Evidence of different pharmacokinetics between cyclosporine and tacrolimus in renal transplant recipients: why cyclosporine is monitored by C2 level and tacrolimus by trough level.

The clinical efficacy of calcineurin inhibitors administered to renal transplant recipients is considered to be a strong function of the area under the concentration time curve (AUC). Monitoring of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CyA) and tacrolimus (TAC) are different. Namely, CyA blood concentration is usually monitored at two hours after administration (C2), a surrogate for peak concentration (Cp), and TAC at trough concentration (Ct). We examined the behavior of blood concentration curves simultaneously for both CyA and TAC in renal transplant recipients with similar clinical backgrounds. Furthermore, we analyzed the correlation of Cp and Ct vs AUC implementing an area under the trough level, or area above the trough level as new pharmacokinetic parameters, so that C2 for CyA and Ct for TAC has validated using controlled clinical data. We observed differences in the pharmacokinetics between.

ABO-incompatible adult living donor liver transplantation for hepatocellular carcinoma.

Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the need for pretransplantation treatment may be eliminated, which may reduce overall morbidity. In this article, we have described 8 adult HCC patients who successfully underwent LDLT from ABO-incompatible donors. Antirejection therapy included multiple preoperative plasmaphereses, splenectomy, and an immunosuppressive regimen with tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of the ABO-identical cases. In addition, we also performed intrahepatic arterial infusion of prostaglandin E1. In 5 patients, we administered a single dose of rituximab, a chimeric CD20 monoclonal antibody. As a result of this treatment, 6/8 patients are still alive. Our experience has shown that it is possible to control antibody-mediated humoral rejection and other complications in adult ABO-incompatible LDLT.

How can we increase living related donor renal transplantations?

BACKGROUND: In Japan, living donor renal transplantation has gained momentum due to an increased number of patients with end-stage renal disease. Living donation not only provides better outcomes, but also the recipients usually need less medications, thereby increasing the quality of life and reducing the potential side effects of immunosuppression. MATERIALS AND METHODS: For the past 25 years, our center had performed 140 open donor nephrectomy (OPNx) renal transplantations. Since July 2003, we changed our procurement operation to living hand-assisted laparoscopic donor nephrectomy (HALNx) in 49 cases. Our operative technique consisted of two 12-mm ports placed in the midaxillary line at the superior and inferior levels of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system fitted through a midline abdominal incision. RESULTS: In 49 cases, HALNx was completed successfully; no patient required conversion to laparotomy. The estimated blood loss was 33.0 +/- 43.4 g and no patient required blood transfusion. In comparison, in OPNx the blood loss was 426.5 +/- 247.6 g (P < .001). The mean operative times were 167.4 +/- 39.7 minutes for HALNx and 228.4 +/- 35.7 minutes for OPNx (P < .001). The postoperative hospital stays were 9.1 +/- 3.8 days for HALNx and 13.0 +/- 1.9 days for OPNx (P < .001). For 3 years prior to introduction of HALNx, we had performed only 10 living donor renal transplantations. Since the introduction of HALNx in 2003, the number of living donors has tripled during the following 3 years. CONCLUSIONS: Herein we have reported that HALNx was superior in terms of less operative time and blood loss, postoperative pain and recovery, and shorter hospital stay. Overall donor patient satisfaction was also better in the HALNx group. HALNx is a safe procedure that makes kidney donation more appealing to potential live donors and has increased the living donor pool at our center.

Similar Outcomes of Kidney Transplantations Using Organs From Donors After Cardiac Death and Donors After Brain Death.

BACKGROUND: To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased. METHODS: At our institution, 28 patients underwent cadaveric kidney transplantation from January 2001 to December 2016. These patients were classified into 2 groups according to DBD or DCD. Furthermore, 10 patients received transplants from expanded criteria donors (ECD) and 18 received them from standard criteria donors (SCD). RESULTS: Kidney graft survival and engraftment were observed for all patients. There were no significant differences in renal function at 6 months for DBD and DCD transplant recipients. Renal function at 1, 3, and 5 years and serum creatinine levels were better for the ECD group. Renal function at 5 years after transplantation was significantly better for the SCD group than for the ECD group; however, there was no difference in delayed graft function between the SCD and ECD groups. Comparisons of the 3 groups showed good renal function for transplants from DBDs, but there was no significant difference in survival rates. CONCLUSIONS: Results were good for all patients. There were no significant differences in outcomes of our patients who received transplants from ECD or SCD.

An Examination of Pregnancy Cases After Kidney Transplantation: Single-Center Experience.

INTRODUCTION: The number of young women who wish to become pregnant opting for kidney transplants is increasing, as becoming pregnant under hemodialysis or peritoneal dialysis is associated with many risks. However, there have been reports indicating that these patients are subject to a higher risk of miscarriage compared to women with normal renal function. We examine and report cases of patients that experienced pregnancy after undergoing kidney transplantation at our hospital. SUBJECTS AND METHOD: Of the kidney transplantation cases that were performed at our hospital between 1985 and 2016, there were 7 cases of pregnancy. The serum creatinine levels, urine protein findings, etc, of these 7 cases were examined during the pre-pregnancy, pregnancy, childbirth, and postpartum periods. RESULTS: All 7 cases were able to give birth. There were two cases of transient postpartum hypertension. There were no cases of obvious pregnancy toxemia or fetal growth retardation. Two of the cases resulted in the failure of the transplanted kidneys. DISCUSSION: According to previous studies on pregnancy and childbirth after kidney transplantation, the presence of high blood pressure and proteinuria as well as the renal function at the time of pregnancy is closely associated with postpartum renal function. Urine protein was detected prior to pregnancy in both cases and resulted in the failure of the transplanted kidneys. The influence of immunosuppressants on the mother and fetus is also an important consideration. CONCLUSION: We believe it is extremely important to ensure a thorough informed consent process prior to pregnancy and systematic use of immunosuppressants for young female transplant recipients.

Early Outcomes of Living-Donor Kidney Transplantation With Immunosuppression Therapy Induction With Tacrolimus Extended-Release: A Comparison With Cyclosporine.

BACKGROUND: Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. METHODS: The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. RESULTS: The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. DISCUSSION: Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. CONCLUSION: TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice.

The role of plasmapheresis therapy for perioperative management in ABO-incompatible adult living donor liver transplantation.

BACKGROUND: Although living donor liver transplantation (LDLT) was established as a treatment for end-stage liver disease in Japan, the indication for LDLT across an ABO-incompatible barrier remains controversial. The purpose of this study was to elucidate the role of plasmapheresis in incompatible LDLT. METHODS: Eleven adult patients (seven men and four women) who underwent incompatible LDLT were enrolled in this study. Of these three patients had hepatocellular carcinoma, three chronic hepatitis C, one Wilson's disease, one autoimmune hepatitis, one chronic hepatitis B, one hemochromatosis, and one fulminant hepatic failure. The immunosuppressive regimen consisted of tacrolimus, prednisolone, mycophenolate mofetil (or cyclophosphamide), and prostaglandin E1 in all patients. Multiple plasmapheresis was performed perioperatively to reduce the recipient's antibody titers against the donor's blood type. RESULTS: Plasmapheresis was useful for the reduction of the recipient's antibody titers to x 16 or lower before and after transplantation. There was no difference in transplant outcome between the 11 patients with incompatible blood group and 30 patients with identical or compatible blood groups. DISCUSSION: Major postoperative complications such as intrahepatic biliary complications and hepatic necrosis may occur in incompatible transplantation. Several investigators suggested that anti-immunoglobulin (Ig) M and anti-IgG antibody titers sustained these complications. The antibody titers must be decreased sufficiently with plasmapheresis. An elevation of anti-ABO titers after transplantation may be a predictive risk factor for increased mortality and morbidity. In order to perform LDLT in a safer manner, plasmapheresis is an indispensable treatment to improve the outcome of ABO-incompatible cases.

Postoperative Compensatory Changes and Blood Flow Parameter of the Preserved Kidney in Elderly Living Related Donors Evaluated by Doppler Ultrasonography.

INTRODUCTION: Elderly kidney donors have recently become more common in living related kidney transplantation in Japan. Therefore, it is important to evaluate whether kidney function in elderly donors after nephrectomy is preserved over long periods of time. Doppler ultrasonography measurement is practical for donors after nephrectomy because it involves simple and noninvasive examinations. Doppler ultrasonography can detect compensatory hypertrophy and blood flow parameters, namely resistive index (RI) and pulsatility index (PI), of the preserved kidney in living donors. PATIENTS AND METHODS: Our study included 58 donors, divided into 2 groups according to age; the elderly donor group was comprised of those 65 years old or older. We measured length, width, and short diameter of the preserved kidney using Doppler ultrasonography, and calculated kidney volume. RESULTS: The elderly group was comprised of 13 patients. In this group, the median preserved kidney volume was 145.0 cm(3) (101.8-193.5) before nephrectomy, and 127.6 cm(3) (99.0-183.4) and 145.5 cm(3) (141.3-148.6) at 1 and 12 months after nephrectomy, respectively. We did not observe significant compensatory hypertrophy in the preserved kidneys of elderly donors postoperatively. Both the mean PI and RI values of elderly donors increased progressively after nephrectomy. No compensatory hypertrophy occurred in the preserved kidneys of elderly donors, although the PI and RI did increase in these donors. CONCLUSION: Our results indicate that nephrectomy caused nephrosclerosis in the preserved kidneys of elderly donors and that prevention of hypertension may be important after nephrectomy in elderly donors.

Study of Cadaveric Kidney Transplantation: A Single Center Experience.

BACKGROUND: To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively perform transplantation from marginal donors. We had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be increases in the number of ECD kidney transplants. METHODS: In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Sixteen of those patients were classified into 2 groups according to donation after brain death (BD) or after cardiac death (CD). We also classified donors as ECDs or standard-criteria donors (SCDs). RESULTS: Kidney graft survival and engraftment were observed in all of the patients. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between the groups in renal function at 3 and 5 years. Renal function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, but there was no difference in renal function between the SDC and ECD groups at 5 years. CONCLUSIONS: The results were good for all of the patients. There are many reports that graft survival rate at 3-5 years after transplantation from ECDs is poorer than from SCDs. However, no statistically significant difference was found in kidney function at ≥5 years between the ECD and SCD groups in our patients.

Clinical Outcomes and Results of Pathological Findings of 1-year Protocol Biopsy in Recipients of ABO-Incompatible Living Donor Kidney Transplantants.

OBJECTIVES: ABO-incompatible kidney transplantation has increased the possibility of finding suitable living donors for patients with renal failure. However, there are inevitable immunological risks, including a high risk of early post-transplantation complications. The purpose of this study was to evaluate recipient outcomes following ABO-incompatible kidney transplantation. METHODS: Seventy-one patients who had undergone living-donor kidney transplantation (LDKT) at our center between January 2008 and December 2013 were divided into ABO-incompatible (ABOi; n = 21) and ABO-compatible (ABOc; n = 50) groups. Baseline data, graft function, immunosuppressant use, and the results of biopsy 1 year after LDKT were compared between the groups. RESULTS: Recipient preemptive LDKT rates were significantly different between groups (P = .017). Graft function, incidence of infection, and rates of T-cell-mediated rejection and borderline changes requiring medication were not significantly different. There was no acute antibody-mediated rejection. Selectivity of the immunosuppressant, tacrolimus, was significantly different between groups (P < .01); however, steroid withdrawal rates, mycophenolate mofetil doses, and calcineurin inhibitor trough levels were not different. Regarding biopsy data, interstitial fibrosis scores were significantly different between groups (P = .011), as were interstitial fibrosis and tubular atrophy scores (P = .045) and arteriolar hyalinosis score (P = .022). CONCLUSION: ABOi LDKT was relatively safe, with no significant difference in the incidence of rejection compared to ABOc LDKT. Managing chronic pathological changes and arteriolar hyalinosis prophylaxis after ABOi LDKT may result in more successful outcomes.

Immunosuppressive Therapy for Elderly Kidney Transplant Recipients.

OBJECTIVES: In elderly kidney transplant (KT) recipients, the incidence of acute rejection is decreased, while that of fatal infections is increased. There are currently no guidelines for an upper age limit for KT, which is very difficult to determine. Here we examined several cases of elderly KT recipients. METHODS: We evaluated 127 KT patients treated at our department between 2003 and 2012 and followed them for 3 years post-transplant. The subjects were divided into two groups by age: ≥60 years (elderly group; n = 24); and <59 years (non-elderly group; n = 103). The presence or absence of acute rejection and infection, dose of immunosuppressive drugs, trough calcineurin inhibitor level, renal function, and graft and patient survival rates were retrospectively examined. RESULTS: Our basic immunosuppressive regimen was a combination of calcineurin inhibitor, methylprednisolone, mycophenolate mofetil, and basiliximab. At 1 year post-transplantation, the average tacrolimus and cyclosporine dose and trough levels were not significantly different. The mean dose of mycophenolate mofetil in the elderly group at 1 year post-transplantation was significantly lower than that of the non-elderly group. The incidences of cytomegalovirus infection and acute rejection during follow-up did not differ significantly between groups. There were no significant differences in creatinine level between the two groups. In the elderly group, the graft survival rates at 1 and 5 years were 100% and 95.4%, respectively, while those in the non-elderly group were 98.1% and 92.5%, respectively. CONCLUSION: Using our current immunosuppressive protocol, the outcomes of patients in the elderly group were considered acceptable.

A Novel Assessment of Vascular Regions Using an Intraoperative Near-Infrared Fluorescence.

INTRODUCTION: The risk of complications and transplant renal function increases in multiple arterial renal transplantations compared with single arterial renal transplantations. Even when multiple arteries are involved, with the introduction of laparoscopic nephrectomy, I mainly choose the left side kidney. Therefore, the number of renal artery reconstructions is increasing, and simultaneous imaging of arterial rebuilding during the donor nephrectomy is important. MATERIAL: Between 2006 and 2015, we performed 132 living donor kidney transplantations at our center and analyzed 32 cases that were diagnosed pre- and intraoperatively. METHOD: We compared the single renal artery (SRA) and multiple renal arteries (MRA) groups and analyzed the number of renal arteries, reconstruction methods, donor and recipient ages, sex, total ischemic times, and 1-month serum creatinine values. RESULT: In the MRA and SRA groups, the average recipient age was 52.3 and 47.0 years, respectively, while the average donor age was 52.9 and 53.1 years, respectively. In SRA and MRA groups, total ischemic time (TIT) was 96.1 and 143.6 min (P < .01). Serum creatinine level 1 month post-transplantation was 1.54 and 1.25, respectively (P < .001). Here we experienced 12 cases of living renal donor nephrectomy with multiple vessels in which the vascular supply territory was first assessed in April 2013 using an intraoperative near-infrared fluorescence camera system. In addition, regarding TIT, it is possible to shorten surgery by using individual anastomosis and ligation. CONCLUSION: By managing multiple donors; arteries by nephrectomy, it is possible to improve kidney transplantation results.

Radial flow bioreactor for the creation of bioartificial liver and kidney.

A radial flow bioreactor (RFB) is used for a three-dimensional perfusion culture of hepatocellular carcinoma (HCC) cells and renal cells, to create a bioartificial liver and kidney. The cylindrical reactor is filled with porous cellulose microcarrier. RFB can be characterized as a system in which the medium flows from the periphery toward the center of the reactor, thereby delivering an adequate supply of oxygen and nutrients to cells at the center as well as at the periphery. HCC cells incubated in the RFB system at high density maintained viability for long periods of time. Proximal tubular cells (LLC-PK1) as well as HCC cells, but not human immortalized mesangial cells (HMC) were cultured in the RFB for more than 14 days. The mRNA expression of some enzymes involved in the urea cycle, cytochrome P450s in HCC cells, and the 1-alpha-hydroxylase (CYP27B1) in LLC-PK1 cells was higher than that in monolayer cultures. These results suggest that the RFB system composed of HCC cells or renal cells may be useful for a bioartificial liver and kidney.

Evaluation of appropriate blood level in continuous intravenous infusion from trough concentrations after oral administration based on area under trough level in tacrolimus and cyclosporine therapy.

The target blood concentrations of tacrolimus (TAC) and cyclosporine (CYA) during continuous intravenous infusion (C(ss)) have been determined based on clinical experience. However, it is desirable that C(ss) should be set so that the AUC after intravenous infusion is equal to the AUC after oral administration (AUC(po)). Accordingly, we performed 12-hour monitoring of blood concentrations to calculate C(ss) from the blood trough levels (C(TL)) on 15 kidney recipients administered TAC and 12 recipients administered CYA (Neoral). We used an area under the trough level (AUTL) as a new pharmacokinetic parameter. The C(ss) was evaluated from C(TL), AUC(po), and AUTL was calculated to be C(ss) = C(TL) x (AUC(po)/AUTL). In addition, AUTL/AUC(po) ratio and blood peak/trough level ratio (C(max)/C(min)) were examined to compare pharmacokinetics of TAC and CYA. The formula for TAC was C(ss) = C(TL) x 1.40 and that for CYA, C(ss) = C(TL) x 2.55. The calculated target C(ss) of TAC was 1.40 times that of C(TL), which was similar to the present clinical C(TL). In contrast, the calculated target C(ss) of CYA was 2.55 times the C(TL), and therefore an extremely high C(ss) was necessary to obtain a sufficient AUC that will be available after oral administration. Consequently, intravenous administration of CYA twice a day was considered to be more appropriate to obtain sufficient CYA pharmacokinetics, rather than a continuous intravenous administration. We conclude that the formula, C(ss) = C(TL) x (AUC(po)/AUTL) was useful to calculate the target blood concentration of calcineurin inhibitors when changing from continuous intravenous infusion to oral administration of these drugs.

Pharmacokinetic differences between morning and evening administration of cyclosporine and tacrolimus therapy.

We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were administered equally divided doses of drugs twice daily orally. Blood samples were taken before and 1, 2, 3, 4, 6, and 12 hours after NEO or TAC administration in the morning and evening. The pharmacokinetic parameters were compared between morning and evening administrations of both drugs. AUC0-12, AUC0-4, C(max), C2, and C(max)/C(min) of NEO and TAC were significantly lower during the evening compared with morning administrations. C(min) values were significantly higher in the evening. T(max) of NEO was longer in evening, although there was not a significant difference; T(max) of TAC was significantly longer in the evening. We found that NEO and TAC administrations in the evening resulted in reduced bioavailability and delayed absorption when compared with drug administrations in the morning. It was thought that the difference in bioavailability between morning and evening administrations was smaller with TAC, because TAC shows lower peak levels and a flatter blood concentration curve than NEO. C(min) was higher after evening administration than morning because of delayed absorption, though the bioavailability of both drugs decreased in the evening. These results suggest that we have to appreciate apparently high trough levels.

Optimal dose and target trough level in cyclosporine and tacrolimus conversion in renal transplantation as evaluated by lymphocyte drug sensitivity and pharmacokinetic parameters.

We evaluated the relative clinical potency of cyclosporine (CyA) and tacrolimus (Tac) using pharmacodynamic and pharmacokinetic parameters of the drug to obtain the most suitable converting dose and target trough level. The relative pharmacodynamic potency was examined by the mean ratio of drug concentrations giving 50% inhibition of blastogenesis of lymphocytes (IC50) in 66 chronic renal failure patients. The relative potency estimated from clinical pharmacokinetic parameters was examined by the mean ratio of each pharmacokinetic parameter value of CyA versus Tac. The pharmacokinetic parameters were estimated by 12-hour monitoring of drug blood concentrations in seven CyA patients and seven Tac patients. The mean IC50 ratio of CyA and Tac (CyA/Tac of IC50) was 25.1. The mean area under the concentration-time curve (AUC) ratio (CyA/Tac of AUC) was 25.5, the mean trough level (C(min)) ratio (CyA/Tac of C(min)) was 13.2, and the mean dose per body weight ratio was 25.2. The relative potency estimated from AUC that is the most reliable pharmacokinetic parameter for the estimation of clinical efficacy of calcineurin inhibitors appeared to agree with the relative pharmacodynamic potency estimated from IC50. The data suggest that TAC 25-fold more potent than CyA, which represents a suitable converting dose ratio, and that target trough level of CyA is about 13-fold greater than Tac based on CyA/Tac of C(min). We conclude that these relative values may be useful to estimate the suitable dose and target trough levels to convert between CyA and Tac.

Adult living-donor liver transplantation for a recipient with a high preoperative 1,3-beta-D-glucan level and positive test result for Aspergillus antigen.

The patient was a 45-year-old man with underlying alcoholic liver cirrhosis. Two years prior, he was repeatedly hospitalized for liver failure symptoms and requested a living-donor liver transplantation (LDLT) because of end-stage cirrhosis. A pretransplantation blood test revealed a high 1,3-beta-d-glucan (BDG) value of 102.0 pg/mL (reference value <20.0 pg/mL) and a high blood Aspergillus antigen (AsAg) value of 1.6 cutoff index (COI; reference value <0.5 COI). Contrast-enhanced thoracoabdominal-pelvic computed tomography (CT) and cranial magnetic resonance imaging revealed no fungal infection. However, latent fungal infection could not be ruled out, hence preoperative antifungal agent treatment was administered. BDG and AsAg levels showed a decreasing trend after treatment initiation. However, normalization did not occur; the BDG and AsAg levels were 25.8 pg/mL and 1.0 COI, respectively. Although the possibility of latent fungal infection was judged low, we prophylactically administered antifungal agents after LDLT. The BDG level consistently increased at 35-39 pg/mL until postoperative day 5 but subsequently normalized. The AsAg level was higher than the limit of detection at 5.0 COI on postoperative day 3 but normalized to 0.2 COI on postoperative day 5 and did not subsequently increase. The postoperative course was uneventful despite bacterial pneumonia and the patient was discharged on postoperative day 35. A histopathologic examination (Grocott methenamine silver staining) and a fungal polymerase chain reaction assay were performed for the resected liver, but the results of both were negative. At 9 postoperative months, the patient was making ambulatory follow-up visits. Currently, the BDG and AsAg values remain normal and clinical progress is favorable. We found no reports of LDLT for a recipient with a high preoperative BDG level and positive test result for AsAg. Thus, we report on such a case with a discussion of the literature on the causes of high preoperative BDG and AsAg values.

Successful case of adult ABO-incompatible liver transplantation: beneficial effects of intrahepatic artery infusion therapy: a case report.

BACKGROUND: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However, <30% are cases involving adults. The difficultly of ABO-incompatible liver transplantation is associated with the high frequency of humoral rejection and local disseminated intravascular coagulation (DIC), leading to many postoperative complications. We report a successful case of adult ABO-incompatible liver transplantation with the use of an intrahepatic artery infusion. METHODS: A 36-year-old man with Wilson disease, underwent living donor liver transplantation from an ABO-incompatible donor. The immunosuppressive therapy included multiple perioperative plasmaphereses, splenectomy, and treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and blood level of tacrolimus were the same as in ABO-compatible cases. In addition to these therapies, we administered an intrahepatic arterial infusion with prostaglandin (PG) E1 alone. RESULTS: After perioperative plasmapheresis and cyclophosphamide, antidonor blood group antibody titers remained undiluted and without vascular complications throughout the postoperative course, but there was a tendency for bleeding that continued for 10 days after transplantation. On postoperative day 10, a reexploration was performed for intraabdominal bleeding. During another operation on postoperative day 59 a biloma was found and drained. The patient has now survived for 120 days after transplantation with normal liver function. CONCLUSIONS: Beneficial effect of intrahepatic artery infusion with PGE1 seems to be useful in adult ABO-incompatible liver transplantation.

[Transfer of cefmenoxime to lung tissue and thoracic muscle in thoracic surgery].

Twenty patients who were performed pulmonary resection for the disease of the lung were administered 2 g of cefmenoxime (CMX) intravenously during the operation. The CMX levels in serum, lung tissue and thoracic muscle were measured by agar-well technique. The CMX levels in lung tissue and thoracic muscle were higher than the MIC80 of CMX for Klebsiella pneumoniae, Haemophilus influenzae and Streptococcus pneumoniae which were commonly as isolated causative organisms from the patients with pulmonary infection. These results indicate that CMX will be useful agent for the prevention and treatment of pulmonary infection.

[Right atrial lipoma with calcification in ascending aorta; report of a case].

A 67-year-old male was diagnosed to have a right atrial tumor by echocardiography incidentally. Computed tomography (CT) indicated a mass which showed very low radiodensity and magnetic resonance imaging (MRI) [T1-weighted] showed the high signal intensity of tumor. We could predict the mass as lipoma. Tumor removal was performed under cardio-pulmonary bypass and under ventricular fibrillation because of the calcification in ascending aorta. Microscopically the tumor was consisted of mature adipose tissue. The postoperative course was uneventful. Cardiac lipomas are rare tumors. CT and MRI are better investigations for preoperative diagnosis. After surgical excision the prognosis is excellent.