Publications by authors named "Daisuke Kurita"

73 Publications

Does synchronous early head and neck cancer with esophageal cancer need treatment after preoperative chemotherapy?

Gen Thorac Cardiovasc Surg 2021 Nov 27. Epub 2021 Nov 27.

Department of Esophageal Surgery, National Cancer Center Hospital, 5-5-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Objective: Treatment options for patients with resectable thoracic esophageal squamous cell cancer (ESCC) and synchronous head and neck cancer (HNC) are unclear. Little has been reported about the effects of chemotherapy on early HNC. The aim of this study was to investigate the treatment outcomes of resectable thoracic ESCC with synchronous early HNC.

Methods: We retrospectively reviewed 37 patients undergoing esophagectomy for thoracic ESCC with synchronous early HNC from January 2008 to December 2018.

Results: Among 37 patients who had synchronous early HNC, 27 patients received preoperative therapy for ESCC before HNC treatment, and 16 of 27 patients achieved a complete response for HNC by preoperative chemotherapy. Fifteen of 16 patients did not receive additional treatment, and regional recurrence of HNC was not observed. In one other case, an oral excision was performed, but no cancer cell remnants were found pathologically. No significant difference in overall survival and disease-free survival was observed between 15 patients with follow-up and 22 patients with surgery or radiation.

Conclusion: Our results indicate that early HNC with comorbid ESCC could be followed up without additional treatment if preoperative chemotherapy is successful.
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http://dx.doi.org/10.1007/s11748-021-01744-9DOI Listing
November 2021

Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery.

Esophagus 2021 Nov 10. Epub 2021 Nov 10.

Esophageal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.

Background: The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery.

Methods: A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed.

Results: The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P < 0.001), lymphovascular invasion (LVI) (HR = 2.608, P < 0.001) were independent factors associated with OS. The LVI+/ypN+ group had a significantly poorer outcome than the other groups (P < 0.001). The 5-year RFS rates for patients with ypStage IIIA or higher among the LVI-negative cases and ypStage II or higher among the LVI-positive cases were around 0.6 or under. The novel pathological staging which was based on the present results was proposed and RFS curves of each novel stage suggested the suitability of these staging for our cohort.

Conclusions: The present results suggest that a novel pathological staging system using the ypTNM classification, in which the supraclavicular lymph node was regarded as a regional lymph node and the presence of LVI was included as a category, was appropriate for patients with LAESCC after NAC prior to surgery.
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http://dx.doi.org/10.1007/s10388-021-00891-5DOI Listing
November 2021

Salvage minimally invasive esophagectomy after definitive chemoradiotherapy for esophageal cancer can improve postoperative complications compared with salvage open esophagectomy.

Surg Endosc 2021 Oct 12. Epub 2021 Oct 12.

Division of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, 104-0045, Japan.

Background: Although the advantage of minimally invasive esophagectomy (MIE) over open esophagectomy (OE) in planned esophagectomy is being established, the utility of salvage MIE (S-MIE) remains unclear. We aimed to investigate the feasibility and advantage of S-MIE compared with salvage OE (S-OE).

Methods: We retrospectively assessed 82 patients who underwent salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer between January 2007 and April 2020. Perioperative factors and postoperative complications were compared between the S-OE group (n = 62) and the S-MIE group (n = 20). Logistic regression analysis was performed to analyze the factors associated with postoperative complications.

Results: Regarding the patients' preoperative characteristics, the S-OE group had a significant number of grade ≥ cT3 patients vs the S-MIE group (69% vs 35%, respectively; p = 0.006), whereas ycT rates were comparable. Compared with S-OE, S-MIE had comparable operative time, number of harvested thoracic lymph nodes, and R0 resection, but significantly less estimated blood loss (150 ml and 395 ml, respectively; p = 0.003). Regarding postoperative complications, total complications (79% vs 50%; p = 0.01) and pneumonia (48.3% vs 20%; p = 0.02) rates were significantly lower with S-OE vs S-MIE, respectively. On multivariate analysis, S-MIE was an independent factor associated with postoperative pneumonia (odds ratio: 0.29, 95% confidence interval: 0.06-0.99; p = 0.04) and total complications (odds ratio: 0.26, 95% confidence interval: 0.07-0.86; p = 0.02).

Conclusion: S-MIE was feasible for salvage esophagectomy, with favorable short-term outcomes vs S-OE regarding postoperative pneumonia and total complications.
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http://dx.doi.org/10.1007/s00464-021-08672-yDOI Listing
October 2021

Feasibility of conversion thoracoscopic esophagectomy after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

Jpn J Clin Oncol 2021 Aug;51(8):1225-1231

Department of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Background: Recently, patients with cT4b esophageal cancer often require conversion surgery following induction therapy, for which the standard procedure is open esophagectomy. However, thoracoscopic esophagectomy, including thoracoscopic esophagectomy in the prone position, is increasingly used. We compared short-term outcomes of thoracoscopic esophagectomy and open esophagectomy in this setting.

Methods: We retrospectively analyzed 14 patients who underwent thoracoscopic esophagectomy, and 10 who underwent open esophagectomy, for locally advanced unresectable esophageal cancer after induction therapy between March 2007 and July 2020.

Results: The two groups did not significantly differ in patient background. Median total and thoracic surgical times were both significantly longer for open esophagectomy than for thoracoscopic esophagectomy. Median blood loss was also greater in the open esophagectomy group than in the thoracoscopic esophagectomy group. The thoracoscopic esophagectomy group also had significantly shorter median chest drain duration; and lower C-reactive protein levels on the second and third postoperative days. The two groups did not significantly differ in total complications or postoperative hospital stay.

Conclusions: Thoracoscopic esophagectomy is as safe and feasible as open esophagectomy for conversion surgery after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.
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http://dx.doi.org/10.1093/jjco/hyab085DOI Listing
August 2021

A stalled-ribosome rescue factor Pth3 is required for mitochondrial translation against antibiotics in Saccharomyces cerevisiae.

Commun Biol 2021 03 8;4(1):300. Epub 2021 Mar 8.

Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu, Gunma, Japan.

Mitochondrial translation appears to involve two stalled-ribosome rescue factors (srRFs). One srRF is an ICT1 protein from humans that rescues a "non-stop" type of mitochondrial ribosomes (mitoribosomes) stalled on mRNA lacking a stop codon, while the other, C12orf65, reportedly has functions that overlap with those of ICT1; however, its primary role remains unclear. We herein demonstrated that the Saccharomyces cerevisiae homolog of C12orf65, Pth3 (Rso55), preferentially rescued antibiotic-dependent stalled mitoribosomes, which appear to represent a "no-go" type of ribosomes stalled on intact mRNA. On media containing a non-fermentable carbon source, which requires mitochondrial gene expression, respiratory growth was impaired significantly more by the deletion of PTH3 than that of the ICT1 homolog PTH4 in the presence of antibiotics that inhibit mitochondrial translation, such as tetracyclines and macrolides. Additionally, the in organello labeling of mitochondrial translation products and quantification of mRNA levels by quantitative RT-PCR suggested that in the presence of tetracycline, the deletion of PTH3, but not PTH4, reduced the protein expression of all eight mtDNA-encoded genes at the post-transcriptional or translational level. These results indicate that Pth3 can function as a mitochondrial srRF specific for ribosomes stalled by antibiotics and plays a role in antibiotic resistance in fungi.
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http://dx.doi.org/10.1038/s42003-021-01835-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940416PMC
March 2021

Simultaneous evaluation of antioxidative serum profiles facilitates the diagnostic screening of autism spectrum disorder in under-6-year-old children.

Sci Rep 2020 11 26;10(1):20602. Epub 2020 Nov 26.

Research Center for Child Mental Development, University of Fukui, Fukui, Japan.

This case-control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical (OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O) and alkoxyl radical (RO) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of OH, O, and RO scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.
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http://dx.doi.org/10.1038/s41598-020-77328-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691362PMC
November 2020

Involvement of GcvB small RNA in intrinsic resistance to multiple aminoglycoside antibiotics in Escherichia coli.

J Biochem 2021 Apr;169(4):485-489

Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Bioscience, Hirosaki University, Bunkyo-cho 3, Hirosaki, Aomori 036-8561, Japan.

Deleting the gene for small RNA GcvB in Escherichia coli was found to increase the sensitivity to several aminoglycoside antibiotics, such as neomycin, streptomycin, kanamycin, kasugamycin and spectinomycin, at low concentrations. GcvB, conserved in gram-negative enteric bacteria, is known to negatively control the expression of many genes for amino acid incorporation systems, especially the periplasmic ABC-transporter proteins. Deletions of several amino acid transporter genes in ΔgcvB cells decreased the antibiotic sensitivity to the wild-type level, suggesting that those genes are involved in uptake of aminoglycosides into the cell. Since GcvB is constitutively synthesized in growing cells, repressing synthesis of amino acid transporters, it contributes to the intrinsic resistance to several aminoglycoside antibiotics.
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http://dx.doi.org/10.1093/jb/mvaa122DOI Listing
April 2021

Does staged surgical training for minimally invasive esophagectomy have an impact on short-term outcomes?

Surg Endosc 2021 11 30;35(11):6251-6258. Epub 2020 Oct 30.

Division of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, 104-0045, Japan.

Background: sophageal cancer has a low incidence, and the anatomy is difficult to understand during esophagectomy. This necessitates a precise and lengthy operation. Therefore, the establishment of a training system in esophageal surgery is of critical importance. In this study, we compared the short-term outcomes of minimally invasive esophagectomy (MIE) performed by consultants versus trainees and explored the factors that impacted the thoracic operation time for each group.

Methods: We have introduced standardized MIE surgical techniques to our trainees in 2016. Our procedure consists of a laparoscopic phase and a thoracoscopic phase and is systematically designed to be learned in a step-by-step manner in each phase. We retrospectively identified 308 patients who underwent MIE from April 2016 to April 2018. The patients were divided into those who underwent MIE by consultants and those who underwent MIE by trainees. The preoperative background factors, operation-related factors, and postoperative complications were compared between the two groups. We also assessed the association between a prolonged thoracic operation time and tumor-and patient-related factors in each of the consults and trainees.

Results: Significantly more patients had stage ≥ III cancer in the consultant than trainee group. However, the postoperative complications were comparable, specifically pneumonia (11% vs. 18%), anastomotic leakage (11% vs. 13%), and mortality (0.6% vs. 1.3%). There was no significant difference in the lymph node yield (20 vs. 17) or R0 resection rate (94% vs. 91%) between the two groups. However, the trainees had a significantly longer thoracic operation time (143 ± 34 vs. 190 ± 28 min) and significantly greater blood loss (93 vs. 183 ml). Oncological factors were correlated with a prolonged thoracic operation time in the consultants, but not in the trainees.

Conclusions: Under standardized surgical management using a stepwise educational program, performance of MIE by trainees has no impact on short-term outcomes.
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http://dx.doi.org/10.1007/s00464-020-08125-yDOI Listing
November 2021

Robotic esophagectomy with total mediastinal lymphadenectomy using four robotic arms alone in esophageal and esophagogastric cancer (RETML-4): a prospective feasibility study.

Esophagus 2021 Apr 10;18(2):203-210. Epub 2020 Oct 10.

Esophageal Surgery Division, National Cancer Center Hospital East, Chiba, Japan.

Background: Robotic-assisted esophagectomy is still in the implementation phase. Robotic surgical systems refine visualization via robotically-enhanced surgical anatomy (RESA), and the stable articulated robotic arms provide precise movements. This prospective feasibility study was conducted to evaluate robotic esophagectomy with total mediastinal lymphadenectomy using four robotic arms exclusively (RETML-4).

Methods: The inclusion criterion was clinical stage I-IIIB esophageal cancer with stable general condition. Patients were positioned hemi-prone with single-lung ventilation, and the operation table was tilted until the patient was prone. The first, second, third, and fourth robotic ports were inserted into the ninth intercostal space (ICS) on the angulus inferior scapulae line, seventh ICS on the posterior axillary line, and the fifth and third ICS on the mid-axillary line, respectively. RETML-4 was performed by precise sharp dissection in wide stable operation fields, with countertraction created by a tip-up fenestrated grasper with gauze. Esophagectomy was performed separately for the middle to lower, and upper esophagus. After mobilizing the middle to lower esophagus and performing lymph node dissection, the upper esophagus was mobilized, with bilateral lymph node dissection along the recurrent laryngeal nerves. The assistant surgeon was involved only during removing gauze and collecting harvested lymph nodes in the thorax.

Results: RETML-4 was performed in all ten patients enrolled in 2018. The median postoperative hospital stay was 15 days, and the complication rate was 60%. Nine cases achieved R0 resection. Recurrence occurred in two cases.

Conclusions: RETML-4 is feasible, and may facilitate minimally invasive esophagectomy by providing precise instrument movements and RESA.
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http://dx.doi.org/10.1007/s10388-020-00788-9DOI Listing
April 2021

Novel universally applicable technique for performing bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy: a truly minimally invasive procedure.

Surg Endosc 2021 09 28;35(9):5186-5192. Epub 2020 Sep 28.

Esophageal Surgery Division, National Cancer Hospital East, Chiba, Japan.

Background: The procedure of mediastinoscopic-assisted transhiatal esophagectomy (MATE) is only performed in a few institutions, despite this being the ultimate form of minimally invasive surgery for performing esophagectomy for esophageal and esophagogastric cancer in that it entails no chest wall trauma. We have developed a novel, universally applicable, surgical procedure for performing bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy (BTC-MATLE) that is an improvement on standard MATE surgery for esophageal and esophagogastric cancer.

Methods: The patient is placed in a supine position under general anesthesia with bilateral lung ventilation. BTC-MATLE combined with mediastinoscopic and transhiatal laparoscopic esophagectomy with total mediastinal lymph node dissection are performed synchronously. After lymph node dissection along both recurrent laryngeal nerves through bilateral cervical skin incisions, bilateral transcervical mediastinoscopic esophagectomy is performed to avoid collision outside the cervical region and ensure operability even in patients with narrow mediastimun. Laparoscopic gastric mobilization and subsequent lower esophageal mobilization meet the bilateral transcervical mediastinoscopic esophagectomy at the border of the middle and lower third of the esophagus. The gastric tube is pulled up into the cervical region via a posterior mediastinal route and anastomosed in the neck.

Results: BTC-MATLE was performed on 16 high-risk patients (Charlson Comorbidity Index ≥ 3 in 14 patients and two octogenarians with complex comorbidities). Median operation time and postoperative hospital stay were 231 min and 15 days, respectively. R0 resection was achieved in 15 patients (94%), and there were no in-hospital deaths.

Conclusions: BTC-MATLE, a procedure for performing minimally invasive esophagectomy, is likely to become the applicable form of MATE surgery for esophageal and esophagogastric cancer, even in high-risk patients because it is truly minimally invasive and has excellent short-term outcomes.
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http://dx.doi.org/10.1007/s00464-020-08012-6DOI Listing
September 2021

Novel minimally invasive approach to lymph node dissection around the left renal vein in patients with esophagogastric junction cancer.

Esophagus 2021 Apr 27;18(2):420-423. Epub 2020 Sep 27.

Division of Esophageal Surgery, National Cancer Center Hospital East, Chiba, Japan.

The left renal vein lymph node (LRVLN) may be the extended locoregional node in esophagogastric junction cancer; however, only open-surgical methods of dissection have been reported. We therefore developed a novel minimally invasive laparoscopic method for LRVLN dissection. Following esophagectomy, the stomach was mobilized and LRVLN dissection was started by taping the pancreatic body using two silicone drains. The transverse mesocolon was then retracted through the superior duodenal fossa to expose the horizontal duodenum and permit LRVLN dissection. We carried out the procedure successfully in 17 patients with advanced esophagogastric cancer. The median total and laparoscopic operative times were 415 and 161 min, respectively. Postoperative esophagectomy-related complications occurred in six patients. The median estimated blood loss was 120 ml and hospital stay was 15 days. This minimally invasive laparoscopic LRVLN dissection method was safe and effective, and may support faster recovery and earlier postoperative adjuvant therapy in patients with esophagogastric junction cancer.
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http://dx.doi.org/10.1007/s10388-020-00786-xDOI Listing
April 2021

Totally Mechanical Collard Technique for Cervical Esophagogastric Anastomosis Reduces Stricture Formation Compared with Circular Stapled Anastomosis.

World J Surg 2020 Dec 11;44(12):4175-4183. Epub 2020 Aug 11.

Division of Esophageal Surgery, National Cancer Center Hospital East, Chiba, Japan.

Background: The optimal technique for cervical esophagogastric anastomosis in esophagectomy has not yet been established. Using circular stapled (CS) technique effectively reduces the incidence of anastomotic leakage and shortens the operating time; however, anastomotic stricture has been reported to be more common. The present study was performed to compare the clinical outcomes of the recently developed totally mechanical Collard (TMC) and CS anastomosis.

Methods: We retrospectively reviewed consecutive esophageal cancer cases who are undergoing transthoracic extended esophagectomy with gastric conduit reconstruction using cervical CS or TMC anastomosis from December 2013 to December 2016. Propensity score matching and multivariate regression were used to adjust for differences in baseline characteristics.

Results: Among 313 patients, 93 underwent CS anastomosis and 220 underwent TMC anastomosis. Stricture formation occurred in 59 patients (18.8%), significantly more often with the CS than TMC anastomosis (30.1% vs. 14.1%, p = 0.001). No significant differences were observed in the refractory stricture rate (9.7% vs. 5.0%, p = 0.134) or the anastomotic leakage rate (11.8% vs. 10.9%, p = 0.845) between the two groups. The propensity score matching cohort study including 86 pairs of patients confirmed a significantly lower stricture formation rate with the TMC than CS technique (27.9% vs. 14.0%, p = 0.038). In the multivariable analysis, anastomotic leakage, the CS technique, and a body mass index of ≥25 mg/m were independently associated with a risk of stricture formation.

Conclusion: TMC technique contributed to a reduced rate of stricture formation compared with CS technique in cervical esophagogastric anastomosis.
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http://dx.doi.org/10.1007/s00268-020-05729-2DOI Listing
December 2020

VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction.

EBioMedicine 2020 Aug 30;58:102917. Epub 2020 Jul 30.

Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan; Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan. Electronic address:

Background: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation.

Methods: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses.

Findings: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children.

Interpretation: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology.

Funding: This study was supported mainly by MEXT, Japan.
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http://dx.doi.org/10.1016/j.ebiom.2020.102917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393524PMC
August 2020

Molecular determinants of release factor 2 for ArfA-mediated ribosome rescue.

J Biol Chem 2020 09 28;295(38):13326-13337. Epub 2020 Jul 28.

Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Japan. Electronic address:

Translation termination in bacteria requires that the stop codon be recognized by release factor RF1 or RF2, leading to hydrolysis of the ester bond between the peptide and tRNA on the ribosome. As a consequence, normal termination cannot proceed if the translated mRNA lacks a stop codon. In , the ribosome rescue factor ArfA releases the nascent polypeptide from the stalled ribosome with the help of RF2 in a stop codon-independent manner. Interestingly, the reaction does not proceed if RF1 is instead provided, even though the structures of RF1 and RF2 are very similar. Here, we identified the regions of RF2 required for the ArfA-dependent ribosome rescue system. Introduction of hydrophobic residues from RF2 found at the interface between RF2 and ArfA into RF1 allowed RF1 to associate with the ArfA-ribosome complex to a certain extent but failed to promote peptidyl-tRNA hydrolysis, whereas WT RF1 did not associate with the complex. We also identified the key residues required for the process after ribosome binding. Our findings provide a basis for understanding how the ArfA-ribosome complex is specifically recognized by RF2 and how RF2 undergoes a conformational change upon binding to the ArfA-ribosome complex.
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http://dx.doi.org/10.1074/jbc.RA120.014664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504928PMC
September 2020

Minimally invasive hybrid surgery: A salvage tumor enucleation for local recurrence of thoracic esophageal carcinoma after definitive chemoradiotherapy.

Asian J Endosc Surg 2021 Jan 6;14(1):77-80. Epub 2020 Jul 6.

Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan.

Local recurrence after definitive chemoradiation for esophageal carcinoma is associated with poor outcomes. Although salvage esophagectomy is a standard treatment that offers a chance of long-term survival, the procedure is associated with high morbidity and mortality. Minimally invasive hybrid surgery (MIHS) employs thoracoscopic and esophagoscopic procedures and is generally used to treat benign esophageal submucosal tumors. A 64-year-old man with thoracic esophageal carcinoma experienced local relapse after definitive chemoradiation. He underwent MIHS and was discharged 18 days after surgery with a slight degree of stricture. Pathological findings revealed squamous cell carcinoma with no residual tumor in the resection margins, and the patient remains free from cancer relapse 24 months after surgery. Here, we report the findings in this patient, in whom MIHS was successfully performed as a salvage tumor enucleation for local recurrence of esophageal carcinoma after definitive chemoradiotherapy.
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http://dx.doi.org/10.1111/ases.12830DOI Listing
January 2021

Distribution of lymph node metastases in locally advanced adenocarcinomas of the esophagogastric junction (cT2-4): comparison between Siewert type I and selected Siewert type II tumors.

Langenbecks Arch Surg 2020 Jun 8;405(4):509-519. Epub 2020 Jun 8.

Department of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku Tokyo, 104-0045, Japan.

Introduction: The distribution of lymph node metastases in locally advanced Siewert type I and type II AEG (adenocarcinoma of the esophagogastric junction) remains unclear. The diversity of data in the literature reflects the non-uniformity of tumor stages and surgical procedures in previous studies.

Materials And Methods: Based on a retrospective analysis from our single-center database, we examined distributions of lymph node metastases in types I and II cT2-4 AEG. The dataset comprised 44 patients; 19 and 25 patients had type I and type II, respectively. All patients underwent subtotal esophagectomy and total mediastinal lymphadenectomy, which included dissection of the upper mediastinal lymph nodes. The histological data of the surgical specimens were analyzed to evaluate metastasis rates in each lymph node station according to the Japanese Esophageal Society (JES) and American Joint Committee on Cancer (AJCC) guidelines.

Results: Lymph node metastases were observed in 75.0% cases (n = 33/44). There was no significant difference in the total lymph node metastasis rate between the two groups (type I 73.7% versus type II 76.0%). On comparing each lymph node region separately, no statistically significant differences were noted between the groups: upper mediastinal (type I 31.6% versus type II 24.0%), middle and lower mediastinal (type I 31.6% versus type II 44.0%), paragastric (type I 61.1% versus type II 76.0%), and celiac lymph nodes (type I 16.7% versus type II 25.0%).

Conclusion: In advanced clinical stages, the metastasis rate is high at all mediastinal lymph node regions in both type I and type II AEGs.
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http://dx.doi.org/10.1007/s00423-020-01894-zDOI Listing
June 2020

Handgrip Strength Predicts Postoperative Pneumonia After Thoracoscopic-Laparoscopic Esophagectomy for Patients with Esophageal Cancer.

Ann Surg Oncol 2020 Sep 4;27(9):3173-3181. Epub 2020 Jun 4.

Division of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Background: Despite advances in minimally invasive surgery, postoperative pneumonia after esophagectomy remains a frequent complication. Sarcopenia, defined as low muscle strength and quantity, has been associated with adverse surgical outcomes in numerous cancers. The recent definition and diagnostic criteria for sarcopenia have emphasized muscle strength rather than muscle quantity as the primary indicator of sarcopenia, although most studies have focused only on muscle quantity. This study aimed to determine the association of muscle strength and quantity with postoperative pneumonia after thoracoscopic-laparoscopic esophagectomy (TLE).

Methods: This retrospective, single-center, observational study investigated 161 men undergoing TLE for esophageal cancer between May 2017 and October 2019. Handgrip strength (HGS) and skeletal muscle mass index (SMI) were used respectively as proxy for muscle strength and quantity. The SMI was assessed using preoperative computed tomography at the L3 vertebral level. Predictors of postoperative pneumonia were determined using multivariate analysis.

Results: The study subjects had TLE performed for squamous cell carcinoma (n = 131), adenocarcinoma (n = 24), and other cancers (n = 6). Postoperative pneumonia developed in 28 patients (17.4%). In the multivariate analysis, HGS was significantly associated with postoperative pneumonia (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.08-1.35; p = 0.001]. No association was found between SMI and postoperative pneumonia (p = 0.964). Comparison of the areas under the receiver operating characteristic curves for postoperative pneumonia prediction showed that the value for HGS was significantly higher than for SMI (0.79 vs 0.65, respectively; p = 0.012).

Conclusions: Low HGS was a significant predictor of postoperative pneumonia after TLE for esophageal cancer.
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http://dx.doi.org/10.1245/s10434-020-08520-8DOI Listing
September 2020

Efficacy of prewarming prophylaxis method for intraoperative hypothermia during thoracoscopic esophagectomy.

Esophagus 2020 10 8;17(4):385-391. Epub 2020 May 8.

Esophageal Surgery Division, Department of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: This study was performed to elucidate the clinical efficacy of the prewarming prophylaxis method for intraoperative hypothermia during thoracoscopic esophagectomy for esophageal cancer.

Methods: We enrolled 100 consecutive patients with esophageal cancer. Two patients in the prewarming group could not undergo thoracoscopic esophagectomy because of conversion to thoracotomy. The intraoperative core temperature was measured in 50 and 48 patients classified into the control and prewarming groups, respectively. Patients in the prewarming group wore a Bair Hugger warming gown (3 M, Maplewood, MN, USA) in the ward for 30 min before entering the operation room. The primary outcome measure was the difference in the intraoperative body core temperature between the control and prewarming groups, and the secondary outcome measure was the difference in postoperative infectious complications between the control and prewarming groups.

Results: The intraoperative core temperature was significantly different between the two groups at each 30-min time point from the starting of operation to the ending of the thoracic procedure (P < 0.001). The incidence of infectious surgical complications was not significantly different between the control and prewarming groups (30.0% vs. 14.6%, respectively; P = 0.11).

Conclusion: The prewarming prophylaxis method was effective for maintaining normothermia during thoracoscopic esophagectomy.
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http://dx.doi.org/10.1007/s10388-020-00743-8DOI Listing
October 2020

Case report: Gastric tube cancer after esophagectomy-Retrograde perfusion after proximal resection of right gastroepiploic artery.

Int J Surg Case Rep 2019 26;59:97-100. Epub 2019 Mar 26.

Department of Esophageal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan. Electronic address:

Introduction: We report a case of a 57-year-old patient with gastric tube cancer after subtotal esophagectomy and retrosternal gastric pull up.

Case Presentation: The patient developed gastric cancer 4 years after undergoing treatment for esophageal squamous cell cancer; the treatments included thoracoscopic subtotal esophagectomy, gastric pull-up reconstruction via a retrosternal route in salvage setting following definitive chemoradiation. Because the gastric tube cancer was located around the pylorus, transabdominal partial resection, which is much less invasive than total resection via sternotomy, was performed. During surgery, retrograde pulsation of the proximally resected right gastroepiploic artery was observed. Owing to an ample blood supply to the oral remnant of the gastric tube, vascular reconstruction of the right gastroepiploic artery was omitted. The postoperative recovery was eventless.

Discussion: The right gastroepiploic artery is considered essential for blood supply to the gastric tube. However, there was no sign of ischemia after proximal resection of this artery, which suggests the vasculature was altered after gastric tube construction.

Conclusion: This case shows that partial distal resection of the gastric tube can be performed safely without vascular reconstruction of the right gastroepiploic artery. Favorable long-term results after gastric tube reconstruction support the possibility of bilateral blood supply to the gastroepiploic arcade.
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http://dx.doi.org/10.1016/j.ijscr.2019.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531823PMC
March 2019

Methotrexate-associated Lymphoproliferative Disorders in Patients With Rheumatoid Arthritis: Clinicopathologic Features and Prognostic Factors.

Am J Surg Pathol 2019 07;43(7):869-884

Departments of Pathology.

Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.
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http://dx.doi.org/10.1097/PAS.0000000000001271DOI Listing
July 2019

Non-occlusive mesenteric ischemia associated with enteral feeding after esophagectomy for esophageal cancer: report of two cases and review of the literature.

Surg Case Rep 2019 Feb 20;5(1):36. Epub 2019 Feb 20.

Division of Esophageal Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

Background: Non-occlusive mesenteric ischemia (NOMI) is a rare but life-threatening complication of early postoperative enteral feeding. We herein report two patients who developed NOMI during enteral feeding after esophagectomy.

Case Presentation: In case 1, a 75-year-old man with no medical history was diagnosed with multiple primary cancers of the esophagus, stomach, and kidney. He underwent percutaneous endoscopic gastrostomy tube placement followed by thoracoscopic esophagectomy and cervical esophagostomy placement as the first-stage operation. Gastrostomy feeding was started on postoperative day (POD) 3 with a polymeric formula (ENSURE H®). On POD 7, he developed acute abdominal pain and distension with bloody drainage through the gastrostomy tube. Dynamic computed tomography showed massive hepatic portal venous gas and pneumatosis intestinalis. Angiography showed diffuse spasms in the branches of the superior mesenteric artery. Under a diagnosis of NOMI, we started intra-arterial infusion of papaverine and prostaglandin E1. His symptoms improved, and he was discharged on POD 48. In case 2, a 68-year-old man with diabetes and atrial fibrillation was diagnosed with esophageal cancer. His medical history was significant for pylorus-preserving gastrectomy for gastric cancer and small bowel resection for trauma. He underwent thoracoscopic esophagectomy, open total gastrectomy, colonic reconstruction, and jejunostomy tube placement. Adhesiolysis for abdominal severe adhesions caused by previous operations was difficult. Jejunostomy feeding was started on POD 3 with a polymeric formula (Racol®). On POD 7, he developed persistent diarrhea and cervical anastomotic leakage. On POD 9, he developed acute abdominal pain and distension with bloody drainage through the jejunostomy tube. Dynamic computed tomography showed the same findings as in case 1. Under a diagnosis of NOMI, we started intravenous infusion of papaverine and prostaglandin E1. His symptoms improved, and he was discharged on POD 28.

Conclusions: The causes of feeding-related NOMI may include the use of a high-osmolarity formula, preoperative malnutrition, abdominal adhesiolysis, systemic inflammation after anastomotic leakage, and a medical history of diabetes and atrial fibrillation. NOMI should be considered as a differential diagnosis in patients with these risk factors and clinical features such as acute abdominal pain and distension during enteral feeding.
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http://dx.doi.org/10.1186/s40792-019-0580-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382915PMC
February 2019

Analysis of GNA13 Protein in Follicular Lymphoma and its Association With Poor Prognosis.

Am J Surg Pathol 2018 11;42(11):1466-1471

Departments of Pathology.

GNA13 is a G protein involved in modulating tumor proliferative capacity, infiltration, metastasis, and migration. Genomic alteration of GNA13 was frequently observed in follicular lymphoma (FL). In this study, we examined 167 cases of FL by immunostaining of GNA13 using tissue microarray to evaluate the clinical significance. There were 26 GNA13-positive cases (15.6%) and 141 GNA13-negative cases (84.4%). GNA13-positive cases had a higher incidence of early progression of disease for which disease progression was recognized within 2 years compared with GNA13-negative cases (P=0.03). There were no significant differences in other clinicopathologic factors including histological grade, BCL2-IGH translocation, immunohistochemical phenotype, and Follicular Lymphoma International Prognostic Index. In addition, overall survival and progression-free survival were poorer in GNA13-positive cases than in GNA13-negative cases (P=0.009 and 0.005, respectively). In multivariate analysis, GNA13 positivity was found to be a poor prognostic factor for overall survival and progression-free survival. Thus, GNA13 protein expression was an independent prognostic factor and may affect disease progression in FL.
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http://dx.doi.org/10.1097/PAS.0000000000000969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266301PMC
November 2018

Primary hepatic carcinosarcoma with multimodal treatment.

Nagoya J Med Sci 2018 Aug;80(3):423-429

Department of Surgery, Yachiyo Hospital, Anjo-shi, Japan.

Hepatic carcinosarcoma (HCS) generally presents in advanced stages, demonstrates aggressive behavior, and has a poor prognosis. Other than curative primary resection, no effective treatment options exist. We present a case of resected HCS with four repeat resections for solitary lymph node recurrence followed by chemoradiotherapy with doxorubicin and ifosfamide. A 67-year-old Japanese man was admitted to our hospital for evaluation of an asymptomatic hepatic tumor. The patient underwent right hepatectomy with a presumptive preoperative diagnosis of atypical hepatocellular carcinoma. Based on histopathological and immunohistochemical findings, the tumor was diagnosed as HCS containing osteosarcoma and chondrosarcoma components. After the initial surgery, the patient underwent four additional resections for solitary lymph node HCS recurrence, and then underwent chemoradiotherapy with doxorubicin and ifosfamide for an unresectable lymph node recurrence. Chemotherapy was stopped after two cycles because of severe adverse events, although chemoradiotherapy markedly reduced the size of the lymph node recurrence and provided a progression-free survival of 12 months. Thirty-seven months after the initial surgery, the patient died of cardiac invasion of multiple mediastinal lymph node metastases. The clinical course outlined in this case report suggests that chemoradiotherapy with doxorubicin and ifosfamide for metastatic HCS may prolong survival in patients with unresectable lesions.
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http://dx.doi.org/10.18999/nagjms.80.3.423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125652PMC
August 2018

Expression pattern of immunosurveillance-related antigen in adult T cell leukaemia/lymphoma.

Histopathology 2018 May 21;72(6):945-954. Epub 2018 Feb 21.

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

Aims: Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and β2 microglobulin (β2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL.

Methods And Results: We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for β2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and β2M in the cell membrane (HLA β2M ). No significant clinical differences other than prognosis were found between the HLA β2M group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1 ) (P = 0.011) of the HLA β2M group than in the other groups. The HLA β2M group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLA β2M with miPD-L1 had the most favourable prognosis among all groups.

Conclusions: The membranous expression of HLA and β2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy.
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http://dx.doi.org/10.1111/his.13461DOI Listing
May 2018

A distinct subtype of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder: adult patients with chronic active Epstein-Barr virus infection-like features.

Haematologica 2018 06 14;103(6):1018-1028. Epub 2017 Dec 14.

Department of Pathology, Kurume University School of Medicine, Niigata University, Japan.

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (=0.005), but greater frequency of skin lesions (<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (<0.001 and =0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (=0.0087, =0.0236, and =0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (<0.001 and =0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.
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http://dx.doi.org/10.3324/haematol.2017.174177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058795PMC
June 2018

Prognostic factors for histiocytic and dendritic cell neoplasms.

Oncotarget 2017 Nov 19;8(58):98723-98732. Epub 2017 Oct 19.

Department of Pathology, Kurume University, School of Medicine, Kurume, Japan.

Histiocytic and dendritic cell neoplasms are rare and poorly studied. We report the clinical characteristics and prognostic factors in such cases in Japan. We investigated the clinical characteristics and survival in adult patients with histiocytic and dendritic cell neoplasms. Fifty patients had histiocytic sarcoma, 12 had Langerhans cell histiocytosis, 11 had follicular dendritic cell sarcoma, 8 had Langerhans cell sarcoma, 6 had interdigitating cell sarcoma and 1 had indeterminate dendritic cell sarcoma. The median follow-up period was 18.0 (range: 9.6-71.8) months, and median overall survival (OS) was . The 2-year OS rate was . In the multivariate analysis, elevated lactate dehydrogenase (LDH) ( =.004), ECOG performance status (PS) 2-4 ( =.006), and Ann Arbor stage III-IV ( =.008) affected OS. Stratification by elevated LDH, ECOG PS 2-4, and Ann Arbor stage III-IV allowed classification of patients into low risk, intermediate risk, and high risk groups. The same classification was applicable for HS and non-HS categories. In the rare neoplasms of histiocytic and dendritic cell sarcoma, ECOG PS, Ann Arbor stage, and LDH are important prognostic factors for predicting survival.
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http://dx.doi.org/10.18632/oncotarget.21920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716762PMC
November 2017

Clinicopathological features of primary splenic follicular lymphoma.

Ann Hematol 2017 Dec 3;96(12):2063-2070. Epub 2017 Oct 3.

Department of Pathology, School of Medicine, Kurume University, 67, Asahi-machi, Kurume, 830-0011, Japan.

Follicular lymphoma (FL) is a low-grade lymphoma that is usually characterized by generalized lymphadenopathy. Extranodal invasion by FL generally involves the bone marrow, skin, and duodenum; splenic infiltration often occurs in the advanced stages. However, primary splenic FL is very rare. Hence, few studies have been performed on splenic FL, and its clinicopathological features have not been established. This study aimed to investigate the clinicopathological features of primary splenic FL, as compared to nodal FL. We analyzed 17 patients diagnosed with primary splenic FL and 153 control patients with systemic FL. Hepatitis C virus (HCV)-positive status was significantly more common in patients with splenic FL than in the control patients (p = 0.02). Ann Arbor stage III or IV (p = 0.0003) and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) (p = 0.03) were significantly less common in patients with splenic FL than in the control patients; however, the overall and progression-free survival curves were not significantly different between the groups. Among the 17 patients with splenic FL, the progression-free survival was significantly worse in patients who underwent splenectomy without receiving postoperative chemotherapy than in those who did (p = 0.03). These results suggest that primary splenic FL should be considered different from systemic FL; accordingly, its management should also be conducted differently.
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http://dx.doi.org/10.1007/s00277-017-3139-yDOI Listing
December 2017

Clinical effect of immunophenotyping on the prognosis of multiple myeloma patients treated with bortezomib.

Oncol Lett 2017 May 27;13(5):3803-3808. Epub 2017 Mar 27.

Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.

In the present study, the effect of immunophenotyping on the prognoses of patients with multiple myeloma (MM) treated with bortezomib plus dexamethasone was investigated. The study involved 46 patients with MM, and analyzed the prognostic significance of the expression of cluster of differentiation (CD)45, CD56 and mature plasma cell (MPC)-1, and other factors including the International Staging System (ISS) stage, age, gender, the immunoglobulin subtype and the treatment line number prior to bortezomib treatment. Although CD56 and MPC-1 expression did not appear to affect the time to next treatment (TNT) or overall survival rate (OS), the univariate analysis determined that CD45 positivity was an adverse prognostic factor for TNT and OS, and that being male was significantly associated with inferior TNT and OS. Multivariate analyses determined that CD45 expression was prognostically significant for TNT and OS. In conclusion, CD45 positivity is an adverse prognostic factor in MM patients treated with bortezomib. The data from the present study demonstrate the clinical importance of classifying MM cells immunophenotypically to determine the prognoses of patients.
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http://dx.doi.org/10.3892/ol.2017.5920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431368PMC
May 2017

RsgA couples the maturation state of the 30S ribosomal decoding center to activation of its GTPase pocket.

Nucleic Acids Res 2017 Jun;45(11):6945-6959

Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain.

During 30S ribosomal subunit biogenesis, assembly factors are believed to prevent accumulation of misfolded intermediate states of low free energy that slowly convert into mature 30S subunits, namely, kinetically trapped particles. Among the assembly factors, the circularly permuted GTPase, RsgA, plays a crucial role in the maturation of the 30S decoding center. Here, directed hydroxyl radical probing and single particle cryo-EM are employed to elucidate RsgA΄s mechanism of action. Our results show that RsgA destabilizes the 30S structure, including late binding r-proteins, providing a structural basis for avoiding kinetically trapped assembly intermediates. Moreover, RsgA exploits its distinct GTPase pocket and specific interactions with the 30S to coordinate GTPase activation with the maturation state of the 30S subunit. This coordination validates the architecture of the decoding center and facilitates the timely release of RsgA to control the progression of 30S biogenesis.
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http://dx.doi.org/10.1093/nar/gkx324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499641PMC
June 2017

Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.

Schizophr Res 2017 07 7;185:33-40. Epub 2017 Jan 7.

Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan. Electronic address:

Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABA receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABA receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (P=0.002; uncorrected) and rs1157122 (P=0.006; uncorrected) showed top hits, followed by rs723432 (P=0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology.
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http://dx.doi.org/10.1016/j.schres.2017.01.003DOI Listing
July 2017
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