[Chronic autoimmune gastritis : a multidisciplinary management]. / La gastrite chronique auto-immune : une prise en charge multidisciplinaire.

Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.

La gastrite chronique auto-immune (GAI) est un continuum d'altérations de la muqueuse gastrique incluant : atrophie, métaplasie intestinale, dysplasie et, enfin, la survenue d'une néoplasie (tumeurs neuroendocrines [NETs] gastriques et adénocarcinome). L'association avec la maladie de Hashimoto et de Graves-Basedow est connue comme syndrome thyrogastrique auto-immun. Alors que l'Helicobacter pylori (Hp) peut s'associer avec la GAI, le rôle du microbiote gastrique est mal défini. L'hypochlorhydrie gastrique détermine une malabsorption de micronutriments (fer, magnésium, calcium, vitamine B12) et de médicaments (thyroxine et autres). L'anémie de Biermer est favorisée par le déficit de production du facteur intrinsèque pariétal, contribuant à la malabsorption de B12. Un rapport diminué de pepsinogène I/II, une augmentation de la gastrine, la présence d'anticorps anti-cellule pariétale, les anticorps anti-facteur intrinsèque et la sérologie pour Hp contribuent à révéler précocement le diagnostic de GAI. L'endoscopie haute définition, associée à la chromoendoscopie virtuelle, semble prometteuse dans le diagnostic et dans le suivi. Le traitement des NETs gastriques de type 1, favorisées par la GAI, inclut : la résection endoscopique/chirurgicale, les analogues de la somatostatine et l'antagoniste de la gastrine nétazépide. Nous résumons ici les avancées diagnostiques et thérapeutiques dans la GAI et dans les affections associées : elles impliquent, de façon multidisciplinaire, l'ensemble des praticiens.

[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.

[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.

[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.

[Radiotherapy in rectal cancer: when, why and how?]. / La radiothérapie dans le cancer du rectum: quand, comment et pourquoi?

Since several decades, radiotherapy plays a crucial role in the management and local control of the rectal adenocarcinoma. The local recurrences pattern of the rectal tumor has completely changed with the systematic use of the Total Mesorectal Excision surgery (TME). In this context, the rate of radiotherapy needs to be reviewed. In this article we propose an overview of the main studies using radiotherapy in a pre- or post-operative setting in the context ofTME surgery. This will help to better define the indications of radiotherapy in rectal cancer.

[Radiotherapy for elderly patient with rectal cancer: which benefit?]. / La radiothérapie dans le cancer du rectum chez la personne âgée: quel bénéfice pour quel traitement?

Age acts as a major risk factor of cancer. In the near future, with the aging of the population, we will treat more and more elderly patients with oncologic disease. Unfortunately, these patients are often excluded from randomized trials. How can we, therefore, define guidelines for this particular population of patients? Moreover, older patients often present multiple morbidities synchronously with the oncologic disease. This constellation of diseases makes the therapeutic strategy even more difficult. The highest incidence of rectal cancer is observed at 80 years old or above. This is significantly older than the mean age of the population included in clinical trials. Although, the prognosis of young patients with rectal cancer has improved over the past few decades, this is not the case for patients over 75 years old. A geriatric evaluation, as a part of a multidisciplinary approach, may allow to better select patient able to benefit from a combined treatment. Radiotherapy plays a crucial role in the treatment of rectal cancer. There are no solid data currently available on the real impact of radiotherapy on survival in an elderly population with rectal cancer. Do these patients really benefit from this treatment and what is the impact of radiotherapy on their quality of life? This review will try to give some answers to these important questions.

[The thyrogastric syndrome: its effects on micronutriments and gastric tumorigenesis]. / Le syndrome auto-immun thyro-gastrique: ses effets sur les micronutriments et la tumorigenèse gastrique.

The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases illustrating the spectrum of pathogical features of TAS. The first case associates Hashimoto's thyroiditis and anemia perniciosa,and develops a gastric neuroendocrine tumor during follow up. The second case presents with a Graves' disease and an autoimmune reversible gastritis, secondary to Helicobacter pylori. Whereas type III autoimmune polyendocrinopathy is rare, TAS is frequent in our experience. Some 13% (32/240) of patients that we have prospectively followed affected with thyroiditis have also autoimmune gastritis. Helicobacter pylori is clearly implicated in 16% of autoimmune gastritis cases. Infection, malabsorption and gastritis are potentially reversible after bacterial eradication treatment. In the other 84% of gastritis patients, no histological or serological proof of Helicobacter pylori is found. Gastric autoimmunity is then irreversible, leading to gastric severe atrophy, hypochlorhydria and hypergastrinemia. Hypergastrinemia stimulates enterochromaffin cell hyperplasia, possibly progressing to neuroendocrine tumors. We propose a diagnostic approach to improve the characterization of TAS. We review the literature on the subject and discuss some interesting animal models of infectious gastric autoimmunity.

Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study.

BACKGROUND: Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in locally advanced rectal cancer (LARC). To evaluate in LARC patients, the feasibility and efficacy of a short intense course of induction oxaliplatin before preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Patients with T2-T4/N+ rectal adenocarcinoma were randomly assigned to arm A-preoperative CRT with 5-fluorouracil (5-FU) continuous infusion followed by surgery-or arm B-induction oxaliplatin, folinic acid and 5-FU followed by CRT and surgery. The primary end point was the rate of ypT0-1N0 stage achievement. RESULTS: Fifty seven patients were randomly assigned (arm A/B: 29/28) and evaluated for planned interim analysis. On an intention-to-treat basis, the ypT0-1N0 rate for arms A and B were 34.5% (95% CI: 17.2% to 51.8%) and 32.1% (95% CI: 14.8% to 49.4%), respectively, and the study therefore was closed prematurely for futility. There were no statistically significant differences in other end points including pathological complete response, tumor regression and sphincter preservation. Completion of the preoperative CRT sequence was similar in both groups. Grade 3/4 toxicity was significantly higher in arm B. CONCLUSIONS: Short intense induction oxaliplatin is feasible in LARC patients without compromising the preoperative CRT completion, although the current analysis does not indicate increased locoregional impact on standard therapy.

[Lynch syndrome and microsatellite instability: a review]. / Le syndrome de Lynch et l'instabilité des microsatellites: revue de littérature.

Microsatellite instability (MSI) phenotype occurs in approximately 15 to 24% of colorectal cancer (CRC) patients and may be sporadic or hereditary. It reflects a mutator phenotype in the tumor due to a lack of mismatch repair system. MSI is indeed one of the characteristics of CRCs occurring in Lynch syndrome and some sporadic cases. CRCs with MSI have a better prognosis than CRCs with microsatellite stability (MSS). This is explained partly by a more important anti-tumor immune response and by apoptosis of tumor cells in which mutations accumulate. However, in some retrospective studies, microsatellite instability in stage II CRCs was associated with no benefit to or even a deleterious effect of 5-FU alone based adjuvant therapy. Nevertheless, results obtained in stage III CRCs with FOLFOX type adjuvant chemotherapy remain favorable in retrospective studies.

Esophageal cancer surgery in patients older than 75: long term results.

PURPOSE: The purpose of this study was to evaluate short and long term results after esophageal cancer resection in patients older than 75. METHODS: We retrospectively analyzed the database of esophageal cancer surgically treated in our department between January 2003 and December 2009 to identify patients older than 75. The preoperative, operative, postoperative and long term characteristics were analyzed. RESULTS: Among 137 patient, 23 were older than 75. The histological subtype was adenocarcinoma in 100%. The surgical techniques were a "Lewis-Santy" procedure in 43%, a trans-hiatal resection in 22%, a "Sweet" procedure in 13%, a stripping in 13% and a McKeown procedure in 9%. The in-hospital postoperative mortality was 13%. The in-hospital postoperative morbidity (Dindo-Clavien Grade >2, deceased patients included) was 26%. In univariate analysis, no statistically significant risk factor of morbidity was found. A Charlson Comorbidity Index >2 was, in univariate analysis, the sole risk factor of postoperative mortality (p = 0.0362). The mean hospital stay was 22 +/- 12 days. The median survival was 24.2 months. The 5-year overall survival was 39% and the 5-year disease free survival was 26%.57% of long-term deaths were not cancer related. CONCLUSION: Esophageal surgery performed in selected patients older than 75 has an acceptable morbidity and mortality but when a severe complication occurs, it leads to death in half of the cases. Surgery enables a long term survival benefit. This study confirmed our attitude of not considering age as a contra-indication for esophageal surgery but rather considering general status, self-reliance and associated comorbidities for patients' selection.

High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma.

Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1alpha after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1alpha expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1alpha suggesting a potential role of HIF-1alpha in CXCR4 and CXCR7 transcription activation. Patients with CXCR4(high) tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with a CXCR7(high)/CXCR4(high) [corrected] tumour had a significantly shorter DFS and OS than patients with a CXCR4(low)/CXCR7(low) [corrected] tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose.

Feasibility of radiotherapy with concomitant gemcitabine and oxaliplatin in locally advanced pancreatic cancer and distal cholangiocarcinoma: a prospective dose finding phase I-II study.

BACKGROUND: The prognosis of pancreaticobiliary tumors is poor. The aim was to assess the feasibility of radiotherapy (RT) and concomitant gemcitabine and oxaliplatin in locally advanced pancreatic cancer and distal cholangiocarcinoma. PATIENTS AND METHODS: Twenty-two patients with locally advanced pancreatic (n = 17) or biliary tract cancer (n = 5) were included. They received two cycles of gemcitabine/oxaliplatin followed by 5 weeks of RT in combination with a weekly fixed dose gemcitabine and an escalating dose of oxaliplatin from 40 up to 70 mg/m(2). National Cancer Institute-Common Toxicity Criteria 3.0 was used to score weekly the treatment-related toxicity. RESULTS: The patients treated at a dose of 40 mg/m(2) of oxaliplatin had no dose-limiting toxicity. At 50 mg/m(2), two patients developed grade 4 thrombocytopenia. Nine patients received 60 mg/m(2), one developed grade 4 thrombocytopenia. Grade 4 thrombocytopenia in two patients and grade 3 diarrhea in one patient were observed with 70 mg/m(2). Median time to progression was 8 months and median overall survival was 17 months. CONCLUSIONS: RT in combination with gemcitabine and oxaliplatin is feasible in patients with locally advanced pancreaticobiliary cancer. The reported time to progression underlines the potential activity of this regimen. The dose of 60 mg/m(2) of oxaliplatin can be considered as the recommended dose.

[Monoclonal antibodies therapies for colorectal cancer: cétuximab, panitumumab and bevacizumab]. / Apports des anticorps monoclonaux dans le traitement du cancer colorectal: cétuximab, panitumumab et bévacizumab.

Colorectal cancer is the third most common form of cancer in Europe, Its prognosis is poor, since median survival time for metastatic patients is about 20 months. Progresses in molecular biology have lead to significant improvement in the management of metastatic colorectal cancer with targeted therapies. The monoclonal antibodies anti-EGFR and anti-VEGFR improve the overall and the progression-free survival. The anti-EGFR antibodies (cétuximab and panitumumab) have been marketed in Belgium, as monotherapy or in association with chemotherapy (FOLFIRI) for third line use in patients with wild type K-ras. The anti-VEGFR bevacizumab is the standard first line treatment in metastatic colorectal cancer with irinotecan based chemotherapy. For the future, the place of monoclonal antibodies therapies in adjuvant or in first line settings and the value of combining targeted therapies have to be further defined.

[Colorectal cancer screening: an absolute necessity and a concrete reality in the French community]. / Le dépistage généralisé du cancer colorectal: une absolue nécessité et une réalité imminente en Communauté française.

Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed to average risk patients in the general population. A total colonoscopy will be performed if FOBT is positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multi-disciplinary program.

[Treatment of (unresectable) hepatocellular carcinoma at an intermediate or advanced stage]. / Straitement des carcinomes hépatocellulaires à un stade intermédiaire ou avancé.

Hepatocellular carcinoma is the main primitive tumor of the liver. It occurs in the setting of liver cirrhosis in more than 90% of the cases in developing countries. The prognosis depends on the size, number and extension of the tumor as well as on the severity of the underlying liver disease. The Barcelona Clinic Classification takes into account these different parameters and helps the clinician in the therapeutic decision. Some patients (around 25%) are amenable to therapy with a curative intent (liver transplantation, resection, destruction by radiofrequency). In patients with hepatocellular carcinoma at an intermediate stage, lipiodolized chemoembolization gives a survival advantage in comparison with placebo. No conventional regimen of chemotherapy has a proven survival benefit. In patients with a hepatocellular carcinoma at an advanced stage, sorafenib, an oral multi-targeted kinase inhibitor, is the first compound to demonstrate a significant effect on survival free of disease progression in a selected group of patients. Its toxicity profile is particularly favourable. Combination of surgical and medical therapies should be properly evaluated in clinical trials in the near future.

[Palliative management of hepatocarcinoma with sorafenib (Nexavar). Results of the SHARP study (sorafenib hepatocarcinoma assessment randomized protocol trial)]. / L'étude clinique du mois traitement de l'hépatocarcinome au stade palliatif par sorafénib (Nexavar). Résultats de l'étude SHARP (sorafenib hepatocarcinoma assessment randomized protocol).

Curative management of early-stage hepatocarcinoma may include partial hepatic resection, liver transplantation or tumoral necrosis using radiofrequency ablation or alcoholisation. Until recently, no efficient therapeutic mean was available for advanced hepatocarcinoma. Sorafenib (Nexavar, Bayer) is a multikinase inhibitor that decreases tumoral proliferation and angiogenesis, and increases apoptosis in many cancer models. The results of a phase 3 randomized, multicentric, study, entitled SHARP, have now demonstrated that sorafenib increases survival in patients with advanced hepatocarcinoma developed in Child A cirrhosis. Mean survival gain was a little less than 3 months, without any radiologic response or improvement in the delay before symptomatic progression of the disease. The monthly cost of sorafenib is a little more than 5,000 euros. It is now crucial to evaluate the potential role of sorafenib in adjuvant therapy after liver resection or radiofrequency ablation of hepatocarcinoma. The CHU of Liège is taking part to a randomized, multicentric study evaluating the use of sorafenib after liver resection or radiofrequency ablation for hepatocarcinoma. Another future evaluation could be the association of sorafenib with other antitumoral agents.

[Colorectal cancer screening: an absolute necessity and an imminent reality in the French community]. / Le dépistage généralisé du cancer colorectal: une absolue nécessité et une réalité imminente en Communauté française.

Colorectal cancer is a true problematic of public health. The screening is an absolute necessity. An ambitious program of screening is launched in French Community. Faecal occult blood test (FOBT) will be proposed to average risk patients in general population. A total colonoscopy will be performed if FOBT will be positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multidisciplinary program.

[When should we resect colorectal liver metastases?]. / Quand doit-on réséquer les métastases hépatiques d'un cancer colorectal?

6000 new cases of colorectal cancer are diagnosed each year in Belgium. 50% of these patients shall develop liver metastasis. Resection remains the only chance of long term survival and must be considered as an endpoint from the beginning of the treatment. It is the result of a multidisciplinary discussion and a global approach of the disease. It is rarely directly feasible, but there are many techniques which may make it achievable in the end. Today, resection criteria are exclusively technical and neither bad prognosis factors, nor the presence of extra-hepatic metastases should exclude liver resection. This resection must be assessed by a confirmed hepatobiliary surgeon and must be proposed to all patients whatever their age as long as their general state of health is good.

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.