A Novel Hypoxia Imaging Endoscopy System

Measurement of tumor hypoxia is required for the diagnosis of tumor and the evaluation of therapeutic outcome. Currently, invasive and noninvasive techniques being exploited for tumor hypoxia measurement include polarographic needle electrodes, immunohistochemical (IHC) staining, magnetic resonance imaging (MRI), radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), optical imaging (bioluminescence and fluorescence), and hypoxia imaging endoscopy. This review provides a summary of the modalities available for assessment of tissue oxygenation as well as a discussion of current arguments for and against each modality, with a particular focus on noninvasive hypoxia imaging with emerging agents and new imaging technologies intended to detect molecular events associated with tumor hypoxia

Halo models in modified gravity theories with self-accelerated expansion

We investigate the structure of halos in the sDGP (self-accelerating branch of the Dvali-Gavadadze-Porrati braneworld gravity) model and the galileon modified gravity model on the basis of the static and spherically symmetric solutions of the collisionless Boltzmann equation, which reduce to the singular isothermal sphere model and the King model in the limit of Newtonian gravity. The common feature of these halos is that the density of a halo in the outer region is larger (smaller) in the sDGP (galileon) model, respectively, in comparison with Newtonian gravity. This comes from the suppression (enhancement) of the effective gravity at large distance in the sDGP (galileon) model, respectively. However, the difference between these modified gravity models and Newtonian gravity only appears outside the halo due to the Vainshtein mechanism, which makes it difficult to distinguish between them. We also discuss the case in which the halo density profile is fixed independently of the gravity model for comparison between our results and previous work.Comment: 15pages, 6 figures, maches the version to be published in Int. J. Mod. Phys. D, typos correcte

Long-term survival without recurrence after surgery for gastric yolk sac tumor-like carcinoma: a case report

Background Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. Case presentation A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller-Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. Conclusions Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor

Intracorporeal semi‐hand‐sewn Billroth I reconstruction in total laparoscopic distal gastrectomy

Introduction Intracorporeal Billroth I (B‐I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi‐hand‐sewn (SHS) B‐I reconstruction. Materials and surgical technique After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B‐I anastomosis. All the transection line of the duodenum and one‐third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand‐sewn technique. Discussion SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra‐abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32‐63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill

Mechanistic investigation into the light soaking effect observed in inverted polymer solar cells containing chemical bath deposited titanium oxide

In the glass-indium tin oxide (ITO)/titanium oxide (TiOx)/regioregular poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C61 butyric acid methyl ester (PCBM)/poly(3,4-ethylenedioxylenethiophene):poly(4-styrenesulfonic acid) (PEDOT:PSS)/Au cell (TiOx cell), which contains amorphous titanium oxide prepared by chemical bath deposition and dried at 150 °C, a light soaking effect has been observed upon irradiation with white light. In contrast, in ITO/titanium oxide (TiO2)/P3HT:PCBM/PEDOT:PSS/Au cell (TiO2 cell), which contains anatase titanium oxide prepared by heat treatment at 450 °C, the maximum power conversion efficiency was obtained just after irradiation with white light. The number of P3HT+• cation radicals in the quartz-ITO/TiOx and TiO2/P3HT:PCBM substrates was estimated by ESR measurements at room temperature upon irradiation with white light. It increased gradually with an increase in irradiation time for the TiOx substrate but increased only slightly just after light irradiation for the TiO2 substrate. Upon irradiation with UV-cut light, the performance of the TiOx cell was inferior to that of the TiO2 cell. This could be related to the resistances of the P3HT:PCBM layers which were estimated by alternating current impedance spectroscopy. The resistance of the P3HT:PCBM layer in the TiOx cell was much larger than that in the TiO2 cell, though the difference between the two cells was merely heat treatment temperature of titanium oxide films using as electron collection layers. That is, the concentration of photocarriers in the P3HT:PCBM of the TiOx cell was significantly less than that in the P3HT:PCBM of the TiO2 cell. From these experimental results, the light soaking effect could be reasonably explained by assuming the existence of charge recombination centers in the TiOx near the TiOx/P3HT:PCBM interface

Radiosensitization by telomerase-dependent oncolytic adenovirus

DNA修復機能阻害は放射線感受性を増強させるため，DNA修復に関与する因子の阻害剤は放射線増感剤となり得る．我々の開発したテロメラーゼ依存的腫瘍融解アデノウイルス製剤OBP-301（テロメライシン）は，アデノウイルスE1B55kDaタンパクを介して細胞のDNA修復に重要な役割を果たすMRN複合体（Mre11，Rad50，NBS1）を分解する機能を有する．このMRN複合体の分解によりATM（ataxia-telangiectasia mutated）の活性化が抑制され結果的にDNA修復機構が阻害される．我々はOBP-301と放射線との併用が強力な相乗効果を生み出すことをマウスの皮下腫瘍モデルおよび食道癌同所性モデルにおいて証明した．これらの結果はOBP-301が将来有望な放射線増感剤となり得ることだけでなく，E1B55kDaタンパクを産生する腫瘍融解アデノウイルス製剤と放射線との併用が悪性腫瘍に対する有力な治療戦略となり得ることを示す

Personalized prediction of overall survival in patients with AML in non‐complete remission undergoing allo‐HCT

Allogenic hematopoietic stem cell transplantation (allo-HCT) is the standard treatment for acute myeloid leukemia (AML) in non-complete remission (non-CR); however, the prognosis is inconsistent. This study aimed to develop and validate nomograms and a web application to predict the overall survival (OS) of patients with non-CR AML undergoing allo-HCT (cord blood transplantation [CBT], bone marrow transplantation [BMT], and peripheral blood stem cell transplantation [PBSCT]). Data from 3052 patients were analyzed to construct and validate the prognostic models. The common significant prognostic factors among patients undergoing allo-HCT were age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The conditioning regimen was a significant prognostic factor only in patients undergoing CBT. Compared with cyclophosphamide/total body irradiation, a conditioning regimen of ≥3 drugs, including fludarabine, with CBT exhibited the lowest hazard ratio for mortality (0.384; 95% CI, 0.266-0.554; p < 0.0001). A conditioning regimen of ≥3 drugs with CBT also showed the best leukemia-free survival among all conditioning regimens. Based on the results of the multivariable analysis, we developed prognostic models showing adequate calibration and discrimination (the c-indices for CBT, BMT, and PBSCT were 0.648, 0.600, and 0.658, respectively). Our prognostic models can help in assessing individual risks and designing future clinical studies. Furthermore, our study indicates the effectiveness of multi-drug conditioning regimens in patients undergoing CBT

RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer

Most cases of colorectal cancers (CRCs) are microsatellite stable (MSS), which frequently demonstrate lower response rates to immune checkpoint inhibitors (ICIs). RNA editing produces neoantigens by altering amino acid sequences. In this study, RNA editing was induced artificially by chemoradiation therapy (CRT) to generate neoantigens in MSS CRCs. Altogether, 543 CRC specimens were systematically analyzed, and the expression pattern of ADAR1 was investigated. In vitro and in vivo experiments were also performed. The RNA editing enzyme ADAR1 was upregulated in microsatellite instability-high CRCs, leading to their high affinity for ICIs. Although ADAR1 expression was low in MSS CRC, CRT including oxaliplatin (OX) treatment upregulated RNA editing levels by inducing ADAR1. Immunohistochemistry analyses showed the upregulation of ADAR1 in patients with CRC treated with CAPDX (capecitabine +OX) radiation therapy relative to ADAR1 expression in patients with CRC treated only by surgery (p <0.001). Compared with other regimens, CRT with OX effectively induced RNA editing in MSS CRC cell lines (HT29 and Caco2, p <0.001) via the induction of type 1 interferon-triggered ADAR1 expression. CRT with OX promoted the RNA editing of cyclin I, a neoantigen candidate. Neoantigens can be artificially induced by RNA editing via an OX-CRT regimen. CRT can promote proteomic diversity via RNA editing

ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer

Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy

Resected Intrahepatic Cholangiocarcinoma with Anaphylactic Shock from a Preoperative Liver Function Test before Hepatectomy

The indocyanine green test is a reliable liver function examination before major hepatectomy, and anaphylaxis is rarely a concern. A 65-year-old male patient without epigastralgia was diagnosed with a 2.2-cm intrahepatic cholangiocarcinoma. He had no history of allergic reactions. Some liver dysfunction was indicated by the laboratory data; however, there was no marked obstructive jaundice and the liver functional reserve was maintained by technetium-99m galactosyl serum albumin. The indocyanine green test was routinely performed, but the patient immediately demonstrated severe anaphylaxis due to indocyanine green administration. He had cardiorespiratory arrest, but recovered after immediate resuscitation. Although acute renal and respiratory failure was significant, the patient recovered at day 10 after the event, and his liver function and other organ functions were improved. Then, the scheduled left hepatectomy with caudate and extrahepatic duct resection was successfully performed without issues. The patient exhibited no allergic response against the administration of antibiotics or other drugs and the postoperative course was uneventful. The patient was discharged on day 17. The tumor was diagnosed as stage III intrahepatic cholangiocarcinoma and R0 resection was accomplished. Preoperative management, including the liver functional loading test, should be carefully carried out before major hepatectomy