Unintentional Infusion of Phenylephrine into the Epidural Space.

We describe a patient who received an unintentionally prolonged epidural infusion of phenylephrine. The patient experienced no major morbidity. However, this case highlights the continuing problem of wrong-route drug administration and the urgent need to adopt route-specific connections.

Short-term preoperative radiotherapy in rectal cancer patients leads to a reduction of the detectable number of lymph nodes in resection specimens.

BACKGROUND AND AIMS: The Union Internationale Contre le Cancer and American Joint Committee on Cancer classification propose that pN(0)-classified colorectal lymphadenectomy specimens will ordinarily include 12 or more tumor-negative lymph nodes. We performed a clinical trial to investigate whether a short-term preoperative radiotherapy (5x5 Gy) leads to a reduction of the number of lymph nodes in rectal cancer specimens after total and partial mesorectal excision (TME and PME, respectively). MATERIALS AND METHODS: Within a 5-year period, 28 (15%) of 148 rectal cancer patients underwent hypofractionated preoperative radiotherapy in this monocenter study, whereas 120 patients (85%) underwent TME/PME surgery alone. The main criterion was the number of lymph nodes in TME/PME specimens. We used a stratified one-sided Wilcoxon-Mann-Whitney test to test for a significant difference in the number of lymph nodes, stratifying for tumor location and postoperative tumor stage. Patients who were suspected of having any alterations in the number of pelvic lymph nodes were excluded from the study. RESULTS: Fewer lymph nodes were detected in the TME/PME specimens of patients who received hypofractionated preoperative radiotherapy compared to patients who underwent TME/PME surgery alone (12 detectable lymph nodes vs 15; p=0.0005). Tumor location (p=0.095) and tumor stage (p=0.093) did not significantly influence the number of lymph nodes in this study. CONCLUSIONS: We conclude that a 5x5 Gy short-term preoperative radiotherapy leads to a reduction in the number of lymph nodes in TME/PME specimens. Because neoadjuvant therapy in rectal cancer for T(2) and T(3) tumors has advanced a new therapeutic standard procedure, in the future, less lymph nodes will be detected in TME/PME specimens. This might influence the required number of lymph nodes in current staging systems for rectal cancer in the future.

Anticipation in familial pancreatic cancer.

BACKGROUND: Previous studies of anticipation in familial pancreatic cancer have been small and subject to ascertainment bias. Our aim was to determine evidence for anticipation in a large number of European families. PATIENTS AND METHODS: A total of 1223 individuals at risk from 106 families (264 affected individuals) were investigated. Generation G3 was defined as the latest generation that included any individual aged over 39 years; preceding generations were then defined as G2 and G1. RESULTS: With 80 affected child-parent pairs, the children died a median (interquartile range) of 10 (7, 14) years earlier. The median (interquartile range) age of death from pancreatic cancer was 70 (59, 77), 64 (57, 69), and 49 (44, 56) years for G1, G2, and G3, respectively. These indications of anticipation could be the result of bias. Truncation of Kaplan-Meier analysis to a 60 year period to correct for follow up time bias and a matched test statistic indicated significant anticipation (p=0.002 and p<0.001). To minimise bias further, an iterative analysis to predict cancer numbers was developed. No single risk category could be applied that accurately predicted cancer cases in every generation. Using three risk categories (low with no pancreatic cancer in earlier generations, high with a single earlier generation, and very high where two preceding generations were affected), incidence was estimated without significant error. Anticipation was independent of smoking. CONCLUSION: This study provides the first strong evidence for anticipation in familial pancreatic cancer and must be considered in genetic counselling and the commencement of secondary screening for pancreatic cancer.

Efficacy of ice packs in the management of epistaxis.

There are no uniformly accepted criteria for the management of epistaxis. The usefulness of ice application in the treatment of epistaxis as a first aid method is not generally accepted, but is widespread. In order to evaluate the effect of cold application on the blood vessels of the nasal mucosa, their blood flow and blood content were investigated on 56 healthy volunteers before and after exposure to cold in the neck area. Nasal mucosal microcirculatory blood flow was measured directly by non-invasive laser Doppler flowmetry in Kiesselbach's area. Changes in the nasal mucosal blood content were estimated using a conventional computer-aided rhinomanometer by measuring alterations in nasal airflow. After ice application in the neck area, no statistically significant effects on the blood vessels of the nasal mucosa were seen. These results do not support the usefulness of this manoeuvre in the treatment of epistaxis.

German national case collection of familial pancreatic cancer - clinical-genetic analysis of the first 21 families.

BACKGROUND: The observation of a familial accumulation of ductal pancreatic adenocarcinoma (PC) and the increased risk for PC in certain hereditary tumor syndromes point to a genetic predisposition for PC. In order to evaluate the characteristics of familial PC, a German national case collection for familial pancreas cancer (FaPaCa) was established. PATIENTS AND METHODS: In FaPaCa, families of patients with PC are being collected, who have at least 1 first-degree relative with PC or with malignant melanoma. Histopathologic verification of tumor diagnoses, acquisition of clinical data, and full genetic counselling are prerequisites for the enrollment of PC families in FaPaCa. RESULTS: So far, 21 families fulfilled the criteria for partaking in FaPaCa. In 11 families, PC represented the sole tumor entity. Additional tumors included malignant melanoma in 5, breast cancer in 3, and prostatic, colon or lung cancer in 2 families. Compared to the preceding generation, a younger age at diagnosis of PC was observed in the offspring of PC patients (offspring median 53 years vs. parents median 75.5 years). CONCLUSION: The association of PC and breast cancer, and of PC and malignant melanoma suggests predisposing mutations in the BRCA2 or CDKN2A genes in about one third of the FaPaCa families. Mutational analyses in both candidate genes may help to identify individuals who are at an increased risk for developing PC. A shift towards a younger age at diagnosis in our PC families may indicate genetic anticipation and/or changes of patterns of exogenous risk factors.

The use of sequential designs in genome scans for asthma susceptibility loci with affected sib pairs.

We use optimized group sequential study designs to analyze data from two genome scans (German and CSGA) for asthma susceptibility loci with affected sib pairs from Genetic Analysis Workshop (GAW) 12. Results are compared with those from a fixed sample design and the sequential probability ratio test (SPRT). The SPRT does not reach significance at any position. Using the fixed sample design, evidence for linkage is found on chromosomes 6 and 9 in the German and on chromosome 1 in the CSGA scan. The group sequential designs identify the same regions on chromosomes 1 and 6 with a reduced sample size.

Update of familial pancreatic cancer in Germany.

BACKGROUND/AIMS: The prevalence of familial pancreatic cancer (FPC) and the characteristics of FPC have not yet been well investigated in the German population. Therefore, a German case collection for FPC was established in July 1999 to collect and evaluate data on FPC families. METHODS: The prevalence of pancreatic cancer (PC) as well as other tumours and diseases was studied in families with at least 2 first-degree relatives with histologically confirmed PC, and in families of patients with PC and a first-degree relative with malignant melanoma. All participating family members were genetically counselled and evaluated by a standardised questionnaire. RESULTS: In an 18-month period, 73 independent kindreds with potential FPC contacted the national case collection. So far, 20 kindreds have fulfilled the criteria for FPC and have undergone complete workups. Most families revealed an autosomal dominant pattern of inheritance. Twelve families revealed an isolated accumulation of PC. Importantly, in 8 of 20 (35%) families, additional tumour types such as melanoma, breast and prostate cancer occurred. CONCLUSION: The observed phenotypic heterogeneity indicates an association with predisposing tumour suppressor genes p16 and BRCA2 in up to 30% of FPC families. Mutation analysis of these candidate genes might lead to the identification of the predisposing gene defect in a proportion of FPC families.

A comparative analysis of thermal blood perfusion measurement techniques.

The object of this study was to devise a unified method for comparing different thermal techniques for the estimation of blood perfusion rates and to perform a comparison for several common techniques. The approach used was to develop analytical models for the temperature response for all combinations of five power deposition geometries (spherical, one- and two-dimensional cylindrical, and one- and two-dimensional Gaussian) and three transient heating techniques (temperature pulse-decay, temperature step function, and constant-power heat-up) plus one steady-state heating technique. The transient models were used to determine the range of times (the time window) when a significant portion of the transient temperature response was due to blood perfusion. This time window was defined to begin when the difference between the conduction-only and the conduction-plus-blood flow transient temperature (or power) responses exceeded a specified value, and to end when the conduction-plus-blood flow transient temperature (or power) reached a specified fraction of its steady-state value. The results are summarized in dimensionless plots showing the size of the time windows for each of the transient perfusion estimation techniques. Several conclusions were drawn, in particular: (a) low perfusions are difficult to estimate because of the dominance of conduction, (b) large heated regions are better suited for estimation of low perfusions, (c) noninvasive heating techniques are superior because they have the potential to minimize conduction effects, and (d) none of the transient techniques appears to be clearly superior to the others.