Perioperative changes of procalcitonin levels in patients undergoing liver transplantation.

BACKGROUND: Severe sepsis is a life-threatening complication after liver transplantation (LT) that can be difficult to diagnose and appropriately treat after LT because of patients being treated with immunosuppressants. The present study examines perioperative changes in serum procalcitonin (PCT), a specific marker of systemic bacterial infection, and determines the value of PCT as a diagnostic tool for bacteremia or rejection. METHODS: Perioperative serum PCT levels were prospectively assessed in 104 consecutive adult patients undergoing LT (living-donor LT, n = 90; deceased-donor LT, n = 14) between May 2010 and August 2012. RESULTS: Serum PCT levels remarkably increased soon after LT and gradually decreased thereafter, but were not increased in patients diagnosed with cytomegalovirus infection or acute cellular rejection. Serum PCT levels in patients who underwent deceased-donor LT were significantly higher than in those who underwent living-donor LT until postoperative day (POD) 7. Serum PCT levels were significantly higher in patients with bacteremia than in those without bacteremia after POD 14. In patients with post-transplant bacteremia, PCT levels increased again after POD 7 in patients who died within 3 months of LT, while levels remained low after POD 7 in patients who were alive. A positive predictive value of 83.3% for bacteremia and a negative predictive value of 97.4% were obtained at PCT cutoffs of 2.0 and 0.5 ng/mL, respectively. CONCLUSION: Serum PCT measurement, using appropriate cutoff values, could help diagnose severe infection, and might be able to differentiate bacteremia from acute cellular rejection.

Prediction of the remnant liver hypertrophy ratio after preoperative portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. METHODS: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. RESULTS: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). CONCLUSIONS: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.

Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation.

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

Coupled regulation of interleukin-12 receptor beta-1 of CD8+ central memory and CCR7-negative memory T cells in an early alloimmunity in liver transplant recipients.

This study investigated how CD8(+) T cell subsets respond to allo- and infectious immunity after living donor liver transplantation (LDLT). Early alloimmunity: 56 recipients were classified into three types according to the post-transplant course; type I demonstrated uneventful post-transplant course, type II developed severe sepsis leading to multiple organ dysfunction syndrome or retransplantation and type III with acute rejection. In 23 type I recipients, the interleukin (IL)-12 receptor beta-1 (R beta 1)(+) cells of central memory T cells (Il-12R beta 1(+) T(CM)) were increased above the pretransplant level. In 16 type II recipients, IL-12R beta 1(+) T(CM) was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL-12R beta 1(+) T(CM) was decreased for a more prolonged period until POD 10. Along with down-regulation of IL-12R beta 1(+) T(CM), the IL-12R beta 1(+) cells of CCR7-negative subsets (CNS) as well as perforin, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha decreased gradually, resulting in the down-regulation of effectors and cytotoxicity. The down-regulation of IL-12R beta 1(+) T(CM) was suggested to be due to the recruitment of alloantigen-primed T cells into the graft, and then their entry into the secondary lymphoid organ, resulting in graft destruction. Infectious immunity: immunocompetent memory T cells with the capacity to enhance effectors and cytotoxicity were generated in response to post-transplant infection along with both up-regulation of the IL-12R beta 1(+) T(CM) and an increase in the CNS showing the highest level of IL-12R beta 1(+) cells. In conclusion, this work demonstrated that the IL-12R beta 1(+) cells of T(CM) and CNS are regulated in a tightly coupled manner and that expression levels of IL-12R beta 1(+) T(CM) play a crucial role in controlling allo- and infectious immunity.

A history of smoking is inversely correlated with the incidence of gemcitabine-induced neutropenia.

BACKGROUND: Smoking may affect the efficacy of chemotherapy and the incidence of adverse events. We investigated the correlation between smoking history and gemcitabine-induced neutropenia. PATIENTS AND METHODS: Data on smoking history and incidence of grade 3-4 neutropenia were retrospectively gathered for 103 chemo-naive patients treated with gemcitabine monotherapy (59 patients with pancreatic, 41 with hepatobiliary and three with other cancers). RESULTS: There was a significantly higher incidence of grade 3-4 neutropenia among patients without a history of smoking (55.7%) than among those with a history of smoking (including current and ex-smokers; 23.6%) [odds ratio (OR) 0.244, 95% confidence interval (CI) 0.105-0.569; P < 0.001]. After adjustment for age, gender, platelet and baseline neutrophil counts, history of surgery for primary cancer, creatinine concentration, hemoglobin concentration, aspartate aminotransferase concentration, alanine aminotransferase concentration and total bilirubin concentration, logistic regression analysis identified a history of smoking as an independent inverse predictor of gemcitabine-induced neutropenia (OR 0.188, 95% CI 0.057-0.618; P = 0.006). CONCLUSION: Patients without a history of smoking may be at higher risk of developing gemcitabine-induced neutropenia. The mechanism underlying this phenomenon is unclear at this point.

Does response rate of chemotherapy with molecular target agents correlate with the conversion rate and survival in patients with unresectable colorectal liver metastases?: A systematic review.

PURPOSE: This study aimed to evaluate whether the response rate of chemotherapy with molecular target agents correlates with the conversion rate, R0 resection rate, and survival in patients with initially unresectable colorectal liver metastases (CRLM). METHODS: We reviewed the literature of prospective, controlled trials of systemic chemotherapy for patients with unresectable liver-only CRLM, including resectable extrahepatic metastases. Pearson's correlation coefficients were calculated. RESULTS: A total of 26 patient groups from 18 studies were reviewed. The response rate was significantly correlated with the conversion rate (r = 0.66) and R0 resection rate (r = 0.43) in overall patients. In subgroup analysis, only the conversion rate in patients with chemotherapy only (r = 0.75) and anti-EGFR therapy (r = 0.78) were significantly strongly correlated with the response rate. A non-significant strong trend toward correlation between response and conversion rates was observed in patients with bevacizumab (r = 0.73, p = 0.10). The regression line in the scatter plot of patients using bevacizumab showed a less steep slope. This indicated that conversion rates were relatively less affected by response rates under anti-VEGF therapy compared with the other patient groups. The response rate in chemotherapy-only patients was significantly correlated with median progression-free survival (r = 0.61) and overall survival (r = 0.66). CONCLUSIONS: Chemotherapy without molecular target agents and with anti-EGFR agents shows similar results of correlation between response and conversion/R0 resection rates. Under anti-VEGF therapy, conversion would be expected, even with a relatively lower response rate.

Disorganization of microtubular network in postischemic liver dysfunction: its functional and morphological changes.

Microtubules in the hepatocytes have been implicated to serve as lines of cytoplasmic transport of secretory materials, but are highly labile structures sensitive to pathological conditions in the cytosol. We examined the role of ischemia/reperfusion-induced cytoskeletal alterations in postischemic liver dysfunction. Rabbit livers were subjected to 60-min warm ischemia followed by 1 h or 24 h of reperfusion. Liver function was assessed by directly measuring hepatic clearance of indocyanine green (ICG), an organic anion whose cytoplasmic transport is assumed to depend on intact microtubules, using near-infrared spectroscopy. Structural alterations of microtubules were observed immunohistochemically using tissue sections stained with monoclonal anti-beta-tubulin antibody. ICG removal from hepatocytes into bile canaliculi deteriorated 1 h but reversed 24 h after reperfusion. Immunohistochemistry showed fragmentation of microtubules at the end of liver ischemia. This cytoskeletal alteration was evident 1 h but was not observed 24 h after reperfusion. Treatment with prostaglandin E1 exerted its beneficial effect by preserving ICG clearance and microtubular network. These results demonstrate that liver ischemia and subsequent reperfusion both affect the organization of microtubular network and suggest that structural disruption of microtubules may be a cause of postischemic liver dysfunction.

Salvage living-donor liver transplantation for liver failure following definitive radiation therapy for recurrent hepatocellular carcinoma: a case report.

A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases.

Postoperative monitoring of the oxygenation state of the graft liver in cases with hepatopulmonary syndrome.

Postoperative changes in the oxygen saturation of hemoglobin in the graft liver (graft SO2) were monitored by near-infrared spectroscopy in four cases complicated by hepatopulmonary syndrome. A plastic cylinder was placed in the abdominal wall, and optical measurements of the graft liver were obtained through this window. Our findings were as follows; (1) graft SO2 decreased after abdominal wall closure, and decreased further 1 day after surgery. (2) Graft SO2 was maintained despite severe hypoxemia, with partial pressure of oxygen in arterial blood as low as 50 mmHg. High hematocrit was beneficial for oxygenating the graft. (3) Graft livers could tolerate hypoxia with a graft SO2 as low as 20%. (4) It may be useful to monitor graft SO2 during the critical period after transplantation for the assessment of graft function.

Hepatic artery thrombosis in living related liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss in pediatric patients. We previously reported that the microsurgical techniques for arterial anastomosis can reduce the incidence of HAT in living related liver transplantation (LRLT). The purpose of this study is to analyze the risk factors for HAT after LRLT. A total of 245 patients received 250 liver transplants. METHODS: Eight arteries in eight patients, reconstructed with the use of loupe magnification (HAT; 1/8, 12.5%), were excluded from this study. We observed HAT in 4 patients of the 242 transplants (1.7%, HAT group). Seventeen factors were compared between the HAT and the control group (those without HAT). RESULTS: HAT occurred in 3 of 33 grafts (9%) from ABO-incompatible donors, whereas it occurred in 1 of 209 grafts (0.5%) from identical or compatible donors (P=0.008). The corrected volume of fresh-frozen plasma intraoperatively transfused in the HAT group (46.9+/-30.3 ml/kg) was significantly (P=0.015) different from that in the control group (10.2+/-1.9 ml/mg). In all four patients with HAT, emergent revisions of the anastomosis were performed. Two patients with ABO-incompatible grafts died of hepatic failure and sepsis. CONCLUSIONS: Although microsurgical techniques can minimize the surgical risk factors for HAT, overtransfusion of fresh-frozen plasma in high-risk patients (ABO incompatible) may be a critical factor in the development of HAT in LRLT.

A comparative study on primary and secondary nerve repair.

The sciatic nerve of rats was severed, and in the first group of rats the nerve repair was made immediately; in the second group, 1 month after severance; and in the third group, 2 months after severance. These rats were allowed to survive for 1, 2, 3, 5, and 7 months after nerve repair. At the seventh month after primary nerve repair, the average weight of the reinnervated anterior tibial muscle was 67 percent of that of the control muscle, and the cytochemical structure of the muscle fibers and subneural apparatuses was almost identical to those of the control. However, in the secondary nerve repair groups with neurorrhaphy 1 and 2 months after nerve severance, the average muscle weight was 50 and 60 percent, respectively, of that of the control. The cytochemical structure of both the muscle fibers and subneural apparatuses was not so mature as that of primary nerve repair. Furthermore, in rats with primary nerve repair, the size of muscle fibers was larger than that of rats with secondary nerve repair. The results observed in this experimental study strongly suggest the superiority of primary nerve repair over secondary nerve repair.

Perioperative changes in hepatic function as assessed by asialoglycoprotein receptor indices by technetium 99m galactosyl human serum albumin.

BACKGROUND/AIMS: Perioperative changes in intrinsic hepatocyte function and functional volume were investigated. METHODOLOGY: 52 cases of liver cancer, including hepatocellular carcinoma, cholangiocellular carcinoma and metastatic carcinoma were studied. There were diagnoses of liver cirrhosis, liver fibrosis and normal liver in 20, 23 and 9 cases, respectively. Hepatic resection of subsegment, one segment, two segments and three segments were performed in 11, 6, 23 and 4 cases, respectively, while 8 cases were diagnosed as inoperable. Assessments were performed before and 4 weeks after hepatectomy with asialoglycoprotein (ASGP) receptor indices, i.e., technetium-99m-galactosyl human serum albumin (TcGSA) uptake by the liver, TcGSA retention in the blood and functional volume as measured by single emission computed tomography (SPECT) with TcGSA as a probe. RESULTS: The hyperbolic relationship between galactosyl human serum albumin (GSA) uptake by the liver and GSA retention in the blood, both of which were independent of functional volume, shifted to the right after hepatectomy. The number of conventional liver function tests correlating to the GSA uptake increased after hepatectomy. By contrast, none of the pre-operative and post-operative tests were correlated with functional volume. Post-operative decrease in intrinsic hepatocyte function can be minimized by selection of mode of hepatic resection. CONCLUSIONS: These results indicate that GSA uptake by the liver can reveal information regarding intrinsic liver function which deteriorates and becomes a decisive factor after hepatectomy.

[A case of Fahr's disease associated with juvenile rheumatoid arthritis].

We studied a case of Fahr's disease type idiopathic intracerebral calcification (Fahr's disease) associated with juvenile rheumatoid arthritis. The patient was a 15-year-old male with a chief complaint of gait disturbance. His family members had no similar signs and symptoms. His parents had no consanguinity. He was born with the normal perinatal course at 1967. He had repeated episodes of convulsive attacks during fever elevation from 2 years and 8 months to 9 years of age. Morning stiffness of bilateral hands, and pernio in the auricles, fingers, planta, and toes had occurred in every winter, since 6 years old. Swelling and pain of the bilateral knee and foot joints appeared, making ambulation difficult in 1983 (15 years old), and the patient was admitted to our hospital in July, the same year. On admission, congenital anomalies such as epicanthus and high-arched palate were noted, and swelling, deformation and contracture of limb joints, and Raynaud phenomenon were shown. His ocular fundus showed no arteriosclerotic change. He didn't have Albright's sign. Mild mental retardation and bilateral pyramidal tract signs were noted, but extrapyramidal tract and cerebellar signs, and sensory disturbance were absent. Laboratory findings exhibited markedly elevated ESR, positive CRP, RA, and antinuclear antibody. The levels of serum Ca, P, alkaline phosphatase and parathyroid hormone were normal. Peripheral blood study showed microcytic and hypochromic anemia. Anti-DNA antibody was negative. Ellsworth-Howard test was positive. Elevated antibody titer to toxoplasma, rubella virus, herpes simplex virus and cytomegalovirus were not proven. He had no chromosomal change.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid in metastatic adrenal tumour from hepatocellular carcinoma.

We present the case of a metastatic adrenal tumour from hepatocellular carcinoma (HCC) showing the uptake of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) on MRI. To our knowledge, this is the first case of metastatic HCC in which Gd-EOB-DTPA uptake was shown on MRI and this finding facilitated the accurate pre-operative diagnosis of a metastatic adrenal tumour.