Prise en charge des métastases hépatiques synchrones d'origine colorectale

At time of diagnosis, 10 to 25% of patients with colorectal cancer present synchronous liver metastases. The treatment of such patients remains controversial without any evidence based organization. Therapeutic sequences are discussed including chemotherapy, colorectal surgery, liver resection and even radio-chemotherapy for some rectal cancers. In case of resectable liver metastases, preoperative chemotherapy offers the advantage of earlier treatment of micro-metastases as well as evaluation of tumor responsiveness, which can help shape future therapy. In this setting, different surgical strategies can be chosen (classical staged procedures with colorectal surgery followed by liver surgery, simultaneous resections or liver first approach) depending on the importance of the primary and metastatic tumors. The literature remains limited, but the results of these strategies seem identical in term of postoperative morbidity and long-term survival. Staged procedures are preferred in case of major liver resection. Location of the primary tumor on the low or mid rectum will necessitate preoperative long course chemoradiotherapy and a more complex multidisciplinary organization. For patients with extensive liver metastases, non-resectability must be assessed by experienced surgeon and radiologist before treatment and during chemotherapy. In this group of patients, improved chemotherapy regimen associated with targeted therapies and new surgical strategies (portal vein embolization, ablation, staged hepatectomies…) have improved resection rate (15 to 30-40%) and long-term survival. Treatment organization for the primary tumor remains controversial. Resection of the primary to manage symptoms such as obstruction, perforation or bleeding is advocated. For patients with asymptomatic primary a non-surgical approach permits to begin rapidly chemotherapy and obtain a better control of the disease. On the other hand, initial resection of the primary may avoid complications and the need for urgent surgical procedures. Both of these strategies are practiced without definitive evidence supporting one treatment option over the other.     

Évaluation de la réponse thérapeutique après radiothérapie stéréotaxique des lésions tumorales hépatiques

Stereotactic body radiation therapy takes more and more an important place in the therapeutic arsenal of primitive and secondary liver tumours. The administration of ablative radiation doses can result in specific changes to both the tumour and the healthy hepatic parenchyma, relative to conventional radiation therapy, making the assessment of local changes after stereotactic body radiation therapy, in terms of local control and reaction of healthy tissue, often difficult. It is mandatory to standardize and simplify our evaluation criteria to benefit from a better understanding of the effectiveness of this new treatment modality and allow better reproducibility of available imaging exams. This article presents a literature review of the various radiological changes observed after stereotactic body radiation therapy for liver tumours according to the multiple assessment methods used to determine local control. From the data available, we recommend using modified RECIST criteria proposed by the American Association for the Study of Liver Diseases (AASLD), as objective and relevant criteria of local control after stereotactic body radiation therapy for liver tumours.     

Place de la radiothérapie stéréotaxique dans la prise en charge des tumeurs hépatiques

Stereotactic radiotherapy is a high-precision technique based on the administration of high doses to a limited target volume. This treatment constitutes a therapeutic progress in the management of many tumours, especially hepatic ones. If surgery remains the standard local therapy, stereotactic radiotherapy is first dedicated to inoperable patients or unresectable tumours. Patients with moderately altered general status, preserved liver function and tumour lesions limited in number as in size are eligible to this technique. Results in terms of local control are satisfying, regarding primary tumours (notably hepatocellular carcinomas) as metastases stemming from various origins. If treatment protocols and follow-up modalities are not standardized to this day, iconographic acquisition using four-dimensional computed tomography, target volumes delineation based on morphological and/or metabolic data, and image-guided radiotherapy contribute to an oncologic efficacy and an improved sparing of the functional liver. The purpose of this literature review is to report the results of the main works having assessed stereotactic radiotherapy in the management of primary and secondary liver tumours. Technical particularities of this radiation modality will also be described.     

La princesse,le monstre,le héros

Man employs symbols as readily as he breathes. He creates images which help him to grasp the truth. His imagination is as much a tool of perception as are his senses and his emotions. It is structured and rational; it remains coherent even as it expresses itself in sometimes obscure and roundabout ways. It feeds on reality. Cancer is not immune from this practice of symbolisation. It gives rise to collective images, myths and a language. This imaginary construct of cancer is classed as a collective representation and is often said to be archaic and accused of encouraging the taboos which are associated with the disease. However, it is rooted in the reality of the illness itself. What is imagined is not an irrational creation of the mind. With cancer we do not have fantasies, irrationality, collective consciousness and ignorance on one side, and reason, knowledge and truth on the other. The boundaries are porous. Science and the collective imagination each express truths about the disease, but they employ different languages to do so. An understanding of this language of the imagination in relation to cancer is equally useful to the doctors, the nurses and the psychologists of the cancer medicine team. It helps us to understand the patient and communicate with him better and it makes it easier to be close to him in his pathway through the disease. We should recall that every carer also possesses an imaginary world of cancer built up from his own history, culture, experience in life and daily practice. It behoves him to be conscious of it.     

Traitement préemptif de la réactivation de l’hépatite virale B des patients sous chimiothérapie anticancéreuse

It is estimated that one third of the world population has been in contact with the hepatitis B virus (HBV) with a prevalence that varies according to geographic area. This prevalence is more prevalent among patients with neoplasic disease. Thus, the risk of viral reactivation of hepatitis B virus during or after chemotherapy is a clinical problem requiring special attention. Reactivation is defined by a significant increase in viral replication in patients with inactive or “resolved” hepatitis B, often accompanied by an increase in serum transaminase levels. The consequences of HBV reactivation range from an asymptomatic hepatitis to a fulminant hepatic failure and death. HBV reactivation also leads to premature termination of chemotherapy or delay in treatment schedules. Thus, HBV serology (HBsAg, anti-HBc, anti-HBs) is recommended for all patients receiving chemotherapy. Patients with HBsAg and/or HBV DNA positive(s) should receive prophylaxis for HBV reactivation. This preemptive treatment, based on nucleosides/nucleotides analogues, has proved its effectiveness in reducing virus reactivation and mortality. Patients HBsAg negative/anti-HBc positive, receiving no intensive immunosuppressive therapy, close monitoring of transaminases and HBV DNA should be established. Antiviral therapy may be started when HBV reactivation is confirmed. When patients have HBsAg, anti-HBc and anti-HBs negatives, anti-HBV vaccination should be established before the introduction of chemotherapy when possible. A multidisciplinary approach involving at least an oncologist and a hepatologist is still needed for better management of these patients.     

Une tumeur stromale pancréatique : cause rare d’une hémorragie digestive haute

Pancreas is an exceptional location of gastrointestinal stromal tumor and its revelation by a gastrointestinal bleeding has never been reported.We report an original case of cephalic pancreatic GIST complicated by gastrointestinal bleeding due to erosion of the duodenal wall which had required a whipple resection.     

Traitements intra-artériels des carcinomes hépatocellulaires : évidence clinique et perspectives à venir

Intraarterial therapies such as transarterial chemoembolization and radioembolization have revolutionized the management of patients with hepatocellular carcinoma. These therapies achieve not only effective local tumor control but also prolong patient survival. The unique advantage of these minimally invasive treatments consists of the administration of high doses of the antitumor agent directly into the tumor feeding arteries. This selective approach preserves the nontumoral liver parenchyma and limits systemic toxicity. In this paper, we provide a brief overview of current evidence and future perspectives of the most frequently used intraarterial therapies.     

Bases référentielles de la radiothérapie en conditions stéréotaxiques pour les tumeurs ou métastases bronchopulmonaires,hépatiques,prostatiques, des voies aérodigestives supérieures,cérébrales et osseuses

Since decades, stereotactic radiotherapy has spread out worldwide. Published results are very numerous. To clarify obviousness among all the publications, this recommendation review was written. Voluntarily, authors limited analysis of international best evidence literature on malignant tumors of lung, liver, prostate, head and neck, and metastasis of bone and brain. These data could be used to advance standardization and quality improvement of treatments performed in the nationwide radiotherapy departments and can provide useful guidance for centers worldwide.     

Développement des greffes haplo-identiques chez l’adulte atteint d’une hémopathie maligne

The possibility to use a family donor sharing only one haplotype with recipient affected by hematological malignancy has been searched from many years because it allows having a donor in every case for every patient. At the beginning, this kind of transplantation was considered too toxic, but after the development of specific strategies of conditioning regimens and ex vivo T-cell depletion, its feasibility and efficacy has been proved, mainly for acute leukemia. However, these haploidentical programs with ex vivo T-cell depletion need of sophisticated and dedicated laboratories and are characterized by frequent infectious complications and relapse, because of delayed immune reconstitution. For these reasons, many groups have developed alternative program for haploidentical transplantation, without ex vivo T-cell depletion, obtaining encouraging results in haematological malignancies. In this review, we analyze data produced by different groups, underscoring their principal characteristics.     

Techniques d’irradiation mammaire complexe : radiothérapie conformationelle tridimensionnelle mono-isocentrique et nomothérapie hélicoïdale

Purpose

To evaluate the dosimetric contribution of helical tomotherapy for breast cancers compared with conformal radiotherapy in mono-isocentric technique.

Biosimilaires d’héparine de bas poids moléculaire: quel degré de similarité pour quel bénéfice clinique ?

The development of biosimilar versions of low molecular weight heparins (LMWHs) raises a real medical concern. To illustrate our concerns regarding biosimilars, we chose the example of the specific clinical setting associated to the antithrombotic management of the acute coronary syndromes (ACS). In this specific indication, the LMWH enoxaparin has consistently shown its superiority in terms of efficacy when compared to unfractionated heparin (UFH) and in some direct or indirect comparison to other LMWHs. This is because of these particular clinical evidences that enoxaparin was considered as the gold standard for anticoagulation in cardiology and became almost universally used in ACS management. We are concerned by the fact that some patients might be treated by a generic copy of enoxaparin, on the basis of simplified criteria which were shown not to be specific enough to enable differentiation among LMWHs, thus, are unable to differentiate between enoxaparin and a biosimilar, in particular. Without any evidence from clinical trials, especially in ACS indication, we believe it is hard to ensure that the benefitrisk ratio between enoxaparin and its copy be equivalent. Indeed along with efficacy, safety issues have to be taken into consideration: biosimilars consist of glycan chain mixtures that exhibit specific immunoallergic features. Furthermore, the contamination of raw material with other components or other glycans during molecule extraction may trigger potentially harmful immune reactions.     

Impact dosimétrique du blocage respiratoire dans le traitement du carcinome hépatocellulaire par irradiation de conformation

ObjectiveTo evaluate the dosimetric impact of breath-hold during radiotherapy of hepatocellular carcinoma (HCC) and to determinate the optimal respiratory phase for treatment (exhale or inhale).Patients and methodsTwo CT scans were performed in inhale and in exhale in 20 patients with HCC. The GTV was delineated slice by slice on the inspiration breath hold acquisition (GTV_insp) and on the expiration breath hold acquisition (GTV_exp). The superposition of two GTV allowed to obtain the global GTV (free respiration). PTV was defined by adding a margin of 1 cm around each GTV. The liver, the duodenum, the two kidneys, the stomach and the spinal cord were delineated on each acquisition as organs at risk (OAR). Three dosimetric plans were created on inspiration, expiration and on global PTV.ResultsThe mean reduction in the volume of PTV with conformal radiation therapy (3D-CRT) in the hold-breath group compared to the free respiration group was of 33.5 ± 11.9%. The average difference of V50%, V20, V30, V40 and V50 were around 4% in favor of the breath hold. The average value of NTCP was 8.9% in free respiration, 4.5% in expiration and 3.2% in inspiration. Further improvement in the OARs dosimetric parameters for the breath hold was observed.ConclusionCompared to the conformal radiotherapy with free respiration, the breath-hold allows reducing the volume of the PTV and the doses to the healthy liver and organs at risk. The use of this modality during different radiotherapy techniques (3D-CRT, IMRT and stereotactic) may be recommended. No difference in dosimetric value has been observed between the breath hold in expiratory and inspiratory phases.     

Microenvironnement et angiogenèse des métastases hépatiques d’origine colorectale : implications chirurgicales

Stephen Paget's proposed an original “seed and soil” theory, with organ-preference patterns of tumor metastasis resulting in interaction between metastatic tumor cells and their specific microenvironment. There is many experimental and clinical data showing that this theory is validated. More recently, it has been suggested that early changes in the microenvironment at the distant sites, could be induced by the primary tumor, reported as “pre-metastatic niche” formation. Tumor cells could produce growth factors, cytokines which could facilitate the recruitment and the mobilization of the bone marrow-derived endothelial progenitor cells, and thus necessary for the tumor neovascularization and metastasis growth. Although the clinical value of the concept of the premetastatic niche is not yet elucidated, these data could encourage surgeons to perform the colorectal surgery first and then the liver surgery, in patients with synchronous colorectal liver metastases. The reciprocal interactions between primary tumor and microenvironment at the distant sites are therefore determinant for tumor progression. Taken together, the microenvironment is an important therapeutic target and surgeons and oncologist could discuss the choice of different surgical strategy for patient with synchronous colorectal liver metastases regarding the interaction with the microenvironment affected by primary tumor resection.     

Intérêt de l’imagerie fonctionnelle TEP dans les tumeurs hépatobiliaires primitives malignes

Primarymalignant hepatobiliary tumors include hepatocellular carcinoma, cholangiocarcinoma, and gallbladder cancer. The importance of PET imaging for these malignancies varies depending on the location and the type of the tumor. The value of PET for the detection of primitive hepatobiliary tumors is still controversial but very useful for staging and prognosis.