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.

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.

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.

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.

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.

Disruption of Tacc3 function leads to in vivo tumor regression.

The formation of the bipolar spindle is responsible for accurate chromosomal segregation during mitosis. The dynamic instability of microtubules has an important role in this process, and has been shown to be an effective target for cancer chemotherapy. Several agents that target non-microtubule mitotic proteins, including the motor protein Eg5, Aurora kinases and Polo-like kinases, are currently being developed as chemotherapeutic drugs. However, because the efficacies of these drugs remain elusive, new molecular targets that have essential roles in tumor cells are desired. Here, we provide in vivo evidence that transforming acidic coiled-coil-3 (Tacc3) is a potential target for cancer chemotherapy. Using MRI, we showed that Tacc3 loss led to the regression of mouse thymic lymphoma in vivo, which was accompanied by massive apoptosis. By contrast, normal tissues, including the thymus, showed no overt abnormalities, despite high Tacc3 expression. in vitro analysis indicated that Tacc3 depletion induced multi-polar spindle formation, which led to mitotic arrest, followed by apoptosis. Similar responses have been observed in Burkitt's lymphoma and T-ALL. These results show that Tacc3 is a vulnerable component of the spindle assembly in lymphoma cells and is a promising cancer chemotherapy target.

Insulin-like growth factor-binding protein 7 alters the sensitivity to interferon-based anticancer therapy in hepatocellular carcinoma cells.

BACKGROUND: A striking efficiency of interferon (IFN)-based anticancer therapy for advanced hepatocellular carcinoma (HCC) has been reported. Because its clinical efficiency greatly depends on each patient's local response, prediction of local response is crucial. METHODS: Continuous exposure of IFN-alpha to parental PLC/PRF/5 cells (PLC-P) and a limiting dilution method resulted in the establishment of IFN-resistant cell clones (PLC-Rs). Microarray analyses of PLC-P and PLC-Rs identified insulin-like growth factor-binding protein 7 (IGFBP7) as one of the most significantly downregulated genes in PLC-Rs. Changes in anticancer effects of IFN-alpha were examined in HCC cells after genetic manipulation of IGFBP7 expression. The correlation between immunohistochemically determined IGFBP7 expression and the response to IFN-alpha/5-fluorouracil (5-FU) therapy was investigated in surgically resected HCC specimens. RESULTS: PLC-R cells showed a remarkable downregulation of IGFBP7 and resistance to IFN-alpha, compared with PLC-P. Parental PLC/PRF/5 cells transfected with short hairpin RNA against IGFBP7 showed a significant resistance to IFN-alpha relative to control cells (IC(50) fold increase=14.38 times). Insulin-like growth factor-binding protein 7 transfection into PLC-R restored sensitivity to IFN-alpha. In resected specimens, IGFBP7 expression significantly correlated with the response to IFN-alpha/5-FU therapy. CONCLUSION: IGFBP7 could be a useful predictor of the response to IFN-based therapy in advanced HCC.

Light-controlled retinal stimulation on rabbit using CMOS-based flexible multi-chip stimulator.

We implemented a light-sensing function on CMOS-based multi-chip stimulator for retinal prosthesis. Using the light-sensing circuitry attached to each stimulation electrode, the flexible multi-chip stimulator is capable of image-based patterned stimulation. We verified the function of the light-controlled decision based on the light intensity measured just beside the stimulation site. We also experimentally demonstrated in vivo retinal stimulation on rabbit's retina with light-controlled decision. The result of the present work is a simplified demonstration for the concept of retinal prosthesis with on-site imaging.

Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma.

Type I IFN receptor type 2 (IFNAR2) expression correlates significantly with clinical response to interferon (IFN)-alpha/5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). However, some IFNAR2-positive patients show no response to the therapy. This result suggests the possibility of other factors, which would be responsible for resistance to IFN-alpha/5-FU therapy. The aim of this study was to examine the mechanism of anti-proliferative effects of IFN-alpha/5-FU therapy and search for a biological marker of chemoresistance to such therapy. Gene expression profiling and molecular network analysis were used in the analysis of non-responders and responders with IFNAR2-positive HCC. The Wnt/beta-catenin signalling pathway contributed to resistance to IFN-alpha/5-FU therapy. Immunohistochemical analysis showed positive epithelial cell adhesion molecule (Ep-CAM) expression, the target molecule of Wnt/beta-catenin signalling, only in non-responders. In vitro studies showed that activation of Wnt/beta-catenin signalling by glycogen synthesis kinase-3 inhibitor (6-bromoindirubin-3'-oxime (BIO)) induced chemoresistance to IFN-alpha/5-FU. BrdU-based cell proliferation ELISA and cell cycle analysis showed that concurrent addition of BIO and IFN-alpha/5-FU significantly to hepatoma cell cultures reduced the inhibitory effects of the latter two on DNA synthesis and accumulation of cells in the S-phase. The results indicate that activation of Wnt/beta-catenin signalling pathway induces chemoresistance to IFN-alpha/5-FU therapy and suggest that Ep-CAM is a potentially useful marker for resistance to such therapy, especially in IFNAR2-positive cases.

Possible involvement of phosphatidylinositol 3-kinase/Akt pathway in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblasts.

In the present study, we investigated whether Akt is involved in insulin-like growth factor-I (IGF-I)-stimulated activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in osteoblast-like MC3T3-E1 cells. IGF-I induced the phosphorylation of Akt in these cells. Akt inhibitor significantly suppressed the IGF-I-stimulated alkaline phosphatase activity. The phosphorylation of Akt induced by IGF-I was reduced by the Akt inhibitor. LY294002 and wortmannin, inhibitors of phosphatidylinositol 3-kinase, significantly suppressed the IGF-I-induced alkaline phosphatase activity. The phosphorylation of Akt induced by IGF-I was markedly reduced by LY294002 and wortmannin. These results strongly suggest that phosphatidylinositol 3-kinase/Akt plays a role in the IGF-I-stimulated alkaline phosphatase activity in osteoblasts.

Tooth development included in the multifocal jaw lesions of Langerhans cell histiocytosis.

Many cases demonstrating the oral manifestations of Langerhans cell histiocytosis (LCH) have been reported; however, tooth development in jaw lesions has rarely been mentioned. This paper reports the case of a 3-year-old Japanese girl with LCH suffering from multiple osteolytic lesions of the skull and jaw bones. She was referred to our paediatric clinic because of swelling of the mucogingival folds in the upper and lower primary molar regions. The patient responded well to steroid therapy and the osteolytic lesions resolved. There was an accompanying development of permanent tooth germs included in the lesions. Langerhans cell histiocytosis in children usually has a long-term clinical course and paediatric dentists should be involved with oral health care for affected patients.

Minimally invasive plate osteosynthesis for comminuted fractures of the metaphysis of the radius.

Five comminuted and displaced fractures of the distal metaphysis of the radius were treated by a technique of minimally invasive plate osteosynthesis (MIPO) with the aim of minimizing soft tissue damage and devascularization of the fracture fragments. This technique used the small AO T-shaped locking compression plate (AO LCP T-plate) and left the pronator quadratus intact. Radial inclination, palmar tilt, and ulnar variance were restored without loss of reduction in all five cases and the fractures healed at an average of 10 weeks, with good to excellent clinical outcomes.

Clinical observations of odontomas in Japanese children: 39 cases including one recurrent case.

Retrospective investigations of odontomas in Japanese children and one recurrent case were carried out. Thirty-nine cases of odontoma in 38 children were treated in the Paediatric Dentistry Clinic of Niigata University Dental Hospital between September 1979 and December 2002. The patients consisted of 23 males and 15 females and their ages ranged from 1 year 2 months to 14 years old. The chief complaints were delayed tooth eruption in 19 cases (five: primary teeth, 14: permanent teeth), retention of primary teeth in 11, incidentally found on the radiographic examination in eight cases, and swelling of the jaw in one case. Thirty-four cases (87%) were associated with tooth eruption disturbances. The most frequently affected region was the maxillary anterior region. Treatment consisted of surgical removal of odontomas in all cases, after which if the impacted teeth did not erupt, exposure of the crown and/or orthodontic traction was performed. Pathological diagnoses were compound odontoma in 30 cases, complex odontoma (n = 7), and compound and complex odontoma (n = 2). A retrospective study of the radiographs revealed the developing process of odontomas in four cases and odontoma disturbed tooth eruption since the early uncalcified developing stage. A recurrent case was a boy aged 6 years 5 months in whom the first surgical removal of odontoma was performed at the age of 1 year 8 months. Recurrence of an odontoma is very rare, but in very young children odontomas are in the early developing stages, containing uncalcified portions, so it is important to perform periodical observations until the succedaneous teeth erupt.