M. Shin

Primary Versus Salvage Living Donor Liver Transplantation for Patients With Hepatocellular Carcinoma: Impact of Microvascular Invasion on Survival

OBJECTIVEnSalvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT.nnnMETHODSnBetween September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT.nnnRESULTSnIntrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion.nnnCONCLUSIONSnFive-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor for survival.

Hormone replacement therapy in postmenopausal women with Alzheimer’s disease: a randomized, prospective study

OBJECTIVEnTo compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimers disease.nnnDESIGNnSix-month, randomized, open-label study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nFifty-five women with mild to moderate Alzheimers disease were randomly assigned to tacrine (n = 26) or HRT (n = 29).nnnINTERVENTION(S)nIn the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26).nnnMAIN OUTCOME MEASURE(S)nMini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL).nnnRESULT(S)nThirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in epsilon 4-negative patients.nnnCONCLUSION(S)nOverall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In epsilon 4-negative patients, tacrine is preferable for cognition and mood.

Can Immune Function Assay Predict Infection or Recovery

BACKGROUNDnRecently, the ImmuKnow assay (Cylex Inc., Columbia, Md) has been reported to be a global immune monitoring tool for organ transplants recipients. We assessed whether immunKnow ATP values predicted infectious syndromes.nnnMETHODSnWe prospectively enrolled 71 kidney transplant patients between September 2008 and May 2011. lmmuKnow assay monitoring was performed at one dav before as well as 4, 8, 12, 16, 20, 24, 36, and 52 weeks after the operation. ImmuKnow assay values were compared as well as BK viral infection pre-infection(PI), at first detection of infectious syndrome (DI), 4 weeks there after (4W), 8 weeks there after (8W) and 12 weeks there after (12W) and pre-recovery (PR), recovery (R) times.nnnRESULTSnSerial ImmuKnow assays showed significant differences over time and BK viral infectious state (P = .026). Interestingly, PI was significantly lower than DI and PR but PR significant greater than PI, 8W and 12W. However, we did not observe an adequate or absolute cutoff value of ImmuKnow by ROC curve: 377 ng/mL ImmuKnow showed 0.471 of AUC and 57.1% and 56.2%, of sensitivity and specificity.nnnCONCLUSIONnLongitudinal evaluation and adjustment of the value of ImmuKnow assay seemed to be a favorable modality to monitor infectious syndromes especially those involving BK virus.

Comparison of Outcomes of Living and Deceased Donor Kidney Grafts Surviving Longer Than 5 Years in Korea

BACKGROUNDnIt is generally recognized that living donor kidney transplantation (LDKT) grafts are superior to deceased donor kidney transplantation (DDKT) grafts. We compared survival and functional outcomes of LDKT and DDKT grafts.nnnMETHODSnAmong 1000 kidneys transplanted from 1995 to 2008, we selected grafts surviving >5 years, excluding pediatric, multi-organ transplantation, and retransplantations (n=454).nnnRESULTSnThere were 179 kidneys from deceased donors and 275 from living donors. Recipients showed no difference in age, gender, or cause of renal failure. Donors were younger in the DDKT group (30.6 vs 38.5 years; P<.05). There were more male donors in the DDKT group (73.2% vs 54.5%; P<.05). Deceased donors showed a greater mean number of HLA mismatches (4.2 vs 2.7; P<.05). Death-censored graft survival at 10 years showed no difference (DDKT 88.9% vs LDKT 88.9%; P=.99). Mean serum creatinine at 5 years was 1.41 mg/dL for DDKT and 1.44 mg/dL for LDKT (P=.75). Mean estimated glomerular filtration rate at 5 years was 67.8 mL/min/1.73 m2 for DDKT and 62.1 mL/min/1.73 m2 for LDKT (P=.23). Twenty-three DDKT grafts (12.8%) and 47 LDKT grafts (17.1%) experienced acute rejection episodes (P=.22). DDKT recipients showed more cases of viral and bacterial infections compared with LDKT recipients (viral, 11.7% vs 2.2% [P<.05]; bacterial, 21.8% vs 7.3% [P<.05]).nnnCONCLUSIONnAmong kidney grafts surviving >5 years, there was no difference in survival or serum creatinine levels at 5 and 10 years between DDKT and LDKT grafts.

Effectiveness of Intraportal Prostaglandin E1 Administration after Liver Transplantation

PURPOSEnProstaglandin E1 (PGE1) has been used to improve hepatic blood flow and to reduce ischemia reperfusion injuries of allografts in liver transplantation. However, PGE1 undergoes extensive metabolic clearance in the pulmonary and splanchnic circulation during intravenous administration. We analyzed the effect of intraportally administered PGE1.nnnMETHODSnSixty living-donor liver transplant recipients received continuous infusions of PGE1 for 10 days immediately after the reperfusion of the allografts. Of them, 40 recipients received PGE1 intravenously (IV group) via the internal jugular vein, and 20 recipients received PGE1 intraportally (IP group) through a catheter in the inferior mesenteric vein. Data were collected for 3 weeks postoperatively.nnnRESULTSnThe IP group exhibited lower initial aspartate aminotransferase and alanine aminotransferase levels compared with the IV group. However, no apparent differences were recognized in the serum albumin, total bilirubin, alkaline phosphatase, r-glutamyl transpeptidase, or prothrombin time levels between the 2 groups. Chylorous ascites were observed more frequently in the IP group. There was no difference in portal venous flow measured by Doppler sonogram between the 2 groups during the first postoperative week.nnnCONCLUSIONnThis study demonstrated that intraportal administration of PGE1 had a better cytoprotective effect against hepatocellular damage than intravenous administration, although it did not have additional benefits for perihepatic hemodynamics.

Presence of Vesicoureteral Reflux in the Graft Kidney Does Not Adversely Affect Long-Term Graft Outcome in Kidney Transplant Recipients

INTRODUCTIONnWe studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function.nnnMETHODSnWe performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function.nnnRESULTSnThirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I (nxa0= 6), grade II (nxa0= 30), or grade III (nxa0= 14) reflux. Patients followed for a median 61 months (range 44-74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR (Pxa0= .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation.nnnCONCLUSIONSnVUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR.

Steroid Withdrawal in Adult Liver Transplantation: Occurrence at a Single Center

BACKGROUNDSnSteroids are the predominant immunosuppressive agent used after liver transplantation even though patients may experience steroid-related side effects.nnnAIMSnThe objective of this study was to determine whether steroid use influenced the outcomes of liver transplantations.nnnMETHODSnThree hundred forty-four adult patients underwent liver transplantation between May 2002 and December 2007. We reviewed the medical records of these patients, excluding those younger than 18 years old or those who died within the first month. The protocol withdrawal group (group 1) ceased steroid use within 5 months after transplantation, while the late withdrawal group (group 2) continued steroid use beyond this 5-month posttransplantation period.nnnRESULTSnAll patients were classified according to the onset of steroid withdrawal (group 1: n = 243; group 2: n = 99). The incidences of biopsy-confirmed and treated acute rejection episodes (ARE) at 12 and 24 months posttransplantation were 7.8% and 12.3% in group 1, but 25.3% and 27.3% in group 2, respectively (P = .001). The incidence of hepatitis B virus (HBV) recurrence in group 2 was higher than that in group 1 (P = .007). The HBV-free survival rates at 1 and 2 years posttransplantation were 99.0% and 97.1% in group 1 and 96.1% and 92.1% in group 2, respectively. New-onset diabetes, avascular necrosis of the femoral head, corticosteroid-resistant ARE, hepatocellular carcinoma recurrence, as well as graft and patient survivals did not differ between the two groups.nnnCONCLUSIONSnAcute rejection episodes and HBV recurrence occurred less frequently when steroids were discontinued within 5 months after liver transplantation.

Thymic Epithelial Tumors: Prognostic Determinants Among Clinical, Histopathologic, and Computed Tomography Findings

BACKGROUNDnThe Masaoka-Koga staging system has been known as the strongest prognostic factor for both survival and recurrence of thymic epithelial tumor (TET). The purpose of our study was to find prognostic determinants among computed tomography (CT), histopathologic, and clinical features of TET.nnnMETHODSnTwo radiologists reviewed retrospectively CT findings of 437 patients (male 242, female 195; mean age, 51 years) with TET. With medical record review, surgico-histopathologic results were subcategorized into Masaoka-Koga stages I through IV and World Health Organization histopathologic classifications A-B1, B2-B3, and carcinoma. Overall survival and progression-free survival were analyzed. Clinical, histopathologic, and CT features were correlated from each other.nnnRESULTSnIn all, 437 tumors were in Masaoka-Koga stage I (n = 147, 33.6%), stage II (n = 121, 27.7%), stage III (n = 76, 17.4%), or stage IV (n = 93, 21.3%); A and B1 (n = 114, 26.1%) and B2 and B3 TET (n = 223, 51.0%); and thymic carcinoma (n = 100, 22.9%). In multivariable analyses, age, Masaoka-Koga stage IV, thymic carcinoma, and CT stages III and IV were significantly correlated with overall survival (p < 0.05), whereas adjuvant treatment, Masaoka-Koga stages III and IV, World Health Organization B2 and B3, thymic carcinoma, R2 resection, CT size, and CT stage IV were significantly associated with progression-free survival (p < 0.05). Computed tomography stages showed moderate association with Masaoka-Koga stages (K = 0.621).nnnCONCLUSIONSnFor TET, CT staging is effective in distinguishing both overall survival and progression-free survival, and patients with Masaoka-Koga stage IV or thymic carcinoma or CT stage IV have the worst prognosis.

Importance of Donor–Recipient Age Gradient to the Prediction of Graft Outcome After Living Donor Liver Transplantation

PURPOSEnAdvanced donor age is a well-known risk factor for poor graft function after living donor liver transplantation (LDLT). In addition, advanced recipient age has a significant impact because of the high prevalence of comorbidities. We investigated the relationship between donor-recipient age gradient (DRAG) and the posttransplant outcomes in LDLT.nnnMETHODSnWe included 821 consecutive adult recipients who underwent LDLT from June 1997 to May 2011. According to the value of DRAG, they were divided into 2 groups: Negative years (the donor was younger than the recipient) and positive years (the donor was older than the recipient). These groups were further divided into subgroups (≤-21,xa0-20 toxa0-1, 0 to 20, andxa0≥21 years). We collected retrospectively patient characteristics, laboratory results, medical and surgical complications, and graft loss.nnnRESULTSnThe positive DRAG group had higher level of posttransplant alkaline phosphatase, but a lower incidence of biliary complications. The negative DRAG group, particularly DRAGxa0≤xa0-21 years was associated with the superior 1-, 3-, 5-, and 10-year graft survivals. Recipients with DRAGxa0≥ 21 showed persistently inferior graft survival during the observation period. In cases of young donors, transplants utilizing lower DRAG seen between young donors and older recipients showed more favorable graft survival than that of young-to-young transplants.nnnCONCLUSIONnThis study demonstrated that DRAG and a fixed donor age limit could be significant factors to predict graft survival after LDLT. Patients should carefully consider the worse graft survival if the donor is older than the recipient byxa0≥20.

Comparison Between Resection and Transplantation in Combined Hepatocellular and Cholangiocarcinoma

OBJECTIVEnThe treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC.nnnPATIENTS AND METHODSnFrom 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively.nnnRESULTSnThe poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (>5 cm), small safety margin (<2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (nxa0= 68) and the liver transplant group (nxa0= 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, Pxa0= .333; 5-year OS: 42.1% vs 50%, Pxa0= .591). In the small tumor subgroup (tumor sizexa0<5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin >2 cm), survival was comparable.nnnCONCLUSIONSnIn well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible.