Incidence of Second Primary Malignancies in Patients with Neuroendocrine Tumours.

BACKGROUND: An association between neuroendocrine tumours (NET) and increased risk of developing second primary malignancies (SPM) has been recognised. METHODS: This was a retrospective review of our institutional prospectively maintained database of NET patients. We identified patients who had been diagnosed with both neuroendocrine and any additional malignancies via examination of patient notes. RESULTS: Clinical data for 169 patients were analysed. After exclusion of patients known to have hereditary tumour predisposition syndromes, 29 SPM were identified in 26 patients (15.38%), the commonest being colorectal (n = 6), breast and renal carcinomas (both n = 5). SPM were classified as previous, synchronous or subsequent relative to NET diagnosis. Rates of SPM in pancreatic and small-bowel NET patients were comparable (15.7 vs. 19.6%, p = 0.78). A person-year methodology was used to compare observed numbers of SPM against expected values generated from age- and sex-specific incidence tables, with standardised incidence ratios (SIR) and 95% confidence intervals (CI) calculated. SPM incidence was significantly elevated in the synchronous subset (SIR 2.732, CI 1.177-5.382) whilst significantly fewer NET patients had a cancer history compared to the general population (SIR 0.4, CI 0.241-0.624). No overall differences were evident between observed and expected incidences of subsequent SPM (SIR 0.36, CI 0.044-1.051). The incidence of synchronous colorectal cancers was markedly elevated (SIR 13.079, CI 4.238-30.474). CONCLUSIONS: Our data support the use of colonoscopy in the diagnostic work-up of NET patients in anticipation of a colorectal SPM. The mechanistic underpinnings of this clinical phenomenon require further genetic investigation, and consideration of this knowledge in patient management pathways is warranted.

A study on variances in multivariate analyses of oral implant outcome.

BACKGROUND: Elaborate studies have shown that interdependency exists between implants being placed in the same patient/jaw. Therefore, interdependency ought to be an important aspect to address, whenever performing statistical analyses of oral implant outcomes. A Jackknife method could be an option when conducting statistical evaluations of oral implant failure prognoses. PURPOSE: The aim of this study was to evaluate whether a statistical difference can be detected by using the Jackknife method in conjunction with life table analyses and/or a log rank test of four different combinations of jaw density and quantity. MATERIALS AND METHODS: Four multicenter studies were pooled and adjusted in order to create a research database consisting of 486 patients and 1,737 implants in preparation for the Jackknife resampling method. Combinations of jaw shapes and bone qualities were constructed to select at-risk patients. STATISTICAL METHODS: Life tables with confidence intervals were calculated and a log rank test was used to determine whether a statistical difference between the combinations could be established. RESULTS: Both statistical analyses, after the Jackknife resampling method, showed that patients with poor bone quality and resorbed jaws (combination IV) had a statistically higher risk of implant failure. CONCLUSION: By rearranging data using the Jackknife method, standardized statistical tests seem to work well even when the study population tested was affected by interdependency.

Evaluation of patient and implant characteristics as potential prognostic factors for oral implant failures.

PURPOSE: The purpose of this study was to evaluate patient, implant, and treatment characteristics to identify possible prognostic factors for implant failure. MATERIALS AND METHODS: Out of a database with different dental implant treatment protocols, a research database of 1 randomly selected implant per patient was created. The database consisted of 487 implants. Of these, 80 were withdrawn, 36 failed, and 371 remained successful during a 5-year follow-up period. Potential risk factors were evaluated by chi-square tests and post hoc analyses. RESULTS: Significant or strongly significant differences were found regarding implant failures as a result of jawbone quality, jaw shape, implant length, treatment protocol, and combinations of jawbone-related characteristics. Responsible clinics and number of implants supporting the restoration were factors that could not be associated with implant failure. DISCUSSION: Implant failures in this study were more often seen when negative patient-related factors were present. Approximately 65% of the patients with a combination of the 2 most negative bone-related factors (jawbone quality 4 and jaw shape D or E) experienced implant failure. However, only 3% of the patients had this combination. Implant length, the only implant-related factor evaluated, was also significantly correlated with the success rate, but implant length could also be regarded as a result of the jawbone volume available. Another negative patient-related factor was the treatment protocol; however, in most cases this was also indirectly or partly related to the status of the jawbone available for implant placement. CONCLUSION: Patient selection appears to be of importance for increasing implant success rates.

Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth.

OBJECTIVE: Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP. DESIGN: We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). RESULTS: Low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if IGF-I was

Evaluation of the cohort size in phase I dose escalation trials based on laboratory data.

A survey of Phase I dose escalation trials published since 1995 shows that there is great disparity in all aspects of the design of the studies, and the cohort sizes range from 2 to 16 subjects with a great variety in the distribution between active and placebo-treated subjects. This study investigates the impact of the cohort size on Type I error and power in Phase I dose escalation trials based on laboratory data, with the hospitalization-induced increase in hepatic enzyme levels taken into consideration. The power of a Phase I dose escalation trial is very low, and only events with a very high probability of occurrence are detectable with acceptable power. For studies with cohort sizes smaller than 6 active subjects, there is much to gain with the inclusion of 1 extra subject, but for more than 10 subjects, little is gained by increasing the cohort size. With increasing cohort sizes, the probability of spontaneous non-drug-related events also increases, and this background rate needs to be considered when evaluating the trial.

Statistical outcome of random versus selected withdrawal of dental implants.

PURPOSE: When performing clinical trials, missing data from withdrawn patients should be evaluated differently, depending on the reason for the withdrawal of the patients. The question is, if a certain type of patient drops out, will that affect the result? Could a randomly selected sample of a study population be used for analyses instead of evaluating each and every patient? The purpose of this study was to answer these questions. MATERIALS AND METHODS: Detailed information on 1,738 implants in 487 patients was pooled together in a new database and used for statistical evaluations. Random or selected withdrawals were pulled from the database. Chi-squared tests were used for significance tests, and lifetables were used for survival analysis. RESULTS: There was a difference in the outcome depending on whether the withdrawals were randomly chosen or selected. Random withdrawals could represent, in this study, as much as 50% of the included patients without changing the statistical results. If selected withdrawals were based on which jaw was treated, the statistical outcome did change, but it did not change if withdrawals were based on gender or age. CONCLUSION: Evaluation of reasons for withdrawals and withdrawn patient characteristics are of utmost importance when evaluating clinical trials. A randomly selected sample of the entire population could, however, be expected to give the same statistical value as the entire group, if the original material were large enough. Therefore, the use of study samples may more easily enable clinicians to do follow-up investigations.