Publications by authors named "Kazushige Kawai"

278 Publications

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

Int J Clin Pract 2021 Sep 13:e14863. Epub 2021 Sep 13.

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
September 2021

Hazard function analysis for development of second primary colorectal cancer after surgery for primary colorectal cancer.

J Gastroenterol Hepatol 2021 Aug 20. Epub 2021 Aug 20.

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

Background And Aim: Although history of colorectal cancer (CRC) is a known risk factor for developing second CRC, the optimal surveillance protocol has not been established. Using hazard function analysis to evaluate changes in the hazard rate for the development of second primary CRCs or high-grade adenomas (HGAs), we aimed to clarify when and on whom to focus in order to effectively identify second primary colorectal neoplasms after initial surgery for CRC.

Methods: We retrospectively enrolled 1823 consecutive patients with stage 0-III CRCs who underwent radical surgery between 2004 and 2015, and subsequent colonoscopic surveillance after surgery. The time-course changes in the risk rates for developing metachronous CRC and HGA after surgery were assessed.

Results: A peak was observed at 1.22 years after surgery in the hazard function curve for secondary colorectal neoplasms, which decreased until 4 years, then plateaued. Older patients were at higher risk than younger patients, both showing a peak at 1 year. Another peak at 6 to 8 years was observed in younger patients. Male patients showed a higher risk than female patients, and patients with synchronous lesions showed a markedly higher hazard rate than those without, with two distinct peaks around 1 and 9 years after surgery.

Conclusions: Intensive colonoscopic surveillance is recommended after surgery for CRC during the first 2 to 3 years, and if the patient is under 60 years old and has concomitant CRC or HGA, surveillance is also recommended at 6 to 8 years after surgery.
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http://dx.doi.org/10.1111/jgh.15669DOI Listing
August 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

Prognostic Impact and Clinicopathological Features of Multiple Colorectal Cancers and Extracolorectal Malignancies: A Nationwide Retrospective Study.

Digestion 2021 Jul 14:1-10. Epub 2021 Jul 14.

Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan.

Introduction: Multiple primary malignancies (MPMs) are likely to develop in patients with colorectal cancer (CRC); however, their prognoses are unclear. This study aims to investigate the prognostic impacts and clinicopathological features of multiple CRCs and extracolorectal malignancies (EMs) with CRC.

Methods: We retrospectively evaluated a total of 22,628 patients with stage I-III CRC who underwent curative resection at 24 referral institutes in Japan between January 2004 and December 2012. MPMs were classified as synchronous CRCs (SCRCs), metachronous CRCs, synchronous EMs (SEMs), and metachronous EMs.

Results: The presence of SCRCs (odds ratio 1.54, p < 0.001) was independently associated with SEMs in the multivariate analyses. SEMs were the strongest poor prognostic factor for OS (hazard ratio [HR] 2.21, p < 0.001) and RFS (HR 1.69, p < 0.001) compared with age, sex, and primary T and N factors. The incidence of stomach cancer was the highest in EMs, followed by lung, breast, and prostate cancers. Multiple CRCs were evenly distributed throughout the right-side colon to the rectum.

Discussion/conclusion: SEMs were a strong poor prognostic factor for patients with stage I-III CRC. Patients with CRC, particularly those with SCRCs, should be surveyed for SEMs, especially for stomach and lung cancers.
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http://dx.doi.org/10.1159/000517271DOI Listing
July 2021

Analysis of the Positional Relationship Among the Operator, Camera, and Monitor: Overcoming the Difficulties of Mirror-image Conditions During Laparoscopic Surgery.

Surg Laparosc Endosc Percutan Tech 2021 Jun 23. Epub 2021 Jun 23.

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

Background: Although methods to overcome difficulties associated with mirror-image conditions have been investigated, the ideal spatial relationship among the operator line of sight, monitor location, and camera location remains unclear. Moreover, the best training method for improving laparoscopic surgical skills under varying operator line of sight, camera, and monitor positions is unknown. We aimed to investigate the role of laparoscopic training under mirror-image conditions in improving surgical efficiency and whether prior surgical experience affects such training.

Methods: This prospective study was conducted at the Department of Surgical Oncology, Tokyo University, Japan. Twenty-five surgeons participated. Novice (n=14), trained (n=7), and expert (n=4) participants performed the simulated task in a box trainer while varying the positional relationships among the surgeons, camera, and monitor. Five patterns were repeatedly performed 5 times per day for 4 days over 2 weeks.

Results: The most significant differences in terms of the time required to complete the task under mirror-image conditions among the 3 groups were on day 1 (novices: 185.8 s, trained: 79.7 s, and experts: 46.5 s, P=0.009). However, after 4 days of training, the corresponding times did not differ among the 3 groups (26.0, 30.7, and 23.1 s, respectively; P=0.415). Laparoscopic training was sufficiently effective under mirror-image conditions.

Conclusions: Mirror-image surgical conditions provided the most difficult setting, because surgeons and assistants often became disoriented, and task performance was most degraded. However, just 4 days of training was found to be sufficient to overcome the difficulties encountered while performing laparoscopic procedures under mirror-image conditions.
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http://dx.doi.org/10.1097/SLE.0000000000000955DOI Listing
June 2021

Development of a novel apoptosis-based tumor regression grade to assess the efficacy of preoperative chemoradiotherapy for rectal cancer: a retrospective single-center study.

Int J Clin Oncol 2021 Sep 3;26(9):1679-1688. Epub 2021 Jun 3.

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

Background: Preoperative chemoradiotherapy is used preferably for locally advanced rectal cancer, followed by a watch-and-wait strategy for cases showing clinical complete response. However, there is a discordance between pathological and clinical complete response rates. We aimed to propose a tumor regression grade (TRG) that truly reflects the therapeutic effects of preoperative chemoradiotherapy in locally advanced rectal cancer.

Methods: Overall, 293 consecutive patients with T3/T4a/T4b rectal cancer who underwent chemoradiotherapy followed by radical surgery between Sep 2003 and Dec 2018 were retrospectively reviewed. We assessed apoptosis using M30 cytoDEATH immunostaining and correlated that with conventional TRG (convTRG) evaluated using hematoxylin-eosin staining, and created a new TRG by evaluating apoptosis and convTRG. The modified TRG1-4 (modifTRG) classification was as follows: modifTRG1 comprised poor TRG, modifTRG2 moderate TRG, modifTRG3 good TRG, modifTRG4 complete apoptosis and convTRG3 (pathological complete response). We assessed the overall survival, relapse-free survival, and local recurrence rate.

Results: Pathological complete response rate was 10.6% when evaluated using conventional staining. Using M30 staining, apoptosis was observed in the residual disease in convTRG 1a 0%, convTRG 1b 0.3%, convTRG 2 9.2%. Combining the two, modifTRG4 was observed in 20.1%. The survival rates were similar between modifTRG4 and convTRG3, suggesting that modifTRG4 was equivalent to pathological complete response. However, in multivariate analysis, modifTRG but not convTRG was an independent risk factor for local and distant recurrences.

Conclusion: The proposed modifTRG truly reflected the therapeutic effects of chemoradiotherapy and may be superior to the convTRG to stratify rectal cancer patients treated with chemoradiotherapy.
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http://dx.doi.org/10.1007/s10147-021-01948-2DOI Listing
September 2021

Rectal neuroendocrine tumor with extracapsular lymph node metastasis: a case report.

Clin J Gastroenterol 2021 Oct 24;14(5):1426-1430. Epub 2021 May 24.

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

The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor in patients with colorectal carcinoma. However, there is no English literature on neuroendocrine tumor (NET) with EX. We report a patient with rectal NET with extracapsular metastasis of a regional lymph node that was considered to be EX. A 51-year-old Japanese woman with diabetes was referred to our hospital for further examination of a submucosal tumor in the lower rectum. She was diagnosed as having rectal NET by immunohistochemical analysis of a biopsy, and underwent laparoscopic low anterior resection with lymph node dissection and covering ileostomy. Pathological findings of the resected specimen showed that the primary tumor was NET-G1 without any lymphatic or venous invasion. A single metastatic deposit was found near the capsule of a NET-negative regional lymph node. She has been free from recurrence for nine months without adjuvant treatments. Extracapsular metastasis of NET on a dissected lymph node in our case was considered to correspond to EX as defined for colorectal carcinoma. This rare case suggests that NET can disseminate to form EX in a similar manner to colorectal carcinoma.
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http://dx.doi.org/10.1007/s12328-021-01447-xDOI Listing
October 2021

Risk factors of mFOLFOX6-induced hyperammonemia in patients with colorectal cancer: an observational study.

Int J Clin Oncol 2021 Aug 15;26(8):1477-1484. Epub 2021 May 15.

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

Background: FOLFOX therapy, a standard treatment for colorectal cancer (CRC), causes a rare, but serious adverse event, hyperammonemia. However, the risk factors of hyperammonemia remain unknown.

Methods: We examined 74 patients who received mFOLFOX6 therapy with or without biologics for CRC between April 2013 and March 2018 in Yaizu City Hospital. Clinicopathological factors were retrospectively reviewed in association with hyperammonemia, and risk factors of hyperammonemia during mFOLFOX6 therapy were analyzed in 32 patients with the available data.

Results: Seven patients developed hyperammonemia, with onset exclusively on day 2 or 3 in the first cycle of therapy. They were treated with branched chain amino acid administration and hydration; however, one patient with stage G4 chronic kidney disease (CKD) died. By multivariate analysis, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m was independently associated with hyperammonemia during FOLFOX therapy (odds ratio: 9.0, p = 0.040).

Conclusions: Reduced eGFR is considered a risk factor of developing hyperammonemia during FOLFOX therapy. Serum ammonia levels should be monitored especially during the first cycle of FOLFOX therapy in patients with CKD stage G3 or higher.
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http://dx.doi.org/10.1007/s10147-021-01932-wDOI Listing
August 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

Therapeutic effects and limitations of chemoradiotherapy in advanced lower rectal cancer focusing on T4b.

Int J Colorectal Dis 2021 Jul 3;36(7):1525-1534. Epub 2021 May 3.

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

Purpose: This study aimed to elucidate the benefits and limitations of preoperative chemoradiotherapy (CRT) in rectal cancer treatment, specifically in T4b rectal cancer.

Methods: This retrospective cohort study reviewed 1014 consecutive patients with clinical T3/4a/T4b adenocarcinomas of the lower rectum, who underwent total mesorectal excision at the Department of Surgical Oncology of the University of Tokyo Hospital and 22 referral institutions affiliated with the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. Patients were divided into two cohorts: cohort 1 comprised 298 consecutive patients who underwent CRT followed by radical surgery and cohort 2 comprised 716 consecutive patients who underwent curative surgery without preoperative therapy. We assessed the prognostic differences between the two cohorts, focusing particularly on T stages.

Results: In T3/4a patients, cohort 1 showed a significantly lower local recurrence rate than cohort 2 (4.8% vs. 9.4%, p=0.024), but not in T4b patients (23.5% vs. 16.0%, p=0.383). In contrast, no significant differences in survival were observed between T3/4a and T4b patients. T4b classification was found to be an independent predictive factor of local recurrence in cohort 1, but not in cohort 2.

Conclusion: In T4b rectal cancer, preoperative CRT demonstrated a limited benefit for local control and survival. In cases of suspected T4b rectal tumors, additional therapies such as induction chemotherapy to conventional CRT may contribute to better outcomes.
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http://dx.doi.org/10.1007/s00384-021-03936-4DOI Listing
July 2021

Extended Left Colectomy with Coloanal Anastomosis by Indocyanine Green-guided Deloyers Procedure: A Case Report.

J Anus Rectum Colon 2021 28;5(2):202-206. Epub 2021 Apr 28.

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

The Deloyers procedure is performed after extended left colectomy, enabling the reach of the proximal colon to the rectum for anastomosis while preserving sufficient blood supply. We report a case of the Deloyers procedure performed safely under indocyanine green (ICG) fluorescence guidance. A 50-year-old man with obesity (body mass index, 35.7 kg/m) and a history of diabetes underwent an extended left hemicolectomy and ultralow anterior resection of the rectum as radical resection for transverse and sigmoid colon cancers and a lower rectal neuroendocrine tumor. Reconstruction was performed by the Deloyers procedure. A necessary length of the transverse colon with reduced blood flow was additionally resected under ICG fluorescence guidance, and a transanal hand-sewn coloanal anastomosis was performed. This is the first report in which the Deloyers procedure was performed successfully with the ICG fluorescence method. ICG fluorescence may be useful when combined with the Deloyers procedure.
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http://dx.doi.org/10.23922/jarc.2020-097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084531PMC
April 2021

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

Establishing a novel method for assessing elasticity of internal anal sphincter using ultrasonic real-time tissue elastography.

ANZ J Surg 2021 06 12;91(6):E360-E366. Epub 2021 Apr 12.

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

Background: Evaluating anorectal function using real-time tissue elastography (RTE) has not been reported. A previous study reported that in the internal anal sphincter (IAS) of surgical specimens of patients with rectal cancer who underwent abdominoperineal resection, there was an increased fibrosis trend in those who underwent pre-operative chemoradiotherapy (CRT) compared with non-CRT. We speculated that CRT might have induced sclerosis of the IAS because of fibrosis. Therefore, we aimed to establish a method of quantitating the degree of IAS hardness using RTE on endoanal ultrasonography.

Methods: RTE was performed with freehand manual compression under a defined pressure at the middle anal canal. Using the most compressive point in the strain graph, we traced the region of interest in the IAS. The strain histogram showed a frequency distribution of colours according to the degree of strain (numeric scan ranging from 0 to 255; smaller number indicated harder tissue). We defined the mean of the strain histogram as 'elasticity'. Ten patients with locally advanced rectal cancer who underwent pre-operative CRT were prospectively enrolled. We statistically evaluated the correlation between IAS elasticity and maximum resting pressure (MRP) values both at pre- and post-CRT. MRP was examined concurrently with the examination of IAS elasticity.

Results: Representativity of elasticity measurements was demonstrated. It revealed a trend: IAS elasticity had a moderate inverse correlation with MRP (r = 0.41, P = 0.07), regardless of whether measurements were made before or after CRT.

Conclusion: We established a completely novel method for the assessment of elasticity of the IAS, using RTE on endoanal ultrasonography.
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http://dx.doi.org/10.1111/ans.16760DOI Listing
June 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

Open and/or laparoscopic one-stage resections of primary colorectal cancer and synchronous liver metastases: An observational study.

Medicine (Baltimore) 2021 Mar;100(11):e25205

Department of Surgical Oncology.

Abstract: One-stage resections of primary colorectal cancer and liver metastases have been reported to be feasible and safe. Minimally invasive approaches have become more common for both colorectal and hepatic surgeries. This study aimed to investigate outcomes of these combined surgical procedures among different approaches.We retrospectively analyzed patients diagnosed as having primary colorectal cancer with synchronous liver metastases and who underwent 1-stage primary resection and hepatectomy with curative intent in our hospital. According to the surgical approach for the primary tumor and hepatic lesions, namely open laparotomy (Op) or laparoscopic approach (Lap), patients were classified into Op-Op, Lap-Op (laparoscopic colorectal resection plus open hepatectomy), and Lap-Lap groups, respectively. Clinicopathological factors were reviewed, and short- and long-term outcomes were compared among the groups.The Op-Op, Lap-Op, and Lap-Lap groups comprised 36, 18, and 17 patients, respectively. The superior/posterior hepatic segments were more frequently resected via an open approach. There was no laparoscopic major hepatectomy. The median volume of intraoperative blood loss was smaller in the Lap-Lap and Lap-Op groups (290 and 270 mL) than in the Op-Op group (575 mL, P = .008). The hospital stay after surgery was shorter in the Lap-Lap and Lap-Op groups (median: 17 days and 15 days, vs 19 days for the Op-Op group, P = .033). The postoperative complication rates and survivals were similar among the groups.Application of laparoscopy to 1-stage resections of primary colorectal cancer and liver metastases may offer advantages of enhanced recovery from surgical treatment, given appropriate patient selection.
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http://dx.doi.org/10.1097/MD.0000000000025205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982201PMC
March 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

Therapeutic significance of D3 dissection for low rectal cancer: a comparison of dissections between the lateral pelvic lymph nodes and the lymph nodes along the root of the inferior mesenteric artery in a multicenter retrospective cohort study.

Int J Colorectal Dis 2021 Jun 3;36(6):1263-1270. Epub 2021 Feb 3.

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

Purpose: D3 dissection is the standard treatment modality for locally advanced low rectal cancer in Japan. The benefit of lateral pelvic lymph node (LPLN) dissection (LPLND) and lymph nodes along the root of inferior mesenteric artery (253 LN) dissection (253 LND) for low rectal cancer has often been studied separately, and few studies have investigated their benefit in the same cohort. This study aimed to clarify the therapeutic significance of dissection of the LPLN in comparison to that of dissection of the 253 LN for low rectal cancer.

Methods: We retrospectively evaluated 3508 patients with treatment-naïve stage I-III low rectal cancer who underwent mesorectal excision between 1997 and 2012. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. The rates of metastasis, survival, and therapeutic value index (5-year overall survival (OS) rate multiplied by metastatic rate for lymph node metastasis) were compared between LPLN and 253 LN.

Results: The rates of LPLN metastasis and 253 LN metastasis were 17.9% and 1.5%, respectively. The 5-year OS was significantly different between patients with and without LPLN metastasis (55.0% vs 85.5%, P < 0.0001) and between patients with and without 253 LN metastasis (36.2% vs 83.3%, P < 0.0001). The therapeutic value indexes of LPLN and 253 LN were 9.85 and 0.54, respectively.

Conclusions: LPLND may have more therapeutic value than 253 LND for patients with treatment-naïve low rectal cancer, although both the patients with LPLN metastasis and those with 253 LN metastasis remained to have poor prognosis.
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http://dx.doi.org/10.1007/s00384-021-03858-1DOI Listing
June 2021

Hazard function analysis of metastatic recurrence after colorectal cancer surgery-A nationwide retrospective study.

J Surg Oncol 2021 Mar 14;123(4):1015-1022. Epub 2021 Jan 14.

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

Background And Objectives: An optimal postoperative surveillance protocol for colorectal cancer (CRC) is dependent on understanding the time line of recurrence. By hazard function analysis, this study aimed at evaluating the time of occurrence of metastasis.

Methods: A total of 21,671 Stage I-III colon cancer patients were retrospectively included from the Japanese study group for postoperative follow-up of colorectal cancer database.

Results: The 5-year incidence by metastasized organ was 6.3% for liver (right:left = 5.5%:7.0%, p = .0067), 6.0% for lung (right:left:rectum = 3.7%:4.4%:8.8%, p = 7.05E-45), and 2.0% for peritoneal (right:left:rectum = 3.1%:2.0%:1.2%, p = 1.29E-12). The peak of liver metastasis hazard rate (HR) (0.67 years) was earlier and higher than those of other metastases. The peak HR tended to be delayed in early stage CRCs (0.91, 0.76, and 0.52 years; for Stages I, II, and III, respectively). When analyzed as per the primary tumor location (right-sided, left-sided, and rectum), the peak HR for lung metastasis was twice as high for rectal cancer than for colon cancer, and peritoneal metastasis had a high HR in right-sided colon cancers.

Conclusion: The time course for the risk of recurrence in various metastatic organs based on the primary tumor site was clearly visualized in this study. This will aid in individualizing postoperative surveillance schedules.
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http://dx.doi.org/10.1002/jso.26378DOI Listing
March 2021

Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Dis Colon Rectum 2021 03;64(3):274-283

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

Background: Although chemoradiotherapy followed by radical surgery without lateral lymph node dissection is the current standard treatment in patients with rectal cancer, recent studies have demonstrated the benefits of adding lateral lymph node dissection to total mesorectal excision in patients with suspected lateral lymph node metastasis. However, the optimal indication for lateral lymph node dissection after chemoradiotherapy has not been determined.

Objective: This study aimed to establish the optimal indication for lateral lymph node dissection after chemoradiotherapy in patients with rectal cancer.

Design: This is a retrospective study.

Settings: This study was conducted at a single referral hospital.

Patients: A total of 279 patients with rectal cancer who underwent chemoradiotherapy followed by radical surgery between 2007 and 2018 were retrospectively enrolled.

Main Outcome Measures: The largest lateral lymph nodes on CT were retrospectively assessed and compared with the pathologic results of dissected lateral lymph nodes and recurrences in lateral lymph node areas.

Results: The incidence of lateral lymph node metastasis after chemoradiotherapy was estimated to be 9.3%. Although patients with lateral lymph node metastasis frequently developed distant recurrence, 40.4% survived for >5 years without recurrence. An analysis of the lateral lymph node sizes showed that lateral lymph node size ≥8 mm before chemoradiotherapy was the optimal criterion for lateral lymph node dissection, with a sensitivity and specificity of 92.3% and 78.7%. Using this criterion, 72.0% of the patients could be spared lateral lymph node dissection.

Limitations: Because of the retrospective nature of the present study, the selection of patients who underwent lateral lymph node dissection was biased.

Conclusions: The optimal indication for lateral lymph node dissection was lateral lymph node size ≥8 mm before chemoradiotherapy. Cancer could be eradicated in >30% of patients with lateral lymph node metastasis by dissecting metastatic lateral lymph nodes. See Video Abstract at http://links.lww.com/DCR/B428.

Criterios De Tamao Ptimo Para La Diseccin De Ganglios Linfticos Laterales Despus De La Quimiorradioterapia Neoadyuvante Para El Cncer De Recto: ANTECEDENTES:Aunque la quimiorradioterapia seguida por cirugía radical sin disección de ganglios linfáticos laterales es el tratamiento estándar actual en pacientes con cáncer de recto, estudios recientes han demostrado beneficios de agregar disección de ganglios linfáticos laterales a la escisión mesorrectal total en pacientes con sospecha de metástasis de ganglios linfáticos laterales. Sin embargo, no se ha determinado la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia.OBJETIVO:Este estudio tuvo como objetivo establecer la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Este estudio se realizó en un solo hospital de referencia.PACIENTES:Se inscribieron retrospectivamente un total de 279 pacientes con cáncer de recto que se sometieron a quimiorradioterapia seguida por cirugía radical entre 2007 y 2018.PRINCIPALES MEDIDAS DE VALORACION:Los ganglios linfáticos laterales más grandes en la tomografía computarizada se evaluaron retrospectivamente y se compararon con los resultados patológicos de los ganglios linfáticos laterales disecados y recidivas en las áreas de los ganglios linfáticos laterales.RESULTADOS:Se estimó que la incidencia de metástasis en los ganglios linfáticos laterales después de la quimiorradioterapia fue del 9,3%. Aunque los pacientes con metástasis en los ganglios linfáticos laterales con frecuencia desarrollaron recurrencia a distancia, el 40,4% sobrevivió durante más de 5 años sin recurrencia. Un análisis de los tamaños de los ganglios linfáticos laterales mostró que la mayor dimensión de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia eran el criterio óptimo para la disección de los ganglios linfáticos laterales, con una sensibilidad y especificidad del 92,3% y 78,7%, respectivamente. Utilizando este criterio, el 72,0% de los pacientes podría evitarse la disección de los ganglios linfáticos laterales.LIMITACIONES:Debido a la naturaleza retrospectiva del presente estudio, la selección de pacientes que fueron sometidos a disección de ganglios linfáticos laterales fue sesgada.CONCLUSIÓN:La indicación óptima para la disección de los ganglios linfáticos laterales fue la dimensión mayor de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia. El cáncer se podría erradicar en más del 30% de los pacientes con metástasis en los ganglios linfáticos laterales disecando los ganglios linfáticos laterales metastásicos. Consulte Video Resumen en http://links.lww.com/DCR/B428.
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http://dx.doi.org/10.1097/DCR.0000000000001866DOI Listing
March 2021

Epithelial-mesenchymal transition and metastatic ability of CD133 colorectal cancer stem-like cells under hypoxia.

Oncol Lett 2021 Jan 9;21(1):19. Epub 2020 Nov 9.

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

Although CD133 is a representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia remains unclear. Therefore, the present study aimed to investigate the associations between CD133, the epithelial-mesenchymal transition and distant metastasis in colorectal cancer. CD133 and CD133 cells were isolated from a single colorectal cancer cell line LoVo, and their adhesive and migratory properties were compared under hypoxic conditions. Immunostaining analysis was performed to determine CD133 expression in clinical samples of primary tumors, as well as liver and peritoneal metastases. Under hypoxia, the expression levels of hypoxia-inducible factor (HIF)-1α and the epithelial-mesenchymal transition markers N-cadherin and vimentin were significantly higher in the CD133 compared with those in the CD133 cells. Furthermore, the migratory ability of the CD133 cells was higher compared with that of the CD133 cells under hypoxia. By contrast, the expression levels of β1 integrin were significantly lower in the CD133 cells under hypoxia compared with those in the CD133 cells. Immunohistochemical analysis of clinical samples revealed that the levels of CD133 expression in metastatic tissues from the liver were significantly higher compared with those in the corresponding primary tumors, whereas CD133 expression levels in peritoneal metastatic tissues were significantly lower compared with those in the corresponding primary tumors. In conclusion, compared with the CD133 cells, the CD133 colorectal cancer cells exhibited enhanced levels of HIF-1α expression and tumor cell migration during hypoxia. This was associated with an increased ability of epithelial-mesenchymal transition, possibly leading to the acquisition of an increased hematogenous metastatic potential and eventually resulting in liver metastasis. High β1 integrin expression levels in the CD133 cells under hypoxia may serve a key role in cell adhesion to the peritoneum, resulting in peritoneal metastasis.
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http://dx.doi.org/10.3892/ol.2020.12280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681219PMC
January 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

Oncological Outcomes of Pathological T1 Lower Rectal Cancer Patients With or Without Preoperative Chemoradiotherapy.

In Vivo 2020 Nov-Dec;34(6):3559-3564

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

Background/aim: It remains unclear whether rectal cancers down-staged by preoperative chemoradiotherapy (CRT) have similar prognoses to those of the same stage without preoperative CRT. We compared prognoses of pT1 rectal cancer patients stratified by preoperative CRT.

Patients And Methods: We retrieved data of patients with pathological T1 rectal cancer between 2003 and 2020. Patients were divided into the "ypT1 group" who received preoperative CRT following surgery and the "pT1 group" who underwent surgery alone. Factors associated with relapse-free survival (RFS) were investigated.

Results: Among 86 patients, ypT1 and pT1 groups comprised 18 and 68 patients, respectively. There was no significant difference in RFS between the groups (p=0.19). Tumor location within 5 cm from the anal verge was associated with recurrence (hazard ratio: 0.13, p=0.034).

Conclusion: The prognosis of patients with ypT1 rectal cancer was similar to that of patients with pT1. Low tumor location was a poor prognostic factor.
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http://dx.doi.org/10.21873/invivo.12199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811633PMC
June 2021

Impact of Surgical Resection on Metachronous Metastases of Colorectal Cancer According to Tumor Doubling Time.

In Vivo 2020 Nov-Dec;34(6):3367-3374

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

Background/aim: We aimed to elucidate the prognostic impact of tumor doubling time (DT) and radical surgery when classified by DT in patients with metachronous liver, lung, or peritoneal metastases of colorectal cancer (CRC).

Patients And Methods: We reviewed the data of 1941 patients who underwent curative surgery for CRC and calculated DT for recurrences using computed tomography.

Results: Short DT was an independent prognostic risk factor in liver (p<0.001) and peritoneal (p=0.03) metastases. Survival was significantly better in patients who underwent surgery than in those who did not, both in short and long DT groups in any metastatic organ (p<0.01). Patients with long DT gained significantly better prognostic benefit from surgery than those with short DT in liver (p=0.01) and peritoneal (p=0.04) metastases.

Conclusion: Surgery is recommended for resectable metastases, especially in patients with liver and peritoneal metastases with long DT.
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http://dx.doi.org/10.21873/invivo.12175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811596PMC
June 2021

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

Less intensive surveillance after radical surgery for stage I-III colorectal cancer by focusing on the doubling time of recurrence.

Surg Today 2021 Apr 15;51(4):550-560. Epub 2020 Sep 15.

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

Purpose: To propose a new and improved surveillance schedule for colorectal cancer (CRC) patients by focusing on the recurrence rate, resectability, and especially, the tumor doubling time (DT) of recurrent tumors.

Methods: The subjects of this retrospective review were 1774 consecutive patients who underwent radical surgery for stage I-III CRC between January, 2004 and December, 2015. We calculated the DT by measuring the tumor diameter using computed tomography (CT).

Results: The median DT for recurrences in the liver, lung, peritoneum, and other locations were 35, 72, 85, and 36 days, respectively, (p < 0.001) and tumor growth rates differed according to the organs where recurrence developed. Multiple linear regression analysis showed that the DT was strongly associated with the relapse-free interval from primary surgery (p < 0.001), and that the DT in patients with recurrence detected ≥ 3 years after primary surgery was longer by 151.1 days than that in patients with recurrence detected within 1 year after primary surgery. We proposed a less intensive surveillance, which achieved an average cost reduction of 32.5% compared with conventional surveillance in Japan.

Conclusion: We propose a new and more cost-efficient surveillance schedule for CRC surgery patients in the clinical setting.
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http://dx.doi.org/10.1007/s00595-020-02135-yDOI Listing
April 2021

Liver Injury Among Japanese Patients Treated Using Prophylactic Enoxaparin After Colorectal Surgery.

Dig Dis Sci 2021 08 5;66(8):2805-2815. Epub 2020 Sep 5.

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

Background: Enoxaparin, a low molecular weight heparin, has been used to prevent thrombotic events during major surgery without increasing the rate of hemorrhage. On the other hand, it was reported to cause liver injury, but the details of liver injury induced by prophylactic enoxaparin after abdominal surgery remain unclear.

Aims: This study aimed to clarify the relationship between prophylactic enoxaparin and liver injury after colorectal surgery, and characterize the injury profile.

Methods: We retrospectively reviewed 732 Japanese patients who underwent elective resection of the colorectum, and compared their clinicopathological background, details of surgery, postoperative complications, including liver injury, and the type of liver injury according to prophylactic use of enoxaparin. Univariate and multivariate analyses were performed to identify risk factors for liver injury during the postoperative period.

Results: The rate of liver injury was 8.9% for patients treated by prophylactic enoxaparin and 1.4% for those who did not receive enoxaparin after colorectal surgery (p < 0.0001). The median onset of liver injury among patients receiving enoxaparin was seven days, and the majority demonstrated the hepatocellular pattern. Enoxaparin was one of the independent risk factors for postoperative liver injury by multivariate analysis (odds ratio: 7.63, p < 0.0001).

Conclusions: Prophylactic use of enoxaparin markedly increased the rate of postoperative liver injury in patients who underwent colorectal surgery. Our study confirmed that close monitoring of liver function parameters is essential for patients receiving enoxaparin during the postoperative period.
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http://dx.doi.org/10.1007/s10620-020-06586-8DOI Listing
August 2021

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

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

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

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

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

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

Conclusion: The ip administration of PTX with systemic chemotherapy can potentially control peritoneal metastases in colorectal cancer.
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http://dx.doi.org/10.1007/s00384-020-03649-0DOI Listing
October 2020

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
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