Why do pancreas treatment in italy?
The importance of expertise in pancreatic surgery: in pancreas surgery, more than any other surgery branch, it is demonstrated that accumulated experience over the years (in terms of surgical volume) is positively correlated with results. Keeping in mind that pancreas operations are technically complex and difficult procedures with a mortality rate superior to many other major surgical procedures.
A multidisciplinary approach to pathologies of pancreas: our surgical unit is part of the Pancreas Institute of Verona, Italy’s first center entirely dedicated to diagnosis and therapy of pancreatic diseases. A multidisciplinary team composed of surgeons, gastroenterologists, radiologists, oncologists and anatomo-pathologists working together, integrating their knowledge and putting them to the service of patients’ needs.
In Verona the most advanced technologies are used to produce the diagnosis and course of treatment of the diseases of the pancreas. In particular, mini-invasive surgical procedures are the most advanced, both with videolaparoscopic and robot-assisted techniques.
ROBOTIC SURGERY AND LAPAROSCOPY
Videolaparoscopic surgery is built on the principle of access to abdominal cavity using small incisions (between 5 and 15mm) and, through them a digital camera capable of projecting images in a screen is inserted along with thin tools to execute the operation. Developed at the end of the ‘80s, it has had more and more success, the indications widened to cover almost all the interventions in abdominal surgery, and the techniques have been standardized.
FINALLY THE NEW TECHNOLOGY TO CURE CANCER
The therapy used is called hadron therapy, and it has an accuracy of two-tenths of a millimeter.
In this way, the therapy focuses ONLY on the tissue affected by cancer and reduces it, session after session, until healed.
The technology that enables this short and focused treatment is called Synchrotron. Synchrotron is an innovative tool to treat those tumors which are resistant to conventional radiotherapy and is partly created in Italy.
Rapid technological progress in recent years has led to an evolution in all areas of medicine and has significantly influenced radiation oncology. Today, a new frontier in radiation therapy is represented by the hadrontherapy, which is the use of protons and atomic nuclei (ions) called hadrons (from the Greek hadrós, strong) that are subjected to a strong nuclear force.
The advantages of hadrontherapy compared to traditional radiotherapy are:
- The release of energy (and thus the destruction of cells) is done selectively, targeting only cancer cells. The damage incurred in the body on initial penetration is relatively small and significant release of energy is confined only to the vicinity where the cancer is located (a phenomenon referred to as the Bragg Peak). This maximizes the destruction of cancerous tissues while minimizing collateral effects on healthy tissues;
- The beam of hadronic particles remains collimated as it penetrates the biological material. The high collimation of the beams of hadrons further minimizes damage to healthy tissues;
- The energy release mechanism for hadrontherapy causes a large amount of breaks on the chemical links present in biological macromolecules, especially DNA. The latter has the ability to repair itself, but if the number of broken links is excessive it loses its function of self-reparation and the cells remain inactive and die. In conventional radiotherapy the DNA damage is modest; on the contrary, in the hadrontherapy with carbon ions the number of breaks allows the destruction even of tumors resistant to conventional therapy.
Together these three benefits result in a significant destructive effect on biological tissues, for which reason the target (tumor) must be positioned with a degree of accuracy which is much greater than that associated with conventional radiotherapy.
Effective application of hadrontherapy requires the following:
- a proton and / or ion accelerator (such as the circular accelerator or synchrotron) producing a number of particle beams
- a system for transporting the beam in the treatment room
- a procedure for precisely positioning the patient for treatment
- complete control of the energy to be released i.e. the dose
- a three-dimensional customized patient treatment system obtained by integrating diagnostic imaging results (CT, MRI, PET).
It is important to note that since hadrontherapy is a relatively recent addition to the modern oncological treatment panorama, a number of indications are still in the experimental stage.
The National Centre of Oncological Hadrontherapy (CNAO), located in Pavia, is the first Centre of Hadrontherapy in Italy provided with a beam able to irradiate patients with protons or carbon ions for the treatment of radioresistant tumors.
These packages are pre- accelerated and sent to the synchrotron where, initially, they travel at about 30,000 kilometers per second. Subsequently they are accelerated to kinetic energies of 250 MeV for protons and 480 MeV for carbon ions (the MeV, equivalent to one million electron volts, is the unit of energy used in nuclear and atomic scale phenomena).
The particle beam is accelerated in the synchrotron and travels at about 30,000 kilometers in a half second to reach the desired energy. The beams are then sent to one of the three treatment rooms. Above this station there is a magnet of 150 tons which bends 90 degrees the particle beam and directs it from above to the person to be healed.
The beam that strikes the cells of the tumor is like a “brush” that moves in a manner similar to that of electrons in a TV and acts with a precision of 200 micrometers (two tenths of a millimeter).
This accuracy is achieved by means of:
- Constant monitoring of the patient to follow any movements of the body (breathing, for example) that can change the location of the tumor, using infrared cameras to measure movement in a three-dimensional way
- Two scanning magnets that, based on feedback of the beam monitoring system, move the “brush” along the outline of the tumor
In this way, section by section, the tumor is destroyed. The transition from one section to another deeper section is achieved by increasing the beam energy. The entire radiation lasts a few minutes.
Hadrontherapy is an advanced form of radiotherapy. Radiation therapy alone, or combined with surgery and/or chemotherapy, improves local control in different tumors. In addition, the non-invasive nature of radiation therapy represents a suitable alternative to surgery for those tumors located in anatomical locations complicated by vital organs or in sites where tumor removal would be too debilitating for the patient. Today, about 50% of patients with cancer are undergoing radiation therapy. Hadrontherapy is not a substitute for conventional radiotherapy, but arises as an ideal technique for those cancers where conventional radiotherapy does not provide significant advantages in particular for “radio-resistant” tumors and for those located close to organs at risk. “Radio-resistant” tumors are those which, because of their biological behavior, are less likely to be cured by conventional radiotherapy. Tumors located in the vicinity of organs deemed “critical” or “at risk”, often cannot be irradiated by doses high enough to be effective, because it could harm healthy organs.
THE EXPERIENCE IN PANCREAS SURGERY IS IMPORTANT
Pancreas surgery is a specialized sector in which very peculiar expertise are required. The incidence of post-surgical complications following the removal of part of or the whole pancreas is much higher than any other major abdominal surgery, and it has remained constant over the years. Collected data of the last ten years, however, show a substantial reduction of its mortality rate, especially in centers with a high surgery volume.
This result demonstrates that the surgery volume (intended as the number of pancreatic resections in a year) of a center is crucial. In 2002 Dr. Birkmeyer published the results of an observational study on 2.5 million operations on different types of surgeries between 1994 and 1999 on the New England Journal of Medicine: the post-operatory death rate after a pancreaticoduodenectomy of the head of the pancreas was of 16.3% in low surgical volume centers, and 3.8% in high volume centers. The absolute difference (12.5 points) resulted to be one of the biggest gaps in the anlized surgical centers (Picture 1).
Dr. Balzano confirmed these results in 2008 on 1576 cases of pancreaticoduodenectomy. In two very high surgical volume centers (Verona, General Surgery B, Ospedale Policlinico and Milan, Surgery Hospital San Raffaele), the post-operatory death rate (2.6%) is sensibly lower than the other centers (Picture 2).
Since 1990 over 1800 pancreaticoduodenectomies have been executed in the Operation Unit of General Surgery B (Picture 3). The total of pancreatic resections operated is over 2800, in no other Italian hospital there has ever been a bigger volume of pancreatic surgery. In the latest years mortality rate after a pancreatic resection stayed around 1.5%: these numbers put Verona among the leading centers of pancreatic surgery worldwide.
Basing on the available literature on the argument, Ministry of Health, in 2010, has fixed a maximum of 30 pancreaticoduodenectomy and of 30 resections of the head or the tail of pancreas and enucleations of pancreatic injuries per year to obtain the high volume center status. The minimum level to obtain this certification of excellence center is fixed at 100 pancreaticoduodenectomies and 100 head/tail resections.
The criteria for the conferral of excellence status includes the presence of a multidisciplinary team that treat pancreatic pathologies, a neoplastic tissue bank and biological liquids of patients affected with pancreatic neoplasia, also, a multidisciplinary team for basic research.
Under this light, our Operations Unit – which is part of the Institute of Pancreas, first interdisciplinary center for diagnosis, cure and research of pancreatic diseases in Italy – puts itself as a landmark, offering to patients a service based on professionality, experience and scientific evidence.
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Thermoablation intervention using radio frequency
Thermoablation using radiofrequency of pancreatic wounds is an experimental method developed by an association between Chirurgia Pancreatica Ospedale of Peschiera of Garda and Chirurgia del Pancreas di Verona research groups and used on patients with locally advanced ductal adenocarcinoma.
It consists in the application of electromagnetic waves directly on the neoplasia. This causes a rise in the intra-tumoral temperature that destroys the cells by coagulation and denaturation of the proteins. Radiofrequency has been used for some time in the multimodal treatment of an unresectable solid neoplasia (liver, kidney, brain, prostate, suprarenal gland). The application to a pancreas solid neoplasia was always judged as extremely dangerous due to the delicate nature of the pancreas itself and the delicate ties with noble vascular structures, with duodenum and the bile.
Our research group on pancreatic radiofrequency demonstrates in 2010 the applicability and the relative safety of ablation using radiofrequency on a group of 50 patients with ductal advanced adenocarcinoma, registering a mortality rate of 2% and a post-surgical complications rate of 24%. With this growing experience the technique gets better and better and, to this day, in the Hospital of Peschiera del Garda and or Unit of Pancreatic Surgery performed over 200 surgeries (highest casuistry worldwide). Picture 1 shows the effects of radiotherapy of pancreatic tumor has seen on a perfusional TAC, that quantifies the blood flow in the region in which new can find the neoplasia after the ablation procedure.
Picture1. Pre-surgical TAC (locally advanced neoplasia on the head of the pancreas, left picture), perfusion-TAC after a thermoablation procedure with radio frequency (on the right). It is clear there is no blood flow on the region of the ablated tissue on the neoplasia level. Copyright Chirurgia del Pancreas Verona.
Radiofrequency remains a procedure with no radical intent, it only produces a partial ablation of the neoplasia. Long-term survival results (which, actually, come from a non-randomized observational analysis) are very encouraging and, this process, might have an important role in a multimodal treatment of ductal adenocarcinoma, with the appropriate timing and cure plan for every single patient. At this moment, we consider radiofrequency thermoablation on patients with:
- Locally advanced adenocarcinoma (radiological staging) confirmed using preparatory biopsies.
- Age between 18 and 80 years old.
- The disease is not in regression after radiotherapy/chemotherapy (regime and number of cycles are at discretion of the Oncologist/Radiotherapist, a minimum of 3 months of therapy).
- Good general conditions (performance status > 50% sec. Karnofsky or ≤ 2 sec. ECOG).
Thermoablation using radiofrequency is performed using a laparotomy (a low abdominal incision). Before a surgeon performs the procedure he will always execute a complete surgical exploration of the abdomen and an ulterior histologic specimen during the operation to confirm diagnose and staging. The localization of the neoplasia and vascular relations is confirmed by an intra-surgery echography, which guides the positioning on the wound of the electrodes medical probe and visualizes the entire tumor necrosis area during the application of electromagnetic waves. If necessary, at the end of the procedure a gastric and/or bilious bypass is performed with a palliative purpose.
Thermoablation using radiofrequency is a high level surgery intervention, to execute only in center in which there is a top quality experience on this method and – more in general – with pancreas surgery. A whole team of multidisciplinary experts (radiologists, oncologists) to establish the most appropriate therapeutic plan according to each patient.
Even though pancreatic radiofrequency is a safe procedure by now, the insurgence of specific post-surgery complications are still possible, among which:
- Portal vein/ superior mesenteric vein thrombosis.
- Duodenal ischemic ulcers.
- Thermal acute pancreatitis.
- Pancreatic fistulas.
Protocol requires the execution of a TAC at the moment of discharge to evaluate the ablated area, the prosecution of chemotherapy if tolerated, and a close clinical and instrumental follow-up by our center.
MINIMALLY INVASIVE SURGERY
Minimally invasive surgery is performed through small incisions, usually between 5-15 mm. The surgeon then inserts specially designed, thin instruments and sophisticated video equipment to perform the operation through the smaller opening. Depending on the procedure, minimally invasive surgery can be performed with the surgeon manipulating the instruments by hand (laparoscopic surgery) or with the surgeon directing robotic arms (robot-assisted surgery).
Minimally invasive surgery offers many benefits over traditional techniques, including less injury to tissue, less postoperative pain, shorter hospital stays, quicker return to normal activities, minimal scarring, less incisional hernias. Over the past 20 years minimally invasive surgery has evolved to such an extent that in suitably qualified hands the majority of general surgical procedures can be safely carried out.
The complexity of pancreatic surgery has meant that the development of laparoscopic techniques and particularly formal resections has been relatively slow compared with procedures in many other surgical specialties. Consequently its incorporation into regular clinical practice is recent, and initial indications were limited to benign and borderline neoplasms. Recent data indicate that laparoscopic pancreatic resections are oncologically adequate, and can be safely applied to malignant neoplasms. The most commonly performed laparoscopic pancreatic resections are left pancreatectomy and enucleation, whereas the experience with pancreaticoduodenectomy and middle pancreatectomy is limited.
Miimally invasive surgery has been further enhanced by the use of robotics. Robotic surgery is a technique in which a surgeon performs surgery using a computer that remotely controls very small instruments attached to a robot. With the surgeon sitting at a console a few metres from the patient, the robot translates that surgeon’s hand movements into corresponding micro-movements of instruments inside the patient’s body. The robotic system provides better visualization, dexterity, precision and control than open surgery, while enabling the surgeon to perform procedures through tiny, 1-2 cm incisions. The world experience on the use of robotic systems for surgery on the pancreas is growing, but remains limited.
The Unit of Pancreatic Surgery in Verona has one of the largest minimally invasive practice in Italy. Our program has a history of pioneering innovative, minimally invasive approaches such as left pancreatectomy with splenectomy, spleen-preserving left pancreatectomy, enucleation, middle pancreatectomy. We have developed experience with the da Vinci Si HD robotic system for left pancreatectomy, with or without splenectomy, and enucleation.