual individualism, of greedy competitiveness, is in crisis. A new individualism has emerged in response to the deconstruction of the friend/foerelational schema, at the basis of sociality. The representation of the danger inherent in the pandemic contagion has made us all potentially enemies of each other. We have all lived as potentially enemies of all, unless we are admittedly sick. The sick, on the other hand, are not experienced as enemies: they are a split otherness, relegated to an elsewhere far from those who are “healthy”. Duringthe lockdown, treatments were confined to the hospital, characterized by isolation, emergency, death experienced in the worst way. The othernesswas reified in a hospital that became symptomatic of the failure of the health system. A “we”has formed here together, healthy and maniacally happy, and a “them”infected, damned, isolated and “elsewhere”. The Internet, by allowing contactless proximity, has become a new context of sociality. It has allowed us to become human again, or friends, unless proven otherwise. But the new friendship is based on the split from the damned other: the sick/caring couple, and all those excluded, for various reasons, from the protection of the lockdown. The experience of being closed at home with the usual cohabitants is also excluded from the new sociality, where the violence of forced family relationships emerges. There are others excluded from a maniacally friendlyus: the elderly who do not use the internet and who most of all risk dying. There is also a culture that, within the failure of habitual social relations, underlines the powerlessness of institutions (political, health, media, etc.) in the pandemic contingency. Finally, there is a pre-lockdown culture, made up of fear that will lead to chooseisolation. In the data, the productive world is missing, which for those interviewed by the research did not find -in the period of time we considered -a shared emotional code that could be gathered in a cluster. The research also had an intervention objective: to create a context in which the pandemicevent could be interpreted, within a setting of participation. In addition to publishing the data quickly, we intend to promote discussion groups onthe internet with participants. The creation of a sharing context is also areason for the high number of Author