International validation of the Chinese University Prognostic Index for staging of hepatocellular carcinoma:a joint United Kingdom and Hong Kong study

The outcome of hepatocellular carcinoma （HCC） patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index （CUPI） for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer （BCLC） classification and the Cancer of the Liver Italian Program （CLIP）. To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom （UK; n = 567; 2006-2011） and Hong Kong （HK; n = 517; 2007-2012）. The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index （C-index） and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be optimal for those     

Use of femur length/abdominal circumference ratio in detecting the macrosomic fetus

The femur length/abdominal circumference ratio, expressed as FL/AC X 100, was determined in 156 fetuses and evaluated as a predictor of fetal macrosomia within one week prior to delivery. The normal range (mean +/- 2 SD) in the 105 normal-weight fetuses was 22.0 +/- 2, while the normal range in the 51 macrosomic fetuses was 20.5 +/- 2; these differences were highly significant (P = less than .0001). The predictive power of a positive ratio was 68%, with a sensitivity of 63%. This ratio was particularly useful in the subset (n = 9) of macrosomic fetuses whose mothers were diabetic, correctly identifying 89% of this group. Because it is age independent, this ratio should prove most helpful in identifying fetuses at risk for macrosomia in patients whose dates are not known, since it may become abnormal before the fetal weight falls above the 90th percentile at term (3,900 g). In patients whose dates are known, early fetal macrosomia is best predicted by evaluating the abdominal circumference against normal standards for age.     

The Heartsink Patient: A Preliminary Study

Eight GPs identified 78 heartsink patients; in an open-endedinterview they were asked to explain why they regarded themin this way. A GP's definition of a heartsink patient was influencedby GP sex, practice location, and time of surgery, althoughthe number of participating GPs was too low to make any definiteassertions. Practitioners' anticipations of heartsink consultationswere generally over-exaggerated, with most of the encountersgoing better than expected. GPs expressed the view that thesepatients raised serious professional issues for them, whilstthere was also a dislike for these patients' personalities andbehaviour. Two levels of the heartsink state are hypothesized:one, a state of inertia, is when the heartsink patient has beena chronic high user of the primary health care system, and aGP has exhausted all avenues. The other is an acute situationwith those heartsink patients who have been low users of thesystem in the past. Recent, new events in these patients' liveshave raised an issue that is just as much to do with patientand doctor reaction to these events, as it is about findinga diagnosis or solution to the problem. We present the results and hypotheses to provoke further discussionand research.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.