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R Ichikawa,
N Hosoe,
H Imaeda,
K Takabayashi,
R Bessho,
Y Ida,
M Naganuma,
T Hisamatsu,
N Inoue,
T Kanai,
Y Iwao, M Mukai,
T Hibi,
H Ogata
Endoscopy 01/2011; 43 Suppl 2 UCTN:E162-3. · 5.21 Impact Factor
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ABSTRACT: The prognostic significance of sentinel lymph node (SLN) micrometastases and the need for axillary lymph node dissection (ALND) on patients with micrometastases in SLNs remain controversial.
A prospective database of 657 breast cancer patients who underwent SLN biopsy (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue dye and small-sized technetium-99m-labeled tin colloid.
Micrometastases in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and no further metastases were found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic SLNs who decided to forego ALND, no axillary lymph node recurrence has been observed during a median follow-up time of 47 months. There is no significant difference in recurrence-free survival between the patients with micrometastatic and negative SLNs (p = 0.90).
These data suggest that it may not be necessary to perform ALND on patients with micrometastases in SLNs and that the presence of micrometastases in SLNs may not be associated with prognosis.
European Surgical Research 11/2010; 45(3-4):344-9. · 0.93 Impact Factor
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T Hayashida,
H Jinno,
M Sakata,
M Takahashi,
T Onishi,
H Seki,
T Sato,
T Nakahara,
N Shigematsu, M Mukai,
T Hibi,
M Kitajima,
Y Kitagawa
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ABSTRACT: Sentinel lymph node biopsy (SLNB) is commonly performed using radioisotopes and/or blue dye. However, it is still undefined which reagent is more suitable for identifying sentinel lymph nodes (SLN).
A consecutive series of 640 breast cancer patients who had undergone SLNB at the Keio University Hospital from 2001 to 2006 was analyzed. The SLN was identified by a combination of technetium-99m tin colloid and isosulfan blue dye. The correlation between clinicopathological factors and the distribution of radioisotopes and blue dye was analyzed. The single metastatic lymph node revealed by axillary lymph node dissection (ALND) is the 'true SLN', and the distribution of radioisotopes and blue dye to the 'true SLN' was also analyzed.
Blue-dye- and radioisotope-positive SLN were identified in 79.6 and 94.7% of the patients, respectively. Taken together, SLN were identified in 625 patients (97.7%) by radioisotope and/or blue dye. No significant correlation was observed between clinicopathological features and the distribution of the reagents. ALND found 73 patients with single lymph node metastasis, and 73 'true SLN' were identified by blue dye in 65.7% (48/73), and by radioisotope in 95.9% (70/73) of the cases.
These data suggest that radioisotopes are superior to blue dye in detecting SLN in breast cancer.
European Surgical Research 01/2010; 44(2):111-6. · 0.93 Impact Factor
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ABSTRACT: Capecitabine (X) and docetaxel (T) have demonstrated a synergistic effect in preclinical models and a survival benefit in metastatic breast cancer. This study's purpose was to determine the efficacy of X and T followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) in the preoperative setting.
Patients with stage II/III breast cancer received four cycles of XT (capecitabine 1650 mg/m(2) on days 1-14 and docetaxel 60 mg/m(2) on day 8 every 3 weeks), followed by four cycles of FEC (5-fluorouracil 500 mg/m(2), epirubicin 90 mg/m(2), and cyclophosphamide 500 mg/m(2) on day 1 every 3 weeks). Primary end points were the pathological complete response (pCR) rate and adverse drug reactions.
Seventy-four patients were enrolled and 71 patients were assessable for clinical and pathological responses. The overall response rate was 91.5%. The pCR rate was 14.1% (10 of 71). Grade 3/4 neutropenia was observed in 32.4% of patients. The most common grade 3/4 non-hematologic adverse event was hand-foot syndrome, observed in 11.3% of patients. With 29 months median follow-up, 2-year disease-free survival was estimated 85% for all patients.
These data indicate that the sequential combination of XT followed by FEC is a well-tolerated, effective neoadjuvant treatment of stage II/III breast cancer.
Annals of Oncology 10/2009; 21(6):1262-6. · 6.43 Impact Factor
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ABSTRACT: Background
Although recent immunochemical analysis enabled the discrimination of gastrointestinal stromal tumour (GIST) to other mesenchymal tumours, preoperative diagnosis of these tumours is not always easy.AimTo discriminate between ectopic pancreas (EP) and mesenchymal tumours, including GIST, 12 years surgical experience at Keio University Hospital was reviewed.Methods
Clinicopathological findings were analysed for 131 patients with gastric submucosal tumours (SMT), including GIST (67 cases), myogenic tumour (21 cases), Schwannoma (11 cases), EP (12 cases) and others (20 cases) surgically treated at Keio University Hospital since 1993.ResultsAnalysis of clinicopathological findings of these tumours showed that GIST, myogenic tumour and Schwannoma mimic each other from the standpoint of size and location of the tumour. In contrast, comparison of mesenchymal tumours showed that, compared with gastrointestinal mesenchymal tumour, EP tends to exist at middle or lower third of the stomach (P = 0.004), and the tumour size was smaller than 3 cm (P = 0.0006). All EPs were laparoscopically resected and no malignant features were evident.Conclusion
To avoid unnecessary surgery for EP, SMT smaller than 3 cm occurring in the middle or lower third of the stomach should be carefully selected as a candidate of surgical resection.
Alimentary Pharmacology & Therapeutics Symposium Series 06/2006; 2(1):292 - 296.
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Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 02/2006; 95(4):256-9. · 1.03 Impact Factor
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ABSTRACT: Many molecular alterations occur in esophageal carcinogenesis; however, little is known about the molecular genetic events responsible for the development of carcinoma. We investigated the expression of ki67, p53, cyclin D1 and pRB in 105 biopsy specimens using immunohistochemistry from iodine unstained lesions as indicators of carcinogenesis of the esophagus. Also, the genetic alternation of esophageal dysplasia from patients with accompanying esophageal squamous cell carcinoma (ESCC) was examined to study the evidence for field carcinogenesis in the esophagus. The expression of p53, cyclin D1 and pRB was detected in 31, 0 and 51.7% respectively of mild dysplasia; 40, 0 and 70% of moderate dysplasia; 40, 20 and 70% of severe dysplasia; and 48, 32 and 80% of carcinoma specimens. p53 expression was significantly increased in mild dysplasia, whereas cyclin D1 and pRB expression were significantly increased in carcinoma as compared to both normal epithelium and esophagitis. The ki67 LI and the rate of p53 expression were significantly higher in dysplasia with ESCC than in dysplasia without ESCC. Ki67, p53, cyclin D1 and pRB expression may be useful biomarkers for assessing the risk of developing esophageal cancer. Dysplasia observed at screening for secondary lesions has a highly malignant potential and careful follow-up studies are required.
Oncology Reports 01/2006; 14(6):1453-9. · 1.84 Impact Factor
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ABSTRACT: Radio-guided detection of sentinel nodes (SNs) has been used to predict regional metastases in patients with malignant melanoma and breast cancer. However, the validity of the SN hypothesis is still controversial for gastrointestinal cancers including gastric cancer. The aim of this study was to test the feasibility and accuracy of radio-guided mapping of SNs for gastric cancer.
Some 145 consecutive patients with gastric cancer diagnosed as T1 or T2 and evaluated clinically as N0 were enrolled. Endoscopic injection of technetium-99m-radiolabelled tin colloid was performed before operation and radioactive SNs were identified with a gamma probe. Standard radical gastrectomy with lymphadenectomy was performed in all patients and all resected nodes were evaluated by routine histopathological examination.
Using radio-guided methods, SNs were detected in 138 (95.2 per cent) of 145 patients. The SN was positive in 22 of 24 patients with lymph node metastasis. The incidence of metastasis in the SNs (7.8 per cent) was significantly higher than that in the non-SNs (0.3 per cent) (P < 0.01). The diagnostic accuracy according to SN status was 98.6 per cent (136 of 138).
Radio-guided SN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with early-stage gastric cancer.
British Journal of Surgery 05/2002; 89(5):604-8. · 4.61 Impact Factor
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ABSTRACT: Radical lymphadenectomy is the standard surgical approach even for early-stage gastric cancer with a relatively low incidence of lymph node metastasis because of the limited sensitivity of diagnostic imaging to detect micrometastasis in regional lymph nodes. The sentinel node (SN) concept is one topic among novel diagnostic procedures for micrometastasis. The SN is defined as the first draining node from the primary lesion and it would be the first site of micrometastasis. SN biopsy has been clinically validated and applied for the surgical treatment of malignant melanoma and breast cancer. Although the feasibility of this technique in other solid tumors including gastric cancer is still controversial, there are several reports demonstrating the diagnostic significance of SN mapping in early gastric cancer. We have established radio-guided SN mapping for early gastric cancer, and the diagnostic accuracy using this procedure in cT1N0 cases reached 98%. The radio-guided method allows us to detect the SN in endoscopic surgery quantitatively and reproducibly. Validation of the SN concept in gastric cancer in a multi-centric clinical trial is essential for clinical application of this procedure, including the establishment of a novel, minimally invasive approach for early-stage gastric cancer.
Nippon Geka Gakkai zasshi 11/2001; 102(10):753-7.
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Y Kitagawa,
M Ohgami,
H Fujii, M Mukai,
T Kubota,
N Ando,
M Watanabe,
Y Otani,
S Ozawa,
H Hasegawa,
T Furukawa,
J Matsuda,
K Kumai,
T Ikeda,
A Kubo,
M Kitajima
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ABSTRACT: Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.
Annals of Surgical Oncology 11/2001; 8(9 Suppl):86S-89S. · 4.17 Impact Factor
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ABSTRACT: Ectopic hamartomatous thymoma (EHT) is a rare benign neoplasm. Since it was named by Rosai et al. in 1984, 24 cases have been reported. We herein report two cases of EHT, one of which presented with massive myoid cells, and review the literature related to EHT. Both of our cases displayed the typical features of EHT: (1) nests of epithelial cells, including solid, cystic, or glandular epithelial islands; (2) spindle cells dominating the microscopic picture; and (3) adipose cells which intermingle haphazardly to impart a hamartomatous quality to the tumor. In this paper, we observed massive myoid cells and the transition from spindle epithelial cell to myoid cell in one of our cases. Immunohistochemical examinations showed that the main component of EHT, spindle cells, was positive for cytokeratin and epithelial membrane antigen (EMA). Intriguingly, the myoid cells simultaneously expressed cytokeratin, EMA, myoglobin, and creatine kinase-mm, suggesting that myoid cells may originate from epithelial cells and are an intermediate state between epithelial cells and muscular cells.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/2001; 437(6):643-7. · 2.49 Impact Factor
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Y Kitagawa,
H Fujii, M Mukai,
T Kubota,
N Ando,
M Watanabe,
M Ohgami,
Y Otani,
S Ozawa,
H Hasegawa,
T Furukawa,
K Kumai,
T Ikeda,
T Nakahara,
A Kubo,
M Kitajima
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ABSTRACT: Evaluation of the clinical significance of the sentinel node concept in GI cancer has just begun. The authors' preliminary data, using intraoperative radiation techniques and the gamma probe, suggest that it is worthwhile to continue the evaluation of this procedure to determine its role in an accurate staging and a minimally invasive approach to GI cancers.
Surgical Clinics of North America 01/2001; 80(6):1799-809. · 2.14 Impact Factor
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ABSTRACT: To describe the characteristics of pancreatoblastoma.
We studied 3 cases of pancretoblastoma and reviewed another 59 cases. Parameters analyzed were tumor site, hemorrhage, capsule formation, necrosis, vascularity, production of alpha-fetoprotein (AFP), cystic changes and calcification.
The diagnostic findings were as follows: pancreatic head origin (24/54, 44%), pancreatic body and tail origin (30/54, 56%), hemorrhage (16/17, 94%), capsule formation (24/26, 92%), necrosis (28/31, 90%), hypervascularity (10/14, 71%), production of AFP (19/28, 68%), cystic changes (11/16, 69%), and calcification (10/21, 48%). All neonatal cases demonstrated cystic changes. Three of them were patients with Beckwith-Wiedmann syndrome. The incidence of capsule formation and calcification was not related to the origin of the tumor.
The most common features of pancreatoblastoma are hemorrhage, capsule formation and necrosis.
Acta Radiologica 08/2000; 41(4):334-7. · 1.37 Impact Factor
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ABSTRACT: To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5-7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa.
British Journal of Cancer 07/2000; 82(11):1814-8. · 5.04 Impact Factor
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T Mori,
S Okamoto,
S Matsuoka,
T Yajima,
M Wakui,
R Watanabe,
A Ishida,
Y Iwao, M Mukai,
T Hibi,
Y Ikeda
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ABSTRACT: We prospectively evaluated a risk-adapted pre-emptive treatment with ganciclovir for CMV diseases in patients undergoing allogeneic bone marrow transplantation (BMT). High-level CMV antigenemia (10 or more positive cells on two slides) or CMV antigenemia at any level in patients with grade II-IV acute graft-versus-host disease (aGVHD) were chosen as risk factors. We also retrospectively evaluated virus reactivation in plasma using quantitative real-time polymerase chain reaction (PCR). Fifty patients were evaluable. None of the 27 patients with or without grade I aGVHD developed high-level CMV antigenemia or CMV disease. Among the 23 patients with grade II-IV aGVHD, 12 patients (52%) developed CMV antigenemia and were treated pre-emptively, of whom two developed CMV gastroenteritis or retinitis in spite of therapy. Six of the remaining 11 patients developed CMV gastroenteritis before CMV antigenemia was detectable. All of the eight patients with CMV diseases were successfully treated with ganciclovir and no deaths directly related to CMV disease occurred. In four of the seven evaluable patients with CMV gastroenteritis, real-time PCR was able to detect virus reactivation earlier than CMV antigenemia. Although our risk-adapted pre-emptive therapy effectively reduced CMV-related mortality, further refinements of this approach, particularly in the prevention of CMV gastroenteritis, may be achieved by incorporating real-time PCR.
Bone Marrow Transplantation 05/2000; 25(7):765-9. · 3.75 Impact Factor
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ABSTRACT: Iodine-nonreactive lesions of esophageal epithelium often are associated with dysplasia and carcinoma. The authors examined the usefulness of telomerase activity as an indicator for esophageal carcinogenesis in such lesions.
Telomerase activity was measured using the telomeric repeat amplification protocol assay in 18 samples of iodine-nonreactive lesions apart from the primary tumor in surgically resected specimens obtained from patients with esophageal squamous cell carcinoma (ESCC) and 55 endoscopic punch biopsies of iodine-nonreactive lesions obtained from 25 patients with ESCC and 30 patients who had undergone endoscopic examination for other reasons.
Ten of 18 iodine-nonreactive samples (56%) obtained from surgically resected specimens showed telomerase activity. In all ten telomerase positive samples, carcinoma in situ (CIS) was observed in iodine-nonreactive mucosa by light microscopy. In eight telomerase negative samples, no tumor tissue was observed in iodine-nonreactive lesions. In a parallel study, telomerase activity was detected in 28 of 55 endoscopic punch biopsy specimens (51%). CIS was observed in 25 of 28 iodine-nonreactive lesions with positive telomerase activity (89%), and tumor tissue was not observed in the other 3 samples (11%), which included 2 cases of severe dysplasia and 1 case of moderate dysplasia. No tumor tissue was observed in any of the 27 telomerase negative samples.
Positive and negative telomerase activity was found to be correlated with the presence and absence, respectively, of immortalized tumor cells in iodine-nonreactive lesions. The measurement of telomerase activity in iodine-nonreactive lesions independently contributes to the selection of an appropriate therapeutic strategy.
Cancer 05/2000; 88(7):1524-9. · 4.77 Impact Factor
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Y Kitagawa,
H Fujii, M Mukai,
N Ando,
T Kubota,
T Ikeda,
M Ohgami,
M Watanabe,
Y Otani,
S Ozawa,
H Hasegawa,
T Furukawa,
T Nakahara,
A Kubo,
K Kumai,
M Kitajima
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ABSTRACT: Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.
Nippon Geka Gakkai zasshi 04/2000; 101(3):315-9.
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ABSTRACT: Ten cases of ductal carcinoma in situ (DCIS) or DCIS with microinvasion were reviewed in order to evaluate the characteristic findings of DCIS and to evaluate the extent of disease on MRI. A 1.5Tesla Signa or Horizon (GE Medical Systems) unit was used with a dedicated receive-only breast coil. The pulse sequence based on RARE was used with the fat suppression technique. After examining both breasts with a large FOV (30 cm), the affected breast alone was examined with a smaller FOV (18 cm) and larger matrix (512 x 384) with and without Gd-enhancement. DCIS showed several types of findings on MRI: linear, spotty enhancement; gathering of linear enhancement; enhanced area or mass without distortion of the surrounding tissue; and well-circumscribed mass mimicking intraductal papilloma. Compared with typical findings of invasive carcinoma, DCIS tended to be enhanced slowly. After performing MR examination in addition to mammography and ultrasonography, a more accurate diagnosis of disease extent was possible in 6 of 10 patients. MRI was useful in providing more precise information on the disease extent of DCIS, and it is considered useful in planning the type of surgery. Further study using larger series and precise pathological correlations are necessary.
Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica 04/2000; 60(4):205-9.
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ABSTRACT: Minimally invasive surgery has revolutionized the treatment of gastrointestinal tumors. Submucosal tumors (SMTs) of the stomach can be resected using laparoscopic techniques. Between 1993 and 1997, laparoscopic wedge resection was performed in 34 patients with an SMT of the stomach. The tumors ranged from 8 to 60 mm in diameter. All surgical margins were clear. The average operative time was 131 minutes. Most of the patients began eating on the first postoperative day and were discharged within 5 to 7 days. Histopathologic examination of the tumors showed gastrointestinal stromal tumor (n = 14), ectopic pancreas (n = 7), leiomyosarcoma (n = 4), schwannoma (n = 3), carcinoid (n = 2), leiomyoma (n = 2), an inflammatory lesion caused by parasites (n = 1), and cyst (n = 1). No recurrences were observed over the 5-year follow-up period. A solid SMT of the stomach larger than 20 mm in diameter can be treated using laparoscopic wedge resection.
Surgical laparoscopy, endoscopy & percutaneous techniques 03/2000; 10(1):19-23. · 1.23 Impact Factor
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M Kimata,
T Kubota,
Y Otani,
M Ohgami,
Y Ishikawa,
T Yokoyama,
S Issiki,
S Abe,
T Egawa,
J Tokuyama,
N Wada,
K Kumai,
M Kitajima, M Mukai
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ABSTRACT: Three cases of gastrointestinal stromal tumors (GIST) were treated by a laparoscopic wedge resection of the stomach. The tumor characteristics were confirmed to be nonepithelial, nonlymphomatous, nonmyogenic, and nonneurogenic gastrointestinal neoplasms with an uncertain origin which were CD34-positive and actin- and S-100-negative. The malignant potential was estimated based on the mitotic figures and growth rates. The results suggest that laparoscopic surgery is an adequate strategy for gastric submucosal tumors including GIST, and also indicates this technique to be a curative, safe, and minimally invasive procedure for both diagnosis and treatment.
Surgery Today 02/2000; 30(2):177-80. · 1.22 Impact Factor
