Publications by authors named "Yasutaka Shuno"

41 Publications

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

Intest Res 2021 Mar 12. Epub 2021 Mar 12.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Change in skeletal muscle index and its prognostic significance in patients who underwent successful conversion therapy for initially unresectable colorectal cancer: observational study.

Therap Adv Gastroenterol 2020 12;13:1756284820971197. Epub 2020 Nov 12.

Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Systemic therapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic therapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy.

Methods: We reviewed 98 stage IV CRC patients who received systemic therapy in our hospital. According to the treatment setting, patients were divided into the conversion, neoadjuvant chemotherapy (NAC), and palliation groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during systemic therapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the conversion group.

Results: The mean SMI increased by 9.4% during systemic therapy in the conversion group ( = 38), whereas it decreased by 5.9% in the NAC group ( = 18) and 3.7% in the palliation group ( = 42,  < 0.0001). Moreover, patients with increased SMI during systemic therapy had a better overall survival (OS) than those whose SMI decreased in the conversion group ( = 0.025). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio 0.25).

Conclusions: Stage IV CRC patients who underwent conversion to resection often had an increased SMI. On the other hand, a decrease in the SMI during systemic therapy was a negative prognostic factor in such patients.
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http://dx.doi.org/10.1177/1756284820971197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672750PMC
November 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Department of Surgical Oncology.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The component changes of lysophospholipid mediators in colorectal cancer.

Tumour Biol 2019 May;41(5):1010428319848616

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

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

Molecular Subtypes Are Frequently Discordant Between Lesions in Patients With Synchronous Colorectal Cancer: Molecular Analysis of 59 Patients.

Anticancer Res 2019 Mar;39(3):1425-1432

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

Background: We aimed to investigate the molecular features of synchronous colorectal cancer (CRC).

Materials And Methods: Out of 1,262 patients with CRC, 130 lesions in 59 patients with synchronous CRC were retrospectively analyzed. Microsatellite, v-Ki-Ras2 Kristen rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), tumor protein 53 (TP53) and β-catenin status were evaluated and compared between synchronous CRC lesions in each patient.

Results: The subtypes of instability, BRAF and β-catenin subtypes was significant but low. Patients with discordant KRAS and TP53 were not concordant between lesions in the same patient, and concordance of microsatellite KRAS/BRAF subtypes comprised 50.8% of those with synchronous CRC. The rate of patients with lesions containing both mutL homolog 1 (MLH1) methylation and microsatellite stable status was 66.7% in those with synchronous CRC, with at least one lesion with high microsatellite instability.

Conclusion: The present study on synchronous CRC demonstrated a low concordance of molecular subtypes between lesions in the same patient. A molecular analysis of metastatic lesions is warranted for molecular targeted therapy of metastatic synchronous CRC.
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http://dx.doi.org/10.21873/anticanres.13258DOI Listing
March 2019

Prognostic significance of doubling time in patients undergoing radical surgery for metachronous peritoneal metastases of colorectal cancer.

Int J Colorectal Dis 2019 May 9;34(5):801-809. Epub 2019 Feb 9.

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

Purpose: The doubling times of tumor volume and tumor markers are associated with the prognosis of liver or lung metastases from colorectal cancer (CRC). However, no studies have assessed peritoneal metastases. Therefore, we aimed to elucidate the association between doubling time and the prognosis of patients who underwent radical surgery for metachronous peritoneal metastases of CRC.

Methods: We calculated the tumor doubling times (TDT) of peritoneal metastases and serum carcinoembryonic antigen-doubling times (CEA-DT) in 33 consecutive patients who underwent radical surgery for metachronous peritoneal metastases between January 2006 and April 2017. The impact of short TDT and CEA-DT on overall survival (OS) and relapse-free survival (RFS) was retrospectively reviewed.

Results: In long TDT (> 137 days) group, the 5-year OS rate was 74.1% and median OS time was 6.6 years. In long CEA-DT (> 102 days) group, the 5-year OS rate was 50.0% and median OS time was 5.6 years. Conversely, in short TDT (≤ 137 days) and CEA-DT (≤ 102 days) group, the 5-year OS rates and median OS times were both 0.0% and 3.2 years, respectively. In the multivariate analysis, short TDT was an independent risk factor for poor RFS (P = 0.006) and OS (P = 0.010). Similarly, short CEA-DT was also a poor risk factor for RFS (P < 0.001) and OS (P = 0.012).

Conclusions: Short TDT and CEA-DT are independent risk factors for poor OS and RFS after surgery for metachronous peritoneal metastases of CRC. TDT and CEA-DT should be considered when selecting candidates for surgical resection.
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http://dx.doi.org/10.1007/s00384-019-03259-5DOI Listing
May 2019

Venous thromboembolism in colorectal surgery: Incidence, risk factors, and prophylaxis.

Asian J Surg 2019 Sep 23;42(9):863-873. Epub 2019 Jan 23.

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

Colorectal surgery is associated with a high risk of perioperative venous thromboembolism (VTE), and this risk is especially high following colorectal cancer resection and surgery for inflammatory bowel disease. Previous analyses of large databases have reported the incidence of postoperative VTE in this population to be approximately 1.1%-2.5%. Therefore, to minimize this risk, patients should be offered appropriate prophylaxis, which may involve a combination of mechanical and pharmacologic prophylaxis with low-dose unfractionated heparin or low molecular weight heparin as recommended by several guidelines. Prior to initiation of treatment, appropriate risk stratification should be performed according to the patients' basic and disease-related as well as procedure-related risk factors, and post-operative factors. Furthermore, a risk-benefit calculation that takes into account patients' VTE and bleeding risk should be performed prior to starting pharmacologic prophylaxis and to help determine the duration of treatment.
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http://dx.doi.org/10.1016/j.asjsur.2018.12.013DOI Listing
September 2019

Neoadjuvant imatinib therapy in rectal gastrointestinal stromal tumors.

Surg Today 2019 Jun 15;49(6):460-466. Epub 2018 Nov 15.

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

Rectal gastrointestinal stromal tumor (GIST) is a rare entity. Thus, its clinical features have not been well documented, and optimal treatment strategies have not been established. Surgery for rectal GISTs may be difficult because they are often large in size. In addition, rectal GISTs were found to be associated with high rates of local recurrence, regardless of the surgical procedure, before imatinib was introduced in the early 2000s. Since the introduction of imatinib therapy, accumulating evidence suggests that neoadjuvant imatinib therapy may improve the outcomes of rectal GIST treatment. Neoadjuvant imatinib therapy for rectal GISTs offers a number of potential benefits, including tumor downsizing, reduction in mitotic activity, reduced morbidity, and a reduced risk of recurrence. Less radical procedures may allow for the preservation of the anal sphincter and avoidance of a permanent colostomy. This review summarizes the current status and future perspectives of neoadjuvant imatinib therapy for the treatment of rectal GISTs.
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http://dx.doi.org/10.1007/s00595-018-1737-5DOI Listing
June 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

Prognostic Significance and Clinicopathological Features of Synchronous Colorectal Cancer.

Anticancer Res 2018 Oct;38(10):5889-5895

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

Aim: This study aimed to clarify the difference in the clinicopathological and prognostic features between synchronous colorectal cancer (CRC) and solitary CRC.

Materials And Methods: A retrospective analysis was conducted in patients with synchronous and solitary CRC.

Results: A total of 92 (7.1%) out of 1,295 consecutive patients had synchronous CRC. Mucinous adenocarcinoma was more frequent in patients with synchronous CRC than in those with solitary CRC (13.0% vs. 3.7%; p<0.001). The 5-year relapse-free survival (RFS) rate was poorer in patients with synchronous CRC than in those with solitary CRC (65.3% vs. 75.1%; p=0.035), which was contrived by the multivariate analysis (hazard ratio=1.52(HR); p=0.039).

Conclusion: Patients with synchronous CRC had a poorer RFS than those with solitary CRC; thus, patients with synchronous CRC might require more intensive care than those with solitary CRC in follow-up.
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http://dx.doi.org/10.21873/anticanres.12932DOI Listing
October 2018

Predictors for High Microsatellite Instability in Patients with Colorectal Cancer Fulfilling the Revised Bethesda Guidelines.

Anticancer Res 2018 Aug;38(8):4871-4876

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

Background: The revised Bethesda guidelines (rBG) are generally used for screening of Lynch syndrome, and few researchers have investigated the associations between microsatellite instability (MSI) status and each item of the rBG.

Patients And Methods: This retrospective study included patients with colorectal cancer who were classified into those fulfilling the rBG (Bethesda group) and those not (control group). The breakdown of each item in the rBG and predictors of high MSI (MSI-H) were determined in the Bethesda group.

Results: Of 809 consecutive patients, 161 (19.9%) were found to fulfil the rBG criteria. As a predictor of MSI-H, items 2 or 5 of the rBG showed a sensitivity of 93.3%. Item 5 and right-sided tumour location were independent predictors of MSI-H in patients fulfilling the rBG (odds ratio(OR)=4.49 and 25.1; p=0.0260 and <0.0001, respectively).

Conclusion: Item 5 of the rBG and right-sided tumour location are significant predictors of MSI-H.
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http://dx.doi.org/10.21873/anticanres.12800DOI Listing
August 2018

Diagnostic performance of F-FDG PET/CT using point spread function reconstruction on initial staging of rectal cancer: a comparison study with conventional PET/CT and pelvic MRI.

Cancer Imaging 2018 Jan 30;18(1). Epub 2018 Jan 30.

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

Background: Accurate staging is crucial for treatment selection and prognosis prediction in patients with rectal cancer. Point spread function (PSF) reconstruction can improve spatial resolution and signal-to-noise ratio of PET imaging. The aim of this study was to evaluate the effectiveness of F-FDG PET/CT with PSF reconstruction for initial staging in rectal cancer compared with conventional PET/CT and pelvic MRI.

Methods: A total of 59 patients with rectal cancer underwent preoperative F-FDG PET/CT and pelvic MRI. The maximum standardized uptake value (SUVmax) and lesion to background (L/B) ratio of possible metastatic lymph nodes, and metabolic tumor volumes (MTVs) of primary tumors were calculated. For N and T (T1-2 vs T3-4) staging, sensitivities, specificities, positive predictive values, negative predictive values, and accuracies were compared between conventional PET/CT [reconstructed with ordered subset expectation maximization (OSEM)], PSF-PET/CT (reconstructed with OSEM+PSF), and pelvic MRI. Histopathologic analysis was the reference standard.

Results: For N staging, PSF-PET/CT provided higher sensitivity (78.6%) than conventional PET/CT (64.3%), and pelvic MRI (57.1%), and all techniques showed high specificity (PSF-PET: 95.4%, conventional PET: 96.7%, pelvic MRI: 93.5%). SUVmax and L/B ratio were significantly higher in PSF-PET/CT than conventional-PET/CT (p < 0.001). The accuracy for T staging in PSF-PET/CT (69.4%) was not significantly different to conventional PET/CT (73.5%) and pelvic MRI (73.5%). MTVs of PSF and conventional PET showed a significant difference among T stages (p < 0.001), with higher values in advanced stages. In M staging, both PSF and conventional PET/CT diagnosed all distant metastases correctly.

Conclusions: PSF-PET/CT produced images with higher lesion-to-background contrast than conventional PET/CT, which allowed improved detection of lymph node metastasis without compromising specificity, and showed comparable diagnostic value to MRI in local staging. PSF-PET/CT is likely to have a great value for initial staging in rectal cancer.
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http://dx.doi.org/10.1186/s40644-018-0137-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789619PMC
January 2018

Induction of IFN-λ3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection.

Gut 2018 02 27;67(2):362-371. Epub 2016 Oct 27.

The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.

Objective: The clinical significance of polymorphisms in the interleukin-28B gene encoding interferon (IFN)-λ3, which has antiviral effects, is known in chronic HCV but not in HBV infection. Thus, we measured IFN-λ3 levels in patients with HBV and investigated its clinical significance and association with nucleos(t)ide (NUC) analogue administration.

Design: Serum IFN-λ3 level was measured in 254 patients with HBV with varying clinical conditions using our own high sensitivity method. The resulting values were compared with various clinical variables. In addition, cell lines originating from various organs were cultured with NUCs, and the production of IFN-λ3 was evaluated.

Results: Higher serum IFN-λ3 levels were detected in the patients treated with nucleotide analogues (adefovir or tenofovir) compared with those treated with nucleoside analogues (lamivudine or entecavir). There were no other differences in the clinical background between the two groups. A rise in the serum IFN-λ3 levels was observed during additional administration of the nucleotide analogues. In vitro experiments showed that the nucleotide analogues directly and dose-dependently induced IFN-λ3 production only in colon cancer cells. Furthermore, the supernatant from cultured adefovir-treated colon cancer cells significantly induced IFN-stimulated genes (ISGs) and inhibited hepatitis B surface antigen (HBsAg) production in hepatoma cells, as compared with the supernatant from entecavir-treated cells.

Conclusions: We discovered that the nucleotide analogues show an additional pharmacological effect by inducing IFN-λ3 production, which further induces ISGs and results in a reduction of HBsAg production. These findings provide novel insights for HBV treatment and suggest IFN-λ3 induction as a possible target.
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http://dx.doi.org/10.1136/gutjnl-2016-312653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868296PMC
February 2018

Comparison of Functional Outcomes of Patients Who Underwent Hand-Sewn or Stapled Ileal Pouch-Anal Anastomosis for Ulcerative Colitis.

Int Surg 2015 Jul;100(7-8):1169-76

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

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment for patients with ulcerative colitis (UC). The purpose of this study was to investigate the long-term functional outcomes and quality of life (QOL) associated with hand-sewn and stapled IPAA. Ninety-one patients with UC had undergone IPAA using hand-sewn anastomosis with mucosectomy (32 patients) or stapled anastomosis (59 patients) from January 1988 to May 2010. Patients were evaluated according to patient characteristics, postoperative complications, functional outcomes and QOL. The QOL of patients were evaluated using the Medical Outcomes Study Short Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Numbers of patients with colorectal cancer or dysplasia were significantly greater in the hand-sewn IPAA group (P < 0.01). These patients had longer disease durations and were older (both P < 0.01). There was no difference in the incidence of complications between the groups, except for a greater incidence of postoperative anal fistula in the stapled group (P = 0.03). In the early postsurgery period, both the frequency of bowel movements and the rate of soiling were significantly higher in the hand-sewn group, but in a later period, there was no difference in these events >3 years after surgery. The SF-36 and IBDQ results were similar in the two groups, indicating that hand-sewn and stapled IPAA result in similar QOL in the late postoperative period. Postoperative complications, functional outcomes, and long-term QOL were similar in patients who had received hand-sewn or stapled IPAA.
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http://dx.doi.org/10.9738/INTSURG-D-15-00012.1DOI Listing
July 2015

Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer.

Oncol Lett 2012 Apr 7;3(4):756-760. Epub 2012 Feb 7.

Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, Tokyo 113-8655, Japan.

Adiponectin is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of tumor growth. The expression and function of the two major adiponectin receptors, AdipoR1 and AdipoR2, in malignant tissue have not been well characterized. In the present study, we evaluated the mRNA levels of AdipoR1 and AdipoR2 expression in 48 surgically resected colorectal cancer specimens, as well as normal colonic mucosa, by quantitative RT-PCR. The values obtained were standardized by β-actin mRNA, and the correlation between their relative expression levels and the clinicopathological characteristics of the patients was examined. The relative expression levels of AdipoR1 and AdipoR2 were significantly reduced in cancer tissue compared with normal tissue (AdipoR1: 0.97±0.39 vs. 1.37±0.41, P<0.0001; AdipoR2: 0.92±0.31 vs. 1.60±0.46, P<0.0001). AdipoR1 and AdipoR2 levels were further reduced in tumors with nodal metastases and the difference was statistically significant in the case of AdipoR2 (0.79±0.27 vs. 1.02±0.30, P=0.012). The results of this study demonstrated that the expression levels of adiponectin receptors are reduced in cancer specimens compared to normal tissue, indicating a downregulation in the course of the development and progression of colorectal cancer. Since adiponectin is abundantly present in the whole body and has inhibitory effects on cancer cells, this downregulation of the receptors may be an escape mechanism of malignant cells from the suppressive effects of adiponectin.
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http://dx.doi.org/10.3892/ol.2012.583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362449PMC
April 2012

Is surveillance endoscopy necessary after colectomy in ulcerative colitis?

ISRN Gastroenterol 2011 2;2011:509251. Epub 2011 Jul 2.

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

The role of surveillance endoscopic followup in colectomized patients with long standing total colitis is controversial. Here, we aimed to clarify its usefulness for the early detection of dysplasia and cancer in this group of patients. Ninety-seven colectomised UC patients followedup by surveillance endoscopy were retrospectively investigated by reviewing the pathological reports. Patients had received either subtotal colectomy and ileo-rectal anastomosis (IRA) or total proctocolectomy and ileal anal anastomosis (IPAA). Definite dysplasia was diagnosed in 4 patients, who had received IRA; among them, 2 were carcinoma with submucosal invasion, and one was a high-grade dysplasia. Postoperative surveillance endoscopy is useful for the detection of early cancer in the remaining colonic mucosa of UC patients, and those receiving IRA, in which rectal mucosa is left intact, would be good candidates. However, its effectiveness for patients receiving IPAA, in which the rectal mucosa is resected, needs further investigation.
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http://dx.doi.org/10.5402/2011/509251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168456PMC
November 2011

CD133(-) cells, derived from a single human colon cancer cell line, are more resistant to 5-fluorouracil (FU) than CD133(+) cells, dependent on the β1-integrin signaling.

J Surg Res 2012 Jun 24;175(2):278-88. Epub 2011 Apr 24.

Department of Surgical Oncology, The University of Tokyo, Faculty of Medical Sciences, Tokyo, Japan.

Background And Aim: Recently, the cancer stem cells (CSCs) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in various cancer types. In the present study, we aimed evaluate CD133 as a potential marker of colorectal CSCs and, for this purpose, isolated CD133(+) and CD133(-) cells from a single colorectal cancer cell line, and compared their features, especially related to the tumor-forming and differentiation abilities, and the sensitivity to chemotherapy.

Methods And Results: CD133(+) cells had higher in vivo tumor-forming ability than CD133(-) cells, and in culture, they progressively differentiated into CD133(-) cells, but not vice-versa. On the other hand, CD133(-) cells were more resistant to 5-fluorouracil (FU) treatment than CD133(+) cells, and it was found to be dependent on the higher expression of ß1-integrins, and consequently, higher ability to bind collagen. Disruption of the ß1-integrin function abrogated the chemoresistance.

Conclusion: From the present results, we concluded that colorectal cancer CD133(+) cells, although showing some features of CSCs, are not more resistant to 5-FU than CD133(-) cells. Therefore, definite conclusions can not be drawn yet, but it is strongly suggestive that CD133 should not be used as a single CSC marker of colorectal cancer.
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http://dx.doi.org/10.1016/j.jss.2011.03.076DOI Listing
June 2012

Radiosensitization of human breast cancer cells to ultraviolet light by 5-fluorouracil.

Oncol Lett 2011 May 1;2(3):471-476. Epub 2011 Mar 1.

Department of Surgical Oncology, Faculty of Medical Sciences, The University of Tokyo, Tokyo, Japan.

Ultraviolet light B (UVB) phototherapy is widely used to treat dermatological diseases and therefore may be a potential optional strategy in the treatment of a skin lesion infiltrated by a malignant tumor. Currently, little is known regarding the effect of UVB phototherapy on human breast cancer cells. The present study aimed to investigate the effect of UVB phototherapy, as well as the potential effect of 5-fluorouracil (5-FU), the first-line anticancer drug for breast cancer, on radiosensitizing MCF-7 human breast cancer cells, in an attempt to develop new therapeutic strategies for the treatment of locoregional recurrence of breast cancer. MCF-7 cells were incubated in the presence of 5-FU for 48 h, and UVB irradiation at 750 mJ/cm(2) was administered in the midterm of 5-FU treatment. The viability of MCF-7 cells was analyzed by the trypan blue staining method. Apoptosis was quantified by flow cytometry and Hoechst 33258 staining. The cell cycle was evaluated by flow cytometry after the staining of cells with propidium iodide. The combination treatment of 5-FU and UVB resulted in a strong potentiation of the inhibitory effect of MCF-7 cell growth, dependent on the intra-S phase cell cycle arrest and induction of apoptosis, when compared to treatment with 5-FU or UVB alone. In conclusion, 5-FU sensitized human breast cancer cells to UVB phototherapy, and this combination therapy is an effective and promising strategy for the treatment of breast cancer, particularly for locoregional recurrence.
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http://dx.doi.org/10.3892/ol.2011.261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410487PMC
May 2011
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