Publications by authors named "Kensuke Otani"

100 Publications

The primary tumor location in colorectal cancer: A focused review on its impact on surgical management.

Glob Health Med 2021 Dec;3(6):386-393

Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan.

The primary tumor location (PTL) has attracted increasing attention in recent years for colorectal cancer (CRC) patients. Although the underlying mechanisms for differences caused by PTL remain still unclear, right-sided colon (RCC) and left-sided colon (LCC) are now considered as distinct entities because of their different molecular profile and clinical response to surgery and chemotherapy. In this article, we review the influence of PTL particularly on surgical management of primary and metastatic CRC settings. For nonmetastatic CRC, RCC could be a slightly superior prognostic factor after curative resection in stage I-II CRC, while RCC could be an inferior prognostic factor in stage III CRC with worse survival after recurrence, suggesting the oncological aggressiveness of recurrent RCC. For metastatic CRC, RCC could be a predictor of worse survival after hepatectomy of liver metastases from CRC with aggressive recurrence pattern and lower chance of re-resection. In lung metastases from CRC, the role of PTL still remains uncertain because of the limited number of studies. As to the impact of PTL on survival outcome after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal metastases from CRC, a discrepancy exists among studies and further investigation will be needed. The very simple clinical factor of PTL could provide important information for the prediction of the survival outcome after surgery in CRC. Further clinical and basic research will facilitate the clinical application of PTL in a more specified and personalized manner.
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http://dx.doi.org/10.35772/ghm.2020.01096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692095PMC
December 2021

Prognostic value of F-FDG PET/CT with texture analysis in patients with rectal cancer treated by surgery.

Ann Nucl Med 2021 Jul 4;35(7):843-852. Epub 2021 May 4.

Department of Surgery, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.

Purpose: The aim of this study was to evaluate the ability of texture analysis using pretreatment F-FDG PET/CT to predict prognosis in patients with surgically treated rectal cancer.

Methods: We analyzed 94 patients with pathologically proven rectal cancer who underwent pretreatment F-FDG PET/CT and were subsequently treated with surgery. The volume of interest of the primary tumor was defined using a threshold of 40% of the maximum standardized uptake value (SUVmax), and conventional (SUVmax, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and textural PET features were extracted. Harmonization of PET features was performed with the ComBat method. The study endpoints were overall survival (OS) and progression-free survival (PFS), and the prognostic value of PET features was evaluated by Cox regression analysis.

Results: In the follow-up period (median 41.7 [interquartile range, 30.5-60.4] months), 21 (22.3%) and 30 (31.9%) patients had cancer-related death or disease progression, respectively. Univariate analysis revealed a significant association of (1) MTV, TLG, and gray-level co-occurrence matrix (GLCM) entropy with OS; and (2) SUVmax, MTV, TLG, and GLCM entropy with PFS. In multivariate analysis including clinical characteristics, GLCM entropy (≥ 2.13) was the only relevant prognostic PET feature for poor OS (hazard ratio [HR]: 4.16, p = 0.035) and PFS (HR: 2.70, p = 0.046).

Conclusion: GLCM entropy, which indicates metabolic intratumoral heterogeneity, was an independent prognostic factor in patients with surgically treated rectal cancer. Compared with conventional PET features, GLCM entropy has better predictive value and shows potential to facilitate precision medicine.
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http://dx.doi.org/10.1007/s12149-021-01622-7DOI Listing
July 2021

Definition and characterization of the descending branch of the left colic artery.

Abdom Radiol (NY) 2021 07 8;46(7):2993-3001. Epub 2021 Feb 8.

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

Purpose: The descending branch of the left colic artery (dLCA) is under-recognized and has not been clearly defined. The dLCA is often confused with the sigmoid artery (SA) originating from the left colic artery (LCA). We clarified the anatomical characteristics of the dLCA and searched for surrogate measures to identify it.

Methods: Arterial phase, venous phase, and three-dimensional images of abdominal arteries were created in 411 patients using contrast-enhanced computed tomography (CT). We analyzed the branching patterns of the inferior mesenteric artery (IMA) based on CT. The dLCA was defined as the artery originating from the LCA that flows into the marginal artery along the descending colon. We tested three candidate diagnostic measures for the dLCA using positional relationships and the segment length of vessels.

Results: Arteries from the LCA were present in 360 patients, among which 459 dLCAs and 165 SAs were identified in 333 and 146, respectively. By the first measure of identifying the artery with its root lateral to the inferior mesenteric vein (IMV) as the dLCA, the sensitivity, specificity, and accuracy rate were 94%, 87%, and 92%, respectively. The second measure of identifying the artery with its root higher than the root of the IMA as the dLCA and the third of identifying the artery with its root located > 27.6 mm from the root of LCA as the dLCA yielded lower accuracy rates (69% and 89%, respectively).

Conclusion: Our study demonstrated that dLCAs are prevalent (93%) and may be easily found lateral to the IMV in clinical practice.
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http://dx.doi.org/10.1007/s00261-021-02969-1DOI Listing
July 2021

Efficacy of intraperitoneally administered paclitaxel for colorectal cancer with peritoneal metastases.

Int J Colorectal Dis 2020 Oct 3;35(10):1945-1949. Epub 2020 Jun 3.

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

Purpose: Prognosis after peritoneal metastases in colorectal cancer is worse than that after lung or liver metastases. Previously, we demonstrated the safety of intraperitoneal (ip) administration of paclitaxel (PTX) combined with mFOLFOX6/CapeOX plus bevacizumab for colorectal cancer with peritoneal metastasis in a phase-I trial. Here, we evaluated the efficacy of this chemotherapy.

Methods: We enrolled six patients with histologically confirmed peritoneal metastases secondary to colorectal cancer. PTX was administered through a peritoneal access port, in combination with oxaliplatin-based systematic chemotherapy. Response rate, progression-free survival, 1-year survival rate, frequency of improvement in peritoneal cancer index (PCI), and cytology in peritoneal lavage were evaluated. This study was registered in the University Hospital Medical Information Network Clinical Trial Registry on July 1, 2016 (UNIN000022924).

Results: Three patients received the mFOLFOX6-bevacizumab regimen, whereas the other three received the CapeOX-bevacizumab regimen. The response rate was 25%. PCI score improved in 50% of the cases. Peritoneal lavage cytology that was positive in five patients before initiating the chemotherapy turned negative during chemotherapy in all patients. One-year survival rate was 100%, progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months.

Conclusion: The ip administration of PTX with systemic chemotherapy can potentially control peritoneal metastases in colorectal cancer.
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http://dx.doi.org/10.1007/s00384-020-03649-0DOI Listing
October 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

The influence of neoadjuvant chemoradiation for lower rectal cancer on urinary function.

Asian J Surg 2019 Jul 7;42(7):731-739. Epub 2019 Jan 7.

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

Background: It is unclear whether neoadjuvant chemoradiation for lower rectal cancer causes a deterioration in urinary function. This study aimed to prospectively compare the postoperative urinary function of patients with lower rectal cancer treated by surgery after neoadjuvant chemoradiation with that of patients treated with surgery alone.

Method: Urinary function was assessed before treatment and 1, 3, and 6 months after surgery by calculating the changes in the scores of the seven items of the International Prostatic Symptom Score (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) and Quality of life index.

Results: Among 123 patients with lower rectal cancer treated with chemoradiotherapy plus surgery and surgery alone between 2014 and 2016, 29 eligible patients in the surgery after neoadjuvant chemoradiation group and 34 eligible patients in the surgery alone group were analyzed. The changes in each item score at 1, 3, and 6 months after surgery were similar between the two treatment groups. The scores of all items were already recovered at 6 months after surgery, except for weak stream and straining in the Surgery + chemoradiotherapy group and nocturia in the Surgery-alone group.

Conclusion: Neoadjuvant chemoradiotherapy for lower rectal cancer did not affect postoperative urinary function.
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http://dx.doi.org/10.1016/j.asjsur.2018.11.004DOI Listing
July 2019

Short- and Long-term Outcomes of Minimally Invasive Versus Open Multivisceral Resection for Locally Advanced Colorectal Cancer.

Dis Colon Rectum 2019 01;62(1):40-46

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

Background: Colorectal cancer invading the adjacent organs/structures is detected in 5% to 20% of all surgical interventions performed for the management of colorectal cancer.

Objective: Our purpose is to verify the safety and feasibility of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the adjacent organs.

Design: This is a retrospective study.

Settings: The study was conducted at a single institution in Japan.

Patients: We compared the morbidity, appropriate oncological resection, and disease-free survival of laparoscopic and open multivisceral resection in patients with colorectal carcinoma in the period between 2007 and 2015.

Main Outcome Measures: The primary outcome measures were curative resection rate, morbidity rate, and recurrence of laparoscopic and open multivisceral resection in patients with colorectal cancer.

Results: Thirty-one patients received laparoscopic surgery, and 50 received open surgery. The amount of blood loss was smaller in the laparoscopic group than in the open group (60 vs 595 mL, p < 0.01). Curative surgery was performed in 46 patients of the open group (92.0%) and in 30 patients of the laparoscopic group (96.8%). Days until oral intake (5 vs 7 days, p < 0.01) and postoperative hospital stay (14 vs 19 days, p < 0.01) were shorter in the laparoscopic group. Overall morbidity was not different between the groups (22.5% vs 40.0%). Three-year disease-free survival rates were 62.7% in the open group and 56.7% in the laparoscopic group (p = 0.5776).

Limitation: This study was a retrospective small study conducted at a single institute.

Conclusion: Laparoscopic multivisceral resection may be a safe, less invasive alternative to open surgery, with less blood loss and shorter hospital stay, and was not inferior to open surgery based on long-term oncological end points. See Video Abstract at http://links.lww.com/DCR/A785.
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http://dx.doi.org/10.1097/DCR.0000000000001255DOI Listing
January 2019

Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial.

Cancer Chemother Pharmacol 2019 01 1;83(1):145-150. Epub 2018 Nov 1.

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

Purpose: Peritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis.

Methods: Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/m of ip PTX was administered weekly, in combination with mFOLFOX6-bevacizumab or CapeOX-bevacizumab. Primary endpoint was the safety of the combination chemotherapy.

Results: Among the six patients enrolled, three received the mFOLFOX6-bevacizumab plus ip PTX regimen and three received the CapeOX-bevacizumab plus ip PTX regimen. Dose-limiting toxicity was not observed. Overall, grade 3 adverse events, such as leukopenia and neutropenia, were observed in two of three patients (66.7%) for each chemotherapeutic regimen, but no grade 4 adverse events were observed. Moreover, adverse events associated with the peritoneal access port, such as infection or occlusion of the catheter, were not observed.

Conclusions: The adverse events of mFOLFOX6-bevacizumab or CapeOX-bevacizumab in combination with ip PTX were considered similar to those described in previous studies of oxaliplatin-based treatment alone. 1 year after the start of chemotherapy, the efficacy of ip PTX will be evaluated as a secondary outcome.
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http://dx.doi.org/10.1007/s00280-018-3714-5DOI Listing
January 2019

High-risk Stage II Colorectal Cancers Carry an Equivalent Risk of Peritoneal Recurrence to Stage III.

In Vivo 2018 Sep-Oct;32(5):1235-1240

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

Background/aim: Several risk factors for recurrence have been identified in stage II colorectal cancer. However, in contrast to stage III, the benefits of adjuvant chemotherapy for these patients remain controversial. We hypothesized that the different impacts of chemotherapy may be due to different patterns of recurrence between these stages. The aim of this study was to characterize recurrence in high-risk stage II colorectal cancer (CRC) in comparison with stage III.

Patients And Methods: A total of 442 patients with curatively resected stage III and high-risk stage II CRCs were evaluated. The recurrence site and frequency were compared between these stages. The risk factors of recurrence by site were identified using multivariate analyses.

Results: During the follow-up (median: 6.4 years), 31% of stage III and 13% of high-risk stage II patients manifested recurrence. Recurrence in the liver, lung, and distant lymph nodes was significantly more frequent in stage III (18%, 12%, 11%) than in high-risk stage II (7%, 6%, 3%). Stage III was independently associated with recurrence in these organs. In contrast, the rate of peritoneal recurrence was 5% in both stages.

Conclusion: Clinicians should be aware that high-risk stage II CRC has a similar risk of postoperative recurrence in the peritoneum to Stage III CRC.
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http://dx.doi.org/10.21873/invivo.11370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199616PMC
December 2018

Efficacy of 18-fluoro deoxy glucose-positron emission tomography computed tomography for the detection of colonic neoplasia proximal to obstructing colorectal cancer.

Medicine (Baltimore) 2018 Aug;97(31):e11655

Department of Surgical Oncology Division of Nuclear medicine, Department of Radiology, Faculty of Medicine, University of Tokyo Department of Radiology, International University of Health and Welfare, School of Medicine, Japan.

Identification of secondary colonic neoplasia proximal to obstructing colorectal cancer is essential for determining the range of colorectal resection.We examined the accuracy of 18-fluoro deoxy glucose-positron emission tomography (FDG-PET) for detection of colonic neoplasia.We recruited patients with obstructing colorectal cancer from our registry. Preoperative FDG-PET was performed, and the detection rate for colonic neoplasia was estimated. Preoperative colonoscopy or postoperative colonoscopy within a year after operation was employed as the indexed standard.Ninety-three patients were included in this study. Colonic neoplasia proximal to obstruction was confirmed in 83 cases. The sensitivity and positive predictive value of FDG-PET were 25.3% and 77.8%, respectively. The sensitivity was higher in larger lesions (3.2% for <5 mm, 29.4% for 6-10 mm, 45.5% for 11-20 mm, and 71.4% for >21 mm) and in higher pathological grade lesions (14.6% for low-grade adenoma, 38.5% for high-grade adenoma, 66.7% for carcinoma in situ, and 100% for invasive carcinoma). The round shape in PET images was a predictor for neoplasia, with an area under the curve of 0.75293 at an aspect ratio of 1.70.FDG-PET should be used as a screening modality for invasive colorectal cancer (CRC) proximal to obstructing colorectal cancer.
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http://dx.doi.org/10.1097/MD.0000000000011655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081081PMC
August 2018

Elevated risk of stoma outlet obstruction following colorectal surgery in patients undergoing ileal pouch-anal anastomosis: a retrospective cohort study.

Surg Today 2018 Dec 25;48(12):1060-1067. Epub 2018 Jul 25.

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

Purpose: Stoma outlet obstruction (SOO) is a complication following colorectal surgery that requires stoma creation. We aimed to clarify the SOO incidence and identify risk factors for SOO after stoma surgery in patients with ulcerative colitis (UC) or rectal cancer.

Methods: The study included 345 patients with sporadic rectal cancer (n = 301) or UC (n = 44) who underwent stoma surgery between 2012 and 2017. Univariate and multivariate analyses were performed to identify risk factors for SOO.

Results: The SOO incidences were 27.3% (n = 12) in patients with UC and 5.6% (n = 17) in patients with sporadic rectal cancer. A multivariate analysis identified UC and loop ileostomy as independent risk factors for SOO. Subanalyses revealed that loop ileostomy was an independent risk factor for patients with UC or sporadic rectal cancer. Most patients who developed SOO were successfully managed with tube drainage through the stoma. However, stoma closure was performed earlier than originally planned in two patients. Among the 29 patients with SOO, 22 (75.9%) developed SOO within 2 weeks postoperatively; the median period between stoma creation and SOO was 6 (range 3-41) days.

Conclusions: UC and loop ileostomy are independent risk factors for postoperative SOO.
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http://dx.doi.org/10.1007/s00595-018-1698-8DOI Listing
December 2018

Over-diagnosis for preoperative T staging of colorectal cancer - A case series.

Ann Med Surg (Lond) 2018 Aug 18;32:10-13. Epub 2018 Jun 18.

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

Introduction: Recent progressive imaging technology such as multiplanar reconstruction on computed tomography (CT) and colonoscopy has made preoperative T staging of colorectal cancer (CRC) more accurate. Nevertheless, it is still difficult to make a correct diagnosis in some cases. The aim of this case study was to investigate the accuracy of T staging diagnosis in patients with CRC who underwent curative operations and to identify the causes of preoperative over-diagnosis.

Method: Medical charts of 1013 colorectal cancer patients who underwent a curative operation in the University of Tokyo Hospital between January 2011 and December 2016 were analyzed retrospectively. We defined a two-level or more difference between clinical and pathological T stages as over-diagnosis or under-diagnosis.

Results: Nine patients were over-diagnosed in T stage preoperatively. The rate of over-diagnosis was 0.9%. At least three main factors for over-diagnosis were identified: close-to-circumferential or obstructive lesion; a rough appearance in the adipose tissues around the tumor on CT; and a tumor with a depressed structure.

Conclusions: Clinical T stage is overestimated with a marked difference from pathological T stage in approximately 1% of CRC patients. Further progress in diagnostic modalities is required for more accurate staging.
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http://dx.doi.org/10.1016/j.amsu.2018.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039894PMC
August 2018

Phase I/II Study of Preoperative Chemoradiotherapy With TEGAFIRI for Locally Advanced Rectal Cancer.

Clin Colorectal Cancer 2018 09 1;17(3):240-246. Epub 2018 Jun 1.

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

Introduction: Chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer; however, the optimal chemotherapy sequence to administer simultaneously with radiotherapy remains unclear. We conducted a phase I/II study to test a new regimen, TEGAFIRI (combination tegafur, uracil [UFT], leucovorin [LV], irinotecan), for patients with locally advanced rectal cancer.

Patients And Methods: A total of 22 patients with locally advanced lower rectal adenocarcinoma were enrolled in the present study. The radiation dose was 50.4 Gy in 28 fractions. UFT (300 mg/m/d) and LV (75 mg/body weight/d) were administered orally 3 times daily. Irinotecan was administered as an intravenous infusion at 3 escalating dose levels. The initial dose was 50 mg/m (level 1; n = 7), the intermediate was 70 mg/m (level 2; n = 8), and the maximum was 80 mg/m (level 3; n = 7). The drug was administered on days 1, 15, 29, and 43.

Results: Dose-limiting toxicity was not observed at any dosing level. The most frequent adverse event was leukopenia (50%), followed by diarrhea (45.5%), anal pain (31.8%), and neutropenia (27.3%). All were well-managed with the appropriate drugs. The total pathologic complete response rate was 22.7%, and the proportion of good responders was 28.6%, 50%, and 71.4% at levels 1, 2, and 3, respectively. None of the patients experienced local recurrence. The 5-year relapse-free and overall survival rates were 80.4% and 80.8%, respectively.

Conclusion: TEGAFIRI is a promising CRT regimen that results in marked tumor regression and good local control. Moreover, its adverse events are well-tolerated.
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http://dx.doi.org/10.1016/j.clcc.2018.05.010DOI Listing
September 2018

Prognostic impact of doublecortin-like kinase 1 expression in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

APMIS 2018 Jun;126(6):486-493

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

Preoperative chemoradiotherapy (CRT) is a standard therapy for locally advanced rectal cancer; however, the response varies depending on cases. Therefore, CRT-response predictors need to be elucidated. Cancer stem cells (CSCs), comprising a small part of tumors, are associated with tumor progression and recurrence due to their self-renewal and proliferation abilities. Doublecortin-like kinase 1 (DCLK1) is one of the several putative CSC markers; however, the clinical impact of its expression in rectal cancer has not been evaluated. The aim of this study was to clarify the clinical impact of DCLK1 expression in rectal cancer. We immunohistochemically evaluated DCLK1 expression in surgical specimens of 106 rectal cancer patients, including those who underwent preoperative CRT. The correlations between DCLK1 expression, and clinicopathological features and patient prognosis were then assessed. In rectal cancer patients treated with preoperative CRT, DCLK1 expression was significantly correlated with lymph node metastasis (p = 0.02) and poor cancer-specific survival (p = 0.049). However, in patients treated without preoperative therapy, no such correlation was found. DCLK1 expression can be associated with lymph node metastasis and poor cancer-specific survival in rectal cancer patients who receive CRT.
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http://dx.doi.org/10.1111/apm.12852DOI Listing
June 2018

Learning Curve of Robotic Rectal Surgery With Lateral Lymph Node Dissection: Cumulative Sum and Multiple Regression Analyses.

J Surg Educ 2018 Nov 19;75(6):1598-1605. Epub 2018 Jun 19.

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

Objective: This study aimed to assess the learning curve of robotic rectal surgery, a procedure that has gained increasing focus in recent years because it is expected that the advanced devices used in this approach provide advantages resulting in a shorter learning curve than that of laparoscopic surgery. However, no studies have assessed the learning curve of robotic rectal surgery, especially when lateral lymph node dissection is required.

Design: This was a nonrandomized, retrospective study from a single institution.

Setting: All consecutive patients who underwent robotic rectal or sigmoid colon surgery by a single surgeon between February 2012 and July 2016 in the University of Tokyo Hospital were enrolled. The learning curve for console time was assessed using a cumulative sum analysis and multiple linear regression analysis.

Participants: A total of 131 consecutive patients underwent robotic rectal or sigmoid colon surgery performed by a single experienced surgeon. Of these, 41 patients received lateral lymph node dissection.

Results: A cumulative sum plot for console time demonstrated that the learning period could be divided into 3 phases: Phase I, Cases 1 to 19; Phase II, Cases 20 to 78; and Phase III, Cases 79 to 131. Multiple linear regression analysis indicated that console time decreased significantly from one phase to another (Phase I-II, Δconsole time 83.0 minutes; Phase II-III, Δconsole time 40.1 minutes). Other factors affecting console time included body mass index, operative procedure, and lateral lymph node dissection, but not neoadjuvant therapy (such as chemoradiotherapy) or depth of invasion. Lateral lymph node dissection required an additional 138.4 minutes.

Conclusions: Our findings suggest that the first phase of the learning curve consists of the first 19 cases, which seems sufficient to master the manipulation of robotic arms and to understand spatial relationships unique to the robotic procedure.
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http://dx.doi.org/10.1016/j.jsurg.2018.04.018DOI Listing
November 2018

Comparison of the guidelines for colorectal cancer in Japan, the USA and Europe.

Ann Gastroenterol Surg 2018 Jan 19;2(1):6-12. Epub 2017 Dec 19.

Department of Surgical Oncology The University of Tokyo Tokyo Japan.

Colorectal cancer (CRC) is one of the most common cancers globally as well as in Japan and has shown a pattern of increasing incidence and mortality rates. Therefore, guidelines for CRC are considered to be crucial for establishing standard medical treatment not only in Japan but also around the world. In this article, we explain the features of the representative guidelines in Japan (Japanese Society for Cancer of the Colon and Rectum [JSCCR]), the USA (National Comprehensive Cancer Network [NCCN]) and Europe (European Society for Medical Oncology [ESMO]) and review the differences among these guidelines for CRC. We focus, in particular, on the descriptions of local treatments, including endoscopic treatment for CRC and transanal excision for lower rectal cancer; surgical treatments with lymph node dissection, including management of lower rectal cancer with lateral lymph node metastasis and laparoscopic surgery; and chemotherapy. Although the guidelines share basic principles, some details are different. Consulting the guidelines of various regions from around the world may aid in more precise and effective examination of the details and backgrounds of our own native guidelines.
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http://dx.doi.org/10.1002/ags3.12047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881304PMC
January 2018

Multidetector-Row Computed Tomography and Colonoscopy for Detecting a Rectal Dieulafoy Lesion as a Source of Lower Gastrointestinal Hemorrhage.

Case Rep Gastroenterol 2018 Jan-Apr;12(1):202-206. Epub 2018 Apr 27.

Department of Gastroenterology, University of Tokyo, Tokyo, Japan.

A Dieulafoy lesion of the rectum is a very rare entity that can cause massive lower gastrointestinal (GI) hemorrhage. Identifying the bleeding point is sometimes difficult because these lesions are very small. We herein describe an 82-year-old man with active hemorrhage due to a rectal Dieulafoy lesion. He was referred to our hospital because of persistent hematochezia from the morning of that day. He had a history of atrial fibrillation, chronic heart failure, diabetes mellitus, and hyperuricemia. Prompt multidetector-row computed tomography (MDCT) enabled us to detect active bleeding from the lower rectum. Subsequently, colonoscopy revealed an exposed vessel in the lower rectum without surrounding ulceration, and hemostasis was successfully achieved using a hemostatic forceps with soft coagulation. After hemostasis had been achieved, the patient recovered and was discharged without complications and rebleeding. He is doing well 6 months after discharge from the hospital. Sequential examination by MDCT and colonoscopy is considered an efficient treatment strategy for patients with active lower GI bleeding.
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http://dx.doi.org/10.1159/000488973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968264PMC
April 2018

Recent advances in neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

J Anus Rectum Colon 2017 25;1(2):39-44. Epub 2018 May 25.

Department of Surgical Oncology, The University of Tokyo.

Preoperative chemoradiotherapy (CRT) has been actively used in Europe and the United States to treat advanced low rectal cancer, and provides excellent local control. In Japan, however, the standard treatment is lateral lymph node dissection, and to date CRT has not been actively used. In recent years, an increasing number of Japanese institutions have been using preoperative CRT to treat locally advanced rectal cancer. In this review, we describe the latest trends in CRT under five headings: short-course or long-course radiation, efforts to improve combined chemotherapy, the addition of preoperative adjuvant chemotherapy, the watch and wait strategy, and the significance of lateral lymph node dissection in patients receiving CRT.
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http://dx.doi.org/10.23922/jarc.2017-005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768670PMC
May 2018

Smoking and tumor obstruction are risk factors for anastomotic leakage after laparoscopic anterior resection during rectal cancer treatment.

J Anus Rectum Colon 2017 25;1(1):7-14. Epub 2018 May 25.

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

Objectives: To clarify the surgical outcomes and risk factors for anastomotic leakage (AL) following laparoscopic anterior resection (Lap-AR) for the treatment of rectal cancer.

Methods: We retrospectively reviewed the records of 175 consecutive primary rectal cancer patients who had undergone Lap-AR at our institution between April 2012 and November 2015. Patient, tumor, and surgical variables were analyzed using univariate analyses.

Results: Of 175 patients, 116 were men (66.3%). All four patients who had AL (2.3%) were men and current smokers with heavy smoking histories. In three of the AL cases, preoperative total colonoscopy was impossible owing to tumor obstruction, and the other case had concomitant obstructive colitis after oral bowel preparation. Univariate analysis identified tumor size, tumor obstruction, and smoking history as factors significantly associated with AL development.

Conclusions: Tumor size, tumor obstruction, and smoking history were risk factors for AL following Lap-AR for the treatment of primary rectal cancer.
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http://dx.doi.org/10.23922/jarc.2016-012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768678PMC
May 2018

Colon cancer with perforation.

Surg Today 2019 Jan 24;49(1):15-20. Epub 2018 Apr 24.

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

Perforation of the colon is a rare complication for patients with colon cancer and usually requires emergent surgery. The characteristics of perforation differ based on the site of perforation, presenting as either perforation at the cancer site or perforation proximal to the cancer site. Peritonitis due to perforation tends to be more severe in cases of perforation proximal to the cancer site; however, the difference in the outcome between the two types remains unclear. Surgical treatment of colon cancer with perforation has changed over time. Recently, many reports have shown the safety and effectiveness of single-stage operation consisting of resection and primary anastomosis with intraoperative colonic lavage. Under certain conditions, laparoscopic surgery can be feasible and help minimize the invasion. However, emergent surgery for colon cancer with perforation is associated with a high rate of mortality and morbidity. The long-term prognosis seems to have no association with the existence of perforation. Oncologically curative resection may be warranted for perforated colon cancer. In this report, we perform a literature review and investigate the characteristics and surgical strategy for colon cancer with perforation.
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http://dx.doi.org/10.1007/s00595-018-1661-8DOI Listing
January 2019

A case of anastomotic stenosis of the small intestine caused by cholesterol crystal embolism.

Surg Case Rep 2018 Apr 4;4(1):29. Epub 2018 Apr 4.

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

Background: Cholesterol crystal embolism (CCE) is caused by small crystals of cholesterol dispersed from atherosclerotic plaques of the aorta. There is an increasing interest in CCE because of the increased use of endovascular treatments. Here, we report a rare case of intestinal stenosis caused by CCE after functional end-to-end anastomosis (FEEA). To our knowledge, this is the first report of CCE causing such an anastomotic stenosis.

Case Presentation: A 77-year-old male patient underwent laparoscopy-assisted low anterior resection and protective ileostomy for rectal carcinoid tumor. He was admitted to our hospital with ileus 1 year after stoma closure. Eosinophils and creatine kinase level were slightly elevated. Computed tomography revealed a stricture with thickened intestinal wall just distal to the anastomosis site of the ileostomy. The wall of the descending aorta appeared shaggy due to thrombosis. The patient underwent laparoscopic small-bowel resection because ileus reoccurred after any oral intake. Histopathological findings of the resected specimen showed fibrotic changes distal to the anastomosis site, and needle-shaped cholesterol embolus was observed in the submucosal layer. Thus, the stenosis was considered to be caused by CCE.

Conclusion: This appears to be the first published report of stenosis due to CCE at such an anastomotic site. Intestinal CCE is difficult to diagnose preoperatively and is associated with poor prognosis. If eosinophilia is present or shaggy aorta is observed, CCE should be suspected to make correct diagnosis and prevent recurrence of CCE.
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http://dx.doi.org/10.1186/s40792-018-0442-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884749PMC
April 2018

Multivisceral resections for locally advanced colorectal cancer after preoperative treatment.

Mol Clin Oncol 2018 Mar 19;8(3):493-498. Epub 2018 Jan 19.

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

Multivisceral resection for colorectal cancer invading into the adjacent organs may often be difficult and may involve serious complications. Preoperative therapy may facilitate resection with safe margins. Between August 2007 and July 2016, 23 patients with colorectal cancer invading into the adjacent organs treated with preoperative treatment (chemoradiotherpay, chemotherapy, radiotherapy) were retrospectively investigated. All 23 patients received surgery with curative intent. Four patients had distant metastases at the time of diagnosis. Two patients had distant metastasis after preoperative treatment. The mean operative time was 535.3±185.5 min and the median amount of blood loss was 1,050 ml. Histopathological examination revealed malignant infiltration of the adjacent organs in 14 patients (60.9%). R0 resection rate was 73.9%. Postoperative complications were identified in nine patients (39.1%) and a high incidence of infectious complications was observed. Patients with curative resection showed a significantly better survival than patients with R1 or R2 resection (P<0.01). Multivisceral resection for locally advanced colorectal cancer invading into the adjacent organ after preoperative treatment may be performed with acceptable morbidity and minimal mortality. R0 resection improves the prognosis of patients with locally advanced colorectal cancer invading into the adjacent organ after preoperative treatment.
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http://dx.doi.org/10.3892/mco.2018.1559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854941PMC
March 2018

DCLK1 Expression in Colorectal Polyps Increases with the Severity of Dysplasia.

In Vivo 2018 Mar-Apr;32(2):365-371

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

Background: The expression of doublecortin-like kinase 1 (DCLK1) has been investigated in cancer; however not in precancerous adenomatous polyps.

Materials And Methods: Immunohistological expression of DCLK1 was evaluated in various grades of adenomas, cancerous polyps, and hyperplastic polyps in resected human tissue specimens.

Results: Ninety-two specimens were positive for DCLK1 and 134 were negative. Cancerous polyps showed a high DCLK1 positivity rate compared to adenomas (68.4% vs. 36.8%; p<0.01). The rate of DCLK1 positivity was not significantly different among the three grades of adenomas (mild, moderate, and severe). DCLK1 was highly positive in advanced adenomas than low risk adenomas (49.6% vs. 29.3%; p<0.01).

Conclusion: The expression of DCLK1 was found in low-grade adenomas and increased with worsening severity of dysplasia. DCLK1 expression was highly observed in advanced adenomas, which had a clinically higher malignant potential.
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http://dx.doi.org/10.21873/invivo.11247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905207PMC
August 2018

Protrusion on the Depressed Surface of Non-polypoid T1 Colorectal Cancer Is Associated with Venous Invasion.

Anticancer Res 2018 02;38(2):993-1002

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

Aim: The treatment strategies for T1 colorectal cancer (CRC) include both surgical and endoscopic resection. Surgical resection is indicated if lymphovascular invasion is present; however, the endoscopic prediction of lymphovascular invasion has not been reported. We aimed to correlate endoscopic morphology with pathological findings, including lymphovascular invasion, in non-polypoid T1 CRC.

Materials And Methods: We retrospectively investigated 63 patients with non-polypoid T1 CRC surgically resected between 2008 and 2016. Four typical endoscopic findings related to deep submucosal invasion, namely protrusion from a depressed surface, fold convergence, fullness and hardness, were assessed to elucidate their association with pathological findings.

Results: Protrusion was the only finding significantly correlated with positive venous invasion (67.9% of the lesions with protrusion vs. 34.3% of those without protrusion, p=0.01), which was also confirmed by a multivariable analysis (odds ratio(OR)=3.72, 95% confidence interval(CI)=1.24-11.2, p=0.02).

Conclusion: The endoscopic finding of protrusion on a depressed surface may be a sign indicating venous invasion in non-polypoid T1 CRC.
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http://dx.doi.org/10.21873/anticanres.12314DOI Listing
February 2018

Surgical management for a huge presacral teratoma and a meningocele in an adult with Currarino triad: a case report.

Surg Case Rep 2018 Jan 19;4(1). Epub 2018 Jan 19.

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

Background: The Currarino triad is a rare hereditary syndrome comprising anorectal malformation, sacral bony defect, and presacral mass. Most of the patients are diagnosed during infancy.

Case Presentation: A 44-year-old man was diagnosed with Currarino triad, with a huge presacral teratoma and meningocele. One-stage surgery via posterior approach was successful.

Conclusions: Treatment of the presacral mass in the Currarino triad, diagnosed in adulthood, is challenging. Multidisciplinary management and detailed planning before surgery are important for a satisfactory outcome.
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http://dx.doi.org/10.1186/s40792-018-0419-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775187PMC
January 2018

Laparoscopic surgery in colon cancer patients treated with chronic anti-thrombotic therapy.

Surg Endosc 2018 08 16;32(8):3509-3516. Epub 2018 Jan 16.

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

Background: Anti-thrombotic medications are commonly used for the treatment and prevention of cardiovascular diseases. Laparoscopic resection of colon cancer has generally been accepted with favorable outcomes being reported in randomized control trials. However, the safety and efficacy of laparoscopic surgery for colon cancer patients receiving chronic anti-thrombotic therapy (AT) remain unclear.

Methods: We identified 951 patients who underwent elective resection for colon cancer between 2009 and 2016 from our database. Patients were classified according to the surgical approach and chronic AT. Clinicopathological factors and surgical outcomes were analyzed between patient groups. Patients' backgrounds were matched using propensity scores in laparoscopic surgery.

Results: Anti-thrombotic drugs were chronically used in 135 patients. Among 714 patients who underwent laparoscopy-assisted surgery, 96 received AT. The laparoscopic approach was superior to open surgery in terms of bleeding, surgical site infections, and hospital stay in patients receiving AT. In laparoscopy-assisted surgery, the AT group patients were older and showed lower hemoglobin and albumin levels than those not receiving AT (non-AT group), and were predominantly male. After propensity score matching, estimated blood loss and operative times were similar between the two groups (93 matched patients). The frequencies of postoperative bleeding (2.2%) and thrombotic complications (0%) in the AT group did not significantly differ from those in the non-AT group (1.1 and 0%, respectively). Moreover, AT did not affect survivals.

Conclusion: Laparoscopic approach appears to be safer and beneficial for colonic cancer patients receiving long-term AT. Bleeding and thrombotic events associated with laparoscopic surgery were not significantly affected by AT.
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http://dx.doi.org/10.1007/s00464-018-6071-xDOI Listing
August 2018

CD133 expression predicts post-operative recurrence in patients with colon cancer with peritoneal metastasis.

Int J Oncol 2018 Mar 8;52(3):721-732. Epub 2018 Jan 8.

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

Despite extensive research on cancer stem cells in colorectal cancer, the impact of stem cell markers on patient survival remains unclear, particularly in those with distant metastasis. In this study, we focused on colon cancer with peritoneal metastasis and investigated the association between the expression of CD133, aldehyde dehydrogenase-1 (ALDH1) and leucine-rich repeating G-protein coupled receptor-5 (Lgr5), and disease prognosis. Putative stem cell marker expression was immunohistochemically evaluated in samples from 142 primary tumours and 75 peritoneal nodules. The associations between the expression of these markers and clinicopathological characteristics, overall survival and disease-free survival were analysed. The expression of CD133, ALDH1 and Lgr5 was found to be positive in 55.6, 47.2 and 78.9% of the primary tumour samples, respectively. While their expression was not associated with overall survival, disease-free survival was significantly worse in the CD133‑negative group (36.1 vs. 13.7%, P=0.041). Multivariable analysis confirmed that a negative CD133 expression was an independent risk factor for a reduced disease-free survival (P=0.005). Furthermore, the benefit of systemic chemotherapy was significantly greater in the CD133-negative group (P=0.039). On the whole, our data indicated that patients with colon cancer with CD133-negative expression had a reduced disease-free survival. Thus, we propose that CD133 expression may be a useful clinical biomarker in the treatment of colon cancer with peritoneal metastasis.
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http://dx.doi.org/10.3892/ijo.2018.4240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807045PMC
March 2018

Marked edema of colonic stoma after colectomy and severe pulmonary hypertension: Report of two cases.

Clin Res Hepatol Gastroenterol 2018 02 29;42(1):e1-e4. Epub 2017 Dec 29.

Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Introduction: Pulmonary hypertension (PH) is a disease with a poor prognosis and is a risk for perioperative heart and respiratory failure. Few reports exist regarding a colectomy performed in patients with PH. Herein, we report two cases of colectomy performed in patients with severe PH, accompanied with marked edema of the colonic stoma after surgery.

Case Presentation: In case 1, a 54-year-old patient with sigmoid cancer and severe primary PH underwent Hartmann's operation. After the operation, his stoma became markedly edematous and ulcerated. Swelling of the stoma became gradually reduced, and the patient was discharged from hospital 36 days after the operation. In case 2, a 62-year-old patient with upper rectal cancer and severe PH also underwent Hartmann's operation; his stoma became markedly edematous without ulceration.

Conclusion: Marked edema of the colonic stoma was observed in two cases with severe PH, with ulceration of the mucosa observed in one case. It was considered reasonable to avoid anastomosis in cases with severe PH.
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http://dx.doi.org/10.1016/j.clinre.2017.04.003DOI Listing
February 2018

Regimens of Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer.

Anticancer Res 2018 01;38(1):15-22

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.

Although systemic chemotherapy has been improved, peritoneal carcinomatosis remains a factor of poor prognosis in patients with colorectal cancer. In order to achieve a higher drug concentration in the peritoneal cavity, intraperitoneal chemotherapy has been performed. However, the optimal regimen for intraperitoneal chemotherapy has not been determined. In this review of intraperitoneal chemotherapy for colorectal cancer, we summarize regimens of hyperthermic intraperitoneal chemotherapy (HIPEC) and other intraperitoneal chemotherapy modalities, such as early postoperative intraperitoneal chemotherapy (EPIC) and sequential postoperative intraperitoneal chemotherapy (SPIC). Mitomycin C and oxaliplatin are the most common chemotherapeutic agents used for HIPEC. Some combination therapies such as those involving bevacizumab, HO, and amifostine have potential to increase HIPEC efficacy. 5-Fluorouracil is used mainly for EPIC and SPIC. Some new agents such as paclitaxel, melphalan, and various nanoparticles have been developed. These novel chemotherapeutic agents may achieve clinical implementation in the future.
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http://dx.doi.org/10.21873/anticanres.12186DOI Listing
January 2018
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