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Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38–85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64–1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings. [ABSTRACT FROM AUTHOR]

Extrahepatic portal vein aneurysm (PVA) is a rare condition in which the extrahepatic portal vein is partially dilated into a sac-like or spindle-like shape. Usually, patients are followed, but surgery is considered in cases of rupture, thrombus, or enlargement. We report a case of thrombus formation in an extrahepatic portal vein aneurysm following trauma that resulted in regression of the aneurysm and extrahepatic portal vein occlusion. Immediately after the trauma, ultrasonography showed moderately hyperechoic structures and comet signs along the vessel wall of the aneurysm and turbulent blood flow in the aneurysm, like in a whirlpool. There were floating point-like echogenic features, which were presumed to be microthrombi. In other words, the trauma might have triggered Virchow's triad: changes in the vessel wall, changes in blood properties, and blood stagnation. This is a valuable case in which ultrasonography imaging revealed interesting changes during the thrombus formation process inside an extrahepatic portal vein aneurysm. The aneurysm's size was reduced by thrombus-induced organization, but the main trunk of the portal vein became deficient in blood flow, resulting in extrahepatic portal vein occlusion. This case is suggestive of the mechanism of extrahepatic portal vein occlusion. [ABSTRACT FROM AUTHOR]

Combining genetic heterogeneity and crop homogeneity serves a dual purpose: disease control and maintaining harvest quality. Multilines, which consist of a genetically uniform mixture of plants, have the potential to suppress disease while maintaining eating quality, yet practical methods that facilitate commercial use over large geographical areas are lacking. Here, we describe effective rice multiline management based on seed mixture composition changes informed by monitoring virulent blast races in Niigata Prefecture, Japan. The most elite nonglutinous cultivar, Koshihikari, was converted into the multiline, Koshihikari BL (blast resistant lines) and planted on 94,000 ha in 2005. The most destructive rice disease, blast, was 79.4% and 81.8% less severe in leaves and panicles, respectively, during the 2005–2019 period compared to the year 2004. In addition, fungicidal application was reduced by two-thirds after the introduction of BL. Our results suggest that seed mixture diversification and rotation of resistant BL provides long-term disease control by avoiding virulent race evolution. [ABSTRACT FROM AUTHOR]

The first cell fate commitment during mammalian development is the specification of the inner cell mass and trophectoderm. This irreversible cell fate commitment should be epigenetically regulated, but the precise mechanism is largely unknown in humans. Here, we show that naïve human embryonic stem (hES) cells can transdifferentiate into trophoblast stem (hTS) cells, but primed hES cells cannot. Our transcriptome and methylome analyses reveal that a primate-specific miRNA cluster on chromosome 19 (C19MC) is active in naïve hES cells but epigenetically silenced in primed ones. Moreover, genome and epigenome editing using CRISPR/Cas systems demonstrate that C19MC is essential for hTS cell maintenance and C19MC-reactivated primed hES cells can give rise to hTS cells. Thus, we reveal that C19MC activation confers differentiation potential into trophoblast lineages on hES cells. Our findings are fundamental to understanding the epigenetic regulation of human early development and pluripotency. Little is known about the epigenetic mechanisms of the first cell fate commitment in humans. Here, the authors show that activation of the miRNA cluster C19MC confers differentiation potential into trophoblast lineages on human embryonic stem cells. [ABSTRACT FROM AUTHOR]

Hyperammonemia is often experienced as a complication of liver cirrhosis, but it is not well known that hyperammonemic encephalopathy is induced by urease-splitting bacteria in the urinary tract. We report two cases of hyperammonemia in two women in their 80s with liver cirrhosis. Both cases were treated as hepatic encephalopathy with usual treatment, but there was no improvement. Urinalysis showed marked alkalinuria and urine culture showed urease-splitting bacteria, which were thought to be related to the pathology. After drainage of urine and administration of antimicrobials, the blood ammonia level decreased and the urine pH level normalized. The mechanism of this is that ammonia is produced by the degradation of urinary urea by urease-producing bacteria in the bladder, and in the presence of dysuria, it is absorbed into the blood circulation from the bladder venous plexus, leading to hyperammonemia. Urine findings should be confirmed when a patient with liver disease develops hyperammonemia or is unresponsive to conventional hepatic encephalopathy treatment. [ABSTRACT FROM AUTHOR]

Red crown rot caused by Calonectria ilicicola, a soil-borne fungus, is one of the main soybean diseases in Japan. In field surveys to understand the present status of the disease in Akita, Fukushima, Niigata, Toyama, and Nagano prefectures, survey data included the cultivation history and conditions as well as the disease ratings for each field. The disease was confirmed to occur in all five prefectures, and the percentage of diseased fields ranged from 38.9 to 100%. Generalized linear mixed model analyses using the data from Akita, Fukushima, and Niigata prefectures revealed the explanatory variables conducive to the disease from the cultivation history, cropping system, and field conditions. Four factors significantly affected disease incidence and severity: past disease incidence in field, number of years with continuous soybean cultivation, sowing date, and number of intertillage ridging applications. Analysis of Niigata Prefecture data revealed additional factors affecting the disease: the use of agrochemical-treated seeds and field drainage-related variables. Early implementation of intertillage ridging was associated with greater disease severity, indicating that the disease was affected not only by the number but also by the timing of intertillage ridging application. Careful planning of cultivation and management methods to avoid these risk factors may reduce damage caused by the disease. To our knowledge, this is the first comparative analysis of the incidence and severity of red crown rot and the factors influencing the disease using a comprehensive data set from five Japanese prefectures. [ABSTRACT FROM AUTHOR]

Background: Daclatasvir (DCV) and asunaprevir (ASV) combination therapy has been primarily used in patients without NS5A L31 or Y93 resistance-associated substitutions (RASs) before treatment. We examined the characteristics of patients without these baseline RASs who did not achieve hepatitis C virus eradication with DCV and ASV combination therapy and identified new baseline NS5A RASs that are closely associated with failure of combination therapy.Methods: Three hundred thirty-five patients with hepatitis C virus genotype 1 infection with no NS5A L31, NS5A Y93, and NS3 D168 RASs before DCV and ASV combination therapy and no history of protease inhibitor therapy were enrolled. All RASs were evaluated by direct sequencing.Results: Sustained virologic response at 12 weeks (SVR12) was achieved in 297 patients (89%). Patients with NS5A Q24, L28, and/or R30 RASs or concomitant NS5A F37 and Q54 RASs had a significantly lower SVR12 rate than patients without these RASs (70% vs 92%, p < 0.001 and 79% vs 92%, p = 0.002 respectively). Multivariate analysis showed that NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs were significantly associated with virologic failure. The SVR12 rate in patients without NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs was 96.2% (202/210).Conclusions: In patients without NS5A L31 or Y93 RASs, the presence of NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs at the baseline was associated with failure of DCV and ASV combination therapy. The coexistence of baseline RASs other than NS5A L31 and Y93 may affect the therapeutic effectiveness of DCV and ASV combination therapy. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) frequently develops postural abnormalities including extreme neck flexion and trunk flexion. Patients with PD sometimes have osteopenia and vertebral deformity due to the destruction of fragile bone can be also associated with the spinal deformity. Surgical treatment for these patients is very difficult. We encountered a patient with PD presenting severe trunk sagittal and frontal deformity. The patient had cauda equina syndrome due to progressive vertebral collapse of the lumbar spine. We performed anterior reconstruction surgery at first in order to achieve improved lordotic alignment of the lumbar spine. Then, we performed 2 posterior surgeries, resulting in total long fusion from T4 to S1. The clinical findings of this patient were presented, and the treatment options were discussed. [ABSTRACT FROM AUTHOR]

Introduction: An axial symptom is one of the postoperative problems after cervical laminoplasty. The range of motion (ROM) of the cervical spine decreases after laminoplasty. It is speculated that the reduction in neck ROM is one of the causes of axial symptoms. However, most reports have focused on ROM of the cervical spine in flexion and extension, and few papers describe the rotational motion after surgery. It is impossible to assess the rotational motion in plain X-rays. This study was undertaken for the following two purposes: (1) to compare segmental rotational angles of the cervical spine between control subjects and patients with cervical laminoplasty ; (2) to analyze the relationship between postoperative axial symptoms and the range of cervical rotational angle after laminoplasty. Methods: Eleven young volunteers (control 1 group) and 10 elderly subjects (control 2 group) who did not have any neck problems and 23 patients who had en bloc cervical laminoplasty due to cervical spondylotic myelopathy were included. Dynamic CT scan was conducted in neutral, right, and left maximum rotational positions from C1 to T1. We measured the rotational angle in each vertebral segment. The axial symptoms, such as limited neck motion and neck stiffness, were assessed by a questionnaire. The rotational angle of the cervical spine was compared between the patients with axial symptoms and the subjects without. Results: The rotational angle in control 1 group was greater than that in control 2 group. The rotational angle was markedly decreased in the patients with cervical laminoplasty compared to that in control 2 group. The reduction was observed at the upper vertebral segment. Twelve patients were judged to have axial symptom after cervical laminoplasty (symptom + group), and 11 patients did not have symptoms (symptom − group). The rotational angle in the symptom + group was significantly smaller than that in symptom − group. The reduction in the rotational angle was found below C2 level, whereas the C1-2 angle was not significantly different in the two symptom groups. Conclusion: Reduction of the rotational angle in the cervical spine was clearly observed in patients with cervical laminoplasty, compared to that in the controls. The marked reduction might be related to the axial symptoms after laminoplasty. [ABSTRACT FROM AUTHOR]

Idiopathic hypertrophic spinal pachymeningitis (IHSP) is a comparatively rare disease characterized by hypertrophic inflammation of the dura mater and clinical symptoms that progress from local pain to myelopathy. We report a case of IHSP followed up for 20 years in a 46-year-old man. Expansive laminoplasty was performed in 1991, and this case has been previously reported by a co-author. After 17 years, the patient's gait disturbance returned. Physical examination and imaging confirmed IHSP that had developed into syringomyelia at the T2-L1 conus level. This case was diagnosed as adhesive spinal arachnoiditis due to pachymeningitis caused by syringomyelia. T1-T4 laminectomy, a syringo-subarachnoid shunt (S-S shunt), and L2-L3 laminectomy were performed. The patient again developed dysesthesia and gait disturbance 3 years after the second operation. Most reports of IHSP have limited their focus to short-term follow-up after initial treatment with no long-term results. At present, there are only five reports referring to long-term results of greater than 5 years. All but one case needed additional surgery. To the best of our knowledge, this is the first case in which syringomyelia occurred in a patient with IHSP. It is important to note that syringomyelia may be a cause of symptom recrudescence during long-term follow-up in IHSP patients. [ABSTRACT FROM AUTHOR]

In 2005, soybean plants with severe mosaic and leaf rugose symptoms were found in Japan. The plants contained flexuous and filamentous virus-like particles with a modal length of 500 nm. Double-stranded RNA analysis revealed a single major band of ~7000 bp. Reverse transcription-PCR for Potyviridae diagnosis generated a 1.5-kbp cDNA fragment, which contained a partial NIb gene, a coat protein (CP) gene, a 3′-noncoding region, and a poly(A) tract. The CP gene consisted of 248 amino acids and had less than 40% amino acid sequence identity with CPs of other member in Potyviridae. The C-terminal region of the NIb gene had ~60% amino acid sequence identity with Barley mild mosaic virus and other Bymovirus isolates. The NIb amino acid sequence contained the GDD motif, while the CP had no motifs associated with aphid transmission. Phylogenetic analyses of the amino acid sequence of the CP core region showed that this virus was independent from other potyvirus genera. In a host range test, the virus infected 10 plant species in four families. The virus was not transmitted via seeds or aphids, but soybeans became diseased when grown in virus-infested soil. The characteristics of this virus suggest that it is not related to any of the previously described soybean viruses; thus, we tentatively propose the name soybean leaf rugose mosaic virus (SLRMV). [ABSTRACT FROM AUTHOR]

The endoscopic abnormalities present in the small bowel (SB) of patients with portal hypertension (PH) are not well understood. This study sought to evaluate endoscopic findings of the SB in patients with PH by double balloon endoscopy (DBE). We evaluated the endoscopic findings of SB in 15 patients with PH and 49 controls without liver disease or PH. A total of 24 and 90 procedures were performed for PH patients and control patients, respectively, through oral and/or anal approaches. Fourteen of the 15 patients exhibited villous abnormalities, including edema (73%), atrophy (40%), and reddening (47%) of villi. Vascular lesions, such as angiodysplasia-like abnormalities (67%), dilated/proliferated vessels (93%), and varices (7%), were observed in all patients with PH. Although they were associated with ascites, these abnormalities did not correlate with any laboratory findings. None of these abnormalities was observed in controls. Definitive or suspected bleeding sources were identified in 9 of 13 patients with both PH and obscure gastrointestinal bleeding (OGIB), which was similar to the incidence in controls with OGIB. Although the frequency of postprocedure fever (>37.5°C) was higher in patients with PH in comparison to controls (29% vs. 2%, P < 0.01), endoscopic treatment under DBE was performed on 3 PH patients without serious complications. Endoscopic abnormalities of the SB may be prevalent in patients with PH. Although postprocedure fever of DBE may occur more commonly in patients with PH, DBE is useful as both a diagnostic and therapeutic tool to evaluate the SB. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine whether, a new synthesized class of benzocycloalkene derivatives (BCs), enhances apoptosis induced by hyperthermia. The combined effects of hyperthermia (44°C, 20 min) and BCs on apoptosis in human lymphoma U937 cells were investigated. Among the tested compounds (BC1 ∼ 9), the combined treatment of 10 μM BC2 or BC4 and hyperthermia showed the largest potency to induce DNA fragmentation at 6 h after hyperthermia. And enhancement of hyperthermia-induced apoptosis by BC2 or BC4 in a dose-dependent manner was observed. When the cells were treated first with BC2 or BC4 at a nontoxic concentration of 20 μM, and exposed to hyperthermia afterwards, a significant enhancement of heat-induced apoptosis was evidenced by DNA fragmentation, morphological changes and phosphatidylserine externalization. Flow cytometry revealed an increase of intracellular superoxide due to BC2 or BC4, which was further increased when hyperthermia was combined. Mitochondrial membrane potential was decreased and the activation of caspase-3 and caspase-8 was enhanced in the cells treated with the combination. The activation of Bid, but no change of Bax and Bcl-2 were observed after the combined treatment. The release of cytochrome c from mitochondria to cytosol, which was induced by hyperthermia, was enhanced by BC2 or BC4. An increase in the intracellular Ca2+ concentration [Ca2+]i, externalization of Fas, and decrease in Hsp70 were observed following the combined treatment. These results indicate that the intracellular superoxide generated by BC2 or BC4 is involved in the enhancement of apoptosis through Fas-mitochondria caspase and [Ca2+]i-dependent pathways, and a decrease in Hsp70 also contributed to the enhancement of apoptosis. [ABSTRACT FROM AUTHOR]

Leaf blast suppression in multilines was evaluated based on the number of susceptible lesions observed in a pure stand of susceptible rice cultivar Sasanishiki, and in 1 : 1 and 1 : 3 mixtures of Sasanishiki and a resistant near-isogenic line, Sasanishiki BL4 or BL7, from 1998 to 2001. The number of lesions first observed in fields in the 1 : 1 and 1 : 3 mixtures were close to theoretical numbers calculated using the number of lesions observed in the pure stands and the ratios of the susceptible Sasanishiki in the mixtures. The ratio of the number of lesions in the 1 : 1 and 1 : 3 mixtures to the number in the pure stand was 0.29 and 0.09, respectively. The relationship between these ratios and the ratios of susceptible Sasanishiki in mixtures was defined in an equation to estimate the degree of leaf blast suppression. Validation studies for the ratios of the number of lesions in the 1 : 1 and 1 : 3 mixtures to the number in the pure stand were conducted in two different locations and showed that the ratios are almost acceptable. The calculated autoinfection to alloinfection ratio was 1.3 and 1.4 in the 1 : 1 and 1 : 3 mixtures, respectively, suggesting that the calculated ratio will affect the degree of leaf blast suppression. Thus, predictors were obtained to estimate leaf blast suppression for effective blast control in multilines. [ABSTRACT FROM AUTHOR]

Background Methods. From February 1999 to September 2001, we treated 104 HCC tumors with an expandable needle with four hooks. Ninety-nine of the 104 tumors were successfully treated by single-session RFA with a single electrode insertion. We investigated the relationships between pretreatment factors (tumor size, tumor staining, tumor capsule, and tumor location) and local recurrence in these 99 tumors. Results. The mean size of the 99 tumors was 21.5 mm in diameter (range, 10 to 33 mm). The overall local recurrence rates were 9.7%, 15.4%, and 20.4%, at 1, 2, and 3 years, respectively. For small tumors (smaller than 25 mm), the local recurrence rates at 1, 2, and 3 years were 4.0%, 8.0%, and 14.6%, respectively. The local recurrence rates were 21.1% and 32.3% at 1 and 2 years, respectively, for large tumors (25 mm or larger), and at 3 years the rate was over 50% for tumors located close to the liver surface. Tumor size and tumor location relative to the liver surface were significantly associated with a higher local recurrence rate. However, other variables tested showed no significant relationship to the local recurrence rate. Conclusions. This study demonstrated that both tumor size and location relative to the liver surface influence the local efficacy of single-session RFA with a single electrode insertion. Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electrode insertion. [ABSTRACT FROM AUTHOR]

Inflammatory pseudotumor of the liver is a rare benign lesion, but exploratory laparotomy and a hepatectomy are often performed unnecessarily after various misdiagnoses, including liver abscess, hepatocellular carcinoma, metastatic liver tumor, and cholangiocarcinoma. We present a case of hepatic inflammatory pseudotumor in a 17-year-old man in whom diagnosis was confirmed by liver needle biopsy under ultrasonographic tomography (UST) guidance. He had complained of fever and right hypochondralgia 2 months after being operated for appendicitis. He was admitted to our hospital because of the persistence of these symptoms and the presence of a hepatic mass lesion detected by UST. He had hepatomegaly, with tenderness; leukocytosis and elevated erythrocyte sedimentation rate and C-reactive protein level were noted. UST showed a hypoechoic mass in the liver and pre-contrast computerized tomography (CT) revealed a low-density area with an ill defined margin, which was barely enhanced by the contrast medium. On the basis of the patient's clinical symptoms and the laboratory data and imaging studies, the presence of a liver abscess was suspected and antibiotics were administered. One month after the initiation of the antibiotic therapy, UST demonstrated that the portal vein had dilated serpiginously and penetrated into the mass. As the heterogeneous appearance displayed by post-enhanced CT indicated the need for a differential diagnosis of the hepatic mass lesion to rule out hepatocellular carcinoma, percutaneous needle biopsy was performed, under UST guidance. Histopathological examination demonstrated marked infiltration of plasma cells and fibrosis, findings which were consistent with those of hepatic inflammatory pseudotumor. There was a spontaneous reduction of the hepatic pseudotumor without continuous antibiotics and this reduction was documented on follow-up UST and CT. [ABSTRACT FROM AUTHOR]

An asymptomatic 49-year-old woman with a diffuse abnormal shadow detected on a routine chest rentogenogram was referred for evaluation. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) revealed space-occupying lesions in the liver and spleen. Lymphadenop athy was observed in the mediastinum and abdomen on CT, and multiple lesions of low signal intensity were observed in the spine on MRI. Furthermore, the presence of multiple tumorous nodules in the liver suggesting metastatic hepatic cancer was demonstrated on laparoscopy. Biopsy of the liver tumors revealed sarcoidosis; transbronchial biopsy specimens showed identical histological features. After administration of prednisolone for one month, the space-occupying lesions in the liver, spleen and spine improved. This case of sarcoidosis exhibited hepatic tumorous nodules and space-occupying lesions in the spleen and the spine which mimicked the presence of metastatic hepatic cancer. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor, on causes of acute hepatic failure.

A new device for chain cystography is described, which was developed to enable an easier and more comfortable insertion of the chain. The device consists of a Teflon tube containing a fine chain, a Y-shaped connecter, and a tube for the injection of contrast medium. Repeat catheterization for instilling contrast medium can be avoided, because the chain is pushed into the bladder by forcing the flow of the contrast medium simultaneously. The procedure is simple, and the chain is painlessly placed in the urethra without failure. To date, no difficulties have been encountered. [ABSTRACT FROM AUTHOR]