Contraception after breast cancer: a retrospective review of the practice among French gynecologists in the 2000's.

PURPOSE OF INVESTIGATION: To describe the French practices regarding contraception after breast cancer in the 2000's. MATERIALS AND METHODS: A total of 2,500 forms were sent to gynecologists practicing in France. Inclusion criteria were premenopausal patients who had a history of breast cancer and who had been prescribed contraception after diagnosis. Between June 1, 2002 and January 1, 2003, 197 evaluable responses were retrieved. RESULTS: The median age of the sample was 38.5 years. The most commonly used form of contraception was an intrauterine device (n = 144, 73.1%). Hormonal contraception was prescribed for 42 patients (21.3%), and other methods were used in 29 patients (14.7%) (Condoms n = 14, tubal sterilization n = 7, and others n = 8). Recurrence occurred in 27 patients (13%); 2.9% in the progestin group, 16.3% in the IUD group, and 14.8% with the other methods). CONCLUSIONS: It is necessary to evaluate current contraception practices after breast cancer to evaluate the efficacy and safety of contraception in these patients.

BI-RADS categorisation of 2,708 consecutive nonpalpable breast lesions in patients referred to a dedicated breast care unit.

OBJECTIVES: To determine the malignancy rate of nonpalpable breast lesions, categorised according to the Breast Imaging Reporting and Data System (BI-RADS) classification in the setting of a Breast Care Unit. METHODS: All nonpalpable breast lesions from consecutive patients referred to a dedicated Breast Care Unit were prospectively reviewed and classified into 5 BI-RADS assessment categories (0, 2, 3, 4, and 5). RESULTS: A total of 2708 lesions were diagnosed by mammography (71.6%), ultrasound (8.7%), mammography and ultrasound (19.5%), or MRI (0.2%). The distribution of the lesions by BI-RADS category was: 152 in category 0 (5.6%), 56 in category 2 (2.1%), 742 in category 3 (27.4%), 1523 in category 4 (56.2%) and 235 in category 5 (8.7%). Histology revealed 570 malignant lesions (32.9%), 152 high-risk lesions (8.8%), and 1010 benign lesions (58.3%). Malignancy was detected in 17 (2.3%) category 3 lesions, 364 (23.9%) category 4 lesions and 185 (78.7%) category 5 lesions. Median follow-up was 36.9 months. CONCLUSION: This pragmatic study reflects the assessment and management of breast impalpable abnormalities referred for care to a specialized Breast Unit. Multidisciplinary evaluation with BI-RADS classification accurately predicts malignancy, and reflects the quality of management. This assessment should be encouraged in community practice appraisal.

Association of serum antibodies against p53 protein with poor survival in patients with Zollinger-Ellison syndrome.

BACKGROUND & AIMS: Long-term survival of patients with Zollinger-Ellison syndrome (ZES) is largely determined by the presence or absence of liver metastases. However, because of the lack of precision of these criteria, development of further indicators is still required. Recent evidence showing that autoantibodies directed against the p53 protein could predict poor survival for some types of cancers prompted us to investigate the presence of such antibodies in sera from patients with ZES and their potential value as survival indicator. METHODS: Anti-p53 antibodies were detected in the sera of 44 consecutive patients with ZES using both an enzyme-linked immunosorbent assay (ELISA) and Western blotting. The mean follow-up of these patients was 92 months. RESULTS: Anti-p53 antibodies were detected in 7 of the patients with ZES (16%) by both ELISA and Western blotting. Univariate and multivariate analyses showed that the presence of anti-p53 antibodies (P = 0.0009 and P = 0.017, respectively) and liver metastases (P = 0.0009 and P = 0.012, respectively) was independently associated with shorter survival. CONCLUSIONS: These results suggest that anti-p53 antibodies are an indicator of survival and could be used in combination with staging to determine which patients with ZES have poor prognoses and therefore require reinforced therapy.

Quality of life in gastroenterology. Interest of a specific questionnaire for duodenal ulcer patients.

Quality of life (QoL), a subjective dimension, should be the most important criterion in the management of any disease. However, relevant methods have not been widely adopted although a large number of general health assessment measures are available. A consensus has now been reached on the importance of five domains: physical, mental, social and role functioning, and general health perception. Questionnaires are generally accepted as convenient tools, particularly when they include an assessment of general health and disease specific questions. In gastroenterology, chronic disease (e.g. Crohn's disease) and prolonged discomforts are ideal fields for QoL studies, and QoL data should be obtained in therapeutic trials. In duodenal ulcer (DU), the long-term nature of treatments and psychological status of patients make QoL studies of major interest, as exemplified by the nizatidine model.

A 'quality of life questionnaire' adapted to duodenal ulcer therapeutic trials.

In order to compare subpopulations of duodenal ulcer (DU) patients a quality of life (QoL) questionnaire (self-administered) was developed with the objective of investigating: (i) general parameters of health and well-being, and (ii) dimensions specifically adapted to patients with DU. For the former, Ware's MOS SF-36 was selected as a central core, with 36 items investigating 9 dimensions, and for the latter the anxiety scale (5 items) of the Psychological General Well-being Index (PGWBI) questionnaire and a further 5 dimensions (13 items) resulting from a preliminary survey of ulcer patients were selected. Validation of the proposed questionnaire was obtained for: linguistic aspects, content (i.e. ability to cover problems of patients suffering from DU), internal consistency, reliability, and sensitivity (i.e. analysis of discrimination between three groups of patients (acute DU episode, remission and control). The final version of the Quality of Life in Duodenal Ulcer Patients (QLDUP) questionnaire, which includes 54 items investigating 15 dimensions, appears to be a sensitive and reproducible tool, the simplicity of which makes it suitable for monitoring long-term treatments in DU.

A quality of life study in five hundred and eighty-one duodenal ulcer patients. Maintenance versus intermittent treatment with nizatidine.

Quality of life (QoL) is commonly assessed for evaluating the process and outcome of treatment but has not been studied in duodenal ulcer (DU) disease. The recently developed and validated Quality of Life in Duodenal Ulcer Patients (QLDUP) questionnaire allowed the study of various dimensions according to treatment regimens. This study was conducted to compare QoL over a one-year follow-up period in DU patients randomized to two treatment regimens: maintenance versus intermittent (no maintenance) treatment with nizatidine. A total of 581 patients with endoscopic evidence of DU healing were randomly allocated to receive either nizatidine 150 mg/day for one year (Group A) or intermittent treatment (Group B). In both groups, symptomatic relapses were treated with nizatidine 300 mg/day for 6 weeks. The QLDUP questionnaire, which provides a QoL profile from 54 items divided up into 15 dimensions, was completed by all patients at entry and again at the time of a visit every 2 months for one year. The one-year symptomatic relapse rates were 8.0% and 33.5% in Group A and Group B, respectively (p < 0.001). The intent-to-treat analysis showed that patients in Group A had better QoL scores than those in Group B as regards 8 QoL dimensions, including ulcer-specific and non-specific dimensions. Differences between treatments were significant after 4 months, and this was sustained until the one-year assessment. The overall gain in QoL was significantly greater in Group A than in Group B with respect to 11 QoL dimensions. In conclusion, maintenance treatment with nizatidine for DU improved QoL to a larger extent than when intermittent therapy was used.

[Effect of enprostil on the healing and the recurrence of duodenal ulcer. Comparison with ranitidine]. / Effect de l'enprostil sur la cicatrisation et la récidive des ulcéres duodénaux. Comparaison à la ranitidine.

Enprostil, a synthetic prostaglandin E2, has been shown to exert both antisecretory and mucoprotective activity. It is effective in duodenal ulcer healing. OBJECTIVE--This study was performed to compare the frequency and the delay of spontaneous duodenal ulcer relapse during a two-year follow up period after initial healing by enprostil (35 micrograms, twice a day) or ranitidine (300 mg per day). METHODS--This multicentric, double-blind, randomized study included 642 patients (324 in the enprostil group and 318 in the ranitidine group). Patients included in the follow up period were evaluated by an endoscopy at 6 months, one and two years after healing. RESULTS--After a 6 weeks treatment period, healing rate was 85% for ranitidine and 70% for enprostil, respectively (P < 0.001). Adverse effects, especially digestive ones, occurred more often with enprostil than with ranitidine (P < 0.001). After initial healing, there was no significant difference between the 2 groups concerning the cumulative rate of relapse, despite a non significant trend for a milder rate of relapse in the enprostil group (P = 0.08). Twenty-seven % of the patients randomized to treatment (intend-to-treat analysis) in the enprostil group and 29% in the ranitidine group had no ulcer recurrence 6 months after ulcer healing, and respectively 12% and 13% at 2 years (difference not statistically significant). CONCLUSIONS--It is concluded that a) ranitidine is more effective and has less adverse effects than enprostil for duodenal ulcer healing, b) after duodenal ulcer healing by enprostil, there is a non significant trend for a lower rate of relapse than after healing with ranitidine, c) there is the same proportion of patients without ulcer in the 2 groups after 6 months and 2 years.

Current approach to the management of gastrinoma and insulinoma in adults with multiple endocrine neoplasia type I.

The difficult and controversial diagnostic and therapeutic management of patients having gastrinoma or insulinoma with multiple endocrine neoplasia type I (MEN-I) has been discussed by reference to the literature and a personal series of 45 gastrinoma/MEN-I patients followed consecutively at Bichat Hospital. In both gastrinoma/ and insulinoma/MEN-I patients, anatomic distribution and morphology of tumoral process(es) are usually multiple, diffuse, of small size, and associated with endocrine cell hyperplasia and even nesidioblastosis. These features enhance the difficulty of tumor localization and eradication. Despite the dramatic development of modern medical imagery and surgical experience, the real possibility, on a long-term basis, of curing the patients from their disease remains limited, especially in the gastrinoma/MEN-I patients. In the latter group, according to our experience, persistence or recurrence of the disease after surgery is usual, and metachronous hepatic metastasis development is frequently observed when the follow-up is long enough. Patients with liver metastases, however, seem to undergo a more indolent course than sporadic gastrinoma cases. In insulinoma/MEN-I patients, removal of the functionally dominant islet cell area(s) is essential. Various preoperative and intraoperative localization techniques allow efficacious selective pancreatic surgery in many cases. The latter refinements and the promises of long-acting somatostatin analogs, if confirmed, might restrict to exceptional circumstances the indication of near-total or total pancreatectomy.

Gastric endocrine cell evolution in patients with Zollinger-Ellison syndrome. Influence of gastrinoma growth and long-term omeprazole treatment.

Evolution of gastrinoma tumoral mass, fasting serum gastrin concentrations, and gastric endocrine cells has been analyzed in 21 patients with the Zollinger-Ellison syndrome committed to long-term omeprazole treatment (up to 7.75 years, median 37 months). Gastrinoma growth was seen in eight patients. Significant increase in serum gastrin was only observed in the group of patients with gastrinoma growth. Fundic argyrophil cell densities were correlated with serum gastrin (r' = 0.68, P = 0.002). Argyrophil and antral gastrin cell densities significantly increased during the survey, but increases were greater in the group with gastrinoma growth (respectively, +136% and +131%) than in the other group (respectively, +34% and +43%). Progression in the degree of argyrophil cell hyperplasia, noted qualitatively, was observed in 11 patients. Fundic carcinoids developed in three of these 11 patients, all three having multiple endocrine neoplasia type 1 (MEN 1). Positive linear individual correlations (r > or = 0.85) between argyrophil cell densities and corresponding durations of omeprazole treatment were found in nine of the 10 patients studied at least three times and who had a clear-cut increase in those cell densities. Thus, increase in serum gastrin and fundic argyrophil cell densities appeared closely associated with gastrinoma growth; however, duration of drug-induced hypochlorhydria may also affect cell proliferation.

Long-term treatment with octreotide in patients with the Zollinger-Ellison syndrome.

This study reports the effects of 4 and 5-year treatment with octreotide (200 micrograms sc bid) in the Zollinger-Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h-1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pretreatment BAO value: 115 mmol h-1), BAO progressively decreased to 42 mmol h-1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30-68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35-89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin-cell density was in the normal range. No long-term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients.

Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia.

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.

Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis.

We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/- 17 years, mean +/- SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 +/- 10 years) and to an age-matched healthy population (63 +/- 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 +/- 0.7, 2.9 +/- 0.9 and 2.8 +/- 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process. This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients.

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80,000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2,700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1,994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity (r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.

Biologic and immunologic gastrin activity in serum of patients with gastrinoma. Bioassay of gastrin activity in serum.

The biologic gastrin activity in serum from 14 patients with the Zollinger-Ellison syndrome was assessed by the stimulation of histamine release and acid secretion from the isolated vascularly perfused rat stomach and compared with the immunologic activity as determined by radioimmunoassay using an antibody directed towards the active site of the gastrin molecule. Biologic gastrin activity assessed by the stimulation of histamine release was more closely correlated to immunologic gastrin activity than biologic activity assessed by the stimulation of gastrin acid secretion. This study does not contradict the concept that gastrin stimulates acid secretion at least partly by releasing histamine and also shows that the immunologic gastrin activity determined with the help of an antibody directed towards the active site reflects biologic activity.

Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome.

The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia, age, and sex on gastric endocrine cell densities were studied in 48 patients with the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women (p < 0.05). It showed no appreciable difference between young and old women but it declined with age in men. The mean argyrophil cell density, when adjusted for sex, was higher (+48.5%, p = 0.06) in patients with Zollinger-Ellison syndrome associated with MEN 1 than in those with sporadic type disease. This measurement was not significantly different between the two groups of patients when antisecretory treatments were considered. In patients with sporadic type disease, fundic argyrophil cells showed a normal pattern (16%) or diffuse (71%) or linear (13%) hyperplasia. In patients with MEN 1 diffuse and linear hyperplasia were of the same order (53% and 47%). Furthermore, fundic argyrophil endocrine tumours developed in five of 17-that is, 29.5% of patients with associated MEN 1 while none was seen in patients with sporadic type disease. These tumours showed an exclusive or prominent enterochromaffin like cell population. Antral gastrin and somatostatin cell densities and fasting serum gastrin concentrations were similar in the two groups of patients with Zollinger-Ellison syndrome. Whatever the underlying mechanism for carcinoidosis, the risk of developing fundic enterochromaffin like cell tumours in Zollinger-Ellison syndrome patients who present with MEN 1 is probably higher than was initially estimated and suggests that regular follow up of these patients is necessary.