Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis

AIMS: To determine the clinicopathological and molecular features of gastric medullary cancer. METHODS AND RESULTS: Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non-medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low-grade non-medullary cancers than in high-grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non-medullary cancers (9.4%, 6/64) (P < 0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non-medullary cancers was 2380/10 high-power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's-like reaction were more common in medullary cancers than in non-medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's-like reaction 70.6%, 12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high-grade non-medullary cancers were more associated with reduced ECD expression in comparison with low-grade cancers (P < 0.05); (v) higher MSI-H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non-medullary (1.6%, 1/64) (P = 0). CONCLUSIONS: Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26-, might have prognostic implications, thus analysis of Bat26 may be of clinical value.     

How we do it: management of tracheobronchial foreign bodies in children

KEY POINTS: Foreign body aspiration remains an important pathology in children. Management of airway foreign bodies must be undertaken in specialized units with experienced staff and known protocols. Development and improvement of rigid bronchoscopes, with advances in anaesthesia have increased the efficacy and the safety of removing endotracheal foreign bodies. A video monitor is advantageous in coordinating the procedure and reducing the stress of the team. Utilization of Fogarty's catheters can be beneficial.     

Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk

In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis, defined by low bone mineral density and/or prevalent vertebral fractures (VF), were randomized to placebo or raloxifene (60 or 120 mg/day). All women received daily calcium (500 mg) and vitamin D (400-600 IU) supplements. Our previous analyses found that changes in BMD and biochemical markers of bone turnover are poorly predictive of the reduction in VF risk observed with raloxifene. This present study evaluated the effects of raloxifene on type I procollagen N-terminal propeptide (PINP), a new marker of bone turnover. Logistic regression analysis models evaluated the relationships between the changes at 1 year in PINP, serum osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and urinary excretion of type I collagen C-telopeptide fragments normalized to creatinine (CTx/Cr), and the risk of new VF at 3 years for placebo and pooled raloxifene. A subset of 967 women (mean age = 68 years) from the MORE cohort had PINP, OC, BSAP, and CTx evaluated at baseline. Both doses of raloxifene significantly decreased (P < 0.001) all biochemical markers of bone turnover from baseline. Compared to baseline, PINP levels were decreased by medians of 11.0% and 40.8% in the placebo and pooled raloxifene groups, respectively. In addition, the placebo and pooled raloxifene groups decreased serum OC by 8.5% and 31.8%, BSAP by 15.8% and 34.6%, and urinary CTx/Cr excretion by 5.6% and 46.5%, respectively, from baseline. In the pooled raloxifene group, the logistic regression relationship between 3-year VF risk and 1-year percentage change for each biochemical marker was statistically significant with PINP (slope estimate = 0.0085, P = 0.009), OC (slope estimate = 0.0068, P = 0.035), and BSAP (slope estimate = 0.0056, P = 0.039), but not with CTx/Cr (slope estimate = 0.0027, P = 0.192). Furthermore, the percent decrease in PINP at 1 year could account for 28% of the total reduction in vertebral fracture risk. In conclusion, a 1-year decrease in PINP, BSAP, or OC, but not CTx/Cr, may be predictive of the 3-year VF risk reduction with raloxifene therapy in this subset of postmenopausal women with osteoporosis.     

Extra vertebrae in Ingres' La Grande Odalisque

"La Grande Odalisque," a painting by Jean-Auguste Ingres (1780-1867), was throughout the 19th century notorious for its anatomical inaccuracy; in particular, the woman was said to have three lumbar vertebrae too many. This view was accepted by all art critics, but never tested and proven. We measured the length of the back and of the pelvis in human models, expressed the mean values in terms of head height, and transferred them to the painting. The deformation was found to be greater than originally assumed (five, rather than three, extra lumbar vertebrae), and to involve both the back and the pelvis. Ingres' paintings skilfully combine realism and symbolism. We suggest that the deformation may have been introduced for psychological reasons. By placing the harem woman's head further away from her pelvis the artist may have been marking the gulf between her thoughts (expressed by her aloof, resigned look) and her social role (symbolized by her deliberately lengthened pelvis).     

Fcgamma receptor IIa, IIIa, and IIIb polymorphisms of systemic lupus erythematosus in Taiwan

OBJECTIVE: To determine whether the distribution of Fcgamma receptor IIa, IIIa, and IIIb polymorphisms confers a risk factor for disease susceptibility, and correlates with the clinical characteristics and serological parameters of patients with SLE in Taiwan. METHODS: Genotyping of Fcgamma receptors IIa H/R131, IIIa F/V158, and IIIb NA1/NA2 was performed in 302 patients with SLE and 311 healthy blood donor controls. The distribution of Fcgamma receptor IIa, IIIa, and IIIb genotypes in patients and controls was analysed. Frequencies of three Fcgamma receptor polymorphisms were also compared between lupus patients with and without different clinical manifestations and autoantibodies. RESULTS: No significant skewing in the distribution of Fcgamma RIIa H/R131, Fcgamma RIIIa F/V158, and Fcgamma RIIIb NA1/NA2 was found between patients and controls in Taiwan. The following clinical associations were found: Fcgamma RIIIb NA1/NA1 protected against neuropsychiatric lupus (p = 0.028) but conferred susceptibility to discoid rash (p<0.005); increased Fcgamma RIIIa V/V158 was associated with infections (p = 0.039); increased Fcgamma RIIa H/H131 was associated with earlier onset of lupus (p = 0.01). CONCLUSION: Fcgamma receptor IIa, IIIa, and IIIb polymorphisms may be responsible for the development of distinct manifestations of lupus patients in Taiwan, but there is no significantly skewed distribution in the susceptibility to lupus as a whole.     

Post-irradiation neuromyotonia of the masseter muscle

INTRODUCTION: Neuromyotonia is a late and rare complication of radiation therapy, consisting of involuntary sustained muscle contractions with a delay in relaxation. OBSERVATION: We report the case of a 68-year-old man who developed neuromyotonia of the masseter muscle 6 years after irradiation for tonsil carcinoma. CONCLUSION: This observation underlines the importance of a correct diagnosis that can lead to an efficient treatment by carbamazepine.     

The Seoul Metropolitan Preschool Vision Screening Programme: results from South Korea

AIM: To report on a new model of preschool vision screening that was performed in metropolitan Seoul and to investigate the distribution of various ocular disorders in this metropolitan preschool population. METHODS: Vision screening was conducted on 36 973 kindergarten children aged 3-5 years in a stepwise manner. The first step was home screening using a set of five picture cards and a questionnaire. The children who did not pass the first step (VA <0.5 in at least one eye or any abnormal responses on the questionnaire) were retested with regular vision charts at the regional public healthcare centres. After this retest, some children were referred to ophthalmologists. The referral criteria for visual acuity were <0.5 at 3 years and <0.63 at 4 or 5 years in at least one eye. RESULTS: Of those screened, 7116 (19.2%) children did not pass the home screening tests and 2058 (28.9%) out of the 7116 were referred. The results of the ophthalmological examination in eye clinics were only available for 894 children (43.4%) of those who were referred. The rest of the children did not visit ophthalmologists because they had been checked at an eye clinic, were currently under treatment, or for personal reasons. Refractive errors were found in 608 (1.6%) children. Astigmatism was associated in 78.2% of ametropes. Amblyopia was discovered in 149 (0.4%) children and refractive error was the major aetiology with a predominant rate (82.5%). Manifest strabismus was detected in 52 children. The positive predictive value of vision screening for any ophthalmological disorder was 0.77, and 0.49 for significant disorders requiring treatment. CONCLUSIONS: This preschool vision screening model was highly accessible to the children and their parents, easy to administer, and effective to detect a variety of ocular disorders. However, the participation rate of the referred children in the examinations by ophthalmologists was quite low. The performance and efficiency of this screening programme need to be optimised with further revision.     

Muscle cell-mediated gene delivery to the rotator cuff

Rotator cuff lesions are one of the most common causes of upper extremity disability. Surgical therapy addresses mostly the extrinsic etiology, but not intrinsic factors such as aging, structural changes, low vascularity, and inflammatory processes. In this study, genetically engineered, highly purified muscle-derived cells (MDCs) were characterized and injected into the supraspinatus tendons of nude rats. The injected cells were monitored for 3 weeks. In vitro, the engineered, highly purified MDCs do not express vimentin; 98% of them are positive for the beta-galactosidase marker gene, and 99% hybridize with the specific pancentromeric mouse probe. beta-Galactosidase marker gene expression of the injected cells was detected up to 21 days. From day 7 after injection, the cell nuclei became spindle shaped, cells were integrated into the tendon collagen bundles, and the cells showed differentiation into vimentin-expressing fibroblastic cells. The results indicate that the rotator cuff tendon matrix and its original cellular components modulated the injected MDCs toward a fibroblastic phenotype. The compatibility and ability of MDCs to differentiate into other cell lineages, such as fibroblasts, might have high potential utility in tissue-engineering applications for tendon healing. This approach facilitates the application of muscle-derived progenitor cells and ex vivo gene therapy for the treatment of rotator cuff lesions.