Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

[Identification of Chinese herbs in the Qing Royals--Fu Shen and Fu Shen Mu].

The use of Fu Shen and Fu Shen Mu as medicines has had a long history. Today Fu Shen is still taken as bulk medicinal materials, whereas Fu Shen Mu had disappeared in the medical market. Fu Shen, Yun Fu Shen, Bai Fu Shen, and Bao Mu Fu Shen were used in clinical application in the Qing Royals. Bai Fu Shen and Fu Shen Mu are still kept as speciment in the Palace Museum today. It was found that Bai Fu Shen in the Qing Royals was the same as Fu Shen after peeling and pine roots recorded in the herbal literatures of the Ming and Qing dynasties, with their character tests and historical analysis. It can be inferred that Fu Shen, Yun Fu Shen and Bai Fu Shen recorded in the Qing Royals were actually Fu Shen, with pine roots in sclerotia and after peeling and pine roots removed in processing. Bao Mu Fu Shen and Bao Fu Shen should refer to Fu Shen with pine roots. Fu Shen Mu should mean Fu Shen without white sclerotia and peel during processing. Fu Shen, currently used clinically, is Bao Mu Fu Shen in the Qing Dynasty. Fu Shen distinguishes greatly from Fu Shen Mu in their effects. Such identification and analysis of herbs provides a way of thinking for further hurb studies of the Qing Dynasty.

Assessment of effects of the rising atmospheric nitrogen deposition on nitrogen uptake and long-term water-use efficiency of plants using nitrogen and carbon stable isotopes.

This study assesses the effects of the atmospheric nitrogen (N) deposition on the N uptake and the long-term water-use efficiency of two C(3) plants (Agropyron cristatum and Leymus chinensis) and two C(4) plants (Amaranthus retroflexus and Setaria viridis) using N and C stable isotopes. In addition, this study explores the potential correlation between leaf N isotope (δ(15)N) values and leaf C isotope (δ(13)C) values. This experiment shows that the atmospheric N deposition has significant effects on the N uptake, δ(15)N and leaf N content (N(m)) of C(3) plants. As the atmospheric N deposition rises, the proportion and the amount of N absorbed from the simulated atmospheric deposition become higher, and the δ(15)N and N(m) of the two C(3) plants both also increase, suggesting that the rising atmospheric N deposition is beneficial for C(3) plants. However, C(4) plants display different patterns in their N uptake and in their variations of δ(15)N and N(m) from those of C(3) plants. C(4) plants absorb less N from the atmospheric deposition, and the leaf N(m) does not change with the elevated atmospheric N deposition. Photosynthetic pathways may account for the differences between C(3) and C(4) plants. This study also shows that atmospheric N deposition does not play a role in determining the δ(13)C and in the long-term water-use efficiency of C(3) and C(4) plants, suggesting that the long-term water-use pattern of the plants does not change with the atmospheric N input. In addition, this study does not observe any relationship between leaf δ(15)N and leaf δ(13)C in both C(3) and C(4) plants.

Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria.

Liver transplantation represents a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). Expansion beyond the Milan criteria for liver transplantation (1 lesion

[Investigation of a measles outbreak caused by genotype D8 virus in Pinghu city of Zhejiang province, 2017].

Objective: To investigate the epidemiological characteristics of measles outbreak caused by genotype D8 virus in Pinghu city of Zhejiang province, and provide evidence for the control of the outbreak. Methods: The measles outbreak data were collected through National Measles Surveillance System. The outpatient records and admission records were checked, field investigation and outbreak response were conducted. Blood samples in acute phase and swab specimens were collected from the patients for laboratory testing, including serology test, RNA extraction and amplification, measles virus isolation and genotype identification. Software SPSS 17.0 and Excel 2016 were used for data analysis. Results: A total of 10 confirmed measles cases were reported in Pinghu city, and 8 cases were aged >40 years. Six blood samples were collected, in which 5 were measles D8 virus positive and 1 was negative in measles virus detection. There were epidemiological links among 10 cases which occurred in a factory, a hospital and a family at the same time. There was no statistical difference in symptoms among cases caused by D8 virus and H1a virus. After the emergent measles vaccination, the measles outbreak was effectively controlled. Conclusion: Untimely response due to the uneasy detection of measles cases in the early stage, nosocomial infection and weak barrier of measles immunity in adults might be the main reasons for this outbreak. Measles vaccination is effective in the prevention of measles D8 virus infection. It is necessary to strengthen measles genotype monitoring for the tracing of infection source and control of outbreaks.

Increased expression of transferrin receptor on membrane of erythroblasts in strenuously exercised rats.

This study investigated the effects of strenuous exercise on transferrin (Tf)-receptor (TfR) expression and Tf-bound iron (Tf-Fe) uptake in erythroblasts of rat bone marrow. Female Sprague-Dawley rats were randomly assigned to either an exercise or sedentary group. Animals in the exercise group swam 2 h/day for 3 mo in a glass swimming basin. Both groups received the same amount of handling. At the end of 3 mo, the bone marrow erythroblasts were freshly isolated for Tf-binding assay and determination of Tf-Fe uptake in vitro. Tissue nonheme iron and hematological iron indexes were measured. The number of Tf-binding sites found in erythroblasts was approximately 674,500 +/- 132,766 and 1,270,011 +/- 235,321 molecules/cell in control and exercised rats, respectively (P < 0. 05). Total Fe and Tf uptake by the cells was also significantly increased in the exercised rats after 30 min of incubation. Rates of cellular Fe accumulation were 5.68 and 2.58 fmol. 10(6) cells(-1). min(-1) in the exercised and control rats, respectively (P < 0.05). Tf recycling time and TfR affinity were not different in exercised and control rats. Increased cellular Fe was mainly located in the stromal fraction, suggesting that most of accumulated Fe was transported to the mitochondria for heme synthesis. The findings demonstrated that the increased cellular Fe uptake in exercised rats was a consequence of the increased TfR expression rather than the changes in TfR affinity and Tf recycling time. The increase in TfR expression and cellular Fe accumulation, as well as the decreased serum Fe concentration and nonheme Fe in the liver and the spleen induced by exercise, probably represented the early signs of Fe deficiency.

Neomycin-induced neuromuscular blockade.

The unusual complication of neuromuscular blockade secondary to neomycin absorption is described. The syndrome characterized by acute muscle flaccidity, diaphragmatic breathing, and central nervous system depression presents a potentially fatal situation. Appropriate treatment of this complication includes respiratory assistance and calcium gluconate administration (IV). A review of the pediatric literature reveals 12 previous cases, of which 2 were secondary to urologic procedures.

The role of the interventional radiologist. Transjugular procedures.

The transjugular route provides a convenient and safe approach for the interventional radiologist to access the hepatic parenchyma and hepatic vascular structures. The transjugular intrahepatic portosystemic shunt has revolutionized the management of the complications of portal hypertension, allowing the establishment of a side-to-side shunt without recourse to surgery and general anesthesia. On a smaller scale, the transjugular approach to obtaining a liver biopsy has also proven its worth in allowing the histologic diagnosis and staging of liver disease in patients in whom such information is required for appropriate management but major contraindications to percutaneous biopsy exist. This article reviews the current techniques, indications, and complications of these interventional procedures and their role in the management of patients with end-stage liver disease.

The effect of low-dose estrogen and progestogen on menopausal symptoms and urinary excretion of calcium.

The effects of low-dose estrogen and progestogen on menopausal symptoms were studied with Kuppermen score and urinary excretion of calcium as fasting morning urine Ca/Cr ratio in 69 perimenopausal women. The subjects were divided into 3 groups: amenorrhea less than 1 year (14 women); post menopause 1-3 years (19); and post menopause more than 3 years (36). Fasting urine Ca/Cr ratio in the post menopause 1-3 years group was 0.19 +/- 0.01, significantly higher than that (0.14-0.01) in the amenorrhea less than 1 year group and (0.11 +/- 0.006) the post menopause more than 3 years group. 18 women had 4 patterns of low-dose oral estrogen and progestogen: MPA 2 mg QOD, EE 5 micrograms QD, EE 5 micrograms QOD, and EE 5 micrograms and MPA 2 mg QOD. Each pattern was used in turn for 3 weeks, and discontinued for 2 weeks, then the next pattern started and so on. EE 5 micrograms and MPA 2 mg QOD alternately gave the best results both in improving symptoms and lowering urine Ca/Cr ratio. Seven women given intermittent large dose, namely, EE 50 micrograms every 10 days or premarin 2.5 mg every 7 days had symptoms relieved but inconsistent decrease of urine Ca/Cr ratio.

[Evaluation of risk factors of the daughters of breast cancer patients].

The determination of salivary hormones on 41 daughters of breast cancer patients and 41 controls and nutritional survey and measurement of the height and weight were carried out. The result was that salivary estradiol (E2) was significantly higher in the daughters than in the controls. This suggest that the free E2 in the body fluid might be the direct factor for the daughters' high susceptibility to breast cancer. It was also found that the mean value of daily intake of fat per capta was significantly higher in the daughters' group than the controls, which indicated that the daily intake of fat might be an indirect factor of the daughters' susceptibility to breast cancer. The preventive measures are early diagnosis and decrease of the daily intake of fat for daughters of breast cancer patients.

Short waitlist time does not adversely impact outcome following liver transplantation for hepatocellular carcinoma.

It has been suggested that patients with hepatocellular carcinoma (HCC) undergoing living donor liver transplantation (LDLT) have worse recurrence-free survival compared to deceased donor liver transplantation (CLT), leading to the hypothesis that short waitlist time or fast-tracking may include more aggressive tumors that would have been selected out by traditionally longer waitlist time. The primary aim of the present study was to evaluate the impact of waitlist time on HCC recurrence. The study cohort included 100 patients meeting T2 criteria by imaging before undergoing CLT (n = 90) or LDLT (n = 10). The 5-year recurrence-free probability was 89.9% for the entire cohort, and 91.9%, 90.5% and 86.6%, respectively, for waitlist time of 3 months or less, 3-6 months and > 6 months (p = 0.81). In the Cox proportional hazards model, waitlist time was also not a significant predictor of HCC recurrence. Tumor under-staging was observed in 20.5% of patients with waitlist time 3 months or less and 23.0% for waitlist time > 3 months (p = 0.81). In conclusion, our results failed to show an association between waitlist time and outcome after CLT or LDLT for HCC, and provided evidence disputing a significant role of waitlist time in the selection against HCC with unfavorable tumor biology.

Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging.

We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1- and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1- and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1- and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria.

Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection.

BACKGROUND/AIMS: Lamivudine is highly effective in suppressing hepatitis B viral replication and hepatic necroinflammatory activity. The potential for recovery of hepatic decompensation in patients with chronic hepatitis B infection treated with lamivudine has not been established. The aim of this study was to evaluate the effectiveness of lamivudine treatment in severely decompensated cirrhosis due to chronic hepatitis B. METHODS: Thirteen consecutive patients with chronic hepatitis B infection, Child's-Pugh-Turcotte (CPT) score of > or =10 (median score=11) and detectable circulating hepatitis B DNA (range 15 to 9634 pg/ml) were included and treated with lamivudine 150 mg once daily. Hepatitis B envelope antigen (HBeAg) was positive in 9 of 13 patients pre-treatment. RESULTS: Two patients underwent liver transplantation at 4 and 6 weeks after starting lamivudine treatment. The remaining 11 patients were followed for a mean of 17.5 months without liver transplantation (range 3 to 39 months). Significant improvement of liver function, defined as a decrease in CPT score of > or =3, was observed in 9 of 13 patients (69%). In five patients, CPT score improved to <7 and they were placed on the inactive status (UNOS status 7) for liver transplantation. Hepatitis B DNA remained negative in all except one patient who developed breakthrough viral replication 12 months after starting lamivudine treatment, while maintaining stable liver function. Three of seven HBeAg-positive patients who did not undergo liver transplantation lost HBeAg during follow-up, but none had sustained seroconversion to hepatitis B e antibody. CONCLUSION: Lamivudine appears highly effective in reversing severe hepatic decompensation due to replicating hepatitis B infection.

Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort.

Uncontrolled studies have suggested a beneficial effect of lamivudine in patients with decompensated cirrhosis caused by replicating hepatitis B virus (HBV). We analyzed the outcome of lamivudine treatment in 23 consecutive patients with severely decompensated HBV-cirrhosis defined as a Child-Pugh-Turcotte (CPT) score of > or =10, and compared with a historical untreated control group of 23 patients matched for age, gender, and baseline CPT score. Significant clinical response, defined as a decrease in the CPT score by > or =3 points, was observed in 14 of 23 (60.9%) treated patients versus none of the controls (P <.0001). The median change in CPT scores was -3.0 (range, -6 to +3) in the treated group versus +1.0 in the controls (range, -1 to +2) (P =.016). Orthotopic liver transplantation (OLT) was performed in 34.8% of treated patients (median, 3.5; range, 1-32 months), versus 73.9% of controls (median, 3.0; range, 1-14 months) (P =.04). Excluding transplanted patients, there were no deaths in the treated group versus 6 deaths in the control group (P =.009). Time to death or OLT was significantly longer in treated patients than in controls (P <.001). Two patients developed lamivudine resistance after 9 and 12 months, respectively. Our results suggest that lamivudine significantly improves hepatic function in over half of the patients with decompensated cirrhosis and replicating HBV, and may confer a survival advantage. However, the small sample size and the use of a retrospective control cohort preclude drawing definitive conclusions. Expedited OLT remains the only viable treatment for lamivudine nonresponders.

Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.

The precise staging of hepatocellular carcinoma (HCC) based on the size and number of lesions that predict recurrence after orthotopic liver transplantation (OLT) has not been clearly established. We therefore analyzed the outcome of 70 consecutive patients with cirrhosis and HCC who underwent OLT over a 12-year period at our institution. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified Tumor-Node-Metastases (TNM) Staging Classification. Tumor recurrence occurred in 11.4% of patients after OLT. The Kaplan-Meier survival rates at 1 and 5 years were 91.3% and 72.4%, respectively, for patients with pT1 or pT2 HCC; and 82.4% and 74.1%, respectively, for pT3 tumors (P =.87). Patients with pT4 tumors, however, had a significantly worse 1-year survival of 33.3% (P =.0001). An alpha-fetoprotein (AFP) level > 1,000 ng/mL, total tumor diameter > 8 cm, age > or = 55 years and poorly differentiated histologic grade were also significant predictors for reduced survival in univariate analysis. Only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis. Patients with HCC meeting the following criteria: solitary tumor < or = 6.5 cm, or < or = 3 nodules with the largest lesion < or = 4.5 cm and total tumor diameter < or = 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years, respectively, after OLT versus a 50% 1-year survival for patients with tumors exceeding these limits (P =.0005). We conclude that the current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT.

Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation.

Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.