Publications by authors named "Takeshi Nishikawa"

256 Publications

Efficacy of the Antigenicity-Retaining Ability of Fixative Solutions for Liquid-Based Cytology: Immunocytochemistry of Long-Term Storage.

Acta Cytol 2021 Sep 14:1-12. Epub 2021 Sep 14.

Department of Pathology, Nara Medical University Hospital, Nara, Japan.

Introduction/objective: Liquid-based cytology (LBC) is advantageous as multiple stained specimens can be prepared and used for additional assays such as immunocytochemical and molecular-pathological investigations. Two types of preservative-fixative solutions (fixatives) are used for nongynecologic specimens used in the BD SurePath-LBC (SP-LBC) method, and their components vary. However, few studies have evaluated the differences in antigen-retaining ability between these fixatives. Therefore, we investigated and compared the antigen-retaining ability of the fixatives in immunocytochemical staining (ICC) under long-term storage conditions.

Materials And Methods: Sediments of cultured RAJI cells (derived from Burkitt's lymphoma) were added to each fixative (red and blue) and stored at room temperature for a specified period (1 h; 1 week; and 1, 3, and 6 months). The specimens were then prepared using the SP-LBC method and subjected to ICC. Positivity rate was calculated using the specimens fixed at room temperature for 1 h as a control. Antibodies against Ki67 expressed in the nucleus and against CD20 and leukocyte common antigen (LCA) expressed on the cell membrane were used.

Results: For CD20 and LCA, the positivity rate increased with time in the red fixative compared with that in the control. In the blue fixative, the positivity rate was highest at 1 h and was maintained at a high level throughout the storage period. In contrast, the Ki67 positivity rate was highest at 1 h in both red and blue fixatives and markedly decreased with time. Therefore, although refrigerated (8°C) storage was used, no improvement was noted.

Conclusions: Long-term storage is possible for cell membrane antigens at room temperature; however, it is unsuitable for intranuclear antigens. Therefore, we conclude that suitable fixative type and storage temperature differ based on antigen location. Further investigation is warranted.
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http://dx.doi.org/10.1159/000518452DOI Listing
September 2021

Analysis of the Positional Relationship Among the Operator, Camera, and Monitor: Overcoming the Difficulties of Mirror-image Conditions During Laparoscopic Surgery.

Surg Laparosc Endosc Percutan Tech 2021 Jun 23. Epub 2021 Jun 23.

Department of Surgical Oncology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.

Background: Although methods to overcome difficulties associated with mirror-image conditions have been investigated, the ideal spatial relationship among the operator line of sight, monitor location, and camera location remains unclear. Moreover, the best training method for improving laparoscopic surgical skills under varying operator line of sight, camera, and monitor positions is unknown. We aimed to investigate the role of laparoscopic training under mirror-image conditions in improving surgical efficiency and whether prior surgical experience affects such training.

Methods: This prospective study was conducted at the Department of Surgical Oncology, Tokyo University, Japan. Twenty-five surgeons participated. Novice (n=14), trained (n=7), and expert (n=4) participants performed the simulated task in a box trainer while varying the positional relationships among the surgeons, camera, and monitor. Five patterns were repeatedly performed 5 times per day for 4 days over 2 weeks.

Results: The most significant differences in terms of the time required to complete the task under mirror-image conditions among the 3 groups were on day 1 (novices: 185.8 s, trained: 79.7 s, and experts: 46.5 s, P=0.009). However, after 4 days of training, the corresponding times did not differ among the 3 groups (26.0, 30.7, and 23.1 s, respectively; P=0.415). Laparoscopic training was sufficiently effective under mirror-image conditions.

Conclusions: Mirror-image surgical conditions provided the most difficult setting, because surgeons and assistants often became disoriented, and task performance was most degraded. However, just 4 days of training was found to be sufficient to overcome the difficulties encountered while performing laparoscopic procedures under mirror-image conditions.
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http://dx.doi.org/10.1097/SLE.0000000000000955DOI Listing
June 2021

Risk factors for non-reaching of ileal pouch to the anus in laparoscopic restorative proctocolectomy with handsewn anastomosis for ulcerative colitis.

Intest Res 2021 Mar 12. Epub 2021 Mar 12.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aims: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis and handsewn anastomosis for ulcerative colitis requires pulling down of the ileal pouch into the pelvis, which can be technically challenging. We examined risk factors for the pouch not reaching the anus.

Methods: Clinical records of 62 consecutive patients who were scheduled to undergo RPC with handsewn anastomosis at the University of Tokyo Hospital during 1989-2019 were reviewed. Risk factors for non-reaching were analyzed in patients in whom hand sewing was abandoned for stapled anastomosis because of nonreaching. Risk factors for non-reaching in laparoscopic RPC were separately analyzed. Anatomical indicators obtained from presurgical computed tomography (CT) were also evaluated.

Results: Thirty-seven of 62 cases underwent laparoscopic procedures. In 6 cases (9.7%), handsewn anastomosis was changed to stapled anastomosis because of non-reaching. Male sex and a laparoscopic approach were independent risk factors of non-reaching. Distance between the terminal of the superior mesenteric artery (SMA) ileal branch and the anus > 11 cm was a risk factor for non-reaching.

Conclusions: Laparoscopic RPC with handsewn anastomosis may limit extension and induction of the ileal pouch into the anus. Preoperative CT measurement from the terminal SMA to the anus may be useful for predicting non-reaching.
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http://dx.doi.org/10.5217/ir.2020.00158DOI Listing
March 2021

Clinical significance of CD8 and FoxP3 tumor-infiltrating lymphocytes and MFG-E8 expression in lower rectal cancer with preoperative chemoradiotherapy.

Mol Clin Oncol 2021 May 5;14(5):87. Epub 2021 Mar 5.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Preoperative chemoradiotherapy (CRT) for rectal cancer contributes to tumor down-staging and decreases locoregional recurrence. However, each patient shows a significantly different response to CRT. Therefore, the identification of predictive factors to CRT response would be beneficial to avoid unnecessary treatment. Cancer immunity in patients has been suggested to play an important role in the eradication of the tumor by CRT. In the present study, the utility of CD8 and forkhead box P3 (FoxP3) tumor-infiltrating lymphocytes (TILs) and the expression of a novel immuno-regulatory factor, lactadherin (MFG-E8), in predicting CRT effectiveness in patients with rectal cancer was examined. A total of 61 patients with rectal cancer, who underwent curative resection following CRT were included in the study. The numbers of CD8 and FoxP3 TILs in a biopsy taken before CRT and MFG-E8 expression level in the specimens obtained at the time of the surgery after CRT were examined using immunohistochemical staining, and their association with clinicopathological characteristics, including patient survival, was determined. The tumors with more CD8 TILs in the biopsy samples before CRT showed a significantly more favorable CRT response. The patients with tumors and a higher number of CD8 TILs before CRT also exhibited significantly longer disease-free and overall survival times. Higher MFG-E8 expression level in post-CRT specimens was significantly associated with favorable CRT response; however, no significant association was found with any other clinicopathological characteristics, including survival time. The number of CD8 TILs before CRT was a valuable predictor for CRT response and was associated with favorable prognosis in patients with lower rectal cancer and who were treated with CRT. High MFG-E8 expression level after CRT was also associated with a favorable CRT response.
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http://dx.doi.org/10.3892/mco.2021.2249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976375PMC
May 2021

Establishment of deformable three-dimensional printed models for laparoscopic right hemicolectomy in transverse colon cancer.

ANZ J Surg 2021 Jul 26;91(7-8):E493-E499. Epub 2021 Feb 26.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Applications of three-dimensional (3-D) printed solid organ models for navigation and simulation were previously reported for abdominal surgeries, and their usefulness was shown by subjective evaluation. However, thus far, no study has examined the effect of intraoperative movements for tissue handling. Novel, deformable 3-D printed models of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) were created to optimize laparoscopic right hemicolectomy. The aim of this study was to establish a method using these individualized models for use in surgical practice.

Methods: Deformable 3-D models for laparoscopic right hemicolectomy were created using a 3-D printing flexible filamentous material (thermoplastic polyurethane). Five patients with transverse colon cancer who underwent laparoscopic right hemicolectomy with D3 lymphadenectomy between April 2017 and September 2019 were enrolled in this study. Then, the created patient-specific models were compared with the previously recorded intraoperative video views.

Results: Transverse colon mobilization changed the spatial arrangement of the branches of the SMA and SMV. The 3-D models reproduced the intraoperative view, although approaches to the dominant vessels to complete D3 lymphadenectomy may vary.

Conclusions: Deformable 3-D models of the SMA and SMV with added branches may aid in optimizing laparoscopic right hemicolectomy operations.
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http://dx.doi.org/10.1111/ans.16659DOI Listing
July 2021

Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Dis Colon Rectum 2021 03;64(3):274-283

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Although chemoradiotherapy followed by radical surgery without lateral lymph node dissection is the current standard treatment in patients with rectal cancer, recent studies have demonstrated the benefits of adding lateral lymph node dissection to total mesorectal excision in patients with suspected lateral lymph node metastasis. However, the optimal indication for lateral lymph node dissection after chemoradiotherapy has not been determined.

Objective: This study aimed to establish the optimal indication for lateral lymph node dissection after chemoradiotherapy in patients with rectal cancer.

Design: This is a retrospective study.

Settings: This study was conducted at a single referral hospital.

Patients: A total of 279 patients with rectal cancer who underwent chemoradiotherapy followed by radical surgery between 2007 and 2018 were retrospectively enrolled.

Main Outcome Measures: The largest lateral lymph nodes on CT were retrospectively assessed and compared with the pathologic results of dissected lateral lymph nodes and recurrences in lateral lymph node areas.

Results: The incidence of lateral lymph node metastasis after chemoradiotherapy was estimated to be 9.3%. Although patients with lateral lymph node metastasis frequently developed distant recurrence, 40.4% survived for >5 years without recurrence. An analysis of the lateral lymph node sizes showed that lateral lymph node size ≥8 mm before chemoradiotherapy was the optimal criterion for lateral lymph node dissection, with a sensitivity and specificity of 92.3% and 78.7%. Using this criterion, 72.0% of the patients could be spared lateral lymph node dissection.

Limitations: Because of the retrospective nature of the present study, the selection of patients who underwent lateral lymph node dissection was biased.

Conclusions: The optimal indication for lateral lymph node dissection was lateral lymph node size ≥8 mm before chemoradiotherapy. Cancer could be eradicated in >30% of patients with lateral lymph node metastasis by dissecting metastatic lateral lymph nodes. See Video Abstract at http://links.lww.com/DCR/B428.

Criterios De Tamao Ptimo Para La Diseccin De Ganglios Linfticos Laterales Despus De La Quimiorradioterapia Neoadyuvante Para El Cncer De Recto: ANTECEDENTES:Aunque la quimiorradioterapia seguida por cirugía radical sin disección de ganglios linfáticos laterales es el tratamiento estándar actual en pacientes con cáncer de recto, estudios recientes han demostrado beneficios de agregar disección de ganglios linfáticos laterales a la escisión mesorrectal total en pacientes con sospecha de metástasis de ganglios linfáticos laterales. Sin embargo, no se ha determinado la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia.OBJETIVO:Este estudio tuvo como objetivo establecer la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Este estudio se realizó en un solo hospital de referencia.PACIENTES:Se inscribieron retrospectivamente un total de 279 pacientes con cáncer de recto que se sometieron a quimiorradioterapia seguida por cirugía radical entre 2007 y 2018.PRINCIPALES MEDIDAS DE VALORACION:Los ganglios linfáticos laterales más grandes en la tomografía computarizada se evaluaron retrospectivamente y se compararon con los resultados patológicos de los ganglios linfáticos laterales disecados y recidivas en las áreas de los ganglios linfáticos laterales.RESULTADOS:Se estimó que la incidencia de metástasis en los ganglios linfáticos laterales después de la quimiorradioterapia fue del 9,3%. Aunque los pacientes con metástasis en los ganglios linfáticos laterales con frecuencia desarrollaron recurrencia a distancia, el 40,4% sobrevivió durante más de 5 años sin recurrencia. Un análisis de los tamaños de los ganglios linfáticos laterales mostró que la mayor dimensión de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia eran el criterio óptimo para la disección de los ganglios linfáticos laterales, con una sensibilidad y especificidad del 92,3% y 78,7%, respectivamente. Utilizando este criterio, el 72,0% de los pacientes podría evitarse la disección de los ganglios linfáticos laterales.LIMITACIONES:Debido a la naturaleza retrospectiva del presente estudio, la selección de pacientes que fueron sometidos a disección de ganglios linfáticos laterales fue sesgada.CONCLUSIÓN:La indicación óptima para la disección de los ganglios linfáticos laterales fue la dimensión mayor de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia. El cáncer se podría erradicar en más del 30% de los pacientes con metástasis en los ganglios linfáticos laterales disecando los ganglios linfáticos laterales metastásicos. Consulte Video Resumen en http://links.lww.com/DCR/B428.
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http://dx.doi.org/10.1097/DCR.0000000000001866DOI Listing
March 2021

Clinical profiles of hyperglycemic crises: A single-center retrospective study from Japan.

J Diabetes Investig 2021 Aug 8;12(8):1359-1366. Epub 2021 Jan 8.

Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Aims/introduction: The aim of the present study was to clarify the pathophysiologies of hyperglycemic crises in Japanese patients.

Materials And Methods: This was a retrospective study of patients with hyperglycemic crises admitted to Kumamoto Medical Center, Kumamoto, Japan, between 2012 and 2019. Patients were classified as having diabetic ketoacidosis (DKA), hyperglycemic hyperosmotic syndrome (HHS) or a mixed state of the two conditions (MIX), and laboratory data and levels of consciousness at hospital admission, as well as the rates of mortality and coagulation disorders, were compared.

Results: The diagnostic criteria for hyperglycemic crisis were met in 144 cases, comprising 87 (60.4%), 38 (26.4%) and 19 (13.2%) cases of DKA, HHS and MIX, respectively. Type 1 diabetes was noted in 46.0 and 26.3% of patients in the DKA and MIX groups, respectively. Fibrin degradation product and D-dimer levels were significantly higher in the HHS group than in the DKA group (DKA and HHS groups: fibrin degradation product 7.94 ± 8.43 and 35.54 ± 51.80 μg/mL, respectively, P < 0.01; D-dimer 2.830 ± 2.745 and 14.846 ± 21.430 μg/mL, respectively, P < 0.01). Mortality rates were 5.7, 13.2 and 5.3% in the DKA, HHS and MIX groups, respectively. Seven patients (4.9%), four of whom were in the MIX group, had acute arterial occlusive diseases.

Conclusions: The low frequency of type 1 diabetes in DKA and MIX might be responsible for reduced insulin secretion in Japanese populations. Patients with hyperglycemic crises have increased coagulability, and acute arterial occlusion needs to be considered, particularly in MIX.
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http://dx.doi.org/10.1111/jdi.13475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354495PMC
August 2021

Synthesis and characterization of conductive flexible cellulose carbon nanohorn sheets for human tissue applications.

Biomater Res 2020 23;24:18. Epub 2020 Oct 23.

Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530 Japan.

Background: Conductive sheets of cellulose and carbon nanomaterials and its human skin applications are an interesting research aspect as they have potential for applications for skin compatibility. Hence it is needed to explore the effects and shed light on these applications.

Method: To fabricate wearable, portable, flexible, lightweight, inexpensive, and biocompatible composite materials, carbon nanohorns (CNHs) and hydroxyethylcellulose (HEC) were used as precursors to prepare CNH-HEC (Cnh-cel) composite sheets. Cnh-cel sheets were prepared with different loading concentrations of CNHs (10, 20 50,100 mg) in 200 mg cellulose. To fabricate the bio-compatible sheets, a pristine composite of CNHs and HEC was prepared without any pretreatment of the materials.

Results: The obtained sheets possess a conductivity of 1.83 × 10 S/m and bio-compatible with human skin. Analysis for skin-compatibility was performed for Cnh-cel sheets by h-CLAT in vitro skin sensitization tests to evaluate the activation of THP-1 cells. It was found that THP-1 cells were not activated by Cnh-cel; hence Cnh-cel is a safe biomaterial for human skin. It was also found that the composite allowed only a maximum loading of 100 mg to retain the consistent geometry of free-standing sheets of < 100 μm thickness. Since CNHs have a unique arrangement of aggregates (dahlia structure), the composite is homogeneous, as verified by transmission electron microscopy (TEM) and, scanning electron microscopy (SEM), and other functional properties investigated by Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), conductivity measurement, tensile strength measurement, and skin sensitization.

Conclusion: It can be concluded that cellulose and CNHs sheets are conductive and compatible to human skin applications.
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http://dx.doi.org/10.1186/s40824-020-00194-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583293PMC
October 2020

Low preoperative maximum squeezing pressure evaluated by anorectal manometry is a risk factor for non-reversal of diverting stoma.

Langenbecks Arch Surg 2021 Feb 19;406(1):131-139. Epub 2020 Oct 19.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: A diverting stoma is created to prevent anastomotic leakage and related complications impairing sphincteric function in rectal surgery. However, diverting stoma may be left unclosed. This study is aimed to analyze preoperative factors including anorectal manometric data associated with diverting stoma non-reversal before rectal surgery. We also addressed complications related to diverting stoma in patients undergoing surgery for rectal malignant tumor.

Methods: A total of 203 patients with rectal malignant tumor who underwent sphincter-preserving surgery with diverting stoma were retrospectively evaluated. The risk factors for non-reversal of diverting stoma were identified by univariate and multivariate analyses. For these analyses, anorectal manometric data were measured before rectal surgery. The association between stoma-related complications and other clinicopathological features was also analyzed.

Results: During the median follow-up of 46.4 months, 24% (49 patients) did not undergo stoma reversal. Among parameters that were available before rectal surgery, age ≥ 75 years, albumin < 3.5 g/dl, tumor size ≥ 30 mm, tumor distance from the anal verge < 4 cm, and maximum squeezing pressure (MSP) < 130 mmHg measured by anorectal manometry (ARM) were independent factors associated with stoma non-reversal. The most common stoma-related complication was peristomal skin irritation (25%). Ileostomy was the only factor associated with peristomal skin irritation.

Conclusion: The current study demonstrated that low preoperative MSP evaluated by ARM, old age, hypoalbuminemia, and a large tumor close to the anus were predictive of diverting stoma non-reversal. Stoma site should be well deliberated when patients have the aforementioned risk factors for diverting stoma non-reversal.
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http://dx.doi.org/10.1007/s00423-020-02011-wDOI Listing
February 2021

Hypoglycemia Induces Mitochondrial Reactive Oxygen Species Production Through Increased Fatty Acid Oxidation and Promotes Retinal Vascular Permeability in Diabetic Mice.

Antioxid Redox Signal 2021 06 28;34(16):1245-1259. Epub 2020 Aug 28.

Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Hypoglycemia is associated with increased reactive oxygen species (ROS) production and vascular events. We have previously reported that low-glucose (LG) conditions induce mitochondrial ROS (mtROS) production in aortic endothelial cells (ECs). However, the mechanism by which hypoglycemia promotes diabetic retinopathy (DR) is unclear. Blood-retinal barrier (BRB) disruption occurs in the early stages of DR. We hypothesized that the mechanisms underlying hypoglycemia-induced DR are associated with BRB breakdown due to mtROS generation during hypoglycemia. Here, we aimed to determine whether hypoglycemia exacerbated mtROS production and induced BRB disruption. We observed that hypoglycemia induced mtROS production by increasing fatty acid oxidation (FAO), which was suppressed by overexpression of mitochondrial-specific manganese superoxide dismutase (MnSOD) in retinal ECs. Furthermore, FAO blockade decreased the hypoglycemia-induced mtROS production. Recurrent hypoglycemia increased albumin leak in diabetic mice retina, which was suppressed in diabetic vascular endothelial cell-specific MnSOD transgenic (eMnSOD-Tg) mice. Pharmacological FAO blockade also reduced mtROS production, reduced vascular endothelial growth factor (VEGF) production during hypoglycemia, and prevented retinal vascular permeability in diabetic mice. MnSOD overexpression or carnitine palmitoyltransferase I (CPT1) blockade suppressed vascular endothelial-cadherin phosphorylation under LG in retinal ECs. Reduction of mtROS and VEGF production pharmacological FAO and/or CPT1 blockade may prevent hypoglycemia-induced worsening of DR.
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http://dx.doi.org/10.1089/ars.2019.8008DOI Listing
June 2021

Anastomotic bleeding following ileocolic end-to-side anastomosis using a circular stapler: incidence and risk factors.

Surg Today 2020 Nov 20;50(11):1368-1374. Epub 2020 May 20.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: To identify the incidence of and risk factors for postoperative bleeding after ileocolic end-to-side anastomosis using a circular stapler.

Methods: We analyzed, retrospectively, the risk factors for postoperative anastomotic bleeding in patients who underwent right-sided colectomy with end-to-side anastomosis done using a circular stapler during colon tumor surgery at our institute between January 2015 and March 2019.

Results: Anastomotic bleeding developed in 10 (3.6%) of the total 279 patients. Univariate analysis revealed that age ≥ 80 years (8.8% vs. 1.9%; P = 0.008) and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 1 (12.5% vs. 2.8%; P = 0.014) were significant risk factors for anastomotic bleeding. Postoperative anticoagulation therapy was not a risk factor for anastomotic bleeding. Multivariate analysis revealed that only age ≥ 80 years was an independent risk factor (odds ratio 4.12, 95% confidence interval 1.02-16.68, P = 0.047). Six of the ten patients with anastomotic bleeding were treated conservatively, three were treated by colonoscopic clipping, and one required surgery.

Conclusion: End-to-side anastomosis is safe and feasible, but must be performed carefully in the elderly, who are at higher risk of anastomotic bleeding.
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http://dx.doi.org/10.1007/s00595-020-02022-6DOI Listing
November 2020

Controlling Electronic States of Few-walled Carbon Nanotube Yarn via Joule-annealing and p-type Doping Towards Large Thermoelectric Power Factor.

Sci Rep 2020 Apr 29;10(1):7307. Epub 2020 Apr 29.

Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan.

Flexible, light-weight and robust thermoelectric (TE) materials have attracted much attention to convert waste heat from low-grade heat sources, such as human body, to electricity. Carbon nanotube (CNT) yarn is one of the potential TE materials owing to its narrow band-gap energy, high charge carrier mobility, and excellent mechanical property, which is conducive for flexible and wearable devices. Herein, we propose a way to improve the power factor of CNT yarns fabricated from few-walled carbon nanotubes (FWCNTs) by two-step method; Joule-annealing in the vacuum followed by doping with p-type dopants, 2,3,5,6-tetrafluo-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). Numerical calculations and experimental results explain that Joule-annealing and doping modulate the electronic states (Fermi energy level) of FWCNTs, resulting in extremely large thermoelectric power factor of 2250 µW m K at a measurement temperature of 423 K. Joule-annealing removes amorphous carbon on the surface of the CNT yarn, which facilitates doping in the subsequent step, and leads to higher Seebeck coefficient due to the transformation from (semi) metallic to semiconductor behavior. Doping also significantly increases the electrical conductivity due to the effective charge transfers between CNT yarn and F4TCNQ upon the removal of amorphous carbon after Joule-annealing.
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http://dx.doi.org/10.1038/s41598-020-64435-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190723PMC
April 2020

Anal canal adenocarcinoma with pagetoid spread and inguinal lymph node metastasis treated with preoperative chemoradiotherapy: A case report.

Mol Clin Oncol 2020 Jun 16;12(6):529-532. Epub 2020 Mar 16.

Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8655, Japan.

Perianal Paget's disease is a rare condition, which is not usually accompanied by cancer. Here, a case of anal canal carcinoma with pagetoid spread and inguinal lymph node metastasis, which exhibited a significant response to preoperative chemoradiotherapy (CRT), is presented. A 58-year-old woman was admitted to The University of Tokyo Hospital with a complaint of discomfort around the anus. Physical examination revealed an erythematous inflamed skin lesion in the perianal region and a tumor of 15 mm in diameter detected on palpation in the left inguinal region, which was diagnosed as metastatic adenocarcinoma by excisional biopsy. Colonoscopy revealed moderately differentiated adenocarcinoma of 15 mm in diameter in the anal canal. Skin biopsy of the perianal region revealed an infiltration of pagetoid cells, which were positive for cytokeratin 7, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. Based on these results, the patient was diagnosed as having anal canal adenocarcinoma with pagetoid spread. The patient received preoperative CRT including the bilateral inguinal region. After CRT, robotic-assisted laparoscopic abdominoperineal resection was performed. The macroscopic findings of the surgical specimen confirmed the formation of a scar as a result of the preoperative CRT. Microscopic examination of the anal tumor revealed no residual carcinoma or lymph node metastasis. In conclusion, this case may suggest the potential applicability of preoperative CRT for the local control of anal canal carcinoma with pagetoid spread.
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http://dx.doi.org/10.3892/mco.2020.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179386PMC
June 2020

Upfront Surgery for Small Intestinal Non-Hodgkin's Lymphoma.

Anticancer Res 2020 Apr;40(4):2373-2377

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: The clinical significance of surgery for secondary small intestinal non-Hodgkin's lymphomas (NHL) remains unknown. This study aimed to investigate the efficacy of resection for both primary and secondary small intestinal NHL.

Patients And Methods: Twenty patients with small intestinal lymphoma who underwent surgical resection at our Institute between 2009 and 2017 were retrospectively evaluated. The clinicopathological and surgery-related factors were reviewed. We also analyzed their surgical outcomes such as postoperative complications, perforation rate, and overall survival (OS).

Results: In total, 13 (65%) and 7 (35%) patients had primary and secondary lymphomas, respectively. A total of 70% of patients were diagnosed with aggressive-type lymphomas. A total of 15 (75%) patients had Lugano system stage IV. Only one (5%) patient experienced postoperative grade II deep vein thrombosis and pulmonary embolism. The 3-year OS rate after surgery was 59.6%.

Conclusion: Surgical resection prior to chemotherapy is a feasible and safe therapeutic strategy for small intestinal NHL.
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http://dx.doi.org/10.21873/anticanres.14206DOI Listing
April 2020

The Influence of Neoadjuvant Chemoradiation for Middle and Lower Rectal Cancer on Anorectal Function.

Anticancer Res 2020 Apr;40(4):2199-2208

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: To date, there is no clear understanding whether preoperative long-course chemoradiotherapy combined with surgery for rectal cancer is detrimental to anorectal function. The purpose of this study was to clarify the influence of preoperative chemoradiotherapy and surgery for middle and lower rectal cancer on postoperative anorectal function.

Patients And Methods: Data of 113 patients with middle or lower rectal cancer treated with preoperative chemoradiotherapy plus surgery or surgery alone between January 2013 and December 2016 were analyzed. A total of 84 and 29 patients underwent low anterior resection and intersphincteric resection, respectively. In patients with T3 or deeper and with any N stage cancer below peritoneal reflection, surgery plus lateral lymph node dissection or preoperative radiation (total: 50.4 Gy/28 fractions) to the pelvis with chemoradiotherapy plus surgery was treated. Anorectal function was assessed prior to treatment and 6 and 12 months postoperatively. Specifically, maximum resting pressure and maximum squeezing pressures were measured. The Wexner score was recorded prior to treatment and 12 months postoperatively.

Results: maximum resting pressure and maximum squeezing pressure decreased post-surgery in both groups. Maximum resting pressure and maximum squeezing pressure at 12 months and the Wexner score at 12 months post-surgery were comparable among patients treated with chemoradiotherapy plus surgery and those treated with surgery alone.

Conclusion: Preoperative chemoradiotherapy did not clearly impair postoperative anorectal function in patients who underwent low anterior resection and intersphincteric resection.
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http://dx.doi.org/10.21873/anticanres.14181DOI Listing
April 2020

Rectocolic and colocolic fistulas accompanied by cytomegalovirus infection: Two case reports.

Asian J Surg 2020 Jul 19;43(7):783-784. Epub 2020 Mar 19.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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http://dx.doi.org/10.1016/j.asjsur.2020.03.004DOI Listing
July 2020

Liquid-like dielectric response is an origin of long polaron lifetime exceeding 10 μs in lead bromide perovskites.

J Chem Phys 2020 Feb;152(8):084704

Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.

Lead halide perovskites are promising materials for optoelectronic applications because of their exceptional performances in carrier lifetime and diffusion length; however, the microscopic origins of their unique characteristics remain elusive. The organic-inorganic hybrid perovskites show unique dielectric functions, i.e., ferroelectric-like phonon responses in the 0.1-10 THz region and liquid-like rotational relaxation in the 1-100 GHz range. To reveal the role of the dielectric responses is of primal importance because the dielectric screening is a key to understanding the optoelectronic properties governed by polarons in the perovskites. Here, we conducted comparative studies of broadband dielectric spectroscopy on both all-inorganic CsPbBr and organic-inorganic hybrid (CHNH)PbBr single crystals to uncover the origin of the liquid-like dielectric relaxation in the 1-100 GHz range. We confirmed the absence of the dielectric response in the range of 10-10 Hz in CsPbBr, which was clearly present in the hybrid (CHNH)PbBr. This suggests that the response is almost purely due to the rotational motions of the organic dipoles in the hybrid perovskites. We evaluated the lifetimes of the polarons using surface-free transient photoluminescence. The lifetime in CsPbBr was up to 1.6 µs, while the lifetime in (CHNH)PbBr was 18 µs. The lifetime in the hybrid (CHNH)PbBr was significantly longer than in CsPbBr, also confirmed by transient infrared spectroscopy. We concluded that the liquid-like dielectric response inhibits polaron recombination due to the efficient separation of opposite charges by the additional dynamic disorder.
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http://dx.doi.org/10.1063/1.5127993DOI Listing
February 2020

Molecular Analysis of Liquid-Based Cytological Specimen Using Virtually Positive Sputum with Adenocarcinoma Cells.

Diagnostics (Basel) 2020 Feb 5;10(2). Epub 2020 Feb 5.

Department of Diagnostic Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.

Liquid-based cytology (LBC) analysis of sputum is a useful diagnostic and prognostic tool for detecting lung cancer. DNA and RNA derived from lung cancer cells can be used for this diagnosis. However, the quality of cytological material is not always adequate for molecular analysis due to the effect of formalin in the commercially available fixation kits. In this study, we examined DNA and RNA extraction methods for LBC analysis with formalin fixation, using lung carcinoma cell lines and sputum. The human non-small cell lung cancer cell lines were fixed with LBC fixation reagents, such as CytoRich red preservative. Quantification of thyroid transcription factor-1 (TTF-1) and actin mRNA, epidermal growth factor receptor (EGFR) DNA in HCC827, H1975, and H1299 cells, and mutation analysis of EGFR in HCC827 and H1975 cells were performed by quantitative PCR (qPCR) and fluorescence resonance energy transfer (FRET)-based preferential homoduplex formation assay (F-PHFA) method, respectively. mRNA and DNA extracted from cell lines using RNA and/or DNA extraction kits for formalin-fixed paraffin-embedded (FFPE) fixed with various LBC solutions were efficiently detected by qPCR. The detection limit of EGFR mutations was at a rate of 5% mutated positive cells in LBC. The detection limit of the EGFR exon 19 deletion in HCC827 was detected in more than 1.5% of the positive cells in sputum. In contrast, the detection limit of the T790M/L858R mutation in H1975 was detected in more than 13% of the positive cells. We also detected EGFR mutations using next generation sequencing (NGS). The detection limit of NGS for EGFR mutation was lower than that of the F-PHFA method. Furthermore, more than 0.1% of positive cells could be cytomorphologically detected. Our results demonstrate that LBC systems are powerful tools for cytopathological and genetic analyses. However, careful attention should be paid to the incidence of false negative results in the genetic analysis of EGFR mutations detected by LBC.
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http://dx.doi.org/10.3390/diagnostics10020084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168204PMC
February 2020

Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer.

Cancer Sci 2020 Apr 22;111(4):1291-1302. Epub 2020 Feb 22.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Postoperative distant metastasis dramatically affects rectal cancer patients who have undergone neoadjuvant chemoradiotherapy (NACRT). Here, we clarified the association between NACRT-mediated mammalian target of rapamycin (mTOR) signaling pathway activation and rectal cancer metastatic potential. We performed immunohistochemistry for phosphorylated mTOR (p-mTOR) and phosphorylated S6 (p-S6) on surgical specimen blocks from 98 rectal cancer patients after NACRT (cohort 1) and 80 colorectal cancer patients without NACRT (cohort 2). In addition, we investigated the association between mTOR pathway activity, affected by irradiation, and the migration ability of colorectal cancer cells in vitro. Based on the results of the clinical study, p-mTOR was significantly overexpressed in cohort 1 (with NACRT) as compared to levels in cohort 2 (without NACRT) (P < .001). High p-mTOR and p-S6 levels correlated with the development of distant metastasis only in cohort 1. Specifically, high p-S6 expression (HR 4.51, P = .002) and high pathological T-stage (HR 3.73, P = .020) after NACRT were independent predictors of the development of distant metastasis. In vitro, p-S6 levels and migration ability increased after irradiation in SW480 cells (TP53 mutation-type) but decreased in LoVo cells (TP53 wild-type), suggesting that irradiation modulates mTOR signaling and migration through cell type-dependent mechanisms. We next assessed the expression level of p53 by immunostaining in cohort 1 and demonstrated that p-S6 was overexpressed in samples with high p53 expression as compared to levels in samples with low p53 expression (P = .008). In conclusion, p-S6 levels after NACRT correlate with postoperative distant metastasis in rectal cancer patients, suggesting that chemoradiotherapy might modulate the mTOR signaling pathway, promoting metastasis.
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http://dx.doi.org/10.1111/cas.14332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156826PMC
April 2020

Assessment of the Changes in Mitochondrial Gene Polymorphism in Ulcerative Colitis and the Etiology of Ulcerative Colitis-associated Colorectal Cancer.

Anticancer Res 2020 Jan;40(1):101-107

Department of Surgical Oncology, the University of Tokyo, Tokyo, Japan.

Background: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer.

Materials And Methods: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared.

Results: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC.

Conclusion: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.
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http://dx.doi.org/10.21873/anticanres.13931DOI Listing
January 2020

Postoperative chemotherapy is associated with prognosis of stage IV colorectal cancer treated with preoperative chemotherapy/chemoradiotherapy and curative resection.

Int J Colorectal Dis 2020 Jan 5;35(1):177-180. Epub 2019 Dec 5.

Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Advances in systemic chemotherapy have increased the resectability in colorectal cancer (CRC) associated with metastases even if it was initially unresectable. However, what determines the prognosis of stage IV CRC patients treated by preoperative therapy and surgery remains unclear. We attempted to identify prognostic factors in such CRC patients.

Methods: We reviewed stage IV CRC patients who underwent curative resection between December 2007 and May 2019. The patients who underwent conversion chemotherapy for initially unresectable disease and those who received neoadjuvant chemotherapy (NAC) for resectable synchronous metastases or neoadjuvant chemoradiotherapy (NACRT) for advanced lower rectal cancer with resectable metastases were included. Recurrence-free survival (RFS) and overall survival (OS) were examined by multivariate analyses using Cox proportional hazard models. The RFS and OS curves were analyzed according to postoperative adjuvant chemotherapy (AC).

Results: Among 70 patients who underwent curative surgery (34 men, mean age: 60 years old), 33 had initially unresectable disease, 23 received NAC, and 14 NACRT. By multivariate analyses, AC was an independent predictor for improved RFS and OS (hazard ratio = 0.29, p = 0.0002, and hazard ratio = 0.37, p = 0.025). Patients treated with AC showed improved RFS and OS than those without AC (2-year RFS rate = 30% vs 19%, p = 0.031, and 3-year OS rate = 87% vs 67%, p = 0.045).

Conclusion: Because of its association with improved prognosis, AC should be considered for stage IV CRC patients after curative resection regardless of initial resectability status and preoperative therapy.
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http://dx.doi.org/10.1007/s00384-019-03461-5DOI Listing
January 2020

Accelerated perineural invasion in colitis-associated cancer: A retrospective cohort study.

Medicine (Baltimore) 2019 Oct;98(42):e17570

Department of Surgical Oncology.

Perineural invasion (PNI) is a prognostic factor in patients with colorectal cancer. Neurotrophic factors, molecular determinants of PNI, are altered in their expression levels in patients with ulcerative colitis. In this study, we evaluated the frequency of PNI in colitis-associated cancer (CAC) and sporadic cancer.We retrospectively reviewed 778 colorectal cancers with pathological T3-T4 in 761 patients all of whom were surgically resected without preoperative treatment. The lesions were classified into either CAC or sporadic cancer based on the clinical information. Clinicopathological findings including PNI were compared between CACs and sporadic cancers. Moreover, we analyzed the risk factors for positive PNI by multivariate analysis using a logistic regression model.Ten of the cancers (1.3%) were diagnosed as CACs, and the remaining 768 as sporadic cancers. CACs were characterized by being nonobstructive and predominantly located in the rectum. The CACs had a larger size and more frequent undifferentiated histology than sporadic cancers. PNI was observed more frequently in CACs (90%) than in sporadic cancers without obstruction (45%, P = .007). On multivariate analysis, CAC was one of the significant factors associated with PNI (odds ratio: 9.05, P = .040).Our results suggest that CAC was more likely to exhibit PNI than sporadic colorectal cancer.
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http://dx.doi.org/10.1097/MD.0000000000017570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824779PMC
October 2019

Management of isolated para-aortic lymph node recurrence of colorectal cancer.

Surg Today 2020 Sep 29;50(9):947-954. Epub 2019 Aug 29.

Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Isolated para-aortic lymph node recurrence (PALNR) after curative surgery for colorectal cancer (CRC) is rare and its optimal management is not defined clearly. This review investigates the best outcomes among published studies on the management of PALNR in the field of CRC. We searched the PubMed database for studies reporting on the management of isolated PALNR in CRC, published in English or Japanese from January, 2000 to December, 2018. Studies including patients with other metastases were excluded. A total of 24 retrospective studies including 227 patients with PALNR were evaluated. The 3-year overall survival (OS) ranged from 60 to 100%, with a median OS of 34-80 months for patients who underwent PALNR dissection, and 14-42 months for patients who received non-surgical treatment. No surgery-related mortality was reported and the incidence of surgical, mainly low-grade, complications ranged from 33 to 52%. The predictors of improved survival outcome included R0 resection margins. Dissection for PALNR from CRC is considered a feasible treatment option that may yield a better prognosis than non-surgical treatment alone. Preoperative chemotherapy or CRT should be considered for their potential benefits, including a reduction in cancer volume and improved R0 resection rates.
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http://dx.doi.org/10.1007/s00595-019-01872-zDOI Listing
September 2020

Clinical outcomes of preoperative chemoradiotherapy in octogenarian with locally advanced rectal cancer.

Mol Clin Oncol 2019 Aug 10;11(2):181-188. Epub 2019 Jun 10.

Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8655, Japan.

The number of elderly patients who receive surgical treatment for rectal cancer has gradually increased with aging of the population. In recent years, preoperative chemoradiotherapy, followed by surgical treatment, has been widely used for treating patients with locally advanced rectal adenocarcinoma. The aim of the present study was to evaluate if preoperative chemoradiotherapy is efficacious and safe for the treatment of rectal cancer in patients older than 80 years. A total of 293 patients with rectal cancer, who received preoperative chemoradiotherapy from 2007 to 2017, were studied. Comorbidities and the short- and long-term outcomes in elderly patients (aged ≥80 years old) were investigated and compared to younger patients. The elderly group comprised of 17 patients (5.8%). Pulmonary disease was the most common comorbidity (23.5%). No significant difference between the two groups regarding the rate of completeness of chemoradiotherapy was detected (P=0.26). Curative resection was performed in 14 patients in the elderly group and 252 patients in the younger group. Among 7 patients from both groups who could not receive curative resection due to their poor general condition, 4 patients had decreased lower respiratory function due to pneumonia (3 patients) or chronic obstructive pulmonary disease (1 patient). Morbidity and mortality rates were similar in elderly and younger groups (35.7% vs. 27.0%, 0% vs. 0%, respectively; P=0.54, P=1.00). No significant difference was found regarding recurrence between the two groups (P=1.00). To conclude, preoperative chemoradiotherapy in elderly patients with rectal cancer is safe and well tolerated.
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http://dx.doi.org/10.3892/mco.2019.1873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589936PMC
August 2019

The influence of pulmonary comorbidities on treatment choice and short-term surgical outcomes among elderly patients with colorectal cancer.

Int J Colorectal Dis 2019 Aug 28;34(8):1497-1501. Epub 2019 Jun 28.

Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Most elderly patients with colorectal cancer have comorbidities and reduced functional reserve, which may increase their risks of postoperative morbidity and mortality, and subsequently influence the treatment choice. Therefore, this study aimed to investigate the treatment choice and compare laparoscopic and open surgery in this setting.

Methods: This retrospective study evaluated 118 patients with colorectal cancer (≥ 85 years old between January 2007 and February 2018) to determine the influence of comorbidities on treatment choice, as well as the safety and feasibility of laparoscopic surgery for these patients.

Results: The patients included 42 men (35.6%) and 106 patients (89.8%) with comorbidities. The treatments were curative resection for 90 patients and palliative surgery for 16 patients, including 5 cases of colostomy/ileostomy because of the difficulty of primary cancer resection, pneumonia, or pulmonary hypertension. Twelve patients received non-surgical treatment, including 7 patients with decreased respiratory function because of chronic obstructive pulmonary disease or pneumonia. Forty-three patients underwent open curative resection and 47 patients underwent laparoscopic curative resection, which was associated with a significantly shorter hospital stay (14 days vs. 19days, P < 0.01), a lower morbidity rate (17.0% vs. 37.2%, P = 0.035), and less blood loss (10 mL vs. 140 mL, P < 0.01). One patient in each group died during the postoperative period because of worsened pre-existing pneumonia.

Conclusion: Laparoscopic surgery was safer and less invasive than open surgery for colorectal cancer among ≥ 85-year-old patients. Pulmonary comorbidities affected the choice of non-curative surgery and may be related to the risk of postoperative mortality.
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http://dx.doi.org/10.1007/s00384-019-03336-9DOI Listing
August 2019

Cecal cancer with essential thrombocythemia treated by laparoscopic ileocecal resection: a case report.

Surg Case Rep 2019 Jun 21;5(1):101. Epub 2019 Jun 21.

Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by thrombocytosis and a propensity for both thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Here, we report a case of colorectal cancer in an ET patient treated using laparoscopic ileocecal resection.

Case Presentation: A 40-year-old woman was admitted to our hospital after presenting with liver dysfunction. She had been previously diagnosed with ET; aspirin and anagrelide had been prescribed. Subsequent examination at our hospital revealed cecal cancer. Distant metastasis was absent; laparoscopic ileocecal resection was performed. Anagrelide was discontinued only on the surgery day. She was discharged on the seventh postoperative day without thrombosis or hemorrhage. However, when capecitabine and oxaliplatin were administered as adjuvant chemotherapy with continued anagrelide administration, she experienced hepatic dysfunction and thrombocytopenia; thus, anagrelide was discontinued. Five days later, her platelet count recovered. Subsequently, anagrelide and aspirin administration was resumed, without any adjuvant chemotherapy. Her liver function normalized gradually in 4 months. One-year post operation, she is well without tumor recurrence or new metastasis.

Conclusions: To our knowledge, this is the first report of laparoscopic colectomy performed on an ET patient receiving anagrelide. Our report shows that complications such as bleeding or thrombosis can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered.
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http://dx.doi.org/10.1186/s40792-019-0660-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588662PMC
June 2019

Laparoscopic surgery in rectal cancer patients taking anti-thrombotic therapy.

Minim Invasive Ther Allied Technol 2020 Aug 22;29(4):202-209. Epub 2019 May 22.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Several previous studies have shown that laparoscopic resection of rectal cancer is a feasible option. However, its safety and efficacy in patients receiving long-term anti-thrombotic therapy (AT) remain unclear. We retrospectively reviewed 364 patients who underwent elective resection for rectal cancer via a laparoscopic approach between 2007 and 2018 in our institute. Patients were classified according to the long-term use of AT. AT was interrupted perioperatively with or without heparin bridging therapy in all anti-thrombotic users. Clinicopathological factors and surgical outcomes were analyzed between patient groups. Thirty-two patients (9%) receiving AT were older and had lower albumin and hemoglobin levels than those not receiving AT (the non-AT group), and were predominantly male. Estimated blood loss and operative time in the AT group (median: 50 mL and 294 min) did not differ from those in the non-AT group (median: 20 mL and 295 min). There were no intergroup differences in the frequencies of other postoperative complications and oncological outcomes. Our results at the very least can support that laparoscopic surgery for rectal cancer is a safe and feasible option for patients taking long-term AT discontinued perioperatively.
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http://dx.doi.org/10.1080/13645706.2019.1619583DOI Listing
August 2020

The component changes of lysophospholipid mediators in colorectal cancer.

Tumour Biol 2019 May;41(5):1010428319848616

1 Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography-tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.
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http://dx.doi.org/10.1177/1010428319848616DOI Listing
May 2019

Diagnostic Efficacy of Liquid-Based Cytology in Endoscopic Ultrasound-Guided Fine Needle Aspiration for Pancreatic Mass Lesions During the Learning Curve: A Retrospective Study.

Pancreas 2019 May/Jun;48(5):686-689

From the The 3rd Department of Internal Medicine, and.

Objectives: The diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology widely varies depending on the treatment method used. Liquid-based cytology (LBC) has gained popularity in the gynecological field because of its efficacy in collection of target cells and simplicity in the manipulation of specimens. Since the introduction of EUS-FNA at our institution, we have used LBC for the diagnosis of pancreatic mass lesions. This study aims to investigate the diagnostic efficacy of EUS-FNA with LBC in patients with pancreatic mass lesions during the learning curve for EUS-FNA.

Methods: In this study, we retrospectively enrolled 222 patients with pancreatic mass lesions who were diagnosed using EUS-FNA with LBC between 2011 and 2016. The diagnostic yields for EUS-FNA with LBC for pancreatic mass lesions were evaluated.

Results: The diagnostic sensitivity, specificity, and accuracy for malignancy were found to be 93.9%, 95.1%, and 94.1%, respectively.

Conclusions: This study suggests that EUS-FNA with LBC for specimens provides good diagnostic efficacy in patients with pancreatic mass lesions even during the learning curve for EUS-FNA.
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http://dx.doi.org/10.1097/MPA.0000000000001304DOI Listing
February 2020

The combination of temsirolimus and chloroquine increases radiosensitivity in colorectal cancer cells.

Oncol Rep 2019 Jul 23;42(1):377-385. Epub 2019 Apr 23.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113‑8655, Japan.

The PI3K/AKT/mTOR pathway and autophagy are known to play important roles in cancer radioresistance. The aim of the present study was to investigate whether the combination of temsirolimus (TEM), an mTOR inhibitor, and chloroquine (CQ), an autophagy inhibitor, can increase radiosensitivity in colorectal cancer (CRC) cells. The efficacies of TEM and/or CQ as radiosensitizers were examined using clonogenic assays in CRC cell lines SW480 and HT‑29. The expression levels of the phosphorylated isoforms of S6 and 4E‑BP1, downstream proteins of mTOR, as well as the expression levels of p62 and LC3, autophagy‑related proteins, were assessed by western blot analysis. The formation of acidic organelles was detected in acridine orange‑stained cells. Apoptosis and caspase activity were assessed using flow cytometry. The results revealed that ionizing radiation (IR) activated the downstream proteins of mTOR and induced autophagy. In the clonogenic assays, neither TEM nor CQ influenced the efficacy of IR, whereas their combination significantly increased the dose‑dependent efficacy of IR. TEM inhibited phosphorylation of the downstream proteins of mTOR and induced autophagy. CQ inhibited autophagy in the late phase and did not influence the downstream proteins of mTOR. TEM and CQ inhibited both the phosphorylation of downstream proteins of mTOR and autophagy. Cell death analysis revealed that the combination of TEM and CQ strongly induced apoptosis in cells exposed to IR. In conclusion, the combination of TEM and CQ increased radiosensitivity in CRC cells through co‑inhibition of mTOR and autophagy.
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http://dx.doi.org/10.3892/or.2019.7134DOI Listing
July 2019
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