Publications by authors named "Kazuhiro Sakamoto"

188 Publications

Analysis of ileostomy stool samples reveals dysbiosis in patients with high-output stomas.

Biosci Microbiota Food Health 2021 17;40(3):135-143. Epub 2021 Feb 17.

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Construction of a diverting stoma can significantly reduce the onset of severe anastomotic leakage in patients with rectal cancer. High-output stoma is one of the most important potential surgical complications after anal function-preserving surgery with ileostomy. Culture-independent techniques have revealed the interaction of the complex intestinal bacterial ecology with various diseases. Our objective was to evaluate the differences in patient characteristics and gut microbiota distribution features in patients with high-output stomas. The cases of 24 consecutive patients who underwent curative resection for rectal cancer at our hospital between November 2016 and June 2018 were reviewed, and the patients were categorized into high-output and low-output groups. Their microbiota were analyzed using next-generation sequencing of ileostomy stool samples collected on postoperative day 7. There was a significant difference in the percentage of Bacteroidetes between the high-output and low-output groups (14.8% vs 0.5%; p=0.01). The percentage of was increased in the low-output group (p=0.01). After the exclusion of those treated with the probiotic Miya-BM, whose principal component is , analyses revealed no significant differences between the high-output and low-output groups. This pilot study provides the first evidence correlating gut microbiota with the pathogenesis of high- output stoma compared with low-output stoma.
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http://dx.doi.org/10.12938/bmfh.2020-062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279886PMC
February 2021

Clinical Significance of Lymph Node Dissection and Lymph Node Metastasis in Primary Appendiceal Tumor Patients After Curative Resection: a Retrospective Multicenter Cohort Study.

J Gastrointest Surg 2021 Jul 13. Epub 2021 Jul 13.

Tokyo Medical and Dental University, Tokyo, Japan.

Purpose: Due to its rarity and biological heterogeneity, guidelines for primary appendiceal tumor (PAT) are based on scarce evidence, resulting in no strong recommendations. The present study explored prognosis-related factors, including the timing of lymph node dissection (LND), in PAT patients after curative resection (CR) to determine the optimal surgical therapies.

Methods: We retrospectively collected and analyzed data from 404 patients with PATs who underwent CR at 43 tertiary hospitals from 2000 to 2017. This manuscript is based on revised manuscript during review process. Please, change the bold characters to normal characters in the manuscript.

Results: After propensity score matching, there were no marked differences in the recurrence-free survival (RFS) or overall survival (OS) between the primary and secondary LND groups (P = 0.993 and 0.728). A multivariate analysis showed that lymph node metastasis (LNM) was an independent factor for the RFS (hazard ratio [HR] 2.59; 95% confidence interval [CI] 1.09-6.13; P = 0.031) and OS (HR 4.70; 95% CI 1.40-15.76; P = 0.012). There were significant associations between the LNM rates and tumor depth (P < 0.0001) and the histological type (P = 0.006). There was no LNM in patients with low-grade appendiceal mucinous neoplasm (LAMN) or well-differentiated mucinous adenocarcinoma (G1) or patients with any Tis or T1 PATs.

Conclusions: LNM was an independent prognostic predictor in PATs after CR with LND. Tumor depth and histological type were not prognostic predictors but were LNM predictors. Secondary LND based on the pathological findings of resected specimens is considered an acceptable surgical management without a worse prognosis than primary LND, and it may be omitted in LAMN+G1 or in any Tis and T1 PATs.
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http://dx.doi.org/10.1007/s11605-021-05070-6DOI Listing
July 2021

A case of simultaneous abdominal wall metastasis of hepatocellular carcinoma with long-term relapse-free survival after laparoscopic resection.

Int Cancer Conf J 2021 Jul 18;10(3):217-221. Epub 2021 Apr 18.

Department of Gastroenterology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan.

We report our experience of an extremely rare case of a simultaneous extrahepatic metastasis of hepatocellular carcinoma (HCC) with long-term relapse-free survival, treated by laparoscopic resection of an abdominal wall tumor and subsequent radiofrequency ablation (RFA) of an intrahepatic lesion. A 76-year-old man visited a local clinic for right lower abdominal pain. He was treated with antibiotics and the symptom resolved. However, a mass was detected in the same region and he was referred to our hospital for further evaluation. Computed tomography (CT) of the abdomen showed a mass 5 cm in diameter, raising suspicions of an intra-abdominal tumor. Laparoscopic surgery was performed, and the tumor was found in the abdominal wall and completely resected. Histopathological examination yielded a diagnosis of extrahepatic HCC. Post-operative positron emission tomography (PET)-CT showed increased uptake of fluorodeoxyglucose in segment 3 (S3) of the liver. On performing a liver biopsy, HCC was diagnosed. Subsequently, the S3 lesion was treated with radiofrequency ablation. The patient has remained relapse-free for 6 years without further treatments.
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http://dx.doi.org/10.1007/s13691-021-00484-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206437PMC
July 2021

The Pre-treatment Lymphocyte-to-Monocyte Ratio Predicts Efficacy in Metastatic Colorectal Cancer Treated With TAS-102 and Bevacizumab.

Anticancer Res 2021 Jun;41(6):3131-3137

Department of Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan.

Background/aim: Our multicenter phase II TAS-CC3 study demonstrated favorable median progression-free survival (PFS) and overall survival (OS) of 32 metastatic colorectal cancer (mCRC) patients treated with TAS-102 + bevacizumab as 3-line treatment.

Patients And Methods: We investigated the predictive and prognostic values of pre-treatment blood inflammation-based scores, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte ratio (LMR) on disease-control (DC), PFS and OS by a post-hoc analysis.

Results: Receiver operating characteristic curve analyses of the 3 inflammation-based scores versus DC showed the best predictive performance for LMR, followed by NLR and PLR. The high-LMR group had a significantly higher DC rate than the low group (87.5 vs. 43.8%). The high-LMR group showed significantly longer survival than the low group (4.9 vs. 2.3 m for median PFS) (21.0 vs. 6.1 m for median OS).

Conclusion: The pre-treatment LMR is a valid predictive and prognostic biomarker for mCRC patients undergoing TAS-102 and bevacizumab treatment.
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http://dx.doi.org/10.21873/anticanres.15098DOI Listing
June 2021

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate.

J Vis Exp 2021 May 3(171). Epub 2021 May 3.

Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University;

The most recent advance in the treatment of osteosarcoma (OS) occurred in the 1980s when multi-agent chemotherapy was shown to improve overall survival compared to surgery alone. To address this problem, the aim of the study is to refine a lesser-known model of OS in rats with a comprehensive histologic, imaging, biologic, implantation, and amputation surgical approach that prolongs survival. We used an immunocompetent, outbred Sprague-Dawley (SD), syngeneic rat model with implanted UMR106 OS cell line (originating from a SD rat) with orthotopic tibial tumor implants into 3-week-old male and female rats to model pediatric OS. We found that rats develop reproducible primary and metastatic pulmonary tumors, and that limb amputations at 3 weeks post implantation significantly reduce the incidence of pulmonary metastasis and prevent unexpected deaths. Histologically, the primary and metastatic OSs in rats were very similar to human OS. Using immunohistochemistry methods, the study shows that rat OS are infiltrated with macrophages and T cells. A protein expression survey of OS cells reveals that these tumors express ErbB family kinases. Since these kinases are also highly expressed in most human OSs, this rat model could be used to test ErbB pathway inhibitors for therapy.
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http://dx.doi.org/10.3791/62139DOI Listing
May 2021

Analysis of appendectomy samples identified dysbiosis in acute appendicitis.

Biosci Microbiota Food Health 2021 14;40(2):92-97. Epub 2020 Nov 14.

Department of Microbiome Research, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Appendicitis is the most common cause of sudden-onset abdominal pain requiring surgery. Culture-independent techniques have revealed that the complex intestinal bacterial ecology is associated with various diseases. To evaluate differences in patient characteristics and gut microbiota distribution in patients with appendicitis, we enrolled 12 patients who underwent appendectomy for appendicitis (appendicitis group) and 13 patients who underwent ileocecal resection or right hemicolectomy for colon cancer (control group). Microbiota were analyzed using next-generation sequencing of surgical specimens from appendix swab samples collected postoperatively. Overall differences in the structure of the gut microbiota were evaluated using the α- and β-diversity indices, which were calculated using the weighted or unweighted UniFrac distance. Changes in the gut microbial distribution were taxonomically evaluated at the phylum and genus levels. The α-diversity of observed species was significantly different between patients with and without inflammation of the appendix. The appendiceal microbiome of patients with appendicitis exhibited the highest unweighted UniFrac distances. There were no significant differences at the phylum level. (p=0.02) and f_erysipelotrichaceae_g_clostridium (p=0.005) were increased in the control group compared with the appendicitis group. This pilot study provides the first report of the correlation of the gut microbiota with the pathogenesis of appendicitis evaluated using mucus-origin sampling.
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http://dx.doi.org/10.12938/bmfh.2020-051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099629PMC
November 2020

Efficacy of CO₂ Infusion for Preoperative Computed Tomographic Angiography with Computed Tomographic Colonography.

Med Sci Monit 2021 May 16;27:e931055. Epub 2021 May 16.

Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

BACKGROUND Computed tomographic colonography (CTC) is useful for patients for whom colonoscopy may be difficult to perform and is widely employed to examine the vasculature prior to colorectal cancer surgery. Computed tomographic angiography (CTA) was shown to be beneficial intraoperatively to manipulate blood vessels and prevent vascular injury. Three-dimensional (3D)-CTA combined with CTC (3D-CTA with CTC) is useful for preoperative evaluations of the anatomy of mesenteric vessels, colon, and lymph nodes. We observed that when the intestine was dilated with carbon dioxide (CO₂), the arteriovenous delineation was often more pronounced than without CO₂. To clarify the effects of gas injection with and without CO₂ on hemodynamics and vascular passage, we compared the effect of contrast for blood vessels. MATERIAL AND METHODS Thirty patients with resectable colorectal cancer who underwent a preoperative CT examination at our institution from January to October 2019 were study participants. Of these, 15 underwent 3D-CTA and 15 had 3D-CTA with CTC. Three board-certified radiologists independently and blindly evaluated 18 blood vessels. CT values for each blood vessel were measured on each image. RESULTS CT values for 3D-CTA with CTC were significantly higher with CO₂ than without CO₂. The quality of 3D-CTA with CTC images for visualization of blood vessels was also significantly greater than that of 3D-CTA, especially those of arterial and intramesenteric venous systems. CONCLUSIONS Based on the higher image quality and CT values obtained by 3D-CTA with CTC for vessels, compared with by 3D-CTA imaging, 3D-CTA with CTC imaging might be useful in evaluating colorectal cancers.
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http://dx.doi.org/10.12659/MSM.931055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135977PMC
May 2021

Laparoscopic Surgery Is Acceptable for Elderly Patients With Colorectal Cancer: A Propensity Score-matched Study.

Anticancer Res 2021 May;41(5):2611-2615

Department of Coloproctological Surgery, Faculty of Medicine, and Medical Technology Innovation Center Clinical Research and Trial Center, Juntendo University, Tokyo, Japan.

Background/aim: The study was performed to examine the suitability of laparoscopic surgery for elderly patients with colorectal cancer.

Patients And Methods: The subjects were 242 patients aged ≥80 years who underwent primary tumor resection of colorectal cancer using laparoscopic assisted colectomy (LAC, n=145) or open colectomy (OC, n=97). Propensity score matching used to balance the characteristics of the groups resulted in 76 patients being assigned to each group.

Results: Before matching, Glasgow Prognostic Score (GPS), American Society of Anesthesiologists physical status (ASA-PS), and previous abdominal surgery differed significantly between the groups (p<0.05), but after matching, all covariates were balanced (p≥0.05). Short-term outcomes were better after LAC (p<0.05), including fewer postoperative complications and less delirium. Regarding long-term outcomes, 5-year overall survival did not differ significantly between the groups (p=0.91).

Conclusion: In elderly patients with colorectal cancer, short-term results are better after LAC than OC and long-term results are similar. These findings indicate that LAC is acceptable in this patient population.
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http://dx.doi.org/10.21873/anticanres.15041DOI Listing
May 2021

Rectal metastasis from bladder urothelial carcinoma: a case report.

Surg Case Rep 2021 Apr 21;7(1):100. Epub 2021 Apr 21.

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Urothelial carcinoma arises from transitional cells in the urothelial tract. In advanced cases, it can metastasize locally to surrounding organs or distally to organs such as the lungs, bones, or liver. Here we describe a case of rectal metastasis from urothelial carcinoma treated with multiple sessions of transurethral resection of bladder tumor (TURBT).

Case Presentation: A 72-year-old woman presented to our department with abdominal bloating andobstructed defecation. She had undergone two sessions of TURBT for early urothelial carcinoma in another hospital at 64 and 65 months ago, respectively. Cystoscopy at 3 months after the second TURBT session had indicated disease recurrence, and thus, she had been referred to our hospital for further examination, followed by TURBT for the third time at 59 months ago and for the fourth time at 48 months ago; thereafter, she had been followed up with cystoscopy every 6 months without any recurrence. However, she returned to our hospital, complaining of difficult defecation. Subsequent colonoscopy demonstrated an obstructive tumor in the rectum, which was pathologically diagnosed as metastatic urothelial carcinoma of the bladder. Laparoscopic examination revealed two small areas of peritoneal dissemination in the pelvis. A sigmoid colostomy was performed without rectal tumor resection. She has been receiving chemotherapy and is still alive 10 months after surgery.

Conclusions: Rectal metastasis is a rare site of metastasis for urothelial carcinomas. It is important to consider the possibility of annular rectal constriction caused by infiltrating or metastasizing urothelial carcinoma when managing patients with urothelial carcinoma and with difficult defecation.
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http://dx.doi.org/10.1186/s40792-021-01186-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060380PMC
April 2021

Risk of emergency surgery for complicated appendicitis: Japanese nationwide study.

Ann Gastroenterol Surg 2021 Mar 9;5(2):236-242. Epub 2020 Nov 9.

The Japanese Society of Gastroenterological Surgery Tokyo Japan.

Aim: Appendicitis is divided into two categories: complicated appendicitis (CA) and uncomplicated appendicitis (UA). In pediatric patients with CA, the use of interval appendectomy (IA), which is non-operative management followed by elective surgery, has decreased the number of postoperative complications. Before discussing the merit of IA for adult patients, we need to clarify whether the frequency and seriousness of the complication rate after emergency surgery is higher for CA than for UA.

Methods: This retrospective cohort study included adult patients who underwent appendectomy and who were registered in the National Clinical Database (NCD) from 2014 to 2016. Patients with CA who underwent emergency appendectomy comprised the CA group. Patients with UA comprised the UA group. Patients with chronic or recurrent appendicitis who underwent elective appendectomy comprised the elective appendectomy (EA) group. Primary outcomes were all morbidity, serious morbidity, and mortality within 30 days after appendectomy.

Results: We included 109 256 patients in the study: 14 798 CA, 86 876 UA, and 7582 EA patients. Compared with the UA group, the rates of all morbidity, serious morbidity, and mortality were significantly higher in the CA group. All morbidity, serious morbidity, and mortality rates were significantly lower in the EA group than in the other two groups.

Conclusions: We confirmed that emergency surgery for CA places the patient at relatively higher risk. We also showed that the risk associated with EA is significantly lower than that for the other methods.
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http://dx.doi.org/10.1002/ags3.12408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034695PMC
March 2021

Histological and immunohistochemical characteristics and status studied by FISH in six incidentally detected cases of well-differentiated papillary mesothelioma of the peritoneum.

Indian J Pathol Microbiol 2021 Apr-Jun;64(2):277-281

Division of Pathology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial neoplasm, which is generally regarded as benign or indolent in terms of its clinical behavior. However, details about WDPM have remained relatively unknown. Therefore, in this study, we examined six incidentally detected cases of WDPM of the peritoneum. All six cases were surgically excised, without any additional therapeutic measures. None of the cases showed recurrence. All six cases presented single lesions and the tumor sizes ranged from 2 to 10 mm. Histologically, all six cases exhibited papillary proliferation of cytologically bland mesothelial cells with a fibroconnective tissue core. One of the cases (Case 6) presented small invasive foci in the stalk. The tumor cells were immunohistochemically positive for mesothelial markers and negative for GLUT-1, p53, and CD146. The Ki-67 labeling index of the tumor cells was lower than 5% at the hot spots. All samples were BAP1-positive. None of the samples presented p16 homozygous deletion, as assessed by fluorescence in situ hybridization (FISH). None of the patients deceased due to WDPM. However, in Case 3, death occurred due to pancreatic cancer. The results of this study indicate the importance of analyzing immunohistochemical markers and p16 status to diagnose WDPM accurately.
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http://dx.doi.org/10.4103/IJPM.IJPM_111_20DOI Listing
April 2021

Significance of postoperative adjuvant chemotherapy with an oxaliplatin-based regimen after simultaneous curative resection for colorectal cancer and synchronous colorectal liver metastasis: a propensity score matching analysis.

BMC Surg 2021 Apr 9;21(1):188. Epub 2021 Apr 9.

Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

Background: Expansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis.

Methods: The subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (-) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed.

Results: Before PS matching, the L-OHP (+) and (-) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1-3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (-) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.40, 95% CI 0.17-0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (-) group (HR 0.42, 95% CI 0.17-1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (-) groups.

Conclusions: PS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.
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http://dx.doi.org/10.1186/s12893-021-01193-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034170PMC
April 2021

Clinicopathological Characteristics of Low-Grade Appendiceal Mucinous Neoplasm.

Dig Surg 2021 10;38(3):222-229. Epub 2021 Mar 10.

Tokyo Medical and Dental University, Tokyo, Japan.

Introduction: Recently, "low-grade appendiceal mucinous neoplasms" (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN.

Methods: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017.

Results: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10).

Conclusions: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.
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http://dx.doi.org/10.1159/000513973DOI Listing
March 2021

GPR120 agonists enhance the fatty orosensation when added to fat-containing system, but do not evoke it by themselves in humans.

Physiol Behav 2021 05 4;234:113383. Epub 2021 Mar 4.

Institute of Food Sciences & Technologies, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-8681, Japan. Electronic address:

Dietary fat, an important macronutrient, has been considered to be perceived by texture and olfaction. Recently, fatty acid transporter, CD36, and fatty acid receptor, GPR120 are considered to be involved in human gustatory fatty acids perception in humans. However, limited information is currently available to show that agonists of CD36 and GPR120 evoke fatty oral sensations regarding to dietary fat in humans. Therefore, the role of GPR120 agonists in dietary fat perception in humans was investigated herein. An emulsion prepared from vegetable oil had a stronger fatty orosensation, an orosensation similar to an oily mouth-coating sensed 5 - 10 s after tasting, than that prepared from mineral oil; however, the physical properties of both emulsions, such as viscosity, particle distribution, interfacial tension, contact angle, frictional load, and ζ-electric potential were similar. The potent GPR120 agonist, TUG-891 enhanced the fatty orosensation when added to the emulsion prepared from vegetable oil, but not to that from mineral oil. All GPR120 agonists tested enhanced the fatty orosensation when added to a low-fat food system whereas they did not evoke any fatty sensation in aqueous solution at the concentrations tested in food system, and sensory activity positively correlated with GPR120 activity. These results suggest that GPR120 agonists enhance the fatty orosensation in humans when added to vegetable oil or a low-fat food system, but do not evoke it by themselves.
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http://dx.doi.org/10.1016/j.physbeh.2021.113383DOI Listing
May 2021

Case of Incarcerated Femoral Hernia Treated with Laparoscopic Surgery after Groin Hernia Repair.

Case Rep Gastroenterol 2021 Jan-Apr;15(1):35-40. Epub 2021 Jan 21.

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan.

An 81-year-old man was brought to our hospital due to a suspicion of left incarcerated femoral hernia. He was previously diagnosed with incarcerated left groin hernia and was treated using the mesh plug method 1 month back at another hospital. Abdominal computed tomography scan revealed small bowel obstruction, incarcerated bowel, and compression of the left femoral vein. Thus, the patient was diagnosed with incarcerated femoral hernia. An emergency laparoscopic surgery was then performed, and we found that the small bowel was incarcerated into the let femoral ring and was necrotic. However, there was no recurrence of left inguinal hernia. The small necrotic bowel was resected and the femoral ring was repaired. The patient was discharged 8 days after the surgery, and there was no recurrence of femoral hernia after 1 year.
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http://dx.doi.org/10.1159/000509950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879298PMC
January 2021

Multimodal Functional Analysis Platform: 2. Development of Si Opto-Electro Multifunctional Neural Probe with Multiple Optical Waveguides and Embedded Optical Fiber for Optogenetics.

Adv Exp Med Biol 2021 ;1293:481-491

Department of Physiology, Tohoku University Graduate School of Medicine, Sendai, Japan.

We have developed a Si opt-electro multifunctional neural probe with multiple waveguides and embedded optical fiber for highly accurate optical stimulation. The Si opt-electro multifunctional neural probe had 16 recording sites, three optical waveguides, and metal cover for suppressing light leakage. The other opt-electro multifunctional neural probe had an optical fiber in the trench of the probe shank, which leads to fewer damages to tissues. We evaluated the electrochemical properties of the recording sites and confirmed that the neural probe had suitable characteristics for neural recording. We also demonstrated the optical stimulation to the neurons expressing ChR2 using our probe. As a result, we succeeded in multisite optical stimulation and observed that no light leakage from the optical waveguides because of the metal cover. From in vivo experiments, we successfully recorded optically modulated local field potential using the fabricated Si neural probe with optical waveguides. Moreover, we applied current source density analysis to the recorded LFPs. As a result, we confirmed that the light-induced membrane current sinks in the locally stimulated area. The Si opto-electro multifunctional neural probe is one of the most versatile tools for optogenetics.
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http://dx.doi.org/10.1007/978-981-15-8763-4_32DOI Listing
February 2021

Meta-analysis of cognitive and behavioral tests in leptin- and leptin receptor-deficient mice.

Neurosci Res 2021 Sep 13;170:217-235. Epub 2020 Dec 13.

Department of Neuroscience, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai 983-8536, Japan; Department of Physiology, Tohoku University School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan. Electronic address:

Leptin is a hormone produced by adipocytes that regulates food intake and metabolism. Leptin-related gene-deficient mice, such as db/db and ob/ob mice, are widely used to study diabetes and its related diseases. However, broad effects of leptin appear to cause variability in behavioral test results. We performed a meta-analysis of major behavioral tests in db/db and ob/ob mice. These mice exhibited significant impairments in the Morris water maze, forced swim, novel object recognition, Y-maze, tail suspension, and light-dark box tests, whereas the elevated plus maze and open field tests did not reveal significant changes. We also performed correlation and regression analyses between the animals' performances and the experimental protocols and conditions. The memory-related tests were characterized by the correlations of their results with animal age, while the performances in the elevated plus-maze and forced swim tests were affected by the width of the devices used. In conclusion, db/db and ob/ob mice mainly exhibit memory deficits and depression-like behavior, although experimenters should be aware of animal age and device size in conducting experiments.
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http://dx.doi.org/10.1016/j.neures.2020.11.002DOI Listing
September 2021

Antitumor effects of novel mAbs against cationic amino acid transporter 1 (CAT1) on human CRC with amplified CAT1 gene.

Cancer Sci 2021 Feb 11;112(2):563-574. Epub 2020 Dec 11.

Cell Biology Laboratory, School of Pharmacy, Kindai University, Osaka, Japan.

Copy number alterations detected by comparative genomic hybridization (CGH) can lead to the identification of novel cancer-related genes. We analyzed chromosomal aberrations in a set of 100 human primary colorectal cancers (CRCs) using CGH and found a solute carrier (SLC) 7A1 gene, which encodes cationic amino acid transporter 1 (CAT1) with 14 putative transmembrane domains, in a chromosome region (13q12.3) with a high frequency of gene amplifications. SLC7A1/CAT1 is a transporter responsible for the uptake of cationic amino acids (arginine, lysine, and ornithine) essential for cellular growth. Microarray and PCR analyses have revealed that mRNA transcribed from CAT1 is overexpressed in more than 70% of human CRC samples, and RNA interference-mediated knockdown of CAT1 inhibited the cell growth of CRCs. Rats were immunized with rat hepatoma cells expressing CAT1 tagged with green fluorescent protein (GFP), and rat splenocytes were fused with mouse myeloma cells. Five rat monoclonal antibodies (mAbs) (CA1 ~ CA5) reacting with HEK293 cells expressing CAT1-GFP in a GFP expression-dependent manner were selected from established hybridoma clones. Novel anti-CAT1 mAbs selectively reacted with human CRC tumor tissues compared with adjacent normal tissues according to immuno-histochemical staining and bound strongly to numerous human cancer cell lines by flow cytometry. Anti-CAT1 mAbs exhibited internalization activity, antibody-dependent cellular cytotoxicity, and migration inhibition activity against CRC cell lines. Furthermore, CA2 inhibited the in vivo growth of human HT29 and SW-C4 CRC tumors in nude mice. This study suggested CAT1 to be a promising target for mAb therapy against CRCs.
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http://dx.doi.org/10.1111/cas.14741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894011PMC
February 2021

Serum micro-RNA Identifies Early Stage Colorectal Cancer in a Multi-Ethnic Population.

Asian Pac J Cancer Prev 2020 Oct 1;21(10):3019-3026. Epub 2020 Oct 1.

John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, MEB, Honolulu, Hawaii, United States.

Objective: Certain microRNAs (miR) have been previously described to be dysregulated in cancers and can be detected in blood samples. Studies examining the utility of miRs for colon cancer screening have primarily been performed in ethnically homogeneous groups of patients, thus the performance of miRs in multiethnic populations is unknown.

Methods: Four miRs were selected that were shown to be aberrantly expressed in the blood or stool of patients with colorectal cancer (CRC) of various ethnicities. In this study, the ability of these miRs to discern early stage CRC was determined in a previously untested multiethnic population of 73 CRC cases and 18 controls.

Results: The ratios of non-vesicular to extracellular vesicular levels of miR's -21, -29a, and -92a were statistically and quantitatively related to CRC stage compared to controls.

Conclusion: Serum levels of miR-21, miR-29a and miR-92a were able to significantly detect early stage CRC in a multiethnic and previously untested population.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.3019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798181PMC
October 2020

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

Int J Clin Oncol 2021 Jan 21;26(1):111-117. Epub 2020 Oct 21.

Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.

Background: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets.

Methods: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety.

Results: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred.

Conclusions: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.
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http://dx.doi.org/10.1007/s10147-020-01794-8DOI Listing
January 2021

A disposable, ultra-fine endoscope for non-invasive, close examination of the intraluminal surface of the peritoneal dialysis catheter and peritoneal cavity.

Sci Rep 2020 10 16;10(1):17565. Epub 2020 Oct 16.

United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, Japan.

The ability to visualize intraluminal surface of peritoneal dialysis (PD) catheter and peritoneal cavity could allow elucidation of the cases of outflow problems, and provide information on changes to the peritoneal membrane leading to encapsulating peritoneal sclerosis. A non-invasive examination that allows those monitoring in need is desirable. We have developed a disposable ultra-fine endoscope that can be inserted into the lumen of the existing PD catheter, allowing observation of the luminal side of the catheter and peritoneal cavity from the tip of the PD catheter, with minimum invasion in practice. In a pre-clinical study in pigs and a clinical study in 10 PD patients, the device provided detailed images, enabling safe, easy observation of the intraluminal side of the entire catheter, and of the morphology and status of the peritoneal surface in the abdominal cavity under dwelling PD solution. Since this device can be used repeatedly during PD therapy, clinical application of this device could contribute to improved management of clinical issues in current PD therapy, positioning PD as a safer, more reliable treatment modality for end-stage renal disease.
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http://dx.doi.org/10.1038/s41598-020-74129-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567793PMC
October 2020

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer.

J Vis Exp 2020 09 18(163). Epub 2020 Sep 18.

Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine.

DNA methylation is an important epigenetic change that is biologically meaningful and a frequent focus of cancer research. Genome-wide DNA methylation is a useful measure to provide an accurate analysis of the methylation status of gastrointestinal (GI) malignancies. Given the multiple potential translational uses of DNA methylation analysis, practicing clinicians and others new to DNA methylation studies need to be able to understand step by step how these genome-wide analyses are performed. The goal of this protocol is to provide a detailed description of how this method is used for the biomarker identification in GI malignancies. Importantly, we describe three critical steps that are needed to obtain accurate results during genome-wide analysis. Clearly and concisely written, these three methods are often lacking and not noticeable to those new to epigenetic studies. We used 48 samples of a GI malignancy (gastric cancer) to highlight practically how genome-wide DNA methylation analysis can be performed for GI malignancies.
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http://dx.doi.org/10.3791/61355DOI Listing
September 2020

Simultaneous robot-assisted surgery for rectal cancer and prostatic lesions.

J Surg Case Rep 2020 Sep 21;2020(9):rjaa338. Epub 2020 Sep 21.

Department of Urology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Robotic surgery has become prevalent in many departments all over the world because of its usefulness. It is used in many cases, as well as in gastrointestinal surgery, which treats the rectum as pelvic surgery, urology and gynecology. We experienced two cases of joint surgery, with urology as pelvic surgery. The patient underwent robot-assisted low anterior resection, combined prostate resection and ileostomy for prostate invasion of rectal cancer. He was discharged without any complications. Robotic surgery was considered to be useful in surgery to manipulate the same area. In addition, it was considered that smoother and safer surgical procedure could be possible by conducting preoperative meetings with the participating departments.
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http://dx.doi.org/10.1093/jscr/rjaa338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505412PMC
September 2020

A case of endosalpingiosis in the lymph nodes of the mesocolon.

Surg Case Rep 2020 Jul 23;6(1):181. Epub 2020 Jul 23.

Department of Human Pathology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Endosalpingiosis in the lymph nodes of the mesocolon is very rare. We reported a case with appendiceal endometriosis who had endosalpingiosis in the lymph nodes of the mesocolon that was found during laparoscopic ileocecal resection.

Case Presentation: The patient was a 44-year-old woman who had visited a physician for fever, bloody stool, and abdominal pain 1 year earlier. She was diagnosed with ulcerative colitis on colonoscopy, and symptoms improved with oral treatment. A colonoscopy performed 2 months after diagnosis detected a hard, 20-mm submucosal tumor (SMT) in the cecum. On abdominal contrast CT, an intensely stained mass, including a low-density region, was observed in the cecum. A boring biopsy was performed after mucosal resection of the cecal SMT at our hospital, but diagnosis could not be made. Since the possibility of a malignant lesion could not be ruled out, laparoscopic ileocecal resection was performed. In the resected specimen, a 29 × 27 × 21-mm mass was present in the appendicular root. On histopathological examination, appendiceal endometriosis and endosalpingiosis in the lymph nodes around the ileocolic artery were observed. The postoperative course was favorable, and the patient was discharged 7 days after surgery.

Conclusion: Differentiation of endosalpingiosis in lymph nodes in the mesocolon from lymph node metastasis of adenocarcinoma is important in patients with an abdominal mass.
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http://dx.doi.org/10.1186/s40792-020-00942-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378132PMC
July 2020

Creatine kinase elevation after robotic surgery for rectal cancer due to a prolonged lithotomy position.

BMC Surg 2020 Jun 16;20(1):136. Epub 2020 Jun 16.

Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Robotic surgery for rectal cancer, which is now performed worldwide, can be associated with elevated creatine kinase levels postoperatively. In this study, we compared postoperative complications between patients undergoing robotic surgery and laparoscopic surgery.

Methods: We identified 66 consecutive patients who underwent curative resection for rectal cancer at Juntendo University Hospital between January 2016 and February 2019. Patients were divided into a conventional laparoscopic surgery (CLS) group (n = 38) and a robotic-assisted laparoscopic surgery (RALS) group (n = 28) before comparing various clinicodemographic factors between the groups.

Results: Patient age and gender, surgical approach (CLS/RALS), pathological T factor, pathological stage, duration of postoperative hospital stay, and postoperative complications were not significantly different between the RALS and CLS groups. However, the operation time was significantly longer in the RALS group (407 min) than in the CLS group (295 min; p < 0.001). Notably, the serum level of creatine kinase on postoperative day 1 was significantly higher in the CLS group (154 IU/L) than in the RALS group (525 IU/L; p < 0.001), despite there being no significant differences in the incidence of rhabdomyolysis. The multivariate analysis showed that RALS/CLS (HR 6.0 95% CI 1.3-27.5, p = 0.02) and operation time (HR 15.9 95% CI 3.79-67.4, p = 0.001) remained independent factors of CK elevation on postoperative day 1.

Conclusions: Clinically relevant positioning injuries and rhabdomyolysis may occur in patients who are subjected to a prolonged and extreme Trendelenburg position or who have extra force applied to the abdominal wall because of remote center displacement. The creatine kinase value should therefore be measured after RALS to monitor for the sequelae of these potential positioning injuries.
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http://dx.doi.org/10.1186/s12893-020-00771-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298864PMC
June 2020

Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.

Virchows Arch 2020 Dec 12;477(6):825-834. Epub 2020 Jun 12.

Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.
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http://dx.doi.org/10.1007/s00428-020-02854-0DOI Listing
December 2020

Sialodochitis fibrinosa: Salivary duct obstruction by eosinophil extracellular traps?

Oral Dis 2020 Oct 11;26(7):1459-1463. Epub 2020 Jun 11.

Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.

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http://dx.doi.org/10.1111/odi.13434DOI Listing
October 2020

Surgical Procedures and Results of Modified Intraperitoneal Onlay Mesh Repair for Inguinal Hernia After Radical Prostatectomy.

J Laparoendosc Adv Surg Tech A 2020 Nov 24;30(11):1189-1193. Epub 2020 Apr 24.

Department of Gastrointestinal Surgery, Juntendo University Urayasu Hospital, Urayasu-shi, Chiba, Japan.

Although inguinal hernia occurs frequently after radical prostatectomy, transabdominal preperitoneal (TAPP) inguinal hernia repair occasionally poses challenges due to fibrosis of the preperitoneal cavity. In patients with severe intrapelvic fibrosis, we have adopted a modified intraperitoneal onlay mesh (IPOM) technique. The surgical factors were compared between patients who underwent modified IPOM and those who underwent TAPP for inguinal hernia repair. In total, 57 patients underwent laparoscopic surgery for inguinal hernias after radical prostatectomy between February 2013 and January 2020. TAPP was successfully completed in 44 patients, whereas 13 patients underwent modified IPOM converted from TAPP. The surgical results were retrospectively compared. The median follow-up duration was 36.0 months (range, 1-84 months). Intraoperative complications, recurrence of hernia, and chronic pain were not observed in both groups. The average duration of surgery in the modified IPOM group was longer than that in the TAPP group (137 versus 107 minutes,  < .05). There was no significant difference in the incidence of the inguinal-related complications such as inguinal pain or inguinal swelling. Postoperative complications including recurrence of hernia after modified IPOM are comparable to those after TAPP hernia repair. Modified IPOM repair is a surgical option for repairing inguinal hernias following radical prostatectomy.
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http://dx.doi.org/10.1089/lap.2020.0141DOI Listing
November 2020

Using the polymeric circulating tumor cell chip to capture circulating tumor cells in blood samples of patients with colorectal cancer.

Oncol Lett 2020 Mar 23;19(3):2286-2294. Epub 2020 Jan 23.

Department of Coloproctological Surgery, Juntendo University School of Medicine, Tokyo 113-8421, Japan.

The current study clarified the accuracy of a circulating tumor cell (CTC) detection system to diagnose colorectal cancer using blood samples. The system uses the 'polymeric CTC-chip,' (CTC-chip), which is a microfluidic device that is used for CTC isolation. CTCs are considered sensitive diagnostic biomarkers. However, their concentration in the peripheral blood is low and requires highly sensitive and specific capturing techniques. The capture efficiency of the polymeric CTC-chip was first assessed using cell suspensions of the colorectal cancer cell line HCT-116, which was reported as 90.9% in a phosphate-buffered saline suspension and 65.0% in the blood. The CTC-chip was then used to detect CTCs in blood samples obtained from 13 patients with stage II-IV colorectal cancer. On average, the CTCs/ml was lower in patients with stages II and III colorectal cancer (3.3±2.3) than in those with stage IV (7.0±6.2). In patients with stages II-IV, 92% had ≥1 CTC per ml, which was significantly higher than the positive rate (15%) detected using the carbohydrate antigen 19-9 test (CA19-9). Furthermore, CTCs were detected in all patients with stage II and III colorectal cancer, including a number of patients with negative results for the carcinoembryonic antigen (CEA) and CA19-9 tests. With the polymeric CTC-chip detection system, CTCs can be effective cancer markers, particularly for patients with stage II and III colorectal cancer who often exhibit negative conventional serum marker test results. The CTC-chip system may also facilitate the detection of cancer progression based on CTC concentration.
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http://dx.doi.org/10.3892/ol.2020.11335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041365PMC
March 2020
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