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Tumor-derived blood-circulating exosomes have potential as a biomarker to greatly improve cancer treatment. However, effective isolation of exosomes remains a tremendous technical challenge. This study presents a novel nanostructured polymer surface for highly effective capture of exosomes through strong avidity. Various surface configurations, consisting of multivalent dendrimers, PEG, and tumor-targeting antibodies, were tested using exosomes isolated from tumor cell lines. We found that a dual layer dendrimer configuration exhibited the highest efficiency in capturing cultured exosomes spiked into human serum. Importantly, the optimized surface captured a > 4-fold greater amount of tumor exosomes from head and neck cancer patient plasma samples than that from healthy donors. Nanomechanical analysis using atomic force microscopy also revealed that the enhancement was attributed to multivalent binding (avidity) and augmented short-range adhesion mediated by dendrimers. Our results support that the dendrimer surface detects tumor exosomes at high sensitivity and specificity, demonstrating its potential as a new cancer liquid biopsy platform.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. The mechanisms underlying PD remain to be fully elucidated, and research into treatments for this condition is ongoing. Recent advances in genetic research have shed light on the mechanisms underlying PD. In this study, we used PD and control mesenchymal stem cells (MSCs) obtained from adipose tissues to confirm the differences between groups at the cellular and molecular levels. The results revealed that in PD MSCs, cell viability was clearly lower, and the rate of cell senescence was higher compared to the controls. Next, to compare the gene expression in PD and control cells, transcriptome analysis was performed. Genes in pathways, including extracellular matrix (ECM) receptor interaction, P53 signaling, and focal adhesion, were down-regulated in PD. Among genes related to ECM receptor interaction, RELN gene expression was markedly decreased in PD cells, however, after being treated with recombinant Reelin protein, a significant increase in cell viability and a decrease in α-Synuclein aggregation and cell senescence were observed. In conclusion, Reelin affects PD by positively influencing the cell characteristics. Our findings will facilitate research into new treatments for PD.

Buerger's disease is a rare disease that causes critical limb ischemia; however, the underlying pathophysiological mechanism remains unclear. Therefore, we investigated the interaction between interleukin (IL)-17 and high-mobility group protein B 1 (HMGB1) and determined whether A disintegrin and metalloproteinase 10 (ADAM10) inhibit this interaction.The study population included 15 patients with Buerger's disease and 10 healthy donors without a history of giving peripheral blood samples. Cytokine levels were measured using a luminex multiplex assay in plasma. Flow cytometry was used to analyze the subtypes of helper T (Th) cells among peripheral blood mononuclear cells (PBMCs). The effect of ADAM10 on PBMCs was analyzed in vitro.The levels of inflammatory cytokines and production of pathogenic Th cells were found to be higher in Korean patients with Buerger's disease. IL-17 treatment induced HMGB1 associated molecules. HMGB1 also induced IL-17 and Th17 associated transcription factors in Buerger's patients. We observed that ADAM10 regulates the interaction between IL-17 and HMGB1 via advanced glycation end products (RAGE)/nuclear factor-kappa B (NF-kB) pathway in patients with Buerger's disease.This study suggests that IL-17 and HMGB1 cytokines contribute to the pathogenesis of Buerger's disease. These results indicate that ADAM10 alleviates inflammation in Buerger's disease via the HMGB1 and RAGE/NF-κB signaling pathway and provides insights into the molecular basis of and a potential therapeutic strategy for Buerger's disease.

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12–23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Parkinson’s disease (PD) is a prevalent motor disease caused by the accumulation of mutated α-synuclein (α-Syn), however, its early stages are also characterized by non-motor symptoms, such as olfactory loss, cognitive decline, depression, and anxiety. The therapeutic effects of environmental enrichment (EE) on motor recovery have been reported, but its effects on non-motor symptoms remain unclear. Herein, we reveal the beneficial effects of EE on PD-related non-motor symptoms and changes in synaptic plasticity in the nucleus accumbens. To investigate its therapeutic effects in the early phase of PD, we randomly assigned eight-month-old mice overexpressing human A53T (hA53T) α-Syn to either the EE or standard condition groups for two months. Next, we performed behavioral tests and biochemical and histological analyses at 10 months of age. EE significantly alleviated locomotor hyperactivity and anxiety during the early stages of PD. It normalized the levels of tyrosine hydroxylase, phosphorylated and oligomeric α-Syn, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex-forming proteins, including synaptosomal-associated protein, 25 kDa, syntaxin1, and vesicle-associated membrane protein 2 (VAMP2). Moreover, the interactions between VAMP2 and pSer129 α-Syn were markedly reduced following EE. The restoration of synaptic vesicle transportation status may underlie the neuroprotective effects of EE in hA53T α-Syn mice.

In the absence of randomized controlled data and even propensity-matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes.Forty-two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short- and long-term outcomes were recorded.Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P 0·001), duration of operation (248(156) versus 285(167) min; P 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086).Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC. MÉTODOS: Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo.El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855). CONCLUSIÓN: La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.

Objectives Metabolic syndrome (MS), as a precursor of diabetes mellitus (DM) and cardiovascular disease, is increasing steadily worldwide. We examined the preventive effects of lifestyle intervention on the occurrence of DM and acute myocardial infarction (AMI) in MS. Study design Observational study on disease occurrence after lifestyle intervention. Methods The lifestyle intervention was administered to subjects with MS participating in a metropolitan lifestyle intervention program for 1 year. The same numbers of non-participating age- and sex-matched subjects with MS were randomly extracted from national health examination data. After intervention or examination, new occurrences of hypertension, DM, and AMI were identified through the national health insurance claims data during 1 year. For DM and AMI, multivariate logistic regression analysis for the factors affecting each disease was performed. Results In the intervention group and the control group (14,918 in each group), the occurrence of hypertension was 555 (6.07%) and 751 (8.33%), the occurrence of DM was 324 (2.55%) and 488 (3.89%), the occurrence of dyslipidemia was 321 (2.59%) and 373 (2.72%), and the occurrence of AMI was 13 (0.09%) and 26 (0.17%), respectively. In multivariate logistic regression analysis, adjusted odds ratios for intervention were 0.752 (95% confidence interval [CI]: 0.644–0.879) and 0.499 (95% CI: 0.251–0.992) for DM and AMI, respectively, indicating that lifestyle intervention has a preventive effect. Conclusions Lifestyle intervention in MS has preventive effects on the occurrence of DM and AMI, and long-term follow-up is needed to evaluate these preventive effects in more detail.

Mixed endometrial stromal and smooth muscle tumor of the uterus is a rare occurrence, and it is truly challenging to diagnose or dif- ferentiate mesenchymal tumors of the uterine corpus, due to their many overlapping features. In most cases, the gross pathology of mixed endometrial stromal and smooth muscle tumor differs from that of pure endometrial stromal and pure smooth muscle tumors. A 59-year-old postmenopausal woman presented with vaginal spotting, low abdominal pain, and an uterine mass. Subsequent pelvic magnetic resonance imaging revealed a 4.0x3.8x3.4-cm sized uterine mass with enhancement. The mass showed restricted diffusion on diffusion-weighted images, and thus, was suspected to be uterine sarcoma rather than degenerative leiomyoma. Levels of tumor markers, CA 125, CA 19-9, and SCC, were within their normal ranges. The patient underwent exploratory laparotomy. Morphological and immunohistochemical evaluations were performed, and a final diagnosis of mixed endometrial stromal and smooth muscle tumor of the uterus was rendered. Her postoperative course was uneventful, and aromatase inhibitor adjuvant therapy was administered.

Uterine rupture during labor is a serious complication resulting in maternal and neonatal morbidity and mortality. We present the extremely rare case of a 38-year-old gravid woman admitted with labor pain at term, about to experience a uterine rupture during labor. She had previously twice delivered vaginally, and during her third pregnancy had a low transverse Cesarean section. Prior to arriving at the hospital with labor pains, she had routine prenatal care with normal prenatal laboratory tests. One day the woman reported to having sudden epigastric pain, and 40 minutes after her admission a pelvic exam was completed. The unborn baby had a persistent revealed, and a live neonate was promptly delivered with an Apgar score of 1 at one minute and 5 at five minutes. On the fifth postoperative day the woman and her baby were discharged home with no maternal and neonatal complications.

SummaryBackground Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. Objectives To explore the QoL of patients with vitiligo and to identify factors affecting QoL. Methods A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. Results Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20–84). The median duration of disease was 3·0 years (range 0–60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20–59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. Conclusions A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.

Summary There have been limited studies of subjective tongue function over long-term follow-up in spite of swallowing and articulation disorders are common complications of glossectomy. To assess long-term subjective swallowing and articulation function after partial glossectomy. A total of 63 patients with the mobile tongue cancer who underwent partial glossectomy without reconstruction were interviewed to score their swallowing and articulation function on a 100-point scale. The relation of this subjective scoring to the perioperative data was subjected to multivariate analysis. The mean patient age was 53·4 (19–81) years, and the mean follow-up duration was 78·9 (14–277) months. Mean swallowing and articulation function score was 87·7 ± 6·1 and 88·6 ± 5·4. Age, follow-up duration, T stage and resection volume were significantly correlated with swallowing function (P = 0·026, 0·029, 0·016, 0·002, respectively); follow-up duration was correlated with articulation function (P = 0·039). Patients who undergo partial glossectomy without reconstruction generally demonstrate good function on long-term follow-up. Subjective dysfunction was correlated with larger resection volume, older age and shorter follow-up duration.

Complications of laparoscopic adjustable gastric banding (LAGB) are well documented including migration, erosion, prolapse, infection, pouch dilatation, and gastric perforation. Band prolapse within the first 5 years after LAGB is observed in about 5 % of cases, requiring an operative procedure. Here we report our experience of endoscopic treatment of band prolapses. From December 2007 to December 2013, 1,347 consecutive patients (202 male, 1,145 female) underwent LAGB; 47 patients had band prolapses and 7 were treated by endoscopy. All patients were women (median age, 34 years). The mean preoperative body mass index was 38.3 ± 2.9 kg/m2. The mean duration to band prolapse after LAGB was 10.6 ± 5.6 months. The mean duration of endoscopy was 12 ± 3 min. One patient had recurrence of the prolapse 3 months after the first endoscopy and was treated by endoscopy again. There was no operative procedure required and no mortality. Endoscopic treatment of band prolapses is effective without the need for an operative procedure.

BACKGROUND AND PURPOSE: Developmental venous anomalies are the most common intracranial vascular malformation. Increased signal-intensity on T2-FLAIR images in the areas drained by developmental venous anomalies are encountered occasionally on brain imaging studies. We evaluated diffusion and perfusion MR imaging findings of the abnormally high signal intensity associated with developmental venous anomalies to describe their pathophysiologic nature. MATERIALS AND METHODS: We retrospectively reviewed imaging findings of 34 subjects with signal-intensity abnormalities associated with developmental venous anomalies. All subjects underwent brain MR imaging with contrast and diffusion and perfusion MR imaging. Regions of interest were placed covering abnormally high signal intensity around developmental venous anomalies on fluid-attenuated inversion recovery imaging, and the same ROIs were drawn on the corresponding sections of the diffusion and perfusion MR imaging. We measured the apparent diffusion coefficient, relative cerebral blood volume, relative mean transit time, and time-to-peak of the signal-intensity abnormalities around developmental venous anomalies and compared them with the contralateral normal white matter. The Mann-Whitney U test was used for statistical analysis. RESULTS: The means of ADC, relative cerebral blood volume, relative mean transit time, and TTP of signal-intensity abnormalities around developmental venous anomalies were calculated as follows: 0.98 ± 0.13 10(−3)mm(2)/s, 195.67 ± 102.18 mL/100 g, 16.74 ± 7.38 seconds, and 11.65 ± 7.49 seconds, respectively. The values of normal WM were as follows: 0.74 ± 0.08 10(−3)mm(2)/s for ADC, 48.53 ± 22.85 mL/100 g for relative cerebral blood volume, 12.12 ± 4.27 seconds for relative mean transit time, and 8.35 ± 3.89 seconds for TTP. All values of ADC, relative cerebral blood volume, relative mean transit time, and TTP in the signal-intensity abnormalities around developmental venous anomalies were statistically higher than those of normal WM (All P < .001, respectively). CONCLUSIONS: The diffusion and perfusion MR imaging findings of the signal-intensity abnormalities associated with developmental venous anomaly suggest that the nature of the lesion is vasogenic edema with congestion and delayed perfusion.

COL6A1 and BMP-2 genes have been implicated in ossification of the posterior longitudinal ligament (OPLL) susceptibility in Japanese and Chinese Han populations. However, no study has yet investigated the DNA of unaffected family members of patients with OPLL. This study investigated differences in genetic polymorphisms of BMP-2 and COL6A1 between Korean patients with OPLL and their family members (with and without OPLL). A total of 321 subjects (110 patients with OPLL and 211 family members) were enrolled in the study. Associations between two single nucleotide polymorphisms (SNPs) of the BMP-2 gene (Ser37Ala and Ser87Ser) and two SNPs of COL6A1 [promoter (-572) and intron 33 (+20)] with susceptibility to OPLL of the cervical spine were investigated between the two groups (OPLL+ and OPLL-). Of the 321 subjects, 162 had cervical OPLL (50.4%; 110 patients, 52 family members). There was a familial tendency of OPLL in 34 of the 110 families (30.9%). Allele and haplotype frequencies of the four SNPs in the BMP-2 and COL6A1 genes did not differ significantly between the OPLL+ and OPLL- groups, even when excluding participants over 50 years of age. This is the first report identifying SNPs of COL6A1 and BMP-2 in Korean patients and family members with OPLL. Although allele and haplotype frequencies were similar with those of a previous study in Japanese and Chinese patients, unaffected family members also showed similar rates of these SNPs in the present study. These results suggest that these SNPs may not directly influence the expression of OPLL.

Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight.

Summary Introduction The main goal of this study was to develop a multiparametric cell population data (CPD) model that combines information from several morphologic parameters generated by DxH800, in addition to the traditional parameters regularly reported in the CBC-diff, and to test the performance of this model in screening the general population for primary tuberculosis (TB). Methods A total of 3741 study cases were divided into two groups, test and validation set at cut-off value of 6000 WBCs/μL. We developed multiparametric model for primary TB screening (TB hemeprint), selected CPD, and calculated parameters which could discriminate primary TB from other non-TB diseases and normal control in test set. We applied it to the validation set, which was a set of completely different samples, to test its reproducibility if applied to a routine laboratory test. Results After screening primary TB using TB hemeprint, sensitivity, specificity, PPV, and NPV were 85.4%, 89.6%, 31.1%, and 99.1%, respectively, in primary TB with lower than 6000 WBCs/μL of test set (test set-L). In primary TB with higher than 6000 WBCs/μL of test set (test set-H), those values were 83.1%, 85.6%, 29.7%, and 98.6%, respectively. There were only 0.4% (2/461) and 0.6% (2/326) of normal control samples included in test set-L and -H, respectively. Diagnostic efficiencies except sensitivity in each validation set were very comparable with those in each test set. Conclusion Tuberculosis hemeprint may allow us to screen primary TB with acceptable sensitivity and specificity using combination of TB-specific CPD and calculated parameters.

ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) is a feasible therapeutic option for countries with a scarcity of deceased donors. This report presents our initial experiences in ABOi ALDLT in 10 patients between December 2008 and September 2009. The mean age of recipients was 48.5 ± 5.7 years (range, 40–54 years). The mean Model for End-stage Liver-Disease score was 13.9 ± 4.0 (range, 9–22). All patients were administered preoperative rituximab once and plasma exchanges according to the hemagglutinin titer. The spleen was preserved in all cases. For local infusion therapy, hepatic arterial infusion was performed in 9 patients and portal vein infusion in 1 subject. The 10 patients experienced no in-hospital mortality. At a mean follow-up period of 31.8 ± 2.9 months (range, 4.1–34.9 months), 1 patient has died (postoperative month 4 due to sepsis following a biliary stricture. The 3-month patient and graft survivals were 100%, and 1- and 2-year survivals, 90.0%. There was no episode of antibody-mediated rejection. The promising results of our initial experience may have been due to the use of preoperative rituximab and the good preoperative conditions of the patients.

The purpose of this clinical trial was to evaluate the effectiveness of a natural extract from Schisandra chinensis for relief of various menopausal symptoms.A randomized, double-blind, placebo-controlled clinical trial was conducted from January 1, 2014 until January 13, 2015. We recruited women between the ages of 40 and 70 years who complained of menopausal symptoms measured by the Kupperman Index (KI). Patients were randomly assigned to treatment with either an extract from Schisandra chinensis (BMO-30) or placebo. They received the treatment for 6 weeks and were followed for 12 weeks. The primary endpoint was the mean interval change in KI score from baseline to week 12. Secondary measures included laboratory studies and the Menopause Rating Scale (MRS) score for sexual and bladder problems.Forty-one patients were considered eligible for enrolment, and 36 completed the study. After screening and randomization, patients were categorized into the placebo group (n = 18) and the BMO-30 group (n = 18). Total KI scores were significantly lower in the BMO-30 group than in the placebo group when evaluated with respect to group and time (p = 0.042).BMO-30 from Schisandra chinensis can be a safe and effective complementary medicine for menopausal symptoms, especially for hot flushes, sweating, and heart palpitations.

Malignant mesonephric tumor (MMT) is a relatively uncommon malignancy of the female genital tract. The diagnosis of metastatic MMT is difficult because cytological, pathological, immunohistochemical characteristics of MMT are under-recognized. The authors present a 55-year-old female with metastatic pulmonary nodules. The bronchial washing cytology revealed three dimensional clusters of bland epithelial cells with slight nuclear grooves. A corresponding lung histology had ductal or tubular clusters of epithelial cells with intraglandular eosinophilic materials. These epithelial cells were positive for immunohistochemical stain of CD10, suggesting metastasis from MMT. The cervical smear showed clusters of bland, gland-forming epithelial cells with intraglandular eosinophilic materials. On histologic examination, mesonephric adenocarcinoma with papillary and solid proliferation was identified in the uterine cervix. A review of the literature for 72 cases of MMT is also included. Clinical and cytopathological features of MMT are herein made available.

Heterotopic bone formation is a very rare event in the gastrointestinal tract including in the appendix. Here we report three cases of heterotopic ossification in appendiceal mucinous neoplasms, one occurring in an appendiceal mucinous cystadenoma, another in a low-grade appendiceal mucinous neoplasm, and the third occurring in an appendiceal mucinous adenocarcinoma. The clinicopathologic characteristics of these three present cases and two previously reported cases are discussed in detail. The mechanism of heterotopic ossification in appendiceal mucinous neoplasm is still unclear, but mucin extravasation and subsequent calcification may be predisposing events.

BACKGROUND To evaluate response to radiation and clinical outcome of uterine cervical cancer patients with tumor-related leukocytosis (TRL) at initial diagnosis and during definitive radiotherapy. PATIENTS AND METHODS We retrospectively analyzed 2456 patients with stage IA-IVA uterine cervical cancer who received definitive radiotherapy with (37.4%) or without (62.6%) platinum-based chemotherapy between 1986 and 2012. TRL was defined as two or more occurrences of leukocytosis over 9000/μl at the time of diagnosis and during the course of treatment. Locoregional failure-free survival (LFFS) and overall survival (OS) were compared between patients with or without TRL. RESULTS The median age of all patients was 55 years, and the median follow-up time was 65.1 months. TRL was observed in 398 patients (16%) at initial diagnosis; TRL (+) patients were younger and had larger tumors, advanced stage, and more frequent lymph node metastases (all P < 0.05). TRL (+) patients showed a significantly lower rate of complete remission than TRL (-) patients (89.9% versus 96.3%, respectively, P = 0.042). Ten-year LFFS and OS for all patients were 84% and 78%, respectively. LFFS and OS were significantly lower in TRL (+) patients than TRL (-) patients (10-year LFFS: 69% versus 87% respectively, P < 0.001; 10-year OS: 63% versus 81% respectively P < 0.001). After propensity score matching, LFFS and OS rates in TRL (+) patients remained significantly lower than for TRL (-) patients; this significant difference was also observed on multivariate analysis. Twenty-six percent of patients with locoregional failure (n = 345) were TRL (+) and had significantly poorer median OS (6 versus 12 months, P = 0.001). CONCLUSION This study reveals the aggressive nature of cervical cancer with TRL and its poor response to radiation therapy. Given the unfavorable prognosis and higher probability of treatment failure, optimal diagnostic and therapeutic approaches and careful monitoring for early detection of recurrence should be considered for these patients.

The University of Washington Quality of Life (UW-QOL) questionnaire is often used to assess health-related quality of life (HRQOL) of head and neck cancer patients. The aim of this study was to translate the UW-QOL version 4 into the Korean language and to carry out an initial validation study. A recognized methodology for translation of questionnaires was used. The validation study used the final Korean version between March and September 2009. Adult patients were recruited, with a confirmed diagnosis of head and neck cancer, therapy completed and disease-free for at least 1 year. The UW-QOL was successfully translated into Korean. 56 patients completed Korean versions of UW-QOL, the Beck Depression Inventory and the World Health Organization Quality of Life-BREF and various expected correlations were confirmed first between the two UW-QOL subscales (Spearman 0.54 p < 0.001) and then of these subscales with the other concurrent measures. Lower (worse) UW-QOL scores were seen for later stage patients in all 12 domains. The Korean version of UW-QOL is ready for use in the assessment of HRQOL for Korean patients. Validation work needs to be continued to further establish psychometric properties of the questionnaire for use in this population.

We investigated the importance, risk factors, and clinical course of the radiolucent “halo” phenomenon around bone cement following vertebral augmentation for osteoporotic compression fracture. Preoperative osteonecrosis and a lump cement pattern were the most important risk factors for the peri-cement halo phenomenon, and it was associated with vertebral recollapse. We observed a newly developed radiolucent area around the bone cement following vertebral augmentation for osteoporotic compression fractures. Here, we describe the importance of the peri-cement halo phenomenon, as well as any associated risk factors and long-term sequelae. In total, 175 patients (202 treated vertebrae) were enrolled in this study. The treated vertebrae were subdivided into two groups: Group A (with halo, n = 32) and Group B (without halo, n = 170), and the groups were compared with respect to multiple preoperative (age, sex, BMD, preoperative osteonecrosis) and perioperative factors (operative approach: vertebroplasty or kyphoplasty; cement distribution pattern; cement leakage; cement volume), and postoperative results (VAS score, recollapse). Logistic regression analysis was used to evaluate the relationship between the incidence of the peri-cement halo and all of the parameters described above. Rates of osteonecrosis were also significantly higher in Group A than in Group B (62.5% vs. 31.2%, p

The WTX, Wilms tumor-associated tumor-suppressor gene, is present on the X chromosome and a single WTX mutation may be sufficient to promote carcinogenesis. Unlike the WT1 tumor suppressor, a transcription factor, WTX lacks conserved functional protein domains. To study the function of WTX, we constructed inducible cell lines expressing WTX and tumor-associated WTX mutants. Induction of WTX inhibited cell growth and caused G(1)/G(0) arrest. In contrast, a short, tumor-associated truncation mutant of WTX358 only slightly inhibited cell growth without a significant cell-cycle arrest, although expression of a longer truncation mutant WTX565 led to the growth inhibition and cell-cycle arrest to a similar extent as wild-type WTX. Like WT1, WTX slowed growth and caused cell-cycle arrest through p21 induction. Gene expression profiling showed that these two tumor-suppressors regulated genes in similar pathways, including those implicated in control of the cellular growth, cell cycle, cell death, cancer and cardiovascular system development. When gene expression changes mediated by wild-type WTX were compared with those affected by mutant forms, WTX565 showed a 55% overlap (228 genes) in differentially regulated genes, whereas WTX358 regulated only two genes affected by wild-type WTX, implying that amino-acid residues 358-561 are critical for WTX function.

Purpose: To understand the changes in gene expression in polycythemia vera (PV) progenitor cells and their relationship to JAK2V617F. Experimental Design: Messenger RNA isolated from CD34+ cells from nine PV patients and normal controls was profiled using Affymetrix arrays. Gene expression change mediated by JAK2V617F was determined by profiling CD34+ cells transduced with the kinase and by analysis of leukemia cell lines harboring JAK2V617F, treated with an inhibitor. Results: A PV expression signature was enriched for genes involved in hematopoietic development, inflammatory responses, and cell proliferation. By quantitative reverse transcription-PCR, 23 genes were consistently deregulated in all patient samples. Several of these genes such as WT1 and KLF4 were regulated by JAK2, whereas others such as NFIB and EVI1 seemed to be deregulated in PV by a JAK2-independent mechanism. Using cell line models and comparing gene expression profiles of cell lines and PV CD34+ PV specimens, we have identified panels of 14 JAK2-dependent genes and 12 JAK2-independent genes. These two 14- and 12-gene sets could separate not only PV from normal CD34+ specimens, but also other MPN such as essential thrombocytosis and primary myelofibrosis from their normal counterparts. Conclusions: A subset of the aberrant gene expression in PV progenitor cells can be attributed to the action of the mutant kinase, but there remain a significant number of genes characteristic of the disease but deregulated by as yet unknown mechanisms. Genes deregulated in PV as a result of the action of JAK2V617F or independent of the kinase may represent other targets for therapy. Clin Cancer Res; 16(17); 4339–52. ©2010 AACR.

BACKGROUND: When the transthoracic approach is used for the treatment of a thoracic ossified posterior longitudinal ligament (OPLL), there could be a lot of operative risks, morbidity, and mortality for the patient. CASE REPORT: A 65-year-old female manifested back pain and tingling sensations in both legs due to OPLL at the T6-7 level. A thoracoscopic procedure was performed to remove the OPLL, achieving complete decompression of thoracic cord. The symptoms were relieved and the patient was discharged on the sixth day after the operation. CONCLUSIONS: A minimally invasive procedure using the thoracoscopic technique could be a good alternative option in selected cases when a conventional transthoracic approach is impossible due to the patient’s general condition.

The purpose of this study was to investigate the acceptability and therapeutic efficacy of a preoperative single administration of long-acting 5-hydroxytryptamine type 3 (5-HT 3) receptor antagonist in an orally disintegrating tablet formulation, ramosetron, in breast cancer patients.Two hundred and forty women, ASA I-II, aged 24-60 yr, undergoing elective breast cancer surgery, were randomized. A standardized anaesthetic technique was used. Patients were assigned to receive one of three treatment regimens (n = 80 in each group): no prophylactic antiemetics (Group A), single prophylactic intravenous injection of ramosetron 0.1 mg at the completion of surgery (Group B) or preoperatively oral administration of 0.1 mg of ramosetron (Group C). Episodes of nausea and vomiting, the use of rescue antiemetic treatment, degree of pain, adverse events and level of satisfaction were recorded.The overall incidence of nausea and vomiting during the first 24 h after the recovery in Groups B (27.8%) and C (25%) was decreased significantly compared with Group A (75.3%). The frequency of the use of rescue antiemetics was significantly lower in Group C (5.0%) compared with Groups A (53.2%) and B (15.2%). The patients in Group C were more satisfied with control of postoperative nausea and vomiting than others.Preoperative oral administration of ramosetron at a dose of 0.1 mg is an acceptable and effective way of reducing the incidence of postoperative nausea and vomiting in breast cancer patients.

Right retroesophageal lymph nodes (RRLNs) should be involved in central lymph nodes (CLNs) dissection in patients with papillary thyroid cancer (PTC). This study assessed the incidence and factors related to RRLNs metastasis.From January 2008 to March 2010, 129 patients who underwent total thyroidectomy with CLNs dissection including RRLNs were enrolled. The predictive value of RRLNs metastasis was assessed.Twenty six (20.1%) of 129 patients exhibited nodal metastasis in RRLNs. Metastasis of RRLNs was associated with large tumor size (1 cm; P0.01), multiplicity (P=0.03), preoperative LN enlargement (P0.01), metastasis of non-retroesophageal lateral LN (P0.01) and large number of CLNs metastases (P0.01) in univariate analysis. Multivariate analysis revealed that tumor size (1 cm) and metastasis of non-retroesophageal lateral LN were independent correlates of RRLNs metastases.RRLNs may be removed during operation for PTC, particularly in patients with tumor1 cm and lateral LN metastases.

Intussusception following gastric surgery is a rare postoperative complication. It may develop in clinical situations following gastroenterostomy, Billroth II gastric surgery with or without Braun anastomosis, or Roux-en-Y gastrojejunostomy. The patients may present with either an acute surgical emergency or with a chronic, relapsing form. The mortality may be up to 50 % in these cases if not treated appropriately, but little is known about the mechanism underlying the condition. Early diagnosis with a high index of suspicion and prompt treatment of the acute form are therefore important. Surgical reduction with laparotomy is mandatory, although definitive corrective and preventative measures have not yet been established.

Udgivelsesdato: Aug Dlk1 (Pref-1) is a transmembrane and secreted protein, which is a member of the epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We have found by real-time RT-PCR that Dlk1 mRNA levels were high in CD34(+) cells in 10 of 12 MDS samples compared with CD34(+) cells from 11 normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during megakaryocytic differentiation of both CMK megakaryoblasts as well as normal CD34(+) hematopoietic stem cells. High serum levels of Dlk1 occurred in RA (4/10) and essential thrombocythemia (2/10) patients. Functional studies showed that forced expression of Dlk1 enhanced proliferation of K562 cells growing in 1% fetal bovine serum. Analysis of hematopoiesis of Dlk1 knockout mice suggested that Dlk1 contributed to granulocyte, megakaryocyte and B-cell clonogenic growth and was needed for generation of splenic B-cells. In summary, Dlk1 is overexpressed in selected samples of MDS (especially RA and RAEB) and AML (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells.

We report a case of split liver transplantation (SLT) for two adult recipients, which was the first successful case in Korea. The brain-dead donor was a 22-year-old man weighing 65 kg, but his liver volume was estimated as 2120 mL on computed tomographic volumetry. As it seemed to be too large for a 60-kg recipient candidate, SLT was planned after assessment of lobar liver volume and middle hepatic vein anatomy. The right lobe was mobilized first and the liver parenchyma transected along the right border of the middle hepatic vein. The 1240-g right lobe (segments 5 to 8) graft was implanted into a 57-year-old male patient with acute-on-chronic liver failure in the same manner as a living-donor graft. After that, routine procedures of cadaveric multiorgan procurement were performed. The 670-g left lobe (segments 1 to 4) with a retrohepatic vena cava, common bile duct, and aortic patch was implanted into another 37-year-old male recipient. These two recipients recovered uneventfully surviving 12 months to date. We integrated the surgical techniques learned from hundreds of adult-to-adult living donor liver transplants into this first trial of two adult SLT.

BACKGROUND Amplification of the N-myc oncogene is associated with adverse outcomes in the common childhood tumor, neuroblastoma. Because the transforming properties of Myc are related to its ability to modulate gene expression, the authors used cDNA microarrays to identify potential Myc target genes. METHODS Expression levels of 4608 genes were analyzed in a series of neuroblastoma cell lines. Identical analyses were performed in a panel of medulloblastoma cell lines to identify c-Myc targets and to determine the extent to which N-Myc targets and c-Myc targets were shared. Comparisons were made between cell lines with high levels versus low levels of Myc protein expression. RESULTS Array analyses yielded 121 genes with increased expression levels (≥ 1.65-fold) and 9 genes with decreased expression levels in N-Myc-expressing versus nonexpressing cell lines. Many of these were newly identified targets of biologic interest. Fifty percent of the N-Myc targets (60 of 121) were mutual c-Myc targets. A significant correlation between the level of N-myc and selected target gene expression was demonstrated independently in 27 neuroblastoma tumor samples and in an N-myc-inducible cell line system. CONCLUSIONS A number of diverse pathways are modulated by N-Myc in neuroblastoma. Although, overall, there was significant correlation between myc and target transcript expression among cohorts of tumors, great variability in levels of target expression was seen among individual tumor samples, and this biologic heterogeneity in the levels of target gene expression may offer insight into differences in the clinical behavior of neuroblastoma and may prove to be of prognostic significance in the future. Cancer 2003;98:841–53. © 2003 American Cancer Society. DOI 10.1002/cncr.11584

OBJECTIVES: Relationships between religion and body weight were examined in a US national sample. METHODS: Data from the National Survey of Midlife Development in the United States (MIDUS), collected through telephone and postal questionnaires, were analyzed for 3032 adults aged 25–74. RESULTS: Religious denomination was significantly related to higher body weight in men after accounting for sociodemographic controls. Conservative Protestant men had a 1.1±0.45 higher body mass index (BMI) than those reporting no religious affiliation. Other religion variables that initially had significant relationships with greater body weight before adjusting for control variables became nonsignificant after smoking was controlled. No significant relationships between religion and body weight were present in women. CONCLUSIONS: Religious denomination was related to body weight in men. Other dimensions of religiosity showing a relationship with higher BMI appeared to be because of the lower rates of smoking among more religious individuals.

Right lobe living-donor liver transplantation (LDLT) is often not attempted in donors with anomalous portal venous branching (APVB). The authors describe their experience with portal vein (PV) reconstruction in 17 cases of APVB in right lobe LDLT. From July 1997 to December 2001, 214 right liver LDLT were performed at the Asan Medical Center. Seventeen of the donors had APVB and successfully underwent right lobectomy. The APVB were type II (trifurcation) in nine cases, type III (independent posterior segmental branching from main PV trunk) in seven, and unclassified in one. All 17 donors and recipients are alive, with good liver function. In type II APVB, the donor PV branches were obtained with separate openings that were joined as a common orifice at the back table in two, with a discoid-patch single opening in four, and with one common opening in three. In type III APVB, the donor PV were divided with two openings in four and with a discoid-patch single opening in three. The discoid-patch defect in the remnant PV was repaired with a vein patchplasty in two donors and resected with end-to-end anastomosis in five. However, one donor developed portal vein thrombosis (PVT) that was managed successfully by re-exploration and insertion of a metallic vascular stent. Of the four type III APVB obtained with two separate PV openings, the first two liver grafts were each reconstructed as double PV anastomoses. One of them required re-exploration because of PVT. In the two succeeding cases, a Y-graft interposition technique using a cryopreserved cadaveric iliac vein or the recipient's own portal confluence was successfully applied. To minimize the risk of PVT in donors with APVB, discoid-patch excision followed by repair with vein patchplasty or segmental resection should be avoided. Individual division of the PV branches creating two separate openings instead is recommended. To decrease the recipient's risk of PVT, interposition Y-graft venous reconstruction at the back table is superior to double PV anastomoses.

Summary Background Data on the incidence of venous thromboembolism (VTE) following major surgery in Asian populations are limited. Methods Using the Korean Health Insurance Review and Assessment Service database, we performed a nationwide population-based epidemiologic study to estimate the incidence of VTE after major orthopedic, cancer, and benign surgeries. VTE cases were identified from all patients undergoing major surgery between 2007 and 2011 using both diagnostic and drug codes as treatment evidence of VTE within 5 weeks of surgery. We also calculated the relative risk of VTE in major orthopedic and cancer surgery compared to benign surgery. Results The overall rates of postoperative VTE were 1.24%, 0.67%, and 0.05% for major orthopedic, cancer, and benign surgeries, respectively. Hip fracture (1.60%) and colorectal cancer surgeries (1.67%) were associated with the highest rates of VTE, and the rates steadily increased during the study period. Advanced age, female sex, and general anesthesia were independent risk factors for VTE. Patients undergoing surgery for colorectal, pancreatic, ovarian, and esophageal cancer, and major orthopedic surgery had a > 20-fold higher risk of VTE than those undergoing benign surgery. Conclusions This is the largest epidemiologic study to investigate the incidence of VTE after major surgery in Asia, demonstrating that the rates of postoperative VTE are lower than in Caucasian populations. This study contributes to a better understanding of the differences in postoperative VTE development between Korean and Caucasian populations; the data also suggest that perioperative prophylactic strategies in Asians should be based on studies of such populations.

Pseudotyped retroviral vectors combine the advantages of broad host range, high expression, stable chromosomal integration, and ease of preparation. These vectors greatly facilitate delivery into mammalian cells of sequences encoding individual peptide inhibitors—including those with therapeutic utility—and inhibitor libraries. However, retroviral vectors vary in behavior, particularly with respect to expression levels in different cell lines. Expression level is especially important in transdominant experiments because the concentration of an inhibitor (for example, an expressed peptide) is one of the key determinants in the degree of complex formation between the inhibitor and its target. Thus, inhibitor concentration should have an impact on the expressivity and/or penetrance of an induced phenotype. Here, we compare several retroviral vectors and human cell lines for relative expression levels using a green fluorescent protein reporter. We show for a subset of these lines that cellular protein concentrations produced by single-copy vectors range up to about 2 μM. We also examine other variables that contribute to expression level, such as the nature of the expressed protein's carboxy terminus. Finally, we test the effect of increased concentration on phenotype with a nine-amino-acid peptide derived from the human papilloma virus protein E7 which overcomes E7-mediated cell growth.

The purpose of this study was to estimate the absorbed dose distribution of Ho-166 endovascular beta irradiation using an angio-catheter. The liquid form of Ho-166 was produced at the Korea Atomic Energy Research Institute (KAERI) by an (n,gamma) reaction. Ho-166 has a half-life of 26.8 h and emits a high-energy beta particle with a maximum energy of 1.85 MeV. GafChromic film was used for the estimation of the absorbed dose of beta particles. A Co-60 teletherapy source and a 6 MV photon beam from a linear accelerator were used to generate dose-optical density calibration curves. The exposed films were read using a videodensitometer. With a modified micrometer, the film was positioned accurately on the surface of the balloon in water. The balloon was filled with Ho-166 solution to a pressure of 4 atm. Several film exposures were made with varying irradiation times and activities. The radiation absorbed dose rates were 1.02, 0.51 and 0.35 Gy x min(-1) x GBq(-1) x ml(-1) at the balloon surface, 0.5 and 1 mm from the balloon surface, respectively. The absorbed dose distribution revealed that Ho-166 is a good source for endovascular irradiation as the beta range is very short, avoiding unnecessary irradiation of normal tissue. A clinically applicable irradiation and duration of exposure were achievable utilizing our system.

The response to standard chloroquine treatment was evaluated, by microscopical examination of blood-smears, among 81 soldiers diagnosed with Plasmodium vivax malaria in South Korea in 1996. The smears were prepared pre-treatment and 3, 14 and 28 days after starting chemotherapy. Parasitaemias were determined after staining the smears with Giemsa's stain. Blood samples from the patients who were not smear-negative by day 3 were carefully checked for parasites, by staining smears with Acridine Orange and by a PCR-based assay. Only two of the patients appeared to be parasitaemic on day 14 and were therefore considered treatment failures. Although both were apparently cured after additional therapy with the same regimen, one had a recurrence 8 months later. Most cases of recent, resurgent malaria in South Korea therefore appear to sensitive to chloroquine.

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. Epidemiologic investigations have shown variability in disease risks among different populations and races. In Korea, however, basic epidemiologic information on bacterial meningitis in children is limited. The main purpose of this study was to analyze bacteriologically proven meningitis cases in terms of the relative frequency of causative organisms, mortality rate, and age distribution beyond the neonatal period. Data was obtained from the hospital records who had been diagnosed with bacterial meningitis at 13 general or university hospitals from 1986 through 1995. The patients had at least one positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5 years cumulatively. Streptococcus pneumoniae was the most common bacteria responsible for 48 (35.0%) of all cases regardless of age, followed by Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%) patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis, S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common organisms of culture-proven bacterial meningitis in the last 10 years have been S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further study should be extended to nation-wide epidemiologic evaluation to show the incidence of bacterial meningitis caused by these three important organisms.

Purpose Pulmonary complications frequently occur after liver transplantation, but the risk factors associated with them have not been fully determined. We therefore sought to identify risk factors for pulmonary complications among adult liver transplant recipients. Methods We retrospectively reviewed the medical records of 128 consecutive adult patients who underwent 131 liver transplantations during 2001. We evaluated the incidence, time of onset, and outcome of radiographically determined pulmonary complications, as well as the factors predictive of infectious complications. Results Postoperative chest roentgenograms detected 68 cases of pulmonary complications, including pleural effusion ( n = 50), atelectasis ( n = 6), pneumonia ( n = 6), pulmonary edema ( n = 5), and acute respiratory distress syndrome associated with pneumonia ( n = 1). Of the seven patients with pneumonia, five died. On univariate analysis the risk factors predictive for pneumonia were high serum creatinine and total bilirubin, hemodialysis at the time of occurrence, and history of acute rejection and on multivariate analysis increased total bilirubin and history of acute rejection. Pulmonary complications were dependent on the medical condition at the time of occurrence rather than on the preoperative condition. Conclusions Although the incidence of pneumonia in liver recipients was relatively low, the mortality rate in patients who developed this complication was high. High-risk patients undergoing liver transplantation thus require early diagnosis and intensive treatment to diminish the morbidity and mortality associated with pulmonary complications.

Accidental slippage of vascular clamps during living donor hepatectomy can induce brisk bleeding and even imperil the donor. After practicing more than 1000 cases of living donor hepatectomy, the investigators realized that specialized suture techniques were important to secure the vascular closure to prevent unnecessary bleeding. For secure division of intrahepatic vein branches, we devised a continuous penetration suture method in which the orders of procedures were changed to clamping-closure-cut sequence. For secure division of the main and accessory hepatic vein branches from the inferior vena cava, we applied stay sutures at each corner and midpoint of the hepatic vein stump so as not to permit its slippage. After application of these methods, we did not experience any episode of accidental clamp slippage. We are sure that these suture techniques are beneficial to prevent unnecessary bleeding during living donor hepatectomy and to make surgeons feel at ease during the living donor operation.

We analyzed the anatomy and reconstruction of the right hepatic artery (RHA) in 96 cases of adult-to-adult living donor right liver transplantations, during 2002. Most right livers had a single orifice (n = 185, 96%). Seven right livers (4%) showed multiple arteries, namely a replaced artery in five cases and accessory arteries in two cases. Three liver grafts had two separate orifices: both arterial stumps were reconstructed in one case, and accessory arteries were ligated in two cases because of sufficient back bleeding. The mean diameter of the graft RHA was 2.4 mm (1-4). More than 60% (59 of 96) of graft arteries were anastomosed with distal branches of recipient RHA for size matching. Eleven graft arteries were anastomosed to vessels other than the RHA, namely the left hepatic artery [LHA] in eight right gastroepiploic artery in three: for size matching in five and due to previous injury of RHA in six. Five cases showed significant size-mismatches of more than twofold. The median follow-up period was 270 days. In one patient, an intramural thrombus developed on postoperative day 3 requiring a revision of the anastomosis. In another patient, arterial stenosis occurred on postoperative day 16 a time when collateral arteries had developed. The overall complication rate related to arterial reconstruction was 2%. In conclusion, with precise knowledge of the anatomy, an adequate selection of recipient arterial stump, and an experienced technique, a desirable result may be achieved in right lobe transplantation.

Background This study sought to establish an actual risk-based long-term screening protocol for hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT). Methods The study was a retrospective review of medical records from 334 HCC patients who underwent primary living donor OLT and followed up for at least 5 years. Results Overall 10-year patient survival rate was 67.5%, with a 4.8% perioperative mortality. HCC recurred in 68/318 (21.4%) surviving patients over a mean follow-up of 77 months. HCC recurrence was 20.7% at 5 and 22.2% at 10 years. Annual recurrence rates were 11.4%, 6.6%, and 2.0% during the first, second, and third years, respectively. Among patients within Milan criteria, the annual incidence of HCC recurrence was highest during the first 3 years; thereafter only 6 sporadic recurrences were observed during next 8 years. Among subjects beyond Milan criteria, recurrence was common during, but not after 3 years. In 43 patients (63.2%) increased alpha-fetoprotein (AFP) was an initial indication to perform further imaging studies to diagnosis recurrence, whereas they were detected incidentally on protocol screening imaging among another 25 patients (36.8%) in the absence of an AFP rise. There was a close correlation between pretransplant AFP level and AFP increase after HCC recurrence. Conclusions Patients beyond the Milan criteria require frequent tumor marker tests and imaging studies over the first 3 years; and those within Milan criteria require 10-years to follow-up primarily with tumor marker tests.

Cancers with Ras mutations represent a major therapeutic problem. Recent RNAi screens have uncovered multiple nononcogene addiction pathways that are necessary for the survival of Ras mutant cells. Here, we identify the evolutionarily conserved gene enhancer of rudimentary homolog ( ERH ), in which depletion causes greater toxicity in cancer cells with mutations in the small GTPase KRAS compared with KRAS WT cells. ERH interacts with the spliceosome protein SNRPD3 and is required for the mRNA splicing of the mitotic motor protein CENP-E. Loss of ERH leads to loss of CENP-E and consequently, chromosome congression defects. Gene expression profiling indicates that ERH is required for the expression of multiple cell cycle genes, and the gene expression signature resulting from ERH down-regulation inversely correlates with KRAS signatures. Clinically, tumor ERH expression is inversely associated with survival of colorectal cancer patients whose tumors harbor KRAS mutations. Together, these findings identify a role of ERH in mRNA splicing and mitosis, and they provide evidence that KRAS mutant cancer cells are dependent on ERH for their survival.

Background Living donor liver transplantation (LDLT) has been the first option for the patients requiring liver transplantation in East Asia because of the scarcity of cadaveric grafts. We have performed consecutively more than 300 LDLTs per year, and herein report our methods. Methods In 1997, the first successful adult LDLTs used a left and subsequently a right lobe. However, congestion in the anterior segment of right-lobe grafts prompted us to initiate reconstruction of middle hepatic venous tributaries in 1998. Dual LDLT grafts using 2 left lobes were developed in 2000 to solve graft-size insufficiency and minimize donor risk. The indications for adult LDLT were broadened to near complete obstruction of the portal vein by application of intraoperative cine-portography and portal vein stenting in 2004. ABO-incompatible adult LDLT was initiated in 2008 to overcome the blood group barrier between recipient and donor. Results With various innovations at our institution, 317 LDLTs were performed yearly in 2010 and 2011: 301 in 2010 and 298 in 2011. The most common primary diseases was hepatitis B virus-related liver cirrhosis with or without hepatocellular carcinoma (64.3%). The most common graft types were right hemiliver (82.6%). There has been no donor mortality. ABO-incompatible LDLT cases were 11.0% of the total. In-hospital mortality in 2011 was 2.5% ( n = 8; adult 6, pediatric 2). Conclusion Innovations in operative techniques and perioperative care as well as dedicated team members have made it possible to perform more than 300 LDLTs per year consecutively with excellent outcomes.

Renal morphometric analysis was performed in 15 (13 male) Alport syndrome patients ages 4 to 26 years, along with 10 controls ages 3 to 26 years, to better understand the structural basis of renal dysfunction in Alport syndrome. The glomerular basement membrane (GBM) width class frequencies of controls were normally distributed; those of Alport syndrome patients were slightly skewed, especially toward thicker classes, although there was also an increase in the proportion of thinner classes. Mesangial volume fraction was not different between Alport syndrome patients (0.21 +/- 0.09) and controls (0.19 +/- 0.04). There was an inverse correlation between mesangial volume fraction and creatinine clearance in Alport syndrome patients (r = -0.72, P < 0.01); however, the creatinine clearances in Alport syndrome patients were far less than in insulin-dependent diabetic patients with similar mesangial volume fraction. Similarly, there was no significant difference in the surface density of the peripheral GBM (in square micrometers per cubic micrometer) in Alport syndrome patients (0.12 +/- 0.04) versus controls (0.13 +/- 0.02). The surface density of the peripheral GBM correlated with creatinine clearance in Alport syndrome patients (r = 0.71, P < 0.01). However, there was a greater reduction in creatinine clearance as related to declining the surface density of the peripheral GBM in Alport syndrome than in diabetic patients. The cortical interstitial volume fraction was highly inversely correlated with creatinine clearance in Alport syndrome patients (r = -0.85, P < 0.01). Global glomerular sclerosis was 0% in five and 5 to 61% in nine Alport syndrome patients and correlated inversely with creatinine clearance (r = -0.74, P < 0.01). However, the creatinine clearance was lower in Alport syndrome than in diabetic patients with similar cortical interstitial volume fraction and percent glomerular sclerosis. There was no significant difference in an index of glomerular number between Alport syndrome patients and controls. Thus, changes in mesangial volume fraction, cortical interstitial volume fraction, percent glomerular sclerosis, and surface density of the peripheral GBM in Alport syndrome patients only partially account for the reduction in creatinine clearance. It was speculated that decreased glomerular capillary wall hydraulic conductivity in Alport syndrome could explain many of these observations.