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.

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.

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.

[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.

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.

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.

Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers.

Primary esophageal squamous cell carcinomas from 41 patients were analyzed for the presence of proto-oncogene alterations associated with this malignancy. The occurrence of activating ras gene mutations in 25 tumors was determined using oligomer hybridization of target sequences amplified by polymerase chain reaction. We found no evidence for mutations in codons 12 and 61 of the H-ras, K-ras, and N-ras genes, nor in codon 13 of the K-ras and N-ras loci in any of these tumors. The apparent absence of activated ras oncogene in esophageal cancers represents a possible exception to the presence of these mutations found consistently in numerous other types of human malignancies, and is in striking contrast to the 40% prevalence of ras mutations in human colorectal cancers. Southern blot hybridization experiments with DNAs from tumors demonstrated amplification of the epidermal growth factor receptor gene (c-erbB) in two of 25 carcinomas. No amplification of the structurally related c-erbB2 (neu) gene was detected. In three out of 12 carcinomas, the level of epidermal growth factor receptor RNA was significantly higher than in normal esophageal mucosal tissue. Our results suggest that enhanced transcription of the epidermal growth factor receptor gene is associated with the development of some esophageal cancers.

Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial.

PURPOSE: The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown. The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery. PATIENTS AND METHODS: Patients with rectal carcinoma accessible to rectal digital examination, staged T2 to T3, NX, M0, were randomized before radiotherapy (39 Gy in 13 fractions) into two groups: in the short interval (SI) group, surgery had to be performed within 2 weeks after completion of radiation therapy, compared with 6 to 8 weeks in the long interval (LI) group. Between 1991 and 1995, 201 patients were enrolled onto the study. RESULTS: A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response (53. 1% in the SI group v 71.7% in the LI group, P =.007) and pathologic downstaging (10.3% in the SI group v 26% in the LI group, P =.005). At a median follow-up of 33 months, there were no differences in morbidity, local relapse, and short-term survival between the two groups. Sphincter-preserving surgery was performed in 76% of cases in the LI group versus 68% in the SI group (P = 0.27). CONCLUSION: A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results. When sphincter preservation is questionable, a long interval may increase the chance of a successful sphincter-saving surgery.

Evaluation of the carcinogenic risks to humans associated with surgical implants and other foreign bodies - a report of an IARC Monographs Programme Meeting. International Agency for Research on Cancer.

A meeting was held within the International Agency for Research on Cancer (IARC) Programme on the Evaluation of Carcinogenic Risks to Humans of surgical implants and other foreign bodies. This meeting report summarises the types of materials considered, their wear and degradation, their cancer epidemiology in both humans and other animals, the published experimental carcinogenicity data and selected data on their toxic, including genotoxic, effects. Evaluations resulting in a classification of Group 2B (possibly carcinogenic to humans) were reached for: (1) polymeric implants prepared as thin smooth films [with the exception of poly(glycolic acid)]; (2) metallic implants prepared as thin smooth films; and (3) implanted foreign bodies consisting of metallic cobalt, metallic nickel and a particular alloy powder consisting of 66-67% nickel, 13-16% chromium and 7% iron. Group 3 classifications (not classifiable as to their carcinogenicity to humans) were made for: (1) organic polymeric materials as a group; (2) orthopaedic implants of complex composition and cardiac pacemakers; (3) silicone breast implants; (4) dental materials; and (5) ceramic implants.

Cancer risks related to electricity production.

The International Agency for Research on Cancer has previously evaluated the cancer risks associated with fossil fuel-based industrial processes such as coal gastification and coke production, substances and mixtures such as coal tars, coal tar pitch and mineral oils, and a number of substances emitted from fossil-fuelled plants such as benzo[a]pyrene and other polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, chromium, nickel, lead and formaldehyde. Based on these evaluations and other evidence from the literature, the carcinogenic risks to the general population and occupational groups from the fossil fuel cycle, the nuclear fuel cycle and renewable cycles are reviewed. Cancer risks from waste disposal, accidents and misuses, and electricity distribution are also considered. No cycle appears to be totally free from cancer risk, but the quantification of the effects of such exposures (in particular of those involving potential exposure to large amounts of carcinogens, such as coal, oil and nuclear) requires the application of methods which are subject to considerable margins of error. Uncertainties due to inadequate data and unconfirmed assumptions are discussed. Cancer risks related to the operation of renewable energy sources are negligible, although there may be some risks from construction of such installations. The elements of knowledge at our disposal do not encourage any attempt toward a quantitative comparative risk assessment. However, even in the absence of an accurate quantification of risk, qualitative indication of carcinogenic hazards should lead to preventive measures.

Cystic endocrine tumors of the pancreas: clinical, radiologic, and histopathologic features in 13 cases.

Cystic endocrine tumors of the pancreas are rare and raise difficult clinical problems. Our aims were to reevaluate the diagnostic and therapeutic strategy and to assess their histopathologic characteristics. Thirteen cystic endocrine tumors diagnosed in 10 patients were included. Clinical, radiologic, and pathologic data were reviewed. There were 6 male and 4 female patients (median age, 46 yrs). Six patients had evidence of multiple endocrine neoplasia type 1 (MEN1) disease. Four had a functional endocrine syndrome. Ten tumors were visible on imaging studies. The most suggestive radiologic features were the existence of a peripheral hypervascular rim (10 cases) and images of cyst into cyst (two cases). On gross and histologic examinations, two distinct types were present. Macrocystic tumors (six cases) were unilocular and limited by a thick wall containing nests of tumor cells. Microcystic tumors (seven cases) were characterized by the presence of multiple cystic spaces directly lined by tumor cells. Surgical resection was performed in all cases. Three patients had lymph node metastases at the time of diagnosis. One patient is dead with metastatic dissemination. The others are alive without recurrence or metastasis. The diagnosis of endocrine tumor must be considered for any pancreatic cyst discovered in a patient with a history of MEN1 syndrome or with clinical features suggestive of this syndrome. Cystic pancreatic endocrine tumors must be treated by surgical resection because of their possible malignant evolution.

An IARC evaluation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans as risk factors in human carcinogenesis.

The International Agency for Research on Cancer (IARC) Monographs program reevaluated polychlorinated dibenzo-p-dioxins and evaluated polychlorinated dibenzofurans as possible carcinogenic hazards to humans in February 1997, using the most recent epidemiologic data on exposed human populations, experimental carcinogenicity bioassays in laboratory animals, and supporting evidence on relevant mechanisms of carcinogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was evaluated as carcinogenic to humans (IARC group 1 classification) on the basis of limited evidence of carcinogenicity to humans derived from follow-up of workers who had been heavily exposed in industrial accidents and sufficient evidence of carcinogenicity in experimental animals. The evaluation also considered the following supporting evidence: TCDD is a multisite carcinogen in experimental animals and has been shown by several lines of evidence to act through a mechanism involving the aryl hydrocarbon receptor; this receptor is highly conserved in an evolutionary sense and functions the same way in humans as in experimental animals; tissue concentrations of TCDD are similar in heavily exposed human populations in which an increased overall cancer risk was observed and in exposed rats that developed tumors in carcinogenicity tests. Other polychlorinated dibenzo-p-dioxins, the nonchlorinated dibenzo-p-dioxin, and polychlorinated dibenzofurans were evaluated as not classifiable as to their carcinogenicity to humans (group 3).

Intra-arterial iodine 131-labeled lipiodol as adjuvant therapy after curative liver resection for hepatocellular carcinoma: a phase 2 clinical study.

HYPOTHESIS: Intra-arterial lipiodol labeled with iodine 131 ((131)I-lipiodol) can be safely used as adjuvant therapy following curative liver resection for hepatocellular carcinoma (HCC). DESIGN: Phase 2 pilot study. SETTING: Large teaching hospital. PATIENTS: Twenty-eight patients (24 men and 4 women; median age, 61.5 years; range, 33-75 years) were treated from January 1991 to June 1997. The liver was cirrhotic in 7 cases and noncirrhotic in 21 cases. An equal number of 14 patients underwent a major and a minor resection, all with clear margins. Median diameter of solitary tumors or the larger tumor when multiple tumors occurred was 5.5 cm (range, 2.5-29 cm). Tumor encapsulation was present in 12 cases and absent in 16 cases. After informed consent, patients who had no evidence of residual or recurrent tumor on computed tomographic (CT) scan and no sign of liver failure 2 to 3 months after curative resection for HCC were included in the trial. Complete follow-up was obtained (median, 51 months; range, 5-93 months). INTERVENTIONS: A 1110-MBq dose of (131)I-lipiodol was administered into the hepatic artery using the Seldinger technique. Patients were kept in a radio-protected room for 5 days. Postinjection radioactive whole scintiscan was performed at 5 days and an abdominal CT scan at 1 month after the injection. A second injection was performed in 16 patients 2 years later using the same protocol. MAIN OUTCOME MEASURE: Procedure safety. RESULTS: All patients experienced transient fever during the first 12 hours following injection. There were no noted adverse clinical effects or significant alteration in hepatic function due to the procedure or at immediate and late follow-up. The radioactive scan demonstrated an intense liver uptake, which was homogeneous in 19 cases and heterogeneous in 9. Mild detectable thyroid and lung uptake occurred in 50% of cases. No lipiodol liver fixation was observed on the 1-month CT scan. At the time of follow-up, 6 patients had died and 12 had developed recurrences, with 5 of the 6 deaths belonging to the recurrent group. Sixteen patients remained disease free. The median time to detected recurrence was 28 months (range, 12-62 months). Overall survival rates were 86% at 3 years and 65% at 5 years. CONCLUSIONS: This pilot study failed to demonstrate any clinically significant adverse effect of adjuvant therapy by intra-arterial (131)I-lipiodol after curative liver resection for HCC. Long-term survival compares favorably with those undergoing only surgery and suggests a benefit in lowering tumor recurrence. A randomized, multicenter, prospective trial comparing patients treated with intra-arterial (131)I-lipiodol with a nontreated control group seems appropriate.

Peripheral cholangiocarcinoma: presentation, diagnosis, pathology and management.

AIMS: To report the clinical presentation, diagnosis and results of aggressive surgical management in patients with intrahepatic cholangiocarcinoma. METHODS: From February 1988 to June 1998, 21 patients underwent laparotomy with a 90% resectability rate (19 resections). The 19 liver resections included right trisegmentectomy in six patients, right lobectomy in five, wedge resection in four, left lobectomy in two, left trisegmentectomy in one and a lateral segmentectomy in one. Resection of the biliary confluence with reconstruction by a Roux en Y hepaticojejunostomy was performed in three patients. RESULTS: Mild abdominal pain, weight loss and gastrointestinal disturbances were the most frequent clinical signs. Jaundice was present in only four patients. Pre-operative radiological investigations (abdominal ultrasound, computed tomography, arteriography) correlated with pathological findings in only 60% of cases. Pre-operative histological findings (fine-needle cytology, liver biopsy), available for 19 patients, did not always provide an accurate diagnosis. The mortality and morbidity rates were 5 and 47%, respectively. The median survival of resected patients was 18 months. Overall patient and tumour-free survival rates were 83 and 31% at 1 year, 33 and 16.5% at 2 years and 16.5 and 16.5% at 3 years in the resected group. Lymph-node spread, vascular invasion, positive margins and bilobar distribution were associated with a high recurrence rate and poor prognosis. CONCLUSION: Despite the advanced stage of these tumours at presentation, patient survival can be improved by aggressive surgical resection. As intrahepatic cholangiocarcinoma usually develops in a non-cirrhotic liver, major hepatic resections to obtain disease-free margins can be performed with low mortality.

Repeated hepatic resections for colorectal metastases.

Repeated hepatic resection (RHR) for recurrent colorectal metastases remains uncommon and controversial. We report our experience in order to assess the feasibility and the potential oncologic benefit of such an aggressive management. From 1981 to 1991, 13 patients underwent a RHR. The first hepatic resection had been an anatomic hepatectomy removing between two and six segments in 10 patients and a wedge resection in three. The RHR was performed after a mean delay of 16 +/- 10 months (5-35) from the first liver procedure. The RHR was an anatomic hepatectomy in eight patients (including a right hepatectomy in three) and a minor resection (tumorectomy or segmentectomy) in five. Three patients underwent a third liver resection for recurrence. There was no post-operative mortality. Eleven patients died from recurrence after a mean survival of 17 +/- 13 months from the second hepatic procedure (range: 6-47). One patient died from unrelated disease after 12 months and one was alive free of recurrence 22, 53 and 84 months after third, second and first hepatectomy respectively. The median survivals from the second and first hepatic resections were 17 and 31 months, respectively. It is concluded that in the well-trained team, RHR is feasible and safe even after major primary hepatectomy. However the oncologic benefit remains questionable.

Necrolytic migratory erythema, first symptom of a malignant glucagonoma: treatment by long-acting somatostatin and surgical resection. Report of three cases.

We report three cases of malignant glucagonoma with necrolytic migratory erythema as the first clinical symptom. Long-acting somatostatin analogue was the first step of a multimodal therapeutic strategy which included surgical resection of the primary tumour in every case. Liver metastases which were present in two patients were treated by hepatic arterial chemoembolization and systemic chemotherapy in one case and by liver resection for cytoreduction and hepatic arterial chemoembolization in another case. Skin lesions resolved in all three patients.

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.

Portal vein aneurysm: report of two cases.

Portal vein aneurysm is a rare entity. We present two cases of extrahepatic portal vein aneurysms, which were incidentally discovered in patients with no evidence of liver disease. Those were assumed to be congenital lesions. Diagnosis was made by Doppler ultrasound. Both patients were managed expectantly.

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.