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Recently, the use of brackish diatoms has been proposed to remove various inorganic constituents, such as dissolved silica, nutrients, calcium, and bicarbonate, to enhance the freshwater recovery in reverse osmosis (RO). In this study, nine strains of brackish diatoms isolated from water and sediment samples from several evaporation ponds in California and Arizona were examined for their ability to assimilate silica and remove other constituents from RO concentrate. In addition to two previously reported strains, namely Gedaniella flavovirens PEWL001 and Nitzschia communis PEWL002, several new isolates including Halamphora sydowii PEWL004, Nitzschia sp. PEWL008, and Halamphora sp. PEWL011 were found to remove more than 95% of silica, 95% of ammonia and orthophosphate, and more than 50% of calcium and carbonate within 6 days. Two additional G. flavovirens strains (Psetr3 and Psetr7) collected from a brackish lake in Aomori, Japan, also showed rapid dissolved silica uptake (32 mg L−1 day−1) comparable to the one isolated from an agricultural drainage water evaporation pond in the Central Valley, California. This study demonstrated that the brackish diatoms isolated from the evaporation ponds could be useful for the treatment of RO concentrate, which would possibly enable more sustainable desalination processes.

Robotic gastrectomy (RG) is a good alternative to laparoscopic gastrectomy, as it improves treatment outcomes and reduces the burden of technical difficulties; however, prolonged operative time may be a disadvantage. This study aimed to identify measures to shorten the operative time during the initial introduction of RG at an institution.We assessed 33 patients with gastric cancer who underwent radical distal gastrectomy with Billroth-I reconstruction and divided them into three groups: laparoscopic distal gastrectomy (LDG), robotic distal gastrectomy in the early phase (RDG-E), and in the late phase (RDG-L). Operative time, six technical steps, and junk time, including the roll-in/roll-out, docking/undocking, and instrument exchange times, were compared among the groups.The median (range) overall operative times of LDG, RDG-E, and RDG-L were 248 (179-323), 304 (249-383), and 263 (220-367) min, respectively, but no significant differences were observed. For each surgical step of RG, RDG-L in suprapancreatic lymph node dissection was significantly shorter than that in RDG-E. The median (range) junk times of LDG, RDG-E, and RDG-L were 16.7 (12.7-26.4), 48.3 (38.6-67.7), and 42.0 (35.4-49.2) min, respectively. Junk time was significantly longer in RDG-L than in LDG (p = 0.003), but not significant between RDG-E and RDG-L. The learning curve effect of overall, console, and junk times were achieved in four cases of RDG.Junk time is a major factor in prolonging RDG operative time. However, to reduce the time after initial introduction, measures to promote robot-specific standardization and more effective use of robotic instruments are essential.

Liposarcoma is one of the most common types of soft tissue sarcomas and can develop at any site, although omental liposarcoma is extremely rare. Omental liposarcoma has a poor prognosis because the diagnosis is difficult, until it presents as a large tumor causing severe noticeable clinical symptoms. A 51-year-old male with lower abdominal pain was referred to our clinic. Abdominal ultrasonography revealed an ill-defined, solid, heterogeneous, and hypoechoic tumor deep in the lower abdomen. Generally, liposarcomas are hyperechoic, though 20% of liposarcomas present as hypoechoic tumors. This variation might occur depending on the pathological classification. We should consider the possibility of a dedifferentiated component if ultrasonography reveals typical features of soft tissue sarcoma with hypoechoic lesion.

535 Background: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. Tumor shrinkage is achieved, and cancer- and treatment-free status is possible in many cases using curative conversion with resection, ablation, or selective transarterial chemoembolization (TACE). This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter study was conducted to clarify the value of curative conversion in intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. Cancer-free rate, treatment-free rate, time to cancer-free status, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, recurrence-free survival (RFS), and overall survival (OS) were assessed in patients who achieved cancer-free status using resection, ablation, selective TACE, or atezolizumab plus bevacizumab alone. Results: Cancer-free status was achieved in 38 patients (35%) (median observation period: 17. 7 months). The modalities of curative conversion were as follows: resection, 7; ablation (including patients who underwent ablation after TACE), 13; and selective TACE (including lenvatinib-TACE sequential therapy), 15. Three patients achieved cancer-free status with only atezolizumab plus bevacizumab therapy. Among the 38 cancer-free patients, 24 achieved treatment-free status. RF5 was 31.8 months (95% confidence interval, 30.5-33.0), and two patients experienced recurrence after reaching cancer-free status. Regarding OS, there were no deaths in any of the groups, and excellent outcomes were obtained. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved cancer-free status, five achieved treatment-free status. Conclusions: The curative conversion rate (cancer-free rate) in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 22% of patients achieved treatment-free status. Thus, achieving cancer-free and/or treatment-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread. Clinical trial information: NCT03434379 .

Diatoms belonging to the family Epithemiaceae have endosymbiont ‘spheroid bodies’, which have received attention as a model to provide new insights into the early stages of organelle evolution. Uniparental organelle inheritance, known in a wide range of sexually reproducing eukaryotes, is considered to be one of the key characteristics acquired during the evolution of an endosymbiont into an organelle. However, there has been no information about the inheritance of spheroid bodies. The aim of the present study was, therefore, to investigate the inheritance modes of the spheroid bodies and plastids in the isogamous diatom Epithemia gibba var. ventricosa, which we established to be heterothallic. We induced sexual reproduction of E. gibba var. ventricosa in culture, using sexually compatible mating strains that differed with respect to nucleotide polymorphisms in the spheroid body and the plastid genomes. The F1 strains were genotyped to reveal the parental origin of the spheroid bodies and plastids using parent-specific polymorphisms. The results suggested that inheritance of the spheroid bodies was uniparental (i.e. progeny have the spheroid body genome from either parent but not both) and random (i.e. with an unbiased ratio of parental origins), while that of the plastids was more complex, being predominantly uniparental but with a few biparental cases. This study is the first to report the inheritance pattern of the spheroid body and will contribute to better understand the evolutionary state of this organelle. info:eu-repo/semantics/acceptedVersion

A 39-year-old woman visited our hospital with complaints of nausea, vomiting, and lower abdominal pain for 2 weeks. Abdominal CT revealed thickening of the transverse colonic wall, dilated bowel, and a metastatic ischemic tumor in the liver (S7). We diagnosed her with obstructive colon cancer, clinical Stage Ⅳa(T, type 2, cT3, N0, M1a[liver]). At first, we placed a self-expanding metallic stent(SEMS)to decompress bowel obstructions. We planned a surgical resection of the primary tumor followed by partial resection of the liver. We performed a laparoscopic right hemicolectomy(D3)24 days after the stenting. Pathologically, we diagnosed her with BRAF-mutated colon cancer, pStage Ⅳa(pT4a, N1b[2/43], M1a[liver]). On completion of 4 courses of mFOLFOXIRI and bevacizumab, we confirmed a reduction of the S7 tumor but found a new tumor in S6. Since the tumors were potentially resectable, we performed partial liver resection(S6, S7)1 month later. A month following the hepatectomy, CT revealed a new tumor in S4. The patient has been receiving general chemotherapy (CapeOX and bevacizumab)without disease progression for 6 months. We experienced a challenging case of BRAF- mutated obstructive colon cancer with liver metastases.

We report 2 cases of neuroendocrine carcinoma(NEC)of colon and rectum with distant metastasis. The treatment of NEC with distant metastasis is based on the treatment of small cell lung cancer, but that is controversial because NEC is relatively rare. Case 1: A 75-year-old man who was admitted for anal pain. Physical examination showed the anal tumor and swelling inguinal lymph nodes. CT showed rectum tumor and multiple lymph node metastases to the pelvis and inguinal region. Colonoscopy showed a Type 3 tumor in the rectum. He was diagnosed with NEC based on biopsy and immunostaining. Colostomy was performed for pain relief and etoposide/cisplatin(EP)therapy was introduced. After 6 courses of the chemotherapy, CT showed progression of the tumor, then we made the shift to palliative treatment. Case 2: A 69-year-old man who was admitted for abdominal pain and back pain. CT showed transverse colon tumor with multiple metastases to the liver, lung, and lymph nodes. Colonoscopy showed a circumferential tumor in the transverse colon. He was diagnosed with NEC based on biopsy and immunostaining. He refused chemotherapy and died 2 months later.

A woman in her mid-50's presented to our hospital with jaundice, fatigue, and fever. Jaundice, elevated tumor markers, and lower bile duct stricture suggested malignancy, for which subtotal stomach-preserving pancreaticoduodenectomy was performed. The patient also had annular pancreas as the second part of the duodenum was surrounded by pancreatic parenchyma. The histopathological diagnosis was adenosquamous carcinoma of the duodenal papilla associated with annular pancreas. Adjuvant chemotherapy with TS-1 was administered for 1 year. Although para-aortic lymph node metastasis was detected radiographically 3 years 9 months after surgery, the recurrence remains under control and she is alive at 5 years 9 months after surgery due to multidisciplinary therapy.

We report a case of advanced gastric cancer with right gastroepiploic vein tumor thrombus treated using preoperative S-1 plus cisplatin(CDDP)in which pathological complete response was achieved. A 78-year-old man was diagnosed with type 2 gastric cancer located at the greater curvature of the antrum, accompanied by right gastroepiploic vein tumor thrombus. Four courses of S-1 plus CDDP were administered as neoadjuvant chemotherapy. After 2 courses, computed tomography(CT) revealed the disappearance of the tumor in the right gastroepiploic vein thrombus. Distal gastrectomy with D2 lymphadenec- tomy was performed, and the diagnosis was pathological complete response(CR). Eight courses of S-1(100mg/day on days 1-28, followed by 2 weeks of rest)were administered as adjuvant chemotherapy. During the 1-year postoperative follow up, the patient showed no recurrence. An S-1 plus CDDP regimen can be a useful preoperative chemotherapy option for advanced gastric cancer with tumor vein thrombus.

Noble metal nanoparticles always show bond length contraction with the decrease in particle size. PVP-protected small Pd metal nanoparticles (MNPs) were reported to have the unique characteristic o...

Spur cell anemia is an acquired hemolytic anemia associated with liver cirrhosis and is characterized by the presence of increased large red blood cells, which are covered with spike-like projections that vary in width, length, and distribution. A 26-year-old man was referred to our hospital presenting with jaundice, lower limb edema, and dyspnea. The patient was subsequently diagnosed with spur cell anemia related to alcoholic liver cirrhosis. Spur cell anemia is an independent predictor of mortality in liver cirrhosis and has been associated with extremely poor prognosis. The most effective treatment for spur cell anemia is liver transplantation. As seen in the literature, the treatment of spur cell anemia without liver transplantation is quite challenging. This report highlights the importance of management and treatment strategies, including control of fluid retention, blood transfusion, plasma diafiltration, and administration of diuretics. Our treatment strategies might be useful in patients who are not candidate of liver transplantation or patients waiting for liver transplantation.

We experienced a successful case in which the patient was treated with a combination of operation and transcatheter arterial chemoembolization for a hypervascular tumor of unknown primary origin in the liver; we report this case with a literature review. A 76-year-old man noticed an upper abdominal tumor and he visited our department for detailed examination. Enhanced CT scan showed multiple hypervascular tumors scattered across both lobes of the liver, and the pattern of contrast effect implied that the tumors were primary neuroendocrine tumors or endocrine metastases. Gastroscopy and colonoscopy showed no tumor in the intestine. TACE was performed mainly for the tumors in the right lobe. One month later, we performed left lateral segmentectomy and partial hepatectomy for segment 6. Histopathological findings showed that the tumors in the left lateral segment had neuroendocrine properties, and the tumor in segment 6 was necrosed. One year has passed since the surgery without recurrence of neuroendocrine tumors in the liver or other organs.

A 62-year-old man presented with complaints of acute abdominal pain. Abdominal enhanced CT showed free air in the abdominal cavity, a thickened stomach wall accompanied by deep ulcer, and enlarged lymph nodes around the stomach. Emergent surgery was conducted, and a perforation in the upper part of the stomach was found. Total gastrectomy was performed. On pathological examination, a mucosa-associated lymphoid tissue lymphoma was diagnosed. Histologic examination revealed the absence of Helicobacter pylori in the gastric mucosa. After the operation, adjuvant chemotherapy was not administered. However, he has been well for 11 months without any recurrence. Gastric MALT lymphoma with spontaneous perforation is considered extremely rare. A brief review of the literature is presented.

We report 2 successful cases treated with trans-catheter arterial embolization(TAE)for hemorrhagic shock due to pseudoaneurysm rupture at the primary tumor site in advanced colorectal cancer. Case 1: A 73-year-old female underwent Hartmann surgery at another hospital for rectal perforation and peritonitis. Six months later, she had a massive bloody stool and was transferred to our hospital. She was diagnosed with bleeding from advanced rectal cancer that remained following the first surgery. Contrast computed tomography(CT)showed that a branch of the superior rectal artery(SRA)developed an aneurysm at the primary tumor site, and TAE was performed to stop bleeding on hospital day 3. Case 2: A 79-year-old male with type 2 sigmoid colon cancer and simultaneous multiple liver metastases developed copious blood in the stool before primary tumor resection and was transferred to our hospital. Contrast CT showed that a branch of the SRA developed an aneurysm at the primary tumor site, and TAE was immediately performed to stop bleeding.

We report a case of colon cancer with simultaneous liver metastases successfully treated with multidisciplinary therapy including two-stage hepatectomy. This is a case of a 72-year-old woman diagnosed with type 1 cecal cancer with 2 simulta- neous liver metastases(S4/8: 98mm, S3: 63mm). At first, laparoscopic resection of the primary site was performed to prevent colon ileus. Liver metastases rapidly grew and became unresectable; fortunately, 11 courses of mFOLFOX6 and bevacizu- mab were effective and liver metastases shrunk(S4/8: 85mm, S3: 67mm). At last, two-stage hepatectomy was performed as conversion surgery, and the patient survived without recurrence for more than 2 years.

A 60-year-old male undergoing pelvic evisceration with D3 lymph node dissection for pR0 in 2006f or carcinoma of the rectum was diagnosed pathologically with moderately differentiated adenocarcinoma, fStage ⅡA(UICC pT3, pN0, M0). Follow-up CT revealed hypovascular liver tumors with intrahepatic bile duct dilation in the right lobe 8 years after the pelvic evisceration. We conducted right lobe hepatectomy. The resected specimens showed that the tumor extended predominantly along the right intrahepatic bile duct. Histological findings and an immunohistochemical examination of CK7, CK20, and CDX2 revealed metastasis of the rectum cancer. We finally diagnosed him with intrahepatic bile duct metastasis from rectal adenocarcinoma.

This work develops a novel method for preparing a moth eye structure, which has a sub-wavelength periodical Si nanocone structure on Si (100) substrate, using two-step metal assisted chemical etching (MACE). The 1st and 2nd MACE were respectively performed with the intention to form perpendicular Si nanowire arrays on a Si substrate and sharpening the Si nanowire arrays. We found the inhomogeneous absorption and aggregation of Au particles used as a catalyst for 2nd MACE was important to obtain the nanocone shape. The obtained Si nanocone arrays showed superior anti-reflecting properties especially in wavelength below 600 nm compared to the Si nanowire arrays. A possible mechanism involved in the formation of the nanocone structure by the 2-step MACE is discussed in this paper., This work was supported by KAKENHI Grant Numbers 25790024, 25600048 and 15K04602 from the Japan Society for the Promotion of Science (JSPS), Strategic Project to Support the Formation of Research Bases at Private Universities: Matching Fund Subsidy from the Ministry of Education, Culture, Sports, Science and Technology(MEXT), and Kansai University Subsidy for supporting Young Scholars 2013.

Bowel endometriosis is a condition caused by endometrial glands and stroma infiltrating the bowel wall and reaching the subserous fat tissue or the adjacent subserous plexus. A 42-year-old woman with changes in stool habits, nausea, and stomach aches experienced complete obstruction in the rectum. Endoscopic ultrasound demonstrated a low echoic lesion outside the rectal mucosa and endoscopic ultrasound-guided fine needle aspiration confirmed the diagnosis of bowel endometriosis. The clinical characteristics of bowel endometriosis are unspecific and this condition is sometimes misdiagnosed as a malignant tumor, irritable bowel syndrome, or any other colorectal disorder. Our aim is to show that endoscopic ultrasound-guided fine needle aspiration might be helpful for bowel endometriosis diagnosis and exclusion of other malignant disease.

Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.

We report a rare case of a extrarenal retroperitoneal angiomyolipoma. A 64-year-old female visited our hospital because of an abdominal mass in her lower right abdomen. Enhanced CT scan revealed a 67×52mm tumor in lower right retroperitoneal space. MRI revealed adipose component in the tumor on T1 weighted images and T2 weighted images. Our preoperative diagnosis was retroperitoneal liposarcoma, and we performed retroperitoneal tumor resection. At operation the tumor was on the fossa iliaca, which was covered with capsule. It did not invade surrounding tissues. The resected tumor measured 90× 60×45 mm, and tiny hemorrhage was seen in the tumor. Histopathological findings showed that the tumor was composed of a mixture of adipose tissue, vessels, and smooth muscle. Immunohistochemistry demonstrated the tumor was stained with asmooth muscle actin(aSMA). We diagnosed the tumor as extrarenal retroperitoneal angiomyolipoma.

We investigated the stability and adsorption properties of a Pd nanoparticles which are used for catalyst of electroless plating on dielectrics substrate. Some additives for Pd nanoparticle dispersion significantly improved the stability of the dispersion without deteriorating the adsorption of the Pd nanoparticles. Furthermore, the additives redispersed agglomerated Pd nanoparticles. These results suggest a method for applying Pd nanoparticles in manufacturing processes.

Effective therapeutic combinations targeting the oncogenic pathway still are unknown in human hepatocellular carcinoma (HCC). The authors previously identified aberrant expression of aurora B kinase as the independent predictor for the lethal recurrence of HCC, showing that AZD1152 induced in vitro and in vivo apoptosis with polyploidy in human HCC cells. In this preclinical study, the combined effects of molecular-targeted therapies were evaluated based on the cellular response of aurora B inhibition. This study analyzed the expression of Bcl-2 family proteins in polyploidization induced by AZD1152 and the in vitro synergistic effects of AZD1152 with control of the Bcl-2 family pathway in human HCC cells. The in vivo effects of the combination therapy targeting the specific molecules were evaluated using subcutaneous tumor xenograft models. The findings showed that Bcl-xL was specifically overexpressed in AZD1152-induced polyploid HCC cells. The combination of AZD1152 followed by Bcl-xL/2 inhibitor ABT263 induced synergistically cellular apoptosis (p

We report a case where resection was performed for pancreatic metastasis from renal cell carcinoma 21 years after nephrectomy. A 72-year-old man had undergone total gastrectomy with distal pancreatomy and splenectomy for gastric cancer, and right nephrectomy for primary renal cell carcinoma in 1993. Incidentally, a CT scan performed in 2014 revealed a tumor in the head of the pancreas. Enhanced MRI suggested that the tumor contained some fat tissue. The tumor in the pancreatic body had sharp margins; therefore, we performed subtotal pancreatectomy. The tumor was considered pancreatic metastasis from renal cell carcinoma. Pathological findings indicated clear-cell type carcinoma(G1-G2), which is very similar to renal cell carcinoma. We diagnosed pancreatic metastasis from renal cell carcinoma. The patient has remained well, with no recurrence 20 months after the pancreatectomy.

Summary In order to obtain insights into the evolution of colorless (apochlorotic) diatoms, we investigated newly established apochlorotic strains of Nitzschia spp. using light and electron microscopy and molecular phylogenetic analyses. Fluorescence microscopic observations demonstrated that the apochlorotic diatoms lack chlorophylls. Transmission electron microscopy of two apochlorotic strains also demonstrated that their plastids lacked thylakoids; instead, having four-membrane-bound organelles without thylakoids, similar to nonphotosynthetic plastid remnants. From the apochlorotic strains, we also found plastid small subunit rRNA genes that were unusually long branched in phylogenetic analyses, as observed in other nonphotosynthetic plastids. Molecular phylogenetic analysis of the nucleus-encoded large subunit rRNA genes showed eight distinct lineages for apochlorotic diatoms. The eight apochlorotic lineages were not monophyletic, suggesting that the loss of photosynthesis took place multiple times independently within Nitzschia. Several diatoms, including Nitzschia spp., are mixotrophic, which is an expected mode of nutrition that would help explain the evolutionary switch from a photosynthetic lifestyle to a heterotrophic lifestyle.

Age-related differences of clinicopathologic features, outcomes, and molecular properties of hepatocellular carcinoma remain unclarified.We classified patients who underwent hepatectomy for hepatocellular carcinoma into 3 groups by age bracket; younger group (50 years), middle-aged group (50 to 79 years), and elderly group (≥80 years) and compared age-related features.Hepatitis viral infection was dominant in the younger group (hepatitis B virus [HBV]; 67%) and middle-aged group (hepatitis C virus [HCV]; 56%), whereas the elderly group showed a significantly higher rate without hepatitis virus infection (absence of HBV and HCV infection, 66%; P = .0001). There was a significantly greater proportion of age-associated pre-existing comorbidity in the elderly group (89%; P = .0004). Liver cirrhosis in the elderly group (24%) was significantly lower than other groups (younger, 67%; middle-aged, 50%; P = .0058). There was no significant difference in perioperative and postoperative outcomes among these groups. Microarray analysis revealed age-related upregulation of androgen and phosphatidylinositol 3-kinase pathways in the tumor tissue and downregulation of the fibrosis-related pathways in the noncancerous liver tissue.Based on increased correlation with the absence of HBV and HCV infection and pre-existing comorbidity, the age-related carcinogenic pathways might play a critical role in elderly hepatocarcinogenesis.

Background In patients with solitary hepatocellular carcinoma ≤5 cm without macrovascular invasion, it is unknown whether the initial anatomic resection improves the long-term survival. Methods Among 545 initial hepatectomies for hepatocellular carcinoma between 2000 and 2012, the 233 patients with the aforementioned criteria of hepatocellular carcinoma were enrolled. Results The mean observation time was 1,125 days. Disease-free 5-year survival rates with and without anatomic resection were 46% and 23%, respectively ( P = .009). Multivariate analyses for disease-free survival rates revealed the risk factors to be α-fetoprotein (odds ratio, 1.6; P = .028) and anatomic resection (odds ratio, .7; P = .048), while increased Child-Pugh score (>5) was the only independent risk factor for overall survival (odds ratio, 1.8; P = .043). The 5-year overall survival rates with and without Child-Pugh score 5 were 74% and 40%, respectively ( P Conclusions Initial anatomic resection for small solitary hepatocellular carcinoma without macrovascular invasion improved disease-free survival rates remarkably.

Gene panels covering hundreds of mutation hotspots for detection of cell-free DNA (cfDNA) have been developed for the establishment of clinically practical circulating tumor (ctDNA) detection system. Although amplicon-based or capture-based genomic profiling of genes commonly mutated in cancer using next-generation sequencing (NGS) system have been developed, they are not sufficiently sensitive nor accurate to be used for clinical diagnosis in hospital. As a result of preliminary study using 87 advanced pancreatic cancer (stage lll/lV), we observed that one or more KRAS mutation(s) could be detected in 60.9% of patients with advanced pancreatic cancer by using the amplicon-based deep sequencing system. To develop more sensitive and accurate ctDNA detection system, we optimized conditions of our DNA chip system. We firstly used 100 synthetic DNA samples, whose KRAS mutant allele frequencies were from 0.1% to 10.0%, and investigated the quantitativity of our DNA chip system. We amplified target regions by PCR to obtain 2,000 copies of synthesized DNA. The PCR product was hybridized with the probe on the DNA chip. The fluorescence ratio (mutant allele fluorescence intensity / total fluorescence intensity) of 100 synthetic DNA samples were clearly distinguished to that of negative control by using the DNA chip system. We defined an appropriate cut-off values of small quantities (0.1%) of mutations. Furthermore, to confirm the accuracy and reliability of this method, we verified our DNA chip system using 15 plasma cfDNA samples from patients with mutant KRAS (0.1~10.0%) and 15 samples from patients without mutant KRAS as negative control. 10 ng of ctDNA which extracted from blood sample is used in PCR. We observed that detected mutant status by DNA chip was completely concordant (100%) with those by amplicon-based deep sequencing system. Our data confirmed that mutant allele in cfDNA can be sensitively and accurately detected by DNA chip system. These results suggest that the ctDNA detection system developed in this study could be a novel diagnostic tool for tumor burden, and could realize the ultra-early detection of refractory tumors including pancreatic cancer. Citation Format: Noriaki Nakamura, Hiroshi Okamura, Hirofumi Yamano, Hiromichi Ito, Hitoshi Zembutsu. The development of novel detection system for circulating tumor DNA using DNA chip system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2420.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies and the identification of new effective therapies for HCC is urgently needed. We have previously identified EpCAM, one of the hepatic stem/progenitor markers, as a prognostic predictor of patients who received curative hepatectomy for HCC. In this preclinical study, the effects of VB4-845, an immunotoxin targeting EpCAM, were evaluated in HCC.In vitro effects of VB4-845 on human HCC cells, the cytotoxic activity, sphere-forming ability, and expression of hepatic stem/progenitor markers were analyzed. In vivo effects of VB4-845 were evaluated using subcutaneous and orthotopic liver xenograft models.In all HCC cell lines expressing EpCAM, VB4-845 showed potent cytotoxicity and was significantly effective in combination with 5-FU (p0.05). Although 5-FU did not affect the sphere-forming ability and increased the populations expressing other stem/progenitor markers CD133 and CD13 (p0.05), VB4-845 strongly suppressed the sphere-formation and decreased the population expressing CD133 and CD13 (p0.0005,0.01, respectively). In subcutaneous xenograft models, the combination of VB4-845 plus 5-FU showed significant regression of tumors compared with the control (p = 0.016). Moreover, in orthotopic liver xenograft models, the combination therapy dramatically decreased the tumor volume compared with the control (p = 0.0011).Our preclinical investigation suggests that EpCAM-targeted therapy may offer a promising and novel approach for the treatment of HCC with a poorer prognosis.

Pd nanoparticles exhibit the abnormal behavior of the Pd lattice expanding as the size of the Pd nanoparticles decreases. We measured extended X-ray absorption fine structure of poly(N-vinyl-2-pyrr...

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies because of recurrence and/or metastasis even after curative resection. Emerging evidence suggests that tumor metastasis and recurrence might be driven by a small subpopulation of stemness cells, so-called cancer stem cells (CSCs). Previous investigations have revealed that glioma and breast CSCs exhibit intrinsically low proteasome activity and that breast CSCs also reportedly contain a lower reactive oxygen species (ROS) level than corresponding nontumorigenic cells. Here we visualized two stem cell features, low proteasome activity and low intracellular ROS, in HCC cells using two-color fluorescence activated cell sorting to isolate cells with stem cell features. These cells were then analyzed for their division behavior in normoxia and hypoxia, expression of stem cell markers, tumorigenicity, metastatic potential, specific gene expression signatures, and their clinical implications. A visualized small subpopulation of HCC cells demonstrated asymmetric divisions. Their remarkable tumorigenicity in nonobese diabetic/severe combined immunodeficient mice suggested the cancer initiation potential of these HCC CSCs. Comprehensive gene expression analysis revealed that chemokine-related genes were up-regulated in the CSCs subpopulation. Our identified HCC CSCs facilitated the migration of macrophages in vitro and demonstrated metastatic potential by way of recruitment of macrophages in vivo. In patients who undergo curative operation for HCC, the CSC-specific gene signature in the liver microenvironment significantly correlates with recurrence. Conclusion: Based on these findings, the stem cell feature monitoring system proposed here is a promising tool to analyze the in vivo significance of CSC microenvironments in human HCCs. (HEPATOLOGY 2013;)

Recurrence determines the postoperative prognosis with hepatocellular carcinoma (HCC). It is unknown how the liver dysfunction involving organic anion transporter failure causes the occurrence of HCCs. This study was designed to elucidate the link between liver dysfunction and multicentric occurrence (MO) after radical hepatectomy.Forty-nine samples of noncancerous liver tissue from HCC patients within the Milan criteria who were treated at our institution between January 2004 and August 2008 were examined as a training set by using genome-wide gene expression analysis. Using the independent 2-institutional cohort of 134 patients between September 2008 and December 2009, we performed a validation study using tissue microarray analysis. Cox proportional hazard regression analyses for MFS were performed to estimate the risk factors.In the Gene Ontology database (GO:0015711), SLC22A7 expression was the best predictor of MO-free survival [MFS] (Fold, 0.726; P = 0.001). High SLC22A7 gene expression prevented the occurrence of HCC after hepatectomy (odds ratio [OR], 0.2; P = 0.004). Multivariate analyses identified SLC22A7 expression as an independent risk factor (OR, 0.3; P = 0.043). In the validation study, multivariate analyses of MFS identified SLC22A7 expression as an independent risk factor (OR, 0.5; P = 0.012). As judged by gene set enrichment analysis, SLC22A7 down regulation was associated with mitochondrion (P = 0.008) and oxidoreductase activity (P = 0.006). Sirtuin 3 as a regulator of mitochondrial metabolism also determined MFS (P = 0.018).The mitochondrial pathways may affect SLC 22A7 function to promote the occurrence of HCC. (Word count: 246).

Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and gene expression analyses were performed according to CEIOUS vasculature patterns. CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and tumor-node-metastasis stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival (P = 0.0193) and overall survival (P = 0.0362) compared with patients who had reticular HCC. Gene expression analysis revealed that a rereplication inhibitor geminin was significantly overexpressed in thunderbolt HCCs (P = 0.00326). In vitro knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed overexpression of geminin protein in thunderbolt HCC (P < 0.0001). Multivariate analysis revealed geminin expression to be an independent factor in predicting poor survival in HCC patients (P = 0.0170). Conclusion: CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with cellular proliferation of HCC and were significantly related to HCC progression and poor prognosis. These findings might be clinically useful as a determinant factor in the postoperative treatment of HCC. (HEPATOLOGY 2013)

We report a case of multiple brain metastases from pancreatic cancer, which had responded remarkably to FOLFIRINOX. A 47-year-old man had hypovascular tumors, 25 mm on the body and 23 mm on the uncus of the pancreas; multiple liver metastases; and skin metastasis. A diagnosis of unresectable pancreatic cancer, cT4N3M1 (HEP, LYM, PUL, SKI), cStage Ⅳb was made. We chose FOLFIRINOX for treatment because of his young age and good performance status. After 6 courses, he showed decreasing tumor marker levels, an almost complete disappearance of the primary lesion, and reduced liver metastases. After 8 courses, abnormal behaviors were noted and we performed a head contrast-enhanced MRI, which revealed diffuse enhancement of the cerebral and cerebellar hemisphere. Multiple brain metastases from pancreatic cancer were diagnosed. We made the shift to palliative treatment, but his general condition was worsening and he died a month later, 7 months after the first diagnosis.

Postoperative early recurrence is a crucial issue in the treatment of hepatocellular carcinoma (HCC) patients. Some early recurrences seem to occur from minute tumors which were overlooked during both preoperative and intraoperative investigations. Therefore, it is urgently necessary to increase detectability of minute HCCs during operation. If they could be detected and resected during surgery, the prognosis should be improved. The purpose of this study is to investigate the usefulness of contrast-enhanced intraoperative ultrasound (CEIOUS) for the diagnosis and treatment of HCC. Institutional ethics committee approval and informed consent were obtained. Fifty-two patients (mean age 65 years; 38 males and 14 females) who underwent liver resection with either preoperative computed tomography during angiography (CTA) or CEIOUS with Sonazoid (perflubutane microbubble contrast agent) were studied. We determined the presence of HCC on the basis of the histopathological findings of resected specimens. The sensitivity of CEIOUS [97.6% (95% CI 91.8–99.4)] was higher than that of CTA [89.4% (95% CI 81.1–94.3)]. The positive predictive values of CEIOUS [91.2% (95% CI 83.6–95.5) and CTA [91.6% (95% CI 83.6–95.9)] were similar. Eight new HCCs from 7 patients, which accounted for 9.4% (8/85) of the total HCCs, were correctly detected and diagnosed by CEIOUS, and we performed an additional partial hepatectomy in 3 of these 7 patients. CEIOUS with Sonazoid provided increased sensitivity of detection of small HCCs compared with preoperative CTA, thereby leading to a more appropriate surgical procedure and contributing to complete tumor removal.