Publications by authors named "Yuichiro Yokoyama"

59 Publications

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

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

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

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

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

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

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

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

Oncology 2021 Nov 24. Epub 2021 Nov 24.

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

Computed tomographic colonography versus double-contrast barium enema for the preoperative evaluation of rectal cancer.

Surg Today 2021 Nov 23. Epub 2021 Nov 23.

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

Purpose: We investigated whether or not computed tomographic colonography (CTC) is a viable alternative to double-contrast barium enema (BE) for a preoperative rectal cancer evaluation.

Methods: The size and distance from the anal canal to the lower or upper tumor borders were laterally measured in 147 patients who underwent CTC and BE. Measurements were grouped into early cancer, advanced, and after chemoradiation therapy (CRT).

Results: In the early and advanced cancer groups, all lesions were visualized by BE. In contrast, 3 (7.8%) early and 8 (7.3%) advanced cases, located at the anterior wall near the anal canal, were not visualized by CTC because of liquid level formation. In the CRT group, 16 (23.5%) and 4 (5.8%) cases were not visualized by CTC and BE, respectively. The BE and CTC size measurements were similar among cohorts. However, the distance from the anal canal's superior margin tended to be longer with BE, especially in early cancer. The differences in distance from the anal canal were significantly larger in the early cancer group than in the other two groups (p = 0.0024).

Conclusion: CTC may be a viable alternative imaging modality in some cases. However, BE should be employed in anterior wall cases near the anal canal and CRT cases.
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http://dx.doi.org/10.1007/s00595-021-02411-5DOI Listing
November 2021

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Surg Today 2021 Aug 4. Epub 2021 Aug 4.

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

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

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

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

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

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

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

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

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

[A Simulation Surgery of Valve-sparing Aortic Root Replacement Using a Three-dimensional Printed Model].

Kyobu Geka 2021 Jun;74(6):413-417

Department of Cardiovascular Surgery, Yotsuba Circulation Clinic, Matsuyama, Japan.

Aortic valve-sparing surgery is a delicate procedure that requires specialized skills to control aortic valve regurgitation. Therefore, simulating the surgery before performing it on a patient is good practice for inexperienced surgeons. Herein, we present our experience of a simulation surgery using a three-dimensionally printed aortic root model of a 60-year-old man with severe aortic regurgitation and aortic root enlargement. We fabricated the model using multi-slice computed tomography data. The model revealed the two pitfalls:unbalanced commissure position and lower coaptation height of the right coronary cusp. We completed the simulation surgery from the proximal suture and valve reimplantation to coronary ostial reconstructions during approximately three hours with medical staffs. In the actual operation, the aortic valve regurgitation completely disappeared by accurately reconstructing the commissure in the Valsalva graft and adjusting the height of the right coronary cusp using central plication procedure. We believe that carrying out simulations before the actual surgery improves the surgeon's confidence and the patient's outcomes.
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June 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

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

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

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

Differential diagnosis and laparoscopic resection of an adrenal pseudocyst: A case report.

Int J Surg Case Rep 2020 9;72:178-182. Epub 2020 Jun 9.

Department of Surgery, Kanto Rosai Hospital, 1-1 Kizukisumiyoshicho, Nakahara-ku, Kanagawa, 211-8510, Japan. Electronic address:

Background: Adrenal pseudocysts are infrequent entities and definite preoperative diagnosis is difficult. We present a case of left adrenal pseudocyst, which was intraoperatively identified as having an adrenal origin and was resected using a laparoscopic approach.

Presentation Of Case: A 41-year-old female was referred to our hospital for examination and treatment of a cystic lesion in the pancreatic tail. Preoperative diagnostic imaging studies showed a cystic lesion with intramural nodular structure, measuring 39 mm in the largest diameter and located between the pancreatic tail and the left adrenal gland. However, the origin of the cystic lesion remained unclear, and a definite preoperative diagnosis was not established. The cystic lesion was intraoperatively identified as having an adrenal origin after the division of the loose connective tissue layer around the lesion under the laparoscopic magnified view. Laparoscopic left adrenalectomy was performed as radical treatment and the histopathological diagnosis confirmed the presence of an adrenal pseudocyst.

Discussion: We could not ascertain the origin of the cystic lesion from the left adrenal gland and establish a definite diagnosis based on the findings of the preoperative diagnostic imaging modalities. Laparoscopic surgery could be more advantageous than the conventional open approach as not only a minimally invasive treatment option but also as an intraoperative diagnostic tool for cystic lesions in the pancreatic tail.

Conclusion: This case report suggests that laparoscopic surgery could be clinically useful as not only a minimally invasive treatment but also an intraoperative diagnostic tool for cystic lesions in the pancreatic tail region.
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http://dx.doi.org/10.1016/j.ijscr.2020.05.082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298542PMC
June 2020

Solitary pancreatic metastasis of gastric cancer with synchronous pancreatic ductal carcinoma: A case report.

Int J Surg Case Rep 2020 7;70:164-167. Epub 2020 May 7.

Department of Surgery, Kanto Rosai Hospital, 1-1 Kizukisumiyoshicho, Nakahara-ku, Kanagawa, 211-8510, Japan. Electronic address:

Background: There have been a few reports on solitary pancreatic metastases of gastric cancer. We present a case of solitary pancreatic metastasis of gastric cancer with synchronous primary pancreatic ductal carcinoma.

Presentation Of Case: An 86-year-old man who had undergone total gastrectomy two and half years prior presented with a poorly enhanced tumor in the pancreatic body. We diagnosed pancreatic ductal carcinoma and performed distal pancreatosplenectomy. Histopathologically, the tumor comprised poorly differentiated adenocarcinoma cells mixed with moderately differentiated tubular adenocarcinoma cells that were compatible with metastasis of gastric cancer. There was also invasive ductal carcinoma of the pancreas. The postoperative course was uneventful. Six months after surgery, computed tomography revealed peritoneal dissemination, and he died of recurrence 10 months after surgery.

Conclusion: Pancreatic metastasis of gastric cancer with synchronous primary pancreatic cancer can occur and should be considered in the differential diagnosis.
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http://dx.doi.org/10.1016/j.ijscr.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229230PMC
May 2020

Early Predictors of Objective Response in Patients with Hepatocellular Carcinoma Undergoing Lenvatinib Treatment.

Cancers (Basel) 2020 Mar 25;12(4). Epub 2020 Mar 25.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.

There are limited reports regarding early predictors of objective response (OR) in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. This retrospective study including 70 patients aimed to investigate the efficacy of hepatic biochemical markers. Changes in tumor marker (alpha-fetoprotein (AFP)/des-gamma-carboxy prothrombin (DCP)) levels and albumin-bilirubin (ALBI) score between the baseline value and that estimated one month after treatment were evaluated. We identified several predictors of OR, including changes in tumor marker levels. The OR rate calculated using modified Response Evaluation Criteria in Solid Tumor (mRECIST) was 41.4%. Response was defined as a reduction in AFP and DCP levels of ≥40% from baseline. OR was significantly associated with AFP response, but not with DCP. Predictors of OR were evaluated in two groups (high-AFP group: baseline AFP ≥ 10 ng/mL; low-AFP group: remaining patients). A multivariate analysis identified AFP response (odds ratio, 51.389; = 0.001) and ALBI score (odds ratio, 6.866; = 0.039) as independent predictors of OR in the high-AFP and low-AFP groups, respectively. Changes in the ALBI score indicated deterioration in both responders and non-responders, with a significant difference in non-responders ( = 0.003). AFP response, baseline ALBI score, and change in the ALBI score were early predictors of OR in patients with HCC undergoing lenvatinib treatment.
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http://dx.doi.org/10.3390/cancers12040779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225985PMC
March 2020

Endoscopic Removal of a Fish Bone Migrating and Penetrating the Stomach.

Am J Gastroenterol 2018 09;113(9):1282

Department of Gastroenterology, Tokuyama Central Hospital, Shunan, Japan. Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube, Japan. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

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http://dx.doi.org/10.1038/s41395-018-0161-1DOI Listing
September 2018

The association of kyphosis assessed in supine and standing positions with future activities of daily living dependence: the Kurabuchi Study.

Arch Osteoporos 2017 Nov 22;12(1):105. Epub 2017 Nov 22.

Department of Orthopaedic Surgery, School of Medicine, Toho University, Tokyo, Japan.

We investigated the longitudinal association of noninvasively evaluated kyphotic posture with future dependence in activities of daily living and death in a community-dwelling older Japanese. We found that the association with outcomes varied according to the types of kyphotic posture.

Introduction: We have previously found an association between severe kyphosis and future dependence in activities of daily living (ADL) in people who manifest the condition in the supine position (structural curvature). However, because some people show severe kyphosis only in the standing position (postural curvature), we combined our noninvasively obtained kyphosis measurements from participants in the supine position (block method) with those obtained from participants in the standing position (kyphosis index) to determine whether not only structural curvature but also postural curvature is associated with ADL dependence and death.

Methods: Between 2005 and 2006, we carried out health evaluations of adults aged 65 years or older in Kurabuchi Town, Japan: 792 participants (337 males, 455 females) who were independent in ADL at baseline and underwent evaluation of kyphotic posture were followed up until March 2014 (mean follow-up: 7.5 years). Participants who experienced one or more admissions to a nursing home, certification of a need for long-term care/support, or a decline in the Katz ADL Index during the follow-up period were defined as being dependent in ADL.

Results: A flat back (straight spine in a standing position) and structural curvature were associated with future ADL dependence, but postural curvature was not. The multivariate-adjusted odds ratios (95% confidence interval) compared with physiological curvature (physiological curvature in a standing position) as the reference were 1.72 (1.04-2.86) for a flat back and 2.76 (1.59-4.79) for structural curvature. A weak association with death was observed in those with structural curvature.

Conclusions: Our results suggest that the prognoses of people with kyphosis differ according to the type of kyphotic posture.
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http://dx.doi.org/10.1007/s11657-017-0401-9DOI Listing
November 2017

ZEB1-regulated inflammatory phenotype in breast cancer cells.

Mol Oncol 2017 09 11;11(9):1241-1262. Epub 2017 Jul 11.

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Japan.

Zinc finger E-box binding protein 1 (ZEB1) and ZEB2 induce epithelial-mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1-regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1-bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB1 controlled the production of the IL-6 and IL-8 proteins. The secretory proteins regulated by ZEB1 enhanced breast cancer cell proliferation and tumor growth. ZEB1 expression in breast cancer cells also affected the growth of fibroblasts in cell culture, and the accumulation of myeloid-derived suppressor cells in tumors in vivo. These findings provide insight into the role of ZEB1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT.
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http://dx.doi.org/10.1002/1878-0261.12098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579340PMC
September 2017

Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer.

Cancer Res 2017 08 13;77(15):4026-4038. Epub 2017 Jun 13.

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Poor prognoses for colorectal cancer patients with metastatic lesions have driven demand for the development of novel targeted therapies. Here, we demonstrate that expression of bone morphogenetic protein 4 (BMP-4) is universally upregulated in human colorectal cancer cells and tissues, resulting in activated BMP signaling. Inhibition of endogenous BMP signaling by the BMP type I receptor inhibitor LDN-193189 elevated expression of the phosphatase DUSP5 in colorectal cancer cells, inducing apoptosis via dephosphorylation of Erk MAPK. Administering LDN-193189 to mice diminished tumor formation of colorectal cancer cells. Our findings suggest inhibition of autocrine BMP-4 as a candidate treatment strategy for colorectal cancer. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-0112DOI Listing
August 2017

Giant solitary fibrous tumor of the pelvis successfully treated with preoperative embolization and surgical resection: a case report.

World J Surg Oncol 2015 Apr 29;13:164. Epub 2015 Apr 29.

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

Solitary fibrous tumors (SFTs) rarely develop in the pelvis. When they do arise, they are usually treated using surgery, although SFTs are often very large by the time of diagnosis, which makes surgical excision difficult. We report a case of a 63-year-old man who was referred to our hospital for the treatment of a giant tumor of the pelvis. Computed tomography (CT) revealed a 30 × 25 × 19 cm sized hypervascular tumor that almost completely filled the pelvic cavity. The diagnosis of SFT was made by CT-assisted needle biopsy. The feeding arteries of the tumor were embolized twice. The first embolization aimed to reduce the tumor volume, while the second one was planned a day prior to the surgery to obtain hematostasis during the operation. Tumor resection was then performed. The blood loss during the operation was 440 ml, and there was no uncontrollable bleeding. The postoperative course was uneventful. No recurrence of SFT was observed during a 2-year follow-up.
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http://dx.doi.org/10.1186/s12957-015-0578-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417519PMC
April 2015

A rare case: bioprosthetic tricuspid valvuloplasty dramatically improved hepatic encephalopathy.

Gen Thorac Cardiovasc Surg 2016 Oct 22;64(10):618-20. Epub 2015 Feb 22.

Yotsuba Circulation Clinic, Minami-edo 4-3-53, Matsuyama, Ehime, 790-0062, Japan.

A 51-year-old woman was diagnosed as severe stenosed tricuspid bioprosthetic valve. She had developed an encephalopathy due to elevated serum ammonia concentration caused by congestive hepatic failure. Re-tricuspid valve replacement was deemed too risky, and balloon bioprosthetic valvuloplasty was instead planned. This procedure was successfully performed using a standard mitral valvuloplasty protocol. The 30-mm INOUE-BALLOON was inflated five times. The mean pressure gradient across the bioprosthetic valve decreased from 7.8 to 3.5 mmHg, and the tricuspid valve orifice area increased from 1.09 to 3.13 cm(2), without worsening of the tricuspid valve regurgitation. Finally, her hepatic encephalopathy was dramatically improved.
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http://dx.doi.org/10.1007/s11748-015-0532-0DOI Listing
October 2016

A case of extraperitoneal stoma-associated internal hernia after abdominoperineal resection.

World J Surg Oncol 2014 May 6;12:141. Epub 2014 May 6.

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

Published reports concerning internal hernias after extraperitoneal stoma construction are scarce. In our present report, we describe the case of a 56-year-old man who was referred to our hospital for the treatment of rectal cancer. He underwent abdominoperineal resection of the rectum with sigmoidostomy using an extraperitoneal route. On the ninth postoperative day, the patient experienced sudden and intense abdominal pain and was diagnosed with strangulation of the small intestine due to a stoma-associated internal hernia. Therefore, an emergency laparotomy was performed. The surgical findings showed that the small intestine protruded through the space between the sigmoid colon loop and the abdominal wall in a cranial-to-caudal direction. The strangulated portion of the small intestine was recovered, and the orifice of herniation was closed. No recurrence of internal herniation was observed during the follow-up period.
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http://dx.doi.org/10.1186/1477-7819-12-141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029971PMC
May 2014
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