The Danish polyposis register

A manual Danish register of patients with familial polyposis coli and their family members was established in 1971. The methods of collection of propositi, preparation of pedigrees, collection of call-up cases, and the organization of the register are described. A country-wide prophylactic proctosigmoidoscopic examination of first-degree relatives, aged 10 to 59 years, resulted in the detection of 42 call-up cases and by December 1982, 319 cases of polyposis were registered in 94 families. An evaluation of the number of collected propositi and call-up cases shows almost complete registration. Dr. Bülow has received grants from the Danish Cancer Society (809/71 and 87/80), “Max and Anna Friedmanns Legat,” and “Ferdinand og Ellen Hindsgauls Fond.”     

Gastroduodenal polyps in familial polyposis coli

A total of 26 patients with familial polyposis coli without extracolonic manifestations were examined by gastroduodenoscopy. Histologically verified polyps were found in 18 patients (69 percent, 95 percent confidence limits 48–86). Gastric adenoma was diagnosed in one patient, fundic gland polyposis in six patients, and duodenal adenomas in 12 patients. It is concluded that the incidence of gastroduodenal polyps is independent of the clinical presence of other extracolonic manifestations. It is advisable that polyposis patients should be followed with gastroduodenoscopy and biopsy of polyps. Grants: Dr. Bülow has received grants from The Danish Cancer Society (809/71 and 87/80), “Max og Anna Friedmanns Legat,” “Ferdinand og Ellen Hindsgauls Fond” and “Arkitekt Holger Hjortenberg og hustru, Dagmar Hjortenbergs Fond.”     

Results of national registration of familial adenomatous polyposis

BACKGROUND AND AIMS: The Danish Polyposis Register was established in 1971 with the aim of improving the poor prognosis of familial adenomatous polyposis (FAP), and in 1975 the register became national. The aim of the present study was to evaluate the prevalence of colorectal cancer and survival rate in FAP patients before and after the establishment of the Danish Polyposis Register. PATIENTS AND METHODS: The Danish Polyposis Register was established by collecting information on probands and construction of their pedigrees. Family members at risk were offered prophylactic endoscopic and molecular genetic examination, and affected individuals were treated by colectomy. RESULTS: At the end of 2001, the Danish Polyposis Register included 434 patients from 165 families. The incidence rate was 1.90x10(-6) and the prevalence rate 4.65x10(-5). Colorectal cancer on the basis of FAP constituted 0.07% of all colorectal cancers in the 1990s. Colorectal cancer was diagnosed in 170/252 probands (67%) and in 5/182 call-up patients (3%) (p<0.001). The cumulative crude survival was 94% in call-up patients compared with 44% in probands (p<0.0001). A comparison of two periods, 1900-1975 and 1976-2001, demonstrated a decreased prevalence of colorectal cancer from 60% to 27% (p<0.0001), and an increased use of colectomy from 52% to 93% (p<0.00001). The cumulative crude survival in FAP showed substantial improvement with time (p<0.00001). CONCLUSION: Since the establishment of the Danish Polyposis Register, the prevalence of colorectal cancer has decreased considerably and the prognosis has improved substantially. The work of the Danish Polyposis Register is probably the main cause of this improvement.     

Centralized Registration,Prophylactic Examination,and Treatment Results in Improved Prognosis in Familial Adenomatous Polyposis: Results from the Danish Polyposis Register

Background: Over the last few decades numerous regional and national registers have been established all over the world with the aim of improving survival in familial adenomatous polyposis (FAP). The Danish Polyposis Register was founded in 1971 and coordinates the screening and subsequent prophylactic colectomy of FAP patients. Methods: The crude cumulative survival in 321 patients (205 probands and 116 call-up cases) with verified FAP was calculated in accordance with the life-table method. Results: At the time of diagnosis of FAP only 2 of 116 (2%) had colorectal cancer versus 142 of 205 probands (69%). The 10-year cumulative survival was 94% (95% confidence limits, 89-99) in call-up cases compared with only 41% (34-49) in probands (p < 0.00001), and survival improved significantly (p < 0.00001) after the establishment of the Danish Polyposis Register. Conclusion: The establishment of a centralized polyposis register has resulted in a substantial improvement of the prognosis in FAP.     

Papillary thyroid carcinoma in Danish patients with familial adenomatous polyposis

All patients from the nationwide Danish Polyposis Register have been followed up with regard to thyroid carcinoma. During the period 1943–1985, 2/107 Danish women and 0/138 men developed papillary thyroid carcinoma after the diagnosis of familial adenomatous polyposis. The expected number among females was 0.02 resulting in an observed/expected ratio of 100 (95% confidence limits 12–361). Consequently, thyroid carcinoma should be included among the extracolonic lesions, which may develop in any female polyposis patient. However, regular thyroid examination is not indicated, as thyroid carcinoma is uncommon and as the prognosis is excellent.     

Causes of death in familial adenomatous polyposis.

BACKGROUND: The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer. METHODS: The material consisted of 328 patients (144 females and 184 males) registered from I January 1943 to 31 December 1992 in the Danish Polyposis Register. The standard mortality rate (SMR) was calculated for known major causes of death, using the entire Danish population as background population. The attributable risk was also calculated for selected death causes. RESULTS: One hundred and thirty-three patients had died, SMR being 4.98 (95% confidence limits, 4.17-5.90). There were significantly lower SMRs in the call-up group than in the proband group. The late cohort (1943-1992) had lower SMRs than the early group (1889-1942). SMR was significantly increased for death due to colorectal cancer (145), duodenal cancer (214), and ovarian cancer (30). No deaths due to desmoids were observed in the examination period. The attributable risk for colorectal cancer was 29% and for duodenal cancer only 0.6%. CONCLUSION: Colorectal cancer is the most frequent cause of death in polyposis patients, followed by duodenal/periampullary cancer, but the latter is still a rare cause of death in FAP.     

Small-intestinal involvement in famialial polyposis diagnosed by operative intestinal fiberscopy: Report of four cases

Summary Operative intestinal fiberscopy, in which the duodenal fiberscope was introduced during laparotomy for colectomy in familial polyposis via the enterotomy opening, permitted the demonstration of small intestinal polyps in six of seven consecutive cases. Four of the six patients had adenomatous polyps in the proximal jejunum, including one patient with the concomitant presence of ileal adenomas. Polyposis due to lymphoid hyperplasia in the terminal ileum was found in three patients. Preoperative upper gastrointestinal surveys revealed adenomas in the duodenums of all seven patients, adenomas in the gastric antrum in three, and multiple hamartomas in the gastric corpus in two. Thus, in familial polyposis or Gardner's syndrome, more or less the entire gastrointestinal tract seems to be involved and the term “gastrointestinal polyposis” seems to describe these conditions.     

The risk of developing rectal cancer after colectomy and ileorectal anastomosis in Danish patients with polyposis coli

Fifty-eight Danish polyposis patients had been treated with colectomy and ileorectal anastomosis by the end of 1982. Three of these patients developed rectal cancer despite regular proctoscopic control, but one was probably an overlooked synchronous cancer. The cumulative risk at five and ten years after operation (actuarial method) was 3.5 and 13.3 per cent (95 per cent confidence limits 0–10.3 and 0–70.3 per cent, respectively), which seem to be acceptably low figures. This study supports the assumption that colectomy and ileorectal anastomosis is still the operation of choice in polyposis patients without rectal cancer.     

The incidence rate of familial adenomatous polyposis

Based on the Danish Polyposis Register epidemiological calculations on familial adenomatous polyposis (FAP) were carried out. The mean annual incidence was 1.85x10^-6 during the years 1971–1992, and the prevalence increasing to about 32x10^-6 at the end of 1992. FAP patients constituted a decreased percentage of all Danish patients with colorectal cancer (0.07% in 1980–1992). The completeness of registration was 97% in 1983–1992. The results are similar to Finnish estimates based on the same direct method of calculation, and as both series are based on almost complete national polyposis registration in well-registered populations we regard our results to be close to the true incidence rate.

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Résumé En se basant sur le registre danois des polyposes, des calculs épidémiologiques ont été réalisés sur la polypose familiale multiple. L'incidence annuelle moyenne est de 1.85x10^-6 au cours des années 1971 à 1992 et la prévalence augmente à environ 32x10^-6 à la fin de 1992. Les patients porterus d'une polypose familiale constituent un pourcentage en diminution de tous les patients porteurs d'un cancer colo-rectal (0.07% entre 1980 et 1992). L'exactitude du registre était de 97% entre 1983 et 1992. Les résultats sont similaries aux estimations finlandaises basées sur une même méthode de calcul; et étant donné que les deux séries témoignent d'un enregistrement pratiquement complet des polyposes à l'échelon national dans une population correctement enregistrée, nos résultats semblent refléter l'incidence réelle de l'affection. and increasing bias due to the significant improval of the prognosis of familial adenomatous polyposis during the last decades. Moreover, most studies are not based on epidemiologically valid patient series without selection bias. Recent calculations of the incidence rate with a direct method have been published on the basis of the national Danish and Finnish polyposis series, showing an annual incidence rate of 1.3–1.6x10^-6 in the early 1980's [5, 6].The aim of the present study was to reevaluate the occurrence of the disease about 25 years after the establishment of the Danish Polyposis Register by presenting estimates on the incidence rate, the point prevalence rate, and the completeness of registration.

     

Liposome-Mediated Adenomatous Polyposis Coli Gene Therapy: A Novel Anti-Adenoma Strategy in Multiple Intestinal Neoplasia Mouse Model

PURPOSE Familial adenomatous polyposis is a highly penetrant, autosomal dominant disease resulting from a germline mutation of the adenomatous polyposis coli gene. Besides colorectal polyps and cancer, more than 90 percent of familial adenomatous polyposis patients also develop duodenal polyposis with an approximately 5 percent lifetime risk of malignant transformation. Because adenomatous polyposis coli protein has a gatekeeper role in the adenoma–carcinoma sequence, replacing its function may reduce polyp formation. We studied the functional outcome of per-oral, liposome-mediated adenomatous polyposis coli gene replacement therapy in a multiple intestinal neoplasia mouse model.METHODS Twenty multiple intestinal neoplasia mice, heterozygous for the human homologue adenomatous polyposis coli gene, were randomly assigned to three groups: no treatment (n = 8); control plasmid containing green fluorescence protein reporter gene (n = 6); and plasmid containing the full-length adenomatous polyposis coli gene (n = 6). For the adenomatous polyposis coli–treated and green fluorescence protein reporter gene–treated groups, each mouse received the appropriate plasmid complexed with liposome, administered twice per week by oral gavage regime. Treatment lasted four weeks and all animals were killed at the end of treatment period with harvesting of intestinal tissue for polyp number estimation.RESULTS There was a statistically significant 25 percent reduction in the total number of polyps in the adenomatous polyposis coli–treated (73.1 ± 1.4) group compared with untreated control (97.8 ± 5.3, P < 0.01, Tukey test) and multiple intestinal neoplasia mice treated with control green fluorescence protein gene (103.3 ± 1.7, P < 0.01, Tukey test).CONCLUSION Adenomatous polyposis coli gene dysfunction underlies tumorigenesis in familial adenomatous polyposis patients and multiple intestinal neoplasia mice. This in vivo study provides evidence to support a novel anti-adenoma strategy using enteral adenomatous polyposis coli gene replacement therapy.Reprints are not available.J. Lee was supported by a grant from the Cancer Research United Kingdom.Presented at the meeting of the Association of Coloproctology of Great Britain and Ireland, Manchester, United Kingdom, July 3 to 5, 2002.     

Impact of Screening Examinations on Survival in Familial Adenomatous Polyposis

Background: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). Methods: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. Results: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P &lt; 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause ofdeath was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. Conclusion: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.     

Is Internet Information Adequate to Facilitate Surgical Decision-Making in Familial Adenomatous Polyposis?

Purpose Prophylactic surgery decisions are difficult. Supplemental information improves patients’ knowledge, promoting active participation in decision-making. Our objective was to examine internet information regarding prophylactic surgery for familial adenomatous polyposis to determine its adequacy in facilitating patient participation in surgical decision-making. Methods We searched the internet for information on surgery for familial adenomatous polyposis, using an intentionally simple strategy to represent patients’ searches. We examined the first 50 sites from each search, assessing each for content by using predefined criteria. Every site was evaluated by two investigators (kappa 0.71) by using the DISCERN criteria, a tool for evaluating quality of health information. Search-efficiency was calculated. Results Searches revealed 307,138 “hits”; 20 sites met inclusion criteria. GOOGLE™ demonstrated the highest search-efficiency (28 percent). Sites were maintained by general health pages (35 percent), hospitals (30 percent), professional organizations (15 percent), familial adenomatous polyposis registries (10 percent), and government (10 percent). Only 40 percent had been developed and/or updated within two years. Most included basic information regarding risk, symptoms, diagnosis, as well as discussion of familial adenomatous polyposis-associated diseases and surveillance (80–100 percent). Although 90 percent of sites presented surgical treatment options, only 60 percent provided details. Few provided information regarding postoperative bowel function (40 percent), sexual function (20 percent), or fertility (5 percent). Seven (35 percent) were identified as being of “good/excellent” quality. Only four were patient-oriented; variable information was provided. Conclusions Internet information regarding surgical treatment of familial adenomatous polyposis is sparse, and insufficient to support active patient participation in decision-making. Despite the time and financial commitment required, development of high-quality internet resources may be justified given the lack of adequate patient-oriented information currently available. Dr. Neuman is a research fellow of the Agency for Healthcare Quality and Research; this project was partially supported by grant number 5 T32 HS000066-13. Dr. Temple is supported in this project by a Career Development Award from the American Society of Clinical Oncology. Presented at the meeting of the Society for Medical Decision Making, Boston, Massachusetts, October 15 to 18, 2006. Reprints are not available.     

Preventive home visitation programmes for older people: the role of municipality organisation

The organisational influence on benefits of preventive home visitation programmes for older people has escaped scientific evaluation. This study aims to investigate organisational structures and processes in relation to preventive home visits. As part of a randomised controlled trial investigating whether educational intervention towards municipality health care professionals could enhance active life expectancy, information of municipality leadership, home visit approach, strengths and limitations of communication within the organisation were obtained using individual and focus group interviews. Thirty-four municipalities in four counties participated. Data was systematically condensed using a phenomenological approach upon which general patterns were categorised into a theory-based formal typology of the preventive home visitation management in the municipalities. Three distinct strategies for preventive home visitation programmes were identified. Eighteen municipalities were categorised as “Framework Management”, 15 as “Management by Rules” and one as “Project Management”. Small municipality size was associated with the “Framework Management” type. “Management by Rules” municipalities had higher population densities and their overall expenses for older people were higher. “Framework Management” municipalities used more resources on preventive home visits, communicated better, experienced less staff changing and had higher social capital than “Management by Rules” municipalities. Municipality structures and management processes of preventive home visitation programmes varied considerably in 34 Danish municipalities, but the majority could be categorised as using either a “Framework Management” or a “Management by Rules” strategy. Each strategy is associated with particular advantages and disadvantages, which may explain differences in the overall benefit of the programme between municipalities. This study was supported by grants from the Danish Medical Research Council, the Research Foundation for General Practice and Primary Care, Eastern Danish Research Forum, the County Value-Added Tax Foundation and the Danish Ministry of Social Affairs.     

Impact of screening examinations on survival in familial adenomatous polyposis

BACKGROUND: Prophylactic family screening and surgery has improved the outcome of patients with familial adenomatous polyposis (FAP) largely preventing deaths due to colorectal cancer. The present study compared the mortality rates and causes of death of FAP patients diagnosed by symptoms (probands) or by family screening (call-up). METHODS: The study comprised all 236 FAP patients registered in the Finnish Polyposis Registry until the end of June 1998. There were 116 probands and 120 call-up patients with a median age of 36.8 and 22.8 at diagnosis and median follow-up times of 6.3 and 9.9 years, respectively. Cumulative crude and relative survival estimates were calculated for each group and the causes of death were determined. RESULTS: The life expectancy was significantly better in the call-up group than in the probands after colectomy (P < 0.001). The survival rates of the call-up group equaled those expected for a comparable group in the general population up to 18 years after colectomy. The main cause of death was colorectal cancer accounting for 54 out of 68 deaths: four in the call-up group (all rectal stump cancer) and 50 in probands. Upper GI-tract cancer caused four deaths (periampullary cancer two, stomach cancer two) and two deaths were due to postoperative pulmonary embolism. CONCLUSION: The survival of FAP patients is significantly improved by prophylactic screening and surgery. Further improvement may be possible by using restorative proctocolectomy instead of colectomy and ileorectal anastomosis and by regular upper GI-tract endoscopic surveillance.     

Mesenteric Desmoid Tumors in Singapore Familial Adenomatous Polyposis Patients: Clinical Course and Genetic Profile in a Predominantly Chinese Population

Purpose This study examined the mutational profile of the adenomatous polyposis coli gene in relation to the development of desmoid tumors in familial adenomatous polyposis patients from a predominantly Chinese population. Methods This is a retrospective review of all patients with familial adenomatous polyposis coli from the Singapore Polyposis Registry. Identification of specific adenomatous polyposis coli gene mutation was performed and clinical course of associated desmoid disease obtained from case records and a computerized database. Results Two hundred five patients from 75 families afflicted with familial adenomatous polyposis coli were reviewed, with gene mutations identified in 107 patients. Of these, 23 (11.2 percent) developed desmoids. The male-to-female ratio was 1:1.3 and the ethnic distribution was Chinese (n=17) and Malay (n=6). Of the 92 patients with mutations 5′ to codon 1444, 11 patients (12 percent) developed desmoids compared with 6 of 15 (40 percent) patients with adenomatous polyposis coli gene mutations 3′ to codon 1444 (P<0.01). The clinical course of desmoid tumors can be divided into stable (n=11), variable (n=3), progressive (n=6), and aggressive growth (n=3). Only 3 (13 percent) patients with aggressive tumor growth required chemotherapy. There was no correlation between the site of mutation and the clinical progression of the desmoids. Seventy-four percent of these desmoids (17/23) developed at a mean interval of 2.98 years after restorative proctocolectomy, while only 30 percent (7/23) were diagnosed preoperatively or discovered during the initial surgery. The most common complications related to the mesenteric desmoids were intestinal obstruction (21.7 percent), ureteric obstruction (17.4 percent), and encasement of superior mesenteric vessels (13 percent). Conclusion The clinical course of desmoids in an individual familial adenomatous polyposis patient remains unpredictable and no reliable genetic marker is available for prognostication in desmoid disease. Poster presentation at the 12th World Congress of the International Society of Digestive Surgery (ISDS), Yokohama, Japan, December 12 to 14, 2004. Presented at the meeting of the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC), Salt Lake City, Utah, October 23 to 24, 2005.     

Cap Polyposis: Further Experience and Review

PURPOSE: Cap polyposis is characterized by the presence of inflammatory polyps with a cap of granulation tissue. It may represent one end of a spectrum of conditions caused by chronic straining. This experience represents the second largest reported series of cap polyposis.METHODS: The case notes of all patients with histologically proven cap polyposis were reviewed retrospectively and clinicopathologic features identified. A MEDLINE search was performed from 1985 to 2002 using cap polyps, polyposis, and inflammatory polyp as key words and further hand search was undertaken of key references.RESULTS: Eleven cases (9 males; median age, 20 (range, 15–54 years) of cap polyposis were diagnosed between 1993 and 2002. The commonest presenting symptoms were rectal bleeding (82 percent) and mucous diarrhea (46 percent). Chronic straining at stool and constipation were noted in seven of these patients (64 percent). Digital rectal examinations revealed polypoidal masses in the rectum in four patients (36 percent). All patients underwent colonoscopy. The commonest site of involvement was in the lower rectum (82 percent). One patient had polyps in the sigmoid colon and one patient in the transverse colon. Of 11 patients, 2 defaulted follow-up after colonoscopy. Three patients with solitary polyps had complete resolution of symptoms after polypectomy and remained symptom-free at three-month follow-up. The remaining six patients had persistent symptoms and required surgical intervention. Four underwent anterior resection and were all symptom-free at median of 48 (range, 18–72) months after surgery. One patient had transanal excision of rectal polyps and had recurrence at three months after surgery. This patient refused further treatment and remains symptomatic to date. One patient presented with recurrence of polyps at the coloanal anastomosis soon after a pull-through procedure. Total colectomy and ileal pouch-anal anastomosis was performed and the patient was free of symptoms at four months after surgery.CONCLUSIONS: Cap polyposis is eminently treatable with good long-term prognosis and function. Patients with solitary cap polyp respond well to endoscopic polypectomy. However, patients with multiple polyps and concurrent anorectal pathology require surgical resection.Presented at the joint meeting: Leeds Castle Polyposis Group and International Collaborative Group Hereditary Non-polyposis Colorectal Cancer, Cleveland, Ohio, September 2 to 6, 2003.Reprints are not available.     

The use of bisphosphonate in the treatment of avascular necrosis: a systematic review

Up to now, there is no uniformly accepted treatment for avascular necrosis (AN) that alleviates pain and retards its progression. The aim of clinical and surgical treatments is usually only to improve blood support in the avascular area. The objective of the present study was to make a systematic review of the use of bisphosphonates in the treatment of AN. Studies in which bisphosphonate was used for the treatment of AN were researched through the MEDLINE databases (from 1966 to 2007) and the Cochrane Central Register of Controlled Trials and using the following terms: “avascular necrosis,” “aseptic necrosis,” “bisphosphonates,” “alendronate,” “pamidronate,” “zoledronate,” and “risedronate”. Only seven articles that met the previously established criteria were obtained from MEDLINE, and none were obtained from the Cochrane Central Register of Controlled Trials. Of these seven articles, two were randomized clinical trials and five were prospective comparative studies; one of them corresponded to an extension of a previous study. The present review demonstrates that there are no controlled and double-blind studies about the efficacy of bisphosphonates in the treatment of AN. Therefore, the data are still insufficient for justifying its use for this indication. On the other hand, noncontrolled studies appear to demonstrate favorable results, particularly in diminishing pain, improving mobility, and lowering the incidence of articular collapse, which justifies new studies being developed in this area.     

Comparison of Mesalazine and Balsalazide in Induction and Maintenance of Remission in Patients with Ulcerative Colitis: A Meta-Analysis

Background 5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention. Aim To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis. Methods Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: “mesalazine” or “5-aminosalicylic acid” and “balsalazide” and “ulcerative colitis.” Data were collected from 1966 to 2007 (up to February). There was no language restriction. “Symptomatic remission,” “complete remission,” “relapse rate,” “total adverse events,” and “withdrawals because of adverse events” were the key outcomes of interest. Results Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these “symptomatic remission,” “complete remission,” “relapse rate,” “total adverse events,” and “withdrawals because of adverse events” were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03–1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002–1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56–1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75–1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37–1.29, P = 0.24). Conclusion Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.     

A European survey on the detection and management of iron overload in transfusion-dependent patients with MDS

To better understand the detection and management of iron overload in transfusion-dependent patients with myelodysplastic syndromes (MDS), a 15-min web- or paper-based survey was conducted among 338 European physicians from 27 countries. Respondents had a mean of 18 years of clinical experience. Forty-six percent and 27% of physicians noted that detecting and treating iron overload were either “very important” or “important,” respectively. The main reason for not actively exploring iron overload was related to poor patient prognosis, while the main reasons for not initiating iron chelation therapy were poor patient prognosis and older patient age. Thirty-seven percent and 31% of physicians believed that treating iron overload in these patients was “very important” or “important,” respectively. Ninety percent of physicians prescribed iron chelation therapy, and 38% of transfusion-dependent patients received iron chelation therapy. The key reasons for not initiating iron chelation therapy were related to poor patient prognosis (72%), patient age ≥85 years (50%), and comorbidities (34%). The views of these experienced MDS physicians reflect available international MDS treatment guidelines.     

The establishment of a polyposis register

Guidelines are presented for the establishment of a regional or national register of patients with familial adenomatous polyposis. The detailed recommendations are based on the work in committees of the Leeds Castle Polyposis Group and the EuroFAP. The aims of national and regional polyposis registers are discussed, and the stages of development of a register are reviewed: Ascertainment of probands, construction of pedigrees, identification of family members at risk, and screening of members at risk. The problem of data confidentiality is discussed.

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Résumé Les consignes sont présentées pour l'établissement d'un registre Régional ou National des patients avec polypose adénomateuse familiale. Les recommandations détaillées sont basées sur les travaux des comités du Leeds Castle Polyposis Group et de EuroFAP. Les buts des registres Régionaux ou Nationaux des polyposes sont discutés et les stades de développement du registre sont passés en revu: l'assurance de probande, la construction de l'arbre généalogique, l'identification des familles des membres à risques et l'étude des membres à risques. Le problème de la confidentialité des faits est discuté.

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This paper is based on a report from committees of the Leeds Castle Polyposis Group and the EuroFAP.