Combined hepatocellular-cholangiocarcinoma: A clinicopathological study

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16–79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n= 18) of tumours were ‘mixed’ tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a ‘fibrolamellar’ tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin-producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin-negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum α-fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC-CC were short. In conclusion, HCC-CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.     

ACR-NEMA digital imaging and communications standards: minimum requirements

The purposes, implications, and history of development of the American College of Radiology-National Electrical Manufacturers Association (ACR-NEMA) Digital Imaging and Communication Standard and its contents are briefly described, and the minimum requirements of the ACR-NEMA Digital Imaging and Communication Standard are described with a concise introduction of each layer. The usefulness, validity, current status, and future development of the standard are also discussed.     

Thin layer chromatography and counter-current analysis in porphyrias

The porphyrin metabolism of 100 patients with porphyria and 351 of their relatives has been studied. Thin layer chromatography of methyl esters of the urinary porphyrin was undertaken in sixty-six patients with different types of porphyria, and forty-five relatives, seventeen patients with hepatic cirrhosis, three patients with lead poisoning and twenty normal control subjects. This investigation was also made on the stools of thirty-six patients with porphyria, and then of their relatives. Countercurrent analysis of the bile of nine selected patients with porphyria was also undertaken. The results provide some evidence that symptomatic hepatic porphyria may be familial. Thin layer chromatography was decisive in the characterization of a new type of porphyria described recently by the authors (hepato-erythrocytic porphyria). The counter-current examination of the bile showed the absence of the 'S 411' porphyrin in all the nine cases investigated.     

Bartonella bacteria in nature: Where does population variability end and a species start?

The application of new molecular approaches has permitted the differentiation of numerous strains belonging to the genus Bartonella and identification of new Bartonella species. However, the molecular typing of these organisms should be coupled with studies aimed at defining the biological properties of the newly described species. The long-history of co-adaptation between bartonella(1) bacteria and their mammalian hosts and possibly arthropod vectors provides a unique opportunity for applying this information for the sub-genus taxonomy. There can be a varying level of association between the bacteria and their hosts, ranging from animal species to animal genus to animal community. The commonality is that any level of association provides a certain degree of isolation for a given bartonella population that can mimic 'biological isolation'. Such an association defines a specific ecological niche and determines some specific characteristics, including sequence types that can be used as markers for demarcation of bacterial species. Usage of a combination of genetic markers and ecological information can delineate a number of species complexes that might combine several genospecies, named strains, and unique genotypes. The identification of such species complexes can be presented as (1) separate phylogenetic lineages distantly related to other species (e.g. Bartonella bacilliformis); (2) clusters of genetically similar strains associated with a specific mammalian group (e.g. Bartonella elizabethae species complex); and (3) clusters of genetically similar strains that combine a number of ecotypes (e.g. Bartonella vinsonii species complex).     

Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.     

Molecular Detection and Identification of Bartonella Species in Rat Fleas from Northeastern Thailand

The presence of Bartonella species in Xenopsylla cheopis fleas collected from Rattus spp. (R. exulans, R. norvegicus, and R. rattus) in Khon Kaen Province, Thailand was investigated. One hundred ninety-three fleas obtained from 62 rats, were screened by polymerase chain reaction using primers specific for the 16S–23S intergenic spacer region, and the presence of Bartonella DNA was confirmed by using the citrate synthase gene. Bartonella DNA was detected in 59.1% (114 of 193) of fleas examined. Sequencing demonstrated the presence of Bartonella spp. similar to B. elizabethae, B. rattimassiliensis, B. rochalimae, and B. tribocorum in the samples tested with a cutoff for sequence similarity ≥ 96% and 4 clustered together with the closest match with B. grahamii (95.5% identity). If X. cheopis proves to be a competent vector of these species, our results suggest that humans and animals residing in this area may be at risk for infection by several zoonotic Bartonella species.Bartonella species are small, pleomorphic, gram-negative bacteria that infect a variety of mammalian hosts, including cats, dogs, rodents, ruminants, and humans. Clinical symptoms associated with Bartonella range from mild, influenza-like symptoms to more severe manifestations such as endocarditis, myocarditis, uveitis, bacillary angiomatosis, and peliosis hepatis.¹ Approximately half of the 20 Bartonella species or subspecies identified to date are known or suspected human pathogens,² and most are believed to be transmitted by arthropod vectors (fleas, lice, sandflies, and ticks).³Xenopsylla cheopis, the Oriental rat flea, is a suspected vector of several Bartonella species (B. tribocorum, B. elizabethae, B. queenslandensis, B. rochalimae, and novel Bartonella genotypes), and Bartonella DNA has been detected in these fleas from various locations worldwide.^3–8 Although generally found on rodents, X. cheopis have been found to parasitize humans and are known vectors of the zoonotic agents Yersinia pestis (plague) and Rickettsia typhi (murine typhus).⁹Numerous surveys have been performed to identify the presence of Bartonella species affecting humans and domestic and peri-domestic animals in Thailand.^10–17 Bartonella henselae, (the agent of cat scratch disease),¹⁴ B. tamiae,¹⁰ B. elizabethae, B. rattimassiliensis, and B. tribocorum have been isolated from febrile patients,¹⁵ B. henselae and B. clarridgeiae have been reported in cats,¹¹ and B. clarridgeiae, B. vinsonii subsp. arupensis, B. elizabethae, B. grahamii, B. quintana, B. taylorii, and novel Bartonella genotypes have been found in dogs.^11,16 In rodent species, B. grahamii, B. elizabethae, Candidatus Bartonella thailandensis, B. coopersplainensis, B. phoceensis, B. rattimassiliensis, B. tribocorum, and novel Bartonella genotypes have been detected by culture and polymerase chain reaction (PCR) analysis.^12,13,17 However, little information has been obtained to identify potential arthropod vectors of Bartonella species in Thailand. Bartonella henselae, B. clarridgeiae and B. koehlerae were detected in Ctenocephalides felis fleas removed from cats^18–20 and B. henselae was identified in two C. canis¹⁹ also collected from cats. Furthermore, a Bartonella sp., similar to B. grahamii, was found in a rodent flea, Nosopsyllus fasciatus, obtained from Rattus surifer.¹⁸ Bartonella tamiae DNA has also been found in chigger mites (genera Leptotrombidium, Schoengastia, and Blankarrtia) and in a tick (genus Haemaphysalis) collected from rodents in Thailand, suggesting a potential role for these arthropods in the transmission of B. tamiae.²¹The aim of the current study was to investigate the prevalence of Bartonella species in rodent-associated fleas collected in Khon Kaen Province, Thailand, and to determine what potential role, if any, these fleas may play in the transmission of Bartonella species to individuals residing in this area.For this study, 62 rats (10 R. norvegicus, 9 R. rattus, and 43 R. exulans) were trapped in and around homes in 4 villages, 1 market, and on farm land (a pig farm and 2 rice fields) in Khon Kaen Province, Thailand during May–June 2011 (22 Work involving rodents was conducted as outlined in our approved animal use protocol (#11-003), under the supervision of the Institutional Animal Care and Use Committee of the Division of Vector Borne Diseases.

Table 1

Number of rats trapped per site by species and total number of fleas examined per site, northeastern Thailand

Identification of Bartonella Infections in Febrile Human Patients from Thailand and Their Potential Animal Reservoirs

To determine the role of Bartonella species as causes of acute febrile illness in humans from Thailand, we used a novel strategy of co-cultivation of blood with eukaryotic cells and subsequent phylogenetic analysis of Bartonella-specific DNA products. Bartonella species were identified in 14 blood clots from febrile patients. Sequence analysis showed that more than one-half of the genotypes identified in human patients were similar or identical to homologous sequences identified in rodents from Asia and were closely related to B. elizabethae, B. rattimassiliensis, and B. tribocorum. The remaining genotypes belonged to B. henselae, B. vinsonii, and B. tamiae. Among the positive febrile patients, animal exposure was common: 36% reported owning either dogs or cats and 71% reported rat exposure during the 2 weeks before illness onset. The findings suggest that rodents are likely reservoirs for a substantial portion of cases of human Bartonella infections in Thailand.     

Household-Based Sero-Epidemiologic Survey after a Yellow Fever Epidemic,Sudan, 2005

From September through early December 2005, an outbreak of yellow fever (YF) occurred in South Kordofan, Sudan, resulting in a mass YF vaccination campaign. In late December 2005, we conducted a serosurvey to assess YF vaccine coverage and to better define the epidemiology of the outbreak in an index village. Of 552 persons enrolled, 95% reported recent YF vaccination, and 25% reported febrile illness during the outbreak period: 13% reported YF-like illness, 4% reported severe YF-like illness, and 12% reported chikungunya-like illness. Of 87 persons who provided blood samples, all had positive YF serologic results, including three who had never been vaccinated. There was also serologic evidence of recent or prior chikungunya virus, dengue virus, West Nile virus, and Sindbis virus infections. These results indicate that YF virus and chikungunya virus contributed to the outbreak. The high prevalence of YF antibody among vaccinees indicates that vaccination was effectively implemented in this remotely located population.