Makio Mukai

Keio University, Edo, Tōkyō, Japan

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Publications (241)786.28 Total impact

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    ABSTRACT: The objectives were to investigate the accuracy of sentinel lymph node (SLN) biopsy, detect the predictors for undetected or false-negative cases, evaluate the indications for SLN-navigated gastrectomy, and characterize the problems of SLN mapping in gastric cancer. The SLN concept may be applicable to early gastric cancer, particularly clinical T1N0M0 or T2N0M0 with tumor diameter ≤4 cm. A total of 385 consecutive patients diagnosed with cT1N0M0 or cT2aN0M0 operable gastric cancer from April 1999 to December 2007 underwent radical gastrectomy with SLN mapping. SLNs were identified using radio-guided and dye-guided methods. Predictors for undetected or false-negative cases on SLN mapping were examined by multivariate regression analysis. The detection rate of hot and/or blue nodes was 96.6% (372 of 385). The accuracy of metastatic status based on SLNs was 98.9% (368 of 372) for all cases in whom SLNs could be detected. Furthermore, the accuracy of metastatic status based on SLNs was 99.1% (344 of 347) in cT1 gastric cancer and 96.0% (24 of 25) in cT2 gastric cancer. Pathologically, the tumors invaded to the muscularis propria or deeper in three of four false-negative cases. All but one case had metastatic lymph nodes within the sentinel basins. In terms of 5-y recurrence free survival, positive SLN cases (SLN(+)) had a worse prognosis than negative SLN cases (SLN(-); P = 0.008). Moreover, SLN(+) and non-SLN(-) cases (SLN(+)/non-SLN(-)) had a similar prognosis as SLN(+) and non-SLN(+) cases (SLN(+)/non-SLN(+)) (P = 0.511). On multivariate regression analysis, undetected or false-negative cases were significantly associated with the time period. The present results appeared to validate the SLN concept for untreated cT1 gastric cancer with tumor diameter ≤4 cm. SLN mapping may provide an effective method of staging the lymph node status of patients undergoing minimized gastrectomy. Sentinel basin dissection guards against the possibility of leaving positive lymph nodes. Stabilization of the procedure and experience with SLN mapping in gastric cancer might decrease undetected or false-negative cases. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Surgical Research 07/2015; DOI:10.1016/j.jss.2015.06.064 · 1.94 Impact Factor
  • 01/2015; 86(1):126-127. DOI:10.11641/pde.86.1_126
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    ABSTRACT: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing, but the surgical strategy for AEG remains controversial. We hypothesized that sentinel node (SN) mapping for AEG could be validated to avoid unnecessary lymphadenectomy and permit minimally invasive surgery. We examined the feasibility of SN mapping for AEG. We enrolled 15 patients with preoperatively diagnosed cT1 N0 M0 primary AEG (Siewert type I, N = 3; Siewert type II, N = 12) lesions measuring <4 cm in diameter. The dual tracer method employing radioactive colloid and blue dye was used to detect SNs. The distribution of SNs was compared with that of metastatic lymph nodes in 52 patients who were surgically treated without SN mapping. SNs were successfully identified in all the patients. Two patients with lymph node metastasis had positive SNs identified via an intraoperative pathological examination, and the diagnostic sensitivity and accuracy based on the SN status were both 100 %. For Siewert type II AEG, the SNs were not detected in the lower mediastinum by intraoperative gamma probing. Thus, all surgical procedures were performed via a transhiatal approach. No patient without SN metastasis experienced cancer recurrence during a 38-month median follow-up. The distribution of SNs was similar to that of lymph node metastasis in the patients who were surgically treated without SN mapping. We achieved 100 % SN detection. Our results suggested that SN mapping is feasible for AEG and highly sensitive and accurate in diagnosing lymph node metastasis. SN mapping may clarify the necessity of mediastinal lymph node dissection and individualize minimally invasive surgery.
    World Journal of Surgery 04/2014; 38(9). DOI:10.1007/s00268-014-2573-4 · 2.64 Impact Factor
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    ABSTRACT: When pathological diagnosis following endoscopic resection (ER) for early gastric cancer (EGC) suggests probable lymph node metastasis, additional surgery with lymphadenectomy should be performed. The sentinel node (SN) concept has yet to be applied to tumors following ER. The aim of this study was to evaluate the feasibility of SN navigation surgery for such tumors. Forty patients diagnosed with EGC lesions <4 cm in diameter underwent gastrectomy with SN mapping following ER. A technetium-99 m tin colloid solution and a dye were injected into the submucosal layer around the post-ER scar in all four abdominal quadrants. We then compared the SN distribution and metastases among the patients who underwent ER and controls (n = 192). SNs were identifiable in all patients, and the mean number of SNs per case was 4.9. The location of the SN basin was similar in the patients who underwent ER and the controls. One patient (3 %) whose primary tumor had invaded the submucosal layer had a metastatic SN. The median time from ER to surgery was 73 days. No postoperative recurrence was observed in any patient over a median follow-up of 1,023 days. Our findings suggest that the SN basin is not greatly affected by ER. The SN concept could be suitable for tumors following ER, but conventional gastrectomy with lymphadenectomy involving the SN basin should be used at present.
    Annals of Surgical Oncology 03/2014; 21(9). DOI:10.1245/s10434-014-3662-1 · 3.93 Impact Factor
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    ABSTRACT: Tumor size and lymphovascular invasion are known high-risk factors for lymph node and distant metastasis in patients with rectal carcinoid tumors. However, the optimal treatment for these tumors remains controversial. The aim of this paper is to compare the outcome of local or radical resection between patients with high-risk (tumor size >10 mm or lymphovascular invasion) disease and those with low-risk (tumor size ≤10 mm, no lymphovascular invasion) disease. Patients with rectal carcinoid tumors treated between January 1990 and March 2010 were identified retrospectively and classified into low- and high-risk groups. In total, 83 patients with rectal carcinoid tumors were included, 53 (64 %) of whom were identified as low-risk and 30 (36 %) as high-risk. Local resection was performed in 50 (60 %) low-risk and 24 (29 %) high-risk patients, and postoperative recurrence was observed in one (1 %) of the high-risk patients who underwent local resection and one (11 %) who underwent radical resection. No recurrence was observed in the low-risk group. Kaplan-Meier analysis of the patients who underwent local resection revealed that the 10-year disease-free survival rate was 100 % in the low-risk group and 83.3 % in the high-risk group. There was no significant difference in outcome between local and radical resection.
    Journal of Gastrointestinal Surgery 02/2014; 18(4). DOI:10.1007/s11605-014-2468-6 · 2.80 Impact Factor
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    ABSTRACT: Desmoplastic fibroma (DF) of the bone is a rare locally aggressive tumor usually occurring in adolescents and young adults. These tumors most commonly occur in the mandibles and metaphyses of long bones but are extremely rare in small bones, often resulting in diagnostic problems. The occurrence of these tumors in the foot is especially limited. We report the clinical, radiographic, and histologic features of DF arising in the distal phalanx of the great toe and a review of the published data.
    The Journal of foot and ankle surgery: official publication of the American College of Foot and Ankle Surgeons 11/2013; 53(1). DOI:10.1053/j.jfas.2013.09.010 · 0.85 Impact Factor
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    Dataset: MALT miR
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    ABSTRACT: Background The accurate diagnosis of lymph node (LN) metastasis is important for making treatment decisions for gastric cancer patients. This multicenter study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp.), an automated system that detects cytokeratin 19 (CK19) mRNA, in detecting LN metastases in gastric cancer patients. Methods LNs retrieved from patients who had undergone gastric cancer surgery at one of the four Japanese hospitals involved in this study were divided into blocks at 2-mm intervals. Alternate blocks were examined with the OSNA assay and the remaining blocks were assessed histologically. Results A total of 394 LNs from 61 patients were examined. The concordance rate between the OSNA assay and the histological examination was 0.942 (95 % CI, 0.914–0.963). Sensitivity and specificity of the OSNA assay compared to the histological examination were 0.833 (95 % CI, 0.707–0.921) and 0.959 (95 % CI, 0.932–0.977), respectively. Discordant results were observed in 23 LNs (5.8 %), and these were mainly the result of tissue allocation bias and/or low CK19 protein expression. Conclusion The OSNA assay can detect lymph node metastases in gastric cancer patients as accurately as the histological examination of blocks sectioned at 2-mm intervals. The OSNA assay is a useful tool for the intraoperative diagnosis of LN metastasis in gastric cancer patients.
    Gastric Cancer 06/2013; 17(2). DOI:10.1007/s10120-013-0271-9 · 3.72 Impact Factor
  • 01/2013; 82(1):164-165. DOI:10.11641/pde.82.1_164
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    ABSTRACT: Mesenchymal chondrosarcoma (MC) is an extremely rare subtype of chondrosarcoma. A tumor specific fusion gene, HEY1-NCOA2 fusion, was recently identified in this tumor. The finding raises the possibility that the diagnosis of MC can be improved by examining the fusion gene. In the present study, we aimed to evaluate the efficacy of fluorescence in situ hybridization (FISH) in detecting HEY1-NCOA2 fusion for the diagnosis of MC. Specimens from 10 patients diagnosed with MC were used for the study. Dual-color FISH was performed using two different probes that specifically hybridize to HEY1 and NCOA2, respectively. Fusion signals were identified in all but two specimens, in which no signal was detected, presumably because of inadequate sample preparation. In accordance with results of a previous study, FISH analysis was highly sensitive in detecting HEY1-NCOA2 fusion in adequately prepared MC samples. The current study adds further support for the use of HEY1-NCOA2 fusion as a valid diagnostic marker for MC.
    Pathology International 12/2012; 62(12):823-6. DOI:10.1111/pin.12022 · 1.69 Impact Factor
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    ABSTRACT: Mesenteric venous thrombosis is an insidious disease, with a high mortality rate typically attributed to the long delay in diagnosis. Rapid diagnosis and treatment are important. Here, we present a patient with idiopathic inferior mesenteric venous (IMV) thrombosis. A 65-year-old man presented with constant abdominal pain associated with fever and bloody diarrhea. He was diagnosed with severe ulcerative colitis and was treated with mesalazine and prednisolone. The prednisolone was tapered because of liver dysfunction, and he received total parenteral nutrition for a month. His abdominal pain and bloody diarrhea worsened, and he lost 5 kg of weight. He was then transferred to our institute. Computed tomography showed thickening of the left colon. Colonoscopy showed diffuse colitis with multiple ulcers, large edematous folds, congested mucosa, and stenosis of the sigmoid colon, with sparing of the rectum, raising the possibility of IMV thrombosis. Angiography confirmed IMV thrombosis. Anticoagulation therapy was initiated with intravenous heparin followed by oral warfarin. His abdominal pain and diarrhea resolved, and he was discharged from hospital. Six months later, he remained asymptomatic with normal colonoscopic findings.
    Clinical Journal of Gastroenterology 12/2012; 5(6). DOI:10.1007/s12328-012-0340-3
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    ABSTRACT: microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma.
    PLoS ONE 11/2012; 7(11):e47396. DOI:10.1371/journal.pone.0047396 · 3.23 Impact Factor
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    ABSTRACT: Introduction: We herein report an extremely rare case of a liposarcoma developing in the ischiorectal fossa that was completely resected using a transsacral approach. Presentation of case: A 74-year-old man was admitted to our institute because of a large perianal tumor. A pelvic magnetic resonance imaging (MRI) revealed an 8cm×7cm×5cm sized encapsulated heterogeneous tumor on the right side of the ischiorectal fossa. Transsacral excision was performed under a diagnosis of liposarcoma. The tumor was partially fixed to the external sphincter and puborectalis. Therefore, the muscles were partially resected to ensure sufficient margins. Histopathological examination revealed a well differentiated liposarcoma and negative surgical margins. Discussion: The basic treatment strategy of liposarcoma is surgical resection, whereas the effects of chemotherapy or radiotherapy remain limited. Although no postoperative adjuvant therapy has been performed in our case, no recurrences have occurred for 1 year after surgery. Conclusion: Although the curative resection of large tumors located in the ischiorectal fossa is usually difficult, the complete resection of liposarcoma is the main potentially curative treatment. A transsacral approach is useful for a complete resection.
    International Journal of Surgery Case Reports 10/2012; 4(1):51-53. DOI:10.1016/j.ijscr.2012.09.011
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    ABSTRACT: Background Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy. Case presentation The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10. Conclusion This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.
    BMC Cancer 10/2012; 12(1):444. DOI:10.1186/1471-2407-12-444 · 3.36 Impact Factor
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    Digestive Diseases and Sciences 09/2012; 58(3). DOI:10.1007/s10620-012-2390-2 · 2.61 Impact Factor
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    ABSTRACT: Although previous studies indicate that gastrointestinal (GI) cancer may originate from cells recruited from bone marrow (BM) in mice, whether similar phenomena occur in humans is controversial. In the current study, we evaluated two female patients who developed colonic adenocarcinoma more than 10 years after gender-mismatched BM transplantation, and followingly underwent successful endoscopic mucosal resection. Fluorescent in situ hybridization (FISH) analysis was used to determine whether the tumours contained donor-derived BM cells. Approximately 1.2% of the tumour cells contained Y-chromosome-positive signals, and a comparable percentage of normal colonic epithelial cells close to the tumour also contained Y-chromosome-positive signals. These results do not support the concept that GI cancer can originate from BM-derived cells.
    Anticancer research 09/2012; 32(9):4097-103. · 1.83 Impact Factor
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    ABSTRACT: Axillary dissection has been considered essential for breast cancer staging because nodal metastasis is the most powerful predictive factor for recurrence. On the other hand, morbidity, such as lymphedema and shoulder dysfunction, may occur. Sentinel node biopsy is a good way to avoid unnecessary axillary dissection. We used tin colloid as a carrier of Tc99m tracer together with the blue dye method. The detection rate of the sentinel node was 27 cases out of 29 (90%) for the blue dye method, 10 cases out of 19 (53%) for the Rl method, and 27 out of 33 (82%) for the combined method. The detection rate of the Rl method was improved after adding the subcutaneous injection over the tumor from 45% before adding the subcutaneous injection to 82% after adding it. The false negative rate was 11% for the blue dye method, 0% for the R1 method, and 10% for the combined method. This yields a sensitivity of 89% for the blue dye method, 100% for the R1 method, and 90% for the combined method. Specificity was 100% for all three methods. Accuracy was 96% for the blue dye method, 100% for the R1 method, and 96% for the combined method. There were two false negative cases. The average number of sentinel lymph nodes was 2.12 for the dye method, 1.66 for the R1 method, and 1.95 for the combined method. There were three of 49 cases with identified parasternal lymph nodes by R1 imaging. Lymphatic mapping using tin colloid may be useful for detecting sentinel nodes.
    Breast Cancer 04/2012; 7(4):284-286. DOI:10.1007/BF02966391 · 1.59 Impact Factor
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    ABSTRACT: Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.
    Sarcoma 04/2012; 2012(12):345161. DOI:10.1155/2012/345161
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    ABSTRACT: Studies have suggested that HOXB9 expression in breast cancer cells promotes cellular invasiveness, metastatic ability, and tumor neovascularization in the surrounding tissue in in vitro and in vivo assays. These findings imply that HOXB9 overexpression may alter tumor-specific cell fates and the tumor stromal microenvironment, contributing to breast cancer progression. The objective of this study was to analyze whether these results could be applied to clinical practice. A total of 141 consecutive, invasive ductal carcinoma patients who underwent surgical treatment were examined. Immunohistochemical staining was performed to evaluate the expression of HOXB9, Ki-67, CD31, and CD34, and the association of tumor proliferation and angiogenesis with HOXB9 expression was analyzed. Of the 141 tumor specimens immunostained for HOXB9, 69 (48.9%) stained positive. Larger primary tumor size, hormone receptor negativity, HER2 positivity, higher nuclear grade, and number of pathologic nodal metastases were significant variables associated with HOXB9 expression. Notably, 12 (92.3%) of 13 triple-negative breast cancer cases showed HOXB9 expression. Disease-free survival and overall survival were significantly different between the HOXB9-positive and HOXB9-negative groups (hazard ratio 20.714, P = 0.001; and hazard ratio 9.206, P = 0.003, respectively). Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for disease-free survival (hazard ratio 15.532, P = 0.009). HOXB9-positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio compared with HOXB9-negative tumors. HOXB9 expression, which promotes tumor proliferation and angiogenesis, is a significant prognostic factor in breast cancer.
    Annals of Surgical Oncology 03/2012; 19(6):1831-40. DOI:10.1245/s10434-012-2295-5 · 3.93 Impact Factor
  • Nippon Daicho Komonbyo Gakkai Zasshi 01/2012; 65(2):51-57. DOI:10.3862/jcoloproctology.65.51

Publication Stats

3k Citations
786.28 Total Impact Points


  • 1986–2015
    • Keio University
      • • School of Medicine
      • • Department of Surgery
      • • Department of Obstetrics and Gynecology
      • • Department of Pathology
      Edo, Tōkyō, Japan
  • 2002–2006
    • National Defense Medical College
      • • Division of Pathology
      • • Division of Environmental Medicine
      Tokorozawa, Saitama-ken, Japan
  • 1992–1994
    • Saiseikai Utsunomiya Hospital
      Utsunomiya, Tochigi, Japan