Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation

Background: Because of the rarity of hilar cholangiocarcinoma, its prognostic risk factors have not been sufficiently analyzed. This retrospective study was undertaken to evaluate various pathologic risk factors which influenced survival after curative hepatic resection or transplantation. Methods: Between 1981 and 1996, 72 patients (43 males and 29 females) with hilar cholangiocarcinoma underwent hepatic resection (34 patients) or transplantation (38 patients) with curative intent. Medical records and pathologic specimens were reviewed to examine the various prognostic risk factors. Survival was calculated by the method of Kaplan- Meier using the log rank test with adjustment for the type of operation. Survival statistics were calculated first for each kind of treatment separately, and then combined for the calculation of the final significance value. Results: Survival rates for 1, 3, and 5 years after hepatic resection were 74%, 34%, and 9%, respectively, and those after transplantation were 60%, 32%, and 25%, respectively. Univariate analysis revealed that T-3, positive lymph nodes, positive surgical margins, and pTNM stage III and IV were statistically significant poor prognostic factors. Multivariate analysis revealed that pTNM stage 0, I, and II, negative lymph node, and negative surgical margins were statistically significant good prognostic factors. For the patients in pTNM stage 0-II with negative surgical margins, 1-, 3-, and 5-year survivals were 80%, 73%, and 73%, respectively. For patients in pTNM stage IV-A with negative lymph nodes and surgical margins, 1-, 3-, and 5- year survivals were 66%, 37%, and 37%, respectively. Conclusions: Satisfactory longterm survivals can be obtained by curative surgery for hilar cholangiocarcinoma either with hepatic resection or liver transplantation. Redefining pTNM stage III and IV-A is proposed to better define prognosis

Close encounters : spatial distances between people and a robot of mechanistic appearance

Peer reviewe

Hepatic resection and transplantation for peripheral cholangiocarcinoma

Background: Recent publications have questioned the role of orthotopic liver transplantation (OLT) in treating advanced or unresectable peripheral cholangiocarcinoma (Ch-Ca). Study Design: We reviewed our experience with Ch- Ca to determine survival rates, recurrence patterns, and risk factors in 54 patients who underwent either hepatic resection or OLT between 1981 and 1994. Liver transplantation was performed in patients with unresectable tumors (n = 12) and in those with advanced cirrhosis (n = 8). There were 33 women (61%) and 21 men (39%), with a mean age of 54.3 years. The median followup period was 6.8 years. Prognostic risk factors were analyzed by univariate and multivariate analyses. Results: Mortality within 30 days was 7.4%. Overall patient and tumor-free survival rates were 64% and 57% at 1 year, 34% and 34% at 3 years, and 26% and 27% at 5 years after operation. Thirty-two patients (59.3%) experienced tumor recurrence. Univariate analysis revealed that multiple tumors, bilobar tumor distribution, regional lymph node involvement, presence of metastasis, positive surgical margins, and advanced pTNM stages were significant negative predictors of both tumor-free and patient survival. Multivariate analysis revealed that positive margins, multiple tumors, and lymph node involvement were independently associated with poor prognosis. When patients with these three negative predictors were excluded, the patient survivals at 1, 3, and 5 years were 74%, 64%, and 62%, respectively. Conclusions: Both hepatic resection and OLT are effective therapies for Ch- Ca when the tumor can be removed with adequate margins, the lesion is singular, and lymph nodes are not involved

Reduced Health-Related Quality of Life in Body Constitutions of Yin-Xu, and Yang-Xu, Stasis in Patients with Type 2 Diabetes: Taichung Diabetic Body Constitution Study

Aim. To evaluate how health-related quality of life (HRQOL) and traditional Chinese medicine (TCM) constitutions of Yin-Xu, Yang-Xu, and Stasis are related in type 2 diabetes patients. Method. Seven hundred and five subjects were recruited in 2010 for this study from a Diabetes Shared Care Network in Taiwan. Generic and disease-specific HRQOL were assessed by the short form 36 (SF-36) and the diabetes impact measurement scale (DIMS). Constitutions of Yin-Xu, Yang-Xu, and Stasis were then assessed by the body constitution questionnaire (BCQ), a questionnaire consisting of 44 items that evaluate the physiological state based on subjective symptoms and signs. Results. Estimated effects of the Ying-Xu and Stasis on all scales of the SF-36 were significantly negative, while estimated effects of the Yang-Xu on all scales (except for SF, RE, MH, and MCS) were significantly negative. For DIMS, the estimated effects of the Ying-Xu and Stasis on all scales were significantly negative except for Stasis on well-being, while Yang-Xu has a significantly negative effect only on symptoms. Conclusions. This study demonstrates that TCM constitutions of Yin-Xu, Yang-Xu, and Stasis are closely related to a reduction in HRQOL. These findings support the need for further research into the impact of intervention for TCM constitutions on HRQOL in patients with type 2 diabetes

CATH: an expanded resource to predict protein function through structure and sequence

The latest version of the CATH-Gene3D protein structure classification database has recently been released (version 4.1, http://www.cathdb.info). The resource comprises over 300 000 domain structures and over 53 million protein domains classified into 2737 homologous superfamilies, doubling the number of predicted protein domains in the previous version. The daily-updated CATH-B, which contains our very latest domain assignment data, provides putative classifications for over 100 000 additional protein domains. This article describes developments to the CATH-Gene3D resource over the last two years since the publication in 2015, including: significant increases to our structural and sequence coverage; expansion of the functional families in CATH; building a support vector machine (SVM) to automatically assign domains to superfamilies; improved search facilities to return alignments of query sequences against multiple sequence alignments; the redesign of the web pages and download site

KSHV SOX mediated host shutoff: the molecular mechanism underlying mRNA transcript processing

Onset of the lytic phase in the KSHV life cycle is accompanied by the rapid, global degradation of host (and viral) mRNA transcripts in a process termed host shutoff. Key to this destruction is the virally encoded alkaline exonuclease SOX. While SOX has been shown to possess an intrinsic RNase activity and a potential consensus sequence for endonucleolytic cleavage identified, the structures of the RNA substrates targeted remained unclear. Based on an analysis of three reported target transcripts, we were able to identify common structures and confirm that these are indeed degraded by SOX in vitro as well as predict the presence of such elements in the KSHV pre-microRNA transcript K12-2. From these studies, we were able to determine the crystal structure of SOX productively bound to a 31 nucleotide K12-2 fragment. This complex not only reveals the structural determinants required for RNA recognition and degradation but, together with biochemical and biophysical studies, reveals distinct roles for residues implicated in host shutoff. Our results further confirm that SOX and the host exoribonuclease Xrn1 act in concert to elicit the rapid degradation of mRNA substrates observed in vivo, and that the activities of the two ribonucleases are co-ordinated

Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation

Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option

Host-Nonspecific Iron Acquisition Systems and Virulence in the Zoonotic Serovar of Vibrio vulnificus

The zoonotic serovar of Vibrio vulnificus (known as biotype 2 serovar E) is the etiological agent of human and fish vibriosis. The aim of the present work was to discover the role of the vulnibactin- and hemin-dependent iron acquisition systems in the pathogenicity of this zoonotic serovar under the hypothesis that both are host-nonspecific virulence factors. To this end, we selected three genes for three outer membrane receptors (vuuA, a receptor for ferric vulnibactin, and hupA and hutR, two hemin receptors), obtained single and multiple mutants as well as complemented strains, and tested them in a series of in vitro and in vivo assays, using eels and mice as animal models. The overall results confirm that hupA and vuuA, but not hutR, are host-nonspecific virulence genes and suggest that a third undescribed host-specific plasmid-encoded system could also be used by the zoonotic serovar in fish. hupA and vuuA were expressed in the internal organs of the animals in the first 24 h of infection, suggesting that they may be needed to achieve the population size required to trigger fatal septicemia. vuuA and hupA were sequenced in strains representative of the genetic diversity of this species, and their phylogenies were reconstructed by multilocus sequence analysis of selected housekeeping and virulence genes as a reference. Given the overall results, we suggest that both genes might form part of the core genes essential not only for disease development but also for the survival of this species in its natural reservoir, the aquatic environment