Clinical relevance of histologic subtyping in small cell lung cancer

Histopathologic specimens from 249 patients with small cell lung cancer (SCLC) were reviewed and classified into oat cell-type, pure intermediate cell-type (excluding specimens with mixed small cell/large cell features), and small cell/large cell-type. One hundred seventy (68%) specimens displayed oat cell features (including 30 with mixed oat cell/intermediate cell features), 66 (27%) displayed intermediate cell features, and 13 (5%) displayed mixed small cell/large cell features. No differences among these subtypes were found with respect to stage of disease, sex, age, performance status, and number and distribution of metastases. Complete and partial remission rates for the oat cell-type were, respectively, 31% and 38%, for the intermediate cell-type 20% and 45%, and for the small cell/large cell-type 38% and 31%. Two-year survival rates were 7%, 11%, and 15%, respectively. These data were all statistically insignificant, and comparisons of log-rank analyses of survival curves for these SCLC subtypes also showed no statistically significant differences. We thus conclude that histologic subtypes of SCLC are not distinct entities of clinical relevance, and that prognostic as well as therapeutic decisions cannot be based on histologic subtyping.     

Immunologische Toleranz nach experimenteller Lebertransplantation

Zusammenfassung Im Vergleich zu anderen primär vaskularisieren Organtransplantaten in der Ratte werden Lebertransplantate schwächer abgestoßen, besitzen eine bessere Überlebensrate und können in bestimmten Spender-Empfänger-Kombinationen eine spenderspezifische Hyporeaktivität oder Toleranz induzieren. In dieser Übersicht werden die immunologischen Mechanismen dieses privilegierten Status beleuchtet. Eine Vielzahl möglicher Mechanismen, wie die Generation von Suppressor-T-Zellen, humorale Faktoren und Mikrochimärismus, sind mit der beobachteten Hyporeaktivität in Verbindung gebracht worden. Eine weitere Analyse dieser Phänomene könnte zur Entwicklung von Protokollen für die klinische Organ-transplantation beitragen, die zur Etablierung einer spenderspezifischen Hyporeaktivität ohne die Notwendigkeit einer lebenslangen Immunsuppression führen.

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Immunologic tolerance following liver transplantation

Allografts in the rat liver are rejected less vigorously than other primarily vascularized allografts; they show a better survival rate and induce donor-specific unresponsiveness or tolerance in some donor-recipient combinations. This overview focuses on the immunologic mechanisms of this privileged status of liver allografts. A variety of possible mechanisms, such as generation of suppressor T-cells, humoral factors and microchimerism, has been related to the observed hyporeactivity. A further analysis of these phenomena may enhance the development of clinical organ transplantation protocols that allow for establishment of donor-specific unresponsiveness without the need for life-long immunosuppression.

     

Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent extended cold storage in University of Wisconsin solution in an extracorporeal rat liver perfusion and rat liver transplantation model.

Adequate flushing for liver donation requires large fluid volumes delivered at a high flow. This can be achieved more effectively with crystalloid solutions than with colloid-based solutions. This study examined the combination of initial histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent storage in University of Wisconsin solution (UW) to that of the single use of each solution. Livers from inbred Wistar rats were procured using aortic perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes using either solution. In a third group, after perfusion with HTK, organs were reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed after 24 hours of cold storage in the subsequent solution, as well as allotransplantation after 18 and 24 hours of cold storage. In extracorporeal perfusion, the HTK flush followed by UW storage was superior compared to the single use of either UW or HTK solution, as measured by portal venous pressure, bile flow, liver enzymes released into the effluent perfusate, glycerol leakage, and histological examinations. These data were consistent with the transplantation study. Histological damage and enzyme release after 5-day survival were lowest in the HTK flush and subsequent UW storage groups following 18 hours of cold storage; likewise, the 5-day survival was superior following 24 hours of cold storage. In conclusion, the combined use of HTK solution for initial graft rinse and subsequent storage in UW solution resulted in a cumulative protection. Choosing low-viscosity HTK solution for the initial organ flush may represent a feasible improvement in liver preservation, which also further reduces the required amount of UW solution.     

Adult living donor liver transplantation: living donation of the right liver lobe

Background Adult living donor liver transplantation (LDLT) has become a routine treatment option for patients waiting for liver transplantation. In European and North American countries, LDLT for adult recipients is mainly performed with right lobe grafts. Indications, when compared to deceased donor liver transplantation, are controversial. Materials and methods In our institution, patients suffering from hepatocellular carcinoma in cirrhosis, non-resectable hilar cholangiocarcinoma, viral hepatitis associated cirrhosis, as well as cholestatic liver and biliary disease are considered good candidates for LDLT. Results In this overview, donor evaluation, graft selection, and the donor operation with special regard to operative techniques and strategies are discussed. For visualization, a 5-min video sequence of the standard donor operation as performed in our institution is attached. Conclusion Given the ongoing shortage of donor organs, adult LDLT has become a routine treatment option for patients waiting for liver transplantation. The associated inevitable risk for the healthy donor, however, remains ethically controversial. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Codon 178 mutation of the human prion protein gene in a German family (Backer family): sequencing data from 72-year-old celloidin-embedded brain tissue

Familial Creutzfeldt-Jakob disease was first described in a family from northern Germany in the 1920s (Backer family). PCR amplification of DNA extracted from brain tissue embedded in celloidin 72 years ago shows a GAC to AAC substitution at codon 178 of the prion protein gene. This mutation is associated with fatal familial insomnia and familial Creutzfeldt-Jakob disease in a number of families of diverse ethnic background.