Clinical impact of C-reactive protein to albumin ratio of the 7th postoperative day on prognosis after laparoscopic colorectal cancer surgery.

PURPOSE: C-reactive protein to albumin ratio (CAR) has been utilized as a prognostic factor in various carcinomas. We investigated the relationship between preoperative, postoperative day (POD) 1, and POD 7 CARs and the prognosis of patients with colorectal cancer (CRC). METHODS: Three hundred twenty patients with CRC who underwent laparoscopic radical resection between May 2011 and December 2016 were enrolled. Patients were selected into 2 groups, high CAR and low CAR (n=72/group), based on preoperative, POD 1, and POD 7 CARs. The relapse-free survival (RFS) and overall survival (OS) were compared between groups using propensity score matching. RESULTS: The high CAR group had a significantly worse RFS (P<0.001) and OS (P=0.002) at POD 7 than those in the low CAR group. However, in preoperative and POD 1 analysis, no differences were observed. CONCLUSION: In patients with CRC, CAR of POD 7 was a significant prognostic factor.

Laparoscopic abdominal perineal rectal resection for rectal cancer with a horseshoe kidney using preoperative 3D-CT angiography: a case report.

BACKGROUND: A horseshoe kidney is a congenital malformation involving the fusion of the bilateral kidneys and is often accompanied by anomalies of the ureteropelvic and vascular systems. When performing resection of colorectal cancer in a patient with horseshoe kidney, damage to the ureter or excessive renal arteries should be avoided. To achieve this purpose, comprehensive preoperative anatomical assessments and surgical planning are important. Here, we report a case of a laparoscopic abdominal perineal rectal resection for lower rectal cancer with a horseshoe kidney. CASE PRESENTATION: A 79-year-old woman presented with bloody stool and was diagnosed with advanced lower rectal cancer, immediately above the rectal dentate line, without metastasis. A preoperative computed tomography (CT) scan revealed a horseshoe kidney, while a three-dimensional CT (3D-CT) angiography revealed aberrant excess renal artery from the aorta to the renal isthmus. The left ureter ran in front of the isthmus of the horseshoe kidney and presented calculus formation. Laparoscopic abdominal perineal rectal resection was performed with D3 lymph node dissection. During the operation, we mobilized the sigmoid colon mesentery via a medial approach and preserved the left ureter, the left gonadal vessels, and the hypogastric nerve plexus in the retroperitoneum in front of the horseshoe kidney. CONCLUSIONS: We report a rare case of rectal cancer surgery in a patient with a horseshoe kidney. We discuss the anatomical peculiarities of a horseshoe kidney, such as excess renal arteries, inferior vena cava, ureter, gonadal vessels, and nerves, that should be preserved according to the literature. We suggest that preoperative 3D-CT angiography is both useful for revealing the relationship between the vascular system and a horseshoe kidney and helpful when performing laparoscopic surgery for a left-sided colon and rectal cancer to avoid intraoperative injury.

MBGD update 2018: microbial genome database based on hierarchical orthology relations covering closely related and distantly related comparisons.

The Microbial Genome Database for Comparative Analysis (MBGD) is a database for comparative genomics based on comprehensive orthology analysis of bacteria, archaea and unicellular eukaryotes. MBGD now contains 6318 genomes. To utilize the database for both closely related and distantly related genomes, MBGD previously provided two types of ortholog tables: the standard ortholog table containing one representative genome from each genus covering the entire taxonomic range and the taxon specific ortholog tables for each taxon. However, this approach has a drawback in that the standard ortholog table contains only genes that are conserved in the representative genomes. To address this problem, we developed a stepwise procedure to construct ortholog tables hierarchically in a bottom-up manner. By using this approach, the new standard ortholog table now covers the entire gene repertoire stored in MBGD. In addition, we have enhanced several functionalities, including rapid and flexible keyword searching, profile-based sequence searching for orthology assignment to a user query sequence, and displaying a phylogenetic tree of each taxon based on the concatenated core gene sequences. For integrative database searching, the core data in MBGD are represented in Resource Description Framework (RDF) and a SPARQL interface is provided to search them. MBGD is available at http://mbgd.genome.ad.jp/.

[Diagnosis of reactive lymphoid hyperplasia of the liver and difficulty in its differentiation from a malignant tumor: a case report].

A 79-year-old woman presented with a chief complaint of abdominal pain. Imaging findings suggested hepatocellular carcinoma although the serum levels of tumor markers were within the normal range. Thus, we performed hepatectomy of S5 and components separation. Histologically, the tumor was diagnosed as reactive lymphoid hyperplasia of the liver. In reactive lymphoid hyperplasia of the liver, a preoperative diagnosis of a malignant tumor was made followed by a definitive diagnosis after resection. Hence, it is imperative to consider reactive lymphoid hyperplasia as a type of liver tumor that is distinct from hepatocellular carcinoma.

A left thoracic approach in a prone position for thoracoscopic thoracic duct ligation in a patient with post-esophagectomy chylothorax: A case report.

INTRODUCTION: We debate whether or not to approach from right thorax for the left chylothorax after esophagectomy. PRESENTATION OF CASE: A 50s-year-old female underwent right-sided thoracoscopic esophagectomy with three-field lymphadenectomy for esophageal carcinoma (type 0-IIa, 3.4×2.2cm, T1bN0M0, Stage IA), followed by reconstruction with esophagogastric anastomosis through the posterior mediastinum. The thoracic duct was excised and ligated. The left thoracic drainage increased to 2115mL/day on the fifth postoperative day. Thoracic duct injury was diagnosed, and surgery was performed on sixth postoperative day. With the patient in a prone position, the thoracic duct was ligated successfully under thoracoscopy in the left thorax. The leakage point was found in the crushed duct by 8.8-mm titanium clips. Then, we performed mass ligation of the thoracic duct with 11-mm titanium clips below the leakage point after careful dissection. The surgery took 58min, with an estimated total blood loss of 0g. DISCUSSION: Although thoracic duct is anatomically located on the right side of the descending aorta, we employed a left-sided thoracoscopic approach due to the chylous leakage in the left thorax. With the patient in the prone position, surgeons can easily convert from a left thoracic approach to a right thoracic approach immediately without postural change if the thoracic duct cannot be found in the left thoracic cavity. CONCLUSION: This technique is useful and should be considered for patients with left chylothorax.

Detection of plant viruses in natural environments by using RNA-Seq.

Sequencing of RNA by next generation sequencers, RNA-Seq, is revolutionizing virus detection. In addition to the unbiased detection of various viruses from wild plants in natural environments, RNA-Seq also allows for the parallel collection of host plant transcriptome data. Host transcriptome data are highly valuable for studying the responses of hosts to viral infections, as well as viral host manipulation. When detecting viruses using RNA-Seq, it is critical to choose appropriate methods for the removal of rRNA from total RNA. Although viruses with polyadenylated genomes can be detected by RNA-Seq following mRNA purification using oligo-dT beads, viruses with non-polyadenylated genomes are not effectively detected. However, such viruses can be detected by RNA-Seq using the rRNA selective depression method. The high-throughput and cost-effective method of RNA-Seq library preparation which is described here allows us to detect a broad range of viruses in wild plants.

MBGD update 2015: microbial genome database for flexible ortholog analysis utilizing a diverse set of genomic data.

The microbial genome database for comparative analysis (MBGD) (available at http://mbgd.genome.ad.jp/) is a comprehensive ortholog database for flexible comparative analysis of microbial genomes, where the users are allowed to create an ortholog table among any specified set of organisms. Because of the rapid increase in microbial genome data owing to the next-generation sequencing technology, it becomes increasingly challenging to maintain high-quality orthology relationships while allowing the users to incorporate the latest genomic data available into an analysis. Because many of the recently accumulating genomic data are draft genome sequences for which some complete genome sequences of the same or closely related species are available, MBGD now stores draft genome data and allows the users to incorporate them into a user-specific ortholog database using the MyMBGD functionality. In this function, draft genome data are incorporated into an existing ortholog table created only from the complete genome data in an incremental manner to prevent low-quality draft data from affecting clustering results. In addition, to provide high-quality orthology relationships, the standard ortholog table containing all the representative genomes, which is first created by the rapid classification program DomClust, is now refined using DomRefine, a recently developed program for improving domain-level clustering using multiple sequence alignment information.

[A case of rectal gastrointestinal stromal tumor in an elderly patient who was successfully treated with imatinib mesylate with no significant adverse events].

An 89-year-old male patient was found to have a mass with a diameter of 54 mm in the pelvic cavity, connected to the rectum, and was diagnosed with a gastrointestinal stromal tumor (GIST)of the rectum by transrectal biopsy. The patient was treated continuously with 400mg/day of imatinib mesylate with no significant adverse events, and the tumor gradually reduced in size. The tumor reduced in size to a diameter of 24 mm at 57 months post-treatment, and a partial response has been maintained for 60 months. Colorectal GIST is rare, comprising 5% of all GIST cases, and surgical resection is the first choice of treatment. In this case, due to a lack of consent, we chose imatinib mesylate as the treatment. However, imatinib mesylate has been reported to induce adverse events more frequently in older patients, and thus we took care to reduce the treatment dosage. We report this case to highlight that a normal quantity of imatinib mesylate can be administered, with no significant adverse events.

MBGD update 2013: the microbial genome database for exploring the diversity of microbial world.

The microbial genome database for comparative analysis (MBGD, available at http://mbgd.genome.ad.jp/) is a platform for microbial genome comparison based on orthology analysis. As its unique feature, MBGD allows users to conduct orthology analysis among any specified set of organisms; this flexibility allows MBGD to adapt to a variety of microbial genomic study. Reflecting the huge diversity of microbial world, the number of microbial genome projects now becomes several thousands. To efficiently explore the diversity of the entire microbial genomic data, MBGD now provides summary pages for pre-calculated ortholog tables among various taxonomic groups. For some closely related taxa, MBGD also provides the conserved synteny information (core genome alignment) pre-calculated using the CoreAligner program. In addition, efficient incremental updating procedure can create extended ortholog table by adding additional genomes to the default ortholog table generated from the representative set of genomes. Combining with the functionalities of the dynamic orthology calculation of any specified set of organisms, MBGD is an efficient and flexible tool for exploring the microbial genome diversity.

Deciphering and prediction of transcriptome dynamics under fluctuating field conditions.

Determining the drivers of gene expression patterns is more straightforward in laboratory conditions than in the complex fluctuating environments where organisms typically live. We gathered transcriptome data from the leaves of rice plants in a paddy field along with the corresponding meteorological data and used them to develop statistical models for the endogenous and external influences on gene expression. Our results indicate that the transcriptome dynamics are predominantly governed by endogenous diurnal rhythms, ambient temperature, plant age, and solar radiation. The data revealed diurnal gates for environmental stimuli to influence transcription and pointed to relative influences exerted by circadian and environmental factors on different metabolic genes. The model also generated predictions for the influence of changing temperatures on transcriptome dynamics. We anticipate that our models will help translate the knowledge amassed in laboratories to problems in agriculture and that our approach to deciphering the transcriptome fluctuations in complex environments will be applicable to other organisms.

Os-GIGANTEA confers robust diurnal rhythms on the global transcriptome of rice in the field.

The circadian clock controls physiological traits such as flowering time, photosynthesis, and growth in plants under laboratory conditions. Under natural field conditions, however, little is known about the significance of the circadian clock in plants. By time-course transcriptome analyses of rice (Oryza sativa) leaves, using a newly isolated rice circadian clock-related mutant carrying a null mutation in Os-GIGANTEA (Os-GI), we show here that Os-GI controlled 75% (false discovery rate = 0.05) of genes among 27,201 genes tested and was required for strong amplitudes and fine-tuning of the diurnal rhythm phases of global gene expression in the field. However, transcripts involved in primary metabolism were not greatly affected by osgi. Time-course metabolome analyses of leaves revealed no trends of change in primary metabolites in osgi plants, and net photosynthetic rates and grain yields were not affected. By contrast, some transcripts and metabolites in the phenylpropanoid metabolite pathway were consistently affected. Thus, net primary assimilation of rice was still robust in the face of such osgi mutation-related circadian clock defects in the field, unlike the case with defects caused by Arabidopsis thaliana toc1 and ztl mutations in the laboratory.

Parallel evolution in eight-barbel loaches of the genus Lefua (Balitoridae, Cypriniformes) revealed by mitochondrial and nuclear DNA phylogenies.

The evolutionary history of eight-barbel loaches of the genus Lefua contains important phylogenetic information that will aid in resolution of the faunal formations and evolutionary histories of Japanese and East Asian freshwater fishes. Our sequencing of the mitochondrial D-loop region in a large number of samples allowed construction of the most comprehensive phylogeny of these loaches to date; we demonstrated monophyly of five Lefua species and identified populations of Lufua. sp. and Lefua echigonia. Loaches inhabiting the Tokai region in Japan were morphologically and ecologically indistinguishable from Lefua sp. However, they were included in the L. echigonia lineage. We determined a novel phylogeny by sequencing the nuclear ribosomal S7 subunit and showed that nuclear DNA phylogeny essentially matched the mitochondrial DNA phylogeny. Loaches from the Tokai region were part of the L. echigonia lineage, indicating parallel evolution between Tokai loaches and Lefua sp. in western Japan. We presented the most robust phylogeny to date using concatenated mitochondrial and nuclear sequences. The wealth of molecular information allowed us to speculate on evolutionary processes in the genus Lefua.

Proapoptotic action of p53-Tom5 in p53-resistant A549 human non-small cell lung cancer cells through direct mitochondrial dysfunction.

Transcription-dependent apoptosis triggered by p53 hardly occurs in alternative reading frame (ARF)-null cancer cells. Loss of ARF leads to hyperactivation of murine double minute 2 (MDM2), resulting in the degradation of p53. In the present study, A549 (ARF-null) human non-small lung cancer cells were transfected with a plasmid DNA encoding human wild-type p53 and the mitochondrial transmembrane domain of Tom5 (p53-Tom5) for delivering p53 to mitochondria. As a result, p53-Tom5 exclusively localized at mitochondria in A549 cells and suppressed the proliferation of them, whereas wild-type p53 did not. In addition, mitochondrial dysfunction and release of cytochrome c were induced by p53-Tom5 in A549 cells. These data suggest that p53-Tom5 suppressed the proliferation of A549 cells through direct mitochondrial dysfunction.

SALAD database: a motif-based database of protein annotations for plant comparative genomics.

Proteins often have several motifs with distinct evolutionary histories. Proteins with similar motifs have similar biochemical properties and thus related biological functions. We constructed a unique comparative genomics database termed the SALAD database (http://salad.dna.affrc.go.jp/salad/) from plant-genome-based proteome data sets. We extracted evolutionarily conserved motifs by MEME software from 209,529 protein-sequence annotation groups selected by BLASTP from the proteome data sets of 10 species: rice, sorghum, Arabidopsis thaliana, grape, a lycophyte, a moss, 3 algae, and yeast. Similarity clustering of each protein group was performed by pairwise scoring of the motif patterns of the sequences. The SALAD database provides a user-friendly graphical viewer that displays a motif pattern diagram linked to the resulting bootstrapped dendrogram for each protein group. Amino-acid-sequence-based and nucleotide-sequence-based phylogenetic trees for motif combination alignment, a logo comparison diagram for each clade in the tree, and a Pfam-domain pattern diagram are also available. We also developed a viewer named 'SALAD on ARRAYs' to view arbitrary microarray data sets of paralogous genes linked to the same dendrogram in a window. The SALAD database is a powerful tool for comparing protein sequences and can provide valuable hints for biological analysis.

In silico identification of short nucleotide sequences associated with gene expression of pollen development in rice.

Microarray analysis of tiny amounts of RNA extracted from plant section samples prepared by laser microdissection (LM) can provide high-quality information on gene expression in specified plant cells at various stages of development. Having joined the LM-microarray analysis project, we utilized such genome-wide gene expression data from developing rice pollen cells to identify candidates for cis-regulatory elements for specific gene expression in these cells. We first found a few clusters of gene expression patterns based on the data from LM-microarrays. On one gene cluster in which the members were specifically expressed at the bicellular and mature pollen mitotic stages, we identified gene cluster fingerprints (GCFs), each of which consists of a short nucleotide representing the gene cluster. We expected that these GCFs would contain cis-regulatory elements for stage- and tissue-specific gene expression, and we further identified groups of GCFs with common core sequences. Some criteria, such as frequency of occurrence in the gene cluster in contrast to the total tested gene set, flanking sequence preference and distribution of combined GCF sets in the gene regions, allowed us to limit candidates for cis-regulatory sequences for specific gene expression in rice pollen cells to at least 20 sets of combined GCFs. This approach should provide a general purpose algorithm for identifying short nucleotides associated with specific gene expression.

Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model.

Bone marrow cells (BMCs) have been reported to behave as tissue-specific stem cells in some organs and to participate in tumorigenesis. However, the roles of BMCs in hepatic regeneration and carcinogenesis are still unknown. A choline-deficient, ethionine-supplemented (CDE) diet leads to the appearance of oval cells, a type of hepatic progenitor cell, and activates their replication. Furthermore, this type of diet induces preneoplastic nodules and hepatocellular carcinomas (HCCs) derived from oval cell progenitors. The aims of this study were to determine whether oval cells are derived from BMCs and whether preneoplastic nodules or HCCs originate from BMCs in the CDE diet rat model. To clarify the origin of constituent cells in the liver, we transplanted BMCs from green fluorescent protein (GFP) transgenic female rats into male Lewis rats, which were then exposed to a CDE diet to induce hepatocarcinogenesis. Some oval cells showed both donor-derived GFP expression and the recipient-specific Y chromosome, indicating that donor BMCs fused with recipient oval cells. Several preneoplastic nodules (precancerous lesions) identified by their glutathione S-transferase placental (GSTp) positivity were induced by CDE treatment. However, these preneoplastic GSTp-positive nodules were not GFP positive. In conclusion, this study has produced two major findings. First, BMCs fuse with some oval cells. Second, BMC-fused oval cells and BMCs might not have malignant potential in the CDE-treated rat model.

Incongruence between mtDNA phylogeny and morphologial and ecological characters in loaches of the genus Lefua (Balitoridae, Cypriniformes).

To elucidate the phylogenetic position of Lefua loaches from Aichi and Shizuoka Prefectures of Honshu Island, Japan, we determined their nucleotide sequences for the mitochondrial D-loop region and compared these to sequences from four other Lefua species: L. costata, L. nikkonis, L. echigonia, and L. sp. Loaches identified as L. sp. on the basis of morphology comprised a clade (the L. sp. Tokai population) that grouped together with L. echigonia; hence, the processes involved in evolution within the genus Lefua were unclear. We performed randomly amplified polymorphic DNA (RAPD) analyses to obtain genetic information on nuclear DNA. The RAPD patterns of the L. sp. Tokai population differed from those of the local L. echigonia and L. sp. populations. The L. sp. Tokai population was similar to L. echigonia with regard to mitochondrial DNA but differed from L. echigonia and L. sp. with respect to nuclear DNA; this indicated that the evolutionary background of the L. sp. Tokai population was unique. We suggest that introgression of mitochondria occurred from L. echigonia to the L. sp. Tokai population, and speculate on the process of evolution of the latter population of Lefua. As with six L. echigonia populations and two L. sp. populations, we regard the L. sp. Tokai population as an evolutionary significant unit (ESU) that qualifies for protection as an endangered loach.

Radical surgery for advanced squamous cell carcinoma of the gallbladder: a report of three cases, including a 10-year survivor.

We report three patients who underwent radical resections for advanced squamous cell carcinoma of the gallbladder, two of whom are still alive without recurrence 10 and 9 years after surgery. The other patient, who had lymph node involvement, suffered recurrence of the disease and died 9 months after surgery. Our experience indicates that radical surgery can sometimes provide a chance for long-term survival in patients with this neoplasm. Lymph node metastasis, albeit a rare event, might be a poor prognostic factor in patients with this type of gallbladder carcinoma.

Is major hepatectomy with pancreatoduodenectomy justified for advanced biliary malignancy?

BACKGROUND/PURPOSE: Major hepatectomy with concomitant pancreatoduodenectomy (M-HPD) is usually indicated for the resection of diffuse bile duct cancer or advanced gallbladder cancer. This is the only procedure that can potentially cure such advanced cancers, so both a low mortality rate and long-term survival could potentially justify performing this procedure. METHODS: Between 1990 and 2005, the morbidity, mortality, and long-term survival of 26 patients with advanced biliary tract carcinoma 14 with diffuse bile duct cancer, 9 with advanced gallbladder cancer, and 3 with hilar bile duct cancer, who underwent hepatopancreatoduodectomy (HPD) were reviewed and analyzed. RESULTS: The overall morbidity and mortality rates were 30.8% and 0%, respectively. Postoperative infectious complications occurred in 6 patients (23.0%). The 5-year survival rate of the 14 patients with diffuse bile duct cancer who underwent HPD was 51.9%, while the 5-year survival rate in the 12 of these patients who underwent M-HPD was 61.4%. Patients with diffuse bile duct cancer without residual tumor and those without lymph node metastasis had 5-year survival rates of 68.6% and 80%, respectively. Thirty-three percent (2 of 6) of the patients who underwent M-HPD for advanced gallbladder cancer survived for more than 5 years. CONCLUSIONS: Preoperative biliary drainage, portal embolization, complete external drainage of pancreatic juice, reduction of intraoperative bleeding, and prevention of bacterial colonization of bile may enable the incidence of mortality and hepatic failure to approach zero in patients who undergo HPD. Surgeons should strive for complete clearance of the tumor with a negative surgical margin to achieve long-term survival when performing M-HPD.

Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery.

BACKGROUND: We performed hepatectomy without lymph node (LN) dissection for intrahepatic cholangiocarcinoma (ICC) limited to the peripheral region of the liver, and hepatectomy with extrahepatic bile duct resection and regional LN dissection for any types of ICC extending to the hepatic hilum. Surgical outcomes were evaluated to elucidate the prognostic factors that influence patient survival with respect to intrahepatic recurrence. METHODS: Forty-one patients underwent resection of ICC with no macroscopic evidence of residual cancer. RESULTS: Significant risk factors for poorer survival included preoperative jaundice (P = 0.0115), serum CA19-9 levels >37 U/ml (P = 0.0089), tumor diameter >4.5 cm (P = 0.017), ICC extending to the hepatic hilum (P = 0.0065), mass-forming with periductal-infiltrating type (P = 0.003), poorly differentiated adenocarcinoma, portal vein involvement (P = 0.0785), LN metastasis at initial hepatectomy (P < 0.0001), and positive surgical margin (P = 0.023). Intrahepatic recurrence, which was the predominant manner of recurrence, was detected in 20 patients (74.1%). Patients with intrahepatic recurrence had a significantly high incidence of high serum CA19-9 levels (>37 U/ml; P = 0.0006), preoperative jaundice (P = 0.0262), ICC extended to the hepatic hilum (P = 0.0349), large tumors (>4.5 cm; P = 0.0351), portal vein involvement (P = 0.0423), and LN metastasis at initial hepatectomy (P = 0.009) compared with disease-free patients. The multiple logistic regression analysis revealed that preoperative CA19-9 elevation and obstructive jaundice influenced intrahepatic recurrence of ICC. CONCLUSIONS: Although LN metastasis is a significant prognostic factor, the most obvious recurrence pattern after surgery was intrahepatic recurrence, which could be predicted preoperatively by a combination of elevated serum CA19-9 levels and manifestation of obstructive jaundice.