Publications by authors named "Franco Roviello"

241 Publications

Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group's analysis.

World J Surg Oncol 2021 Nov 24;19(1):334. Epub 2021 Nov 24.

General and Emergency Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy.

Background: The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery.

Methods: It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences.

Results: Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment.

Conclusion: The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with "radical oncological intent", that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.
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http://dx.doi.org/10.1186/s12957-021-02442-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611869PMC
November 2021

2-Dimensional ultra-high performance liquid chromatography and DMT-MM derivatization paired with tandem mass spectrometry for comprehensive serum N-glycome characterization.

Anal Chim Acta 2021 Sep 9;1179:338840. Epub 2021 Jul 9.

Characterisation and Comparability Laboratory, The National Institute for Bioprocessing Research and Training, Foster Avenue, Mount Merrion, Co. Dublin, A94 X099, Ireland; School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, D04 V1W8, Ireland. Electronic address:

Glycosylation is a prominent co- and post-translational modification which contributes to a variety of important biological functions. Protein glycosylation characteristics, particularly N-glycosylation, are influenced by changes in one's pathological state, such as through the presence of disease, and as such, there is great interest in N-glycans as potential disease biomarkers. Human serum is an attractive source for N-glycan based biomarker studies as circulatory proteins are representative of one's physiology, with many serum proteins containing N-glycosylation. The difficulty in comprehensively characterizing the serum N-glycome arises from the absence of a biosynthetic template resulting in great structural heterogeneity and complexity. To help overcome these challenges we developed a 2-dimensional liquid chromatography platform which utilizes offline weak anion exchange (WAX) chromatography in the first dimension and hydrophilic interaction liquid chromatography (HILIC) in the second dimension to separate N-glycans by charge, corresponding to degree of sialylation, and size, respectively. Performing these separations offline enables subsequent derivatization with 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) for sialic acid linkage determination and the identification of sialic acid linkage isomers. Subsequent tandem mass spectrometry analysis revealed the identification of 212 complete and partial N-glycan structures including low abundant N-glycans containing acetyl and sulphate modifications. The identifications obtained through this platform were then applied to N-glycans released from a set of stage 3 gastric cancer serum samples obtained from patients before (pre-op) and after (post-op) tumour resection to investigate how the serum N-glycome can facilitate differentiation between the two pathological states.
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http://dx.doi.org/10.1016/j.aca.2021.338840DOI Listing
September 2021

Signet ring cell percentage in poorly cohesive gastric cancer patients: A potential novel predictor of survival.

Eur J Surg Oncol 2021 Sep 7. Epub 2021 Sep 7.

Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.

Background And Objectives: Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA.

Methods: We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: "pure" SRC (containing ≥90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC-NOS) (containing ≤10% of SRCs), and PC-NOS/SRC (containing <90% but >10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared.

Results: Among 143 enrolled patients, 51% were male and 49% were female. The mean (±SD) age at diagnosis was 61 ± 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as "pure" SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than four-fold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5-7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival.

Conclusions: The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival.
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http://dx.doi.org/10.1016/j.ejso.2021.09.003DOI Listing
September 2021

Development and validation of deep learning classifiers to detect Epstein-Barr virus and microsatellite instability status in gastric cancer: a retrospective multicentre cohort study.

Lancet Digit Health 2021 10 17;3(10):e654-e664. Epub 2021 Aug 17.

Department of Medicine II, Mannheim Institute for Innate Immunoscience and Clinical Cooperation Unit Healthy Metabolism, Center of Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Background: Response to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides.

Methods: In this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA). We trained a deep learning-based classifier to detect microsatellite instability and EBV positivity from digitised, haematoxylin and eosin stained resection slides without annotating tumour containing regions. The performance of the classifier was assessed by within-cohort cross-validation in all ten cohorts and by external validation, for which we split the cohorts into a five-cohort training dataset and a five-cohort test dataset. We measured the area under the receiver operating curve (AUROC) for detection of microsatellite instability and EBV status. Microsatellite instability and EBV status were determined to be detectable if the lower bound of the 95% CI for the AUROC was above 0·5.

Findings: Across the ten cohorts, our analysis included 2823 patients with known microsatellite instability status and 2685 patients with known EBV status. In the within-cohort cross-validation, the deep learning-based classifier could detect microsatellite instability status in nine of ten cohorts, with AUROCs ranging from 0·597 (95% CI 0·522-0·737) to 0·836 (0·795-0·880) and EBV status in five of eight cohorts, with AUROCs ranging from 0·819 (0·752-0·841) to 0·897 (0·513-0·966). Training a classifier on the pooled training dataset and testing it on the five remaining cohorts resulted in high classification performance with AUROCs ranging from 0·723 (95% CI 0·676-0·794) to 0·863 (0·747-0·969) for detection of microsatellite instability and from 0·672 (0·403-0·989) to 0·859 (0·823-0·919) for detection of EBV status.

Interpretation: Classifiers became increasingly robust when trained on pooled cohorts. After prospective validation, this deep learning-based tissue classification system could be used as an inexpensive predictive biomarker for immunotherapy in gastric cancer.

Funding: German Cancer Aid and German Federal Ministry of Health.
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http://dx.doi.org/10.1016/S2589-7500(21)00133-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460994PMC
October 2021

Structured and shared CT radiological report of gastric cancer: a consensus proposal by the Italian Research Group for Gastric Cancer (GIRCG) and the Italian Society of Medical and Interventional Radiology (SIRM).

Eur Radiol 2021 Aug 12. Epub 2021 Aug 12.

Division of Radiology, University of Campania Luigi Vanvitelli, Naples, Italy.

Objectives: Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients.

Methods: Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up).

Results: In the final round, 23 out of 24 items obtained agreement ( ≥ 8) and consensus ( ≤ 2) and 19 out 24 items obtained a good stability (p > 0.05).

Conclusions: The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making.

Key Points: • Imaging represents the cornerstone for tailored treatment in GC patients. • CT-structured radiology report in GC patients is useful for multidisciplinary decision making.
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http://dx.doi.org/10.1007/s00330-021-08205-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359760PMC
August 2021

Predictors of morbidity and mortality in patients submitted to cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for ovarian carcinomatosis: a multicenter study.

Pleura Peritoneum 2021 Mar 4;6(1):21-30. Epub 2020 Dec 4.

Emergency Surgery Unit, University Hospital, Messina, Italy.

Objectives: The aim of this retrospective study is to assess the incidence of morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and to evaluate their predictors, in patients with peritoneal metastasis of ovarian origin.

Methods: A retrospective multicenter study was carried out investigating results from eight Italian institutions. A total of 276 patients met inclusion criteria. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis.

Results: Overall morbidity was 71.4%, and severe complications occurred in 23.9% of the sample; 60-day mortality was 4.3%. According to univariate logistic regression models, grade 3-4 morbidity was related to Peritoneal Cancer Index (PCI) (OR 1.06; 95% CI 1.02-1.09; p<0.001), number of intraoperative blood transfusions (OR 1.21; 95% CI 1.10-1.34; p<0.001), Completeness of Cytoreduction (CC) score (OR 1.68; 95% CI 1.16-2.44; p=0.006) and number of anastomoses (OR 1.32; 95% CI 1.00-1.73; p=0.046). However, at the multivariate logistic regression analysis, only the number of intraoperative blood transfusions (OR 1.17; 95% CI 1.5-1.30; p=0.004) and PCI (OR 1.04; 95% CI 1.01-1.08; p=0.010) resulted as key predictors of severe morbidity. Furthermore, using multivariate logistic regression model, ECOG score (OR 2.45; 95% CI 1.21-4.93; p=0.012) and the number of severe complications (OR 2.16; 95% CI 1.03-4.52; p=0.042) were recorded as predictors of exitus within 60 days.

Conclusions: The combination of CRS and HIPEC for treating peritoneal metastasis of ovarian origin has acceptable morbidity and mortality and, therefore, it can be considered as an option in selected patients.
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http://dx.doi.org/10.1515/pp-2020-0139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223801PMC
March 2021

Delta-radiomics and response to neoadjuvant treatment in locally advanced gastric cancer-a multicenter study of GIRCG (Italian Research Group for Gastric Cancer).

Quant Imaging Med Surg 2021 Jun;11(6):2376-2387

Department of Medical, Surgical and Neuro Sciences, Unit of Surgical Oncology, University of Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Background: To predict response to neoadjuvant chemotherapy (NAC) of gastric cancer (GC), prior to surgery, would be pivotal to customize patient treatment. The aim of this study is to investigate the reliability of computed tomography (CT) texture analysis (TA) in predicting the histo-pathological response to NAC in patients with resectable locally advanced gastric cancer (AGC).

Methods: Seventy (40 male, mean age 63.3 years) patients with resectable locally AGC, treated with NAC and radical surgery, were included in this retrospective study from 5 centers of the Italian Research Group for Gastric Cancer (GIRCG). Population was divided into two groups: 29 patients from one center (internal cohort for model development and internal validation) and 41 from other four centers (external cohort for independent external validation). Gross tumor volume (GTV) was segmented on each pre- and post-NAC multidetector CT (MDCT) image by using a dedicated software (RayStation), and 14 TA parameters were then extrapolated. Correlation between TA parameters and complete pathological response (tumor regression grade, TRG1), was initially investigated for the internal cohort. The univariate significant variables were tested on the external cohort and multivariate logistic analysis was performed.

Results: In multivariate logistic regression the only significant TA variable was delta gray-level co-occurrence matrix (GLCM) contrast (P=0.001, Nagelkerke R: 0.546 for the internal cohort and P=0.014, Nagelkerke R: 0.435 for the external cohort). Receiver operating characteristic (ROC) curves, generated from the logistic regression of all the patients, showed an area under the curve (AUC) of 0.763.

Conclusions: Post-NAC GLCM contrast and dissimilarity and delta GLCM contrast TA parameters seem to be reliable for identifying patients with locally AGC responder to NAC.
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http://dx.doi.org/10.21037/qims-20-683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107341PMC
June 2021

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of 'Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O.'

Ann Surg Oncol 2021 Dec 31;28(13):9060-9070. Epub 2021 May 31.

Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.

Background: The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer.

Methods: The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers.

Results: A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022).

Conclusions: In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.
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http://dx.doi.org/10.1245/s10434-021-10157-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590997PMC
December 2021

Robotic versus laparoscopic gastrectomy for gastric cancer: an umbrella review of systematic reviews and meta-analyses.

Updates Surg 2021 Oct 25;73(5):1673-1689. Epub 2021 May 25.

Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy.

An umbrella review was performed to summarize literature data and to investigate benefits and harm of robotic gastrectomy (RG) compared to laparoscopic (LG) approach. To overcome the intrinsic limitations of laparoscopy, the robotic approach is claimed to facilitate lymph-node dissection and complex reconstruction after gastrectomy, to assure oncologic safety also in advanced gastric cancer. A literature search was conducted in PubMed, Cochrane and Embase databases for all meta-analyses published up to December 2019. The search strategy was previously published in a protocol. We selected fourteen meta-analyses comparing outcomes between LG and RG with curative intent in patients with diagnosis of resectable gastric cancer. We highlight that RG has a longer operation time, inferior blood loss, reduction in hospital stay and a more rapid recovery of bowel function. In meta-analyses with statistical significance the number of nodes removed in RG is higher than LG and the distal margin of resection is higher. There is no difference in terms of total complication rate, mortality, morbidity, anastomotic leakage, anastomotic stenosis, intestinal obstruction and in conversion rate to open technique. The safety and efficacy of robotic gastrectomy are not clearly supported by strong evidence, suggesting that the outcomes reported for each surgical technique need to be interpreted with caution, in particular for the meta-analyses in which the heterogeneity is large. Certainly, robotic gastrectomy is associated with shorter time to oral intake, lesser intraoperative bleeding and longer operation time with an acceptable level of evidence. On the other hand, the data regarding other outcomes are insufficient as well as non-significant, from an evidence point of view, to draw any robust conclusion.
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http://dx.doi.org/10.1007/s13304-021-01059-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500879PMC
October 2021

ASO Author Reflections: Gastric Cancer with Synchronous Peritoneal Disease-A Clinically Meaningful Survival After CRS and HIPEC in Selected Patients from Italian Peritoneal Surface Malignancies Oncoteam Network.

Ann Surg Oncol 2021 Dec 20;28(13):9071-9072. Epub 2021 May 20.

Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.

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http://dx.doi.org/10.1245/s10434-021-10206-8DOI Listing
December 2021

Maintenance in gastric cancer: New life for an old issue?

Crit Rev Oncol Hematol 2021 Apr 19;160:103307. Epub 2021 Mar 19.

Department of Medical, Surgical and Neuro Sciences, Section of Surgery, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy; Department of Surgical Oncology, Gdansk Medical University, Gdansk, Poland.

The interest in maintenance therapy for patients with advanced cancers has been rapidly growing. Maintenance therapy is a useful strategy that may strengthen results of induction therapy thus extending survival and preserving the quality of life (QoL) with less toxicity. Maintenance also represents a suitable setting to investigate novel agents. The value of maintenance therapy after first-line chemotherapy has been well established in several solid tumours, such as colorectal, lung, breast, and ovarian cancer in which it is largely adopted. To date, there is no established role for maintenance therapy following first-line chemotherapy for advanced gastric cancer (GC). This review summarizes the current knowledge regarding maintenance strategies in advanced GC exploring cytotoxic agents, biologic agents and immunotherapy. We also critically review new issues to optimize randomized clinical trials for maintenance therapies and suggest clinical consideration to guide a personalized approach in daily clinical practice for this setting.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103307DOI Listing
April 2021

Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?

Gastric Cancer 2021 07 19;24(4):765-779. Epub 2021 Mar 19.

School of Human Health Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

Gastric cancer is one of the most common malignancy worldwide. In unresectable or metastatic disease, the prognosis is poor and in generally less than a year. HER2 expression remains an important biomarker to lead the addition of trastuzumab to first-line systemic chemotherapy in unresectable or metastatic gastroesophageal adenocarcinoma. To date, a major issue is represented by resistance to trastuzumab developed during treatment, considering the not improved outcomes in this molecular subtype of gastroesophageal adenocarcinoma to other HER2 target strategies. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance to HER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Furthermore, we describe the prognostic value of new non-invasive screening methods, under development novel agents (e.g., HER2 antibody-drug conjugates and bispecific antibodies) and strategies with antitumor activity in early studies.
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http://dx.doi.org/10.1007/s10120-021-01182-9DOI Listing
July 2021

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer.

Surg Oncol 2021 Jun 31;37:101523. Epub 2021 Jan 31.

Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy.

Background: Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).

Materials And Methods: Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.

Results: A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26-45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29-76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19-27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.

Conclusions: A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.
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http://dx.doi.org/10.1016/j.suronc.2021.101523DOI Listing
June 2021

Upper GI training of young surgeons: a reality full of hurdles. An international survey.

Updates Surg 2021 Apr 8;73(2):627-637. Epub 2021 Jan 8.

University of Turin, Department of Oncology, San Luigi University Hospital, Surgical Oncology and Digestive Surgery Unit, Regione Gonzole 10, Orbassano, 10043, Turin, Italy.

Objective: Anecdotal evidence suggests that the training of young surgeons in Upper GI is not homogeneous across the world. This survey aimed to investigate the different training programs and the level of satisfaction of young surgeons with their surgical and scientific education pathway.

Design: A multiple-choice and single best answer format questionnaire was sent to 36 Upper GI chairs from international referral centres and then forwarded to young surgeons (attending physician less than 40 years old). The same questionnaire containing 5 main topics (demographics, residency, fellowship, academic research and activities, manual skill improvement) was posted online on a Surveymonkey website.

Setting: San Luigi University Hospital, Orbassano (Turin), Italy; Tertiary University Hospital.

Results: Fourteen replies were received from colleagues in 36 referral centres (39% response rate) and 65 voluntary answers from the survey monkey platform. During residency training, only 43% of residents had a specific training in upper GI tract surgery, which was characterized by a small number of interventions performed both with trainer scrubbed and unscrubbed. Fellowship programmes were undertaken by 49% of participants and 64% spent this training period abroad. Operative experience was reported by nearly all respondents with only 27% performing > 10 gastrectomies and only 11% performing > 10 oesophagectomies with the trainer scrubbed. The majority attended less than 10 meetings (58%), and 70% of them published less than 5 papers.

Conclusions: The present survey reveals that the young surgeons of the twenty-first century face many hurdles during their surgical training. Overall, the surgical education settings are limited for both practical and scientific training for upper GI trainees. As a result, it is not possible to train in upper GI surgery to a level of competent independent practice.
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http://dx.doi.org/10.1007/s13304-020-00955-8DOI Listing
April 2021

The effect of learning curve on perioperative outcomes of robotic gastrectomy in two western high-volume centers.

Int J Med Robot 2021 Apr 8;17(2):e2212. Epub 2021 Jan 8.

General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy.

Introduction: To compare outcomes of robotic gastrectomy (RG) performed during the learning curve (P1) with those after its completion (P2).

Methods: In this retrospective study, all consecutive RG patients (n = 92) performed between 2008 and 2018 were included. Primary outcome was conversion rate.

Results: D2 lymphadenectomies were more common in P2 (41, 97.6%) than P1 (41, 82.0%) (p = 0.019). Conversions were 11 (22%) in P1 versus 2 (4.8%) in P2 (p = 0.006). Postoperative morbidity was comparable between the groups. Median hospital stay was significantly shorter in P2. The only factor significantly associated with conversion was P2 (odds ratio = 0.18; 95% confidence interval, 0.04-0.85; p = 0.039). The 5-year overall survival in P1 was 79.6% versus 79.7% in P2 (p = 0.373).

Conclusions: The learning curve affected operative and postoperative outcomes: during the learning curve, conversion to open surgery was significantly more frequent, the number of D2 was higher and patients were discharged earlier.
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http://dx.doi.org/10.1002/rcs.2212DOI Listing
April 2021

Surgical management of oncologic patient during and after the COVID-19 outbreak: practical recommendations from the Italian society of Surgical Oncology.

Updates Surg 2021 Feb 12;73(1):321-329. Epub 2020 Nov 12.

Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

The recent outbreak of COVID-19 in Italy caused a limitation of the resources of the health system, which necessarily led to their rationalization in the critical phase (phase 1) and a reorganization of the system in the following phase (phase 2). The Italian Society of Oncological Surgery-SICO has drafted these practical recommendations, calibrated on the most recent scientific literature and taking into account current health regulations and common sense. Surgical activity during phase 1 and 2 should follow a dynamic model, considering architectural structures, hospital mission, organizational models. Surgical delay should not affect oncological prognosis. However, COVID-19-positive cancer patients should be postponed until the infection is cured. The patients to consider more carefully before delaying surgery are those who have completed neoadjuvant therapy, patients with high biological aggressiveness tumors or without therapeutic alternatives. The multidisciplinary discussions are fundamental for sharing clinical decisions; videoconference meetings are preferable and use of telemedicine for follow-up is recommended. Especially in phase 1, maximum effort must be made to reduce the spread of the pandemic. Prefer intra-corporeal rather than open anastomosis during laparoscopy and mechanical rather than hand-sewn anastomosis in open surgery. Consider PPE for caregivers during stoma management. Minimal invasive surgery is not discouraged, because there is little evidence for augmented risk. Specific procedures have to be followed and use of energy devices has to be limited. Training programs with COVID-19 + patients are not recommended. All staff in OR should be trained with specific courses on specific PPE use. Differentiate recommendations are presented for every district cancer. Surgical oncology during phase 2 should be guaranteed by individual and distinct protocols and pathways between cancer patients and COVID-19 + patients with resources specifically addressed to the two distinct kind of patients to limit diagnostic/therapeutic interferences or slowdowns. These recommendations are based on currently available evidence about management of oncologic patients during COVID-19 pandemic, were endorsed by the SICO Executive Board, and are considered suitable for nationwide diffusion. They will be subject to updates and revisions in case of new and relevant scientific acquisitions.
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http://dx.doi.org/10.1007/s13304-020-00921-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660129PMC
February 2021

Methylene Blue-Current Knowledge, Fluorescent Properties, and Its Future Use.

J Clin Med 2020 Nov 2;9(11). Epub 2020 Nov 2.

Department of Surgical Oncology, Medical University of Gdansk, 80-214 Gdansk, Poland.

Methylene blue is a fluorescent dye discovered in 1876 and has since been used in different scientific fields. Only recently has methylene blue been used for intraoperative fluorescent imaging. Here, the authors review the emerging role of methylene blue, not only as a dye used in clinical practice, but also as a fluorophore in a surgical setting. We discuss the promising potential of methylene blue together with the challenges and limitations among specific surgical techniques. A literature review of PubMed and Medline was conducted based on the historical, current and future usage of methylene blue within the field of medicine. We reviewed not only the current usage of methylene blue, but we also tried to grasp its' function as a fluorophore in five main domains. These domains include the near-infrared imaging visualization of ureters, parathyroid gland identification, pancreatic tumors imaging, detection of breast cancer tumor margins, as well as breast cancer sentinel node biopsy. Methylene blue is used in countless clinical procedures with a relatively low risk for patients. Usage of its fluorescent properties is still at an early stage and more pre-clinical, as well as clinical research, must be performed to fully understand its potentials and limitations.
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http://dx.doi.org/10.3390/jcm9113538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693951PMC
November 2020

Robotic-assisted gastrectomy for gastric cancer: single Western center results.

Updates Surg 2021 Jun 14;73(3):865-872. Epub 2020 Oct 14.

Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strada Delle Scotte, 4, 53100, Siena, Italy.

A robotic approach to abdominal surgery procedures may improve postoperative outcomes compared to either open or laparoscopic approaches. The role of robotics for gastric surgery, however, is still being evaluated. A retrospective review of the prospectively maintained database for robotic gastric surgery at University of Siena between 2011 and 2020 was conducted. Data regarding surgical procedures, early postoperative outcomes, and long-term follow-up were analyzed. 38 patients underwent robotic partial or total gastrectomy. Conversion to open occurred in two patients (5.2%) due to locally advanced disease as well as difficult identification of primary lesion. Postoperative morbidity was 13.1% while no postoperative mortality was registered. The mean length of operation was 358.6 (220-650) minutes and the mean number of retrieved lymph nodes was 35.8 (range: 5-73). The median OS of all population was 70.9 months. The median 5-year OS for the patients with positive nodes was worse than that of patients without metastatic lymph nodes [51.4 months (95% CI 35.5-67.4) vs. 79.5 months (95% CI 67.1-91.8); p = 0.079]. The interesting results including postoperative morbidity as well as mortality rate, the surgical outcomes, and the 5-year OS, were to be acceptable considering the data recorded by previous studies on robotic gastrectomy. This study demonstrated that robotic gastrectomy is feasible and can be safely performed. However, further follow-up and randomized clinical trials are required to confirm the role of a robotic approach in gastric cancer surgery.
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http://dx.doi.org/10.1007/s13304-020-00896-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184723PMC
June 2021

Preoperative or Perioperative Docetaxel, Oxaliplatin, and Capecitabine (GASTRODOC Regimen) in Patients with Locally-Advanced Resectable Gastric Cancer: A Randomized Phase-II Trial.

Cancers (Basel) 2020 Sep 29;12(10). Epub 2020 Sep 29.

General Surgery Unit, Ospedale del Casentino, 52010 Bibbiena, Italy.

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively ( 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18-1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2-65.8) in arm A and 40.3% (95% CI: 28.9-55.2) in arm B ( 0.300). Five-year survival was 58.5% (95% CI: 41.3-72.2) and 53.9% (95% CI: 35.5-69.3) ( 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.
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http://dx.doi.org/10.3390/cancers12102790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599648PMC
September 2020

New technologies in breast cancer sentinel lymph node biopsy; from the current gold standard to artificial intelligence.

Surg Oncol 2020 Sep 7;34:324-335. Epub 2020 Jul 7.

Department of Surgical Oncology, Medical University of Gdansk, Gdańsk, 80-211, Poland.

Sentinel lymph node biopsy is an important diagnostic procedure performed in early breast cancer patients with clinically negative axillary lymph nodes. Detection and examination of sentinel lymph nodes determine further therapy decisions, therefore a choice of optimal technique minimising the risk of false-negative results is of great importance. Currently, the gold standard is the dual technique comprising the blue dye and radiotracer, however, this method creates a logistical problem for many medical units. The intrinsic constraints of the existing methods led to the development of a very wide range of alternatives with varying clinical efficiency and feasibility. While each method presents with its own advantages and disadvantages, many techniques have improved enough to become a non-inferior alternative in the sentinel lymph node biopsy. Along with the improvement of the existing technologies, there are evolving trends such as multimodality of the techniques maximising the diagnostic outcome or an emerging use of artificial intelligence (AI) improving the workflow of the procedure. This literature review aims to give an overview of the current status of the standard techniques and emerging cutting-edge technologies in the sentinel lymph node biopsy.
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http://dx.doi.org/10.1016/j.suronc.2020.06.005DOI Listing
September 2020

Smartphone application supplements laparoscopic training through simulation by reducing the need for feedback from expert tutors.

Surg Open Sci 2019 Oct 5;1(2):100-104. Epub 2019 Jul 5.

Digestive Surgery Department, Division of Surgery, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background: Simulation training is a validated, highly effective tool for learning laparoscopy. Feedback plays a crucial role in motor skills training. We present an app to guide students during advanced laparoscopy simulation training and evaluate its effect on training.

Methods: A smartphone(iOS)-app was developed. A group of trainees were randomized to use the app (YAPP) or not use the app (NAPP). We used blinded analysis with validated rating scales to assess their performance before and after the training. The number of requests for tutor feedback per session was recorded. Finally, the participants in the YAPP group completed a survey about their experience with the app.

Results: Fifteen YAPP and 10 NAPP completed the training program. There were no statistically significant differences between their skills performance scores (P = .338). The number of tutor feedback requests in the YAPP and NAPP was of 4 (3-6) and 13 (10-14) (P < .001), respectively. All participants in the YAPP group found the app was useful.

Conclusion: The use of a smartphone app reduces the need for expert tutor feedback without decreasing the degree of skills acquisition.
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http://dx.doi.org/10.1016/j.sopen.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391878PMC
October 2019

Preoperative oral immunonutrition in gastrointestinal surgical patients: How the tumour microenvironment can be modified.

Clin Nutr ESPEN 2020 08 30;38:153-159. Epub 2020 Jun 30.

Universita degli Studi di Siena, Siena, Italy.

Background & Aims: This study is focused on the impact of enteral immunonutrition on the cell-mediated immune response in the microenvironment of gastric and colorectal cancers.

Methods: This is a prospective pilot study approved by the local Ethics Committee. The immunophenotypic structure of the immune cells before (on the biopsy) and after (on the surgical sample) the administration of the immunonutrition in 16 patients is compared with 8 patients receiving regular diet. The samples of non-tumour tissue from sleeve-gastrectomy are used as non-neoplastic control. Antibodies were tested: CD4, CD8, PD-1, FOX-P3, CD68, CD163, CD80, CD21, CD56, PD-L1. We applied already well-known scoring systems for the evaluation of the immunohistochemistry and compared our data in the different groups by statistical analysis.

Results: In treated patients, we detected a modulation of the immune response with higher number of cytotoxic and helper T-lymphocytes in the tumour microenvironment of the surgical specimens compared to the pre-operative biopsy, and a lower number of lymphocytes presenting an exhausted (i.e. double positive CD8 and PD-1 lymphocytes) and regulatory (i.e. double positive CD4 and FOX-P3 lymphocytes) phenotype. Moreover we observed the M1 polarization with a lower number of CD163 positive macrophages and the inhibition of the PD-1/PD-L1 pathway in treated patients.

Conclusions: The immunonutrition impacts on the tumoral microenvironment of gastric and colorectal cancer activating the inflammatory pathway, in terms of humoral and cellular response.
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http://dx.doi.org/10.1016/j.clnesp.2020.05.012DOI Listing
August 2020

Clinical evaluation of the Mannheim Prognostic Index in post-operative peritonitis: a prospective cohort study.

Updates Surg 2020 Dec 23;72(4):1159-1166. Epub 2020 Jun 23.

Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strada delle Scotte 4, Siena, 53100, Italy.

Postoperative peritonitis (PoP), despite their relatively low incidence, are associated with high mortality. Such poor outcomes are also related to the high proportion of aged patients, whose intra-abdominal infections are difficult to manage. The study included 84 consecutive patients with PoP. The aim was the validation of the Mannheim Prognostic Index (MPI) in the context of PoP and the assessment of the prognostic impact of age and other clinical factors in a large series from a tertiary center. PoP had an incidence of 3.9% in all the abdominal surgeries in the study period. Surgical control of POP focus was achieved in 90.5% of cases and a complete abdominal clearance in 58.3%. Complication rate was 75% with a mortality of 26.2%. For MPI score, the ROC curve indicated a cut-off value of 29 with a sensitivity of 72.7% and specificity of 67.7% in predicting death. At univariate analysis, factors significantly related to poorer prognosis included advanced age (p 0.001), site of primary surgery (p 0.05), lack of abdominal clearance (p 0.003), generalized peritonitis (p 0.04) and high MPI score (p < 0.001). Age, MPI score and absence of abdominal clearance resulted in independent prognostic factors at multivariate analysis. MPI showed good efficacy in identifying POP patients at high risk of death. The increased risk of mortality related to advanced age should be considered with MPI score in planning the treatment. An aggressive and early diagnostic-therapeutic approach is required to reduce the MPI score and improve the prognosis.
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http://dx.doi.org/10.1007/s13304-020-00831-5DOI Listing
December 2020

Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review.

Cancers (Basel) 2020 Jun 17;12(6). Epub 2020 Jun 17.

Division of Cancer Prevention and Genetics, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy.

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as-(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC).
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http://dx.doi.org/10.3390/cancers12061598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352390PMC
June 2020

TAS-102 in gastric cancer: Development and perspectives of a new biochemically modulated fluroropyrimidine drug combination.

Crit Rev Oncol Hematol 2020 Aug 21;152:102987. Epub 2020 May 21.

School of Human Health Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

TAS-102 is a preconstituted drug combination comprising an oral fluoropyrimidine (trifluridine, TFT) and a potent inhibitor of thymidine phosphorylase (tipiracil hydrochloride, TPI). TFT/TPI has recently received Food and Drug Administration (FDA) approval also for the treatment of gastric cancer after at least two lines of chemotherapy. The approval was based on a large phase 3 trial (TAGS), in which TAS-102 showed a 31 % decrease in the risk of death compared with placebo. Here, we review the pharmacological properties, clinical development and potential future directions of TAS-102 in gastric cancer.
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http://dx.doi.org/10.1016/j.critrevonc.2020.102987DOI Listing
August 2020

Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer.

Transl Oncol 2020 Sep 26;13(9):100795. Epub 2020 May 26.

Azienda Ospedaliera Careggi University Hospital of Florence and University of Florence, 50134 Florence, Italy.

BRAFV600-mutated colorectal cancer (CRC) accounts for 8% to 12% of all CRC diagnoses. These tumors are often associated with specific patient features, including right-sided primary tumor location, peritoneal and non-regional lymph node involvement, and poor prognosis. In approximately 30% of cases, a simultaneous mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) phenotype is identified. The prognostic impact of the BRAF mutation appears to be less marked in patients with MSI-H CRC than in patients with microsatellite stable (MSS) tumor. The treatment of BRAFV600-mutated CRC is still a challenge for the clinicians, mainly due to the poor survival outcomes obtained with traditional chemotherapy regimens. In recent years, two novel treatment strategies have offered remarkable changes in the treatment of this specific patient subgroup. The first approach has included targeted therapies directed against BRAF and MEK, with support from the epidermal growth factor receptor (EGFR) blockade. The second approach has included immunotherapeutic agents that have been shown to be particularly promising for patients with simultaneous dMMR/MSI-H phenotype. Here we review the clinical trials that specifically enrolled patients with BRAF-mutated CRC, from the phase I/II studies to the phase III trial BEACON CRC. We also examine the future directions towards a molecularly guided therapy for patients with BRAF-mutated CRC and the crucial role of a molecularly and clinically based algorithm in order to offer the best choice of treatment for these patients.
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http://dx.doi.org/10.1016/j.tranon.2020.100795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260582PMC
September 2020

Germline mutations of the E-cadherin gene (CDH1) in early onset gastric cancer.

Semin Oncol 2020 Apr - Jun;47(2-3):125-126. Epub 2020 May 6.

Department of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.

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http://dx.doi.org/10.1053/j.seminoncol.2020.04.002DOI Listing
January 2021

MSI and EBV Positive Gastric Cancer's Subgroups and Their Link With Novel Immunotherapy.

J Clin Med 2020 May 11;9(5). Epub 2020 May 11.

Department of Surgical Oncology, Gdansk Medical University, 80-210 Gdansk, Poland.

Gastric cancers have been historically classified based on histomorphologic features. The Cancer Genome Atlas network reported the comprehensive identification of genetic alterations associated with gastric cancer, identifying four distinct subtypes- Epstein-Barr virus (EBV)-positive, microsatellite-unstable/instability (MSI), genomically stable and chromosomal instability. In particular, EBV-positive and MSI gastric cancers seem responsive to novel immunotherapies drugs. The aim of this review is to describe MSI and EBV positive gastric cancer's subgroups and their relationship with novel immunotherapy.
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http://dx.doi.org/10.3390/jcm9051427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291039PMC
May 2020

Cancer care under the outbreak of COVID-19: A perspective from Italian tertiary referral center for surgical oncology.

Eur J Surg Oncol 2020 Jun 15;46(6):1184-1185. Epub 2020 Apr 15.

Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.

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http://dx.doi.org/10.1016/j.ejso.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158818PMC
June 2020
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