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Multidisciplinary management of potentially resectable liver metastases: the role of the radiologist. Poster No.: C-1011 Congress: ECR 2015 Type: Educational Exhibit Authors: M. D. Monedero, R. Pastor Juan, J. A. González Masiá, J. I. Miota de LLama, E. Lozano Setién, E. Julia; Albacete/ES Keywords: Abdomen, Liver, CT, MR, Percutaneous, Diagnostic procedure, Chemoembolisation, Ablation procedures, Neoplasia, Metastases, Multidisciplinary cancer care DOI: 10.1594/ecr2015/C-1011 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myESR.org Page 1 of 34 Learning objectives 1. Describe the management of patients with resectable liver metastases in the context of a multidisciplinary committee. 2. Show the role of the radiologist in the diagnosis, treatment and follow-up of these patients. 3. Describe the diagnosis and treatment algorithm followed in our center. 4. Reflect our experience with these patients since the launch of the multidisciplinary committee hepatobiliary pathology in our center. Background OVERVIEW OF OUR HEPATOBILIOPANCREATIC MULTIDISCIPLINARY COMMITTEE PATHOLOGY OPERATION OF OUR COMMITTEE ROLE OF RADIOLOGISTS IN THE COMMITTEE POTENTIALLY RESECTABLE LIVER METASTASES: AN INCREASING CLINIC SITUATION INDICATION OF SURGICAL RESECTION IN THE LIVER RECURRENCES INDICATION OF SURGICAL RESECTION IN PATIENTS WITH EXTRAHEPATIC DISEASE DOWNSTAGING OR DOWNSIZING THE ROLE OF RADIOLOGISTS IN THE MANAGEMENT OF POTENTIALLY RESECTABLE LIVER METASTASES Page 2 of 34 • DIAGNOSIS - ULTRASOUND - ¿MDCT or MRI? - USE OF GADOXETATE (Gd-EOB-DTPA, Primovist®) - PET-CT - INTRAOPERATIVE ULTRASOUND • TREATMENT - PORTAL VEIN EMBOLIZATION (PVE) - CT-GUIDED RADIOFREQUENCY - INTRAOPERATIVE RADIOFREQUENCY - INTRA-ARTERIAL CHEMOTHERAPY OUR EXPERIENCE ......................................................................................................... Page 3 of 34 Fig. 1: Hepatobiliary pathology multidisciplinary committee in our hospital. References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES OVERVIEW OF OUR HEPATOBILIOPANCREATIC MULTIDISCIPLINARY COMMITTEE PATHOLOGY Clinical cases involving hepatobiliopancreatic (HBP) area represent a group of heterogeneous disorders with potentially complicated management, requiring multiple and different imaging techniques for diagnosis and treatment. Skilled and qualified clinicians and surgeons, as well as radiologists, are necesary to take care of these patients. The HBP committee was created in the University Hospital of Albacete (CHUA) in 2009. Different specialties are included as General Surgery Specialists (BPH Pathology Unit), Radiology, Interventional Radiology, Gastroenterology, Oncology, Radiation Oncology and Pathology. Eventually, other specialists attend to present related cases, mainly from Internal Medicine. Page 4 of 34 As a reference center in the spanish region of Castilla-La Mancha, not only patients from Albacete are included, but patients of near provinces as Cuenca too. The multidisciplinary management of these patients has made posible to establish new protocols. Continuing education is stimulated with periodic monographic lectures. This approach has allowed a saving and optimization of tests or procedures, avoiding to repeat imaging procedures or perform inadequate techniques. It has also allowed certain subspecialties within each Department, allowing improvement and progress in the diagnosis and treatment of these patients. As an example, we can cite the liver metastases surgical resection technique itself as well as intraoperative ultrasound and radiofrequency performed by radiologists and surgeons. Images for this section: Page 5 of 34 Fig. 1: Hepatobiliary pathology multidisciplinary committee in our hospital. Page 6 of 34 Findings and procedure details OPERATION OF OUR COMMITTEE The committee meets once a week. The referrals include new patients, recurrences of pathologies, plan updates on diagnosis and/or treatment of patients already known and relevant case results already presented previously. These cases are sent by clinicians to the Secretary of General Surgery, centralizing information and sends the other participants relevant information to be discussed at the next committee, so that all participants know in advance and can review cases properly. After being presented cases, the relevant decisions jointly agreed and binding are taken, sending the final consensus all participants once the meeting ends. ROLE OF RADIOLOGISTS IN THE COMMITTEE Radiologists dedicated to the diagnosis prepare the patient images presented, discussed them in cases of doubt or have special interest for patient management. They provide also guidance on the most appropriate diagnostic algorithm for patients under study or monitoring. Interventional radiologists act as consultants in their area, assessing the indications of the different procedures they are required. POTENTIALLY RESECTABLE LIVER METASTASES: AN INCREASING CLINIC SITUATION In Spain, there are over 20.000 cases/year of colorectal cancer (CRC), finding liver metastases (LM) along the disease in 50-70% of patients: 20-25% synchronous and 25-35% metachronous. 10-15% of these metastases are potentially resectable. The concept of RESECTABLE metastases involves the ability to completely remove the lesions with negative margins (R0), whatever their number, size and location, leaving a liver sufficient to allow normal liver function remnant (Fig. 2 on page 21) . The following data reflect the survival of CRC with MH: Page 7 of 34 • • • Untreated: 6-16 months of median survival (5-year, zero) With chemotherapy: 20% at 3 years Surgical resection (R0) + chemotherapy: approximately 42-58% at 5 years (varies depending on the series by the multitude of prognostic factors). Thus, the treatment of choice of in CRCLM is complete surgical resection (Fig. 3 on page 22). These close to 60% survival at 5 years in the last group results occurred due to several factors: • • • • advances in preoperative imaging techniques, improvement in surgical and anesthetic techniques, the introduction of new cytotoxic and biological agents for pre- and postoperative chemotherapy and proper selection of patients. These changes have increased the number of patients for resection surgery CRCLM and require a complex management of these patients. Therefore, it is accepted that treatment of all patients with CRC and surgical indication of CRCLM should be the responsibility of a multidisciplinary team including oncologists, radiologists and liver surgeons to coordinate the most appropriate action in each case. In our hospital, there are two multidisciplinary committees related to CRC. One of them decide the treatment of all patients with CRC and our HBP committee in consensus with the CRC team defines the treatment of patients with CRC and liver metastases. INDICATION OF SURGICAL RESECTION IN THE LIVER RECURRENCES In patients treated surgically with curative intent recurrence of the disease recurrence is present in about 60% of cases, of which 20% will be exclusively liver recurrence. It has been shown that surgical mortality and morbidity are comparable to the first resection and a median survival of 32 to 46 months is achieved. Therefore, it seems reasonable to consider reoperation in patients with liver disease recurrence if they fulfill the criteria followed in the indication of the first resection. Page 8 of 34 INDICATION OF SURGICAL RESECTION IN PATIENTS WITH EXTRAHEPATIC DISEASE Traditionally, extrahepatic disease was almost universally regarded as a contraindication to resection of the CRCLM. However, it has been able to demonstrate a survival rate of 12-37% five years after liver resection in selected patients with extrahepatic disease, regardless of their location (lung, lymph nodes of the primary tumor, retroperitoneal or hepatic pedicle, peritoneal carcinomatosis...). The presence of peritoneal metastases is controversial. In some series the total number of metastases is considered more important to be resected, rather than the location, also including peritoneal. Currently there is agreement that peritoneal metastases localized in small numbers, are not an absolute contraindication to resection. The metastatic lymph nodes in area 1 (hepatic hilum or retroduodenal) worsen the prognosis but not absolutely contraindicate removal. However, lymph node metastases in area 2 (around the hepatic artery or celiac trunk) are associated with such a poor prognosis than they should be considered a contraindication to resection. Therefore, these patients should be carefully selected and resection should be considered only after confirming stability of the disease or after a good response to systemic chemotherapy. Moreover, obtaining a R0 resection of the intra- and extrahepatic disease should be ensured. DOWNSTAGING OR DOWNSIZING Page 9 of 34 Fig. 4 References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES This concept refers to the process of converting liver metastases that were initially unresectable into resectable with neoadjuvant chemotherapy. New chemotherapy regimens combining 5-fluorouracil, folinic acid and oxaliplatin or irinotecan have succeeded to allow surgery 10 to 30% of patients, and higher numbers are anticipated with the new monoclonal antibodies (cetuximab and bevacizumab). The long-term survival achieved in these patients are almost superimposable to those of patients resected by first intention. Liver surgery should be performed as soon as the disease becomes resectable, without prolonging chemotherapy. Tumor progression during the administration of neoadjuvant chemotherapy should be considered a relative contraindication to resection. Page 10 of 34 Other ways to increase the resection of CRCLM are scheduled two-stage procedures, resection combined with radiofrequency, intraarterial radiotherapy with Yttrium spheres and portal embolization. THE ROLE OF RADIOLOGISTS IN THE MANAGEMENT OF POTENTIALLY RESECTABLE LIVER METASTASES • DIAGNOSIS Early detection and appropriate characterization of the CRCLM are critical to addressing the patient's treatment in order to increase their chances of survival. What the radiologist should contribute to liver surgeon is: • • • • Determine number, size, location and resectability of liver metastases. Possible existence of metastatic lymph nodes. Assess possible extrahepatic disease (abdominal, pelvic, lung). Primary tumor staging in case of synchronous metastases. ULTRASOUND (US) US is performed in selected cases to complement the characterization of liver lesions, making differential diagnosis of cystic and solid, especially in small lesions. Sometimes, it is useful preoperatively to confirm the location before the intraoperative ultrasound. MDCT or MRI In our hospital, the routine imaging technique to evaluate and follow patients with CRC is MDCT. For this reason, it generally consists of a single liver acquisition. If it is previously known the existence or suspect of LM, a triphasic acquisition is planned. If the MDCT study can not confirm the diagnosis of LM and the suspicion persists, liver MRI is performed with nonspecific extracellular gadolinium distribution (dynamic study). In our case we use gadobutrol (Gadovist®). We don't perform always a liver MRI as a first-line imaging study in patients with CRC due to high number of staging and follow-up studies and limited access to MRI (we have only one 1.5T MR scanner in our institution). The realization of a liver volumetry (Fig. 5 on page 23) is reserved for selected patients. It is made from MDCT or MRI with gadobutrol in cases where there is doubt Page 11 of 34 about the postoperative remnant liver and always if # 4 segments resection is required. Insufficient remnant liver volume is considered if it is <25% in healthy livers and <35% in pathological liver (steatosis by diabetics or prior chemotherapy). USE OF MRI USING GADOXETATE (Gd-EOB-DTPA, Primovist®) WITH BOTH DINAMYC AND HEPATOCITE PHASE IMAGES If the diagnosis of CRCLM is confirmed, the patient is presented to the committee. If surgical resection is decided, an MRI with Primovist® (Fig. 6 on page 24) is planned (preferably the same week of the surgical procedure). Page 12 of 34 Fig. 6: Only one CRCLM was found in this patient: a) MDCT after iv contrast; b) MR, STIR transversal image; c) MR, T1-weighted image and d) MR, Fat supression T1weighted image after 30 minutes of iv Primovist® injection. References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES MRI performed with Primovist® is used to confirm with the highest sensitivity the number, size and location of liver metastases in order to avoid unexpected findings during surgery. In the first patients evaluated in our committee before the current protocols established, it was not routinely performed, often due to lack of coordination between the Department of Surgery and Radiology. Thus, we found several discrepancies between the findings of MDCT and MRI with gadolinium compared with findings in surgery, especially in small lesions. These discrepancies have decreased dramatically since we program the MRI with Primovist® in coordination with the surgeons before each surgical resection. MRI with Primovist® acquiring a late hepatobiliary phase increases the sensitivity for detecting liver metastases less than 1 cm compared with standard extracellular gadolinium studies. It is useful to add diffusion-weighted acquisitions to increase diagnostic accuracy. PET-CT It is not routinely performed for the detection of liver metastases because other techniques such as MRI have shown greater sensitivity. It is done in some selected patients for the detection of extrahepatic disease not identified by CT or MRI when resection is being considered. INTRAOPERATIVE ULTRASOUND (Fig. 7 on page 25) It is always performed. Intraoperative ultrasound is done jointly by radiologists and surgeons in our hospital. • TREATMENT PORTAL VEIN EMBOLIZATION (PVE) Fig. 8 on page 26 Page 13 of 34 The PVE is used before surgery to redistribute portal flow toward the future remaining segments liver to increase their size. Thus, the future remnant results in hipertrophy increasing a 10-15% of volume in 3-9 weeks, while in livers with chronic conditions can be lower. It can be done before liver surgery or between a two-stage procedure. The PVE can be percutaneously performed (ultrasound and fluoroscopic guidance) with the patient under conscious sedation in the Interventional Radiology room. Fig. 8: Figures a) and b) are X-ray acquisitions in portal embolization procedure. Figures c) and d) show the end result in a MDCT control. Page 14 of 34 References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES CT-GUIDED RADIOFREQUENCY It is considered a palliative therapy that not replace surgical resection if this is technically feasible. Their results in terms of long-term survival are lower than those of resection, although recently they have obtained comparable survival to 3 years. Radiofrequency only replace surgical resection if the general conditions of the patient discourage the latter. It may be indicated in case of limited peritoneal metastases. In some cases it may be associated with metastases surgical resection when complete resectability is technically difficult or doubtful. This partnership entails lower survival than complete surgical resection although lead to superior survival that the exclusive treatment with RF and chemotherapy. This practice is under evaluation. There are different techniques that ultimately induce coagulative necrosis, obtaining very similar results. We use radiofrequency ablation (RFA), which induces heating of the soft tissues in the vicinity of a monopole antenna that produces an alternating current. Depending on the volume treated, recurrences are described in CRCLM between 12-31%, with a 2.8% rate of major complications and 17% of minor complications. In patients with small tumoral volume, until a 50% survival at 5 years is described, while most of the studies show percentages of approximately 35%. After performing the CRCLM RFA, a thin marginal enhanced ring can be found during late arterial phase until 4-5 months after the procedure. The RFA procedure is considered adequate, if subsequent follow-up after this time shows no enhancement in the portal phase and this ring is disappeared. If there is an increase in the size of the lesion or progressive distortion of the lesion margin after six weeks of the RFA, the existence of local progression should be considered. INTRAOPERATIVE RADIOFREQUENCY Fig. 9 on page 27 Page 15 of 34 When possible, we prefer to perform the RFA in the operating room while surgical resection in lesions that can not be resected, according to the decisions taken in our committee. Fig. 9: Ultrasound-guided radiofrequency ablation procedure in the operating room. References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES INTRA-ARTERIAL CHEMOTHERAPY In case of unresectable tumors, hepatic intra-arterial chemotherapy with floxuridine has produced higher overall response rates but no consistent improvement in survival when compared to systemic chemotherapy. In our hospital we have little experience with this treatment. OUR EXPERIENCE Page 16 of 34 Between october 2009 and september 2013 we collected 42 patients with 50 surgical procedures for resection of CRCLM. 7 patients required a second intervention by hepatic recurrence. One patient underwent 3 surgeries for resection of liver metastases. In our series, 35 resections were performed in men and 15 in women (Fig. 10 on page 28). The mean age of all patients was 63.2 years and the median 64 years (Fig. 11 on page 29). The maximum age was 78 years and minimum 27 years. In men, the mean age was 64.2 years and the median 62 years. In women, the mean age was 61 years and the median 60 years. The number of liver resections increased progressively as the unit of liver surgery has gained more experience, from 3 patients operated in 2010 until 20 patients in 2012 (Fig. 12 on page 30). Also, the experience of radiologists involved in the management of patients has been increasing in the same way, on the one hand regarding the updating of protocols and secondly, to perform more diagnostic procedures (volumetries, MRI with Primovist®) and treatment (ultrasound and intraoperative RFA, PVE). Fig. 13 on page 31 Many patients were operated at first with a single test image (MDCT), mainly due to a lack of coordination and communication between the Department of Surgery and Radiology and the limited experience of the physicians involved. The appearance of a discrepancy between the findings of a single test and those obtained in the operating room forced us to rethink the presurgical imaging algorithms, accelerating our learning curve in both the management of this condition and the workflow of a multidisciplinary team. All cases were operated with at least one MDCT scan and intraoperative ultrasonography. In 9 cases (18%) MRI was performed with gadolinium to confirm the diagnosis of metastases. In 19 cases (38%) MRI was performed with Primovist® as a preoperative study to confirm the number and location of metastases. These cases have steadily increased over the years and in 2013 70% had this study before surgery. 4 patients (9%) underwent PVE to increase liver remnant, being evaluated with a liver volumetry pre- and post treatment to control growth of the future remnant. In 4 patients an intraoperative RFA was performed, all in 2013. Page 17 of 34 Fig. 10 References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES Page 18 of 34 Fig. 11 References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES Page 19 of 34 Fig. 12 References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES Page 20 of 34 Fig. 13 References: RADIOLOGY, SESCAM, COMPLEJO HOSPITALARIO UNIVERSITARIO ALBACETE - Albacete/ES Images for this section: Page 21 of 34 Fig. 2: The surgeon examinates a resected liver metastases with free macroscopic margin in the operating room. Page 22 of 34 Fig. 3: Survival data in patients who have undergone CRC liver metastases resection. Page 23 of 34 Fig. 5: Liver volumetry held in the workstation of our General Electric MDCT, in a patient after CRCLM resection (see metal clips). Two new metastatic lesions were found and a new surgical resection was planned. Page 24 of 34 Fig. 6: Only one CRCLM was found in this patient: a) MDCT after iv contrast; b) MR, STIR transversal image; c) MR, T1-weighted image and d) MR, Fat supression T1-weighted image after 30 minutes of iv Primovist® injection. Page 25 of 34 Fig. 7: Ultrasound equipment used in the operating room. Page 26 of 34 Fig. 8: Figures a) and b) are X-ray acquisitions in portal embolization procedure. Figures c) and d) show the end result in a MDCT control. Page 27 of 34 Fig. 9: Ultrasound-guided radiofrequency ablation procedure in the operating room. Page 28 of 34 Fig. 10 Page 29 of 34 Fig. 11 Page 30 of 34 Fig. 12 Page 31 of 34 Fig. 13 Page 32 of 34 Conclusion Surgical management of patients with CRCLM has begun in the last five years in our center. We treate these patients within a multidisciplinary team (hepatobiliary pathology committee). The management of CRCLM should be customized and, where possible, reviewed by a multidisciplinary team to take the best therapeutic option for patients. With the formation of this multidisciplinary team we have supplied deficiencies that previously existed in our hospital related to the management of these patients. We have been able to solve problems that previously implied to refer many of these patients to other spanish hospitals in near regions such as Madrid, Murcia and Valencia. The accumulated experience of the participants, makes us consider it one of the best tools at our disposal to get the most of our resources in the service of the best care we are able to provide our patients. The implementation of this Committee has meant hours of extra work and effort for its members, thrilled by performing a job well done even in these times of economic crisis that has hit the public health system in Spain and specifically Castilla-La Mancha, and satisfaction after checking every week that this effort translates into a better patient care that attempts increase their quality day after day. The radiologist plays an important role in the diagnosis and follow-up of CRC, with an increasingly relevant role in the interventional treatment of these patients. Personal information References • Abdalla EK et al. Recurrence and Outcomes Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection/Ablation for Colorectal Liver Metastases. Ann Surg 2004; 239: 818 Page 33 of 34 • • • • • • Adam R, Delvar V, Pascal V, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghémard O, Levi F, Bismuth H. Rescue Surgery for Unresectable Colorectal Liver Metastases Downstaged by Chemotherapy. A Model to Predict Long-term Survival. Ann Surg 2004; 240: 644-658 Bipat y cols. Colorectal Liver Metastases: CT, MR Imaging, and PET for Diagnosis-Meta-analysis. Radiology 2005; 237: 123 Durán Jiménez-Rico H y cols. Metástasis hepáticas de origen colorrectal: ¿es posible la cirugía basada en la mejor evidencia clínica?. Cir Esp 2005; 78: 75 King AJ, Breen DJ. Understanding the current status of image-guided ablation for metastatic colorectal disease. Abdom Imaging (2013) 38:1234-1244 Sahani DV, Bajwa MA, Andrabi Y, Bajpai S, Cusack JC. Current status of imaging and emerging techniques to evaluate liver metastases from colorectal carcinoma.Ann Surg. 2014 Feb 6. [Epub ahead of print] Bonanni L, De'liguori Carino N, Deshpande R, Ammori BJ, Sherlock DJ, Valle JW, Tam E, O'Reilly DA. A comparison of diagnostic imaging modalities for colorectal liver metastases. Eur J Surg Oncol. 2014 Jan 15. pii: S0748-7983(14)00007-9. doi: 10.1016/j.ejso.2013.12.023. [Epub ahead of print] Page 34 of 34