Isolated Pulmonary Cryptococcosis Confused with Lung Tumor 5 Years After Kidney Transplantation: A Case Report.

BACKGROUND: In transplant recipients, due to the use of immunosuppressive therapy, it is occasionally difficult to distinguish between an infection and malignancy, especially in the case of a lung lesion. Here, we report a case of isolated pulmonary cryptococcosis after kidney transplantation that was difficult to distinguish from a lung tumor. CASE REPORT: A 52-year-old man underwent a kidney transplant from his mother when he was 44 years old. Immunosuppression was maintained with tacrolimus, methylprednisolone, and mycophenolate mofetil. His post-transplant course was uneventful and serum creatinine levels were maintained. Five years post-transplantation, a non-contrast computed tomography (CT) examination revealed a nodule measuring 3 mm in diameter in the middle lobe of the right lung. The nodule gradually increased to 12 mm in 2 years. Positron emission tomography/CT examination showed a maximum standardized uptake value of 0.5 for the nodule. Biochemical examination revealed no elevation in total leucocyte count and C-reactive protein levels. However, tumor markers were elevated: serum carcinoembryonic antigen, 5.9 ng/mL; pro-gastrin-releasing peptide, 84.6 pg/mL. Furthermore, the serum cryptococcus antigen was negative. Therefore, thoracoscopic partial lung resection was performed. Pathologically, a number of spherical fungi from the necrotic substance of the tumor were confirmed positive by periodic acid-Schiff and Grocott-Gomori staining. The patient was therefore diagnosed with pulmonary cryptococcosis. Two years later, the patient is alive and has shown no evidence of recurrence. CONCLUSIONS: In lung nodules after kidney transplantation, even if serum cryptococcus antigen is not identified, it is necessary to keep in mind the possibility of pulmonary cryptococcosis.

Memory-like Liver Natural Killer Cells are Responsible for Islet Destruction in Secondary Islet Transplantation.

We previously demonstrated the pivotal role of natural killer (NK) cells in islet graft loss during the early phase after intraportal syngeneic islet transplantation (IT). Liver-resident DX5- NK cells were reported to possess memory-like properties, distinguishing them from conventional DX5+ NK cells. Here, we investigated the impact of primary IT-induced liver DX5- NK cells on the engraftment of secondary-transplanted islets in mice. The culture of liver NK cells isolated from naive mice with TNF-α, IFN-γ, and IL-lß, mimicking instant blood-mediated inflammatory reaction, led to significantly increased DX5- NK cell percentage among total liver NK cells. Consistently, the prolonged expansion of DX5- CD69+ TRAIL+ CXCR3+ NK cells was observed after intraportal IT of 300 syngeneic islets (marginal mass). In most diabetic mice, 400 syngeneic islets of primary IT were sufficient to achieve normoglycaemia, whereas the same mass after secondary IT failed to induce normoglycaemia in mice that received 200 syngeneic islets during primary IT. These findings indicated that liver-resident DX5- NK cells significantly expanded even after syngeneic IT, and that these memory-like NK cells may target both originally engrafted and secondary-transplanted islets. Furthermore, anti-TNF-α treatment suppressed the expansion of liver-resident DX5- NK cells, resulting in successful islet engraftment after sequential ITs.

Impact of Steroids on Natural Killer Cells Against Cytotoxicity and Hepatitis C Virus Replication.

BACKGROUND: Natural killer (NK) cells play important roles in killing tumor and virus-infected cells. Immunosuppression used after organ transplantation is thought to increase the risk of tumor recurrence and viral infections. However, the effect of immunosuppressive drugs on NK cells has not yet been clearly established. Therefore, we examined the effect of immunosuppression on NK cells. METHODS: NK cells were cultured for 7 days in the presence of interleukin-2 (100 U/mL) with or without the following immunosuppressive drugs: tacrolimus, cyclosporine A, corticosteroid (methylprednisolone [MP]), mycophenolate mofetil, and rapamycin. The effect of the drugs on NK cell activation was tested on the basis of the following: NK cell phenotype, NK cell proliferation, cytotoxicity against K562 cells, cytokine production by NK cells, and anti-hepatitis C virus (HCV) activity with HCV genomic replicon cells. RESULTS: NK cells showed relatively robust functions in the presence of tacrolimus and cyclosporine A. Mycophenolate mofetil and rapamycin significantly prevented only NK cell proliferation (P < .05). In contrast, MP significantly inhibited the proliferation, cytotoxicity, and anti-HCV effect (10.9%, 18.5%, and 1.9%, respectively) of NK cells. Furthermore, MP specifically inhibited the expression of NK cell activation markers and the production of interferon-γ (P < .05). CONCLUSIONS: Corticosteroids have distinct effects on NK cells, which may have important implications for NK cell function in cytotoxicity and HCV effect after transplantation.

MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates.

BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed. RESULTS: Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor-related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta. CONCLUSIONS: Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.

KRAS mutation leads to decreased expression of regulator of calcineurin 2, resulting in tumor proliferation in colorectal cancer.

KRAS mutations occur in 30-40% of all cases of human colorectal cancer (CRC). However, to date, specific therapeutic agents against KRAS-mutated CRC have not been developed. We previously described the generation of mouse models of colon cancer with and without Kras mutations (CDX2P-G22Cre;Apc(flox/flox); LSL-Kras(G12D) and CDX2P-G22Cre;Apc(flox/flox) mice, respectively). Here, the two mouse models were compared to identify candidate genes, which may represent novel therapeutic targets or predictive biomarkers. Differentially expressed genes in tumors from the two mouse models were identified using microarray analysis, and their expression was compared by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemical analyses in mouse tumors and surgical specimens of human CRC, with or without KRAS mutations, respectively. Furthermore, the functions of candidate genes were studied using human CRC cell lines. Microarray analysis of 34 000 transcripts resulted in the identification of 19 candidate genes. qRT-PCR analysis data showed that four of these candidate genes (Clps, Irx5, Bex1 and Rcan2) exhibited decreased expression in the Kras-mutated mouse model. The expression of the regulator of calcineurin 2 (RCAN2) was also observed to be lower in KRAS-mutated human CRC. Moreover, inhibitory function for cancer cell proliferation dependent on calcineurin was indicated with overexpression and short hairpin RNA knockdown of RCAN2 in human CRC cell lines. KRAS mutations in CRC lead to a decrease in RCAN2 expression, resulting in tumor proliferation due to derepression of calcineurin-nuclear factor of activated T cells (NFAT) signaling. Our findings suggest that calcineurin-NFAT signal may represent a novel molecular target for the treatment of KRAS-mutated CRC.

Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy.

AIM: This study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. METHODS: Clinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker.

Two patients treated with simeprevir plus pegylated-interferon and ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation: case report.

We previously reported our data on telaprevir (TVR) used in combination with pegylated-interferon and ribavirin (PEG-IFN/RBV) for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). TVR substantially increases the blood levels of immunosuppressive agents such as cyclosporine and tacrolimus for drug-drug interactions. On the other hand, the effect of simeprevir (SMV) on the blood levels of these immunosuppressive agents is unclear. We report 2 patients who achieved viral responses with little effect on the blood levels of cyclosporine and tacrolimus using SMV plus PEG-IFN/RBV treatment. The first was a 71-year-old woman with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. She was treated with 40 mg/d of cyclosporine, and received SMV plus PEG-IFN/RBV treatment. The second was a 65-year-old man with HCV-related liver cirrhosis who failed to respond to PEG-IFN/RBV after living donor LT. He was treated with 3 mg/d of tacrolimus, and received SMV plus PEG-IFN/RBV treatment. Serum HCV RNA became undetectable using TaqMan polymerase chain reaction (PCR) test after 4 weeks of treatment in both patients, and no remarkable fluctuation in blood concentration was observed either in cyclosporine or tacrolimus during the 12 weeks of SMV treatment. Completion of 12-week SMV triple therapy was followed by PEG-IFNα2b plus RBV, and both patients achieved sustained virological response 12 weeks after the end of treatment. SMV plus PEG-IFNRBV treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.

Oxaliplatin and molecular-targeted drug therapies improved the overall survival in colorectal cancer patients with synchronous peritoneal carcinomatosis undergoing incomplete cytoreductive surgery.

PURPOSE: To estimate the feasibility and limitations of incomplete cytoreductive surgery and modern systemic chemotherapy in patients with synchronous peritoneal carcinomatosis from colorectal cancer and to identify risk factors for death and factors associated with the patient prognosis. METHODS: Sixty-five consecutive patients underwent surgery for synchronous peritoneal carcinomatosis from colorectal cancer at Hiroshima University, Japan between 1992 and 2012. The clinical, histological, and survival data were analyzed for independent risk factors and prognostic factors. The patients were retrospectively stratified into two groups according to the extent of surgery: complete cytoreductive surgery or incomplete cytoreductive surgery. RESULTS: The median survival times in the complete and incomplete cytoreductive surgery groups were 29.8 and 10.0 months, respectively. Receiving systemic chemotherapy alone was an independent risk factor for death in the incomplete cytoreductive surgery group (P < 0.001). Oxaliplatin and molecular-targeted drug (cetuximab or bevacizumab) therapies were also independent prognostic factors (P < 0.001), whereas irinotecan therapy was not a prognostic factor (P = 0.494). CONCLUSION: Oxaliplatin and molecular-targeted drug therapies improved the overall survival in patients undergoing incomplete cytoreductive surgery. Future trials for patients with synchronous peritoneal carcinomatosis from colorectal cancer should be undertaken, with patients stratified according to treatment with complete cytoreductive surgery or incomplete cytoreductive surgery with modern chemotherapy.

Bile CXC motif chemokine 10 levels correlate with anti-donor cytotoxic T cell responses after liver transplantation.

BACKGROUND: CXC motif chemokine 10 (CXCL10), known as interferon-γ-induced protein 10, is an inflammatory cytokine secreted by various cells in response to interferon-γ. CXCR3, the receptor of CXCL10, is predominantly expressed on activated T, B, natural killer, and dendritic cells, as well as macrophages. CXCR3 promotes chemotaxis upon binding CXCL10. Serum CXCL10 levels have recently attracted attention as a post-transplantation biomarker for graft rejection. However, the correlation between the degree of T cell response to allostimulation and CXCL10 levels remains unclear. In this study, we investigated the serum and bile CXCL10 levels of patients who underwent living donor liver transplantation (LDLT) and compared them with the T cell responses to allostimulation. PATIENTS AND METHODS: Between February 2009 and August 2012, 41 patients underwent LDLT at Hiroshima University Hospital. Serum and bile CXCL10 levels were measured weekly for 4 weeks after surgery, while the T cell responses to allostimulation were evaluated using a mixed lymphocyte reaction with an intracellular carboxyfluorescein diacetate succinimidyl ester-labeling technique that we regularly use to monitor the immune response to anti-donor and anti-third-party stimulation after liver transplantation. The stimulation index (SI) and CD25 expression of the CD4+ and CD8+ T cell subsets in response to allostimulation were then analyzed using flow cytometry. RESULTS: Serum CXCL10 levels were significantly correlated with the SI values for CD8+ T cells in response to both types of allostimulation. Bile CXCL10 levels were significantly correlated with CD25 expression of CD8+ T cell subsets, especially in response to anti-donor stimulation. Patients with higher bile CXCL10 levels suffered from severe acute cellular rejection that was refractory to steroid pulse. CONCLUSION: Measurements of bile CXCL10 levels could predict anti-donor cytotoxic T cell responses in liver transplant recipients.

Multiple hepatic vein reconstruction using an all-in-one sleeve patch graft technique in living donor liver transplantation: a case report.

Maintaining hepatic inflow and appropriate venous drainage is important for maximizing the capacity of the retrieved graft in liver transplantation. Here, we report a successful case of multiple hepatic vein (HV) reconstruction using an all-in-one sleeve patch graft of the autologous great saphenous vein to ensure adequate blood flow through the HV. A patient with hepatocellular carcinoma caused by hepatitis C virus-induced cirrhosis underwent living donor liver transplantation using a right lobe graft. A preoperative dynamic computed tomography scan and intraoperative findings revealed that the graft had three middle HV tributaries, a superficial vein, segment VIII HV (V8), and segment V HV (V5). The openings of the superficial vein and V8 were located very close to that of the right hepatic vein (RHV) in the cutting surface. Each HV had significant diameter and drainage territory requiring reconstruction. An autologous great saphenous vein was used to create a sleeve patch to incorporate the close-packed HV openings. The autologous sleeve patch graft was sutured to the openings of the RHV and the superficial vein and the hole created on the sleeve patch graft was anastomosed to the openings of V8 directly on the back table to create an all-in-one sleeve patch. For the V5 reconstruction, the recipient's intrahepatic portal vein graft was used to create an interpositional conduit from the recipient's V5 to the inferior vena cava. The postoperative course was uneventful and postoperative studies revealed good graft function with excellent blood flow in the HV.

Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

OBJECTIVE: The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). METHODS: Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. RESULTS: All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). CONCLUSIONS: We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery.

Comparative analysis of T-cell depletion method for clinical immunotherapy-anti-hepatitis c effects of natural killer cells via interferon-γ production.

Liver transplantation (LT) is a life-saving treatment for liver cirrhosis patients with hepatocellular carcinoma (HCC). However, 10%-20% HCC recurrence rate after LT is due to the immunosuppression inducing tumor growth. We recently reported a novel immunotherapy with donor liver natural killer (NK) cells to prevent HCC and hepatitis C virus (HCV) recurrence after LT. In this cell processing procedure, Muromonab-CD3 (Orthoclone OKT3, an anti-CD3 antibody) was added to the culture medium to deplete CD3(+) T cells to prevent graft-versus-host disease. However, the manufacture of OKT3 was discontinued in 2010, when other treatments with similar efficacy and fewer side effects became available. In this study, we examined alternative reagents for T-cell depletion-MACS GMP CD3 pure (GMP CD3), antithymocyte globulin, and alemtuzumab-for NK cell immunotherapy in the allogeneic setting. We observed that GMP CD3 showed exactly the same effects on liver mononuclear cells as OKT3, including activation of NK cells and depletion of T cells. Interestingly, binding of T-cell depletion antibodies to NK cells led to an anti-HCV effect via interferon-γ production. These results with the use of in vitro culture systems suggested that antibodies which produce T-cell depletion affected NK cell function.

Complex vascular reconstruction using donor's vessel grafts in orthotopic liver transplantation.

The vascular abnormalities of recipients are associated with reconstructive difficulties with an increased risk of postoperative complications. We performed an orthotopic liver transplantation that required a complex vascular reconstruction using donor vascular grafts. A patient with hepatitis B virus cirrhosis received a liver from a brain-dead donor. Dynamic computed tomography revealed complete obstruction of the portal vein due to thrombosis as well as narrowing of the hepatic arteries. We employed orthotopic liver transplantation using the piggy-back technique with complex reconstruction of the portal vein and the hepatic arteries. For portal vein reconstruction, we used the donor's iliac vein as an interpositional conduit from the recipient's gastric coronary vein to graft the portal vein. The hepatic arteries of the graft were reconstructed at the back-table before anastomosis to the side of superior mesenteric artery using an interpositional conduit of the donor's external iliac artery. All postoperative studies revealed good graft function with an excellent blood flow through all vascular anastomoses during the first year postoperatively.

Single-incision laparoscopic colectomy using the Gelport system for early colon cancer.

BACKGROUND: Laparoscopic surgery has spread quickly during the past twenty years, and has become one of the important treatments in the field of colorectal surgery. Recently, natural orifice transluminal endoscopic surgery (NOTES) has been studied as the next generation of minimally-invasive surgery, but the feasibility and safety of the NOTES method have not been evaluated. In such a situation, single-incision laparoscopic surgery has attracted interest from surgeons worldwide. However, single-incision laparoscopic colorectal surgery has not yet been standardized. METHODS: From February 2010, single-incision laparoscopic colectomy was performed for 7 patients presenting with early colon cancer. All procedures were performed by two experts with the License of Endoscopic Surgical Skill Qualification System (ESSQS) of Japan Society for Endoscopic Surgery (JSES) in the field of colorectal Surgery. RESULTS: We used the Gelport system (Applied Medical, Rancho Santa Margarita, CA, USA) as the access port and 3 trocars of different sizes (Ethicon, Inc., Cincinnati, OH, USA). Using this technique, we did not experience any difficulties or use any articulated instruments. All of the present 7 patients underwent the single-incision laparoscopic colectomy successfully and had no complications. CONCLUSION: Single-incision laparoscopic surgery using the Gelport was performed safely in the present cases. The use of the Gelport as an access port can address the technical difficulty associated with this new technique.

IL28B polymorphism may guide pegylated interferon plus ribavirin therapy even after curative treatment for hepatitis C virus-related hepatocellular carcinoma.

The present study was designed to determine the predictive factors for the viral response to pegylated interferon-alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV-genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013] for patients with genotype 1. Multivariate analysis identified male gender (OR 8.72, P = 0.001) and interleukin-28B (IL-28B) genotype (rs8099917) TT (OR 7.93, P = 0.007) as independent predictors of pEVR. Multivariate analysis also identified IL-28B genotype GG+TG (OR 14.1, P = 0.021) and α-fetoprotein >30 (OR 5.4, P = 0.031) as independent predictors of null response. Patients with SVR showed a better survival rate than those without SVR (P = 0.034). The second HCC recurrence rate tended to be lower in patients with SVR than in those without SVR (P = 0.054). With regard to the prognosis of patients with SVR, it is desirable to achieve SVR with interferon therapy even when administered after HCC treatment. IL-28B genotype is a potentially useful marker for the response to PEGIFN/RBV therapy administered after curative treatment of HCV-related HCC.

Long-term outcome of hepatic artery reconstruction during living-donor liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) after living-donor liver transplantation (LDLT) is a potentially life-threatening complication. Although the introduction of microsurgical techniques has significantly decreased the incidence of HAT after LDLT, it remains a challenge for microsurgeons. We previously reported the use of the microsurgical hepatic arterial reconstruction technique during LDLT using the head-mounted surgical binocular system. METHODS: In this study, we describe the long-term outcome of microsurgical hepatic artery reconstruction using the head-mounted surgical binocular system and our hepatic arterial reconstruction techniques on LDLT patients, including intimal dissection cases and clinical courses. Between August 2001 and February 2010, 146 patients underwent LDLT at our institution. Using a surgical loupe, the Varioscope AF3, which is a head-mounted surgical binocular system with automatic focusing and continuous zoom magnification from 3.6× to 7.2×, 150 arteries of 146 liver grafts were reconstructed. When the tunica intima was separated from the tunica media, suturing was performed from the inside of the vessels to the outside using an 8-0 monofilament Prolene with double needles, which facilitates secure sutures with good intima adaptation. RESULTS: The 1- and 3-year survival rates of the 146 patients were 80.3% and 74.9%, respectively, with a mean follow-up of 40.2 months. The mean diameter of the graft hepatic artery was 2.79 mm. HAT was not encountered in this series of patients. CONCLUSION: The use of the Varioscope and the application of our suturing techniques have provided entirely satisfactory long-term results of hepatic artery reconstruction during LDLT, even in intimal dissection cases.

Preliminary trial of adjuvant surgery for advanced gastric cancer.

In patients with stage IV gastric cancer, systemic chemotherapy is the key treatment. Combination chemotherapy (cis-diamminedichloride platinum plus S-1 and docetaxel plus S-1) results in long-term survival in clinical practice. In selected cases, additional (adjuvant) surgery may result in further long-term survival. This study aimed to evaluate the efficacy of adjuvant surgery following the response to chemotherapy for advanced gastric cancer. Based on response to chemotherapy, the indications for adjuvant surgery (surgery after the response to chemotherapy) are that resection is expected to be curative rather than palliative, provided that no other distant metastases occur. The study included 20 advanced gastric cancer patients who had undergone gastrectomies after the response to the combination chemotherapy of docetaxel and S-1, between September 2003 and December 2008 at Hiroshima University Hospital. At a median follow-up of 980 days, the median overall survival was 855 days. A 2- and 3-year survival was observed in 80 and 54.9% of patients, respectively, following macroscopic curative surgery. In the palliative group, the median overall survival was 510 days, but a 3-year survival was not observed. In the partial response group, the median overall survival was 865 days and a 3-year survival was observed in 37% of patients. One-year survival was not observed in the stable disease group. The patient survival in the partial response group was statistically more prolonged than in the stable disease group. The median overall survival in patients with liver metastasis was 865 days, while that in patients with peritoneal dissemination was 510 days. In conclusion, adjuvant surgery may be effective in gastric cancer patients diagnosed as stage IV by means of liver or distant lymph node metastasis, except in cases of peritoneal dissemination.

Remission of splenic volume in the recipient during the course of adult-to-adult living donor liver transplantation: evaluation using multislice computed tomography and semiautomatic software.

AIM: The purpose of the study was to examine changes in splenic volume among recipients during the course of adult-to-adult living donor liver transplantation (LDLT) using multislice computed tomography (CT) scanning with a semiautomatic volumetry software. MATERIALS AND METHODS: Forty-eight patients, including 33 males and a mean overall age of 54 +/- 8 years), underwent liver transplantation for the primary disease of liver cirrhosis with or without hepatocellular carcinoma (n = 31/17, respectively). The mean MELD score was 14 +/- 6. The liver graft mass compared with recipient weight was 74% +/- 28%. Splenic artery embolization was not performed. Dynamic CT scans splenic volume, and platelet counts (10(3)/cm(3)) were obtained pre, < or =50 day and > or =90 days postoperatively. RESULTS: The total time to generate volumetry and image postprocessing per examination was <10 minutes. One-factor analysis of variance (ANOVA) revealed that the average splenic volume tended to be reduced from pre- to post-LDLT, although not significantly: pre-LDLT, 469 +/- 270 mL; < or =day 50, 369 +/- 212 mL; and > or =day 90, 378 +/- 210 mL (P = .066). One-factor ANOVA revealed that the average platelet count was significantly different in the 3 periods: pre-LDLT, 69 +/- 32 x 10(3)/cm(3); < or =day 50, 181 +/- 253 x 10(3)/cm(3); and > or =day 90, 126 +/- 64 x 10(3)/cm(3) (P < .01). The post hoc Scheffé test revealed the statistical significance of the platelet counts between pre-LDLT and < or =day 50 (P < .01). CONCLUSION: Splenic volumetry with multislice CT and semiautomatic software, which is simple and not time consuming, was able to evaluate remission from hypersplenism during the course of LDLT.

Successful living donor left liver transplantation by using liver graft with multiple large cysts: a case report.

There are few reports regarding the use of liver grafts with multiple large cysts in living donor liver transplantation. A 40-year-old woman who was diagnosed with Wilson's disease underwent living donor left liver transplantation; the donor was her 67-year-old mother. The liver graft had multiple large cysts, with a maximum diameter of 9 cm. At donor hepatectomy, the largest cyst and one small cyst were fenestrated, because they were located in the left paramedian sector; the other cysts were left intact. After transplantation, the liver graft exhibited good function with no cyst-related complications, such as hemorrhage, infection, or rupture, despite slight enlargement of the cysts. Thus, a liver graft with multiple large cysts is transplantable. However, the necessity of treating large cysts remains debatable.

Near-infrared spectroscopic analysis of hemodynamics and mitochondrial redox in right lobe grafts in living-donor liver transplantation.

Near-infrared spectroscopy (NIRS), which enables non-destructive evaluation of hemoglobin (Hb) oxygenation and the redox state of cytochromeoxidase (Cyt.aa3) in living tissues, has been employed during surgery to detect possible impairment of hemodynamics and mitochondrial respiration in the anterior segment of a right lobe liver graft in living-donor liver transplantation (LDLT). Thirty-six patients undergoing LDLT using a right lobe graft without the middle hepatic vein (MHV) were enrolled in this study. During the course of harvesting and implantation, NIRS measurements were performed on the anterior segments of the liver grafts. In two recipients of liver grafts with Hb residue over 70% in the anterior segment after ex vivo flushing, the MHV tributary was reconstructed, while it was not reconstructed in the other 34 recipients. Of those 34 recipients, 16 recipients of liver graft with 40-70% Hb residue showed transient increase of transaminase levels after LDLT. Of those 16 recipients, six recipients who showed reduction in oxidized Cyt.aa3 in the anterior segment suffered from persistent hyperbilirubinemia after LDLT. In patients showing impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries, reconstruction of the MHV tributaries might have a beneficial effect.