Publications by authors named "Yuzo Nagai"

17 Publications

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Predictive factors of survival of colorectal cancer patients after para-aortic lymph node metastasis.

Int J Clin Oncol 2021 Nov 27. Epub 2021 Nov 27.

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

Background: Para-aortic lymph node (PALN) metastasis is an ominous manifestation indicating a poor prognosis in colorectal cancer (CRC) patients; however, some treatments prolong survival. In this study, we investigated predictors of prolonged survival in CRC patients after PALN metastasis.

Methods: We examined 141 patients with CRC that metastasized to the PALNs from CRC with or without extra-PALN metastasis. Among clinicopathological parameters, factors associated with survival after PALN metastasis were identified by multivariate analyses using Cox's proportional hazard models.

Results: The mean hemoglobin and albumin values at diagnosis were 12.3 g/dL and 3.7 g/dL, respectively. Rectal cancer was predominant (n = 81). Mutated RAS was detected in 43%. One hundred and four patients had differentiated adenocarcinoma. Patients underwent PALN dissection (n = 11), radiotherapy (n = 6), and systemic therapy (n = 120). Biologics were administered to 95 patients. The median survival time was 29.1 months. On multivariate analysis, independent factors associated with reduced survival after PALN metastasis were low albumin (hazard ratio [HR] 2.33 per -1 g/dL), mutated RAS (HR 2.55), other than differentiated adenocarcinoma (HR 2.75), rectal cancer (HR 3.38 against right-sided colon, and 3.48 against left-sided colon), the presence of extra-PALN metastasis (HR 6.56), and no use of biologics (HR 3.04).

Conclusions: This study revealed that hypoalbuminemia as well as RAS mutation, undifferentiated histology, rectal cancer, other site metastasis, and no use of biologics contribute to poor prognosis in CRC patients with PALN metastasis. Nutritional management may be important for improving survival of these patients.
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http://dx.doi.org/10.1007/s10147-021-02095-4DOI Listing
November 2021

Prognoses in Pathologically Confirmed T1 Lower Rectal Cancer Patients with or without Preoperative Therapy: An Analysis Using the Surveillance, Epidemiology, and End Results Database.

Oncology 2021 Nov 24. Epub 2021 Nov 24.

Introduction Preoperative chemoradiotherapy (CRT) is the standard therapy for downstaging in locally advanced lower rectal cancer. However, it remains unclear whether rectal cancers down-staged by preoperative therapy show similar prognoses to those of the same stage without preoperative therapy. We previously demonstrated that preoperative CRT did not affect prognosis of rectal cancer with pathological T1N0 (pT1N0) stage in a single institute. Here, using a larger dataset, we compared prognoses of (y)pT1 rectal cancer stratified by the use of preoperative therapy and analyzed prognostic factors. Methods Cases of pT1N0 rectal cancer, registered between 2004 and 2016, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized as the 'ypT1 group' if they had undergone preoperative therapy before surgery or as the 'pT1 group' if they had undergone surgery alone. overall survival (OS) and cancer-specific survival (CSS) between these groups of patients was compared. Factors associated with CSS and OS were identified by univariate and multivariate analyses. Results Among 3,757 eligible patients, ypT1 and pT1 groups comprised 720 and 3,037 patients, respectively. While ypT1 patients showed poorer CSS than ypT1 patients, there was no significant difference in OS. Preoperative therapy was not an independent prognostic factor for CSS or OS. Multivariate analysis identified age and histological type as significant factors associated with CSS. Sex, age, race, and number of lymph nodes dissected were identified as significant factors associated with OS. Conclusions Prognosis among patients with (y)p T1N0 rectal cancer was similar irrespective of whether they underwent preoperative therapy, which is consistent with our previous observations.
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http://dx.doi.org/10.1159/000521033DOI Listing
November 2021

Preoperative sarcopenia is a poor prognostic factor in lower rectal cancer patients undergoing neoadjuvant chemoradiotherapy: a retrospective study.

Int J Clin Oncol 2021 Nov 6. Epub 2021 Nov 6.

Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: This study aimed to investigate the effect of sarcopenia on the prognosis of advanced lower rectal cancer patients receiving neoadjuvant chemoradiotherapy (CRT). Sarcopenia has been recognized as an adverse factor for surgical outcomes in several malignancies. However, the impact of preoperative sarcopenia on rectal cancer patients receiving CRT is still unknown.

Methods: This retrospective study included cT3-T4 anyN M0 lower rectal cancer patients who underwent CRT followed by R0 resection at our institution between October 2003 and December 2016. CRT consisted of 5-fluorouracil-based oral chemotherapy and long course radiation (50.4 Gy/28 fr). The psoas muscle area at the third lumbar vertebra level was evaluated by computed tomography before and after CRT, and was adjusted by the square of the height to obtain the psoas muscle mass index (PMI). Sarcopenia was defined as the sex-specific lowest quartile of the PMI. We assessed the association between pre- and post-CRT sarcopenia and postoperative prognosis.

Results: Among 234 patients, 55 and 179 patients were categorized as sarcopenia and non-sarcopenia patients, respectively. Although post-CRT sarcopenia correlated with residual tumor size, it had no association with other pathological features. The median follow-up period was 72.9 months, and the 5-year DFS and OS were 67.0% and 85.8%, respectively. Multivariate analysis showed that post-CRT sarcopenia was independently associated with poor DFS (HR: 1.76; P = 0.036), OS (HR: 2.01; P = 0.049), and recurrence in the liver (HR: 3.01; P = 0.025).

Conclusions: Sarcopenia is a poor prognostic indicator in lower advanced rectal cancer patients treated with CRT.
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http://dx.doi.org/10.1007/s10147-021-02062-zDOI Listing
November 2021

Poor nutrition and sarcopenia are related to systemic inflammatory response in patients with rectal cancer undergoing preoperative chemoradiotherapy.

Int J Colorectal Dis 2021 Oct 11. Epub 2021 Oct 11.

Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: Preoperative chemoradiotherapy (CRT) is the standard therapy for locally advanced rectal cancer (LARC). However, the changes that the patient's physical status during CRT, such as host systemic inflammatory response, nutritional status, and muscle depletion, are still unclear. We evaluated the clinical significance of malnutrition and sarcopenia for patients with LARC undergoing CRT.

Patients And Methods: Patients with LARC treated with CRT following radical surgery at our institution between 2006 and 2016 (N = 225) were retrospectively analyzed. A new prognostic score (PNSI) was devised based on the prognostic nutritional index (PNI) and the psoas muscle mass index (PMI): patients with malnutrition/sarcopenia were scored 2; patients with one and neither abnormality were scored 1 and 0, respectively.

Results: Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and platelet/lymphocyte ratio increased, whereas PNI and PMI decreased after CRT. There were 130, 73, and 22 patients in the PNSI 0, 1, and 2 groups, respectively. Patients with higher PNSI had higher residual tumor size (p = 0.003), yT stage (p = 0.007), ypStage (p < 0.001), post-CRT platelet/lymphocyte ratio (p = 0.027), and post-CRT C-reactive protein/albumin ratio (p < 0.001). Post-CRT PNSI was associated with overall survival and was an independent poor prognosis factor (PNSI 1 to 0, hazard ratio 2.40, p = 0.034, PNSI 2 to 0, hazard ratio 2.66, p = 0.043) together with mesenteric lymph node metastasis, lateral lymph node metastasis, and histology.

Conclusion: A combined score of post-CRT malnutrition/sarcopenia is promising for predicting overall survival in LARC.
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http://dx.doi.org/10.1007/s00384-021-04039-wDOI Listing
October 2021

Impact of Inferior Mesenteric Artery Occlusion on the Calibre of Collateral Arteries of the Colon.

Anticancer Res 2021 Oct;41(10):5189-5193

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

Background/aim: The inferior mesenteric arteries (IMA) are occluded in some colorectal cancer patients. This study evaluated the impact of IMA occlusion on the calibre of collateral arteries.

Patients And Methods: As an IMA obstruction model, 20 patients who underwent abdominal aortic aneurysm surgery, with ligated, excluded, or embolised IMA, were enrolled. Changes in the calibre of the left colic arteries (LCAs) and marginal arteries after surgeries were evaluated.

Results: The cross-sectional area of the LCA significantly increased after surgery (4.34 mm vs. 6.34 mm, p=0.0009) and that of the marginal artery did not change significantly (2.69 mm vs. 3.01 mm, p=0.33).

Conclusion: The calibre of the LCA increased after IMA occlusion. The descending branch of the LCA should be confirmed preoperatively to preserve blood flow during a low tie procedure.
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http://dx.doi.org/10.21873/anticanres.15337DOI Listing
October 2021

Women are predisposed to early dose-limiting toxicities during adjuvant CAPOX for colorectal cancer.

Int J Clin Pract 2021 Nov 18;75(11):e14863. Epub 2021 Sep 18.

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

Aim: Oxaliplatin-based adjuvant chemotherapy was demonstrated to be beneficial for stage III or high-risk stage II colorectal cancer (CRC). Moreover, a recent international collaborative trial suggested 3-months CAPOX as an alternative regimen for low-risk stage III colorectal cancer (CRC) patients. Thus, it is important to clarify the frequency and predictive markers of dose-limiting toxicities (DLTs) developed within the short-course CAPOX cycles.

Methods: We investigated CRC patients who underwent radical surgery and adjuvant CAPOX therapy at our hospital between December 2010 and February 2021. Patients who received initially reduced doses of CAPOX and those who had early recurrence were excluded. We reviewed the age, sex, comorbidities, physical, laboratory and oncological data and other perioperative factors. The associations between these variables and early DLTs within four cycles of CAPOX were examined by multivariate analyses using logistic regression models.

Results: Among 168 patients (96 men, mean age: 58.3 years), 120 (71%) developed early DLTs. Patients with early DLTs were predominantly women and sarcopenic and habitual alcohol consumers. On multivariate analyses, only the female sex was an independent predictive factor for early DLTs (odds ratio: 2.61, P = .027).

Conclusion: Women were prone to early DLTs during adjuvant CAPOX in the current study. Doctors should be aware of the sex difference in the incidence of early DLTs, adjust the CAPOX dosage and provide supportive care for female CRC patients.
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http://dx.doi.org/10.1111/ijcp.14863DOI Listing
November 2021

Vascular anatomy of the splenic flexure: a review of the literature.

Surg Today 2021 Aug 4. Epub 2021 Aug 4.

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

Surgical treatment of the transverse colon is difficult because of the many variations of blood vessels. We reviewed the patterns of vascular anatomy and the definition of the vessels around the splenic flexure. We searched the PubMed database for studies on the vascular anatomy of the splenic flexure that were published from January 1990 to October 2020. After screening of full texts, 33 studies were selected. The middle colic arteries were reported to arise independently without forming a common trunk in 8.9-33.3% of cases. The left colic artery was absent in 0-7.5% of cases. The accessory middle colic artery was present in 6.7-48.9% of cases and was present in > 80% of cases without a left colic artery. The reported frequency of Riolan's arch was 7.5-27.8%. The frequency was found to vary widely across studies, partially due to the ambiguous definition of Riolan's arch. A comprehensive preoperative knowledge of the branching patterns of the middle colic artery and left colic artery and the presence of collateral arteries would be helpful in surgery for colon cancer in the splenic flexure.
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http://dx.doi.org/10.1007/s00595-021-02328-zDOI Listing
August 2021

Risk of extracolonic malignancies and metachronous rectal cancer after colectomy and ileorectal anastomosis in familial adenomatous polyposis.

Asian J Surg 2021 Jul 27. Epub 2021 Jul 27.

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

Background: Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients.

Methods: Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed.

Results: The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer.

Conclusion: Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients.
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http://dx.doi.org/10.1016/j.asjsur.2021.06.034DOI Listing
July 2021

Expression of Lysophosphatidylinositol Signaling-relevant Molecules in Colorectal Cancer.

Anticancer Res 2021 May;41(5):2349-2355

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

Background/aim: Lysophosphatidylinositol (LPI) is a subspecies of the lysophospholipid mediators produced when phospholipase hydrolyzes membrane phosphatidylinositol. Previously, we used mass spectrometry-based lipidomics to demonstrate that LPI is selectively elevated in colorectal cancer (CRC) tissues. Here, we hypothesized that the expression levels of the LPI biosynthetic enzyme and LPI receptor - DDHD domain containing 1 (DDHD1) and G protein-coupled receptor 55 (GPR55), respectively - may be correlated with malignant potential, and we evaluated their roles in the context of CRC.

Materials And Methods: Colorectal specimens from 92 CRC patients underwent DDHD1 and GPR55 immunolabeling. Correlation between protein expression levels and clinicopathological variables was examined.

Results: Depth of tumor invasion was positively correlated with DDHD1 expression. Regardless of the degree of invasion depth, GPR55 was highly expressed in CRC tissues. Neither DDHD1 nor GPR55 expression levels were associated with disease-free survival.

Conclusion: DDHD1 expression is associated with depth of tumor invasion in CRC tissues and may be involved in tumor progression.
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http://dx.doi.org/10.21873/anticanres.15009DOI Listing
May 2021

LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer.

Oncotarget 2017 Feb;8(7):11906-11916

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

Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]. Greater LHI values indicated enhanced hypomethylation. In our clinicopathological analysis, CRC patients with large tumors (≥6.0 cm), advanced N stage (≥2), and distant metastasis (M1) had statistically significantly higher cfDNA LHI than other CRC patients, suggesting cfDNA LHI as a disease progression biomarker for CRC. Furthermore, early stage I/II (n = 57) as well as advanced stage III/IV (n =57) CRC patients had significantly higher cfDNA LHI than healthy donors (n=53) [stage I/II: median 0.369 (95% confidence interval, 0.360-0.380) vs. 0.332 (0.325-0.339), P < 0.0001; stage III/IV: 0.372 (0.365-0.388) vs. 0.332 (0.325-0.339), P < 0.0001]. The receiver operating characteristic analysis showed that cfDNA LHI had the detection capacity of CRC with area under the curve(AUC) of 0.79 and 0.83 in stage I/II and stage III/IV CRC patients, respectively. The present study demonstrated for the first time the potential of plasma cfDNA LHI as a novel biomarker for CRC, particularly for early stage detection.
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http://dx.doi.org/10.18632/oncotarget.14439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355314PMC
February 2017

Perianal and Vulvar Extramammary Paget Disease: A Report of Six Cases and Mapping Biopsy of the Anal Canal.

Ann Dermatol 2016 Oct 30;28(5):624-628. Epub 2016 Sep 30.

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

Treatment of perianal and vulvar extramammary Paget disease (EMPD), rare intraepithelial malignancies, is often challenging because of its potential to spread into the anal canal. However, there is still no consensus regarding the optimal resection margin within the anal canal. Between 2004 and 2014, six patients (three with perianal EMPD and three with vulvar EMPD) in which the spread of Paget cells into the anal canal was highly suspected were referred to our department. To evaluate the disease extent within the anal canal, preoperative mapping biopsy of the anal canal was performed in five out of six patients. Two patients were positive for Paget cells within the anal canal (one at the dentate line and the other at 0.5 cm above the dentate line), whereas in three patients, Paget cell were present only in the skin of the anal verge. Using 1 cm margin within the anal canal from the positive biopsy sites, we performed anal-preserving wide local excision (WLE), and negative resection margins within the anal canal were confirmed in all five patients. The remaining one patient with perianal EMPD did not undergo mapping biopsy of the anal canal because preoperative colonoscopy revealed that the Paget cells had spread into the lower rectum. Therefore, WLE with abdominoperineal resection was performed. During the median follow-up period of 37.3 months, no local recurrence was observed in all patients. Our small case series suggest the usefulness of mapping biopsy of the anal canal for the treatment of perianal and vulvar EMPD.
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http://dx.doi.org/10.5021/ad.2016.28.5.624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064193PMC
October 2016

Usefulness of preoperative CT colonography for colon cancer.

Asian J Surg 2017 Nov 20;40(6):438-443. Epub 2016 May 20.

Department of Surgical Oncology, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.

Background: Computed tomographic colonography (CTC) is reported to be feasible for screening of colorectal polyps; however, its efficacy in preoperative workup remains unknown. This study was done to define our CTC methodology and assess CTC's potential for preoperative examination in patients with colon cancer.

Methods: A total of 86 colon cancer patients underwent CTC prior to laparoscopic colectomy in our department from February 2014 to November 2015. The location of primary colon cancer determined by CTC was compared with that confirmed during the surgery. CTC was performed just after preoperative colonoscopy; for a small colon cancer, we performed clipping during colonoscopy to enhance CTC detectability. We classified wall deformities and compared them with the pathological T stage.

Results: CTC accurately located all 87 primary colon cancers prior to surgery. No patient experienced complications associated with CTC. The deformity classification correlated significantly with the pathological T stage (p < 0.001, Kruskal-Wallis nonparametric tests). CTC provided reconstructed images depicting the feeding artery of the primary colon cancer; feeding artery information obtained by CTC facilitated precise lymph node dissection.

Conclusion: CTC appears to be a feasible and useful preoperative examination modality for colon cancer treatment.
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http://dx.doi.org/10.1016/j.asjsur.2016.04.002DOI Listing
November 2017

Clinicopathological Features of Colorectal Cancer Patients Under the Age of 50: Recent Experience and Case-Control Study of Prognosis in a Japanese Cohort.

Digestion 2016 18;93(4):272-9. Epub 2016 May 18.

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

Background/aims: The incidence of colorectal cancer (CRC) in young people is increasing, indicating an urgent need for understanding young-onset CRC. This study serves to clarify the characteristics and prognosis of young CRC patients.

Methods: Using a detailed database, various clinicopathological findings including symptoms, family history and prognosis of 70 young CRC patients under 50 years who underwent surgical resection between 2005 and 2011 were compared to 786 old CRC patients over 50 years. For the comparison of prognosis, a matched 1:4 case-control study adjusting for gender, tumor location, tumor differentiation type, and Union For International Cancer Control stage was conducted.

Results: The young group had a higher proportion of rectal cancer (51.4 vs. 36.4%, p = 0.004) and a higher positive rate for the Amsterdam criteria II (7.1 vs. 1.9%, p = 0.02) than the old group. There was no significant difference in overall survival (OS) or cancer-specific survival (CSS) between the young and old groups (5-year OS: 84.7 vs. 76.9%, p = 0.18; 5-year CSS: 84.7 vs. 82.8%, p = 0.55).

Conclusion: This study may add a new perspective to understanding young-onset CRC. The prognosis of young CRC patients was equivalent to that of old CRC patients.
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http://dx.doi.org/10.1159/000446344DOI Listing
March 2017

Hereditary gastrointestinal cancer.

Surg Today 2016 Oct 16;46(10):1115-22. Epub 2015 Dec 16.

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

Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.
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http://dx.doi.org/10.1007/s00595-015-1283-3DOI Listing
October 2016

High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients.

Oncotarget 2015 Aug;6(25):21064-73

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.

We recently reported a specific mechanism that RAD54B, an important factor in homologous recombination, promotes genomic instability via the degradation of p53 protein in vitro. However, clinical significance of RAD54Bin colorectal cancer (CRC) remains unclear. Thus we analyzed RAD54B geneexpression in CRC patients. Using the training set (n = 123), the optimal cut-off value for stratification was determined, and validated in another cohort (n = 89). Kaplan-Meier plots showed that distant recurrence free survival was significantly lesser in high RAD54B expression group compared with that of low expression group in both training (P = 0.0013) and validation (P = 0.024) set. Multivariate analysis using Cox proportional-hazards model showed that high RAD54B expression was an independent predictor in both training (hazard ratio, 4.31; 95% CI, 1.53-13.1; P = 0.0060) and validation (hazard ratio, 3.63; 95% CI, 1.23-10.7; P = 0.021) set. In addition, a negative significant correlation between RAD54B and CDKN1A, a target gene of p53, was partially confirmed, suggesting that RAD54B functions via the degradation of p53 protein even in clinical samples. This study first demonstrated RAD54B expression has potential to serve as a novel prognostic biomarker, particularly for distant recurrence in CRC patients.
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http://dx.doi.org/10.18632/oncotarget.4222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673250PMC
August 2015

Chemoradiation provides a physiological selective pressure that increases the expansion of aberrant TP53 tumor variants in residual rectal cancerous regions.

Oncotarget 2014 Oct;5(20):9641-9

Neoadjuvant chemoradiotherapy has been introduced in patients with surgically resected rectal cancer and reduced the local recurrence. Heterogeneity exists in rectal cancer, and we hypothesized that there are subclones resistant to chemoradiotherapy within the cancer mass. We performed DNA-targeted sequencing of pre- and post-treatment tumor tissues obtained from 20 rectal cancer patients who received chemoradiotherapy. The variant frequency of the mutant clones was compared between pre- and post-treatment samples of nine non-responder patients. RNA-targeted sequencing of 57 genes related to sensitivity to chemotherapy and radiotherapy was performed for the paired samples. Immunohistochemical analyses of p53 expression were also performed on the paired samples from the nine non-responder patients. DNA-sequencing detected frequent mutations of suppressor genes including TP53, APC and FBXW7 in the post-treatment samples of the nine non-responders. The frequency of TP53 mutations showed significant increases after chemoradiotherapy. RNA-targeted sequencing of 29 tumor tissues demonstrated that decreased expression of three genes and increased expression of four genes were detected in the post-treatment samples. Significantly increased expression of TP53 was observed in the post-treatment samples. Immunohistochemical staining for p53 revealed that increased p53 intensity scores were observed after chemoradiotherapy. These results suggest that the tumors with TP53 mutations tend to accumulate through chemoradiotherapy.
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http://dx.doi.org/10.18632/oncotarget.2438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259426PMC
October 2014

[Diagnosis and treatment for carcinoma associated with anal fistula].

Nihon Rinsho 2014 Jan;72(1):154-8

Department of Surgical Oncology, The University of Tokyo Hospital.

In this article, we focus on the diagnosis and treatment of carcinoma associated with anal fistula. Carcinoma associated with anal fistula is relatively rare, representing 6.9% of all anal carcinoma in Japan. It arises from long-standing anal fistula with more than 10 years duration. Clinical suspicion is crucial in diagnosis, however, early detection is challenging. A biopsy under anesthesia is often needed for histological confirmation of the tumor. Magnetic resonance imaging can facilitate the diagnosis and is essential to determine the range of the surgical resection. Abdominoperineal resection is usually performed as the surgical treatment of choice. Combined chemoradiation therapy may improve the outcome of locally advanced tumor.
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January 2014
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