Liver resection with thrombectomy for patients with hepatocellular carcinoma and tumour thrombus in the inferior vena cava or right atrium.

BACKGROUND: Hepatocellular carcinoma (HCC) with tumour thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is a rare advanced disease state with a poor prognosis. The aim of this study was to examine survival after surgical resection. METHODS: Patients with HCC and TT of either the IVC or RA, who underwent liver resection between February 1997 and July 2017, were included. Their short- and long-term outcomes and surgical details were analysed retrospectively. RESULTS: Thirty-seven patients were included; 16 patients had TT in the IVC below the diaphragm, eight had TT in the IVC above the diaphragm, and 13 had TT entering the RA. Twelve patients had advanced portal vein TT (portal vein invasion (Vp) greater than Vp3 and Vp4), ten had bilobar disease, and 12 had extrahepatic disease. There were no in-hospital deaths, although two patients died within 90 days. Median survival did not differ between patients who had resection with curative intent (18·7 months) and those with residual tumour in the lung only (20·7 months), but survival was poor for patients with residual tumour in the liver (8·3 months). CONCLUSION: Liver resection with thrombectomy for advanced HCC with TT in the IVC or RA is safe and feasible, leading to moderate survival.

ANTECEDENTES: El carcinoma hepatocelular con trombo tumoral (TT) en la vena cava inferior (inferior vena cava, IVC) o en la aurícula derecha (right atrium, RA) es un estado avanzado de la enfermedad raro, con un pronóstico desfavorable. En este estudio analizamos la supervivencia después de la resección quirúrgica. MÉTODOS: Se incluyeron pacientes con carcinoma hepatocelular con TT en la IVC o en la RA, que se sometieron a resección hepática entre febrero de 1997 y julio de 2017. Los resultados a corto y a largo plazo de estos pacientes y los detalles quirúrgicos se analizaron retrospectivamente. RESULTADOS: Se incluyeron 37 pacientes. Entre estos pacientes, se identificaron 16 pacientes con TT en la IVC infradiafragmática, 8 pacientes con TT en la IVC supradiafragmática y 13 pacientes con TT entrando en la AR. Doce pacientes asociaron TT avanzado en la vena porta más allá de vp 3 y 4, 10 pacientes tenían enfermedad bilobar y 12 pacientes tenían enfermedad extrahepática. A pesar de que la tasa de mortalidad hospitalaria fue cero, dos pacientes fallecieron a los 90 días. Aunque la mediana del tiempo de supervivencia no fue diferente entre el grupo al que se le realizó resección con intención curativa (18,7 meses) y aquellos con tumor residual solo en el pulmón (20,7 meses), la supervivencia fue extremadamente pobre para los pacientes con tumor residual en el hígado (8,3 meses). CONCLUSIÓN: La resección hepática con trombectomía para el carcinoma hepatocelular avanzado con trombo tumoral en la vena cava inferior o en la aurícula derecha es segura y factible, asociándose a una supervivencia moderada.

Nine genes abundantly expressed in the epididymis are not essential for male fecundity in mice.

BACKGROUND: Spermatozoa become competent for fertilization during transit through the epididymis. As spermatozoa from the proximal caudal epididymis can fertilize eggs, proteins from the caput and corpus epididymis are required for sperm maturation. OBJECTIVES: Microarray analysis identified that more than 17,000 genes are expressed in the epididymis; however, few of these genes demonstrate expression restricted to the epididymis. To analyze epididymis-enriched gene function in vivo, we generated knockout (KO) mutations in nine genes that are abundantly expressed in the caput and corpus region of the epididymis. MATERIALS AND METHODS: KO mice were generated using the CRISPR/Cas9 system. The histology of the epididymis was observed with hematoxylin and eosin staining. KO males were caged with wild-type females for 3-6 months to check fertility. RESULTS: We generated individual mutant mouse lines having indel mutations in Pate1, Pate2, or Pate3. We also deleted the coding regions of Clpsl2, Epp13, and Rnase13, independently. Finally, the 150 kb region encoding Gm1110, Glb1l2, and Glb1l3 was deleted to generate a triple KO mouse line. Histology of the epididymis and sperm morphology of all KO lines were comparable to control males. The females mated with these KO males delivered pups at comparable numbers as control males. DISCUSSION AND CONCLUSION: We revealed that nine genes abundantly expressed in the caput and corpus epididymis are dispensable for sperm function and male fecundity. CRISPR/Cas9-mediated KO mice generation accelerates the screening of epididymis-enriched genes for potential functions in reproduction.

Withdrawal of the Decision to Donate Kidney by Living Related Donors: A Single-center Study in Japan.

BACKGROUND: In Japan, 90% of kidney transplantations involve living related donors. A third-party interview is conducted during latter stages of preparation for transplantation to ensure the donor's voluntary decision-making. In this study, we investigated the factors responsible for withdrawal of decision for kidney donation by related living donors after third-party interview. METHODS: Related living donor candidates were divided into 2 groups based on their final decision: those who finally donated the kidney (FDG; n = 435); and those who withdrew their decision after third-party interview (WG; n = 11). The psychosocial and medical variables were compared and the reasons for withdrawal were investigated. RESULTS: Multiple logistic regression analysis revealed that none of the variables were significantly related to WG. Six categories of reasons for withdrawal were identified: "avoiding pregnancy risk"; "selecting alternative treatment"; "avoiding physical burden for donor"; "recipients' intemperance"; "need to take more time for decision-making"; and "psychological pressure." CONCLUSION: A certain number of donor candidates withdrew their decision for different reasons, even in the latter stages of the transplant preparation. Careful verification of the donor candidates' individual situation and provision of adequate information and time are important to protect the donor's right to refuse.

Case Report of Living Kidney Transplantation Using Ectopic Pelvic Kidney Harvested by Reduced Port Laparoscopic Donor Nephrectomy.

A 28-year-old woman was diagnosed as having an ectopic kidney in adolescence. She desired to donate her ectopic kidney to her mother, who was diagnosed as having renal failure. The ectopic kidney was located behind the sigmoid colon with 3 renal arteries and 3 renal veins. Laparoscopic donor nephrectomy was performed by reduced port surgery using the GelPOINT access platforms at a midline incision below the umbilicus with 1 accessory port. A thin artery of the donated kidney was ligated. An artery of the upper pole was anastomosed to the internal iliac artery, and a second artery was anastomosed directly to the inferior epigastric artery. Three veins were anastomosed to the external iliac vein: 1 anastomosed directly, 1 interposed by saphenous vein graft, and 1 interposed by harvested ovarian vein. To our knowledge, this is the first successful case of transplantation using an ectopic pelvic kidney by reduced port laparoscopic donor nephrectomy.

Quantitative Assay of Macroautophagy Using Pho8△60 Assay and GFP-Cleavage Assay in Yeast.

It is intrinsically difficult to directly measure a specific protein reduction that is mediated by nonselective autophagy, because the degradation proceeds at a relatively slow pace, and the residual nondegraded part becomes the background. Several methods for measuring nonselective autophagy have been reported in the past. One classical simple method is called bulk degradation assay, which measures the release of degraded amino acids after radioisotope labeling of the total cellular proteins. In 1995, we developed a quantitative Pho8△60 assay in the yeast, Saccharomyces cerevisiae, for studying autophagy, which is widely used for its advantages that are described in the following sections. Another method used in recent times is the GFP-based processing assay in yeast. We will describe these two methods in this chapter.

Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells.

Human colorectal cancer is often initiated by the aberrant activation of Wnt signaling, notably following adenomatous polyposis coli (Apc) inactivation. Recent studies identified adult intestinal stem cells (ISCs) and demonstrated their role as the cells of origin for intestinal tumors. However, the early consequences of aberrant Wnt signaling activation remain to be fully elucidated. Here, using organoid cultures established from conditional knockout mice and in vitro gene ablation, we show that Apc inactivation led to aberrant ISC proliferation and the expansion of the crypt domain. This system was used to evaluate the potential of a cancer-related spindle protein, Tacc3, as a target of cancer therapy, as its disruption led to the suppression of tumor formation in an animal model of intestinal tumors. We found that Tacc3 is required for the proper mitosis of Apc-deficient ISCs, and its disruption significantly attenuated the expansion of the crypt domain. In vivo analysis of corresponding mutant mice demonstrated that Tacc3 disruption led to a significant decrease in tumor number and prolonged survival. These observations demonstrated that Tacc3 is a potential chemotherapeutic target for intestinal tumors by perturbing the aberrant cell proliferation of Apc-deficient ISCs and provides an opportunity for the development of novel cancer prevention and treatment.

Covariation of pupillary and auditory cortical activity in rats under isoflurane anesthesia.

Very slow fluctuations of spontaneous activities significantly influence not only behavioral performance in a conscious state, but also neural activities in an unconscious state. Covariation of pupil and cortical activities may lend important insights into the state-dependent modulation of stimulus encoding, yet this phenomenon has received little attention, especially with regard to non-visual cortices. In the present study, we investigated co-fluctuation of pupil size and neural activity in the auditory cortex of rats under isoflurane anesthesia. Pupil fluctuation consisted of longitudinal irregular shifts, and 1-min cyclic modulations. Both spontaneous and auditory-evoked potentials (AEPs) covaried with the longitudinal fluctuation of pupil size, but not with the 1-min cycle. Pupil size exhibited a positive correlation with spontaneous activity and negative correlation with AEP amplitude, particularly when the pupil size was beyond the normal range. Stimulus-specific adaptation characterized using an oddball paradigm was less dependent on pupil size than AEP. In contrast to the cortical activity, heart rate covaried with pupil size with the 1-min oscillatory component, but not the non-oscillatory component. Furthermore, light exposure induced the pupil reflex through the autonomic system, but did not modify cortical activity, indicating that autonomic activity was not causing the cortical modulation. These results together suggest that cortical activities spontaneously covary with pupillary activity through central cholinergic modulation that triggers sympathetic nerve activation. Such a state-dependent property may be a confounding factor in cortical electrophysiology studies.

Roles of extracellular Ca(2+) in the occurrence of full-type hyperactivation in boar ejaculated spermatozoa pre-incubated to induce the cAMP-triggered events.

There are species differences in the regulatory system for sperm capacitation and subsequent hyperactivation between livestock and laboratory animals. In livestock spermatozoa, it is poorly understood when and how extracellular Ca(2+) is necessary for hyperactivation, although it has been demonstrated that the [Ca(2+) ]i increase is indispensable to occurrence of hyperactivation. In this study, we examined necessity of extracellular Ca(2+) for the initiation and maintenance of hyperactivation and then sought possible target molecule of Ca(2+) that was involved in hyperactivation of boar spermatozoa. Boar ejaculated spermatozoa were pre-incubated with a cell-permeable cyclic adenosine monophosphate (cAMP) analog 'cBiMPS' and without CaCl2 to induce the cAMP-triggered events including capacitation-associated changes. Subsequently, they were incubated with CaCl2 to induce hyperactivation and then used for motility assessment. Many of the spermatozoa after the incubation exhibited full-type hyperactivation which was characterized by high-amplitude and extremely asymmetrical beating of whole middle piece and principal piece. The initiation of full-type hyperactivation required the millimolar concentration of CaCl2 in the medium. However, CaCl2 of the medium was less necessary for maintenance than initiation of full-type hyperactivation, as hyperactivated spermatozoa were barely affected by the incubation with the Ca(2+) -chelating reagent. On the other hand, the pre-treatment with the inhibitor for Ca(2+) -dependent protease 'calpain 1 and 2' clearly suppressed the occurrence of CaCl2 -induced hyperactivation without influences on the percentages of motile spermatozoa. Western blotting and indirect immunofluorescence showed distribution of calpain 2 in the middle and principal pieces in which full-type hyperactivated spermatozoa exhibited extremely asymmetrical beating. On the basis of these results, we conclude that the millimolar concentration of extracellular Ca(2+) is necessary for the initiation, but not for the maintenance of full-type hyperactivation in boar spermatozoa that beforehand undergo the cAMP-triggered events including capacitation-associated changes. Moreover, we suggest possible involvement of calpain 2 in the intracellular Ca(2+) signal transduction leading to full-type hyperactivation.

Cochlear implants for mumps deafness: two paediatric cases.

BACKGROUND: Good outcomes have been reported regarding the use of cochlear implants for mumps deafness. The mumps virus induces meningitis and/or encephalitis, which can cause central nervous system damage resulting in retrolabyrinthine hearing loss, for which a cochlear implant would be less effective. CASES: We installed a cochlear implant in two patients with bilateral mumps deafness; one achieved a good result with the cochlear implant, but the other did not. We discuss two possible reasons for the different outcomes. Case 1 was a three-year-old girl with bilateral parotid swelling, vomiting and walking disorder. One year after cochlear implant insertion, speech perception did not develop despite of good pure tone thresholds. Case 2 was an eight-year-old girl with bilateral parotid swelling. A cochlear implant enabled her to improve hearing perception. CONCLUSION: Although cochlear implants have been reported to be helpful for mumps deafness, cases that involve central nervous system damage may not achieve good results.

Images created in a model eye during simulated cataract surgery can be the basis for images perceived by patients during cataract surgery.

PURPOSE: To evaluate the images created in a model eye during simulated cataract surgery. PATIENTS AND METHODS: This study was conducted as a laboratory investigation and interventional case series. An artificial opaque lens, a clear intraocular lens (IOL), or an irrigation/aspiration (I/A) tip was inserted into the 'anterior chamber' of a model eye with the frosted posterior surface corresponding to the retina. Video images were recorded of the posterior surface of the model eye from the rear during simulated cataract surgery. The video clips were shown to 20 patients before cataract surgery, and the similarity of their visual perceptions to these images was evaluated postoperatively. RESULTS: The images of the moving lens fragments and I/A tip and the insertion of the IOL were seen from the rear. The image through the opaque lens and the IOL without moving objects was the light of the surgical microscope from the rear. However, when the microscope light was turned off after IOL insertion, the images of the microscope and operating room were observed by the room illumination from the rear. Seventy percent of the patients answered that the visual perceptions of moving lens fragments were similar to the video clips and 55% reported similarity with the IOL insertion. Eighty percent of the patients recommended that patients watch the video clip before their scheduled cataract surgery. CONCLUSIONS: The patients' visual perceptions during cataract surgery can be reproduced in the model eye. Watching the video images preoperatively may help relax the patients during surgery.

A small compound targeting TACC3 revealed its different spatiotemporal contributions for spindle assembly in cancer cells.

The mitotic spindle is assembled by the coordinated action of centrosomes and kinetochore microtubules. An evolutionally conserved protein family, transforming acidic coiled-coil (TACC), has been shown to be involved in this process. In humans, TACC3 is aberrantly expressed in a variety of human cancers, but its biological significance remains to be elucidated. Here, using a novel compound targeting TACC3, spindlactone (SPL), we show that the perturbation of TACC3 selectively inhibited the nucleation of centrosome microtubules in ovarian cancer cells. In contrast to centrosome microtubules, the kinetochore microtubules were robustly assembled, forming ectopic spindle poles that resulted in multipolar spindles. Interestingly, the extensive inhibition of TACC3 partially suppressed the nucleation of kinetochore microtubules. These dose-dependent effects of SPL were consistent with the results observed by the depletion of TACC3 and its binding partner, colonic and hepatic tumor overexpressed gene protein (TOGp). Although these proteins both have roles in the assembly of centrosome and kinetochore microtubules, their contributions were spatiotemporally different. Notably, SPL did not affect spindle assembly in normal cells. Furthermore, the oral administration of SPL significantly suppressed tumor growth in vivo. The unique mechanism of action of SPL not only enables it to be used as a tool to dissect the molecular basis of spindle assembly but also to provide a rationale for the use of TACC3 as a molecular target for cancer treatment. This rationale offers an opportunity to develop new strategies for cancer chemotherapy that overcome the limitations of microtubule toxins and expand their scope and clinical efficacy.

An in vitro demonstration of CMOS-based optoelectronic neural interface device for optogenetics.

A CMOS-based neural interface device equipped with an integrated micro light source array for optogenetics was fabricated and demonstrated. A GaInN LED array formed on sapphire substrate was successfully assembled with a multifunctional CMOS image sensor that is capable of on-chip current injection. We demonstrated a functionality of light stimulation onto ChR2-expressed cells in an in vitro experiment. A ChR2-expressed cell were successfully stimulated with the light emitted from the fabricated device.

Extensive hybridization and associated geographic trends between two rockfishes Sebastes vulpes and S. zonatus (Teleostei: Scorpaeniformes: Sebastidae).

Interspecific hybridization is an important evolutionary process, which has significant influence on the diversity within and between participating taxa. Although interspecific hybridization in terrestrial and freshwater organisms has been subjected to many detailed studies, studies in marine realm have been limited in terms of both numbers and detail. In this study, the potential for interspecific hybridization between two rockfishes, Sebastes vulpes and S. zonatus, occurring in the western North Pacific, was assessed on the basis of 177 specimens collected from three sampling localities within the main geographic distribution of both species, and analysed using a combination of amplified fragment length polymorphisms (AFLP), mitochondrial DNA (mtDNA) markers and morphometric characters. Bayesian-based individual genetic assignment based on 364 AFLP loci detected a total of 63 (35.6%) hybrid specimens in the data set, the presence of interspecific hybrids also being rigorously supported by mtDNA analysis using partial sequences from the control region and morphological analysis based on 31 morphometric characters. Hybrids from all three localities were found, showing a common pattern of biased introgression across the localities whereby hybrids were more closely related to S. zonatus than to S. vulpes. Apart from this common pattern, rates of hybridization varied considerably among the localities, being greater in the northern localities. Variations in the local rates of hybridization were associated with variations in habitat segregation and thermal regime, implying that vertical water temperature regimes determined the extent of habitat segregation of the two species and, accordingly, the opportunity for hybridization.

Efficacy of endotoxin adsorption therapy (polymyxin B hemoperfusion) for methicillin-resistant Staphylococcus aureus toxic shock syndrome: a case report about five patients.

BACKGROUND: Toxic shock syndrome (TSS), which can be life-threatening, is clinically and pathologically characterized by the presence of high fever, skin rash, desquamation, hypotension, and multiple organ failure caused by an enterotoxin produced by Staphylococcus aureus. In this study, we evaluated the effects of endotoxin adsorption therapy (polymyxin B [PMX] hemoperfusion) in critical patients with methicillin-resistant Staphylococcus aureus TSS (MRSA-TSS) who showed no improvement with the conventional therapy. METHODS: Five MRSA-TSS patients (men/women: 3/2; median age: 39 years) who showed no improvement with the conventional therapy underwent PMX hemoperfusion in addition to the conventional therapy. The primary outcomes were change in the systolic arterial pressure (SAP) and requirement of a vasopressor after PMX hemoperfusion, and the secondary outcomes were change in laboratory data and sequential organ failure assessment (SOFA) scores 24 h after the therapy. RESULTS: The median duration of PMX hemoperfusion was 9 h (range, 4-20 h). SAP significantly increased (from 89 to 125 mmHg, P<0.05) and the requirement of a vasopressor significantly decreased (from 10 to 2, P<0.05) after PMX hemoperfusion. Furthermore, the patients' white blood cell count decreased (from 17640 to 10090 /uL, P<0.05), and SOFA scores decreased (from 13 to 9, P<0.05) after PMX hemoperfusion. All patients recovered and were discharged from the ICU. CONCLUSION: Our results showed that PMX hemoperfusion significantly improved the hemodynamics and severity in patients with life-threatening MRSA-TSS.

Detection of the activator cAMP responsive element modulator (CREM) isoform ortholog proteins in porcine spermatids and sperm.

It is necessary to obtain basic information on transcription factors expressed in the spermatids of livestock to determine mechanisms of defective spermiogenesis. In this study, we characterized the activator cAMP responsive element modulator (CREM) ortholog isoforms in porcine testicular germ cells and ejaculated sperm. At least two kinds of porcine activator CREM τ family ortholog mRNAs were more strongly expressed in the testis than in kidney or liver. The activator CREM isoform ortholog proteins were localized in nuclei of round spermatids and around nuclei of elongated spermatids. Furthermore, approximately 34% of ejaculated sperm had the activator CREM isoform ortholog proteins at their connecting piece. This is apparently the first report demonstrating the expression and localization of the activator CREM isoform ortholog proteins in spermatids and ejaculated sperm of a livestock species.

Attitudes towards different containment measures: a questionnaire survey in Finnish adolescent psychiatry.

Use of containment measures in the treatment of underage patients is controversial, and empirical evidence about which containment methods are preferred is lacking. This study aimed to investigate attitudes of staff towards various containment measures in the field of adolescent psychiatry. The sample comprised 128 Finnish nurses and doctors working in closed wards with 13- to 17-year-old patients. The attitudes were studied using the Attitude to Containment Measures Questionnaire. The three methods with the most approval were as-needed medication, transfer to specialist locked wards and mechanical restraint. The method with the least approval was the net bed. Total approval scores for the various containment measures were very similar among nurses and doctors. The differences appeared in attitudes towards mechanical restraint and constant observation, doctors showing a more critical attitude. Women tended to be more critical than men, but only intramuscular medication and mechanical restraint reached statistical significance. The results emphasize the importance of wide-ranging and in-depth training as well as the difficulty of changing practices in psychiatric wards while attitudes are so strongly pro-containment.