TAILORED APPROACH TO PERITONEAL METASTASIS IN GASTRIC CANCER PATIENTS: who can benefit from intensive surgical treatment
A.D’Ignazio1*, E. Marino2*, L. Graziosi2, M.C. Vannoni2 , S. Ministrini3, M. Bencivenga4, L. Solaini5,S. Sofia7, B. Molteni3, M.S. Alfano3, C. Cipollari4, K. Polom1, M. Degiuli7, P. Morgagni5, G. Mura6,, G. De Manzoni4 G.A.M. Tiberio3, D. Marrelli1, A. Donini2, F. Roviello1
Surgical approach to stage IV gastric cancer patients for peritoneal metastasis has always been considered a palliative treatment. The aim of our paper is to identify patients with peritoneal disease from gastric cancer that could benefits from an intensive surgical treatment.
Material and methods
122 patients with gastric cancer and synchronous peritoneal macroscopic metastases, treated from 2010 to January 2017 in 8 Italian centres were retrospectively analysed. All the patients were metastatic only for the peritoneal location stratified according to Japanese classification.
Patients were divided into 2 groups: 84 underwent surgery up-front, debulking alone or associated with HIPEC, and 38 received preoperative chemotherapy. Curative surgery was defined when R0 resection was performed.
Survival analysis were generated according to the Kaplan-Mayer method; p < 0.05 was considered statistically significant.
The overall survival was 15% at 5 years, with a median of 15 months.
Median overall survival of patients that underwent surgery upfront was 12.1 vs. 10.0 months median survival of patients that underwent chemotherapy before the surgical treatment (P> 0.05).
Surgical resection completeness and HIPEC influenced survival in both groups (p=0.036).
In the upfront surgery group: pN stage, Lauren istotype , peritoneal involvement grade and D2 lymphoadenectomy were signficant prognostic factor at the univariate analysis.
At the multivariate of the upfront surgery population the independent prognostic factor was R0( p=0.025).
Our preliminary results show that also patients with peritoneal metastasis from gastric cancer have an option of curative treatment when R0 resection can be made. This data need to be validated in larger studies.
Surgery for stage IV Gastric Cancer: an Italian perspective
B. Molteni, S. Ministrini1, M. Bencivenga2, E. Marino3, A. D’Ignazio4, L. Solaini5, G. Mura6, S. Sofia7, M.S. Alfano1, C. Cipollari2, M.C. Vannoni3, K. Polom, M. Degiuli7, P. Morgagni5, D. Marrelli4, F. Roviello, A. Donini3, G. De Manzoni2, G.A.M. Tiberio1
1 University of Brescia, Brescia – Italy
2 University of Verona, Verona – Italy
3 University of Perugia, Perugia – Italy
4 University of Siena, Siena – Italy
5 Hospital of Forlì, Forlì – Italy
6 Hospital of Arezzo, Arezzo – Italy
7 University of Torino, Torino – Italy
Objectives: Surgical approach to gastric cancer with hepatic metastases is becoming more and more accepted but few information exist concerning the surgical management of gastric cancer with extra-hepatic metastases. With this retrospective study we evaluated if the prognosis is influenced by different metastatic sites and we looked for the presence of prognostic factors.
Methods: We analysed 287 patients with gastric cancer and synchronous metastases treated at our Institutions from 2010 to January 2017. We investigated survival performances after surgery according to the site of metastases: peritoneal, hematogenous, hepatic, distant lymph nodes and more than one site. Furthermore, we investigated how survival was influenced by patient-, gastric cancer-, metastases- and treatment-related prognostic factors.
Results: Median overall survival was 10.9 months. We found no survival differences according to the site of metastases: median survival was 11.2, 11.6, 9.8, 21.4, 7.0 months for peritoneal, hepatic, lymph-nodal, hematogenous and more than1 site of metastases respectively (p=0.797). In all subgroups we observed an interesting number of long-term survivors (peritoneal 14.3% ≥36 months, 7.6% ≥60 months; hepatic 13.0% ≥36 months, 2.2% ≥60 months; lymph nodes 12.5% ≥36 months, 3.1% ≥60 months; > 1 site 18.7% ≥36 months, 1.6% ≥60 months).
At multivariate analysis the factors that influenced survival were: number of resected lymph-nodes (p=0.013), pN (p<0.001), curativity (p=0.001) and histology (p=0.022).
Conclusion: We showed that no differences in overall survival according to site of metastases exist and we suggest that patients in whom a curative resection is possible, should be treated by resection of both gastric cancer and metastases.
Upper GI training of young surgeons. An international survey.
Rossella Reddavid, Maurizio Degiuli
University of Torino; Italy
Surgical education plays an important role in safe patient care. How is the training pathway of young surgeons in upper GI nowdays? Should they complete the learning curve during their residency? The aim of this Survey is to investigate their actual training pathway all around the world.
An open question about the Upper GI training of young surgeons was sent to the Heads of 33 referral centres all over the world. A questionnaire with ten topics (demographics, residency, fellowship, participation to congresses and workshops as uditor, posters and lectures presentations, cadaver and simulation labs, publications and additional degrees) was forwarded to young surgeons from each of these centres to assess the training pathway during their residency and fellowship and their satisfaction level.
The response rate at this moment is 30%; replies came back from Italy, Poland, Japan, Korea, USA, Brazil and Chile. During their residency young surgeons from Chile and Brasil performed more procedures compared with surgeons from other countries (>20 gastrectomies in both countries, >10 esophagectomies and functional procedures in Brazil). Young surgeons from all countries improved their case series during fellowship. Most of the western young surgeons do their fellowship in Korea and in Japan while eastern surgeons remain in their own country. Scientific training is mostly the same in all examined countries.
Upper GI training of young surgeons seems more adequate in countries from Latin America while Japan and Korea are mostly choosen for fellowship.
Early Gastric Cancer: identification of molecular markers able to distinguish penetrating lesions with different prognosis
Molinari C1, Capelli L1, Morgagni P2, Ulivi P1 , Ravaioli S1, Tumedei M, Abou Khouzam R3, Scarpi E4, Calistri D1, Monti M5, Verona6, Siena7, , Bonafè M1 and Saragoni L8
1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
2Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy.
3Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
4Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
5Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
8Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.
Objectives: The objective of this study was to perform a phenotypical and molecular characterization of a series of Early Gastric Cancers (EGC), classified as PEN A and PEN B, also in comparison to a series of T3N0 GC, with the aim to identify markers associated with the worse prognosis of PEN A with respect to PEN B. Methods: Twenty EGC PEN A, 20 PEN B and 20 T3N0 GC were characterized for CDX2, CD10, MUC-2, MUC-6, MUC-5AC and EGFR expression by immunohistochemistry, for microsatellite instability (MSI) by CC-MSI and for KRAS, NRAS, BRAF and PIK3CAmutations by MassARRAY Sequonom. Results: Samples were confirmed to be predominantly positive for CDX2 and negative for CD10, independently of subtype. MUC-2 expression resulted significantly associated with subtypes, with the significantly higher number of positive tumors among PEN B. Although not statistically significant, a trend was observed for EGFR overexpression in PEN A and T3N0 GC. With regard to MSI, there was a significant difference between PEN B and T3N0 tumors. No associations with the mutational status of analysed genes and tumor subtypes were observed.
Conclusions: Based on our preliminary results MUC-2 expression seems to be able to distinguishing PEN A and PEN B EGC. To further confirm if the mucin phenotype and MSI could be useful for EGC prognosis characterization we are planning to analyze a bigger case series.
Prognostic impact of tubular-papillar/poorly cohesive-Signet Ring Cell ratio in
WHO mixed gastric adenocarcinomas.
C. Castelli1, M. Bencivenga2, A. Tomezzoli1, L. Saragoni3, G. Tiberio4, L.
Alessandrini5, C. Belluco6,2
1Verona University Hospital, Pathology, Verona, Italy.
2University of Verona, Surgery, Verona, Italy.
3Hospital of Forlì, Pathology, Forlì, Italy.
4University o Brescia, Brescia, Italy.
5CRO Aviano, Pathology, Aviano, Italy.
6CRO Aviano, Aviano, Italy.
The aim of the present study is to compare clinico-pathological characteristics
and survival of gastric cancer mixed tumours according to their tubularpapillar/
poorly cohesive-Signet Ring Cell ratio.
122 patients with mixed GC treated from 2000 and 2014 at 5 dedicated centers
belonging to the Italian Research Group for Gastric Cancer (GIRCG) were
enrolled. Expert pathologists in each centre re-evaluated pathological slides in
order to assess the tubular-papillar/poorly cohesive-SRC ratio. Association
between the tubular-papillar/poorly cohesive-SRC ratio and tumor stage and
recurrence pattern was investigated by Fisher’s exact test. Survival curves
were estimated by Kaplan-Meier method. Cox regression model was also
51 cases (42%) had equal percentage of tubulo-papillar and poorly
cohesive/SRC components, 28 (23%) had a predominant tubulo-papillar
component, while 43 (35%) were predominantly composed of poorly
cohesive/signet ring cells. Tumours with predominant tubulo-papillar features
tend to be less advanced as regard the T stage (p= 0.056). Pattern of
recurrence significantly differs according to tubular-papillar/poorly cohesive-
SRC ratio. Indeed, hematogenous metastases were more frequent in cases with
predominant tubulo-papillar components, while peritoneal, lymphnodal and
multiple sites metastases were more frequent in cases with predominant
poorly cohesive/SRC features (p=0.016). Overall survival tended to be higher
(56%) in cases of tubulo-papillar predominance compared to 36% in tumours
with predominance of poorly cohesive-SRC features (p=0.573). In multivariable
analysis, tubular-papillar/poorly cohesive-SRC ratio was not an independent
risk factor for overall survival.
The tubular-papillar/poorly cohesive-SRC ratio significantly affects the
recurrence pattern in mixed GC. These features are important to plan tailored
treatment strategies for these tumours.
LIMITED USEFULNESS OF 18F-FDG-PET/CT IN PREDICTING TUMOUR REGRESSION AFTER PREOPERATIVE CHEMOTHERAPY FOR NON-CARDIA GASTRIC CANCER. THE GIRCG EXPERIENCE
M. Sacco1, P. Morgagni2, M. Bencivenga1, E. Colciago2, D. Tringali1, G. Verlato3, M. Framarini2, L. Saragoni4, G. Mura5, L. Graziosi6, E. Marino7, U. Romario Fumagalli8, G.L. Baiocchi9, A. Moretti10, V. Rossi11, S. Giacopuzzi1, G. de Manzoni1.
1University of Verona, General and Upper GI Surgery Department, Verona, Italy. 2Morgagni-Pierantoni Hospital, Department of Surgery, Forlì, Italy. 3University of Verona, Unit of Epidemiology and Medical Statistics, Verona, Italy. 4Morgagni-Pierantoni Hospital, Pathology Unit, Forlì, Italy. 5Montevarchi General Hospital, Surgical Unit- Santa Maria alla Gruccia, Arezzo, Italy. 6University of Perugia, Department of Surgery, Perugia, Italy. 7Perugia University, Department of Surgery, Perugia, Italy. 8Humanitas Clinical Institute IRCCS, General Surgey, Milano, Italy. 9University of Brescia, Surgical Clinic- Department of Clinical and Experimental Sciences, Brescia, Italy. 10Morgagni-Pierantoni Hospital, Nuclear Medicine Unit, Forlì, Italy. 11San Donato Hospital, Nuclear Medicine Unit, Arezzo, Italy.
The present study aimed at better defining the usefulness of 18F-FDG-PET/CT in predicting pathological tumour response (PTR) and survival in patients with non-cardia gastric cancer treated with preoperative chemotherapy.
71 patients were recruited in 6 Italian centers. The standard uptake value (SUV) of 18F-FDG-PET/CT was measured at baseline and after treatment, and the difference (dSUV) was computed. The association between PET indexes and PTR, assessed by Becker score, was evaluated by non-parametric regression. The discriminant power of PET indexes, with respect to absence of PTR (Becker 2/3) was tested by ROC curves, and synthesized by area under the curve (ROC-AUC).
dSUV somewhat allowed to discriminate between absence/presence of PTR, when expressed both as absolute value (ROC-AUC 0.73, 95% CI 0.59-0.87) or percentage (ROC-AUC 0.74, 0.59-0.89). However, only extreme values of percent dSUV were informative: all the 7 patients, whose 18F-FDG uptake had increased during preoperative treatment, presented no tumour regression at pathologic examination; 7 of the 10 patients, whose metabolic response had been larger than 70%, had complete or nearly complete pathologic tumour regression (Becker score 1a or 1b); for the remaining 54 patients, whose metabolic response ranged between 0 and 70%, metabolic response did not allow to forecast pathologic tumour regression. Survival significantly decreased with increasing Becker score, while being unaffected by metabolic response.
The present study suggests that 18F-FDG-PET/CT has limited usefulness in predicting cancer regression. Lack of metabolic response in serial measurements likely allows to exclude effectiveness of preoperative treatment.
Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study
Leonardo Solaini, Silvia Ministrini, Maria Bencivenga, Chiara Cipollari, Elisabetta Marino, Alessia D’Ignazio, Gianni Mura, Daniele Marrelli, Annibale Donini, Franco Roviello, Giovanni De Manzoni, Guido AM Tiberio, Paolo Morgagni.
Objectives. The aim of this study is to report the experience with conversion surgery from six GIRCG centers, focusing our analysis on factors affecting survival and the risk of recurrence.
Methods. A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017 in 6 Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis.
Results. Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI>6) (n=38, 84.4%), distant metastatic nodes (n= 2, 4.4%) and extensive liver involvement (n=5, 11.1%). After palliative chemotherapy metastases were no more visible at preoperative and operative re-assessment in 5 cases (2 hepatic, 2 peritoneal and 1 nodal). Median follow-up was 25 months (IQR 9-50). Median overall survival was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median disease-free survival was 12 months with 1- and 3-year survival of 48 and 33%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 2.57, 95% CI 1.04-6.33, p=0.042).
Conclusions. In conclusion, technically unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survival. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement.
SURGERY FOR STAGE IV GASTRIC CANCER WITH EXTRA-REGIONAL LYMPH NODE METASTASES
M. Sacco1, S. Sofia2, L. Torroni1, M. Bencivenga1, G. Tiberio3, P. Morgagni4, A. D'Ignazio5, G. Verlato1, G. de Manzoni1.
1University of Verona, Upper GI Surgery, Verona, Italy. 2Univrsity of Torino, Surgery, Torino, Italy. 3University of Brescia, Surgery, Brescia, Italy. 4Hospital of Forlì, Surgery, Forlì, Italy. 5University of Siena, University of Siena, Siena, Italy.
The aim of the present study was to evaluate the outcomes of surgery with curative intent in patients with gastric cancer (GC) carrying metastases to extra-regional lymph nodes (ERLM).
The present observational multicenter retrospective study included all patients (n=58) with pathologically detected ERLM (pERLM), undergoing R0/R1 resection at 7 centres belonging to the Italian Research Group for Gastric Cancer (GIRCG) from 2010 to 2017.
Fourty-four patients (76%) had clinically detected ERLM (cERLM). Eleven of these (25%) had also clinically detected extra-nodal metastases (cENM) and 23 (52%) underwent preoperative chemotherapy. Three-year overall survival (OS) was 31% (95%CI 17-45%) in all patients with cERLM, increased to 38% (20-56%) in 33 patients with cERLM but without cENM, and further to 41% (20-62%) in 21 patients with cERLM located at stations 12p/13/16a2/16b1. In the whole series with pERLM, 28 (48%) underwent preoperative chemotherapy and 16 (28%) had also pathologically detected ENM (pENM). Median survival was 7.4 months (range 5-13.2), and 3-year OS was 24% (14-36%) in the whole series. Three-year OS increased to 30.2% (16-45%) in the 42 patients without pENM, and to 30.2% (13-49%) in the subgroup of 16 patients with pERLM located at stations 12p, 13, 16a2 and 16b1.
Gastrectomy with curative intent could be indicated also in patients with GC harboring ERLM, as their survival is not negligible after radical-intent surgery, especially in cases without other ENM. These findings could be the starting point to plan future prospective studies.