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Clinical-scientific Departments

Medical Oncology Department Hematology and Pediatric Onco-Hematology Department Anesthesia, Intensive Care, Pain Therapy, and Palliative Care Department Diagnostic Imaging and Radiotherapy Department Pathology and Laboratory Medicine Department Experimental Oncology and Molecular Medicine Department Preventive and Predictive Medicine Department

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scientific report 2012 SURGERY DEPARTMENT DIRECTOR OF DEPARTMENT Ugo Pastorino +39 02 2390 2906 ugo.pastorino@istitutotumori.mi.it The Department of Surgery is composed of 10 surgical divisions and 3 departmental units, organized for homogeneity of performance, with 240 inpatient beds and 14 outpatient beds. The Department treats oncological diseases that affect all areas of the body except for the brain, providing elective and emergency surgical activity, in ordinary inpatient and day hospital regimens, and specialistic oupatient activity for diagnosis and follow-up. Routine clinical activity ensures a high standard of care for all surgically-treated patients, providing conservative surgery (organ/function preserving or minimally invasive) for early stage disease and combined treatment modalities for advanced disease. UNITS Gastrointestinal, Hepato Pancreatobiliary Surgery, and Liver Transplantation Vincenzo Mazzaferro Colorectal Surgery Ermanno Leo Breast Surgery Roberto Agresti Melanoma and Sarcoma Mario Santinami Diagnostic Endoscopy and Endoscopic Surgery Emanuele Meroni Otolaryngology Surgery Gabriele Scaramellini Gynecologic Oncology Francesco Raspagliesi Thoracic Surgery Ugo Pastorino Plastic and Reconstructive Surgery Maurizio B. Nava Urologic Surgery Roberto Salvioni Pediatric Surgery Luigi Piva Laser Therapy Anna Colombetti Day Surgery Aldo Bono 33

scientific report 2012 GASTROINTESTINAL, HEPATOPANCREATOBILIARY SURGERY, and LIVER TRANSPLANTATION Our clinical research activity aims at improving the standard of care for primary and secondary tumors affecting the liver, biliary system, pancreas, and gastrointestinal tract. In the field of hepato-oncology, we offer the complete range of the most up-to-date therapeutic options for liver cancer, including liver transplantation, minimally-invasive and computer assisted surgery, transarterial chemoembolization and radioembolization, percutaneous and laparoscopic tumor ablation, and targeted molecular therapies. The multidisciplinary approach is routinely applied thanks to the presence of gastroenterologists in the Unit and the collaboration with other specialties (radiology, oncology, nuclear medicine and other surgical units). The Liver Transplant Program is mainly focused on establishing oncological guidelines and plays a leading role worldwide in defining consistent indications and prospective lines of research. More than 40% of patients are included in prospective clinical trials. Patient care and support are at the highest standard with about 900 admissions and 450 major surgical procedures/year, among which treatment of colorectal liver metastases and hepatocarcinoma represent the majority. The Gastrointestinal Unit has an extremely complex structure. It is part of the International Consortium on Liver Cancer, and participates in a transplantation research program with the Barcelona Clinic and Mt. Sinai University, New York. The Unit also leads various clinical research programs that are part of FP7 European Project and trials aimed at extending transplantation criteria. Decisionmaking analyses and criteria focus on patient benefit and are part of research programs on pancreatic and biliary tract cancers. Research projects on positive prognostic markers are also ongoing and require the implementation of a biobank for gastric and esophageal-gastric junction cancers as well as for Gep-NET. Teaching and training activities attract a large number of specialists to the Unit. A permanent laboratory staff at INT participates in a program of the Consortium on Translational Research on Liver Tumors already active in the two sister labs at Barcelona and New York. A special interest in the tumor microenvironment/cancer interaction has been pursued thanks to a tight collaboration with the Immunotherapy of Human Tumors Unit. In addition, clinical technologies are routinely used in the management of patients. A state of the art radiology and interventional radiology technology provides pre-operative work-up (CT, MRI, PET, and nuclear medicine dosimetry). Laparoscopic procedures are performed in a dedicated interactive operating room in which all devices are integrated. The equipment used is of the highest technological standards: ultrasonic and radio-frequency dissectors, bipolar vessel sealers, radiofrequency and microwave needles for tumor ablation, highdefinition video cameras and monitors. We perform ultrasound-guided surgery and ablation with the newest ultrasound machines with or without contrast enhancement, using intraoperative and laparoscopic probes. The Unit is a pioneer in computed-assisted liver surgery performed using an ultrasound navigation system that allows localization of tumors deep in the liver that are not visible with conventional ultrasound. Keywords: liver cancer, liver transplantation, pancreatic and biliary tract cancers Vincenzo Mazzaferro, MD CLINICAL RESEARCH STAFF Carlo Battiston, MD Sherrie Bhoori, MD hepatogastroenterologist Jorgelina C. Coppa, MD Christian Cotsoglou, MD Alessandro Germini, MD Andrea Pulvirenti, MD Enrico Regalia, MD Raffaele Romito, MD Carlo F. Sposito MD RESEARCH STAFF Marco A. Bongini, MD Maria F. Reyes, MD Daniela Sia, MD Elisa Sottotetti, MD RESIDENTS Davide Citterio, MD Glenda Grossi, MD Cecilia Muscarà, MD Marco Nencioni, MD Matteo Origi, MD Elisa Giavari and Francesco Roncacci, unit secretaries; Daniela Guarneri and Nela Zito, scientific secretaries; Simona G. Marchesi, data manager Paola Serafin (coordinator), Adriana Blanco, Salvatore Bonafede, Annateresa Bugada, Morena De Santis, Milda Di Giacomo, Angela Mihaela Farcas, Stefania Fici, Francesca Maiorano, Antonella Masiello, Monica Mitarotonda, Nadia Nicoletti, Patrizia Perotto Ghi, Patrizia Rota, Rossina Sitta, Stefania Sperandio, Cristina Stracquadaini, Patrizia Valentini HEALTHCARE ASSISTANTS Nicoletta Damiani, Rosa De Felice, Mariangela Lopriore, Annamaria Pancari, Angela Restaini, Enza Spina, Anna Vecchio 34

scientific report 2012 Colorectal Surgery Ermanno Leo, MD CLINICAL RESEARCH STAFF Dario Baratti, MD Luigi Battaglia, MD Filiberto Belli, MD Giuliano Bonfanti, MD Alessandro Cesa Bianchi, MD Marcello Deraco, MD Shigeki Kusamura, MD, PhD Marco Vitellaro, MD RESIDENTS Marcello Guaglio Mario Moschita Giovanni Piscitelli Vincenzo Pruiti Monica Zisa Roberta Aceto Fabiana Bettoni, Lucia Caracciolo, Rut Cittadin, Angela Colamonaco, Stefania Labori, Magdalena-Alonso Manuel, Marica Melis, Vanessa Neri, Palma, Mirtha Ybazeta Ramos, Riccardo Vacca HEALTHCARE ASSISTANTS Monica Anzaghi, Isabella Damasi, Nunzia Di Perna, Fabio Lizzano, Maria Petrosina The Colorectal Cancer Unit is a recognized European referral center. The annual case load was about 600 cases during the last years. Over the last three decades, the Unit has devoted special attention to tumors of the distal rectum and established very high standards of care for the management of this subset of patients. Conservative, functionpreserving surgical techniques to avoid extensive resection and definitive colostomy have been perfected. A further area of expertise is treatment of complex local recurrences of rectal cancer. Thanks to a muldisciplinary effort, we were able to offer technically demanding surgeries to patients affected by extensive recurrent disease. This collaborative effort involves the Melanoma and Sarcoma Unit and the Intensive Care Unit. Moreover, the Colorectal Surgery Unit has recently stregthened its collaboration with the Experimental Oncology and Molecular Medicine Department for the development and implementation of translational studies in colorectal cancer. In the second half of 2012, the Peritoneal Surface Malignancies (PSM) program, active at INT since 1995, was attached to the Colorectal Surgery Unit. This program is responsible for the treatment of pseudomyxoma peritonei, peritoneal mesothelioma, and peritoneal carcinomatosis from colorectal cancers. Thanks to a vast experience of more than 500 procedures of cytoreduction associated with hyperthermic intraperitoneal chemotherapy, the program has achieved the highest standard in the management of peritoneal surface oncology and has become an important international reference center for this procedure. The PSM program carried out several prospective multidisciplinary studies in collaboration with clinical and pre-clinical departments. Topics of interest are translational research in peritoneal mesothelioma, and translational research in pseudomyxoma peritonei [funded by National Organization for Rare Disorders (NORD) 2011]. Furthermore, prospective randomized multicenter trials on patients with peritoneal carcinomatosis from colorectal cancer were planned. Keywords: surgery, colorectal cancer, peritoneal carcinomatosis 35

scientific report 2012 Breast surgery The clinical activity of the Unit includes all aspects of breast cancer treatment: diagnosis, primary and adjuvant therapy, and follow-up. Treatment is performed by multidisciplinary teams involving other Units and Departments. The results from a randomized clinical trial comparing axillary dissection with observation in patients over 65 years of age with T1N0 breast cancer have been published in the Annals of Surgery. Moreover, in a consecutive series of elderly breast cancer patients without palpable axillary nodes we investigated whether biological markers may predict axillary relapse and breast cancer mortality. The paper was accepted for publication. In a joint study with the MRI Unit, we evaluated the ability of MRI to show the extent and location of tumor in a breast surgical specimen by ex vivo MRI. The paper was accepted for publication. A pilot study is in progress comparing FDG-PET with sentinel lymph node biopsy for staging of regional lymph nodes, following previous experience in the use of PET in preoperative evaluation of axillary lymph nodes. Enhanced understanding of the pathogenesis of breast cancer coupled with growing interest in improved esthetic results led to the investigation of skin- and nipple-sparing mastectomy as a potential improvement over conventional mastectomy. In cooperation with the Medical Genetics Unit, an approach tailored for women at high genetic risk has been developed. During genetic counseling, genetic risk is estimated to design a personalized program including available preventive options and treatments. Keywords: breast cancer, surgical treatment, axillary management Roberto Agresti, MD CLINICAL RESEARCH STAFF Silvia Bohm, MD Alberto Rudy Conti, MD Cristina Ferraris, MD Massimiliano Gennaro, MD Maria Ilaria Grosso, MD Gabriele Martelli, MD Cristina Pellitteri, MD Domenico Piromalli, MD POSTDOCTORAL FELLOWS Ilaria Maugeri, MD Research FELLOWS Mario Rampa, MD Alessandra Moscaroli, MD Angela Allegri Irene Alessandrini, Giovanni Cavaliere, Myria P. Conti, Stefano Licata, Bruna Nuscis, Maria C. Puddu, Michele Rossello, Gelsomina Sasso, Francesco A. Spagnolo, Liliane Venafra HEALTHCARE ASSISTANTS Maria C. Fadda, Luigi Magnifico, Caterina Pianu 36

scientific report 2012 Melanoma and Sarcoma Mario Santinami, MD CLINICAL RESEARCH STAFF Melanoma Andrea Maurichi, MD Daniele Moglia, MD Roberto Patuzzo, MD Roberta Ruggeri, MD Surgery of Sarcoma Alessandro Gronchi, MD (Head) Marco Fiore, MD RESEARCH STAFF Federica Crippa, MD Valentina Girgenti, MD Elena Tolomio, MD RESIDENTS Giulia Baffa, MD Ilaria Mattavelli, MD Stefano Redaelli, MD Carlotta Tinti, MD Antonella Vescera Data Managers Annabella Di Florio, Katia Pinamomti AND HEALTHCARE ASSISTANTS Giovanna Lomartire (coordinator), Nicola Abatangelo, Roberta Allenza, Annamaria Biondo, Sonia Cappellini, Annarita Carluccio, Alessio Cremonesi, Nello Curatolo, Floarea Dorca, Loridana Marino, Silvana Mirante, Erica Panigada, Giusy Pede, Lucia Preto, Esther Reinoso Crespo, Francesca Ruiu, Claudia Sonzogni, Antonella Tomasicchio, Monica Ullio, Addolorata Volpe Melanoma. During 2012, more than 550 melanoma patients were treated with major surgery. More than 17,000 patients were seen in the outpatient clinic and 1000 were treated with minor surgery; a unit database containing data from more than 5000 patients treated over the last 10 years has been managed. Sarcoma. Our Institution is a referral center for soft tissue sarcomas of the limbs and trunk, as well as retroperitoneal sarcomas, GIST, and axial bone sarcomas. In 2012, we performed 300 major operations on new patients. We visited 1200 new patients in consultation and provided routine followup visits for over 4000 cases. Keywords: melanoma, sarcoma, loco-regional therapy, limb salvage, immunotherapy 37

scientific report 2012 Diagnostic Endoscopy and Endoscopic Surgery The activities of the multidisciplinary endoscopy Unit include diagnostic and therapeutic procedures of the gastrointestinal, biliopancreatic, respiratory, and urinary tracts. The Unit is particularly committed to cancer prevention and diagnosis and treatment of early cancer. A special effort is dedicated to the Regional Colorectal Cancer Screening Program as well as to endoscopic surveillance of patients affected by familial adenomatous polyposis (FAP) or Lynch syndrome. Detection and staging of early cancer is potentiated by the use of advanced diagnostic technologies, such as wireless capsule endoscopy (WCE) for the study of the small intestine, and endoscopic ultrasonography (EUS) for the study of gastrointestinal tract and biliopancreatic malignancies. The Unit is a core partner of the institutional GastroEntero Pancratic NeuroEndocrine Tumors (GEP-NET) Center, following ENETS guidelines. The Endoscopy Unit is also a referral center within the Lombardy Region for endoscopic treatment of pre-cancerous esophageal conditions, such as Barrett s esophagus using endoscopic radiofrequency ablation (RFA). With regard to advanced cancers, endoscopic palliative therapy is routinely provided using argon plasma electrocoagulation, laser photocoagulation, and stenting for tracheobronchial, esophageal, duodenal, and colorectal malignancies. Keywords: cancer prevention, endoscopic diagnosis, endoscopic therapy Head Emanuele Meroni, MD Clinical research staff Giovanni Ballardini, MD Giuseppe Calarco, MD Gabriele Delconte, MD Gianfranco Di Felice, MD Massimo Falsitta, MD Andrea Mancini, MD Vittorio Mauro (coordinator), Francesco Bottani, Raffaele Calò, Roberto Fiocco, Daniele Lo Curcio, Francesca Mannai, Giovanni Sammartino, Raffaele Quagliolo TECHNICIANS Silvia Cara, Rosanna Loi, Salvatore Morfeo Concetta Di Quattro, Annamaria Mercuri 38

scientific report 2012 OTOLARYNGOLOGY SURGERY Gabriele Scaramellini, MD Clinical Research STAFF Roberto Bianchi, MD Sarah Colombo, MD Letizia M. C. Ferraro, MD Walter Fontanella, MD Paolo Formillo, MD Marco Guzzo, MD Tullio M. Ibba, MD, PhD Natalia R. E. Pizzi, MD Madia Pompilio, MD Stefano Riccio, MD Vincenzo Spanò (coordinator), Giovanna V. Bello, Petronilla D Agostino, Elena Cotellessa, Angelo Di Caro, Giorgio Fumi, Giorgio Inverni, Carmen Minio, Rosita A. Nanna, Laura Ongari, Daniele Pezzera, Francesca Pisano, Federica Prudenzano, Raffaella Repetto, Maura Rimoldi, Maria Stefania Selva TECHNICIANS Pablita Endaya, Vincenzo Marotta, Giuseppe Messana, Laura Somma Sabrina Zazzera The Unit is highly specialized in the treatment of benign and malignant tumors of the head and neck area. State-of-the-art surgical treatment for patients with head and neck tumors is guaranteed by experts from across disciplines: otolaryngologists and maxillofacial surgeons. We have extensive experience in skull base and paranasal sinus tumors and in complex reconstruction of surgical defects of head and neck using free microvascular flaps, with the largest series in Italy for both. In particular, we have focused on the use of customized stereolithographic models in bone reconstruction (to obtain the most effective cosmetic and functional long-term result); ozone-therapy, followed by conservative surgery for the treatment of BRONJ; and intraoperative rehabilitation after resection of the maxilla, by using a prefabricated dental obturator. Another area of interest is thyroid surgery, where treatment is planned by a multidisciplinary team including specialists in endocrinology and nuclear medicine. Special care is given to the treatment of multiple endocrine neoplasia and pediatric malignancies of the thyroid gland. Furthermore, the Unit is specialized in the surgical treatment of parathyroid gland diseases using the intraoperative parathormone monitoring. We are focused on quality-of-life issues such as retaining the patient s ability to speak and swallow, maintaining a normal appearance, and minimizing the functional outcome of surgical treatments. In this context, we are specialized in the use of minimally-invasive surgery such as rigid endoscopy and new sources of light (narrow band imaging) for diagnosis and treatment of cavity cancers. We have developed a multidisciplinary team including specialists in radiation oncology, medical oncology, radiology, pathology, plastic and reconstructive surgery, neurosurgery, dental prosthetics, nutrition, and pain management. Weekly multidisciplinary meetings ensure that each patient receives adequate and customized treatment, as well as rehabilitation and prevention services that are tailored to their needs. Preclinical research is conducted in collaboration with medical oncologists, pathologists, molecular biologists, and endocrinologists on prognostic features and molecular targets of head and neck cancer. The clinic of outpatient oral precancerous lesions deals with diagnosis and conservative treatment of oral lesions, with a particular focus on HPV-related lesions and the cancerogenetic role of this virus. Keywords: head neck cancer, ultidisciplinary approach, organ preservation, thyroid cancer, parathyroid gland tumors 39

scientific report 2012 GYNECOLOGIC ONCOLOGY The Unit deals mainly with primary and secondary tumors of the female genital tract. The activities of staff members are dedicated to clinical practice, research, and teaching (three tumor boards weekly, international meetings, three surgical master courses yearly) The clinical activity of Gynecologic Oncology is mainly focused on: First entry gynecologic oncology evaluation Familial cancer Abnormal pap and primary and second colposcopy HPV multidisciplinary office 1st and 2nd level ultrasound Hysteroscopy Follow-up All surgical and medical treatments are coordinated on a weekly basis by a multidisciplinary team including surgeons, medical oncologists, pathologists, and radiotherapists. The research activity of the group involves both basic science and clinical studies. In collaboration with the Experimental Oncology Department, we conducted several studies on mirna, gene expression, folate receptor levels, and apoptosis in ovarian carcinoma. Studies on the detection of stem cells in normal ovaries and ovarian cancer to preserve the endocrine potential in ovarian cancer patients by selecting new drugs against these cells are ongoing. Clinical research to evaluate the efficacy of chemotherapeutic agents in gynecological cancer, in particular in ovarian cancer, was carried out. Active collaborations in international and national multicenter clinical controlled studies with both medical and surgical protocols are ongoing. To improve the prognosis of early stage cancer, several studies are being conducted on the efficacy and safety of laparoscopic techniques in gynecologic oncology. We extended the concept of mini-invasiveness to laparotomy in order to reduce the complications of radical hysterectomy. Surgical research was conducted on the following techniques: Nerve sparing radical surgery Debulking surgery Mini-invasive surgery Laparoscopic surgery in diagnosis, staging and treatment of early gynecological tumors Sentinel node detection in endometrial cancer Fertility-sparing surgery (cervical, ovarian, and endometrial cancer) Surgery in advanced cases and/or recurrences from all origins Photodynamic treatment of recurrent Paget s vulvar disease Vulvar, vaginal, and uterine melanoma surgical treatment Reconstructive surgery (in collaboration with Plastic and Reconstructive Surgery unit) We perform about 1200 procedures each year in ambulatory surgery. About 500 major surgical procedures are currently carried out per year. Keywords: gynecologic surgery, chemotherapy, clinical studies Francesco Raspagliesi, MD CLINICAL RESEARCH STAFF Antonino Ditto, MD Rosanna Fontanelli, MD Barbara Grijuela, MD Domenica Lorusso, MD Marina Merola, MD Andrea Papadia, MD Eugenio Solima, MD Flavia Zanaboni, MD RESEARCH FELLOWS Fabio Martinelli Stefano Ramondino Maria Mancini Italo Sarno Patricia Acosta, Alice Casali, Francesco Crugliano, Floriana Dimo, Lorenza Greco, Eva Guitti, Antonio Micello, Marianna Miranda, Claudio Oppido, Rossana Penasa, Ylenia Ponti, Paolo Re, Patrizia Valente HEALTH CARE ASSISTANTS Rosa Farro, Alessia Formicola, Natalia Munante, Cecilia Muzzupappa Cinzia Marretta, Rosella Zennoni, Stefano Ramondino, Maria Mancini, Italo Sarno 40

scientific report 2012 Thoracic Surgery Ugo Pastorino, MD CLINICAL RESEARCH STAFF Leonardo Duranti, MD, PhD student Riccardo Giovannetti, MD Francesco Leo, MD Paolo Scanagatta, MD Luca D. Tavecchio, MD FELLOWS Andrea Billè, MD, PhD Student Simone Furia, MD Giuseppe Garofalo, MD Stefano Sestini, MD RESIDENTS Lara Girelli, MD, Roberta Rota, MD Federica Pirovano (coordinator), Brice Atiomeguim, Francesco Auletta, Marcella Bernardo, Claudia Costa, Yesica Del Rio Mendez, Antonino De Vita, Raffaele Di Nino, Margherita Fersurella, Hilda A. Martinez, Daniele Marino, Maria L. Quitadamo, Anna M. Panareo, Antonio Pantano, Antonella Prete, Antonino Proto TECHNICIANS OSS Nekpen Eguavoen, Angela Di Luglio, Diego Risuglia, Svitlana Shulzhenko, Pamela K. Soto Fernandez Tiziana Negri (unit secretary) RESEARCH STAFF Elena Bertocchi, Anna Maria Calanca, Carolina Ninni (scientific secretaries), Claudio Jacomelli, Paola Suatoni (Biol Sci D) EXTERNAL COLLABORATORS Francesca Bravi, Statistician, Benedetta Finamore, Radiologist, Marta Rossi, Statistician Nicola Sverzellati, Radiologist High-standard clinical care and scientific research, translational research and education and training are at the heart of this Unit s activity. Clinical activities cover all aspects of thoracic oncology, focusing on pulmonary, mediastinal, chest wall, and esophageal tumors. In the management of lung cancer, the mainstay of surgical treatment is maximal functional sparing. All patients undergo muscle-sparing thoracotomy, avoiding any muscular section. Lung-sparing procedures (bronchoplasty and/or angioplasty) are adopted to avoid the removal of the entire lung, when possible. A clinical randomized trial is ongoing, searching for the best drainage strategy to limit postoperative air leak (airintrial). In the domain of secondary lung tumors, the Thoracic Surgery Unit cooperates with different INT Units (mainly with Oncology, Pediatric Oncology and Sarcoma Units), performing standard metastasectomy by innovative parenchyma-sparing procedures. Extended resections are proposed when an acceptable postoperative impairment of the quality of life can be expected. Innovative techniques for tridimensional chest wall reconstruction have been developed (rib-like technique), permitting appropriate reconstruction even in case of removal of an entire hemithorax. In mediastinal surgery, superior vena cava (SVC) replacement is performed by procedures not requiring SVC cross-clamping, avoiding intraoperative hemodynamic instability. Pleuropneumonectomy is proposed in limited malignant mesothelioma, after induction chemotherapy. In the more advanced disease, a clinical trial has been approved to measure the advantage of pleurectomy/decortication after chemotherapy in terms of disease-free survival and quality of life, compared to chemotherapy only (PASS trial). Esophageal surgery is performed in cooperation with different Units (Otorhinolaryngology, Gastrointestinal-Pancreatic Liver Surgery, Endoscopy). Our group employs a multidisciplinary approach to better define the strategy for diagnosis and treatment for each clinical case. Every week we organize a meeting with the colleagues from all the Units involved: radiology, oncology, endoscopy, pulmonology, radiotherapy and nuclear medicine. Continuing education for physicians and nurses is provided by a structured program on particular aspects of clinical management (The thoracic drainage) and surgical techniques (surgical technique in pleural mesothelioma and endoscopic technique in thoracic oncology), and a course on scientific writing. Keywords: lung cancer, secondary lung tumors, thoracic oncology 41

scientific report 2012 Plastic and Reconstructive Surgery Reconstructive surgical procedures are related to extensive breast and head and neck surgeries, soft-tissue tumors, chest-wall surgery, and other types of aggressive oncologic surgeries, as well as surgical treatment and repair of skin cancer. Oncoplastic surgery represents a new standard for reconstructive procedures after tumor excision. Plastic procedures related to breast cancer surgery account for the main workload, and fat and implant hybrid breast reconstruction is planned and started concurrently with breast ablation. Fat cell transplantation allows implant-based reconstruction in some cases even after tissue damage by radiotherapy. In patients who are not candidates for hybrid breast implant insertion, reconstruction is carried out with flaps. Both DIEP and free flaps have been used for delayed or immediate breast reconstruction, after ablation of large soft tissue tumors, and in reconstruction after head and neck demolitions. Cohesive gel breast implants together with fat cell transplantation and microsurgery represent the highest standard in reconstructive surgery. Fat tissue transplantation using fat cells together with adipose-derived fat cells and platelet-rich plasma allow us to regenerate damaged tissue. We collaborate with the Department of Experimental Oncology and Molecular Medicine to evaluate the stem cell activity of injected fat cells and the Bioengeneering Unit, Politecnico University of Milan, for three-dimensional breast imaging. Oncoplastic surgery is the main activity of the Unit and the core of its clinical and experimental investigations. Clinical trials such as EORTC (quality of life after breast reconstruction), Suri-2 for breast reconstruction, Acellular Dermal Matrix breast reconstruction (Strattice), and the development of an Oncoplastic Workflow are a fundamental part of our research activities. Keywords: plastic, oncoplastic-breast-skin surgery, microsurgery, fat cell transplantation Maurizio B. Nava, MD CLINICAL RESEARCH STAFF Novella Bruno, MD Pierfrancesco Cadenelli, MD Umberto Cortinovis, MD Joseph Ottolenghi, MD Angela E. Pennati, MD Egidio Riggio, MD Andrea Spano, MD Maria Saracino (coordinator), Samantha F. Castelli, Cinzia Gentilini, Giusppe L Abbate, Marisa Labò, Giovanna Melia, Caterina Pireddu, Irene Rossi, Raffaella Tupputi TECHNICIANS Nadia Casati, Provvidenza Peci, Nomi Ibazeta Ramos, Iolanda Panipucci, Annunziata Rugolo Luisa Morandi 42

scientific report 2012 urologic surgery Roberto Salvioni, MD CLINICAL RESEARCH STAFF Davide Biasoni, MD Mario A. Catanzaro, MD Patrizia Giannatempo, MD (Resident, Department of Medical Oncology, Medical Oncology Unit 2) Giovanni Lughezzani, MD (fellow Università Salute HSR Milan) Angelo Milani, MD Andrea Necchi, MD (Faculty, Department of Medical Oncology, Medical Oncology Unit 2) Nicola Nicolai, MD (Head, Testicular Cancer Surgery Unit) Luigi Piva, MD (Head, Pediatric Surgery Unit) Daniele Raggi, MD (Fellow, University of Milan School of Medicine) Silvia Stagni, MD Tullio Torelli, MD Graziella Russo (coordinator), Maria L. Cennamo, Anna M. Cercaci, Zino Ferro, Maria R. Leo, Francesca Marelli, Giovanni Mazzilli, Lucia Mesiano, Arturo Monetta, Valentina Musarò, Giuseppa Napoli, Veronica P. Rojas, Maria Silva, Annalisa Simone, Rossi Raffaella Maria G. Bodini TECHNICIANS Antonio Bonelli, Elena Cristiani, Isabella Vurchio, Olimpia Liberatore De La Cruz Velesmoro Rocio Del Pilar Urothelial cancer A study with pazopanib in relapsing urothelial cancer ended enrolment in July 2011, and very impressive responses were observed. Concomitant trials were planned, and in particular a phase II study with a monoclonal antibody against the TGF-β receptor ALK1 was accepted for funding and support within the Rete Oncologica Lombarda (ROL). Two other clinical trials are ongoing: a clinical study on sorafenib in combination with chemotherapy as neoadjuvant therapy and another randomized phase II study on vinflunine and gemcitabine versus vinflunine and carboplatin as first-line therapy for patients who are unfit for cisplatin. Enhanced visualization technologies (use of 6-ALA and NBI filter) were implemented to improve diagnosis and treatment of early flat bladder lesions. Testicular cancer The observational study on the quality of life of patients undergoing retroperitoneal lymph-node dissection (RPLND) as primary treatment for clinical stage I disease ended accrual in March 2012, and the study closed on December 2012. A definitive data set is currently available that shows a general increase in the FACT-G QoL scale scores from baseline to follow-up evaluations. The optimization of laparoscopic RPLND showed that the treatment had an acceptable, low morbidity, which may actually replicate the historical results of open RPLND. Post-chemotherapy RPLND was standardized in 2011 as an alternative to open-rplnd in selected patients with a unilateral residual mass <6 cm and an encasement to gross retroperitoneal vessels <25%. Preliminary data on 18 cases showed comparable efficacy with open 43

scientific report 2012 counterparts with a significant reduction of hospital stay, convalescence time, and need for analgesics. A project aimed to re-evaluate the expression of CD30 antigen in residual masses yielding viable malignant cells after chemotherapy was started in late 2011. The objective of this project was to establish the basis for a phase II study with the immunoconjugated anti-cd30 monoclonal antibody (SGN-35, brentuximab) in metastatic and chemotherapy resistant disease. The phase II study of tandem highdose chemotherapy for relapsing germ cell tumors continued enrolling throughout the year. Penile cancer We continued a multimodal project for clinically node-positive squamous cell carcinoma of the penis aimed to evaluate the activity of neoadjuvant TPF chemotherapy followed by lymph node dissection after primary tumor control that included the use of PET/CT for both staging and response evaluation prior to surgery. The technique of dynamic sentinel lymph node biopsy underwent further improvement to reduce false negative cases among patients with clinically negative inguinal nodes. A re-evaluation of the role of perioperative chemotherapy in patients with nodal metastases undergoing lymph node dissection was undertaken to define the best sequence for patients with locally advanced disease. Kidney cancer We extended the indications for nephron-sparing surgery. A new multidisciplinary approach with controlled intraoperative hypotension was adopted. Optimization of the type of approach (zero ischemia vs cold ischemia) is under investigation to minimize renal damage. Keywords: genitourinary cancer, multidisciplinary, mini-invasive therapy 44

scientific report 2012 Pediatric Surgery Luigi Piva, MD PhD The Unit collaborates with pediatric oncologists and provides a high standard of treatment for the most frequent solid non-cns tumors in children and adolescents. The role of surgery is established according to ongoing European treatment protocols. During 2012, the following surgical interventions were performed: Wilms tumor. Surgery on patients enrolled in the TW 2003 AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study: 3 nephrectomies and 2 partial monolateral renal excisions. Neuroblastoma. Four surgeries. Germ cell tumors/gynecological and andrological procedures. 2 orchiectomies, 1 hysteroscopy, 1 oophoropexy, 1 surgery on a patient with a germ cell tumor, 2 testicular reposition in scrotum after transposition for radiotherapy, 5 urological procedures. Soft tissue sarcomas and rare tumors. Surgeries on soft tissue sarcomas were performed in collaboration with the Melanoma and Sarcoma Unit. 16 soft tissue tumors, 1 cystoscopy, and 7 cutaneous lesions. Cranio-maxillofacial tumors. Surgeries performed in cooperation with the ORL Unit. Three hemi-thyroidectomies, 1 parotidectomy, and 1 facial surgery. Lung metastases. Surgeries performed in cooperation with Thoracic Surgery Unit, 9 metastasectomies, 1 pneumonectomy. Three patients underwent thoracotomies for different diseases. Breast procedures. Two quadrantectomies. 13 surgical biopsies (3 for sarcoma, 3 for benign lesions, 2 for lymphoma, 1 for renal tumor, 1 for carcinoma of the nasopharynx, 1 for neuroblastoma, 1 for neuroectodermal carcinoma), 11 lymphadenectomy, and 2 perfusions. Keywords: renal tumors, pediatric sarcoma, multidisciplinary team 45

scientific report 2012 LASER THERAPY The Unit uses high-quality instrumentation including four lasers for a total of 20 wavelengths. This allows both conservative and ablative therapies in those diseases where laser therapy is the first or only treatment choice. Selective photothermolysis laser treatment is performed for keloids as well as pigmented and vascular lesions, and laser ablation is used for mucosal and skin cancer lesions requiring histological evaluation. Treated lesions can be conveniently classified into five groups: Tumor lesions: skin carcinomas, melanoma in-transit metastases, cutaneous and mucosal localizations of Kaposi s sarcoma, precancerous lesions such as actinic keratosis Vascular lesions: flat-type congenital capillary angiodysplasia, angiomas, and venous lymphatic angiodysplasia Nevi: giant melanocytic nevi Scars: traumatic and post-burn hypertrophic scars and keloids Cutaneous localizations originating from complex syndromes, such as adenomas in tuberous sclerosis, angiodysplasias related to Sturge-Weber syndrome, neurofibroma, and cafe-au-lait spots in neurofibromatosis (with the INT serving as national referral center for this disease). Compared with previous years, an increasing rate of tumoral and vascular diseases and complex syndromes was observed. Keywords: laser therapy, skin cancer, angiodysplasia Anna Colombetti, MD CLINICAL RESEARCH STAFF Silvia Aiello, MD Mario Z. Raso, MD Maria Saracino (coordinator), Emilia D Arrigo HEALTHCARE ASSISTANT Domenica Lo Prete ADMINISTRATIVE Personnel M. Rosaria Aceto 46

scientific report 2012 Day Surgery Aldo E. Bono, MD Giovanna R. Colaci, Mariangela Lena, Mara D. Luisoni, Pina P. Mele, Anna Picciallo, Domenica Violi, Marina Zocchi HEALTHCARE ASSISTANTS Antonella Bordoni, Silvia Cara, Rosa Selvati Maria R. Bignamini, Anna Corella, Loredana Orezzi The Day Surgery Unit is devoted to surgical procedures performed in ambulatory and day hospital settings. The Unit includes 10 beds, 2 operating rooms where various surgical activities are carried out, and one operating room for laser surgery. The clinical activity covers many aspects of oncologic surgery, and in particular includes the treatment of different lesions involving skin, soft tissues, breast, as well lesions in gynecologic, urologic, and head and neck areas. This activity involves the collaboration of physicians from the Department of Surgery. During 2012, 5118 surgical procedures were performed. Of these, 2970 were performed in a day hospital setting, whereas 2148 patients underwent outpatient surgery. A total of 4598 operations were performed under local anesthesia, while 520 procedures were performed under sedoanalgesia or general anesthesia. In addition to normal surgical activity, particular procedures were performed, such as electrochemotherapy of secondary skin tumors (in collaboration with the Melanoma and Sarcoma Unit) and fat injection or lipostructure with the Coleman technique to lessen local skin and sub-cutaneous damage (in collaboration with Plastic and Reconstructive Surgery Unit). Clinical research activity is, at present, mainly conducted in cooperation with the Melanoma and Sarcoma Unit. The aim of this activity is to better define the initial clinical features of early melanoma to allow for minimallyinvasive curative surgery. Further scientific cooperation with the Unit of Immunotherapy of Human Tumors focuses on blood measurements of circulating mirna in patients with cutaneous melanoma. Keywords: day surgery, ambulatory surgery, early melanoma 47

Medical Oncology Department 48