[«Watch and Wait¼ strategy in the management of rectal adenocarcinoma]. / Stratégie «Watch and Wait¼ dans la prise en charge des adénocarcinomes du rectum.

Currently, the standard management of locally advanced adenocarcinoma of the middle and lower rectum consists in first intention of pre-operative radio-chemotherapy. This treatment is then usually followed by rectal surgery with removal of the mesorectum. The local recurrence rate is quite low, but at the cost of a non negligible morbidity (urinary, anal and sexual functional sequelae). This raises the question of a possible sparing of surgery and therefore organ preservation in well selected patients with a complete response after radio-chemotherapy. The Brazilians are pioneers in this field. Already in 2004, their publications suggested that the «Watch and Wait¼ strategy was safe and effective in patients with a complete clinical response. Other publications have followed and tend to confirm that there is no oncological risk in proposing a «watch and wait¼ strategy for these well selected patients in complete clinical, endoscopic and iconographic remission on the basis of magnetic resonance imaging (MRI). In these conditions, an attentive surveillance strategy allows to avoid operative morbi-mortality without oncological compromise. Monitoring is therefore multi-modal, clinical and endoscopic, but also based on MRI.

Actuellement, la prise en charge classique de l'adénocarcinome localement avancé du moyen et du bas rectum consiste d'abord en de la radio-chimiothérapie préopératoire. Ce traitement est ensuite habituellement suivi d'une chirurgie rectale avec exérèse du mésorectum. Le taux de récidive locale est assez bas, toutefois au prix d'une morbidité non négligeable (séquelles fonctionnelles urinaires, anales et sexuelles). Se pose alors la question d'une éventuelle épargne chirurgicale et donc d'une préservation d'organe chez des patients bien sélectionnés en réponse complète après radio-chimiothérapie. Les chercheurs brésiliens font office de pionniers dans le domaine. Déjà en 2004, leurs publications suggéraient que la stratégie de surveillance rapprochée («Watch and Wait¼) était sûre et efficace chez les patients en réponse clinique complète. D'autres publications ont suivi et tendent à confirmer qu'il n'y a pas de risque oncologique à proposer une surveillance attentive chez ces patients bien sélectionnés, en rémission complète clinique, endoscopique et iconographique sur base de la réalisation d'une imagerie par résonance magnétique (IRM). Dans ces conditions, une stratégie de surveillance attentive permet d'éviter la morbimortalité opératoire sans compromis oncologique. La surveillance est donc multi-modale: clinique et endoscopique, mais également basée sur l'IRM.

[Multidisciplinary management of the primary liver cancers]. / Prise en charge multidisciplinaire des tumeurs malignes primitives du foie.

In Belgium and around the world, the incidence of primary malignant liver tumours is increasing, both for hepatocarcinoma and cholangiocarcinoma. Their curative treatment is based on multidisciplinary and specialized care, of which surgery (including liver transplantation) remains the cornerstone, often associated with other logoregional treatments, as radioembolisation, radiofrequency ablation, and chemoembolisation. For advanced cases, the prognosis remains poor, in particular due to a certain chemoresistance of these tumours. New treatments include targeted therapies (including various tyrosine kinase inhibitors) and immunotherapy. A specialized multidisciplinary discussion is therefore necessary to define the best therapeutic management, individualized to each patient. In this article, the authors review the most recent data relating to the treatment of hepatocarcinoma and cholangiocarcinoma.

En Belgique et dans le monde, l'incidence des tumeurs malignes primitives du foie augmente, tant pour l'hépatocarcinome que le cholangiocarcinome. Leur traitement curatif repose sur une prise en charge multidisciplinaire et spécialisée, dont la chirurgie (incluant la transplantation hépatique) reste la pièce angulaire, souvent associée à d'autres traitements logo-régionaux (radioembolisation, radiofréquence, chimio-embolisation). Pour les cas avancés, le pronostic reste sombre, notamment en raison d'une certaine chimiorésistance de ces tumeurs. Les nouvelles prises en charge incluent des thérapies ciblées (notamment, divers inhibiteurs de tyrosine kinase) et de l'immunothérapie. Une discussion pluridisciplinaire spécialisée est donc nécessaire pour définir la meilleure prise en charge thérapeutique, individualisée pour chaque patient. Dans cet article, les auteurs revoient les données récentes relatives au traitement de l'hépatocarcinome et du cholangiocarcinome.

[Mesogastric desmoid tumor, a rare entity]. / Tumeur desmoïde mésogastrique, une entité rare.

Desmoid tumors, also called «agressive fibromatosis¼, are rare soft tissue tumors, locally invasives with a high recurrence tendency but non metastatic. They arise mainly in people with sporadic somatic CTNNB1 gene mutation or with history of trauma, surgery or during pregnancy. These tumors are often extra-abdominal but may also develop in the abdominal wall or, more rarely, in the mesentery or retroperitoneum. It is hard to distinguish local malignancy recurrence with another type of tumor such as desmoid tumor during the follow-up of intra-abdominal resected malignancy. Even if rare, desmoid tumors must be part of the differencial diagnosis, a fortiori in the context of a surgical history. Clinical behavior, high potential of local invasion and recurrency risk of the tumor must be at the center of the therapeutic decision. A conservative approach is totally justified at the price of a close clinical and radiological follow-up.

Les tumeurs desmoïdes, aussi appelées «fibromatoses agressives¼, sont des tumeurs rares des tissus mous, localement invasives et hautement récidivantes, mais ne présentant toutefois pas de potentiel métastatique. Elles surviennent principalement chez des patients ayant une mutation sporadique somatique du gène CTNNB1 ou ayant des antécédents de traumatisme, de chirurgie ou durant une grossesse. Ces tumeurs sont, le plus souvent, de localisation extra-abdominale, mais peuvent aussi se développer au sein de la cavité abdominale, en général aux dépens des parois et, plus rarement, du mésentère ou du rétropéritoine. Dans le contexte du suivi de patients opérés d'un cancer intra-abdominal, il est difficile de distinguer une récidive du cancer primitif d'un autre type de tumeur. Aussi rares soient les tumeurs desmoïdes, elles doivent faire partie du diagnostic différentiel, a fortiori dans un contexte postopératoire. Les répercussions cliniques de la tumeur, le haut potentiel invasif local ainsi que le risque de récidive après traitement doivent être au centre de la décision thérapeutique. Une prise en charge conservatrice est tout à fait indiquée, au prix d'un suivi clinique et radiologique rapproché.

[Atypical metastasis from a colorectal cancer : the pons is undermined !] / Métastase atypique d'un cancer colo-rectal : le pont est miné !

Brain metastases occur in 1 to 4 % of patients with colorectal cancer and are unique in 0.5 % of them. Because of their infrequent nature, brain imaging is not recommended in the systematic follow-up of these patients. We report here an exceptional case of a unique brain metastasis in a very unusual position. An 82-year-old patient with a colorectal cancer of the splenic angle that was treated with surgery and adjuvant chemotherapy, developed a series of neurological symptoms over four to six weeks: difficulty swallowing, loss of strength in the four limbs and balance disorders. These symptoms urged the performance of a nuclear magnetic resonance to exclude a central neurological lesion. MRI revealed a nodular tumor of 20 millimeters in the major transverse axis and 17 millimeters in the cerebro-caudal axis, located on the ventral portion of the protuberance. Because of its localization, surgery was not possible and the lesion was treated with Cyberknife radiosurgery. Thanks to the treatment, the lesion decreased in size and the symptoms improved significantly. Despite an initially very poor prognosis in view of the localization of the metastasis, the patient is alive and in excellent general condition more than eight months after the diagnosis of recurrence.

Les métastases cérébrales surviennent chez 1 à 4 % des patients atteints de cancer colo-rectal et sont uniques chez 0,5 % d'entre eux. De par leur caractère peu fréquent, une imagerie cérébrale n'est pas recommandée dans le suivi systématique de ces patients. Nous rapportons ici un cas exceptionnel de métastase cérébrale unique de localisation atypique. Un patient de 82 ans, suivi pour un cancer de l'angle splénique du côlon traité par chirurgie de résection et chimiothérapie adjuvante, a développé en quatre à six semaines une série de symptômes neurologiques : troubles de la déglutition, perte de force des quatre membres et troubles de l'équilibre. Ces symptômes ont motivé la réalisation d'une résonance magnétique nucléaire afin d'exclure une lésion neurologique centrale. L'IRM a mis en évidence une lésion tumorale nodulaire de 20 millimètres de grand axe transverse et 17 millimètres d'axe céphalo-caudal, située sur la portion ventrale de la protubérance. Inaccessible à la chirurgie, la lésion a été traitée par radiothérapie stéréotaxique CyberknifeTM. Grâce au traitement, la lésion a régressé et les symptômes se sont nettement améliorés. Malgré un pronostic initial extrêmement mauvais au vu de la localisation de la métastase, le patient est vivant et en excellent état général à plus de huit mois du diagnostic de récidive.

WITHDRAWN: A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

The article has been withdrawn at the request of the authors and editor because of incorrect authorship, which is considered a form of unethical publication. The Publisher apologizes for any inconvenience this may cause.

[Comprehensive therapeutic strategy for localized esophageal cancer. Second part : interest of multimodal approaches with or without surgery]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 2ème partie : l'intérêt des approches multimodales avec ou sans chirurgie.

In recent years, the treatment of esophagus cancer has been completely changed, thus competing the dogma of surgery as the cornerstone treatment. Multimodality treatments as radio-chemotherapy directly followed by surgery, or delayed surgery, significantly improve patient survival compared to surgery alone. Neoadjuvant radiochemotherapy is associated with a higher complete pathologic response rate and improved survival compared to chemotherapy alone. Immediate surgery after radio-chemotherapy is challenged for patients who present a complete clinical response, especially in case of squamous cell carcinoma. Indeed, systematic resection is associated with a significant postoperative mortality rate and has not proven any survival advantage in complete clinical responders as opposed to delayed resection in case of locally persistent or recurrent disease. In squamous cell carcinoma, this could lead to organ preservation, thus avoiding the mortality and durable functional impairment of esophagectomy. This review will discuss the positioning of the multimodality treatment strategy with neoadjuvant radiochemotherapy and chemotherapy and also the strategy of organ preservation.

Depuis quelques années, le traitement du cancer de l'œsophage est en pleine mutation, bousculant ainsi le grand dogme de la chirurgie comme pierre angulaire du traitement. Par rapport à la chirurgie seule, les traitements multimodaux de radiochimiothérapie suivis, directement ou de façon différée, par la chirurgie améliorent significativement les chances de survie prolongée des patients. Comparée à la chimiothérapie néodjuvante, la radiochimiothérapie néoadjuvante démontre un taux de réponse pathologique complet plus élevé qui résulte en une survie prolongée. Chez les très bons répondeurs cliniques, la question de la place de la résection chirurgicale d'emblée est remise en question, surtout pour les carcinomes épidermoïdes. Chez ces patients, la résection systématique par rapport à un acte différé n'offre pas d'avantage en survie, expose le patient à un risque de mortalité significatif alors qu'un certain nombre de patients n'auront jamais à être opérés. Le seul bénéfice actuellement démontré de la résection est une amélioration du contrôle local; or, le devenir du patient est principalement lié à la récidive métastatique. Dans cette revue, nous positionnons et discutons la place des différents traitements multimodaux, chimiothérapie et radiochimiothérapie néoadjuvantes, ainsi que la place de la préservation d'organe par rapport à une chirurgie d'emblée après une radiochimiothérapie.

[Comprehensive therapeutic strategy for localized esophageal cancer]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 1ère partie : le point sur les approches chirurgicales et non chirurgicales.

Esophageal cancers represent a highly heterogeneous entity mixing two different tumour types : AdenoCarcinoma (ADC) and Squamous Cell Carcinoma (SSC). Developing in the same organ, they are very often considered as a unique pathology and, consequently, the same therapeutic strategy is indiscriminately applied. Esophageal cancer treatments are particularly complex and require a multidisciplinary approach. Despite impressive advances in the tumour statidifaction, surgery, radiotherapy and chemotherapy, the overall prognosis remains grim even at an early stage of the disease. In order to improve the treatment of esophageal cancers and the patient’s survival, we need to consider that ADC and SCC represent two different pathologies requiring specific therapeutic strategies. This review in two parts will present recent data from clinical trials under the scope of tumour histology to set up dedicated therapeutic strategies. In this first part, we explain the restricted role of surgical resection, the prognostic factors and the results of exclusive combined chemotherapy and radiation in localized esophageal cancer.

Les cancers de l'œsophage concernent deux entités d'histologie et de pathogenèse différentes : les carcinomes épidermoïdes (CE) et les adénocarcinomes (ADC). Ils se développent dans un même organe et sont souvent considérés comme une seule et unique maladie avec, comme conséquence, une stratégie thérapeutique identique. Leur traitement est complexe et requiert une prise en charge multidisciplinaire. Bien que les techniques de mise au point de la pathologie, de traitement par chirurgie, de radiothérapie et de chimiothérapie se soient améliorées, le pronostic de la maladie reste péjoratif, même à un stade précoce. L'amélioration de la prise en charge et de la survie des patients nécessite de considérer les CE et les ADC comme deux pathologies distinctes, impliquant des approches thérapeutiques qui leur soient spécifiquement dédiées. Cette revue en deux parties analyse les différents aspects thérapeutiques des cancers de l'œsophage sous l'angle de l'histologie et permet de dégager des stratégies spécifiques. Cette première partie est consacrée aux limites de la résection chirurgicale, aux facteurs pronostiques et aux résultats des traitements par radio-chimiothérapie exclusive des cancers localisés.

A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

BACKGROUND AND STUDY AIMS: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. PATIENTS METHODS: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. RESULTS: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. CONCLUSIONS: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

[Evolution in the therapeutic strategy of localized resectable pancreatic ductal adenocarcinoma]. / Evolution dans la prise en charge de l'adénocarcinome du pancréas localisé estimé résécable.

Pancreatic ductal adenocarcinoma is characterized by a high rate of early metastatic relapse. Surgical resection is still recognized as the cornerstone upfront therapy. However, reported 5 years survival rates are inferior to 20-25% even when surgery is followed by chemotherapy. Margins involvement on the surgical specimen (50 to 85%) and lymph node involvement (around 70%) both strongly impact survival. Median survivals are close to those of locally advanced diseases treated by chemotherapy or chemoradiotherapy, 15 to 16 months. This review focuses on adverse prognostic factors, post-operative outcomes and their impact on multimodality therapy completion rates and survivals in patients undergoing upfront surgery. Current data and emerging results from neoadjuvant series could lead to a change in the therapeutic strategy.

[CRITICAL VIEWPOINT ON THE CURRENT APPROACH OF LOCALIZED PANCREATIC DUCTAL ADENOCARCINOMA]. / COMMENT JE TRAITE ... Point de vue critique sur l'approche actuelle du cancer du pancréas localize.

Surgical resection followed by chemotherapy is the actual standard of care for localized, deemed resectable, pancreatic ductal adenocarcinoma. Despite a better selection of surgical candidates and the actual performance of expert teams, the proportion of patients with a prolonged survival has not been ameliorated during the last three decades. The morphological determinants of resectability are the subject of limitations. In the future, only a better understanding of the biological process, an earlier diagnosis of purely localized disease and more efficient systemic therapies may lead to a better prognosis. Meanwhile, taking into account the prognostic factors associated with a lower chance of cure is currently a matter of debate. The optimal therapeutic sequence, being a surgery-first or a neoadjuvant approach is controversial. The theoretical advantages of preoperative chemotherapy eventually associated with chemo-radiation are demonstrated in other tumours and applicable to pancreatic cancer without any excess of operative mortality, early progression rates and, on the contrary with positive survival data. The completion rates of multi-modal therapy are in favour of the preoperative approach, which also gives the opportunity to select the best candidates for surgical resection.

[Chemotherapy of ovarian cancer: state of the art]. / Traitement chimiotérapique actuel du cancer de l'ovaire.

Epithelial ovarian cancer is frequently diagnosed at advanced-stage disease and chemotherapy is nearly always required. Optimally debulked patients may need adjuvant chemotherapy while, most of the time this chemotherapy will be given to those with advanced-stage disease. Also relapses will be treated differently whether they occur early or late in the course of the disease. This paper reviews medical treatment modalities according to stage based on published data. Maintenance and consolidation treatments are also discussed. Finally a brief insight into new therapeutic tools is also given.