Resection of segment VIII for hepatocellular carcinoma.

BACKGROUND: Anatomical resection of segment VIII (SVIII) is technically demanding. Only two small studies have published short-term outcomes. The aim of the present study was to evaluate short- and long-term outcomes after anatomical resection involving SVIII for hepatocellular carcinoma (HCC), and to compare long-term outcomes with those after non-anatomical resection of SVIII. METHODS: Outcomes after anatomical resection of SVIII or its subsegments for HCC were compared with those in patients who underwent primary non-anatomical resection of SVIII during the same period. RESULTS: A total of 154 patients underwent anatomical resection involving SVIII and 122 had non-anatomical resection. In patients undergoing anatomical resection, the preoperative indocyanine green retention rate at 15 min ranged from 2·9 to 32·2 (median 13·6) per cent, and was 10 per cent or more in 109 patients (70·8 per cent). Median duration of operation and blood loss were 378 min and 705 ml respectively. There were no postoperative deaths, but major adverse events occurred in ten patients (6·5 per cent). The cumulative 5-year recurrence-free and overall survival rates were 28·5 and 79·6 per cent, which were significantly better than rates of 19·4 and 64·8 per cent respectively after non-anatomical resection (P = 0·036 and P < 0·001). CONCLUSION: Complete resection of SVIII or its subsegments can be performed safely and the long-term outcomes seem acceptable. This can be a curative procedure for HCC, especially in patients with limited liver function reserve, in whom right hepatectomy or right paramedian sectorectomy might otherwise be needed.

Venous reconstruction based on virtual liver resection to avoid congestion in the liver remnant.

BACKGROUND: Hepatic vein (HV) reconstruction may prevent venous congestion following resection of liver tumours that encroach on major HVs. This study aimed to identify criteria for venous reconstruction based on preoperative evaluation of venous congestion. METHODS: A volumetric analysis using image-processing software was performed in selected patients with liver tumours suspected on preoperative imaging of major HV invasion. The size of the non-congested liver remnant (NCLR) was calculated by subtracting the congested area from the liver remnant. Venous reconstruction was scheduled in patients who met the following criteria: normal liver function (indocyanine green retention rate at 15 min (ICGR(15) ) of less than 10 per cent) with a NCLR smaller than 40 per cent of total liver volume (TLV), or liver dysfunction (ICGR(15) 10-20 per cent) with a NCLR smaller than 50 per cent of TLV. Surgical outcomes and liver regeneration were investigated. RESULTS: A total of 55 patients with suspected HV invasion were enrolled. Sacrifice of one or more HVs was deemed possible in 37 patients. Venous reconstruction was scheduled in 18 patients. At operation, there was seen to be no venous involvement in 11 patients. The HV was sacrificed in 29 patients, and preserved or reconstructed in 24. Volume restoration ratios at 3 months were similar in the sacrifice (88 per cent) and preserve (87 per cent) groups. Operating time was shorter (465 min) and blood loss was lower (580 ml) in the sacrifice than in the preserve group (523 min and 815 ml respectively). CONCLUSION: The HV can be sacrificed safely according to the proposed criteria, reducing surgical invasiveness without influencing the postoperative course.

Polymorphism of human minor histocompatibility antigens: T cell recognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules.

To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line); those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B*3502, B*3507, and B*3508 molecules. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B*3501 molecules purified from C1R-B*3501 cells. Small amounts of human mH peptides were isolated from B*3503 molecules purified from these three CTL weakly sensitive cell lines. Taken together, these results indicate that weak recognition by the CTL clones of three CTL weakly sensitive cell line results from a small amount of the human mH peptides presented by B*3503 molecules. The CTL-resistant cell line carrying B*3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B*3502 or B*3508 loaded with the peptides were not. The human mH peptides were not isolated from B*3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B*3502 and B*3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B*3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B*3502 and B*3508 is not explained by only the amount of the human mH peptides binding to these B35 subtype molecules because the amount of the human mH peptides eluted from B*3502 and B*3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B*3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)

Dual recognition of a human cytotoxic T-cell clone for melanoma antigens.

It is well known that tumor-specific CTLs have a crucial role in the elimination of tumors and that different CTL populations recognize tumor antigens in MHC-restricted and MHC-unrestricted manners. We have established two alpha beta CTL clones that recognize melanoma antigens in both human lymphocyte antigen (HLA)-A2-restricted and HLA-unrestricted manners. Flow cytometry analysis showed that these CTL clones carry CD3, CD8, and alpha beta T-cell receptor (TCR) and express low levels of CD56. In contrast, these CTL clones do not express CD16, indicating that they do not contain natural killer cells. TCR analysis of these CTL clones using an anchored PCR method revealed that each clone carries a single alpha beta TCR. Both CTL clones contained the same Valpha and Vbeta gene segments although they carried different Jalpha and Jbeta gene segments. Taken together, these results confirm that CTL clones that carry a single alpha beta TCR recognize melanoma antigens in both HLA-A2-restricted and HLA-unrestricted manners. It is strongly suggested that the dual recognition of these CTL clones for the melanoma antigens is mediated by TCRs. The novel mechanism for antitumor immunity by these CTLs may be important in the effective elimination of tumors in vivo.

Characterization of crystals of genetically engineered human manganese superoxide dismutase.

The genetically engineered human manganese superoxide dismutase crystallizes in space group P2(1)2(1)2 with a = 75.51 A, b = 79.00 A, c = 67.95 A. At room temperature the crystals are not stable against radiation, so we cooled them to 90 K and collected a data set to 3 A resolution at this temperature.

Intrathymic inoculation of donor HLA class I-derived peptide generates donor-specific CD4+CD25+ regulatory T cells.

CD4(+)CD25(+) regulatory T cells are selected in the thymus to control autoreactive thymic escapees preventing autoimmunity that cannot be achieved by negative selection or deletion alone, thus playing an important role in the maintenance of immunological homeostasis. Not only significant in preventing autoimmunity, CD4(+)CD25(+) regulatory T cells have also been shown to be involved in allograft tolerance in organ transplantation. We have formerly introduced two lines of HLA class I transgenic mice to elucidate the role of HLA class I molecules in transplantation biology. Using a heterotopic cardiac transplantation model, we show herein that intrathymic inoculation of donor HLA class I-derived synthetic peptide results in the generation of CD4(+)CD25(+) regulatory T cells, which induce graft specific tolerance without any preconditioning of the recipient or use of immunosuppressive drugs. This study provides evidence of the novel therapeutic potential of CD4(+)CD25(+) regulatory T cells for clinical transplantation.

Molecular cloning of Proteus morganii phenylalanine deaminase gene in Escherichia coli.

The gene for phenylalanine deaminase (PAD) of Proteus morganii strain 2815 has been isolated on a 6.3-kb HindIII restriction fragment and cloned within RP4-prime plasmids, pYB2321 and pYB2322, in both orientations. Expression of the cloned gene in Escherichia coli strains was comparable to that in P. morganii 2815. The hybrid plasmids mobilized the 2815 chromosome with trajectories in reverse directions from an origin between ser-2 and ade-1, suggesting the map location of the PAD gene.

Cell-mediated graft rejection observed in two lines of human histocompatibility leukocyte antigen class I transgenic mice.

BACKGROUND: Human histocompatibility leukocyte antigen (HLA) class I molecules are essential for graft rejection. However, to determine the specific role of these molecules in clinical situations is difficult. We investigated the applicability of HLA class I transgenic mice (C3H.B35 and C3H.B51) for elucidation of the role of HLA class I molecules. METHODS: Skin or heart grafts were transplanted. Cytotoxic T cells (CTL) of C3H.B51 against C3H.B35 were generated and their cytotoxicity against various transfectant cell lines was determined. RESULTS: C3H.B35 skin and heart grafted to C3H.B51 were rejected within 17 and 28 days, respectively. Cytotoxic T cells generated from C3H.B51 showed cytotoxicity against a HLA-B*3501-transfectant cell line that did not express H-2 molecule, which indicates that these cytotoxic T cells recognize HLA-B35 molecules directly without H-2 restriction. CONCLUSION: Our results suggest that C3H.B51 recognize C3H.B35 grafts as allo-MHC class I-incompatible grafts, and these mice are valuable to elucidate the role of HLA class I molecules in transplantation.