Publications by authors named "Shinsuke Kazama"

100 Publications

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

Immunohistochemical Expression of CD133 and LGR5 in Ulcerative Colitis-associated Colorectal Cancer and Dysplasia.

In Vivo 2019 Jul-Aug;33(4):1279-1284

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

Background/aim: Cluster of differentiation 133 (CD133) and leu cine-rich orphan G-protein-coupled receptor 5 (LGR5) are the most putative stem cell markers for colorectal cancer (CRC), and are associated with poor prognosis of patients with CRC. However, the role of CD133 and LGR5 in the inflammation-dysplasia-carcinoma sequence has not been fully elucidated. We examined the expression of CD133 and LGR5 in ulcerative colitis-associated CRC (UC-CRC; n=20) and UC-associated colorectal dysplasia (n=16) by immunohistochemistry.

Results: The rate of CD133-positive cases in UC-CRC was significantly higher than that in dysplasia (p=0.026), but that of LGR5 expression was not. Moreover, LGR5 expression was significantly positively associated with p53 expression (p=0.03), whereas CD133 expression positively correlated with p53 expression, but not significantly (p=0.10).

Conclusion: CD133 may play an important role in tumor development in the context of the inflammation-dysplasia-carcinoma sequence. LGR5-positive cancer stem cells may play a critical role in the development of UC-CRC, particularly upon loss of p53 function.
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http://dx.doi.org/10.21873/invivo.11600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689354PMC
December 2019

G-CSF-producing Undifferentiated Pleomorphic Sarcoma Adjacent to the Ascending Colon and in the Right Iliopsoas Muscle: A Case Report and Review of the Literature.

Intern Med 2019 Oct 27;58(19):2783-2789. Epub 2019 Jun 27.

Department of Gastroenterological Surgery, Saitama Cancer Center, Japan.

Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on F-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.
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http://dx.doi.org/10.2169/internalmedicine.2762-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815886PMC
October 2019

[Three Long-Surviving Cases of Recurrent Rectal Carcinomas Treated Non-Surgically and Cured].

Gan To Kagaku Ryoho 2018 Dec;45(13):2453-2455

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

Few cases of recurrent colorectal carcinomas were treated non-surgically and cured. Here, we report 3 such cases. Case No. 1 was of a 66-year-old woman, who underwent ISR for very low rectal cancer. Her disease Stage was tub2, T2N0M0. Two years and 6 months later, she developed intrapelvic recurrence involving sacral bones(S1-S3). Radiotherapy of 50 Gy followed by mFOLFOX6 with bevacizumab was administered for a year. She has been cancer-free for 6 years. Case No. 2 was of a 47-year-old man who underwent preoperative CRT of 40 Gy with 5-FU plus Leucovorin, and LAR was performed for very low rectal cancer. The disease Stage was tub2, T3N2M0. One year later, he was diagnosed with recurrent aortic lymph node metastasis. After 7 months of mFOLFOX6 with bevacizumab, he developed an anastomotic fistula. His chemotherapy was discontinued; he was cancer-free for 6 years. Case No. 3 was of a 56-year-old man who underwent TPE for low rectal cancer. The disease Stage was muc, T4b(urinary bladder)N0M1a(perianal skin). One year and 6 months later, he developed ileus and was diagnosed with intrapelvic recurrence. He underwent intestinal bypass operation, and CRT of 46 Gy with capecitabine was administered. He attained CR quickly, and was cancer-free for 5 years. Collecting similar cases to analyze the key to successful treatment is important.
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December 2018

A case of unique endoscopic findings of intestinal endometriosis exposed to the mucosa: aggregation of papillary protruded bulges from the submucosal elevation of the rectum.

Clin J Gastroenterol 2019 Apr 22;12(2):166-170. Epub 2018 Sep 22.

Department of Pathology, Yaizu Municipal Hospital, 1000 Dobara, Yaizu, Shizuoka, 425-8505, Japan.

Intestinal endometriosis exposed to the mucosa is relatively rare. Therefore, its endoscopic findings with pit pattern and magnifying endoscopy with narrow-band imaging and clinicopathological features of intestinal endometriosis exposed to the mucosa have not been well documented until now. A 44-year-old woman was suspected to have gastrointestinal bleeding by positive fecal occult blood test. Colonoscopy revealed a hemicircular submucosal tumor whose surface was covered with easy-bleeding papillary bulges in the rectum. Pit pattern analysis and magnifying endoscopy with narrow-band imaging revealed straight microvessels among the straight pits arranged in a radial manner, and the avascular area with no pit pattern of the top of the bulge. These findings were different from those of polyps or cancer. Biopsy specimens from the protruded lesions were diagnosed as rectal mucosal endometriosis by hematoxylin-eosin staining and immunohistochemical examination. Surgical resection was suggested to the patient, but the patient did not favor surgical treatment. After the diagnosis dienogest treatment started and successfully relieved her abdominal pain. Malignant transformation of the endometriotic lesion has not arisen to this date.
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http://dx.doi.org/10.1007/s12328-018-0912-yDOI Listing
April 2019

Prognostic impact of doublecortin-like kinase 1 expression in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

APMIS 2018 Jun;126(6):486-493

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

Preoperative chemoradiotherapy (CRT) is a standard therapy for locally advanced rectal cancer; however, the response varies depending on cases. Therefore, CRT-response predictors need to be elucidated. Cancer stem cells (CSCs), comprising a small part of tumors, are associated with tumor progression and recurrence due to their self-renewal and proliferation abilities. Doublecortin-like kinase 1 (DCLK1) is one of the several putative CSC markers; however, the clinical impact of its expression in rectal cancer has not been evaluated. The aim of this study was to clarify the clinical impact of DCLK1 expression in rectal cancer. We immunohistochemically evaluated DCLK1 expression in surgical specimens of 106 rectal cancer patients, including those who underwent preoperative CRT. The correlations between DCLK1 expression, and clinicopathological features and patient prognosis were then assessed. In rectal cancer patients treated with preoperative CRT, DCLK1 expression was significantly correlated with lymph node metastasis (p = 0.02) and poor cancer-specific survival (p = 0.049). However, in patients treated without preoperative therapy, no such correlation was found. DCLK1 expression can be associated with lymph node metastasis and poor cancer-specific survival in rectal cancer patients who receive CRT.
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http://dx.doi.org/10.1111/apm.12852DOI Listing
June 2018

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

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

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

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

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

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

Conclusions: Although robotic surgery for rectal cancer was associated with a longer operation time, it was associated with a very low incidence of SSIs. The degree of safety was comparable to both open and laparoscopic surgery.
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http://dx.doi.org/10.1007/s00384-018-3056-0DOI Listing
August 2018

[Three Long-Surviving Cases of Peritoneal Metastasis after Colorectal Cancer Resection].

Gan To Kagaku Ryoho 2018 Feb;45(2):356-358

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

We experienced 3 impressive colorectal cancer patients who developed peritoneal recurrences and underwent surgery several times and survived for more than 5 years. Case No. 1 was of a 44-year-old woman who underwent right hemicolectomy for her stage II A ascending colon cancer. She developed left ovarian metastasis, which was resected 3 years later. Five years later, she developed a pelvic peritoneal recurrence, which was resected successfully. Thirteen years later, she is doing well. Case No. 2 was of a 61-year-old man who underwent transverse colectomy for his stage II B colon cancer. He developed ileus 2 years 9 months later due to peritoneal recurrence, which was removed successfully. He underwent another resection for peritoneal metastasis 2 years 6 months later. He was administered 15 courses of FOLFOX6. He has remained cancer-free since 2009. Case No. 3 was of a 62-year-old man who underwent sigmoidectomy for his stage II A colon cancer. One year 8 months later, he underwent resection for a painful abdominal wall metastasis. Eight months later, he developed another abdominal wall recurrence, which was resected successfully. He underwent thoracoscopic resection 4 times for lung metastases and was given 16 courses of FOLFOX6. In 2009, he developed pelvic peritoneal nodules, which were resected. He later needed lymphadenectomy twice. He has remained cancer-free for the last 5 years and 6 months. Curative resection must be performed for a patient with peritoneal recurrence of colorectal cancer when surgery is indicated.
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February 2018

DCLK1 Expression in Colorectal Polyps Increases with the Severity of Dysplasia.

In Vivo 2018 Mar-Apr;32(2):365-371

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

Background: The expression of doublecortin-like kinase 1 (DCLK1) has been investigated in cancer; however not in precancerous adenomatous polyps.

Materials And Methods: Immunohistological expression of DCLK1 was evaluated in various grades of adenomas, cancerous polyps, and hyperplastic polyps in resected human tissue specimens.

Results: Ninety-two specimens were positive for DCLK1 and 134 were negative. Cancerous polyps showed a high DCLK1 positivity rate compared to adenomas (68.4% vs. 36.8%; p<0.01). The rate of DCLK1 positivity was not significantly different among the three grades of adenomas (mild, moderate, and severe). DCLK1 was highly positive in advanced adenomas than low risk adenomas (49.6% vs. 29.3%; p<0.01).

Conclusion: The expression of DCLK1 was found in low-grade adenomas and increased with worsening severity of dysplasia. DCLK1 expression was highly observed in advanced adenomas, which had a clinically higher malignant potential.
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http://dx.doi.org/10.21873/invivo.11247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905207PMC
August 2018

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

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

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

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

Results of a 36-year surveillance program for ulcerative colitis-associated neoplasia in the Japanese population.

Dig Endosc 2018 Mar 2;30(2):236-244. Epub 2017 Nov 2.

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

Background And Aim: Surveillance colonoscopy has been carried out for patients with long-standing ulcerative colitis who have an increased risk for colorectal cancer. The aim of the present study was to determine the incidence of and the risk factors for neoplasia.

Methods: We evaluated 289 ulcerative colitis patients who underwent surveillance colonoscopy between January1979 and December 2014. Cumulative incidence of neoplasia and its risk factors were investigated. Clinical stage and overall survival were compared between the surveillance and non-surveillance groups.

Results: Cumulative risk of dysplasia was 3.3%, 12.1%, 21.8%, and 29.1% at 10, 20, 30 and 40 years after the onset of ulcerative colitis, respectively. Cumulative risk of colorectal cancer was 0.7%, 3.2%, 5.2%, and 5.2% at 10, 20, 30 and 40 years from the onset of ulcerative colitis, respectively. Total colitis was a risk factor for neoplasia (P = 0.015; hazard ratio, 2.96).

Conclusions: Our surveillance colonoscopy program revealed the incidence and risk factors of ulcerative colitis-associated neoplasias in the Japanese population. Total colitis is a risk factor for neoplasia.
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http://dx.doi.org/10.1111/den.12955DOI Listing
March 2018

Predictive model for high-frequency microsatellite instability in colorectal cancer patients over 50 years of age.

Cancer Med 2017 Jun 23;6(6):1255-1263. Epub 2017 May 23.

Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.

Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high-frequency MSI (MSI-H). The created prediction model was validated in an external cohort (n = 992). The frequency of MSI-H was 5.5% among CRC patients aged ≥ 50 years. The following five predictors of MSI-H were identified in the test cohort: female (1 point), mucinous component (2 points), tumor size ≥ 60 mm (2 points), location in proximal colon (3 points), and BRAF mutation (6 points). The area under curve (AUC) in the receiver-operating characteristic (ROC) analysis of this prediction model was 0.832 (95% confidence interval: 0.790-0.874). The sensitivity and specificity were 74.4% and 77.7%, respectively, for a cut-off score of 4 points. The receiver-operating characteristic curve of the validation cohort also showed an AUC of 0.856 (95% CI: 0.806-0.905). This prediction model is useful to select elderly CRC patients who should undergo MSI testing, and who may benefit from treatment with 5-FU-based adjuvant chemotherapy and cancer immunotherapy.
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http://dx.doi.org/10.1002/cam4.1088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463087PMC
June 2017

Expression of the stem cell marker CD133 is related to tumor development in colorectal carcinogenesis.

Asian J Surg 2018 May 10;41(3):274-278. Epub 2017 Feb 10.

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

Background/objective: CD133 is currently considered the most robust surface marker for colorectal cancer stem cells. Two meta-analysis reports have suggested that CD133 expression is significantly associated with shorter survival, and CD133 may play an important role in the progression of colorectal cancer. However, the role of CD133 in colorectal adenoma has not been fully elucidated.

Methods: We used immunohistochemistry to evaluate CD133 expression in 200 endoscopically resected colorectal polyps from 200 patients and 20 normal mucosae between January 1993 and December 1996.

Results: CD133 staining was positive in 17.9% of the colorectal adenomas. Moreover, CD133 expression was associated with differentiation status (p = 0.003) and tumor size (p = 0.03).

Conclusion: CD133 might play an important role in tumor development.
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http://dx.doi.org/10.1016/j.asjsur.2016.12.002DOI Listing
May 2018

[Case of Laparoscopic Sigmoidectomy for a Patient with Persistent Descending Mesocolon].

Gan To Kagaku Ryoho 2016 Nov;43(12):1806-1808

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

A 65-year-old man with bloody stools was diagnosed with sigmoid colon cancer on colonoscopy. A preoperative barium enema and a computed tomography colonography scan showed a medial displacement of his descending colon. The preoperative clinical diagnosis was stage cT1 colon cancer, N0, M0, cStage I . Laparoscopic sigmoidectomy was performed. We found adhesions between the descending colon mesentery and the pelvic wall, and noted that the descending colon was not fused with the retroperitoneum and was shifted to the midline. The patient was diagnosed with persistent descending mesocolon (PDM). PDM is a congenital anomaly of fixation resulting from the failure of the descending colon mesentery to fuse with the parietal peritoneum. Anatomical findings should have been noted during the operation, including the fact that the descending colon artery, sigmoid colon artery, and superior rectal artery often branch radially from the inferior mesenteric artery. It is important to understand the anatomical characteristics of PDM and to improve on existing surgical procedures to ensure safe laparoscopic surgery for these patients.
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November 2016

[Three Successful TUR Treatments of Urinary Bladder Recurrence of Colorectal Carcinoma].

Gan To Kagaku Ryoho 2016 Nov;43(12):1638-1640

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

We analyzed whether TUR was feasible in 4 cases of urinary bladder recurrence of sigmoid colon cancer that invaded into the bladder. Case No. 1 involved a 66-year-old male who presented with sigmoid colon cancer that had invaded the urinary bladder; he underwent sigmoidectomy with partial bladder resection. Six months after the operation, a small, protruded lesion in his urinary bladder was detected and TUR was performed. He has been cancer free for 10 years. Case No. 2 involved a 53- year-old female who underwent sigmoidectomy and hepatectomy for her sigmoid colon cancer and liver metastasis. She developed bladder and liver metastases, which were resected. Four months later, she underwent TUR because she developed a small recurrent tumor in the bladder. Since then, she has had no intrapelvic recurrence for 6 years. Case No. 3 was a 44- year-old male who underwent bladder-preserving resection for a sigmoid colon cancer that had invaded his bladder. He developed a relatively large bladder tumor 1 year 6 months later. TUR was performed and he was administered CRT. He has had no recurrences for 2 years 5 months. Case No. 4 was a 68-year-old male who underwent bladder-preserving surgery for a sigmoid colon cancer that had invaded his bladder. Because he developed a recurrence in the bladder, he underwent TUR 3 months later. He developed a recurrence in the bladder again 1 year 7 months later, and he underwent TUR again. Multiple organ metastases became evident and was prescribed chemotherapy for 2 years. From these cases, we conclude that TUR may be a feasible option for small, protruded recurrences in the bladder, but we should not hesitate to perform total cystectomy if the first TUR is unsuccessful.
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November 2016

Clinical significance of mucinous components in rectal cancer after preoperative chemoradiotherapy.

Surg Today 2017 Jun 22;47(6):697-704. Epub 2016 Sep 22.

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

Purpose: The clinical implications of mucinous components in rectal tumors, especially with regard to the efficacy of neoadjuvant chemoradiotherapy, remain unclear.

Methods: One hundred and thirty rectal cancer patients who received curative resection after neoadjuvant chemoradiotherapy were retrospectively reviewed. Patients were classified into 3 groups according to the proportion of extracellular mucin: low (<5 %), moderate (5-25 %), and high (>25 %).

Results: There were 82 (63.1 %), 26 (20.0 %), and 22 (16.9 %) patients in the low, moderate, and high mucin groups, respectively. Patients with a high mucinous tumor component were significantly more likely to have an advanced tumor stage (p = 0.010) and a shorter disease-free (p = 0.002) and distant recurrence-free survivals (p < 0.001), whereas the mucinous tumor component showed no correlation with local recurrence (p = 0.101). A high mucinous component was also an independent predictive factor for a shorter disease-free survival (p = 0.041, hazard ratio = 2.56) and distant recurrence-free survival (p = 0.001, hazard ratio = 5.74) according to a multivariate analysis.

Conclusions: Because the mucinous components showed little correlation with local recurrence, mucinous cancer should not be a determining factor for chemoradiotherapy. However, the frequent occurrence of metachronous distant metastasis among patients with a high mucin component makes this a possible indicator for more robust postoperative adjuvant treatment and close surveillance of recurrence.
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http://dx.doi.org/10.1007/s00595-016-1419-0DOI Listing
June 2017

Oncological benefit of lateral pelvic lymph node dissection for rectal cancer treated without preoperative chemoradiotherapy: a multicenter retrospective study using propensity score analysis.

Int J Colorectal Dis 2016 Jul 30;31(7):1315-21. Epub 2016 May 30.

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

Purpose: We aimed to clarify the prognostic impact of lateral pelvic lymph node (LPN) dissection (LPND) for rectal cancer through a multicenter retrospective study using propensity score analysis.

Methods: A total of 1238 patients with pathological T2-4, M0 rectal cancer who had undergone curative operation between 2007 and 2008 were examined. Majority of the patients (96 %) were treated without preoperative chemoradiotherapy (CRT). Clinical background data of the patients treated with LPND and those treated without LPND were matched using propensity scores, and hazard ratios (HRs) for cancer-specific mortality were compared.

Results: LPND was performed more frequently for lower rectal cancers and in patients with more advanced disease, and 29 % of the patients were treated with LPND. After matching background features by propensity scores, LPND did not correlate with improved cancer-specific survival (CSS) among the entire study population [HR, 0.73; 95 % confidence interval (CI) 0.41-1.31; P = 0.28]; however, LPND was correlated with significantly improved CSS in female patients (HR, 0.23; 95 % CI, 0.06-0.89; P = 0.04) but not in male patients (HR, 0.95; 95 % CI, 0.48-1.89; P = 0.89). The results were similar when patients treated with LPND finally diagnosed as pathologically negative for LPN metastasis were compared with those curatively treated without LPND.

Conclusions: It is suggested that the prognostic impact of LPND for rectal cancer treated without CRT might be different between sexes, and LPND should be considered for female rectal cancer patients although they are diagnosed as clinically negative for LPN metastasis.
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http://dx.doi.org/10.1007/s00384-016-2607-5DOI Listing
July 2016

Usefulness of preoperative CT colonography for colon cancer.

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

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

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

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

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

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

Colonic perforation in a patient with systemic lupus erythematosus accompanied by cytomegalovirus infection: A case report.

Int J Surg Case Rep 2016 11;23:70-3. Epub 2016 Apr 11.

Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address:

Introduction: Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection.

Presentation Of Case: The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days. She additionally manifested vomiting, high fever, and right abdominal pain within two weeks thereafter, and was diagnosed with perforation of the intestine. Emergency operation was carried out for panperitonitis due to perforation of one of the multiple colon ulcers. Multidisciplinary postoperative treatment could not save her life. Pathological examination suggested that cytomegalovirus infection as well as cholesterin embolization contributed to the rapid progression of colitis.

Discussion: There have been only a limited number of case reports of CMV enteritis in SLE. Moreover, only two SLE patients on multiple medications have been reported to experience gastrointestinal perforation. Viral infections, including CMV, can induce clinical manifestations resembling SLE and for this reason we suspect that there are potentially many more patients misdiagnosed and/or unreported.

Conclusion: Our case underscores the importance of exploring the possibility of CMV infection as a differential diagnosis in SLE patients with obvious gastrointestinal symptoms who were treated by immunosuppressive drugs.
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http://dx.doi.org/10.1016/j.ijscr.2016.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855785PMC
June 2016

A case of disseminated carcinomatosis of the bone marrow originating from gastric cancer 3 years after intraperitoneal chemotherapy against peritoneal carcinomatosis.

World J Surg Oncol 2016 Apr 14;14:107. Epub 2016 Apr 14.

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

Background: Clinical studies of intraperitoneal chemotherapy with paclitaxel in patients of gastric cancer with peritoneal carcinomatosis is well tolerated and effective, and rare cases of metastasis and recurrence have experienced during the treatment. Disseminated carcinomatosis of the bone marrow is highly rare in gastric cancer and associated with a poor prognosis.

Case Presentation: A 59-year-old woman of gastric cancer with peritoneal carcinomatosis received five courses of chemotherapy with intraperitoneal administration of paclitaxel, and laparoscopy showed disappearance of the peritoneal carcinomatosis. She subsequently underwent total gastrectomy, and the histopathological findings showed a complete response to the chemotherapy. Postoperatively, chemotherapy with intraperitoneal administration of paclitaxel was continued for 30 months, without apparent recurrence. However, the gastric cancer recurred as disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation, and we hence changed the chemotherapy regimen to weekly irinotecan. Remission was achieved, and she did not experience any major symptoms; however, she died 6 months after the diagnosis of disseminated carcinomatosis of the bone marrow.

Conclusions: Since intraperitoneal paclitaxel administration can strongly suppress peritoneal carcinomatosis of gastric cancer, careful attention should be paid not only to peritoneal recurrence but also for rare site metastases, such as bone marrow metastases.
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http://dx.doi.org/10.1186/s12957-016-0851-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831094PMC
April 2016

Effect of nutrient starvation on proliferation and cytokine secretion of peripheral blood lymphocytes.

Mol Clin Oncol 2016 Apr 3;4(4):607-610. Epub 2016 Feb 3.

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

Proliferating cancer cells are exposed to nutrient deprivation. Numerous previous studies have demonstrated how nutrient deprivation affects cancer cells; however, immune cells exposed to the identical conditions have not been completely examined. Furthermore, T-helper 2 lymphocyte predominance in certain neoplastic diseases has been reported; however, the mechanism remains unclear. The present study aimed to confirm whether nutrient deprivation affected proliferation and cytokine secretion of peripheral blood lymphocytes (PBLs). The proliferation of PBLs from healthy donors, cultured in a medium containing various glucose levels, was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. The expression levels of interleukin (IL)-4 and interferon (IFN)-γ among CD4(+) T cells, cultured with or without glucose and activated with phorbol 12-myristate 13-acetate and ionomycin, were examined using an intracellular cytokine staining method. The proliferation of PBLs cultured in a medium containing <100 mg/dl glucose of the standard blood sugar (BS) level was significantly reduced compared with the proliferation observed in a medium containing a standard BS level or higher. PBLs cultured in a glucose-free medium contained a significantly higher percentage of IL-4-positive and a lower percentage of IFN-γ-positive CD4(+) T cells compared with those cultured in a high-glucose medium. Nutrient deprivation suppressed the proliferation of PBLs, fostered the secretion of IL-4 and reduced secretion of IFN-γ. It is therefore possible that glucose-deficient microenvironments in local cancer tissues cause a partial immunodeficiency, which is advantageous to cancer growth.
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http://dx.doi.org/10.3892/mco.2016.763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812150PMC
April 2016

Prognostic impact of lymph node dissection is different for male and female colon cancer patients: a propensity score analysis in a multicenter retrospective study.

Int J Colorectal Dis 2016 Jun 29;31(6):1149-55. Epub 2016 Mar 29.

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

Purpose: Colon cancers in male and female patients are suggested to be oncologically different. The aim of this study is to elucidate the prognostic impact of lymph node dissection (LND) in male and female colon cancer patients.

Methods: A total of 5941 stage I-III colon cancer patients who were curatively operated on during the period from 1997 to 2007 were retrospectively studied. Cancer-specific survival (CSS) was individually compared between for male and female patients treated with D3, D2, and D1 LND. Background differences of the patients were matched using propensity scores.

Results: D3, D2, and D1 LND were performed in 3756 (63 %), 1707 (29 %), and 478 (8 %), respectively, and more extensive LND was indicated for younger patients and more advanced disease. D2 LND was significantly associated with decreased cancer-specific mortality compared to D1 LND in male patients (HR 0.54, 95 % CI 0.32-0.89, p = 0.04), but not in female patients. D3 LND did not correlate to an improved prognosis compared to D2 LND both in male and female patients.

Conclusions: D2 LND was associated with an improved CSS in male, but not female colon cancer patients, compared to D1 LND. This suggested that colon cancer in male and female patients might be oncologically different, and that the prognostic impact of the extent of surgical intervention for colon cancer might therefore be different between sexes.
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http://dx.doi.org/10.1007/s00384-016-2558-xDOI Listing
June 2016

Small bowel adenocarcinoma arising in a patient with hereditary hemorrhagic telangiectasia: A case report.

Oncol Lett 2016 Mar 1;11(3):2137-2139. Epub 2016 Feb 1.

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

Patients with hereditary hemorrhagic telangiectasia (HHT) are reportedly at a lower overall risk of malignancies, and small bowel adenocarcinoma (SBA) arising in a HHT patient is extremely rare. In this study, the case of a 37-year-old female with HHT who developed a poorly differentiated jejunal adenocarcinoma five years after ileocecal resection for multiple colonic adenomas is presented. The patient underwent curative resection of the cancer invading the ileum and the mesentery of the transverse colon, but had to overcome critical complications perioperatively, stemming from HHT-associated peripheral capillary dilatation and arteriovenous malformation, including nosebleeds and possible infusion-induced air embolism through pulmonary shunts. The patient subsequently received adjuvant chemotherapy including capecitabine and oxaliplatin for 6 months, and currently remains alive without any evidence of recurrence 12 months after the second surgery. This patient with SBA was an instructive case demonstrating the necessity of careful attention during major surgery in HHT.
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http://dx.doi.org/10.3892/ol.2016.4173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774470PMC
March 2016

Incidence of neoplasias and effectiveness of postoperative surveillance endoscopy for patients with ulcerative colitis: comparison of ileorectal anastomosis and ileal pouch-anal anastomosis.

World J Surg Oncol 2016 Mar 9;14:75. Epub 2016 Mar 9.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.

Background: The incidence of neoplasia after surgery has not been sufficiently evaluated in patients with ulcerative colitis (UC), particularly in the Japanese population, and it is not clear whether surveillance endoscopy is effective in detecting dysplasia/cancer in the remnant rectum or pouch. The aims of this study were to assess and compare postoperative development of dysplasia/cancer in patients with UC who underwent ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA) and to evaluate the effectiveness of postoperative surveillance endoscopy.

Methods: One hundred twenty patients who received postoperative surveillance endoscopy were retrospectively reviewed for development of dysplasia/cancer in the remnant rectal mucosa or pouch.

Results: Three hundred seventy-nine endoscopy sessions were conducted for 30 patients after IRA, while 548 pouch endoscopy sessions were conducted for 90 patients after IPAA. In the IRA group, 5 patients developed dysplasia/cancer during postoperative surveillance and in all cases, neoplasia was detected at an early stage. In the IRA group, no patient developed neoplasia within 10 years of diagnosis; the cumulative incidence of neoplasia after disease onset was 7.2, 12.0, and 23.9% at 15, 20, and 25 years, respectively. In one case after stapled IPAA, dysplasia was found at the ileal pouch; a subsequent 9 endoscopy sessions in 8 years did not detect any dysplasia. Neoplasia was found more frequently during postoperative surveillance in the IRA group than in the IPAA group (p = .0028). The cumulative incidence of neoplasia after IRA was 3.8, 8.7, and 21.7% at 10, 15, and 20 years, respectively, and that after IPAA was 1.6% at 20 years.

Conclusions: The cumulative incidence of neoplasia after IPAA was minimal. Those who underwent IRA had a greater risk of developing neoplasia than those who underwent IPAA, although postoperative surveillance endoscopy was able to detect dysplasia/cancer at an early stage. IRA can be the surgical procedure of choice only in selected cases in which it would be of benefit to the patient, with more careful surveillance.
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http://dx.doi.org/10.1186/s12957-016-0833-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784460PMC
March 2016

A giant mucinous cystadenocarcinoma of the appendix: a case report and review of the literature.

World J Surg Oncol 2016 Mar 5;14:64. Epub 2016 Mar 5.

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

Background: Mucinous cystadenocarcinoma is the second most common etiology of appendiceal mucocele. We report a relatively rare case of a giant appendiceal mucocele caused by mucinous cystadenocarcinoma, which occupied the entire abdomen of an adult woman.

Case Presentation: A 63-year-old woman presented with a chief complaint of abdominal distention. Imaging studies showed a giant cystic mass occupying her entire abdomen. Laparotomy confirmed a giant appendiceal mucocele, and the patient underwent ileocecal resection. A mucinous deposit was not found in her abdominal cavity, and the ovaries were grossly normal bilaterally. The pathological diagnosis was mucinous adenocarcinoma with a low-grade mucinous neoplasm that invaded the subserosa. Regional lymph node metastasis was not found. She has had recurrence-free survival for 5 years.

Conclusions: The present case is the largest appendiceal cystadenocarcinoma ever reported. The optimal treatment of an appendiceal neoplasm requires further research based on consensus terminology of an appendiceal mucocele.
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http://dx.doi.org/10.1186/s12957-016-0828-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779566PMC
March 2016

Clinical Characteristics and Postoperative Complications of Patients Undergoing Emergency Surgery for Ulcerative Colitis.

Hepatogastroenterology 2015 Jun;62(140):853-8

Background/aims: Despite recent advances in medical therapy, the role of surgery for severe ulcerative colitis remains important and determining the timing and indications for colectomy are difficult for both gastroenterologists and surgeons. We compared the clinical characteristics and postoperative complications of emergency surgeries for ulcerative colitis to those of elective surgeries.

Methodology: We retrospectively examined 77 patients with ulcerative colitis who underwent colectomy without cancer or dysplasia in our institute in 1989-2012. Clinicopathological features, cytomegalovirus involvement, and postoperative complications were evaluated.

Results: Twenty-seven patients underwent emergency surgeries and the other 50 underwent elective surgeries. Emergency surgeries were performed significantly earlier in the disease course than elective surgeries. Postoperative complications were more frequent in emergency surgeries than in elective surgeries. Those who underwent emergency surgeries with relative indications tended to develop postoperative complications more frequently when intensive long-term steroid therapy was introduced.

Conclusions: Emergency surgeries were associated with frequent postoperative complications. For refractory severe ulcerative colitis, cytomegalovirus involvement should be determined and prolonged steroid therapy is associated with postoperative complications; therefore, early treatment decisions are important.
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June 2015

CD133 Expression at the Metastatic Site Predicts Patients' Outcome in Colorectal Cancer with Synchronous Liver Metastasis.

Ann Surg Oncol 2016 06 29;23(6):1916-23. Epub 2016 Jan 29.

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

Background: CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods: CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results: CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133- patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions: Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133- patients had a significantly higher rate of extrahepatic recurrence.
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http://dx.doi.org/10.1245/s10434-016-5099-1DOI Listing
June 2016

[Recurrence of Rectal Cancer with Submucosal Invasion in the Bone and Lymph Nodes 89 Months after Surgery--A Case Report].

Gan To Kagaku Ryoho 2015 Nov;42(12):2288-90

Dept. of Gastroenterological Surgery, Saitama Cancer Center.

A woman in her 60s showed positive results on a fecal occult blood test and consulted her doctor. Early-stage cancer of the lower rectum was diagnosed, and a transanal local excision was performed. Histopathological examination revealed that the depth of submucosal invasion was ≧1,000 mm, and the submucosal invasive part of the tumor was a poorly differentiated adenocarcinoma. Therefore, she was referred to our hospital for additional resection. Intersphincteric resection was performed 11 months after the initial operation. The cancer stage was T1N0M0, Stage Ⅰ(UICC 7th edition), and the cancer did not recur. The patient visited our hospital again, 78 months after the additional resection, because of left hip-joint pain. Positron-emission tomography revealed fluorodeoxyglucose uptake in the left acetabulum, para-aortic lymph nodes, and left external iliac lymph nodes; these findings indicated recurrence of the rectal cancer. The patient received radiation therapy (57 Gy) and FOLFIRI; bevacizumab was added from the third course onward. The therapy reduced the size of the tumor recurrence in the bone. This was a rare case of rectal cancer with submucosal invasion that showed recurrence in the bone and lymph nodes 78 months after the additional resection.
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November 2015

A patient with gastric cancer with peritoneal carcinomatosis treated with intraperitoneal chemotherapy who survived more than 5 years receiving repeated laparoscopic examinations: a case report.

J Med Case Rep 2016 Jan 19;10:14. Epub 2016 Jan 19.

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

Background: Peritoneal dissemination of gastric cancer is still a dismal disease and has extremely poor prognosis even with systemic intensive chemotherapy. However, intraperitoneal chemotherapy using paclitaxel has recently shown good results. In order to perform optimal intraperitoneal chemotherapy, laparoscopic examination is necessary to assess the condition of peritoneal disseminated lesions. This is the first report of a case of a patient with gastric cancer with massive peritoneal metastasis treated with intraperitoneal administration of paclitaxel and repeated laparoscopic examinations who survived more than 5 years.

Case Presentation: Here we report a case of a 60-year-old Japanese woman with peritoneal carcinomatosis of gastric cancer who underwent intraperitoneal chemotherapy receiving repeated laparoscopic examinations. The patient was referred to our institution for the treatment of peritoneal carcinomatosis of gastric cancer. The staging laparoscopy showed peritoneal metastasis in the whole peritoneal space with a peritoneal cancer index score of 23. An intraperitoneal access port was subcutaneously implanted. Paclitaxel was intraperitoneally and intravenously administered with oral administration of S-1. The second-look laparoscopy, which was performed after nine courses of intraperitoneal chemotherapy, revealed the disappearance of peritoneal carcinomatosis. A total gastrectomy with D2 lymphadenectomy was performed and intraperitoneal chemotherapy was continued after the surgery. The third laparoscopic examination, which was performed after 67 courses of intraperitoneal chemotherapy showed bilateral ovarian metastasis without recurrence of peritoneal carcinomatosis. Since multiple bone metastases developed after the third-look laparoscopy, bilateral adnexectomy was not performed and the chemotherapy was changed to the regimen including CPT-11. Our patient survived more than 5 years since the intraperitoneal chemotherapy started.

Conclusions: Sequential intraperitoneal chemotherapy could strongly suppress the development of peritoneal metastasis for several years. Repeated laparoscopic examinations are considered to be essential to evaluate the efficacy of intraperitoneal chemotherapy on peritoneal carcinomatosis of gastric cancer.
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http://dx.doi.org/10.1186/s13256-016-0799-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719221PMC
January 2016

Hereditary gastrointestinal cancer.

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

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

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