In questa pagina sono riportati gli abstracts inviati dei Centri del GIRCG partecipanti al 12th IGCC che si terrà a Pechino dal 20 al 23 aprile 2017.
Abstract 1
Total vs Proximal Gastrectomy for Adenocarcinoma of the Upper Third of the Stomach: a multicentre observational western experience on perioperative outcomes (On behalf of the Italian Research Group for Gastric Cancer – GIRCG).
Authors: Fausto Rosa, MD1; Claudio Fiorillo, MD1; Massimiliano Bissolati, MD2; Chiara Cipollari, MD3; Stefano Rausei, MD4; Damiano Chiari, MD2; Laura Ruspi, MD4; Giovanni de Manzoni, MD3; Guido Costamagna, MD5; Giovanni Battista Doglietto, MD1; Sergio Alfieri, MD1.
Affiliations: 1 Department of Digestive Surgery, “A. Gemelli” Hospital, Catholic University of Rome
2 Department of Surgery, Vita-Salute San Raffaele University, Milan, Italy
3 1st Division of Surgery, University of Verona
4 Department of Surgical Sciences, University of Insubria (Varese-Como)
5 Department of Digestive Endoscopy, “A. Gemelli” Hospital, Catholic University of Rome
Key words: Upper third gastric cancer; Surgery; Total Gastrectomy; Proximal Gastrectomy
Objective:
To compare surgical results including postoperative complications and prognosis between total gastrectomy (TG) and proximal gastrectomy (PG) for proximal gastric cancer (GC).
Methodology:
Among 457 patients who were diagnosed with GC between January 1990 and December 2010 from 4 Italian centres, 91 underwent PG and 366 underwent TG. Clinicopathologic features, postoperative complications, and survivals were reviewed and compared between these two groups retrospectively.
Result:
The PG group (n: 91) had smaller tumors, shorter resection margins, and smaller numbers of retrieved lymph nodes than the TG group (n: 366). N stages and 5-year survival rates were similar after TG and PG. Postoperative complication rates after PG and TG were 25.3% and 26.2%, respectively, (P= 0.084). Postoperative morality rates were 5.5% and 1.4%, respectively, (P= 0.04). Rates of reflux esophagitis and anastomotic stricture were 16.5% and 6.6% after PG and 1.4% and 0.8% after PG, respectively (P<0.001 and P=0.002).
Five-year overall survival for PG and TG group was 56.7% and 46.5%, respectively. Survival according to the tumor stage were not different between the groups.
Multivariate analysis showed that type of resection was not an independent prognostic factor.
Conclusion:
Although PG for upper third GC showed good results in terms of survival, it is associated with an increased risk of reflux esophagitis and anastomotic stricture than TG.
Abstract 2
Validation of a model of orthotopic transplantation of human gastric cancer in NOD SCID mice for generation of a gastro-esophageal Patient-Derived Xenograft (PDX) platform to improve therapeutic outcome
Reddavid R., Menegon S., Corso S., Giordano S., Degiuli M
Introduction: Gastric cancer is the third leading cause of cancer mortality worldwide. Surgery is the only curative treatment strategy; conventional chemotherapy has shown limited efficacy and only two molecular therapies are currently approved (Trastuzumab for HER2+ GCs and Ramucirumab). To explore in depth the molecular mechanisms sustaining tumor growth and response to therapy, animal models are very useful. At the moment, the best preclinical model to validate targets and positive/negative response predictors of response to therapy is represented by Patient-Derived Xenografts (PDXs), an experimental model that retains the principal histologic and genetic characteristics of the donor tumor, is predictive of clinical outcome and is a valuable tool for personalized medicine decisions. Indeed, this strategy combines the flexibility of preclinical analysis with the informative value of population-based studies. We have recently generated a molecularly annotated colony of gastro-esophageal PDXs (at the moment >90 PDXs) by subcutaneous transplantation in NOD SCID mice. This platform also comprises primary cell lines and 3D-coltured organoids. Although this platform has already been helpful in investigating therapeutic approaches against activated receptor tyrosine kinases, the subcutaneous tumor implantation very rarely allows metastatic dissemination.
Material and Methods: To verify if gastric tumors can grow and give rise to metastases when implanted in their original organ, we orthotopically transplanted either cancer cell suspensions or intact cancer tissues. Cancer cell suspensions were inoculated under the serosal coat of mice's stomach while tumor samples were implanted inside the stomach and fixed to the mucosal coat with stitches. Growth of the primary tumor and appearance of metastases have been monitored in vivo using IVIS technology (In Vivo Imaging System, IVIS Spectrum). Pathological analysis has been performed after animal sacrifice.
Results and Discussion: With both techniques we have been able to observe local tumor growth which was monitored along time through fluorescent 2-Deossi glucose (Xenolight RediJect 2-DG-750 probe) revealed by IVIS. In animals injected with gastric cells we observed local tumor growth, several intraperitoneal neoplastic lesions and metastatic growth in the lungs. In animals orthotopically transplanted with gastric tumor samples, engraftment was observed and experiments are ongoing to reveal the development of metastases.
Conclusion: We have been able to orthotopically transplant gastric cancer cells and gastric tumors which grew and originated metastases. We intend to use these models to evaluate the efficacy of therapies targeting molecular lesions identified in the implanted tumors. We believe that orthotopic transplantation will better mimic the original microenvironment of the tumor and will thus recapitulate the therapeutic responses observed in patients.
Abstract 3
Good lymphatic regression after neoadjuvant treatment with Docetaxel Capecitabin and Oxaliplatin (DOC). Interim results of the Italian GASTRODOC randomizad multicentre trial
Paolo Morgagni1, Framarini Massimo1, Simone Giacopuzzi1, Gianni Mura1, Uberto Fumagalli1, Gian Luca Baiocchi1, Barbara Lazzari 1, Giovanni Sgroi1, Francesca Steccanella1, Luigina Graziosi1, Elisabetta Marino1, Carlo Milandri1, Stefano Rausei1, Laura Ruspi, Manlio Monti2, Domenico Tringali1 ,Luca Saragoni 1, Anna Tomezzoli 1, Maria Antonietta Mazzei1, Petrella Enrico1 , Franco Roviello1 , DanieleMarrelli1, Chiara Tronconi1 , Giovanni de Manzoni1
on behalf of the Italian Research Group for Gastric Cancer (GIRCG)
2IRST IRCCS (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori), Meldola
Keywords
Advanced gastric cancer, neoadjuvant chemotherapy.
Objective
Neoadjuvant treatment is frequently proposed and currently accepted in ESSO ESMO guidelines. Several drugs and association are proposed with different results. We present interim data of the GASTRODOC randomized trial with DOC treatment on patients submitted to accurate preoperative staging with standardized guidelines on CT scan.
Methodology
We analyzed data on a series of patients with advanced non-metastatic gastric cancer (T3-4a, M0), age< 75 years old, submitted to neoadjuvant treatment at 13 GIRCG centers between January 2010 and September 2016.
Clinical TNM stage was supposed on common radiologic GIRCG guidelines and staging laparoscopy.
Cancer regression was evaluated with Becker score system, and pathologic lymphatic involvement is reported.
Result
85 patients were considered. Clinical lymphatic involvement was described in 66 patients (77.6%) .
A median number of 34 lymph nodes were dissected after D2/D3 lymphadenectomy (range 6-88). 26 patients (36%) were N0
In 46 patients (64%) lymphatic involvement was confirmed at the pathological report (13 N1,15N2,18N3)
with a median number of 2 positive lymph nodes (range 0-60).
Conclusion
Considering literature data and the advanced stages of the gastric cancers enrolled, few involved lymph nodes were retrived.
Even if we don't have any score based on lymphatic regression, in our experience neoadjuvant treatment with Docetaxel, Oxaliplatin and Capecitabin allows good results also on lymph nodes.
Abstract 4
How the staging laparoscopy impacts on the choice of the best treatment for advanced gastric cancer?
Domenico Tringali, Paolo Morgagni, Framarini Massimo, Simone Giacopuzzi, Gianni Mura, Uberto Fumagalli, Gianluca Baiocchi, Giovanni Sgroi, Francesca Steccanella, Luigina Graziosi, Elisabetta Marino, Carlo Milandri, Stefano Rausei, Maria Bencivenga, Giovanni de Manzoni, Beatrice Verdelli, Luca Saragoni, Sarah Molfino, Stefano de Pascale, Laura Ruspi, Manlio Monti*.
The Italian Research Group for Gastric Cancer (GIRCG)
*IRST (Istituto Romagnolo per lo Studio e la Cura dei Tumori), Meldola
Keywords:
Staging laparoscopy, advanced gastric cancer, palliative chemotherapy, conversion surgery.
Background:
The accuracy of conventional staging exams for gastric cancer is around 63% to 80% to determing “T” and “M”, especially in detecting peritoneal carcinosis. This causes roughly 30% of unnecessary laparotomies. Staging laparoscopy (SL) is used to improve the accuracy of gastric cancer staging.
Patients and methods:
We analized the cohort of patients candidate to neoadjuvant chemotherapy in the IRST 151.01 multicentric prospective trial from 2010 to 2016. If locally advanced disease was confirmed at SL, patients were enrolled in the trial. If stage IV disease was found, the patient were submitted at palliative treatment. We analized the role of staging laparoscopy in changing treatment plan, the effect of palliative chemotherapy to allow cyto-reductive surgery and the OS of the patients who underwent surgery.
Results:
168 patients underwent SL. In 72 cases (42,9%) SL was negative and the patients were enrolled in the IRST 151.01 trial; other 60 SL (35.7%) were negative, but the patients were treated alternatively due to different reasons (patient refuse, important comorbidities...); in the last 36 patients (21,4%), SL changed the therapeutic strategy since unexpected stage IV disease was found during the procedure. Among these 36 patients, 21 (58,3%) underwent palliative chemotherapy and 2 patients underwent directly to cyto-reductive surgery and HIPEC. At the end of the palliative treatment, 9 patients (42,86%) underwent surgery with a median OS of 8 (range 1-29) months from surgery. Two patients who underwent surgery after palliative chemotherapy presented a follow-up longer than 20 months from surgery. One patient who was directly submitted to surgery and HIPEC is alive 44 months after surgery.
Conclusions:
SL improves the accuracy of staging: it helps in avoiding unnecessary laparotomies and related morbidity and mortality. This approach involves tailored treatment and it allows to start faster palliative chemotherapy which may leads to complete resective surgery (conversion surgery).
Abstract 5
Conversion surgery after palliative chemotherapy for not resectable gastric cancer: may we achieve curative treatment?
Tringali Domenico1, Morgagni Paolo2, Framarini Massimo2, La Barba Giuliano2, Vittimberga Giovanni2, Monti Manlio3, Frassineti Luca3, Andrea Gardini2 , Saragoni Luca4, Ercolani Giorgio2
1Department of General Surgery , Borgo Trento Hospital, Verona
2Department of General Surgery , Forlì
3Istituto Romagnolo per lo Studio e la cura dei Tumori, Meldola
4Department of Pathological Anatomy, Forlì
Keywords:
Not resectable gastric cancer, Palliative chemotherapy, Gastrectomy, HIPEC
Background:
The standard of care for not resectable gastric cancer is chemotherapy with really poor prognosis. Sometimes, after intensive chemotherapy surgical R0 treatment is achievable (conversion surgery) and this allows a better outcome respect to chemotherapy alone.
Patients and Methods:
We retrospectively investigated the role of palliative chemotherapy regimens to allow radical resection in 73 patients with diagnosis of unresectable gastric cancer between 2005 and 2015 in our hospital. We analized separately the OS from diagnosis of the patients who underwent best supportive care, only chemotherapy and chemotherapy followed by surgery.
Results:
Of 73 patients with unresectable gastric cancer, 16 (21,9%) underwent just best supportive care due to extension of disease or unable to chemotherapy, the other 57 (78,1%) underwent palliative chemotherapy. Of these 26 (45.6%) at the revaluation after chemotherapy became elegible for surgery. In 22 patients R0 surgery (84,6%%)was performed, in 4 patients (15,4%) only explorative laparotomy was performed. Surgical procedure were total gastrectomy (68,2%), distal gastrectomy (22,7%), others (9,1%). The main lyphadenectomy permormed is D2 (45,4%) and if at the diagnosis peritoneal carcinosis was found, during the surgical intervention HIPEC was performed (9 patients, 40,9%). The median OS from diagnosis was 3 months (0-12), for best supportive care group, 9 months (1-17) for only chemotherapy group (including the explorative laparotomies after palliative chemotherapy) and 30,5 months (11-136) for chemotherapy plus surgery group. 3-years OS was 0% for best supportive care group 0% for chemotherapy alone and 40,9% for chemotherapy plus R0 surgery. 3 patients (13.6%) of the chemotherapy plus surgery group were alive after 60 months after surgery. The median OS for the group underwent HIPEC was 31 months (14-136) with a 3-years and 5-years OS of 44.4% and 22.2% respectively.
Conclusions:
Treatment for not resectable gastric cancer based on association of chemotherapy and surgery (R0 resection) improve the prognosis of these patients. This leads to the assumption of curative purpose and not just palliative role of surgery after chemotherapy.