More deaths from pancreatic cancer than breast cancer in the EU by 2017.

INTRODUCTION: Pancreatic cancer currently ranks below female breast cancer in terms of the number of deaths in both males and females in the EU. While breast cancer mortality rates have been declining in many higher income EU countries during recent decades, rates of pancreatic cancer in contrast are either stable or moderately increasing; a comparative analysis of the short-term future rates of both is warranted. METHODS: We extracted the annual number of deaths from cancers of the pancreas and breast by gender together with population at risk in each of 28 countries of the EU for the period 2001-2010. We fitted cancer- and gender-specific time-linear regression models and predicted deaths from pancreatic and breast cancer mortality for the years 2011-2025. RESULTS: We estimated that by the year 2017 more deaths from pancreatic cancer will occur (91 500 annual deaths) than breast cancer (91 000) in the EU. By 2025, deaths from cancer of the pancreas are predicted to be 25% higher (111 500 and 90 000, respectively). Pancreatic cancer may become the third leading cause of death from cancer in the EU after lung and colorectal cancers. CONCLUSION: Although strategies may emerge in the near future that will enhance the prospects of improving the very poor five-year survival from pancreatic cancer, coordinated efforts are necessary to reduce the foreseeable high mortality burden of disease within the EU.

Surgical hemostatic agents: assessment of drugs and medical devices.

Surgical hemostatic agents are indicated to improve hemostasis when conventional techniques (compression, sutures or electrocoagulation) are inadequate. The National French Authority for Health (Haute Autorité de santé [HAS]) set out to assess these products (medical devices and agents) to determine their optimal utility. This evaluation included one class of products containing some form of human fibrinogen and thrombin and eight classes of medical devices and automated devices to prepare autologous fibrin. The assessment was based on a systematic review of the literature and expert opinion of health care professionals. The main measures of effectiveness of hemostatic agents were the success rate as expressed in terms of the time necessary to obtain adequate hemostasis, the volume of intra and/or postoperative blood loss, the need for blood transfusions, complication rate, duration of operations and hospital stay. A meta-analysis and 52 controlled randomized studies were selected involving cardiac or vascular surgery (19), ENT surgery (11), gastrointestinal surgery (5), urology (4), orthopedic surgery (4). Approximately half of the studies retained in this analysis evaluated blood derived agents (fibrin sealants) while the other half evaluated medical devices. The working group considered that there is not any evidence that these surgical hemostatic agents decrease the rates of transfusion, complications, reoperation, mortality, duration of operation and/or hospital stay. The working group considered that the use of surgical hemostatic agents to improve the safety of hemostasis in the absence of identified bleeding as an alternative to adequate conventional hemostasis was not justified. Surgical hemostatic agents can be used in ad hoc settings, as a complement to conventional methods to control persistent bleeding after conventional hemostatic techniques, or when abundant bleeding has led to biologic hemostatic disorders. The working group also distinguished several particular settings (mouth and dental care in patients under antiagregant or anticoagulation therapy, central nervous system surgery or acute aortic dissection). Comparative data are insufficient to determine if one product is superior to another for a specific use. To evaluate the clinical value of these products, methodologically sound clinical studies are necessary.

[New insights in oncology: epigenetics and cancer stem cells]. / Nouvelles perspectives en oncologie : épigénétique et cellules souches cancéreuses.

Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either "gain" (oncogenes) or "lose" (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ("epimutations") turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms.

[Histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma]. / Chimioradiothérapie préopératoire des adénocarcinomes du pancréas: évaluation anatomopathologique de l'efficacité thérapeutique.

PURPOSE: Several phase II studies have shown the feasibility of neoadjuvant chemoradiation regimens for resectable localized pancreatic adenocarcinoma. However, there is to date no completed phase III study to validate this approach and treatment effects evaluation still remains an active area of investigation. From the mature results of the SFRO-FFCD 9704 trial, we explored the antitumoral effect of a 5-fluoro-uracil and cisplatin-based preoperative chemoradiation regimen, with a special highlight on the histopathological response and performed a literature review. PATIENTS AND METHODS: Treatment consisted of concurrent radiotherapy (50 Gy within five weeks) and chemotherapy with 5-fluoro-uracil (300 mg/m(2)/day, five days/week, weeks 1-5) and cisplatin (20mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumour in patients without progression. RESULTS: In all, 41 patients were enrolled, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (≥ 80% of severely degenerative cancer cells), with one complete pathologic response. The local recurrence and two-year survival rates were 4 and 32%, respectively, for the 26 operated patients. CONCLUSION: Our results suggest that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant chemoradiation may serve as a surrogate marker for treatment efficacy and further research is needed to determine new prognostic and predictive factors of treatment response.

Liver transplantation for multiple angiomyolipomas complicating tuberous sclerosis complex.

Tuberous sclerosis complex is a genetic multisystem disorder characterised by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Hepatic multiple, bilateral angiomyolipomas are a rare and usually asymptomatic complication in patients with tuberous sclerosis. We report here the case of a patient who needed liver transplantation because of debilitating manifestations and mechanical complications of massive liver involvement by multiple angiomyolipomas (severe malnutrition, anorexia and abdominal pain). Seventeen tumors, from 2 to 16 cm in diameter, were identified at examination of the liver explant. No feature suggestive of malignant behaviour was identified at histological examination. In conclusion, this unusual indication of liver transplantation underlines the interest of this therapeutic approach for benign tumors for which the multiplicity of the lesions and their huge volume prevent any attempt at surgical resection.

[Prosthetic mesh for hernia repair: which mesh for which indication? Analysis of the Committee for the Assessment of Devices and Health Technologies of the French National Authority for Health (HAS). Assessment of prosthetic meshes for hernia repair]. / Implants de réfection de paroi : lequel, dans quelle indication ? Analyse de la Commission d'évaluation des produits et prestations de la Haute Autorité de santé (HAS). Evaluation des implants de réfection de paroi.

UNLABELLED: The Committee for the Assessment of Devices and Health Technologies (CEPP), one of the specialist committees of the French National Authority for Health (HAS), reassessed the use of prosthetic mesh for hernia repair in 2008. Mesh use is reimbursed by French national health insurance for use in adult and pediatric surgery. This reassessment had two primary purposes: (a) to define the indications and clinical situations justifying the use of mesh, and to describe the technical requirements; (b) to define the conditions of prescriptions and of use and to contribute to decisions for the renewal of inscription. METHODS: We performed a systematic review of published data and manufacturers' licenses and applied the judgment of a multidisciplinary working group of involved healthcare professionals. The CEPP first analyzed the different sorts of prosthetic mesh according to operative indications; they then compared the performance of each prosthesis based on comparative data from the literature or based on expert opinion when there was no available comparative data. The committee recommended three types of prosthesis: flat patch mesh, three-dimensional mesh (plug), and double-sided patch. Additional studies were recommended to confirm the benefits of selected products. The cost of meshes has been integrated into the reimbursement of each Diagnostic Related Group (DRG) and is no longer included in the List of Reimbursable Products and Services (Liste des produits et prestations remboursables [LPPR]); the High Authority for Health (HAS) recommends the selection of those prostheses evaluated by the CEPP in order to optimize the quality and cost of health care.

Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review.

BACKGROUND: We explored the feasibility and the histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks) and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, weeks 1-5) and cisplatin (20 mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. RESULTS: In all, 41 patients were enrolled; 38 (93%) received >or=47 Gy; 30 patients (73%) received >or=75% of the prescribed doses of chemotherapy. Among 40 assessable patients, 27 (67.5%; 95% confidence interval 50.9% to 81.4%) were successfully treated (entire dose of radiation, >or=75% of the chemotherapy dose, no grade 4 non-hematologic toxicity). In all, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (>or=80% of severely degenerative cancer cells), with one complete pathologic response. Operative mortality was 2.8%. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. CONCLUSIONS: This proposed preoperative scheme is feasible, does not prevent successful surgery, and provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate.

Long-term survival (superior to 20 years) after pancreaticoduodenectomy for pancreatic duct adenocarcinoma: report of two cases.

Pancreatic duct adenocarcinoma (PDA) is associated with dismal survival. This study reports two cases of very long survival after pancreatectomy for PDA. These were two male patients with pT30M0 and pT2N0M0 tumour. Both received adjuvant treatment and are currently alive after 21y 6 months and 22 y 2 months respectively. Very long term survival for PDA can be achieved for some patients who benefit from R0 resection.

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study.

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m(-2)) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5(1/2) weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m(-2)) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35-79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control.

Expression of beta-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases.

AIMS: To clarify the role of beta-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of beta-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in beta-catenin expression. METHODS: 229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of beta-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene. RESULTS: The distribution of immunoreactive beta-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of beta-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months. CONCLUSIONS: Immunohistochemically detectable nuclear accumulation of beta-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in beta-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.

Unresectable hepatocellular carcinoma: survival and prognostic factors after lipiodol chemoembolisation in 89 patients.

BACKGROUND: The majority of patients with hepatocellular carcinoma are not eligible for surgical radical treatment (resection or liver transplantation) and lipiodol chemoembolisation is an efficient alternative procedure in this indication. AIMS: To identify prognostic factors in patients treated with lipiodol chemoembolisation. PATIENTS AND METHODS: During 10 years, 89 consecutive patients with unresectable hepatocellular carcinoma underwent lipiodol chemoembolisation as a single treatment. There were 80 males and 9 females, with a median age of 65 years. Treatment consisted of one to six courses of hepatic intra-arterial lipiodol with doxorubicine and gelatin sponge. RESULTS: The median survival was 13 months with a 13.6% survival rate at 4 years. Univariate analysis showed that serum levels of albumin, bilirubin, alkaline phosphatase and alpha-fetoprotein, Child's class, tumour type, tumour size and intensity of lipiodol capture after the first course of lipiodol chemoembolisation were significant prognostic factors of survival. In the multivariate analysis, four parameters remained associated with a significantly better outcome: Child's class A, largest lesion<5 cm, uninodular tumour and intense lipiodol capture. CONCLUSIONS: While lipiodol chemoembolisation is associated with good results only in some patients, in the absence of lipiodol capture, it should be ruled out.

Unusual cystic presentation of an endocrine carcinoma of the jejunum.

The cystic presentation of endocrine tumours is rare and raises difficult diagnostic problems. So far, the only cases of cystic digestive endocrine tumours reported in the literature are of pancreatic origin. We report the unusual observation of a jejunal endocrine carcinoma presenting as a cystic abdominal mass. A 59-year-old woman was referred for chest and abdominal pain. Imaging studies revealed multiple cystic nodules in the liver and a large sus-mesocolic cystic lesion of probable intestinal origin. Biopsies of the extra-hepatic mass and liver nodules showed endocrine tumour. Surgical resection of the jejunal mass and of liver segment III were performed. Histological examination confirmed the diagnosis of jejunal endocrine carcinoma metastatic to the liver. Large areas of the primary and secondary tumours presented an unusual vesicular architecture, responsible for the cystic presentation. No adjuvant treatment was attempted. This observation underlines the difficult diagnostic problems raised by the cystic presentation of digestive endocrine tumours.

Preaortic paraganglioma mimicking a hypervascular tumor of the pancreas.

Paragangliomas are rare tumors that arise from neuroepithelial cells. They are most frequently located in the para-aortic region and they may be confused with other retroperitoneal tumors, especially pancreatic tumors. We present a case of a secreting preaortic paraganglioma in a young patient which was mimicking a hypervascular tumor of the pancreas, and that was completely resected 5 years after the failure of a first attempt to remove the tumor.

[Chemoradiation for pancreatic adenocarcinoma]. / Chimioradiothérapie des adénocarcinomes pancréatiques.

Surgery remains the cornerstone treatment for pancreatic adenocarcinoma. However, 5% to 20% of tumors only are regarded as resectable, and, among them, only few benefit from an histological complete resection, major survival parameter. These data explain the overall poor prognosis of this disease, with a respectively 20% and 5% 1- and 5-year survival rates. These results justify an adjuvant or neoadjuvant therapeutic approach, mainly based on concurrent chemoradiation, with and without surgery. This paper reviews the different therapeutic approaches of non metastatic pancreatic adenocarcinoma.

Diagnosis and treatment of biliary obstruction caused by portal cavernoma.

While hemorrhagic complications of portal cavernoma are frequent, compression of the bile ducts by portal cavernoma is uncommon and treatment is still a matter for debate. We report here six new cases in order to describe: (a) the clinical, biological, and morphological features of this condition, and (b) the long-term results of a combined endoscopic and surgical treatment. The median age of patients at the time of diagnosis was 36.5 years. The circumstances of diagnosis were acute cholangitis (n=3), asymptomatic biological cholestasis (n=1), pruritus, jaundice and asthenia (n=1) and jaundice alone (n=1). Portal cavernoma and bile duct dilatation were confirmed by abdominal ultrasonography with pulsed color doppler and endoscopic retrograde cholangiography (ERC). Gallstones were found in four patients. Following stenting of the bile duct, there was a good outcome in two patients. In four patients, after failure of prolonged endoscopic treatment, second-line surgical portal-systemic shunting allowed removal of the biliary stent, and no recurrence of disease. In conclusion, biliary involvement in portal cavernoma is now a well-recognized entity, and our results suggest that combined endoscopic and surgical treatment could be required.

Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma.

BACKGROUND: Although the prognosis in malignant resectable intraductal papillary mucinous tumours of the pancreas (IPMT) is often considered more favourable than for ordinary pancreatic ductal adenocarcinoma, the long term outcome remains ill defined. AIMS: To assess prognostic factors in patients with malignant IPMT after surgical resection, and to compare long term survival rates with those of patients surgically treated for ductal adenocarcinoma. METHODS: Seventy three patients underwent surgery for malignant IPMT in four French centres. Clinical, biochemical, and pathological features and follow up after resection were recorded. Patients with invasive malignant IPMT were matched with patients with pancreatic ductal adenocarcinoma, according to age and TNM stages; survival rates after resection were compared. RESULTS: Surgical treatment for IPMT were pancreaticoduodenectomy (n=46), distal (n=14), total (n=11), or segmentary (n=2) pancreatectomy. The operative mortality rate was 4%. IPMT corresponded to in situ (n=22) or invasive carcinoma (n=51). In the latter group, 17 had lymph node metastases. Overall median survival was 47 months. Five year survival rates in patients with in situ and invasive carcinoma were 88% and 36%, respectively. On univariate analysis, abdominal pain, preoperative high serum carbohydrate antigen 19.9 concentrations, caudal localisation, invasive carcinoma, lymph node metastases, peripancreatic extension, and malignant relapse were associated with a fatal outcome. Using multivariate analysis, lymph node metastases were the only prognostic factor (OR 7.5; 95% CI: 3.4 to 16.4). Overall five year survival rate was higher in patients with malignant invasive IPMT compared with those with pancreatic ductal carcinoma (36 v 21%, p=0.03), but was similar in the subset of stage II/III tumours. CONCLUSIONS: The prognosis of patients with resected in situ/invasive stage I malignant IPMT is excellent. In contrast, prognosis of locally advanced forms is as poor as in patients with pancreatic ductal adenocarcinoma.

[IMesenteric and mesocolic cystic lymphangiomas. Diagnostic and therapeutic management]. / Les lymphangiomes kystiques du mésentère et du méso-côlon. Prise en charge diagnostique et thérapeutique.

STUDY AIM: Study of clinical, diagnostic and therapeutic aspects of mesenteric and mesocolic cystic lymphangiomas. MATERIAL AND METHODS: 15 cases were retrospectively analysed: 5 adults (mean age 36.8 years, range 26 to 46) and 10 children (mean age 23 months, range 0 to 5 years). Diagnosis was prenatal in 1 case. Symptoms were: abdominal pain (80%), fever (20%), abdominal mass (46%), occlusive syndrome (33%), chylous ascitis 1 case. Tumours were mesenteric (86%) or mesocolic (13%). RESULTS: Complete resection was performed in 11 cases (including 10 bowel resections), incomplete resections in 3 and doxycycline sclerotherapy once. Mean follow-up is 5 years. One recurrence occurred 6 years after complete resection and 1 tumour increased after incomplete resection. Patient treated by sclerotherapy was non symptomatic with a 3.5 years follow-up after last injection. CONCLUSION: Mesenteric and mesocolic cystic lymphangiomas are congenital benign tumours. Complete resection should be performed whenever possible. Intracystic sclerotherapy with doxycyclin is possible for unresectable lymphangiomas.

[Total pancreatectomy for mucinous pancreatic tumor]. / Pancréatectomie totale pour tumeur mucineuse du pancréas.

AIM OF THE STUDY: To report our experience of total pancreatectomy (TP) in ten patients with mucinous pancreatic tumors (MPT), to discuss pre and peroperative investigations in the management of MPT, and operative, functional and carcinologic results after TP. PATIENTS AND METHODS: This retrospective study from January 1985 to January 2001 included ten patients, 5 men and 5 women (mean aged: 64 years). Six patients underwent one step TP for intraductal papillary mucinous tumor of the pancreas (IPMT) in 5 cases, and multifocal mucinous cystadenoma in one case. Four patients underwent a second step TP for tumor recurrence (2 IPMT, and 2 cystadenocarcinomas) which occurred 12 to 121 months post operatively (mean: 49 months). RESULTS: Post TP diabetes was controlled by insulinotherapy (3 injections a day), except in one patient who needed insulin administration through a pump. One patient, with cystadenocarcinoma, died from cancer recurrence 18 months after TP and 140 months after the initial pancreaticoduodenectomy. One patient died from heart disease 34 months postoperatively. The 8 other patients were alive with a mean follow-up of 33 months (range 11-61 months). CONCLUSION: Curative surgery for mucinous tumors of the pancreas may require TP, which is indicated preoperatively according to imaging, or intraoperatively following surgical findings and frozen section of the pancreatic margin. Totalization of a previous partial pancreatectomy is mandatory in case of tumoral persistence or recurrence in the pancreatic remnant. Postoperative diabetes can be managed successfully by a specialized team.