Koji Komori - Academia.edu (original) (raw)
Papers by Koji Komori
Cancers
The current standard of care for patients with locally advanced rectal cancer (LARC) is neoadjuva... more The current standard of care for patients with locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision surgery. However, the response to nCRT varies among patients and only about 20% of LARC patients achieve a pathologic complete response (pCR) at the time of surgery. Therefore, there is an unmet need for biomarkers that could predict the response to nCRT at an early time point, allowing for the selection of LARC patients who would or would not benefit from nCRT. To identify blood-based biomarkers for prediction of nCRT response, we performed in-depth quantitative proteomic analysis of pretreatment plasma from mice bearing rectal tumors treated with concurrent chemoradiation, resulting in the quantification of 567 proteins. Among the plasma proteins that increased in mice with residual rectal tumor after chemoradiation compared to mice that achieved regression, we selected three proteins (Vascular endothelial growth factor rec...
Nagoya Journal of Medical Science, 2019
We report a case of ileal conduit necrosis after total pelvic exenteration for recurrence of gast... more We report a case of ileal conduit necrosis after total pelvic exenteration for recurrence of gastrointestinal stromal tumor. A 47-year-old man was diagnosed with recurrence of gastrointestinal stromal tumor adjacent to the prostate after abdominoperineal resection 10 years prior. With imatinib administration for 18 months, the local recurrence decreased in size but did not separate from the prostate. We performed urinary diversion with conventional total pelvic exenteration. Ileal conduit necrosis was suspected the following day and emergency surgery was performed. The serosa of the ileal conduit showed segmental necrosis extending about 10 cm from the orifice. The ureterointestinal anastomotic site was opposite the orifice and was not necrotic. We resected the necrotic ileum and reconstructed an ileal conduit. The patient was discharged without any symptoms 46 days after surgery for further adjustment to use of a urostomy.
We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection ... more We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection for peritoneal recurrences. A 58-year-old woman was diagnosed with descending colon cancer. Resection of the descending colon along with lymph node dissection was performed in September 2006. The pathological findings revealed Stage IIA colorectal cancer. The following peritoneal recurrences were removed: two in July 2007, two in the omental fat and two in the pouch of Douglas in June 2008 resected by low anterior resection of the rectum, one in the uterus and right ovarian recurrence resected via bilateral adnexectomy and Hartmann’s procedure in May 2011, and one in the ascending colon by partial resection of the colon wall in December 2011. Postoperative adjuvant chemotherapy (uracil and tegafur/leucovorin, fluorouracil/levofolinate/oxaliplatin/bevacizumab, 5-fluorouracil/leucovorin/bevacizumab, irinotecan/bevacizumab, and irinotecan/panitumumab) was administered. The patient did not d...
From the Dep Data Cen zColorect §Departm Chiba, Jap Japan; jjD Departm cular Dis University Okaya... more From the Dep Data Cen zColorect §Departm Chiba, Jap Japan; jjD Departm cular Dis University Okayama Surgery, Surgery, K Ishikawa Surgery, T Surgery, S Kurume U Gastroente Depa Japan; jj Japan This study wa Developm Research Grants fo Research Health and the Minis The authors r This is an open Attributio where it is cited. The permissio Reprints: Shin Yohnan, U Copyright 2 ISSN: 0003-4 DOI: 10.1097
Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since lundi ... more Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since lundi 4 avril 2016
The relative risk of cancer recurrence with postoperative adjuvant FOLFOX/CapeOX therapy(Ox)for s... more The relative risk of cancer recurrence with postoperative adjuvant FOLFOX/CapeOX therapy(Ox)for stage III colorectal cancer is reduced by approximately 20%when compared to that with fluorouracil plus Leucovorin. We performed a questionnaire survey to evaluate the quality of life(QOL)and extent of side effects in patients who received adjuvant chemotherapy. In order to evaluate the risks and benefits of oxaliplatin administration, we also examined the differences in awareness of oxaliplatin side effects between patients and medical staff. Responses were obtained from 147 patients, 54 doctors, and 84 nurses. Analysis of the patient responses showed higher current QOL scores regardless of the chemotherapy regimen, although patients in the Ox group had a high rate of residual sensory peripheral neuropathy. In the Ox group, 81% of patients responded that the side effects were moderate. In contrast, 40% of medical staff identified the side effects of oxaliplatin as severe, which differed ...
Clinical Journal of Gastroenterology
We describe a case of repair of the antegrade anastomosis between the “ileal segment” and amputat... more We describe a case of repair of the antegrade anastomosis between the “ileal segment” and amputated ureter for recurrent rectal cancer, in which some postoperative complications occurred but eventually resolved. If the length of the ureter is inadequate for end-to-end anastomosis, an ileal segment can be used as a conduit. This surgical technique is not difficult because an ileal conduit is typically created during total pelvic exenteration of rectal cancers. Therefore, anastomosing the ureter to an “ileal segment” is easy and feasible. Hence, we consider that knowledge of this technique would be beneficial for surgical oncologists who perform colorectal surgeries.
Journal of Clinical Oncology
PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorec... more PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because...
International Journal of Clinical Oncology
Background Different genetic characteristics according to tumor location result in variations in ... more Background Different genetic characteristics according to tumor location result in variations in survival rates and treatment responses in advanced colorectal cancer (CRC). However, the effects of tumor location during early CRC are still unclear. Methods Patients with T1 CRC treated between 2003 and 2019 were enrolled from a prospectively collected database. Patients were once divided into four groups, then combined into two groups (right-and left-sided CRC) according to the tumor location, and clinical features and oncologic behaviors were compared. Results In total, 458 patients were analyzed. Right-sided CRC had a lower incidence of polypoid type tumor than left-sided CRC (36/126 (28.6%) vs 186/332 (56.0%), p < 0.001). There were no differences in tumor size, pathological grade, pT1 substage and lymphovascular invasion between right-and left-sided CRC. Overall, lymph nodal involvement was observed in 42/458 (9.1%) patients. Right-sided CRC had a lower rate of patients with lymph nodal involvement than left-sided CRC (6/126 (4.8%) vs 36/332 (10.8%), p = 0.04). Conclusion The present study revealed that there were significant differences in the macroscopic type and the incidence of lymph node involvement between right-and left-sided CRC. The clinical features and oncologic behaviors of T1 CRC are possible to vary according to tumor location.
Journal of Clinical Oncology
7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy... more 7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy (CTX) improves overall survival (OS) of colorectal cancer (CRC) patients (pts) with synchronous unresectable metastases. There are several retrospective analyses suggesting better outcomes in pts who underwent PTR compared to pts without it, but no prospective studies confirming these results. We conducted a randomized controlled trial to confirm the superiority of PTR plus CTX to CTX alone in asymptomatic unresectable stage IV CRC patients. Methods: Eligibility criteria included histologically proven colon and upper rectal adenocarcinoma, cT1-4 without involvement of other organs, presence of three or less unresectable factors confined to either liver, lungs, distant lymph nodes, or peritoneum, aged 20-74, no symptoms due to primary tumor and PS 0-1. Eligible patients were randomized to either PTR followed by CTX or CTX alone. CTX regimens were declared before study entry; options incl...
Journal of Clinical Oncology
3617Background: Efficacy of adjuvant chemotherapy in stage II colon cancer patients is still cont... more 3617Background: Efficacy of adjuvant chemotherapy in stage II colon cancer patients is still controversial. The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer in a large population. Methods: 20-80 aged patients with curatively resected stage II colon cancer were randomly assigned to the surgery alone group or UFT group (UFT at 500-600 mg/day as tegafur in 2 divided doses for 5 days, followed by 2-day rest, then repeated for 1 year). Primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), recurrence-free survival (RFS), and safety. Sample size was 2000 determined with an assumed hazard ratio (HR) 0.729, respectively, a two-sided significance level of 5%, and a power of 90%. Results: A total of 1982 patients (997 in the surgery alone group and 985 in the UFT group) were included in the efficacy analysis. Median follow-up was 69.5 months, the ...
Biochemical and Biophysical Research Communications
The disruption of intestinal mucosal immune tolerance can lead to the development of intestinal i... more The disruption of intestinal mucosal immune tolerance can lead to the development of intestinal immune diseases such as food allergy (FA). Regulatory T cells (Tregs) in the mucosa play a critical role in maintaining peripheral immune tolerance in the intestine, and retinoic acid (RA) is absolutely required for the induction of Tregs. We have previously reported that kakkonto, a traditional Japanese herbal medicine, suppresses FA in a murine FA model due to the induction of Tregs in the colonic mucosa. However, the precise molecular mechanisms underlying the induction of Tregs remain unclear. Puerarin, an isoflavone derivative, is a major constituent of kakkonto. Thus, we investigated the effect of puerarin on the induction of Tregs. BALB/c mice were systemically sensitized and then orally challenged with ovalbumin (OVA) as an FA model. Puerarin treatment suppressed the development of allergic diarrhea in FA mice. The gene expression levels of IL-4 and mast cell protease I (mMCP-1) were significantly upregulated in the proximal colon of FA mice but were reduced by puerarin. The proportions of Foxp3+CD4+ cells and CD103+CD11c+ dendritic cells (DCs) were significantly higher among the colonic lamina propria (cLP) cells of puerarin-treated FA mice than among those of untreated FA mice. The gene expression of Aldh1a1, an RA synthesis enzyme, in colonic epithelial cells (CECs) was significantly higher in the puerarin-treated FA mouse colon than in the untreated FA mouse colon. In addition, the preventive effect of puerarin was suppressed in the FA model by pretreatment with LE540, an RA receptor (RAR) antagonist. The induction of Foxp3+CD4+ cells and CD103+CD11c+ DCs by puerarin was reduced by pretreatment with LE540. The present findings indicate that the augmentation of RA production in CECs induced by puerarin enhances the induction of Tregs and suppresses the development of FA in a mouse model. Thus, a natural enhancer of RA production, such as puerarin, has the potential to treat immune diseases attributed to Treg deficiency.
Journal of Clinical Oncology
3515 Background: The no-touch isolation technique (NTIT) aims to reduce cancer cells flowing from... more 3515 Background: The no-touch isolation technique (NTIT) aims to reduce cancer cells flowing from the primary tumor site to the liver and other organs by first ligation of blood vessels that feed the primary tumor. The efficacy of NTIT has not been proved in previous studies. To acquire the answer of an unsolved problem more than 60 years, we conducted a phase III trial to confirm the superiority of NTIT in patients with cT3/T4 colon cancer. This is the primary analysis of the disease-free survival (DFS) as the primary endpoint. Methods: Eligibility criteria included histologically proven colon cancer; tumor located in the cecum, ascending, transverse, descending, sigmoid or rectosigmoid colon; clinical T3 or T4, N0-2, M0; patients age 20-80 years. Patients were randomized preoperatively to either conventional technique (CoT) arm or NTIT arm. Operation was performed in open surgery. Patients with pathological stage III received adjuvant chemotherapy with capecitabine. The primary en...
Surgery Today
Purpose This study aimed to clarify the prognosis of patients after resection of stage IV colorec... more Purpose This study aimed to clarify the prognosis of patients after resection of stage IV colorectal cancer and synchronous peritoneal metastasis (no residual disease: R0 status) based on histopathologic findings. Methods The subjects of this study were 26 patients who underwent radical resection of synchronous peritoneal metastases of stage IV colorectal cancer. Only patients with one synchronous peritoneal metastasis were included in this study. The peritoneal lesions were initially classified into two categories based on the presence or absence of adenocarcinoma on their surface: RM-negative or RM-positive. The lesions were subsequently classified as being of massive or diffuse type and of small (< 6 mm) or large (≥ 6 mm) type according to the maximum metastatic tumor dimension. Results Multivariate analysis revealed that massive type metastatic tumors were associated with a better disease-free survival (DFS; p = 0.047) and overall survival (OS; p = 0.033), than diffuse type tumors. Conclusion A detailed stratification of pathological findings could contribute remarkably to prognostic predictions for patients with synchronous peritoneal metastases.
Diseases of the Colon & Rectum
638 DISEASES OF THE COLON & RECTUM VOLUME 62: 5 (2019) It is thought that achieving complete ... more 638 DISEASES OF THE COLON & RECTUM VOLUME 62: 5 (2019) It is thought that achieving complete mesocolic excision and central vascular ligation improves the prognosis of patients undergoing right-side colon cancer surgery. In the middle colic artery (MCA) areas, the lymph nodes are distributed around the superior mesenteric vein (SMV) and the superior mesenteric artery (SMA); thus, identifying the anatomical location of the SMA and the MCA is an essential procedure for performing radical lymph node dissection. We present our procedure for radical lymph node dissection along the SMA using a multidirectional approach. The procedure is started with a posterior approach. The mesentery is divided from the retroperitoneal organs. An anterior approach is used in the second step. The anterior approach is divided into the distal side and the proximal side across the transverse colon mesentery. Through a distal anterior approach, the front of the SMV and the SMA are exposed. The left edge of the SMA is set as the landmark of the complete mesocolic excision. A proximal anterior approach is used in the third step. The mesentery of the transverse colon is cut off along the lower edge of the pancreas. The front of the SMV and the SMA are exposed, and the origins of the MVC and the MCA are identified. Finally, the MCV is dissected at the origin and the MCA is dissected with the right branch. We performed laparoscopic right colectomy using this approach for 47 patients with right-side colon cancer. The median number of harvested lymph nodes was 34. No grade ≥3 complications occurred. The median follow-up period was 12 months. Long-term results have not been obtained. In conclusion, the use of a multidirectional approach makes it possible to successfully perform laparoscopic right hemicolectomy with radical lymph node dissection along the SMA. See Video at http://links. lww.com/DCR/A827.
Cancers
The current standard of care for patients with locally advanced rectal cancer (LARC) is neoadjuva... more The current standard of care for patients with locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision surgery. However, the response to nCRT varies among patients and only about 20% of LARC patients achieve a pathologic complete response (pCR) at the time of surgery. Therefore, there is an unmet need for biomarkers that could predict the response to nCRT at an early time point, allowing for the selection of LARC patients who would or would not benefit from nCRT. To identify blood-based biomarkers for prediction of nCRT response, we performed in-depth quantitative proteomic analysis of pretreatment plasma from mice bearing rectal tumors treated with concurrent chemoradiation, resulting in the quantification of 567 proteins. Among the plasma proteins that increased in mice with residual rectal tumor after chemoradiation compared to mice that achieved regression, we selected three proteins (Vascular endothelial growth factor rec...
Nagoya Journal of Medical Science, 2019
We report a case of ileal conduit necrosis after total pelvic exenteration for recurrence of gast... more We report a case of ileal conduit necrosis after total pelvic exenteration for recurrence of gastrointestinal stromal tumor. A 47-year-old man was diagnosed with recurrence of gastrointestinal stromal tumor adjacent to the prostate after abdominoperineal resection 10 years prior. With imatinib administration for 18 months, the local recurrence decreased in size but did not separate from the prostate. We performed urinary diversion with conventional total pelvic exenteration. Ileal conduit necrosis was suspected the following day and emergency surgery was performed. The serosa of the ileal conduit showed segmental necrosis extending about 10 cm from the orifice. The ureterointestinal anastomotic site was opposite the orifice and was not necrotic. We resected the necrotic ileum and reconstructed an ileal conduit. The patient was discharged without any symptoms 46 days after surgery for further adjustment to use of a urostomy.
We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection ... more We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection for peritoneal recurrences. A 58-year-old woman was diagnosed with descending colon cancer. Resection of the descending colon along with lymph node dissection was performed in September 2006. The pathological findings revealed Stage IIA colorectal cancer. The following peritoneal recurrences were removed: two in July 2007, two in the omental fat and two in the pouch of Douglas in June 2008 resected by low anterior resection of the rectum, one in the uterus and right ovarian recurrence resected via bilateral adnexectomy and Hartmann’s procedure in May 2011, and one in the ascending colon by partial resection of the colon wall in December 2011. Postoperative adjuvant chemotherapy (uracil and tegafur/leucovorin, fluorouracil/levofolinate/oxaliplatin/bevacizumab, 5-fluorouracil/leucovorin/bevacizumab, irinotecan/bevacizumab, and irinotecan/panitumumab) was administered. The patient did not d...
From the Dep Data Cen zColorect §Departm Chiba, Jap Japan; jjD Departm cular Dis University Okaya... more From the Dep Data Cen zColorect §Departm Chiba, Jap Japan; jjD Departm cular Dis University Okayama Surgery, Surgery, K Ishikawa Surgery, T Surgery, S Kurume U Gastroente Depa Japan; jj Japan This study wa Developm Research Grants fo Research Health and the Minis The authors r This is an open Attributio where it is cited. The permissio Reprints: Shin Yohnan, U Copyright 2 ISSN: 0003-4 DOI: 10.1097
Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since lundi ... more Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since lundi 4 avril 2016
The relative risk of cancer recurrence with postoperative adjuvant FOLFOX/CapeOX therapy(Ox)for s... more The relative risk of cancer recurrence with postoperative adjuvant FOLFOX/CapeOX therapy(Ox)for stage III colorectal cancer is reduced by approximately 20%when compared to that with fluorouracil plus Leucovorin. We performed a questionnaire survey to evaluate the quality of life(QOL)and extent of side effects in patients who received adjuvant chemotherapy. In order to evaluate the risks and benefits of oxaliplatin administration, we also examined the differences in awareness of oxaliplatin side effects between patients and medical staff. Responses were obtained from 147 patients, 54 doctors, and 84 nurses. Analysis of the patient responses showed higher current QOL scores regardless of the chemotherapy regimen, although patients in the Ox group had a high rate of residual sensory peripheral neuropathy. In the Ox group, 81% of patients responded that the side effects were moderate. In contrast, 40% of medical staff identified the side effects of oxaliplatin as severe, which differed ...
Clinical Journal of Gastroenterology
We describe a case of repair of the antegrade anastomosis between the “ileal segment” and amputat... more We describe a case of repair of the antegrade anastomosis between the “ileal segment” and amputated ureter for recurrent rectal cancer, in which some postoperative complications occurred but eventually resolved. If the length of the ureter is inadequate for end-to-end anastomosis, an ileal segment can be used as a conduit. This surgical technique is not difficult because an ileal conduit is typically created during total pelvic exenteration of rectal cancers. Therefore, anastomosing the ureter to an “ileal segment” is easy and feasible. Hence, we consider that knowledge of this technique would be beneficial for surgical oncologists who perform colorectal surgeries.
Journal of Clinical Oncology
PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorec... more PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because...
International Journal of Clinical Oncology
Background Different genetic characteristics according to tumor location result in variations in ... more Background Different genetic characteristics according to tumor location result in variations in survival rates and treatment responses in advanced colorectal cancer (CRC). However, the effects of tumor location during early CRC are still unclear. Methods Patients with T1 CRC treated between 2003 and 2019 were enrolled from a prospectively collected database. Patients were once divided into four groups, then combined into two groups (right-and left-sided CRC) according to the tumor location, and clinical features and oncologic behaviors were compared. Results In total, 458 patients were analyzed. Right-sided CRC had a lower incidence of polypoid type tumor than left-sided CRC (36/126 (28.6%) vs 186/332 (56.0%), p < 0.001). There were no differences in tumor size, pathological grade, pT1 substage and lymphovascular invasion between right-and left-sided CRC. Overall, lymph nodal involvement was observed in 42/458 (9.1%) patients. Right-sided CRC had a lower rate of patients with lymph nodal involvement than left-sided CRC (6/126 (4.8%) vs 36/332 (10.8%), p = 0.04). Conclusion The present study revealed that there were significant differences in the macroscopic type and the incidence of lymph node involvement between right-and left-sided CRC. The clinical features and oncologic behaviors of T1 CRC are possible to vary according to tumor location.
Journal of Clinical Oncology
7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy... more 7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy (CTX) improves overall survival (OS) of colorectal cancer (CRC) patients (pts) with synchronous unresectable metastases. There are several retrospective analyses suggesting better outcomes in pts who underwent PTR compared to pts without it, but no prospective studies confirming these results. We conducted a randomized controlled trial to confirm the superiority of PTR plus CTX to CTX alone in asymptomatic unresectable stage IV CRC patients. Methods: Eligibility criteria included histologically proven colon and upper rectal adenocarcinoma, cT1-4 without involvement of other organs, presence of three or less unresectable factors confined to either liver, lungs, distant lymph nodes, or peritoneum, aged 20-74, no symptoms due to primary tumor and PS 0-1. Eligible patients were randomized to either PTR followed by CTX or CTX alone. CTX regimens were declared before study entry; options incl...
Journal of Clinical Oncology
3617Background: Efficacy of adjuvant chemotherapy in stage II colon cancer patients is still cont... more 3617Background: Efficacy of adjuvant chemotherapy in stage II colon cancer patients is still controversial. The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer in a large population. Methods: 20-80 aged patients with curatively resected stage II colon cancer were randomly assigned to the surgery alone group or UFT group (UFT at 500-600 mg/day as tegafur in 2 divided doses for 5 days, followed by 2-day rest, then repeated for 1 year). Primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), recurrence-free survival (RFS), and safety. Sample size was 2000 determined with an assumed hazard ratio (HR) 0.729, respectively, a two-sided significance level of 5%, and a power of 90%. Results: A total of 1982 patients (997 in the surgery alone group and 985 in the UFT group) were included in the efficacy analysis. Median follow-up was 69.5 months, the ...
Biochemical and Biophysical Research Communications
The disruption of intestinal mucosal immune tolerance can lead to the development of intestinal i... more The disruption of intestinal mucosal immune tolerance can lead to the development of intestinal immune diseases such as food allergy (FA). Regulatory T cells (Tregs) in the mucosa play a critical role in maintaining peripheral immune tolerance in the intestine, and retinoic acid (RA) is absolutely required for the induction of Tregs. We have previously reported that kakkonto, a traditional Japanese herbal medicine, suppresses FA in a murine FA model due to the induction of Tregs in the colonic mucosa. However, the precise molecular mechanisms underlying the induction of Tregs remain unclear. Puerarin, an isoflavone derivative, is a major constituent of kakkonto. Thus, we investigated the effect of puerarin on the induction of Tregs. BALB/c mice were systemically sensitized and then orally challenged with ovalbumin (OVA) as an FA model. Puerarin treatment suppressed the development of allergic diarrhea in FA mice. The gene expression levels of IL-4 and mast cell protease I (mMCP-1) were significantly upregulated in the proximal colon of FA mice but were reduced by puerarin. The proportions of Foxp3+CD4+ cells and CD103+CD11c+ dendritic cells (DCs) were significantly higher among the colonic lamina propria (cLP) cells of puerarin-treated FA mice than among those of untreated FA mice. The gene expression of Aldh1a1, an RA synthesis enzyme, in colonic epithelial cells (CECs) was significantly higher in the puerarin-treated FA mouse colon than in the untreated FA mouse colon. In addition, the preventive effect of puerarin was suppressed in the FA model by pretreatment with LE540, an RA receptor (RAR) antagonist. The induction of Foxp3+CD4+ cells and CD103+CD11c+ DCs by puerarin was reduced by pretreatment with LE540. The present findings indicate that the augmentation of RA production in CECs induced by puerarin enhances the induction of Tregs and suppresses the development of FA in a mouse model. Thus, a natural enhancer of RA production, such as puerarin, has the potential to treat immune diseases attributed to Treg deficiency.
Journal of Clinical Oncology
3515 Background: The no-touch isolation technique (NTIT) aims to reduce cancer cells flowing from... more 3515 Background: The no-touch isolation technique (NTIT) aims to reduce cancer cells flowing from the primary tumor site to the liver and other organs by first ligation of blood vessels that feed the primary tumor. The efficacy of NTIT has not been proved in previous studies. To acquire the answer of an unsolved problem more than 60 years, we conducted a phase III trial to confirm the superiority of NTIT in patients with cT3/T4 colon cancer. This is the primary analysis of the disease-free survival (DFS) as the primary endpoint. Methods: Eligibility criteria included histologically proven colon cancer; tumor located in the cecum, ascending, transverse, descending, sigmoid or rectosigmoid colon; clinical T3 or T4, N0-2, M0; patients age 20-80 years. Patients were randomized preoperatively to either conventional technique (CoT) arm or NTIT arm. Operation was performed in open surgery. Patients with pathological stage III received adjuvant chemotherapy with capecitabine. The primary en...
Surgery Today
Purpose This study aimed to clarify the prognosis of patients after resection of stage IV colorec... more Purpose This study aimed to clarify the prognosis of patients after resection of stage IV colorectal cancer and synchronous peritoneal metastasis (no residual disease: R0 status) based on histopathologic findings. Methods The subjects of this study were 26 patients who underwent radical resection of synchronous peritoneal metastases of stage IV colorectal cancer. Only patients with one synchronous peritoneal metastasis were included in this study. The peritoneal lesions were initially classified into two categories based on the presence or absence of adenocarcinoma on their surface: RM-negative or RM-positive. The lesions were subsequently classified as being of massive or diffuse type and of small (< 6 mm) or large (≥ 6 mm) type according to the maximum metastatic tumor dimension. Results Multivariate analysis revealed that massive type metastatic tumors were associated with a better disease-free survival (DFS; p = 0.047) and overall survival (OS; p = 0.033), than diffuse type tumors. Conclusion A detailed stratification of pathological findings could contribute remarkably to prognostic predictions for patients with synchronous peritoneal metastases.
Diseases of the Colon & Rectum
638 DISEASES OF THE COLON & RECTUM VOLUME 62: 5 (2019) It is thought that achieving complete ... more 638 DISEASES OF THE COLON & RECTUM VOLUME 62: 5 (2019) It is thought that achieving complete mesocolic excision and central vascular ligation improves the prognosis of patients undergoing right-side colon cancer surgery. In the middle colic artery (MCA) areas, the lymph nodes are distributed around the superior mesenteric vein (SMV) and the superior mesenteric artery (SMA); thus, identifying the anatomical location of the SMA and the MCA is an essential procedure for performing radical lymph node dissection. We present our procedure for radical lymph node dissection along the SMA using a multidirectional approach. The procedure is started with a posterior approach. The mesentery is divided from the retroperitoneal organs. An anterior approach is used in the second step. The anterior approach is divided into the distal side and the proximal side across the transverse colon mesentery. Through a distal anterior approach, the front of the SMV and the SMA are exposed. The left edge of the SMA is set as the landmark of the complete mesocolic excision. A proximal anterior approach is used in the third step. The mesentery of the transverse colon is cut off along the lower edge of the pancreas. The front of the SMV and the SMA are exposed, and the origins of the MVC and the MCA are identified. Finally, the MCV is dissected at the origin and the MCA is dissected with the right branch. We performed laparoscopic right colectomy using this approach for 47 patients with right-side colon cancer. The median number of harvested lymph nodes was 34. No grade ≥3 complications occurred. The median follow-up period was 12 months. Long-term results have not been obtained. In conclusion, the use of a multidirectional approach makes it possible to successfully perform laparoscopic right hemicolectomy with radical lymph node dissection along the SMA. See Video at http://links. lww.com/DCR/A827.