Confocal Laser Endomicroscopy in early detection of esophagus dysplasia.

This compared the diagnostic potential of Confocal Laser Endomicroscopy in detecting the dysplasia associated with Barrett’s esophagus vs. the current standard Seattle biopsy protocol.

Locally advanced resectable gastric cancer.

Currently investigating the role of perioperative chemotherapy and post-operative radiation therapy in gastric cancer (ITACA-S2 Italian multicenter, 4-arm, randomized trial).

Lymphadenectomy in gastric cancer.

We analysed data derived from out Tumor Registry for 114 patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between in the 2000-2005 period. This study clarified that more extended lymph node resection offered survival benefit, and lymphadenectomy involving more than 15 lymph nodes should therefore be performed. Results were published in Eur J Surg Oncol 2011 Apr;37(4):305-11; additional research efforts in this issue are ongoing.

Metastatic gastric cancer.

HER2 positive tumors: currently investigating whether pertuzumab can ameliorate the results of trastuzumab (international randomized, JACOB trial).

HER2 negative tumors: investigating the role of S1 (an oral fluoropyrimidine) in the diffuse histotipe (international, multicenter, phase III, randomized trial), and comparing two different regimens of three drug polichemotherapy (GISCAD trial: low TOX vs EOX).

Hereditary Diffuse Gastric Carcinoma. In collaboration with the Division of Genetics and Oncology Prevention, a study for detection of CDH-1 germ-line mutation in patients under 45 affected by diffuse gastric carcinoma is currently run.

Pancreatic and biliary tract carcinoma. We participated in a successful phase III study with NAB-paclitaxel combined with Gemcitabine for metastatic patients, and are now futher investigating this same regimen in the locally advanced study (GISCAD trial). We are participating in a multicenter randomized phase II-III study entitled “Peri- or post-operative chemotherapy in resectable pancreas carcinoma” (PACT-15).  For biliary tract carcinoma, we are conducting a retrospective biological study to detect the expression of Hedgehog pathway.

Liver metastases. An observational, prospective, multicenter study entitled “Analysis of phosphoproteomics for targeted therapy of colorectal liver metastases (TASK 2)” is now ongoing.

Quality assurance in colonoscopy practice.

An observational multicenter study is now ongoing, aimed at evaluating patients’ compliance for different bowel cleansing preparations for colonoscopy. In collaboration with the Italian Society of Digestive Endoscopy (SIED), a Quality Assurance program was started, with the aim to prospectively assess quality indicators of good endoscopy practice (e.g. rate of full colonic examinations - intended as cecum visualization - or detection rate of polyps and adenomas). Moreover, a prospective multicenter study dealing with complications’ rate after endoscopic polypectomy is now ongoing.

Chromoendoscopy.

A multicenter, prospective, randomized, controlled, single-blind trial is now ongoing with the objective to evaluate whether chromoendoscopy – in conjunction with confocal laser endomicroscopy – is able to more accurately identify neoplasms arising in ulcerative colitis patients as compared to standard video-endoscopy.

Quality assurance in rectal cancer surgery.

Two observational studies are active:

a. Clinical pathway (PDTA) in radically-resected rectal tumors, reconstructed through BDA (Regional Patient Database) methodology.

b. Comparison of appropriateness, quality and costs of surgical procedures for colo-rectal tumors with open vs laparoscopic vs robotic techniques.

Factors affecting prognosis in colon cancer.

We retrospectively analyzed data from consecutive patients, extracted again by our institutional Tumor Registry, admitted for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Data of 137 patients were obtained, with a median follow-up of 77 months (range 6-131). Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events. The risk of events was found inversely proportional to the number of dissected lymphnodes. These results were published in Int J Colorectal Dis. 2012 Aug 30. An extension of this study is under evaluation.

Metagenomics of colorectal cancer.

This project is carried out with IFOM-IEO Researchers, and aims to identify new biological markers in the blood of colon cancer patients for diagnosis and prognosis. We postulate a correlation between neutrophils, coagulation defects and HMGB1 in colorectal cancer. HMGB-1 has been recently linked to coagulation. We associated different redox forms of HMGB1 with two exclusive functions of the molecule (chemoattractant or inflammatory mediator), but the identity of the form involved in coagulation or neutrophil polarization is unknown. We want to characterize an unconventional subset of N2 neutrophils found only in the blood of cancer patients and elucidate the role of HMGB-1 in the development of this phenotype.

Robot-assisted minimally invasive surgery for rectal cancer.

An international, randomized clinical trial comparing laparoscopic vs robotic rectal resection for treatment of rectal cancer (ROLARR trial , RObotic vs LAparoscopic Rectal Resection) was started in 2012; 32 patients were so far  enrolled.

Laparoscopic radioguided detection of colon cancer with the use of a portable gamma camera.

This trial is aimed at evaluating the utility of radiotracers in detection of small colon cancer lesions during minimally-invasive surgery  and evento map the lymphatic pathway in order to study sentinel lymphnodes. This study is in cooperation with the Divisions of Nuclear Medicine, Endoscopy and Pathology.

Preservation of the genito-urinary function in patients undergoing surgery with robotic technique for rectal cancer. This study is aimed at assessing prospectively preservation of genitor-urinary function in patients undergoing nerve sparing robotic surgery for the treatment of rectal cancer.

Integration of Diffusion-Weighted magnetic resonance imaging in surgical planning for robotic nerve sparing total mesorectal excision. Magnetic Resonance (MRI) is used to stage patients with rectal tumors and new techniques like diffusion-weighted magnetic resonance imaging (DW-MRI) should improve the identification and depiction of the hypogastric plexus. The potential benefits on preservation of genito-urinary function in routine use of this technique integrated with robotic surgery are under investigation in this prospective trial.

Circulating Tumor Cells (CTC).

An observational, prospective, IEO single-center study entitled “Identification and possible prognostic significance of Circulanting Tumor Cells (CTC) in peripheral venous blood of patients affected by locally advanced rectal cancer, diagnosed through traditional clinical exams undergoing oncologically radical surgery (open or laparoscopic)” is ongoing.

Medical oncology-adjuvant setting.

A prospective study is ongoing, having reached full accrual, aimed at evaluation of the impact of 3 versus 6 months of FOLFOX/XELOX regimens in patients with colon cancer staged as II-high risk or III (TOSCA trial):

we have included 90 patients and we are among the top ten Italian centers for enrollment. Translational research is currently carried out on biological prognostic and predictive factors (circulating tumor cells and their characterizations, the role of isolated tumor cells in

regional limphnodes in radically resected patients, biomolecular texts as Microsatellite Instability or pharmacogenetic/pharmacogenomic profile, when indicated).

Medical oncology-metastatic setting.

The role of immunogenic response after EGFR-inhibitors (in collaboration with IFOM) and the mechanism of primary and acquired resistance to biological agents is investigated.

New anticancer drugs and combinations are tested;

international multicenter trials: MEHD7945A/FOLFIRI in K-RAS Wild Type, sintuzumab/FOLFIRI in K-RAS mutated cases).

Italian multicenter phase I-II trial (AMOR trial) as first line sistemic treatment with aflibercept/FOLFIRI in patient with untreated metastatic colorectal cancer.

Italian multicenter trial (CENTRAL study): FOLFIRI/bevacizumab as first line in patient with ubnormal LDH value.

Together with IEO interventional radiologists, we are investigating hepatic intra-arterial injection of drug-eluting bead (MIRACLE III trial).

Together with IEO radiotherapists we are investigating the administration of selective intra-hepatic radiotherapy treatment (in collaboration with SITILO, trial to be submitted to EC) in pretreated patients.

In liver-dominant colorectal cancer patients with unresectable or borderline resectable metastases, we are participating in a multicenter firstline clinical trial (ABOVE study, in collaboration with Niguarda Hospital in Milan) with the aim to evaluate the percentage of conversion to surgery obtained with bevacizumab/FOLFOX regimen.

Prospective evaluation of the role of sistemic treatment in patients with resectale and unresectale lung metastases.

Radiation therapy - rectal cancer.

We actively participate to the INTERACT trial (Phase III randomized study), regarding patients with limited local disease suitable for neoadjuvant chemo-radiotherapy.

A trial evaluating the role of conservative surgery after primary chemoradiotherapy is upcoming, aiming to reduce the morbidity of extended surgery and to contribute to a better patient’s quality of life.

Other upcoming trials are investigating the role of adjuvant therapy after radically resected metastases and the role of “induction”chemotherapy in locally advanced rectal cancer with the

aim to reduce radiotherapy use.

Miscellaneous : Totally implantable central venous access devices

A cost analysis of a randomized 3-arm trial on best approach to central veins for long-term chemotherapy deliverance is under evaluation.

A new revision of the International Guidelines on evidence-based overview of all topics related to ultrasound vascular access is programmed.