Cancer incidence and mortality in France over the period 1978-2000.

BACKGROUND: Monitoring cancer incidence and mortality time trends is essential for cancer research and health-care planning. French cancer registries do not cover the entire population and do not provide a representative sample of the national population. Our study aimed at estimating national cancer incidence and mortality trends over the longest period available. METHODS: Incidence and mortality data were collected over the period 1978-1997. Twenty-seven cancer sites were selected and age, sex and site specific incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The person-years of observation were calculated cohort-wise from census data provided by the national institute of statistics RESULTS: Cancer incidence increased by 63% throughout the study period, from 170,000 new cases in 1980 to 278,000 in 2000. This evolution was due to demographic changes but also to an increase in the risk of cancer which was estimated to more than 35% during the same period. In men, this change is largely explain by the increase of prostate cancer incidence. Among women, the increase was dominated by the continuing increase in breast cancer incidence. Large increases were also seen for non-Hodgkin lymphoma, melanoma, and thyroid cancer in both genders and for lung cancer in women. Cancer mortality increased by 20% from 125,000 deaths in 1980 to 150,000 in 2000. This increase is less than that predicted from changes in demographic factors and corresponds in fact to a decrease in the risk of death estimated to about 8%, slightly greater for women than for men. This decrease is associated with a decreasing incidence for stomach cancers for both sexes, alcohol-related cancer for men and cervical cancer for women. Colo-rectal cancer decreasing mortality contributes to this improvement despite an incidence increase. CONCLUSION: Between 1980 and 2000, the study showed a large change in the cancer burden both quantitatively and qualitatively. Decrease in exposure, earlier diagnosis and therapeutic improvement explained part of this change, but overall the distribution of cancer cases shifted toward a distribution including less aggressive cancers. A striking divergence between incidence and mortality trends is observed for a great number of cancers. Prostate cancer shares with breast cancer the same pattern of a severe increasing incidence and a stable mortality. This points to important changes in medical practice and needs further analysis. The trend of lung cancer mortality among women should be emphasised since the situation will inevitably worsen in the coming years. It is already the third cause of cancer death among women.

Mutational screening of the cationic trypsinogen gene in a large cohort of subjects with idiopathic chronic pancreatitis.

Several missense mutations, including R122H, N29I, K23R, A16V and D22G, in the cationic trypsinogen gene (PRSS1), have been associated with certain forms of hereditary pancreatitis (HP). Their occurrence in the idiopathic chronic pancreatitis (ICP) and whether novel mutations could be identified in PRSS1 remain to be further evaluated. These were addressed by the mutational screening of the entire coding sequence and the intronic/exonic boundaries of the PRSS1 gene in 221 ICP subjects, using a previously established denaturing gradient gel electrophoresis technique. Among the known PRSS1 mutations, only the R122H was detected in a single subject and the A16V in two subjects in the cohort, strengthening that HP-associated PRSS1 mutations are rare in ICP. Additional missense mutations, including P36R, E79K, G83E, K92N and V123M, were identified once separately. By analogy with the known PRSS1 mutations, predisposition to pancreatitis by some of them, particularly the V123M autolysis cleavage site mutation, is suspected. Functional analysis is expected to clarify their possible medical consequences.

Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis.

Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by recurrent episodes of pancreatitis often beginning in early childhood. The mode of inheritance suggests an autosomal dominant trait with incomplete penetrance. The gene, or at least one of the genes, responsible for hereditary pancreatitis has been mapped to the long arm of chromosome 7 and a missense mutation, an arginine to histidine substitution at residue 117 in the trypsinogen cationic gene (try4) has been shown to segregate with the HP phenotype. The aim of this work was to investigate the molecular basis of hereditary pancreatitis. This study was performed on 14 HP families. The five exons of the trypsinogen cationic gene were studied using a specific gene amplification assay combined with denaturing gradient gel electrophoresis (DGGE). The present paper describes three novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter region. We also found a polymorphism in exon 4, D162D. In eight of these families we found a mutation which segregates with the disease. A segregation analysis using microsatellite markers carried out on the other families suggests genetic heterogeneity in at least one of them. Our findings confirm the implication of the cationic trypsinogen gene in HP and highlight allelic diversity associated with this phenotype. We also show that the pattern of inheritance of HP is probably complex and that other genes may be involved in this genetic disease.

[Natural history of non alcoholic and non familial chronic pancreatitis. Results of a multicentre study]. / Evolution de la pancréatite chronique non alcoolique et non familiale.Résultats d'une étude multicentrique.

UNLABELLED: The natural history and complications of non alcoholic chronic pancreatitis (NACP) is poorly understood compared to that of alcoholic chronic pancreatitis (ACP). PATIENTS AND METHODS: From April 1993 to April 1996, 77 patients with NACP were prospectively evaluated in 17 French centres. This population was compared to a cohort of 417 patients with ACP. RESULTS: No significant difference was observed with respect to mean age between NACP and ACP (43 +/- 20 vs 44 +/- 11 years, respectively). The median patient follow-up time was also comparable: 7 years (1-28) and 6 years (1-34) respectively for NACP and ACP. There were significantly more males in the ACP group (9/1 in ACP group and 1.3/1 in NACP group; P<10(- 7) ). Patients with NACP were less likely to have calcifications (58% vs 77%; P=0.01), pseudocysts (19 vs 47%, P<0.001), portal vein thrombosis (5 vs 16%, P<0.02). Importantly, patients with NACP required less surgical procedures than those with ACP (26% vs 44%, P=0.004). The actuarial death rate at 15 years was 0% in the NACP group compared to 20.5% in those with ACP (no CP related death). CONCLUSION: NACP has a less severe disease progression, fewer complications and requires less surgical interventions than ACP. The lower actuarial survival rate in patients with ACP correlates with the extra-pancreatic complications encountered in patients with alcohol related diseases and not with the evolution of CP itself.

Frequency and risk factors of recurrent pain during refeeding in patients with acute pancreatitis: a multivariate multicentre prospective study of 116 patients.

BACKGROUND/AIMS: The period of refeeding in patients with acute pancreatitis is critical because they may have pain relapse. A multicentre, multidimensional, prospective study was performed to assess the frequency and the risk factors of pain relapse in these patients. METHODS: Patients were included if they had acute pancreatitis severe enough to stop oral feeding for more than 48 hours. Clinical, biochemical, radiological, and therapeutic data were prospectively recorded and analysed by unidimensional and multidimensional analysis. The moment to refeed patients was chosen by the clinician but the diet was the same in all centres. RESULTS: A total of 116 patients were included with a Ranson's bioclinical score > or = 3 in 35% and a Balthazar's CT score > or = D in 42%. The cause of acute pancreatitis was biliary in 47% and alcohol misuse in 31%. During the oral refeeding period, 21% of the patients had pain relapse. This occurred on days 1 and 2 in 50% of patients. The duration of the painful period was longer in patients who relapsed than in others (p < 0.002). Pain relapse occurred in 39% of patients with a serum lipase concentration > 3x the upper limit of the normal range the day before refeeding and in 16% of other patients (p < 0.03). Patients with higher Balthazar's CT scores had pain relapse more often than the others (p < 0.002). None of the therapeutic procedures significantly modified the frequency of pain relapse. Using multidimensional analysis, Balathazar's CT score, period of pain, and serum lipase concentration the day before refeeding were independently associated with an increased risk of pain relapse. At a threshold of 0.5, a logistic score had a 37% sensitivity, 95% specificity, and 83% accuracy to predict pain relapse. Pain relapse nearly doubled total hospital stay and hospital stay after the first attempt at oral refeeding. CONCLUSION: Pain relapse occurred in one fifth of the patients with acute pancreatitis during oral refeeding and was more common in patients with necrotic pancreatitis and with longer periods of pain. The results of this study can be used to predict high risk patients and are a first step in the prevention of pain relapse.

An exceptional genealogy for hereditary chronic pancreatitis.

Nearly one hundred families affected with hereditary chronic pancreatitis (HCP) have been reported in the literature. However, the fact that the disease involved only a few members of each family limits the informativeness of these reports and accounts for the infrequency and disappointing results of pathogenetic and genetic research. Our study concerned an exceptional HCP genealogy which would seem to provide an ideal model for the detection of a genetic anomaly linked to the expression of the disease. We studied 249 members of a family (214 still alive), covering eight generations born between 1800 and 1993. According to the customary criteria, 63 had definite and 17 probable HCP. Fifty-eight members under 18 years of age were still susceptible to developing the disease. This series confirms the mode of autosomal dominant heredity with variable penetrance. The clinical features and disease course were typical, except that symptoms tended to appear earlier. The series represents the most extensive HCP genealogy compiled and is one of the largest families studied in the field of genetic disease, regardless of etiology. Blood samples were taken from 146 subjects to facilitate pathogenetic and genetic research.

The hereditary pancreatitis gene maps to long arm of chromosome 7.

Hereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. Although this disorder has only been recently described, about 100 families have been documented worldwide. The pathophysiology of this disorder is unknown. Here, a large French family of 147 individuals (47 of whom were affected) from a four-generation kindred with HP has been examined and a genome segregation analysis of highly informative microsatellite markers has been performed. Linkage has been found between HP and six chromosome 7q markers. Maximal two point lod scores between HP and D7S 640, D7S 495, D7S 684, D7S 661, D7S 676 and D7S 688 were 4.00 (theta = 0.143), 5.85 (theta = 0.143), 4.91 (theta = 0.156), 8.58 (theta = 0.077), 8.28 (theta = 0.060), 4.40 (theta = 0.169), respectively. Multipoint linkage data combined with recombinant haplotype analysis indicated that the most likely order is: D7S 640-D7S 495-D7S 684-D7S 661-D7S 676-D7S 688, with the HP gene situated in the underlined region. As in all families reported in the literature, the clinical presentation of the disease is identical to the presentation of sporadic cases, one could expect that the knowledge of the HP gene could be a clue to pancreatitis in general. Based on its map position, this is the first step towards the positional cloning of the Hereditary Pancreatitis Gene (HPG).

[Surgically treated severe acute inflammatory colitis. Immediate results and long-term outcome]. / Colites inflammatoires aiguës graves traitées chirurgicalement. Résultats immédiats et devenir à long terme.

UNLABELLED: The goal of this study was to analyse the management and the long-term evolution of 40 patients surgically treated for acute colitis (AC) during a 10 year period. PATIENTS AND METHODS: From June 1985 to June 1995, 40 patients (22 males and 18 females, mean age: 33,5 y.o.) have been consecutively operated on for AC. Assessment of severity was based on clinico-biological, endoscopic and radiological criterias: AC was complicated in 3, failing to respond to medical therapy in 9, resisting to medical therapy in 28. Sub-total colectomy (STC) with ileostomy and sigmoidostomy was the most frequently performed procedure (27 cases-68%). RESULTS: 1) The preoperative diagnosis of colitis was modified 6 times (15%) after histological assessment of the specimen: the final diagnosis was ulcerative colitis, indeterminate colitis and Crohn colitis respectively in 36 (90%), 2, and 2 cases. The established diagnosis had to be modified 4 times during follow-up. 2) Postoperative complications occurred in 5 after STC (18%) and in 4 in the other procedures (31%), without mortality. 3) After a mean follow-up of 55 +/- 10 months of the all series, 7 patients (17,5%) had a stoma: 2 had ileo-anal anastomosis taken down and 2 returned to ileostomy for Crohn disease, 1 patient with protected ileo-rectal anastomosis stayed with an ileostomy, 1 patient refused ileo-anal anastomosis, and 1 with imperforate anus had terminal ileostomy. Respectively 25, 6 and 2 patients had a functional ileo-anal, ileo-rectal, and colo-rectal anastomosis and experienced good to excellent digestive comfort in 85% of the cases.

[Primary sclerosing cholangitis and systemic lupus erythematosus]. / Cholangite sclérosante primitive et lupus érythémateux systémique.

We report the association of primary sclerosing cholangitis and systemic lupus erythematosus in a 39 year-old man. Six months after a diagnosis of primary sclerosing cholangitis was established, the patient was hospitalized for a pleural effusion and acute pericarditis. Emergency pericardiocentesis, was required due to sudden cardiac tamponnade. Plasmatic anti-DNA and anti-nuclear antibodies were present. Treatment by steroids greatly improved symptoms. This clinical association suggests that some immune disorders may be common to the two diseases.

[Quality of life and ileo-anal anastomosis with pouch. Results of a prospective series of 35 surgically treated cases of hemorrhagic rectocolitis. Proposal for a score of quality of life]. / Qualité de vie et anastomose iléo-anale avec réservoir. Résulats d'une série prospective de 35 rectocolites hémorragiques opérée. Proposition d'un score de qualité de vie.

Ileal-pouch anal anastomosis (IPAA) following coloproctectomy avoids permanent ileostomy, and allows complete excision of diseased mucosa in ulcerative colitis (UC) and adenomatous polyposis. Preserving normal intestinal pattern, the goal of IPAA is to improve quality of life for patients. This study was designed to measure the impact of IPAA on quality of life in a series of 35 surgically treated UC. Four fields of quality of life were explored: diet, professional activity, sport practice, sexual activity. Interview with independent observer and prospective follow-up allowed to establish a score from 0 (excellent quality of life) to 19 (bad quality of life). In the same time, functional score evaluating pouch evacuation and continence was established (0 = excellent function, 30 = bad function) to be compared to quality of life. The series included 35 IPAA in function for more than 6 months (mean follow-up = 46 +/- 31 months), performed for UC (14 females and 21 males, mean age: 34 y-a). Respectively 30 (86%) and 5 (14%) of the patients had an excellent and fair quality of life, according to the scoring system: 25 had no diet, all but one had a normal professional activity and all were satisfied of sport practice; 33 had no sexual disturbances related to IPAA, but 3 female patients complained of infertility. Functional results were excellent, fair and bad respectively in 25 (72%), 9 (26%) and 1 patients: stool frequency was 4.6 +/- 2 per day, 60% of patients having no nocturnal emission, and 90% being able to delay for more than 1 hour.(ABSTRACT TRUNCATED AT 250 WORDS)

[Multiple granular cell tumor of the colon]. / Tumeur à cellules granuleuses colique plurifocale.

With reference to a case of multiple colorectal granular cell tumors, the authors briefly review the literature concerning this unusual tumor localization. This case demonstrates the most common appendicular, caecal and rectal forms among the localizations of colonic granular cell tumors: as well as the possible proliferation of many other tumors especially in caecal localizations. However the course of the disease is slow, and at the present time only one case report of malignant colonic TCG has been published.

[Prevention of recurrent hemorrhage in patients with cirrhosis. Results of a controlled trial of propranolol versus endoscopic sclerotherapy]. / Prévention des récidives hémorragiques chez des malades atteints de cirrhose. Résultats d'une étude contrôlée comparant propranolol et sclérose endoscopique.

Between July 1984 and March 1986, we conducted a prospective randomized trial comparing propranolol and endoscopic sclerotherapy in the prevention of recurrent variceal hemorrhage in a group of non selected alcoholic cirrhotics. Seventy-six patients with variceal hemorrhage were randomized to receive propranolol (P) (34 patients), or sclerotherapy (S) (42 patients) approximately 12 days after initial bleeding. The 2 groups were similar as concern age, sex, etiology of cirrhosis, severity of liver failure, the number of previous hemorrhages, and the severity of initial hemorrhage. No side effects were observed in the P group; 20 patients (48 percent) in the group S had at least one side effect although minor. After an average follow-up of 36 months, 18 patients in group P (53 percent) and 23 in group S (55 percent) had hemorrhagic recurrence. Rebleeding occurred from other sources than esophageal varices in 5 patients, in the group S only. Five patients in group P and 8 patients in group S died of rebleeding. During the follow-up period, 8 patients in group P (23 percent) and 13 patients in group S (31 percent) died. No significant difference could be demonstrated between the 2 groups as regards the percentages of patients without variceal rebleeding or survival, calculated according to the Kaplan Meier method. In conclusion, in this trial, no significant difference could be demonstrated between propranolol and endoscopic sclerosis in the prevention of recurrent variceal hemorrhage in alcoholic cirrhotic patients.

Endoscopic photodynamic therapy with haematoporphyrin derivative in gastroenterology.

Endoscopic photodynamic therapy (PDT) with haematoporphyrin derivative was used in the primary treatment of 69 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups: 31 with oesophageal squamous cell carcinoma, 17 with adenocarcinoma of the stomach or lower third of the oesophagus and 21 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg haematoporphyrin derivative per kilogram of body weight, lesions were irradiated using an argon dye laser (632 nm). During a follow-up period averaging 20 months (27.9 months for 35 surviving patients), complete local tumour destruction and negative histology were observed in 32 out of 69 cases. Flow-cytometric analysis of DNA content before and after PDT suggests that a clonal selection occurs in some cases of treatment failure. The results of this open pilot study suggest the potential efficacy of PDT as a curative treatment for selected cases of inoperable gastrointestinal cancers.