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PDF file - 271K, Correlation between survivin and activated Chk2 expression during colorectal tumorigenesis, in vivo. A. Patient-derived surgical or endoscopic specimens representative of progressive stages of the colorectal adenoma-to-carcinoma transition (normal mucosa, hyperplasia, moderate dysplasia, severe dysplasia and adenocarcinoma) were analyzed for expression of Thr68-phosphorylated (T68) Chk2, survivin, p53, or Chk2, by immunohistochemistry. B. Tissue slides representative of the indicated histologic diagnoses (20 cases/each) were scored for positively stained cells using a 5% cutoff. IHC, immunohistochemistry.

PDF file - 59K, Expression of Aurora B during DNA damage. HCT116 cells on glass coverslips were transfected with the indicated cDNAs, treated with etoposide for 16 h and fixed in 1% paraformaldehyde for 15 min and 70% ethanol for 30 min. After permeabilization in 0.2% Triton X-100 in 1% BSA in PBS, pH 7.4, for 10 min, cells were incubated with primary antibody to Aurora B (1:500) followed by secondary antibody (Alexa Fluor� 594) and analyzed by fluorescence microscopy. DNA was stained with DAPI.

PDF file - 39K, siRNA targeting of survivin-DeltaEx3. A. MCF-7 cells stably transfected with survivin were left untreated (None) or transfected with control (Ctrl) non-targeting or survivin-DeltaEx3-directed siRNA and analyzed by RT-PCR for expression of WT survivin (SVV) or survivin-DeltaEx3 transcripts (left). Right, densitometric quantification of mRNA bands for SVV or survivin-DeltaEx3 mRNAs in siRNA-transfected cells. RU, relative units. B. MCF-7 cells transfected with the indicated siRNAs as in A were analyzed for DNA content by propidium iodide (PI) staining and flow cytometry. The percentage of cells in the G2/M or >G2/M fraction is indicated.

PDF file - 21K, Pull down experiments. Recombinant GST, GST-survivin (SVV) or GST-survivin-DeltaEx3 was incubated with LN229 total cell extracts (TCE) and bound proteins were analyzed with an antibody to Chk2 (A) or Hsp60 (B) by Western blotting. Recombinant proteins used for the pull down experiments were stained with Coomassie blue (bottom panels).

PDF file - 93K, Multiparametric flow cytometry detection of GammaH2AX reactivity. HCT116 cells were transfected with vector, WT survivin (SVV), survivin-DeltaEx3 or Chk2 phosphorylation-defective survivin-DeltaEx3-Mut3 cDNA, treated with etoposide (A) or camptothecin (B), and analyzed after 16 h for GammaH2AX (y-axis) and PI (x-axis) staining by multiparametric flow cytometry. In panel A, numbers in parenthesis correspond to GammaH2AX fluorescence units after background subtraction.

PDF file - 99K, GEO mRNA datasets used in this study. The data were used as preprocessed and normalized by the GEO contributors, and any technical replicates were averaged. CNS=central nervous system, LCL=lymphoblastoma cell line, NB=neuroblastoma

Survivin is an oncogene that functions in cancer cell cytoprotection and mitosis. Here we report that differential expression in cancer cells of a C-terminal splice variant of survivin, termed survivin-ΔEx3, is tightly associated with aggressive disease and markers of unfavorable prognosis. In contrast to other survivin variants, survivin-ΔEx3 localized exclusively to nuclei in tumor cells and was phosphorylated at multiple residues by the checkpoint kinase Chk2 during DNA damage. Mutagenesis of the Chk2 phosphorylation sites enhanced the stability of survivin-ΔEx3 in tumor cells, inhibited the expression of phosphorylated H2AX (γH2AX) in response to double-strand DNA breaks, and impaired growth after DNA damage. DNA damage induced Chk2 phosphorylation, stabilization of p53, induction of the cyclin-dependent kinase inhibitor p21, and homologous recombination–induced repair were not affected. In vivo, active Chk2 was detected at the earliest stages of the colorectal adenoma-to-carcinoma transition, persisted in advanced tumors, and correlated with increased survivin expression. Together, our findings suggest that Chk2-mediated phosphorylation of survivin-ΔEx3 contributes to a DNA damage–sensing checkpoint that may affect cancer cell sensitivity to genotoxic therapies. Cancer Res; 72(13); 3251–9. ©2012 AACR.

Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After

Summary Mouse monocyte/macrophage major histocompatibility complex (MHC) receptor 1 (MMR1; or MMR2) specific for H-2Dd (or H-2Kd) molecules is expressed on monocytes from non-H-2Dd (or non-H-2Kd), but not those from H-2Dd (or H-2Kd), inbred mice. The MMR1 and/or MMR2 is essential for the rejection of H-2Dd- and/or H-2Kd-transgenic mouse skin onto C57BL/6 (H-2Db Kb) mice. Recently, we found that human leucocyte antigen (HLA)-B44 was the sole ligand of human MMR1 using microbeads that had been conjugated with 80 types of HLA class I molecules covering 94·2% (or 99·4%) and 92·4% (or 96·2%) of HLA-A and B molecules of Native Americans (or Japanese), respectively. In the present study, we also explored the ligand specificity of human MMR2 using microbeads. Microbeads coated with HLA-A32, HLA-B13 or HLA-B62 antigens bound specifically to human embryonic kidney (HEK)293T or EL-4 cells expressing human MMR2 and to the solubilized MMR2-green fluorescent protein (GFP) fusion protein; and MMR2+ monocytes from a volunteer bound HLA-B62 molecules with a Kd of 8·7 × 10−9 M, implying a three times down-regulation of MMR2 expression by the ligand expression. H-2Kd (or H-2Dd) transgene into C57BL/6 mice down-regulated not only MMR2 (or MMR1) but also MMR1 (or MMR2) expression, leading to further down-regulation of MMR expression. In fact, monocytes from two (i.e. MMR1+/MMR2+ and MMR1–/MMR2–) volunteers bound seven to nine types of microbeads among 80, indicating ≤ 10 types of MMR expression on monocytes. The physiological role of constitutive MMRs on monocytes possibly towards allogeneic (e.g. fetal) cells in the blood appears to be distinct from that of inducible MMRs on macrophages toward allografts in tissue.

We previously reported that S-1 plus cisplatin was feasible as adjuvant chemotherapy for stage III gastric cancer after D2 gastrectomy. Herein we evaluate the recurrence-free survival and overall survival rates as secondary endpoints based on updated follow-up data.Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Treatment consisted of 3 cycles of S-1 (40 mg/m(2) PO) twice daily on days 1-21 and cisplatin (60 mg/m(2) IV) on day 8, and S-1 was given on days 1-28 every 6 weeks until 1 year after surgery.From August 2007 to September 2009, 63 patients were accrued. Overall, 34 and 25 patients had stage IIIA and IIIB disease, respectively. After a median follow-up of 3.9 years, 16 patients experienced recurrence and 11 patients died. The 3-year recurrence-free survival rate was 74.1 % (95 % CI: 60.8-83.5 %, IIIA 81.8 %, IIIB 64.0 %). The 3-year overall survival rate was 84.5 % (95 % CI: 72.3-91.6 %, IIIA 87.9 %, IIIB 80.0 %). Recurrence sites included the peritoneum (n = 8), hematogenous sites (n = 6), and lymph nodes (n = 4).The present results indicate that adjuvant therapy with S-1 plus 3 cycles of cisplatin may provide a survival benefit to patients with stage III gastric cancer.

Making a clinicopathological diagnosis of dysplasia is crucial. We herein assess the significance of the DNA methyltransferase 3b (DNMT3b) expression as a diagnostic marker of ulcerative colitis (UC)-associated neoplasia. Thirty-one patients with long-standing and extensive UC were included in this study. The expression of DNMT3b in non-neoplastic rectal epithelium (non-dysplasia in 31 patients) and colorectal neoplasia (dysplasia in 43 patients and invasive cancer in 34 patients) was determined using immunohistochemistry. The presence of immunoreactive DNMT3b was assessed in the areas with the highest density of cells with positively staining nuclei. DNMT3b was expressed as the percentage of positive cells relative to the total number of cells counted under high power magnification. The DNMT3b expression in neoplastic rectal epithelium (0.76, range 0.59–0.84) was increased compared to that observed in non-neoplastic epithelium (0.32, range 0.18–0.67, P

Survivin is an oncogene that functions in cancer cell cytoprotection and mitosis. Here we report that differential expression in cancer cells of a C-terminal splice variant of survivin, termed survivin-ΔEx3, is tightly associated with aggressive disease and markers of unfavorable prognosis. In contrast to other survivin variants, survivin-ΔEx3 localized exclusively to nuclei in tumor cells and was phosphorylated at multiple residues by the checkpoint kinase Chk2 during DNA damage. Mutagenesis of the Chk2 phosphorylation sites enhanced the stability of survivin-ΔEx3 in tumor cells, inhibited the expression of phosphorylated H2AX (γH2AX) in response to double-strand DNA breaks, and impaired growth after DNA damage. DNA damage induced Chk2 phosphorylation, stabilization of p53, induction of the cyclin-dependent kinase inhibitor p21, and homologous recombination–induced repair were not affected. In vivo, active Chk2 was detected at the earliest stages of the colorectal adenoma-to-carcinoma transition, persisted in advanced tumors, and correlated with increased survivin expression. Together, our findings suggest that Chk2-mediated phosphorylation of survivin-ΔEx3 contributes to a DNA damage–sensing checkpoint that may affect cancer cell sensitivity to genotoxic therapies. Cancer Res; 72(13); 3251–9. ©2012 AACR.

Background and study aims: Pyloric stenosis is currently managed using open or laparoscopic pyloromyotomy. However, with recent improvements in flexible endoscopic instrumentation and techniques, totally peroral endoscopic approaches could reduce the invasiveness of myotomic procedures. The aim of the study was to establish the feasibility and efficacy of endoscopic submucosal pyloromyotomy in a porcine model. Methods: Four pigs were included in a preliminary study and a 2-week survival study was performed in another four pigs. An esophagogastroduodenoscope was inserted perorally into the stomach. Saline solution was injected into the submucosal space proximal to the pylorus. The gastric mucosa was incised and a 5-cm submucosal tunnel was created. After exposure of the muscular layer in a submucosal tunnel, myotomy of the circular muscle layer was performed until the longitudinal muscular layer was reached. Once myotomy was completed, endoscopic clips were used to re-approximate the mucosal incision. Results: Submucosal dissection, identification of the circular muscular layer, and pyloromyotomy were achieved in all animals. Acute complications such as bleeding and perforation were not observed in any cases. Median pyloric resting pressure was reduced from 16.5 mmHg to 6.1 mmHg immediately after myotomy and 8.4 mmHg at 14 days after myotomy. Conclusion: Peroral endoscopic submucosal pyloromyotomy appears to be technically feasible and effective. Potential clinical applications, such as for infantile hypertrophic pyloric stenosis or delayed gastric emptying after esophagectomy, could be considered after confirmation of safety in additional survival studies.

To identify the proteins involved in 5-fluorouracil (5-FU) resistance, a comparison of the total and phosphorylated proteins between the human colorectal cancer (CRC) cell line DLD-1 and its 5-FU-resistant subclone DLD-1/5-FU was performed. Using 2-DE and MALDI-TOF/TOF-based proteomics, 17 up-regulated and 19 down-regulated protein spots were identified in the 5-FU-resistant DLD-1/5-FU cells compared with the parent cell lines. In DLD-1/5-FU cells, 7 anti-apoptotic proteins (HSPB1, proteasome subunit α-5, transitional endoplasmic reticulum ATPase, 14-3-3 β, 14-3-3 γ, 14-3-3 σ, and phosphoglycerate kinase 1) were up-regulated and 4 proapoptotic proteins (cofilin-1, pyruvate kinase M2, glyceraldehyde-3-phosphate dehydrogenase, and nucleophosmin) were down-regulated. The results show that the acquired drug resistance of DLD-1/5-FU cells is caused by the prevention of drug-induced apoptosis, in particular through the enhanced constitutive expression of HSPB1 and its phosphorylated form. Short interfering RNA knockdown of endogenous HSPB1 in DLD-1/5-FU cells restored the sensitivity to 5-FU. Furthermore, MALDI-TOF/TOF and 2-DE Western blot analysis identified the phosphorylated residues of HSPB1 as Ser-15 and Ser-82 in the main (diphosphorylated) form and Ser-15, Ser-78, and Ser-82 in the minor (triphosphorylated) form. The current findings indicate that phosphorylated HSPB1 may play an important role in 5-FU resistance.

Background The role of laparoscopic surgery in management of transverse and descending colon cancer remains controversial. The aim of the present study is to investigate the short-term and oncologic long-term outcomes associated with laparoscopic surgery for transverse and descending colon cancer. Methods This cohort study analyzed 245 patients (stage II disease, n = 70; stage III disease, n = 63) who underwent resection of transverse and descending colon cancers, including 200 laparoscopic surgeries (LAC) and 45 conventional open surgeries (OC) from December 1996 to December 2010. Short-term and oncologic long-term outcomes were recorded. Results The operative time was longer in the LAC group than in the OC group. However, intraoperative blood loss was significantly lower and postoperative recovery time was significantly shorter in the LAC group than in the OC group. The 5-year overall and disease-free survival rates for patients with stage II were 84.9% and 84.9% in the OC group and 93.7% and 90.0% in the LAC group, respectively. The 5-year overall and disease-free survival rates for patients with stage III disease were 63.4% and 54.6% in the OC group and 66.7% and 56.9% in the LAC group, respectively. Conclusion Use of laparoscopic surgery resulted in acceptable short-term and oncologic outcomes in patients with advanced transverse and descending colon cancer.

The aim of this study is to evaluate the appropriate treatment for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC).Of 151 patients who underwent initial hepatectomy for HCC, 82 had intrahepatic recurrence and were divided into two groups: group A, ≤2 tumors, each 3 cm in size; and group B, beyond the group A. Survival and treatment in each group were analyzed retrospectively to determine the best therapeutic modality for intrahepatic recurrence.The 5-year overall survival and recurrence rate were 65% and 58%, respectively. Overall 1-, 3-, and 5-year survival rates after recurrence were better in group A (100%, 76%, and 54%) than in group B (74%, 23%, and 5.8%; p 0.001). The clinical backgrounds were not different for each modality. Of the 43 patients in group A, 10 underwent hepatectomy, 21 ablation therapy, and 12 transcatheter arterial chemoembolization (TACE). The survival rate of hepatectomy was similar to that of ablation therapy and significantly better than that of TACE (p = 0.0248). Of the 39 patients in group B, the results of TACE were similar to other therapies after recurrence.Repeat hepatectomy and ablation therapy were more effective than TACE in the group with ≤2 tumors up to 3 cm in size at recurrence, while any treatment modality was more effective than best supportive care, but the outcome was poorer in the group with ≥3 tumors or tumor size ≥3 cm at recurrence.

Hepatocellular carcinoma (HCC) shows a high rate of recurrence after hepatectomy; predictive factors for early recurrence would help determine optimal therapeutic and management strategies. Among 163 patients with HCC undergoing hepatectomy with curative intent, 46 patients developed recurrence within 1 year. Clinicopathological data were retrospectively analyzed to identify predictive parameters for early recurrence. Survival rates in cases of recurrence within 1 year were worse than those of no recurrence within 1 year or recurrence after 1 year. Protein induced by vitamin K absence/antagonist II (PIVKA-II) greater than 150, positive fucosylated alpha-fetoprotein (L3-AFP), and deviancy from Milan criteria (MC) on preoperative imaging were associated with high risk of early recurrence and total number of these three risk factors predicted the survival. With multivariate analysis, 1) preoperatively, positive factors of two or more among three items of PIVKA-II, L3-AFP, and deviancy from MC; 2) and postoperatively, pathological cancer spread (microscopic vascular invasion and/or intrahepatic metastasis) both represented risks for early recurrence. A combination of three preoperative factors, PIVKA-II, L3-AFP, and MC status, in conjunction with the postoperative factor of cancer spread status represents a significant indicator for recurrence within 1 year. Improving the prognosis of patients with HCC would depend on how to adequately treat those at high risk of early recurrence.

Background This study compared postoperative pain following four-port laparoscopic cholecystectomy (LC) and single-port cholecystectomy (SPC). Method This prospective, quasi-randomized, single-centre trial focusing on postoperative pain included 49 patients undergoing elective surgery with either a conventional LC, or SPC using a surgical glove port. Postoperative pain was evaluated using a visual analogue scale (VAS) and postoperative analgesic use as primary outcome measures. Total duration of operation, length of hospital stay, blood test results on the day after surgery and total port cost were secondary outcome measures. Results Twenty-five LCs and 24 SPCs were undertaken. The VAS score on day 1 after surgery was significantly less in the SPC group than in the LC group: median (range) 24 (12–38) versus 45 (33–57) mm (P = 0·002). Significantly fewer patients in the SPC group required analgesia (9 of 24 versus 19 of 25 in the LC group; P = 0·007). There were no significant differences in total duration of operation, length of hospital stay, and blood test results on the day after surgery. Conclusion Single-port surgery using a surgical glove port reduces postoperative pain compared with conventional LC. Registration number: UMIN000002539 (http://www.umin.ac.jp/ctr/index.htm).

In gastric cancer, various methods of gastric resection and reconstruction have been devised according to the location of the primary tumor and the depth of invasion. The functional outcomes of patients treated by laparoscopy-assisted or totally laparoscopic distal gastrectomy were compared with respect to the approach, size of the remnant stomach, and type of reconstruction.Patients who required distal gastrectomy to treat early-stage cancer between May 2000 and December 2008 were treated by one of the four following procedures: Billroth Type I (B-1) reconstruction for 1/2 remnant stomach (1/2B1ML) or B-1 for 1/3 remnant stomach (1/3B1ML), through a mini-laparotomy following laparoscopy-assisted surgery; intra-corporeal B-1 for 1/2 remnant stomach (1/2 B1IC); or intra-corporeal Roux-en-Y for 1/3 remnant stomach (1/3RYIC). The primary outcome measure was digestive function, assessed by body weight, food intake, and degree of abdominal symptoms. The secondary outcome was morbidity.The 1/2B1ML (n = 27) and 1/2B1IC (n = 56) groups were significantly superior to the 1/3 resection groups in terms of the preservation of body weight. The 1/3B1ML (n = 29) and 1/3RYIC (n = 64) groups were associated with significantly decreased food intake compared with the 1/2B1ML group. Endoscopy revealed a greater incidence of esophagitis and gastritis among the 1/3B1ML patients compared with the 1/3RYIC patients. There were no operative deaths, and no differences in morbidity between the groups.Patients with early-stage cancer actually benefit from 1/2 gastrectomy rather than the typical 2/3 gastrectomy. B-1 reconstruction is appropriate for patients with large gastric remnants, and intra-corporeal reconstruction in experienced hands is associated with no apparent disadvantages, while offering a favorable cosmetic result.

Introduction: In laparoscopic rectal surgery, there are some limitations on a surgeon's ability to maneuver, especially in transection of the lower rectum. To achieve minimally invasive surgery, safe anastomosis, including proper rectal transaction, is necessary. Methods: To overcome the difficulty in lower rectal resection, we followed a series of steps. First, we completely mobilized the rectum to the pelvic bottom, just above the anal canal, making the lower rectum mobile and allowing for an easy rectal transection. To secure the transaction, the mesorectum around the transection must be properly divided. We recommend placing the lower right quadrant port as caudal as possible to properly staple the rectum. We found a 60 mm compression-type stapler most suitable for rectal transection. To wash and flatten the rectum, a detachable intestinal clip is quite useful because of its flexibility. Finally, in addition to conventional abdominal drains around the anastomotic site, we employed transanal tube to actively decompress rectal pressure inside the anastomotic site. Results: Between August 2009 and July 2010, 101 patients underwent laparoscopic low anterior resection using this technique. Most patients, 98.0% (99/101), underwent lower rectum transection using a single-fire cartridge. The anastomotic leakage rate was only 1.0% (1/101) in total and 1.3% (1/78), when not including patients with diverting stoma. Conclusion: We have to follow up with more patients to conclude whether our technique is effective in the long term. However, this step-by-step technique could lead to safe anastomosis in laparoscopic low anterior resection for rectal cancer.

Aim: Chymase converts angiotensin I to angiotensin II, which may promote the development of liver fibrosis. In this study, whether a chymase inhibitor TY-51469 attenuated tetrachloride (CCl4)-induced liver fibrosis was examined. Methods: Liver fibrosis was induced by the s.c. injection of 1 mL/kg of CCl4 twice weekly for 8 weeks, and each hamster was given TY-51469 (1 mg/kg per day) or placebo. Untreated hamsters were used as a control group. Results: Significant increases of serum alanine aminotransferase, total bilirubin and hyaluronic acid levels were observed in the placebo-treated group compared with the control group, but these levels were significantly attenuated in the TY-51469-treated group. Liver chymase activity was significantly higher in the placebo-treated group than in the control group, whereas the activity in the TY51469-treated group was not. Total angiotensin II-forming activity in the liver was also significantly higher in the placebo-treatedgroup than in the control group or the TY-51469-treated group. The ratio of the fibrotic area to the total area in the liver was significantly higher in the placebo-treated group than in the control group, but the ratio was significantly lower in the TY-51469-treated group than in the placebo-treated group. A significant decrease in the number of α-smooth muscle actin (SMA)-positive cells was seen in the TY-51469-treated group compared to the placebo-treated group. Conclusion: Significant correlations between the number of chymase-positive cells and the degree of fibrosis and between the numbers of chymase-positive cells and α-SMA-positive cells were observed. Thus, chymase inhibition may be a useful strategy for preventing liver fibrosis.

Background Laparoscopic gastrectomy (LG) is becoming increasingly popular for management of early gastric cancer (EGC). Although short-term efficacy is proven, reports on long-term effectiveness are still infrequent. Study Design All patients with a diagnosis of gastric cancer undergoing LG from the beginning of our laparoscopic experience were included in the analysis. At our unit, LG is indicated for all cancers up to preoperative stage T2N1. Results Six-hundred and one laparoscopic resections were included in the analysis. There were 392 men and 209 women. Mean age was 64.2 ± 10.9 years. Distal gastrectomy was performed in 305 patients, pylorus-preserving gastrectomy in 148, segmental gastrectomy in 42, proximal gastrectomy in 53, total gastrectomy in 27, and wedge resection in 26. Histological staging revealed that 478 patients had stage IA disease, 47 had stage IB, 44 had stage IIA, 19 had stage IIB, 8 had stage IIIA, 3 had stage IIIB, and 2 had stage IIIC. Morbidity and mortality rates were 17.6% and 0.3%, respectively. Median follow-up was 35.9 months (range 3 to 113 months). Cancer recurrence occurred in 15 patients and metachronous gastric remnant cancer was detected in 6 patients. The 5-year overall and disease-free survival rates were 94.2% and 89.9%, respectively, for stage IA tumors, 87.4% and 82.7% for stage IB, 80.8% and 70.7% for stage IIA, and 69.6% and 63.1% for stage IIB. Conclusions In our experience, long-term oncological outcomes from LG for EGC are acceptable. Wherever expertise permits, LG should be considered as the primary treatment in patients with EGC.

Aim: Mast cells may be involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). The mast cell protease chymase contributes to the formation of angiotensin II and matrix metalloproteinase (MMP)-9, both of which are intimately involved in liver fibrosis. Therefore, we hypothesized that chymase plays an important role in the development of NASH. Methods: Hamsters were fed a methionine- and choline-deficient (MCD) diet for 8 weeks. These animals were divided into two groups and received either TY-51469 (1 mg/kg per day) or placebo. A third group was fed a normal diet as a control. Results: Total plasma bilirubin, triglycerides, and hyaluronic acid levels were significantly higher in the MCD diet-fed hamsters than in the normal diet-fed hamsters, but the levels were significantly lower in chymase inhibitor-treated MCD diet-fed hamsters than in placebo-treated MCD diet-fed hamsters. Using histological analysis, marked steatosis and fibrosis were observed in MCD diet-fed hamsters, but these changes were significantly attenuated by treatment with the chymase inhibitor. Increases in mast cells and chymase-positive cells were observed in the liver after the MCD diet, but the increases disappeared in the chymase inhibitor-treated group. The significant increase observed in chymase activity in liver tissue extract from the MCD diet-fed group was also reduced by treatment with the chymase inhibitor. Chymase inhibition significantly reduced not only angiotensin II expression but also matrix metallopeptidase 9 activity in MCD diet-fed hamsters. Conclusion: These findings demonstrate that the mast cell protease chymase may play a crucial role in the development of NASH in hamsters.

Abstract #3011 [Objective] In the treatment of breast-conserving surgery, positive margins are closely related to intramammary recurrence, but methods of assessing resection stumps during breast-conserving surgery have not been standardized. The present study investigated the usefulness of intraoperative touch smear cytology at our department. [Subjects and Methods] From 2005 to 2007, a total of 308 patients underwent breast cancer surgery. Subjects comprised 160 patients who underwent breast-conserving surgery and touch smear cytology. Results of touch smear cytology were compared to those of histological tissue analysis. [Results] Touch smear cytology displayed 70% sensitivity (14/20), 97.1% specificity (136/140) and a diagnostic accuracy of 93.8% (150/160). Six false-negative cases and 4 false-positive cases were identified. Of the 6 false-negatives, cancer cells were seen in the mammary duct in 5 cases, and the degree of cancer cell atypia in the stump was low. Residual cancer cells were seen in the stump in 18 cases, and additional resection was performed on 16 cases. Cancer cells were identified histologically in the additionally resected tissue in 8 of these 16 cases (50.0%). The direction of positive cytology was towards the mammary papilla in 16 cases, lateral tissue in 5 cases and contralateral mammary papilla in 2 cases. The tendency was that that the greater the cancer cell volume as assessed by touch smear cytology, the higher the frequency of positive margins as assessed by histological tissue analysis. [Discussion] Histological tissue analysis and touch smear cytology can be performed to assess resection stumps during breast-conserving surgery. Histological tissue analysis is accurate, but: 1) analyzing all areas of a large resection stump is difficult; 2) preparing high-quality frozen sections is difficult due to the high adipose content of breast tissue; 3) assessing the malignancy of intraductal proliferating lesions is difficult; and 4) part of the tissue sample is damaged. Touch smear cytology is easy to perform, offering a very useful technique yielding comparable results to histological tissue analysis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3011.

新臨床研修制度の影響を強く受けて，外科の門をくぐる若手医師の数は減少してきており，外科医療の崩壊も一部に危惧されている．これに至った問題点を明確にして，どのような解決法があるのかを検討することを本学会総会の一つの目的としているが，こうした状況においては若手外科医の教育，人材育成がさらに重要である．そうした意味合いから本メインテーマを表記のようにしている．臨床外科医に求められていることはまさしく「高度な手術技能と知識を備えていること」であり，また同時に「豊かな人間性を備えていていること」が，その付託に応えられる必要条件となる．このような外科医をどう育成していくのかがまた，指導者たちには求められている．大阪医科大学外科学教室は一般・消化器外科学教室となった昭和51年より35年の歴史を持つが，その間の手術の内容と実数の年次的推移を検討すると各臓器疾患において，ことに近年に至って増加傾向が顕著である．これらは乳癌に対する乳房温存手術，食道癌に対する術前・術後化学放射線療法の導入，胃癌・大腸癌・胆嚢・一部の肝・膵疾患については内視鏡外科の積極的導入など治療の低侵襲化が大きく関与してきた．悪性腫瘍を主として対象にするだけに，手術方法の変更は腫瘍学的裏づけの確認が必要であり，同時に，新規の手術方法の習得に向けた系統的教育・訓練カリキュラムの実践が重要である．そうしたわれわれの努力は全国規模の内視鏡外科セミナーの定期的開催や，国際的先進施設群との交流とe-learning 用の内視鏡外科教材WebSurgの協調開発などに結びついてきた． こうした手術手技の教育環境の成果であろうか，現在まで11名の日本内視鏡外科学会技術認定医が教室関係者から誕生している．“医療は進化を続けており，常に次世代に向けた過渡期にある”とされている．当教室の外科治療の変遷をみても，それは明確であり，そうであるなら次世代の外科学も現状の継続であるとは考えられない．内視鏡外科学の近未来についてはNOTESや単孔式手術が注目され，またロボット手術など医用工学の発展に裏付けられた近代外科学の到来も遠くないことが考えられる．外科技能と精神性など臨床医として求められる要件を指導しながら，正しい将来予測のもとに次世代につながる外科医達を養成することがわれわれの大切な務めであると感じている．

はじめに：肝切除術後の予防的ドレナージの有用性を否定している論文が多いにもかかわらず，依然多数の施設で挿入されている．今回，自験例をもとにドレーン挿入の是非と必要例について検討した．対象と方法：2001年5月から2009年10月までの胆道・消化管吻合のない肝切除術でドレーンを挿入した259例をDrainage群（以下，D群），ドレーンを挿入しなかった118例をNon drainage群（以下，ND群）とし，術後合併症頻度をretrospectiveに比較した．さらに，術後胆汁漏症例とND群の術後ドレーン挿入例から，ドレーン挿入必要例を検討した．結果：術後合併症は，創感染のみND群で5.9％とD群の13.5％に比べ有意に低く，術後入院日数もND群が12日と，D群18日に比べ短かった．ND群の術後早期ドレーン挿入例は，肝不全を併発した3例であった．また，術後胆汁漏発生の危険因子は，再肝切除，主要Glisson鞘の露出術式（中央2区域・前区域切除）と術中胆汁漏が同定されたが，胆汁漏発生日が術後19.5日と遅かった．まとめ：胆道再建などを伴わない肝切除後は，全例にドレーンを留置する必要はなく，肝不全発症予知の点からは門脈腫瘍栓を伴う大量肝切除症例や，術後胆汁漏の点からは中央2区域・前区域切除あるいは再肝切除で術中胆汁漏を認めた症例に予防的なドレーン挿入が有用である可能性が示唆された．

Background. Multiple gastric carcinomas often arise in gastric mucosa with chronic gastritis, particularly severe intestinal metaplasia. In regard to such characteristics, several clinicopathological risk factors for multiple carcinomas have been reported, but no clinically useful criteria are available at present for assessing the onset of multiple gastric carcinomas. If the risk for multiple gastric carcinomas could be accurately assessed, effi cient and accurate surveillance could be performed following minimally invasive therapies. Methods. In the present study, we investigated clinicopathological differences between 94 cases of multiple early gastric carcinomas and 285 cases of solitary early gastric carcinoma. We tested 379 specimens of gastric carcinomas that had been surgically resected at the Department of General and Gastroenterological Surgery of Osaka Medical College, Japan, from April 1999 to December 2006. Results. Univariate analysis of clinicopathological factors in the present study showed that multiple gastric carcinomas were signifi cantly correlated to old age (≥65 years), well- and moderately differentiated histological type, mucin phenotype (intestinal type), distribution of atrophic mucosa in the stomach (severe), degree of intestinal metaplasia in the surrounding mucosa (severe), and heterotopic glandular cysts. Multivariate analysis using the stepwise method identifi ed age (≥65 years) and degree of intestinal metaplasia in the surrounding mucosa (severe) as signifi cant independent risk factors for multiple gastric carcinomas. Conclusion. While other studies have shown risk factors for multiple gastric carcinomas, the present study is unique in showing risk assessment criteria based on a combination of risk factors for multiple gastric carcinomas.

The application of laparoscopic gastrectomy in management of gastric cancer is being propagated rapidly. Training and education play important role during this process. The purpose of this study is to define the learning curve of laparoscopic gastrectomy to obtain an insight into this training process.All 362 cases of laparoscopic gastrectomy from January 1998 to July 2007 were enrolled and divided into 12 groups of 30 cases each in time sequence. The learning curve was defined with the split group method. Laparoscopic distal gastrectomy was extracted from the 12 groups and the means of operation time and intraoperative blood loss were compared to define the learning curve. Then general data and variables including occurrence of systematic inflammatory response syndrome (SIRS), complications, and conversion to open surgery were compared among the phases of learning curve.A three-phase learning curve of laparoscopic gastrectomy was defined from the laparoscopic distal gastrectomy-based analysis, which included a training phase for the first 120 cases of operation, an intermediate phase for the following 90 cases, and a well-developed phase for the last 152 cases. Learning was considered to be complete after 60-90 operations in the training phase. For most variables, the differences among three phases were statistically significant except for the rate of complications.There was a significant learning curve, composed of three phases. Experience of about 60-90 cases of operation was required for completion of learning.

This retrospective study evaluated the safety and efficacy of combination chemotherapy using docetaxel and nedaplatin in an outpatient setting compared with those of chemotherapy using cisplatin (CDDP) and 5-Fu under hospitalization. Subjects comprised 21 patients who had been diagnosed with recurrent esophageal squamous cell carcinoma (ESCC), with 10 patients receiving combination chemotherapy comprising CDDP and 5-fluorouracil (5-Fu) under hospitalization (FP group; n = 10), and 11 patients receiving combination chemotherapy comprising docetaxel and nedaplatin in an outpatient setting (Doc/Ned group; n = 11). In the Doc/Ned group, patients received 30 mg/m(2) of docetaxel over a 1-h infusion on day 1, followed by 40 mg/m(2) of nedaplatin over a 2-h infusion on day 1 in an outpatient setting. In the Doc/Ned group, complete response was observed in two patients (18.1%), one with liver metastasis and one with abdominal lymph node metastasis, and two (18.1%) achieved partial response. In contrast, no complete responses were obtained in the FP group, and partial response was observed in only one patient (10.0%) with local recurrence. Response rates were thus 36.3% for the Doc/Ned group and 10.0% for the FP group. With a median follow-up of 234 days in the Doc/Ned group and 279 days in the FP group, median survival time (MST) was 234 days in the Doc/Ned group and 378 days in the FP group. No significant differences in MST were identified between groups. Thus regimen based on docetaxel and nedaplatin allows administration on an outpatient basis and appears feasible for recurrent ESCC as a second-line chemotherapy.

A case of primary NK/T-cell lymphoma of the rectum accompanied with ulcerative colitis (UC) in a 73-year-old man is reported. He had a 6-year history of repeated admission to our hospital for UC. Total colonoscopy performed 4 months after resolution of refractory UC complicated by cytomegalovirus colitis showed a markedly submucosal tumor in the rectum, which was histologically diagnosed as malignant lymphoma. The findings of computed tomography of the chest and abdomen, gallium scintigraphy, abdominal ultrasonography, and upper gastrointestinal endoscopy showed no abnormal lesions. Therefore, based on a diagnosis of localized rectal lymphoma with UC, proctocolectomy was performed. The resected specimen showed three submucosal tumors in the rectum with local nodal involvement. Histologically, the tumors were characterized by diffusely infiltrating sheets of large atypical lymphoid cells, which were negative for CD4, CD8, and CD20 but were positive for CD56, CD3, and granzyme B. The presence of Epstein-Barr virus (EBV) infection in neoplastic cells was shown by in situ hybridization for EBV-encoded early small RNA1 (EBER-1). Based on these findings, the patient was diagnosed with primary CD56+ NK/T-cell lymphoma of the rectum (stage IIE). This is the first case report of primary rectal NK/T-cell lymphoma accompanied with UC.

Detection of novel tumor-related antigens and autoantibodies in cancer patients is expected to facilitate the diagnosis of early-stage malignant tumor and establish effective new immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. TE-2 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, followed by Western blot analysis in which sera from patients with ESCC, healthy controls and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser disorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Sera from patients with ESCC yielded multiple spots, one of which was identified as heat shock protein 70 (Hsp70) by MALDI-TOF/TOF-MS. Concentrations of serum Hsp70 autoantibody were significantly higher for patients with ESCC (mean, 0.412+/-0.096 mg/ml) than for patients with gastric (0.236+/-0.112 mg/ml, P

症例は44歳，女性．2005年2月27日に自己触診にて右乳房の腫瘤を認め当院外来を受診した．視触診上，右乳房C領域に3.1×3.0cm大の腫瘤を認め，右乳房は左乳房に比べ明らかに小さく，右乳輪は左乳輪と比べ高位置であった．マンモグラフィー，超音波検査，穿刺細胞診の結果，右乳癌（classV）と診断した．また胸部CT検査にて右側の大胸筋，小胸筋，前鋸筋の欠損が疑われた．術前に右上肢の機能障害は認めなかった．2005年3月24日，当院にて乳房切除術（児玉法）を施行，術中所見でも大胸筋，小胸筋，前鋸筋は認めなかった．病理組織検査では2.3×2.0×1.1cm，papillotubular carcinoma，f，pT2，n0，M0 stage IIA，免疫組織学的検討ではER(+)，PgR(+)，Her2(2+)と診断された．先天性胸筋欠損症に併発した乳癌は極めて希有であり，文献的考察を加えて報告する．

目的:乳腺診断において，非侵襲的な手技である穿刺吸引細胞診（fine needle aspiration biopsy cytology:以下FNAC）の役割は大きいが，良悪性の鑑別に難渋する症例にも遭遇する．FNACのピットフォールや有用性に関して検討した．対象:FNACを施行した506例（悪性463例，良性43例）を対象とし，FNACと永久組織標本を比較検討した．結果:悪性疾患463例中，FNACで「悪性」と診断しえたのは341例（73.7％）で，「悪性疑い」23例（5.0％）を含めると364例（78.7％）であった．「鑑別困難」が17例（3.7％），「良性」が39例（8.4％）で，「検体不適正」が43例（9.3％）であった．「検体不適正」症例は，非浸潤性乳管癌（37.5％）や非触知癌（26.3％）にて頻度が高く，腫瘍径が有意に小さく，grade1症例に多い傾向にあった．「鑑別困難」症例には，まれな疾患が含まれ核異型度grade3の症例が少なかった（6.7％）．一方，良性疾患中「鑑別困難」症例には，乳頭状病変，葉状腫瘍が多く含まれていた．また，良性疾患に過大手術を行ったDuctal adenomaおよび肉芽腫性乳腺炎を1例ずつ経験した．結語:乳腺診断においてFNACは有用であるが，類推組織型を念頭におき，診断が困難な場合は積極的に組織診を行い，整合性を得ながら診断すべきである．

目的:胃癌手術後の重篤な合併症のひとつとして，膵液漏に起因する腹腔内出血がある．同症例の治療方針について検討を行ったので報告する．対象と方法:1997年1月から2007年9月，当科で施行した胃癌切除症例1176例のうち，膵液漏に起因する腹腔内出血を認めた15例に対して行った治療と成績について検討を行った．結果:1176例中，78例（6.6％）に膵液漏を認め，うち15例（1.3％）に腹腔内出血を認めた．合併症の発生には，リンパ節郭清と合併切除による膵損傷が関与している可能性が示唆された．止血法として，IVRによる動脈塞栓術が，開腹止血術と同等の成績を示した．また，予後に関しても同等の成績であった．結語:胃癌術後の膵液漏による腹腔内出血時は，IVRによる動脈塞栓術を中心とする早期の対処が重要であると考えられた．

Nuclear factor-kappaB (NF kappaB) plays a pivotal role in cancer progression. In this study, we developed a decoy cis-element oligo-deoxyribonucleic acid against NF kappaB-binding site (NF kappaB-decoy), which effectively inhibits NF kappaB activity, and tested the effect of combined therapy comprising local transfection of NF kappaB-decoy into the liver and transportal injection of paclitaxel on cancer growth and metastasis using an orthotopic murine model of colon cancer liver metastasis. For NF kappaB-decoy transfection, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison. We examined the influence of NF kappaB-decoy transfer on susceptibility to paclitaxel in cancer cells and the mechanism involved using several in vitro analysis systems. We then studied the in vivo effect of combined NF kappaB-decoy transfer and paclitaxel in preventing cancer progression using a murine model of liver metastasis created by splenic injection of a human colon cancer cell line, HT29. In vitro experiments, including MTT-assay, fluorescence-activated cell sorter and cDNA array analysis, revealed that NF kappaB-decoy transfer significantly increased the susceptibility of cancer cells to paclitaxel, and that decreased expression of anti-apoptotic genes along with increased expression of genes relevant to the apoptosis-promotor may be involved. In vivo experiments showed that local transfection of NF kappaB-decoy into the liver followed by portal injection of paclitaxel effectively induced cancer cell apoptosis in the liver metastasis, and significantly prolonged animal survival compared to controls, without notable side effects. In conclusion, a combination of local NF kappaB-decoy transfer into the liver and transportal injection of paclitaxel may be a safe and effective new therapy for liver metastasis.

Objective To evaluate local invasion and lymph nodes metastasis of colorectal cancer and mesenteric vascular variations using multidetector-row computed tomography (MDCT) before laparoscopic colorectal surgery. Methods Fifty-one patients with colorectal cancer underwent MDCT. The evaluation items were as follows: (1) local invasion; (2) detected lymph nodes evaluated by short-axis diameter, long-axis diameter, short/long axis diameter ratio, and computed tomography (CT) attenuation; and (3) visualization of mesenteric artery and vein by 3-dimensional-CT angiography. Results First, in the evaluation of local invasion, overall accuracy was 94.1%. Second, the point of 0.8 or greater in short/long-axis diameter ratio was best index for the diagnosis of metastatic lymph nodes. Using this index, the accuracy of the diagnosis per node was 80.5%. Third, 3-dimensional-CT angiography correctly demonstrated variations of the mesenteric artery and vein. Conclusions The MDCT was effective for evaluation of local invasion and lymph nodes metastasis of colorectal cancer and mesenteric vascular variations before laparoscopic surgery.

Background We assessed the utility of enhanced magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph node metastases in patients with breast cancer. Study design MR examination of the axilla was performed before and 24–36 h after USPIO administration for patients with stage II or III breast cancer. Diagnostic performance was compared using size criteria (metastasis was defined when short axis diameter >5 or >10 mm) or morphologic criteria on conventional MRI, the combined study of USPIO precontrast and postcontrast images, and USPIO postcontrast study alone. Results A total of 622 nodes (503 metastatic and 119 nonmetastatic nodes) were dissected from 33 patients. The results of conventional MRI for nodes >5 mm were 59.1% sensitivity, 86.7% specificity, and 80.4% overall accuracy. Results for nodes >10 mm were 15.7% sensitivity, 99.2% specificity, and 80.2% overall accuracy. Results based on morphology were 36.5% sensitivity, 94.1% specificity, and 81.0% overall accuracy. The results of the combined study of USPIO precontrast and postcontrast images were 86.4% sensitivity, 97.5% specificity, 91.1% positive predictive value, 96.1% negative predictive value, and 95.0% overall accuracy. The results of USPIO postcontrast images alone were 84.7% sensitivity, 96.8% specificity, and 94.0% overall accuracy. Patient-based results of postcontrast USPIO study alone were 100.0% sensitivity, 80.0% specificity, and 93.9% overall accuracy. Conclusions USPIO postcontrast study alone was useful in the assessment of axillary lymph node metastases in patients with breast cancer.

The KCNQ1 gene encodes a voltage-dependent potassium ion channel, and mutations in this gene are the most common cause of congenital long QT syndrome (LQTS). In the present study, we investigated the various phenotypic characteristics of vertigo 2 Jackson (C3H/HeJCrl-Kcnq1(vtg-2J)/J) mice with a Kcnq1 mutation. Both heterozygotes (vtg-2J/+) and homozygotes (vtg-2J/vtg-2J) showed prolonged QT intervals in electrocardiograms (ECGs) compared to C3H/HeJ control (+/+) mice. Furthermore, vtg-2J/vtg-2J mice showed gastric achlorhydria associated with elevation of their serum gastrin levels. The serum corticosterone levels were also significantly increased in vtg-2J/vtg-2J mice. In addition, vtg-2J/vtg-2J mice exhibited significantly higher blood pressure. These findings indicate that the Kcnq1 mutation in vtg-2J mice alters various physiological functions in the cardiac, gastric and adrenocortical systems, and suggest that vtg-2J mice may represent a useful model for studying Kcnq1 functions.

中腸軸捻転を伴う腸回転異常症は多くが新生児期に発症し, 1歳以降は稀である. 今回年長児中腸軸捻転を伴う腸回転異常症の2例を経験したので報告する. 症例1は6歳, 男児. 症例2は12歳, 男児. いずれも腹痛, 胆汁性嘔吐を主訴に来院した. 腹部カラードプラ超音波検査にてWhirlpool signがみられ中腸軸捻転を伴う腸回転異常症と診断した. 症例2は3D-CT検査も行い診断の一助となった. 過去15年間に当科で経験した本症は4例と稀ではあるが, 1歳から15歳児での嘔吐, 腹痛の原因疾患として虫垂炎, 腸重積についで3番目であった. また4例のうち新生児は1例のみであった. 小児専門病院以外では年長児の症例に遭遇することが多く, 嘔吐, 腹痛症例に際して本症も念頭におくべきと考えられた.

Between January 2012 and June 2013, we performed laparoscopic choledocholithotomy on 10 cases of common bile duct stone disease. Laparoscopic surgery for common duct stone disease is technically demanding. Particularly, laparoscopic intracorporeal suturing and knot tying for repair of choledochotomy are the most difficult skills in this operative procedures. Barbed sutures has recently been proposed to facilitate laparoscopic suturing. This is the first report demonstrating that the barbed suture could potentially improve the efficacy of the intracorporeal repair of choledochotomy following extirpation of biliary tract stones with less time needed to suture.Consecutive 10 patients with common bile duct stones who underwent laparoscopic choledocholithotomy were enrolled in this study. Choledochotomy was closed with V-Loc sutures (15 cm V-Loc 180 sutures) for 7 patients, and a V-20 needle (26 mm, tapered) for 3 patients.The mean choledochotomy closure time was significantly shorter in the V-Loc group (15.2 ± 1.6 min) than in the Vicryl group (23.5 ± 1.5 min). The unidirectional barbed sutures allowed surgeons to use both their hands effectively and to focus exclusively on the placement of the subsequent stitches, without the need to maintain tension on preceding stitches to prevent slippage. And also the unidirectional barbed sutures were able to distribute tension evenly along the suture line, allowing good tissue apposition.The knotless unidirectional barbed sutures are a safe and effective tool for choledochotomy repair during surgery for common bile duct stones.

Background Extended lymphadenectomy (D2) provides accurate nodal staging of gastric cancer. The aim of this study was to clarify the degree of stage migration seen with D2 combined with para-aortic lymph node dissection for gastric cancer invading the subserosa, the serosa and adjacent structures (T2ss–4) in patients considered not to have distant metastases (M0). Methods Between July 1995 and April 2001, 523 patients were recruited and randomized in a prospective phase III trial comparing D2 with D2 and para-aortic nodal dissection for T2ss–4 gastric cancer without macroscopic para-aortic nodal metastases. Stage migration was evaluated by Japanese Gastric Cancer Association staging in 260 patients who underwent D2 with para-aortic dissection by analysing pathological information from the dissected lymph nodes. Results Node (N)-stage migration was observed in 1 per cent (1 of 82) of patients with N1 disease, 20 per cent (12 of 59) with N2, 43 per cent (10 of 23) with N3 and 8·8 per cent (23 of 260) of all patients. Final stage migration occurred in 9 per cent (5 of 58) of patients with stage IIIa, 19 per cent (8 of 42) with stage IIIb, 56 per cent (9 of 16) with stage IVa and 8·5 per cent (22 of 260) of all patients. Metastasis to N4 nodes was found in 4 per cent (four of 95) of tumours invading the subserosa and 17·4 per cent (19 of 109) of tumours penetrating the serosa. The overall incidence of N4 involvement was 8·8 per cent (23 of 260). Conclusion Extended para-aortic lymphadenectomy for gastric cancer provides accurate nodal staging and results in stage migration, which may improve stage-specific survival regardless of overall survival benefit.

In the surgical field, benign esophageal tumors are much more uncommon than esophageal malignancies. In particular, fibrovascular polyps of the esophagus are extremely rare. We present a case involving a giant fibrovascular polyp (22 cm × 9 cm) in which not only location and site of origin but also precise polyp type were diagnosed preoperatively using magnetic resonance imaging (MRI). The lesion was then resected safely using a cervical approach. MRI is useful for acquiring valuable information about fibrovascular polyps. This case demonstrates the utility and safety of transcervical esophagotomy in the treatment of giant fibrovascular polyp of the esophagus.

Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer.Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide--ferumoxtran-10 (2.6 mg Fe/kg of body weight)--and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery.Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region.The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.

Sclerosing mesenteritis is a rare and benign inflammatory entity characterized by fibrofatty thickening of the mesentery. To our knowledge, there are only a few reports on the features of sclerosing mesenteritis on magnetic resonance (MR) imaging and computed tomography (CT). In this present case, MR imaging demonstrated tissue characterization of fibrosis, and partial maximum intensity projection (MIP) and three-dimensional angiography images obtained using multislice CT clearly revealed the extent of the tumor and the vascular appearance affected by the mass. However, a mesenteric metastasis from the carcinoid tumor may show such imaging features. Therefore, when encountering such a case, we suggest that a tentative diagnosis of sclerosing mesenteritis be made, followed by a biopsy for intraoperative histopathologic analysis to avoid aggressive surgery.

Background Accurate detection of metastasis to lymph nodes is an essential component of the approach to treatment. The purpose of this study was to evaluate the utility of magnetic resonance imaging with ferumoxtran-10 in diagnosing lymph node metastasis in esophageal cancer. Study design Sixteen patients with esophageal cancer who were scheduled for surgical lymph node dissection were enrolled. All patients underwent MRI scanning before and 24hours after intravenous administration of ferumoxtran-10, an ultrasmall, superparamagnetic iron oxide. The presence or absence of metastasis was identified in lymph nodes by their enhancement patterns. Nonmalignant nodes contained macrophages that phagocytosed ferumoxtran-10. Metastatic nodes exhibited a decrease in phagocytic activity, and consequently showed little or no uptake of ferumoxtran-10. So we subdivided the enhancement patterns into the following three patterns: (A) node having an overall low signal intensity, (B) node having an area of high signal intensity, and (C) node having an overall high signal intensity. We identified that patterns (B) and (C) were metastatic patterns. The imaging results were compared with histopathologic findings. Results Of the 408 resected lymph nodes, imaging results of 133 nodes could be compared with histopathologic findings. Twenty-four lymph nodes had histopathologic metastases. Using our enhancement criteria, sensitivity was 100%, specificity was 95.4%, and accuracy was 96.2% for diagnosis of metastatic nodes. Conclusions Ferumoxtran-10 is useful for characterizing benign or malignant lymph nodes in esophageal cancer patients based on the defined enhancement criteria.

In this study, we evaluated the efficacy of dual-phase 3D CT angiography (CTA) during a single breath-hold using 16-MDCT in the assessment of vascular anatomy before laparoscopic gastrectomy.The study involved 20 consecutive patients (10 men, 10 women; mean age, 59 years) scheduled for laparoscopic gastrectomy for the treatment of early gastric cancer. A dual-phase contrast-enhanced CT scan using 16-MDCT was obtained before laparoscopic gastrectomy. After rapid infusion of a nonionic contrast agent, arterial and venous phase scans were obtained serially with an interval of 15 sec during a single breath-hold of 31 sec. Three-dimensional CTA images in the arterial phase (3D CT arteriography) and venous phase (3D CT venography) were individually reconstructed using the volume-rendering technique, and then the images were fused together. We evaluated the detectability of the celiac trunk, left gastric artery (LGA), right gastric artery (RGA), left gastric coronary vein (LCV), Henle's gastrocolic trunk, right gastroepiploic vein (RGEV), and accessory right colic vein on 3D CTA to compare with surgical findings.In all 20 patients, 3D CT arteriography and venography clearly showed the celiac trunk, LGA, RGA, Henle's gastrocolic trunk, RGEV, and accessory right colic vein, which were correctly identified during surgery. The branching pattern of the celiac trunk was classified as Michels type I in 19 patients and Michels type II in one patient. Imaging showed the RGA originating from the proper hepatic artery (PHA) in nine patients; from the gastroduodenal artery (GDA) in seven patients; and from the left hepatic artery (LHA) in four patients. In 12 patients, the LCV joined the portal vein (PV) and in eight, the splenic vein (SV). In all patients, the accessory right colic vein joined the RGEV, and Henle's gastrocolic trunk proximal to the joining point flowed to the superior mesenteric vein (SMV). In all 20 patients, the fused image simultaneously showed arteries and veins around the stomach, with no mismatch between the arterial and venous phase images. In 10 patients, the LCV joined the PV after running along the dorsal side of the PHA, common hepatic artery (CHA), or splenic artery (SA). In eight patients, the LCV joined the SV after running along the ventral side of the PHA, CHA, or SA. In two patients, the LCV joined the PV after running along the ventral side of the CHA, which correlated with the surgical findings. Both the sensitivity and positive predictive values of 3D CTA revealed 100% correct identification of the celiac trunk, LGA, RGA, LCV, Henle's gastrocolic trunk, RGEV, and accessory right colic vein.Dual-phase 3D CTA using 16-MDCT clearly revealed individual arteries and veins around the stomach before laparoscopic gastrectomy. The fused image of 3D CT arteriography and venography during a single breath-hold enabled the simultaneous assessment of arteries and veins before laparoscopic gastrectomy.

乳腺invasive micropapillary carcinoma (IMP)は,リンパ管侵襲やリンパ節転移を高率に伴う生物学的悪性度の高い浸潤性乳管癌の-亜型である.穿刺吸引細胞診にて術前診断しえた2症例を経験した.症例1は, T2N1M0, stage IIBで胸筋温存乳房切除術を施行した. IMP成分80%, n(+) 23個陽性, ER(+), PgR(+)で化学療法(CAF, weekly paclitaxel)施行後,放射線照射,内分泌療法施行中である.症例2は, T2N0M0, stage IIAで胸筋温存乳房切除術を施行した. IMP成分60%, ly(+), v(-), n(-), ER(+), PgR(+)で内分泌療法施行中である. 2症例とも, IMPに特徴的な細胞所見がみられ術前に診断しえた. IMPの細胞像を念頭におき診断することが重要である.

化学療法後に孤立性に再燃した,卵巣癌術後脾転移の1例を報告するとともに, 2005年11月までの卵巣癌孤立性脾転移の本邦報告例と自験例を含めた14例について検討した. 70歳,女性, 2002年7月,当院産婦人科にて左卵巣癌に対し準広汎子宮全摘術, CDDPによる抗癌剤腹腔内投与(IP)および術後化学療(Paclitaxel+Carboplatin: TJ療法)が施行された.術前の腹部CTで脾転移および腹膜播種性病変を認めていたが,術中,術後の化学療法によりそれらは一旦消失した. 2003年9月よりCT上再度脾転移が顕性化し,次第に増大した.しかし,他に再発病変を認めず脾に限局していたため手術適応と判断し, 2005年1月に脾摘術を施行した.脾の転移巣の抗癌剤感受性検査において, Paclitaxelは0%であった. 本症例では,播種巣はIPおよびTJ療法により完全にコントロールされていたが, Paclitaxeiに抵抗性をもった脾の転移細胞が再燃したものと考えられた.