Publications by authors named "Tomomichi Kiyomatsu"

135 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

Current status of immune checkpoint inhibitor therapy for advanced esophageal squamous cell carcinoma.

Glob Health Med 2021 Dec;3(6):378-385

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

Esophageal cancer is the seventh most common cancer, with an estimated 572,000 new cases, and the sixth most common cause of cancer-related deaths in 2018 with 509,000 annual worldwide deaths. Advanced esophageal squamous cell carcinoma (ESCC) is one of devastating tumors with a 5-year survival rate of less than 5% in patients with metastatic disease. Treatment options for patients with advanced ESCC are limited. Current guidelines recommend chemotherapy containing a platinum and a fluoropyrimidine agent as a first-line treatment. Recently, immune checkpoint inhibitors (ICIs), including nivolumab and pembrolizumab, have demonstrated antitumor activity and clinical efficacy in patients with advanced ESCC that is refractory or intolerant to first-line chemotherapy. ICIs are game-changers that not only transformed oncological strategy but also have a wide range of clinical potential in combination with conventional cytotoxic chemotherapy and radiotherapy. There is still an urgent, unmet need for reliable treatment options to conquer this intractable disease.
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http://dx.doi.org/10.35772/ghm.2020.01112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692100PMC
December 2021

Right-sided Bochdalek hernia in an adult with hepatic malformation and intestinal malrotation.

Surg Case Rep 2021 Jul 17;7(1):169. Epub 2021 Jul 17.

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

Background: Bochdalek hernia is a common congenital diaphragmatic defect that usually manifests with cardiopulmonary insufficiency in neonates. It is very rare in adults, and symptomatic cases are mostly left-sided. Diaphragmatic defects generally warrant immediate surgical intervention to reduce the risk of incarceration or strangulation of the displaced viscera.

Case Presentation: A 47-year-old woman presented with dyspnea on exertion. Computed tomography revealed that a large part of the intestinal loop with superior mesenteric vessels and the right kidney were displaced into the right thoracic cavity. Preoperative three-dimensional (3D) simulation software visualized detailed anatomy of displaced viscera and the precise location and size of the diaphragmatic defect. She underwent elective surgery after concomitant pulmonary hypertension was stabilized preoperatively. The laparotomic approach was adopted. Malformation of the liver and the presence of intestinal malrotation were confirmed during the operation. The distal part of the duodenum, jejunum, ileum, colon, and right kidney were reduced into the abdominal cavity consecutively. A large-sized oval defect was closed with monofilament polypropylene mesh. No complications occurred postoperatively.

Conclusion: Symptomatic right-sided Bochdalek hernia in adults is exceedingly rare and is frequently accompanied by various visceral anomalies. Accurate diagnosis and appropriate surgical repair are crucial to prevent possible incarceration or strangulation. The preoperative 3D simulation provided comprehensive information on anatomy and concomitant anomalies and helped surgeons plan the operation meticulously and perform procedures safely.
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http://dx.doi.org/10.1186/s40792-021-01232-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286215PMC
July 2021

Effects of COVID-19 vaccination on FDG-PET/CT imaging: A literature review.

Glob Health Med 2021 Jun;3(3):129-133

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

COVID-19 vaccination using mRNA technology began at the end of 2020 in several countries, approximately 9 months after the WHO declared the new coronavirus a pandemic, and began in Japan at the end of February 2021. Several studies have reported FDG avidity in enlarged axillary lymph nodes as a specific feature of FDG-PET/CT imaging after COVID-19 vaccination. A major concern is that this finding could lead to a misdiagnosis in patients with various types of malignancy. We review the impact of COVID-19 vaccination on the management of patients scheduled for FDG-PET/CT in the setting of nationwide mass vaccination.
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http://dx.doi.org/10.35772/ghm.2021.01076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239370PMC
June 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

Current status of doublet combinations of platinum and fluoropyrimidines using oxaliplatin for advanced gastric cancer.

Glob Health Med 2021 Feb;3(1):31-36

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

The most common treatment for advanced gastric cancer (AGC) is systemic chemotherapy. The standard treatment for advanced gastric cancer differs worldwide. In Japan, two phase III clinical trials demonstrated the non-inferiority of S-1 compared with 5-fluorouracil (5-FU) and superiority of cisplatin plus S-1 (CS), compared with S-1, with respect to overall survival (SPIRITS trial). Oxaliplatin (L-OHP) has a favorable toxicity profile compared with cisplatin; hence, a phase III clinical trial (G-SOX trial) demonstrated the progression-free survival (PFS) and overall survival in CS was 5.4 and 13.1 months and those in SOX was 5.5 and 14.1 months, respectively. Serious adverse events were more frequently seen in CS than in SOX. So, SOX is as effective as CS for advanced gastric cancer with favorable safety profile. After the publication of this G-SOX trial, the combination of oral or intravenous 5-FU and various doses of L-OHP have been reported. And FOLFOX6 regimen (FOLFOX: a combination of 1-LV and FU with L-OHP) was approved for the treatment of AGC in Japan in 2017. FOLFOX was promising for patients with severe peritoneal metastasis from AGC, because the FOLFOX regimen does not require hydration and does not include oral agents. This review summarizes the efficacy and safety of doublet combinations of platinum and fluoropyrimidines using L-OHP for advanced gastric cancer.
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http://dx.doi.org/10.35772/ghm.2020.01075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936367PMC
February 2021

Deformation of the Pelvic Arteries Caused by Pneumoperitoneum and Postural Changes in an Animal Model.

In Vivo 2021 Jan-Feb;35(1):275-281

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

Background/aim: We investigated pelvic arterial deformation and shift due to intraoperative pneumoperitoneum and postural changes in an animal model.

Materials And Methods: Computed tomography images of pigs were acquired in different body positions (supine, head down at 5° and 10°, right lateral recumbent at 5° and 15°) before and after insufflation. We used a free software (3D Slicer) for image analysis. After landmark registration using 10 markers inserted into the pelvis, pelvic arterial deformation and shift of seven arterial bifurcation points were evaluated. The distance moved was the target registration error (TRE) from the points registered in the supine position. Fiducial registration error (FRE) was measured using the 10 pelvic markers.

Results: TRE average from postural changes ranged from 0.7 to 1.2 mm and was 1.4 mm due to pneumoperitoneum. TRE and FRE averages were 2.1 mm and 0.2 mm, respectively.

Conclusion: The pelvis was useful for registering anatomical landmarks.
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http://dx.doi.org/10.21873/invivo.12256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880756PMC
June 2021

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

Pancreatology 2020 Sep 7;20(6):1226-1233. Epub 2020 Jul 7.

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

Background/objectives: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN.

Methods: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared.

Results: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP.

Conclusions: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.
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http://dx.doi.org/10.1016/j.pan.2020.06.008DOI Listing
September 2020

Pseudomyxoma peritonei: visceral scalloping on CT is a predictor of recurrence after complete cytoreductive surgery.

Eur Radiol 2020 Aug 24;30(8):4193-4200. Epub 2020 Mar 24.

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

Objectives: Pseudomyxoma peritonei (PMP) is characterized by peritoneal dissemination of gelatinous ascites following rupture of a mucinous tumor. Treatment by cytoreductive surgery (CRS) has improved its prognosis. Although visceral scalloping, notably liver scalloping, on computed tomography (CT) is a typical feature of PMP, its prognostic value remains unknown. We aimed to investigate the efficacy of liver scalloping in predicting recurrence in PMP patients.

Methods: Among 159 consecutive patients with PMP who had contrast-enhanced CT between September 2012 and December 2018, 64 treatment-naïve patients who subsequently underwent CRS with complete resection (i.e., completeness of cytoreduction score (CC)-0 or CC-1), were included in analysis. Presence of liver scalloping and maximum thickness of mucin deposition at the liver surface were evaluated on CT. Disease-free survival (DFS) was determined based on the combination of postoperative CT features and tumor marker values.

Results: Median follow-up was 24.3 months. CT revealed liver scalloping in 40/64 (63.4%) patients. Kaplan-Meier analysis showed significantly shorter DFS in patients with scalloping than in those without (p = 0.001; hazard ratio, 4.3). In patients with scalloping, greater mucin deposition (thickness ≥ 20 mm) significantly correlated with poorer DFS (p = 0.042). In multivariate Cox proportional hazards regression including CC status, pathologic type, and tumor markers, the presence of scalloping independently and significantly correlated with DFS (p = 0.031).

Conclusions: Liver scalloping was an independent predictor even after adjusting for clinical covariates. The presence of liver scalloping can lead to a high recurrence rate after CRS.

Key Points: • The presence of liver scalloping is a prognostic factor independent of histological grade and tumor markers. • Greater mucin deposition (thickness ≥ 20 mm at the liver surface) is associated with higher recurrence rates in patients with liver scalloping.
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http://dx.doi.org/10.1007/s00330-020-06756-2DOI Listing
August 2020

Complete remission of multiple liver metastases with only partial response of the primary rectal cancer after neoadjuvant chemotherapy.

Surg Case Rep 2020 Feb 27;6(1):46. Epub 2020 Feb 27.

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

Background: Colorectal cancer is commonly diagnosed among the Japanese population, and various strategies in treating the colorectal liver metastasis have been introduced over the years. Here, we present a case of colorectal liver metastases in which we devised a multidisciplinary treatment plan for a better prognosis.

Case Presentation: We report a case of a 44-year-old female who developed rectal cancer with advanced synchronous liver metastases and was treated by a liver-first surgical approach following neoadjuvant chemotherapy. At diagnosis, there were 12 bilobular lesions in the liver, and the primary rectal cancer was asymptomatic and unprogressive. We adopted a liver-first strategy because the control of the liver metastases was considered the key prognostic factor. Furthermore, because the lesions were highly progressive, we planned neoadjuvant systemic chemotherapy first to provide an observational period to identify potential new metastatic lesions that were refractory to systemic chemotherapy or contraindicative for surgical resection. We administered two courses of S-1 + oxaliplatin (SOX)+ bevacizumab (BV) and an additional course of SOX without BV as neoadjuvant chemotherapy in preparation for surgery. This resulted in a prominent minimalization of colorectal liver metastases, and no other remote metastasis was observed. Then, surgical resection of the colorectal liver metastases was performed safely, and the pathological result revealed complete remission of all tumors by neoadjuvant chemotherapy. The primary tumor in the colon was successfully resected 2 months after the hepatectomy. Although the patient experienced a recurrence in two different sites in the lungs 10 months after resection of the primary rectal lesion, these metastases were successfully resected after diagnosis. The patient is alive with no signs of recurrence 3 years after the diagnosis of colorectal cancer with synchronous liver metastases.

Conclusions: The combination of a liver-first strategy and neoadjuvant chemotherapy is a possible treatment of choice to cure colorectal cancer with simultaneous advanced colorectal liver metastases.
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http://dx.doi.org/10.1186/s40792-020-00807-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046888PMC
February 2020

Hepatectomy for metachronous colorectal liver metastases following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases: a report of three cases.

World J Surg Oncol 2019 Jun 13;17(1):99. Epub 2019 Jun 13.

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

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis (PM) from colorectal cancer (CRC) has been reported to substantially improve the prognosis and the quality of life of patients in comparison to systemic chemotherapy or palliative approaches. This study aimed to demonstrate the safety and feasibility of hepatectomy for metachronous liver metastases from CRC following CRS and HIPEC for PM on the basis of three case reports.

Case Presentation: We describe three cases involving patients who underwent hepatectomy for metachronous liver metastases from CRC after CRS and HIPEC for PM. All patients underwent CRS and HIPEC after primary tumor resection, and hepatectomy was performed for the metachronous liver metastases after CRS and HIPEC. The hepatectomy procedures for cases 1, 2, and 3 were left hemihepatectomy and partial resection of S5, posterior sectionectomy, and left-lateral sectionectomy and partial resection of S5 and S8, respectively. Although adhesion of surrounding organs to the liver surface was observed on a broad level, dissections and hepatectomy could be performed safely. No recurrence was detected in cases 1 and 2 after hepatectomy. In case 3, liver metastases were detected from the time of the initial diagnosis of the primary tumor, and complete remission was achieved once with systemic chemotherapy. Although we performed hepatectomy for the recurrence of liver metastases after complete remission, early re-recurrence was observed after hepatectomy.

Conclusions: Hepatectomy for metachronous liver metastases after CRS and HIPEC for PM could be a multi-modality treatment option for CRC recurrence.
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http://dx.doi.org/10.1186/s12957-019-1646-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567639PMC
June 2019

Nomogram Predicting Survival After Recurrence in Patients With Stage I to III Colon Cancer: A Nationwide Multicenter Study.

Dis Colon Rectum 2018 09;61(9):1053-1062

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

Background: Although a number of studies have been conducted to investigate factors affecting colon cancer recurrence and patient overall survival after surgical treatment, no prognostic risk models have been proposed for predicting survival specifically after postsurgical recurrence.

Objective: We aimed to identify factors affecting the survival of the patients with recurrent colon cancer and to construct a nomogram for predicting their survival.

Design: This was a retrospective study.

Settings: This study used the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database, which contains retrospectively collected data of all consecutive patients with stage I to III colorectal cancer who underwent surgical curative resection between 1997 and 2008 at 23 referral institutions.

Patients: A total of 2563 patients with stage I to III colon cancer who experienced recurrence after surgery were included in the present study.

Main Outcome Measures: A nomogram predicting survival was constructed using a training cohort composed of patients from 15 hospitals (n = 1721) using a Cox regression hazard model analysis. The clinical applicability of this nomogram was validated in patients from the 8 remaining hospitals (the validation cohort; n = 842).

Results: Eight factors (age, location of the primary tumor, histopathological type, positive lymph node status, presence of peritoneal metastasis, number of organs involved in the first recurrence, treatment for recurrence, and the interval between initial surgery and recurrence) were identified as nomogram variables. Our nomogram showed good calibration, with concordance indexes of 0.744 in the training cohort and 0.730 in the validation cohort. The survival curves stratified by the risk score calculated by the nomogram were almost identical for the training and validation cohorts.

Limitations: The study was conducted using the data until 2008, and more advanced chemotherapeutic agents and multidisciplinary therapies that might have improved the outcomes predicted by our nomogram were not available. In addition, treatment strategies for recurrence might differ between countries.

Conclusions: Our nomogram, which is based on a nationwide multicenter study, is the first statistical model predicting survival after recurrence in patients with stage I to III colon cancer. It promises to be of use in postoperative colon cancer surveillance. See Video Abstract at http://links.lww.com/DCR/A687.
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http://dx.doi.org/10.1097/DCR.0000000000001167DOI 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

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

The short-term outcomes of robotic sphincter-preserving surgery for rectal cancer: comparison with open and laparoscopic surgery using a propensity score analysis.

Int J Colorectal Dis 2018 Aug 23;33(8):1047-1055. Epub 2018 Apr 23.

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

Purpose: The aim of this study is to clarify the short-term outcomes of robotic sphincter-preserving surgery for rectal cancer in a retrospective study.

Methods: The short-term outcomes of robotic sphincter-preserving surgery (n = 130) were retrospectively compared to open (n = 234) and laparoscopic surgery (n = 318) by a propensity score analysis.

Results: Robotic surgery was performed more frequently for patients with lower rectal cancer (55%) than open (30%, p < 0.0001) or laparoscopic surgery (36%, p < 0.0001). None of the robotic surgery cases were converted to open surgery. After propensity score matching, robotic surgery was found to be associated with a longer operation time (342 vs. 230 min, p < 0.0001) and less blood loss (7 vs. 420 mL, p < 0.0001) than open surgery. The overall complication rate of robotic surgery was lower than that of open surgery (13 vs. 28%, p = 0.032). Robotic surgery was associated with a lower incidence of surgical site infections (SSIs) than laparoscopic surgery (0 vs. 7%, p = 0.028). There were no cases of anastomotic leakage after robotic surgery. The circumferential resection margin was involved in 0.8% of the patients who underwent robotic surgery; the incidence did not differ among the treatment groups.

Conclusions: Although robotic surgery for rectal cancer was associated with a longer operation time, it was associated with a very low incidence of SSIs. The degree of safety was comparable to both open and laparoscopic surgery.
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http://dx.doi.org/10.1007/s00384-018-3056-0DOI Listing
August 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

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

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

Nine primary malignant neoplasms-involving the esophagus, stomach, colon, rectum, prostate, and external ear canal-without microsatellite instability: a case report.

BMC Cancer 2018 01 4;18(1):24. Epub 2018 Jan 4.

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

Background: Although cases of multiple primary malignant neoplasms are increasing, reports of more than three or four primary metachronous malignant neoplasms are extremely rare. Moreover, very few publications have provided a genetic mutational analysis or have evaluated risk factors associated with such neoplasms. We present an extremely rare case of nine primary malignant lesions in a man who was successfully treated. We also report on microsatellite stability status, analyze risk factors, and discuss the relevant literature.

Case Presentation: Between 67 and 73 years of age, a male patient developed nine primary metachronous malignant lesions: Three were located in the esophagus, two in the stomach, two in the colorectum, one in the prostate gland, and one in the external ear canal. The patient's clinical history included hypertension, atrial fibrillation, an acoustic schwannoma, and heavy smoking. The lesions were diagnosed during regular screening over a six-year period. He was successfully treated with surgery (both open surgical and endoscopic resection of lesions) and adjuvant chemotherapy. Immunohistochemistry and mutational analysis showed that the lesions were microsatellite stable, and the KRAS, BRAF, p53, and nuclear β-catenin status was not uniform among the lesions.

Conclusions: Given that the presence of more than three or four neoplasms is extremely rare, the present case of nine primary malignancies with no associated microsatellite instability and no apparent predisposing hereditary conditions, is extraordinary. Our case study shows that it is possible for up to nine sporadic neoplasms to occur, and efficient disease management requires diligent screening and early detection.
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http://dx.doi.org/10.1186/s12885-017-3973-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753511PMC
January 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

LMR predicts outcome in patients after preoperative chemoradiotherapy for stage II-III rectal cancer.

J Surg Res 2018 02 4;222:122-131. Epub 2017 Nov 4.

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

Background: Recently, lymphocyte-to-monocyte ratio (LMR) has attracted attention as a new marker of the chronic systemic inflammatory response and has been associated with patient prognosis in those who underwent chemoradiotherapy (CRT) for several solid cancers. This study aimed to evaluate the association between LMR and the prognosis of patients with rectal cancer.

Methods: A total of 183 stage II-III rectal cancer patients who underwent preoperative CRT followed by surgical R0 resection were retrospectively reviewed. The LMR was calculated from pre- and post-CRT blood samples. To determine the optimal cutoff value for pre- and post-CRT LMR for predicting relapse-free survival (RFS) and overall survival (OS), a receiver operator characteristic curve was used. Cox's proportional hazard models were applied to identify risk factors for recurrence and overall mortality.

Results: Low LMR was observed in 54 patients (pre-CRT <4.0) and 29 patients (post-CRT <1.5). Although pre-CRT LMR correlated with tumor size and ypT stage, post-CRT LMR showed no correlation to any pathologic features. Median follow-up term was 66.3 months; the 5-year RFS and OS of all patients were 72.5% and 88.7%, respectively. We found that a low pre-CRT LMR was an independent risk factor for OS (hazard ratio, 2.83; 95% confidence interval 1.03-8.13; P = 0.043).

Conclusions: In rectal cancer patients who have undergone preoperative CRT, a low pre-CRT LMR is a poor prognostic factor for OS.
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http://dx.doi.org/10.1016/j.jss.2017.09.053DOI Listing
February 2018

Leucine-rich repeat-containing G protein-coupled receptor 5 and CD133 expression is associated with tumor progression and resistance to preoperative chemoradiotherapy in low rectal cancer.

Oncol Lett 2017 Dec 18;14(6):7791-7798. Epub 2017 Oct 18.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.

Preoperative chemoradiotherapy has been performed as a standard therapy for advanced low rectal cancer. Cancer stem cells (CSCs) have been reported to contribute to resistance to treatment and patient prognosis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and cluster of differentiation (CD133) are putative markers for CSCs. However, their prognostic ability remains unknown, and evaluation of a single marker can be insufficient due to the heterogeneity of cancer. LGR5 and CD133 expression was immunohistochemically evaluated in surgical specimens of 56 patients who received curative resection following chemoradiotherapy for advanced low rectal cancer. In addition, the correlations between their expression levels, and clinicopathological features and patient prognosis were asessed. LGR5 expression was significantly correlated with lymphatic invasion, lymph node metastasis, and tumor node metastasic (TNM) stage. CD133 expression was significantly correlated with vascular invasion and the tumor regression grade. Combined expression was significantly correlated with lymphatic invasion, tumor regression grade and TNM stage, but not with overall, and disease-free survival. LGR5 and CD133 expressions may represent useful markers associated with tumor progression and resistance to chemoradiotherapy in patients with low rectal cancer. Furthermore, combined expression of these markers may be a more useful marker compared with the expression of each single marker.
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http://dx.doi.org/10.3892/ol.2017.7207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727605PMC
December 2017

Conversion to Resection in Patients Receiving Systemic Chemotherapy for Unresectable and/or Metastatic Colorectal Cancer-Predictive Factors and Prognosis.

Clin Colorectal Cancer 2018 03 19;17(1):e91-e97. Epub 2017 Oct 19.

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

Background: Systemic chemotherapy increases the possibility of resection in patients with initially unresectable colorectal cancer (CRC), especially patients with hepatic metastasis. However, the predictive factors and prognosis of conversion to resection after chemotherapy in patients with various organ metastases remain largely unknown.

Patients And Methods: We reviewed the data from metastatic CRC (mCRC) patients who had received oxaliplatin- or irinotecan-based systemic chemotherapy from 2005 to 2016. The predictors for conversion to surgery were assessed by multivariate analyses. Cancer-free survival and overall survival after the initiation of treatment were compared between patients who had undergone successful conversion therapy and those who had undergone surgery first for resectable stage IV CRC.

Results: Of 99 mCRC patients receiving first-line chemotherapy, 23 underwent secondary surgical resection. Single organ metastasis, the presence of liver metastases, and the use of biologic agents were independent predictors of successful conversion therapy. The long-term survival of patients who underwent successful secondary surgery did not differ significantly from that of the 112 patients with resectable stage IV CRC who had undergone surgery first.

Conclusion: Liver metastases and single organ metastasis were more likely to be resected after chemotherapy than were other metastatic lesions in mCRC. The use of biologic agents contributed to the increased conversion rate. Successful conversion resulted in outcomes similar to those of resectable stage IV CRC.
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http://dx.doi.org/10.1016/j.clcc.2017.10.002DOI Listing
March 2018

Rectovaginal fistula after low anterior resection for rectal cancer healed by nonoperative treatment.

Int J Surg Case Rep 2017 18;41:121-123. Epub 2017 Oct 18.

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

Background: Rectovaginal fistula (RVF) is a serious complication after colorectal anastomosis using a double-stapling technique. RVF following this procedure has been considered to be refractory to conservative treatment.

Case Presentation: A 75-year-old woman who underwent laparoscopy-assisted low anterior resection for early rectal cancer developed RVF on the 12th postoperative day. Conservative treatment was chosen and was successful. She was discharged from the hospital after 3 weeks with a normal oral diet. Colonoscopy on the 50th postoperative day showed that the RVF was closed.

Conclusion: Conservative treatment may be effective for RVF after colorectal anastomosis using a double-stapling technique when there is no evidence of defecation through the vagina.
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http://dx.doi.org/10.1016/j.ijscr.2017.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655408PMC
October 2017

Laparoscopic hemicolectomy for a patient with situs inversus totalis: A case report.

Int J Surg Case Rep 2017 16;41:93-96. Epub 2017 Oct 16.

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

Introduction: Situs inversus totalis (SIT) is a rare congenital anomaly in which the left and right aspects of the thoracic and intra-abdominal organs are inverted, like a mirror image. Surgical procedures in a patients with SIT is difficult as their anatomy is abnormal. In particular, laparoscopic procedures are considered more difficult in patients with SIT because of the mirror-image anatomy.

Presentation Of Case: The patient was a 75-year-old woman with ascending colon cancer. Laparoscopic hemicolectomy with radical lymphadenectomy was performed. After surgery, no specific complications developed. On the ninth postoperative day, the patient was discharged from our hospital. Recognition of the inverted anatomy by the surgeon using preoperative imaging permitted safe operation using techniques not otherwise differing from those used in ordinary cases.

Discussion And Conclusions: Laparoscopic colectomy is considered to be a safe and feasible option for patients with colorectal cancer and SIT.
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http://dx.doi.org/10.1016/j.ijscr.2017.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651547PMC
October 2017

Polymeric micelles loaded with (1,2-diaminocyclohexane)platinum(II) against colorectal cancer.

J Surg Res 2017 10 22;218:334-340. Epub 2017 Jul 22.

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

Background: We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model.

Materials And Methods: The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28). The accumulation of drugs in tumors and liver parenchyma was analyzed using ion coupled plasma-mass spectrometry 24 h after administration of DACHPt/m or oxaliplatin (n = 5). We assessed renal and hepatic toxicities through changes in creatinine, aspartate transaminase, and alanine transaminase on the last day of the antitumor activity experiment.

Results: Mice receiving DACHPt/m had significantly fewer metastatic nodules (P = 0.038) and lower liver weights (P = 0.038) than those receiving oxaliplatin. The accumulation of DACHPt/m in the metastatic liver was significantly higher than that of oxaliplatin, whereas the distribution of micelles in healthy liver tissues was limited. Mice treated with DACHPt/m also showed significantly lower serum creatinine levels than those treated with oxaliplatin (P = 0.007), whereas serum aspartate transaminase and alanine transaminase levels for both drugs were not different.

Conclusions: High levels of DACHPt/m accumulate in metastatic livers, producing a strong antitumor effect without severe adverse effects. DACHPt/m is a safe approach for managing liver metastasis from colorectal cancer.
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http://dx.doi.org/10.1016/j.jss.2017.06.056DOI Listing
October 2017

Microsatellite Status of Primary Colorectal Cancer Predicts the Incidence of Postoperative Colorectal Neoplasms.

Anticancer Res 2017 10;37(10):5785-5790

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

Background/aim: Few studies have evaluated the risk of postoperative colorectal neoplasms stratified by the nature of primary colorectal cancer (CRC). In this study, we revealed it on the basis of the microsatellite (MS) status of primary CRC.

Materials And Methods: We retrospectively reviewed 338 patients with CRC and calculated the risk of neoplasms during postoperative surveillance colonoscopy in association with the MS status of primary CRC. A propensity score method was applied.

Results: We identified a higher incidence of metachronous rectal neoplasms after the resection of MS stable CRC than MS instable CRC (adjusted HR 5.74, p=0.04). We also observed a higher incidence of colorectal tubular adenoma in patients with MSS CRC (adjusted hazard ratio 7.09, p<0.01) and a higher incidence of postoperative tubulovillous/villous adenoma in patients with MS instable CRC (adjusted HR=8.50, p=0.03).

Conclusion: The MS status of primary colorectal cancer influenced the risk of postoperative colorectal neoplasms.
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http://dx.doi.org/10.21873/anticanres.12020DOI Listing
October 2017

Use of a nomogram to predict the closure rate of diverting ileostomy after low anterior resection: A retrospective cohort study.

Int J Surg 2017 Nov 22;47:83-88. Epub 2017 Sep 22.

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

Introduction: Although temporary ileostomy is widely used to prevent complications due to anastomotic leakage after middle and low rectal cancer surgery, some patients fail to achieve stoma closure after primary surgery. The aim of this study was to identify the risk factors for permanent stoma following low anterior resection (LAR) or intersphincteric resection (ISR) with a temporary ileostomy for rectal cancer, while focusing on the time course, to develop a nomogram that can predict the rate of unreversed ileostomy 1 year after initial surgery.

Method: A total of 212 consecutive rectal cancer patients who underwent LAR or ISR with or without a temporary stoma between 2012 and 2015 at the University of Tokyo Hospital were retrospectively reviewed. Data analyses were performed using JMP Pro 11.0 and R 3.0.1 with rms and Hmisc packages to identify the risk factors for diverting ileostomy resulting in un-reversed stoma, and to develop a nomogram using these factors.

Results: Among 212 patients, diverting ileostomy and colostomy were performed in 116 and 11 patients, respectively, and a stoma was not created in 85 patients. Among the ileostomy cases, 94 underwent stoma reversal, and the median interval from initial surgery to stoma closure was 6.9 months. Three patients eventually underwent stoma re-creation, and hence, 25 patients had permanent stoma. The following variables were correlated with the stoma non-reversal rate and were included in the nomogram: depth of invasion (p = 0.02), presence of metastatic organs (p = 0.07), and preoperative chemoradiotherapy (p = 0.03). The nomogram C-index was 0.612, indicating moderate predictive ability.

Conclusions: The most common factors preventing stoma closure included distant metastasis or rectal cancer recurrence. The nomogram developed in the present study can help identify rectal cancer patients with high risk of stoma non-reversal.
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http://dx.doi.org/10.1016/j.ijsu.2017.09.057DOI Listing
November 2017

Comparison of volumetric-modulated arc therapy using simultaneous integrated boosts (SIB-VMAT) of 45 Gy/55 Gy in 25 fractions with conventional radiotherapy in preoperative chemoradiation for rectal cancers: a propensity score case-matched analysis.

Radiat Oncol 2017 Sep 21;12(1):156. Epub 2017 Sep 21.

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

Background And Purpose: The aim of this retrospective study was to compare volumetric-modulated arc therapy using simultaneous integrated boosts (SIB-VMAT) of 45 Gy/55 Gy in 25 fractions with three-dimensional conformal radiotherapy (3D-CRT) in preoperative chemoradiation for rectal cancers.

Methods And Materials: In the propensity score-matching analysis of 1:2, we selected 60 patients from the SIB-VMAT group and 120patients from the 3D-CRT group matched pairings out of 145 patients between 2005 and 2015. The regimen of concurrent combined chemotherapy was oral uracil/tegafur plus leucovorin with/without irinotecan.

Results: There were no significant differences between the two groups, in pathological complete response rates (pCR) (11% in the 3D-CRT group vs. 17% in the SIB-VMAT group, P = 0.39), pathological response rates (44% vs. 60%, P = 0.77), disease-free survival (P = 0.32), or local control (P = 0.52). The SIB-VMAT method marginally improved the rate of pathological grade 2-3 effects and the OS was significantly better in patients with grade 2-3 effects. Recurrence was seen in 36 patients (30%) in the 3D-CRT group and 19 patients (32%) in the SIB-VMAT group. The first distant recurrence site in the SIB-VMAT group was liver in 6 patients and lung in 8 patients. The obvious radiation-induced late toxicity in the SIB-VMAT group was recto-vesical fistula in two patients.

Conclusions: The SIB-VMAT may be a promising method for preoperative CRT of rectal cancer.
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http://dx.doi.org/10.1186/s13014-017-0894-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607844PMC
September 2017
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