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Purpose:Postoperative diarrhea, including high-output stoma (HOS), frequently occurs after colorectal surgery; its risk factors and clinical implications on subsequent complications remain unknown. This study aimed to evaluate the risk factors and clinical implications of postoperative diarrhea after primary colorectal cancer (CRC) surgery., Methods: This prospective observational study included patients with CRC who underwent radical surgery at six hospitals between June 2016 and December 2017. The patients were categorized into three groups (non-stoma, colostoma, and ileostoma groups)., Results:A total of 178 patients participated in the study. In the non-stoma group, the incidence of postoperative diarrhea was 18.4% (27/147). The incidence of HOS was 28.6% (4/14) in the ileostoma group, and 0% in the colostoma group. Multivariable analyses of the incidence of diarrhea in the non-stoma group indicated that habitual smoking and hypertension were significantly associated with postoperative diarrhea (P = 0.012 and P = 0.0274, respectively). Postoperative diarrhea was more likely to occur in patients with rectal cancer than in those with colon cancer (P = 0.0501). In the non-stoma and ileostoma groups, the probability of the occurrence of other complications with Clavien-Dindo (C-D) grades II or higher was significantly higher in patients with C-D grade I diarrhea, including HOS, than in patients without diarrhea (39.3% vs. 14.6%, P = 0.0061)., Conclusions:Smoking and hypertension are the independent predictors of postoperative diarrhea after an elective CRC surgery. Rectal cancer surgery seems to be associated with postoperative diarrhea more than colon cancer surgery does. Mild postoperative diarrhea may lead to more severe complications.

Introduction:This study aimed to clarify the frequency and risk factors of intercurrent venous thromboembolism (VTE) in patients undergoing major curative gastric cancer surgery., Methods:This prospective, multicenter, observational study included patients with gastric cancer who underwent radical gastrectomy at 5 hospitals between June 2016 and May 2018. Patients who were preoperatively administered anticoagulants were excluded., Results:A total of 126 patients were eligible to participate. VTE occurred within 9 days postoperatively in 5 cases (4.0%; 2 symptomatic and 3 asymptomatic). Postoperative day (POD) 1 plasma D-dimer and soluble fibrin (SF) levels were significantly higher in the VTE group than in the non-VTE group. Receiver-operating characteristic curve (ROC) analysis indicated a statistically significant ability of POD 1 D-dimer and SF levels to predict postoperative VTE development after gastrectomy; this finding was reflected by an area under the curve (AUC) of 0.97 (95% CI 0.92-1.0) and 0.87 (95% CI 0.74-1.0), respectively. Cutoff values of D-dimer (24.6 µg/mL) and SF (64.1 µg/mL) were determined. Intraoperative blood transfusion (odds ratio [OR] 7.86), POD 1 D-dimer ≥24.6 µg/mL (OR 17.35), and POD 1 SF ≥64.1 µg/mL (OR 19.5) were independent predictive factors for postoperative VTE (p < 0.05)., Conclusion:VTE occurred in 4.0% patients (1.6% symptomatic and 2.4% asymptomatic) after gastric cancer surgery; however, with an early diagnosis and anticoagulant therapy, no patients experienced progression. Careful observation of patients with a high risk for VTE, including intraoperative blood transfusion and high POD 1 D-dimer or SF levels, would contribute to the early detection of VTE.

Objectives In Japan, there are three grades of peritoneal metastasis from colorectal cancer. The grade depends on the extent and number of lesions (P classification). The P classification is useful for its simplicity but lacks objectivity. On the other hand, the peritoneal cancer index (PCI) objectively indicates the peritoneal metastasis grade. However, the evaluation process is complicated clinically. In this study, we compared these two methods and investigated how to improve the P classification's objectivity by referring to PCI. Methods We investigated 150 cases of synchronous peritoneal metastasis from colorectal cancer. We inspected the correlation between the P classification and the PCI and pointed out the problems which prevented objective evaluation when using the P classification. We also estimated new criteria for extent and number in the P classification. Results We found the ideal definition for the best alignment between the P classification and the PCI was: ・P1 is metastases confined to one peritoneal region, ・P2 is 19 or fewer peritoneal metastases in two or more regions, and ・P3 is 20 or more metastases in two or more regions. This revision improved the P classification's objectivity and correlated with the PCI. Conclusions Grading using the P classification was both imprecise and subjective. We propose a new standard value of extent and number in the P classification based on the PCI. This improvement would provide an objective, simple method of grading for peritoneal metastasis from colorectal cancer.

ObjectiveWe aimed to evaluate whether Gram stain results from smear preparations of bile are useful in determining the optimal perioperative antimicrobial agents.Summary of background dataSurgical site infections (SSIs) are common complications in emergency cholecystectomy.MethodsA total of 185 patients who underwent emergency cholecystectomy for acute cholecystitis were enrolled (Bell Land General Hospital Ethic Board approval number 2017-0003). Bile was collected from 121 patients. The Gram stain results from bile smear and culture preparations were evaluated. Furthermore, the antimicrobial resistance was evaluated according to bile Gram stain results.ResultsBile bacteria were detected in 82 patients (67.8%) with the culture preparation and in 72 patients (59.5%) with the smear preparation. The average rate of correspondence in the Gram stain results between smear and culture preparations was 86.3% among patients with bile bacteria in the smear preparation. Cefepime and meropenem had a low antimicrobial resistance rate for all Gram stain results (ConclusionsThe Gram stain results from the smear preparation appear to be useful in choosing optimal perioperative antimicrobial agents.

Introduction: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often used to diagnose pancreatic tumors. In rare cases, preoperative EUS-FNA can be complicated by gastric wall implantation of pancreatic cancer. Case presentation: A 66-year-old woman with pancreatic tail cancer underwent evaluation by EUS-FNA, followed by distal pancreatectomy and splenectomy. Twelve months postoperatively, a submucosal tumor was detected at the posterior gastric wall, at the location where the EUS-FNA was performed, and a boring biopsy from the submucosal tumor showed an adenocarcinoma. Therefore, we performed partial gastrectomy. Immunostaining results of the resected specimen were identical to those of the resected pancreatic cancer. The patient was diagnosed as having gastric wall implantation of pancreatic cancer due to EUS-FNA. Conclusion: This case emphasizes the importance of monitoring the site of EUS-FNA for gastric wall implantation of pancreatic cancer, and boring biopsy is a useful diagnostic tool.

Neuroleptic malignant syndrome (NMS) with characteristic symptoms is a potentially lethal reaction to antipsychotic drugs. Atypical NMS usually lacks major symptoms and frequently occurs after treatment using atypical antipsychotics, such as aripiprazole. A 64-year-old man developed aripiprazole-induced NMS after surgery, and our early recognition of the NMS was based on high creatine kinase levels and low serum iron levels. His characteristic symptoms (a fever, rigidity, and altered mental status) were only present for a few hours and were resolved by aripiprazole discontinuation and supportive care. Aripiprazole-induced NMS can present with brief but major symptoms, and clinicians may overlook this "brief" appearance of NMS.

Aim Bladder ruptures are commonly misdiagnosed as gastrointestinal perforations or intestinal ischemia. If a diagnosis is made preoperatively, conservative treatment is a safe and effective option. We evaluated the validity of using the attenuation value of ascites, measured by non-contrast computed tomography (CT), to identify patients with bladder ruptures. Methods A retrospective search of our hospital database identified 7 patients with confirmed bladder ruptures between 2007 and 2013. We also enrolled 18 patients with gastrointestinal perforations and 10 patients with intestinal ischemia with detectable ascites on abdominal CT that had undergone emergency exploratory laparotomy between 2007 and 2013. Between-group comparisons of attenuation values of ascites as obtained by non-contrast CT were evaluated. Results All attenuation values were less than 10 Hounsfield units (HU) in bladder rupture patients. Moreover, the attenuation value of ascites in cases of bladder rupture (median, 5.7; range, 3.1–6.1) was significantly lower than in cases of gastrointestinal perforation (median, 14.7; range, 4.7–25.4) and intestinal ischemia (median, 13.3; range, 6.0–18.1) (P = 0.004 for both comparisons). Conclusion Bladder rupture mimics gastrointestinal perforation and intestinal ischemia with acute kidney injury. Therefore, the diagnosis of bladder rupture using the attenuation value of ascites on non-contrast CT is both useful and highly significant. We suggest that bladder rupture be considered in the differential diagnosis of patients presenting with acute abdominal pain and attenuation values of ascites of less than 10 Hounsfield units.

An 80-year-old man who had undergone distal gastrectomy and Billroth-II gastrojejunostomy 38 years previously, for a benign gastric ulcer, was diagnosed with remnant gastric cancer based on upper gastrointestinal endoscopy findings. He presented at our emergency department with acute-onset epigastric pain due to perforated remnant gastric cancer. Conservative medical management was selected, including nasogastric tube insertion, antibiotics, and proton pump inhibitors, because his peritonitis was limited to his epigastrium and his general condition was stable. Twenty-one days after the perforation occurred, curative total remnant gastrectomy and D2 lymphadenectomy were performed. Adhesion between the lateral segment of the liver and the dissected lesser curvature of the gastric remnant may have contributed to the peritonitis in this case, which was limited to the epigastrium. This is the first report of perforated remnant gastric cancer in which conservative treatment was effective prior to curative resection. The protocol reported here may be of use to other clinicians who may encounter this clinical entity in their practices.

A 76-year-old previously healthy Japanese man experienced severe diarrhea (8,000 mL per day) after undergoing laparotomy for small bowel obstruction and was diagnosed with Clostridium difficile infection. Although he developed a maculopapular rash secondary to the systemic absorption of enteral vancomycin (VCM), the patient was successfully treated with the continuous administration of VCM through a long intestinal tube placed in the terminal ileum. This method ensured the reliable delivery of VCM to the colon, while the continuous administration maintained high fecal levels of the drug. This treatment approach is an effective minimally invasive option for patients with severe diarrhea.

Case An 88-year-old woman presented with abdominal pain, massive ascites, and acute kidney injury. She was clinically hypervolemic and the computed tomography attenuation value of the ascites was near that of water. Subsequent abdominocentesis revealed ammonia-smelling ascites fluid, leading to a suspicion of urinary tract injury, and a conclusive diagnosis of spontaneous bladder rupture was achieved using cystography. Outcome The patient was managed conservatively with antibiotics, percutaneous drainage, and bladder catheter. As a result, she was discharged with normal renal function. Conclusion The diagnosis of bladder rupture is difficult, and is rarely confirmed in the absence of a diagnostic suspicion. This case indicates that ascitic fluid odor, patient volume status, and the computed tomography attenuation value of ascites are potential indicators of bladder rupture.

Clinical diagnosis of internal hernias is challenging because of their nonspecific signs and symptoms. Many types of internal hernias have been defined: paraduodenal, small bowel mesentery-related, greater omentum-related, lesser sac, transverse mesocolon-related, pericecal, sigmoid mesocolon-related, falciform ligament, pelvic internal, and Roux-en-Y anastomosis-related. An internal hernia is a surgical emergency that can develop into intestinal strangulation and ischemia. Accurate preoperative diagnosis is crucial for appropriate management. Multidetector computed tomography (CT), with its thin-section axial images, high-quality multiplanar reformations, and three-dimensional images, currently plays an essential role in preoperative diagnosis of internal hernias. The diagnostic approach to internal hernias at multidetector CT includes detecting an intestinal closed loop, identifying the hernia orifice, and analyzing abnormal displacement of surrounding structures and key vessels around the hernia orifice and hernia sac. At each step, multidetector CT can depict pathognomonic findings. A saclike appearance suggests an intestinal closed loop in several types of internal hernias. Convergence, engorgement, and twisting of mesenteric vessels in the hernia orifice can be seen clearly at multidetector CT, especially with use of multiplanar reformations. For definitive diagnosis of an internal hernia, analysis of displacement of anatomic landmarks around the hernia orifice is particularly important, and thin-section images provide the required information. Detailed knowledge of the anatomy, etiology, and imaging landmarks of the various hernia types is also necessary. Familiarity with the appearances of internal hernias at multidetector CT allows accurate and specific preoperative diagnosis. (©)RSNA, 2015.

目的 : 大腸癌大動脈リンパ節（216LN）転移は遠隔転移の扱いであり通常化学療法の対象となるが，外科的切除により長期予後が得られることがある．そこで当科で216LN転移巣に対して大動脈周囲の系統的郭清を行った症例を検討し手術適応について考察した．対象 : 当科で経験した大腸癌症例580例中（2003年12月-2010年3月），他臓器遠隔転移がなく216LNを系統郭清した9例．男：女＝4：5，平均年齢63歳，原発巣は横行結腸2例，S状結腸3例，直腸4例．結果 : 216LN転移は，再発6例（初回手術時Stage II：1例，IIIa：1例，IIIb：4例），同時性（Stage IV）3例であった．StageIV症例のうち2例は原発巣との同時切除，1例は原発巣切除後1年間化学療法を行ったのち216LN郭清を施行した．216LN郭清後の2年生存率は64％で（異時的郭清例：85％，同時郭清例：0％），最長生存期間は6年9か月であった．生存6例（全例無再発），死亡3例であったが，両者に年齢・性別・原発巣占居部位・組織型の差はなく，相違点として216LN切除を原発巣と異時的に施行した症例の予後が有意に良好であったことがあげられた（p=0.035）．結論 : 大腸癌術後に216LNのみに再発し，また原発巣とは異時的に郭清術を施行した症例は良好な長期予後が得られ，積極的な外科的治療の対象と思われた．

症例は76歳，男性．急速に増大する右腋窩腫瘤を主訴に当院を受診した．初診時，右腋窩に70mm大の腫瘤を認めた．穿刺細胞診では確定診断がつかず，診断目的で腫瘤摘出術を施行した．CK20による免疫染色にて陽性所見を認め，Merkel細胞癌と診断した．全身検索を行うも右腋窩以外に病変を認めなかったことから，右腋窩リンパ節原発Merkel細胞癌と考えた．リンパ節原発Merkel細胞癌は稀であり標準的な治療法は報告されていないものの，本症例は切除および術後放射線照射を施行し，現在術後3年3カ月経過するが再発なく長期生存を得ている．

A 50-year-old man presented with epigastric pain after eating raw mackerel. Abdominal computed tomography revealed submucosal edema of the gastric antrum and pelvic ileum. Gastroscopy revealed an Anisakis simplex in the gastric antrum. His epigastric pain resolved after endoscopic removal of the Anisakis; however, he developed right lower quadrant pain the following day. Abdominal computed tomography showed submucosal edema of the terminal ileum involving different ileal loops, which was not present on admission. The patient developed delayed intestinal anisakiasis. A serving of raw fish may contain more than one Anisakis. After gastric anisakiasis, a second Anisakis may cause intestinal anisakiasis.

80歳，女性．心窩部痛を主訴に近医受診．CT像上，肝左葉に9 cmの占拠性病変が認められた．白血球数とCRP，ALP，LDH値が上昇していたが，腫瘍マーカーは正常範囲内であった．血管造影像上，乏血管性の腫瘍として描出され，Gaシンチ像上，肝内病変にのみ異常集積像が認められた．肝内胆管癌の診断のもとに切除した．腫瘍は白色充実性の腫瘍であり，病理組織検査では異型細胞のびまん性増殖が認められ，酵素抗体法ではLCA，L-26陽性，UCHL-1，CD5，CD10陰性でありDiffuse large B cell type malignant lymphomaと診断された．非癌部肝組織所見は原発性硬化性胆管炎と診断された．術後，エトポシド25 mg/日の投与を継続し術後6カ月間を経過した時点で肝以外に病変はみられないため，最終的に肝原発悪性リンパ腫と診断した．術28カ月後の現在，再発兆候なく通院中である．

肝門部および大動脈周囲リンパ節転移を有する横行結腸癌で，原発巣に対する根治度C手術の1年後に根治的リンパ節郭清を施行し，その後1年5カ月無再発生存中の1例を経験したので報告する．症例は79歳女性．2006年7月に右半結腸切除D3郭清と肝門部リンパ節のsamplingを施行．組織診断は低分化型腺癌，mp，n3，H0，P0，M1（肝門部リンパ節），stageIV，根治度Cであった．術後肝門部・大動脈周囲リンパ節遺残に対してS-1の内服を開始し，一旦PRとなるも，1年後同リンパ節の再増大を認めたため2007年7月に根治的肝門部・大動脈周囲リンパ節郭清を施行した．郭清リンパ節17個中no.8，12a，13，16aに計6個転移を認めた．郭清術後，化学療法は施行せずに1年5カ月経過する現在，再発徴候は認めていない．領域外リンパ節転移を有する結腸癌の治療において，他臓器転移がなく病変部が限局していることを見極めたうえでの根治的なリンパ節郭清術は意義があると思われる．

症例は69歳男性．膀胱三角部に浸潤するS状結腸進行癌Stage IIIbに対し，2008年1月にS状結腸切除D3・膀胱合併切除・尿路再建術を行った．術後2日目に高熱および全身痙攣を呈し昏睡となった．画像上，脳出血・梗塞などは認めず，髄液は無菌性髄膜炎の所見を呈したことから抗ウイルス薬による治療を行い，状態は改善した．後日髄液から単純ヘルペスウイルスDNA陽性を確認した．続いて術後18日目に敗血症性ショックを呈した．当初感染源は不明であったが血液培養よりMRSAを検出し，バンコマイシン投与および透析治療を行った．その後左腸腰筋膿瘍を確認し保存療法により軽快した．2008年4月に退院し，現在再発兆候は認めていない．結腸癌術後早期のウィルス性髄膜炎と腸腰筋膿瘍の合併は他に例がない．遠因として術前の長期担癌状態による低栄養や免疫力低下が推測され，また徹底した原因検索・早期治療と栄養の継続投与により救命し得たと考えられた．

症例は74歳, 女性. 突然の心窩部痛を主訴に来院. 腹部CTにて十二指腸下行脚～水平脚に線状の石灰化像と後腹膜にガス像を認めた. 異物による十二指腸穿通と診断し, 腹膜刺激症状を認めることから緊急開腹術を施行した. 十二指腸下行脚背側に膿の貯留を認め, 水平脚後壁に穿通する異物を確認した. 異物除去, 十二指腸縫合閉鎖術を施行し, 良好な経過を得た. 摘出した線状異物は55mm大で, 鰤の摂取歴があったことおよび成分分析の結果から魚骨と診断した. 魚骨による十二指腸の穿孔・穿通例は本邦においてこれまでに6例の文献報告しかなく, 非常に稀な症例と考えられた.

A 76-year-old previously healthy Japanese man experienced severe diarrhea (8,000 mL per day) after undergoing laparotomy for small bowel obstruction and was diagnosed with Clostridium difficile infection. Although he developed a maculopapular rash secondary to the systemic absorption of enteral vancomycin (VCM), the patient was successfully treated with the continuous administration of VCM through a long intestinal tube placed in the terminal ileum. This method ensured the reliable delivery of VCM to the colon, while the continuous administration maintained high fecal levels of the drug. This treatment approach is an effective minimally invasive option for patients with severe diarrhea.

経仙骨的直腸切除術後に瘢痕ヘルニアをきたした症例を経験した.症例は57歳男性で主訴は仙骨部腫瘤であった.直腸癌に対し経腹仙骨的直腸切除術を施行した8カ月後より右臀部仙骨右縁下端の手術創部の皮下に腫瘤を自覚するようになり, 2004年10月には8cm×6cmにまで増大した.骨盤部CTにて仙骨右側下方の臀部皮下に腸管が入り込んでいることを認め,瘢痕ヘルニアと診断し手術を施行した.ヘルニア門は仙骨右縁下端の尾骨切除部近傍で,ヘルニア嚢は後腹膜,ヘルニア内容は小腸であった.ヘルニア嚢を骨盤腔側へ内翻後ヘルニア門をメッシュプラグで修復し,さらに大殿筋回転皮弁を作成してメッシュ部を被覆した.仙骨的直腸切除後の瘢痕ヘルニアは文献的には前例がなく修復法を熟考したが,メッシュを使用したtension freeのヘルニア門閉鎖方法に加え大殿筋皮弁の使用を付加することが最良であるという印象であった.

Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. This technique represents a minimally invasive, highly accurate method of axillary staging and is an alternative to conventional axillary lymph node dissection. The combination of the radioisotope and dye-staining methods is the most accurate way to identify SLN. We had reported feasibility and safety of a new technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection without any need for training. Recently, SLN identification using computed tomography lymphography (CTLG) has been reported in Japan. This study investigated a usefulness of the combination of CTLG and fluorescence imaging for SLN biopsy of early breast cancer patients. Patients and method: Between January 2013 and March 2016, 296 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector CT. We performed an intradermal injection in the periareolar area, using 4 ml of contrast agent with 1 ml of local anesthetic. The contrasted lymph route and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. We established typical pattern of the lymphography: stain defect of SLN, stagnation of lymphatic route for preoperative diagnosis of metastatic SLN. During the operation, fluorescence images were obtained using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan). After 0.5 ml dye mixed indigocarmin and ICG was injected intradermally into the periareolar skin, lymphatic route was observed with fluorescence images. SLN biopsy was performed referring to the point by axillary compression technique by plastic device. Intraoperative pathological analysis of SLN was examined. Results: The median age of the 296 patients was 59 (range 28 – 90) years old. One patient was male and others were female. CTLG and fluorescence imaging were safely performed in all patients. CTLG could visualize lymphatic route and accurately identify SLN in 284 (95.9 %) and 290 (98.0 %) cases, respectively, whereas fluorescence imaging identified successfully lymphatic route and SLN in all patients. Lymphatic routes of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p Conclusion: The combination of CTLG and fluorescence imaging revealed easy and effective to detect SLN. The fluorescence imaging was more high detection rate and number of SLN than CTLG. Otherwise, preoperative diagnosis of SLN metastasis using CTLG would be useful to detect negative SLNs. Citation Format: Abe H, Teramoto A, Yamasaki K, Yoneda K, Ogawa M, Kawasaki M, Kameyama M. The combination of preoperative computed tomography lymphography and intraoperative fluorescence imaging navigation for sentinel lymph node biopsy of early breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-17.

Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. This technique represents a minimally invasive, highly accurate method of axillary staging and is an alternative to conventional axillary lymph node dissection. The combination of the radioisotope and dye-staining methods is the most accurate way to identify sentinel lymph nodes. We had reported feasibility and safety of a new technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection without any need for training. Recently, SLN identification using computed tomography-lymphography (CTLG) has been reported in Japan. This study investigated the comparison of significance with fluorescence imaging method and CTLG. Patients and method: Between January 2013 and May 2015, 213 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector CT. We performed an intradermal injection in the periareolar area, using 4 ml of contrast agent with 1 ml of local anesthetic. The contrasted lymph flow and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. During the operation, fluorescence images were obtained using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan). After 5 mg / 0.3ml ICG was injected intradermally in to the periareolar skin, lymphatic drainage was observed with fluorescence images. SLN biopsy was performed referring to the point by axillary compression technique by plastic device. Results: The median age of the 213 patients was 59 (range 28 – 87) years old. CTLG and fluorescence imaging was safely performed in all patients. CTLG could visualize lymphatic flow and accurately identify SLN in 189 (89 %) and 196 (92 %) cases, respectively, whereas fluorescence imaging identified successfully lymphatic flow and SLN in all patients. Fluorescence imaging with axillary compression technique was visually easy to identify the location of SLN on the axillary skin even in obese patients. Lymphatic flows of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p Conclusion: Both of fluorescence imaging and CTLG revealed easy and effective to detect SLN. The fluorescence imaging with fluorescence mapping showed strong fluorescence from all parts of the surgical field, which hindered identification of SLNs, and fluorescence imaging was more high detection rate of SLN. Citation Format: Abe H, Yamasaki K, Teramoto A, Yoneda K, Ogawa M, Kawasaki M, Kameyama M. A comparison of significance with indocyanine green fluorescence imaging method and computed tomography-lymphography in sentinel lymph node identification for early breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-02.

Background: Sentinel lymph nodes (SLN) biopsy has been established as a standard of care in the treatment of early breast cancer. The combination of the radioisotope and dye-staining methods is the most accurate way to identify sentinel lymph nodes. We had reported a novel technique of SLN identification using fluorescence imaging of indocyanine green (ICG) injection. However, if any lymphatic vessels are injured, further fluorescence navigation will be difficult because of ICG contamination in the surgical field in overweight or obese patients. In this study, a new diagnostic approach for imaging lymphatic drainage and identifying SLN using preoperative computed tomography-lymphography (CTLG) and an intraoperative ICG fluorescence method was investigated. Patients and method: Between January 2013 and April 2014,105 breast cancer patients without clinical evidence of lymph node metastasis were treated. On the day before the operation, CTLG was performed using 64-row multidetector CT. We performed an intradermal injection in the periareolar area, using 4 ml of contrast agent with 0.5 ml of local anesthetic. The contrasted lymph flow and SLN were identified in reconstructed three-dimensional imaging. The SLN spot was indicated by CT laser light navigator system. During the operation, fluorescence images were obtained using the fluorescence imaging system, Photpdynamic Eye (pde-neo, Hamamatsu Photonics Co., Japan). After ICG was injected intradermally in to the periareolar skin, lymphatic drainage was observed with fluorescence images. SLN biopsy was performed by referring to the marker preoperatively placed on the CTLG. Moreover, we classified enhancement of SLN as "whole" and "partial" by CTLG with visual patterns, and examined the relation with SLN metastasis. Results: The median age of the 105 patients was 63 (range 33 – 87) years old. CTLG and fluorescence imaging was safely performed in all patients. This method was visually easy to identify the location of SLN on the axillary skin even in obese patients. CTLG could visualize lymphatic flow and accurately identify SLN in 99 (94%) of 105 patients, whereas fluorescence imaging identified successfully lymphatic flow and SLN in all patients. Lymphatic flows of CTLG were completely consistent with those of fluorescence imaging. The number of SLN identified by CTLG was significantly lower than that by fluorescence imaging (1.1 vs. 1.6, p Enhancement of SLNs by CTLG Metastasis(+)Metastasis(-)Whole459Partial1026Not identified15 Conclusion: This new navigation method of CTLG and fluorescence imaging revealed more easy and effective to detect SLN intraoperatively than fluorescence imaging alone. In addition, the information from CTLG may be helpful for the prediction of SLN metastasis. Citation Format: Hajime Abe, Keiichi Yamazaki, Masao Ogawa, Masayasu Kawasaki, Kohri Yoneda, Masao Kameyama. Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative computed tomography lymphography for early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-24.

We have demonstrated previously that kinin-free high molecular weight kininogen, its domain 5 (D5H, Gly402–Lys502), and peptides derived from D5H inhibited vitronectin-mediated migration and invasion of cancer cells in vitro (Kamiyama, F., Maeda, T., Yamane, T., Li, Y. H., Ogikubo, O., Otsuka, T., and Ohkubo, I. (2001) Biochem. Biophys. Res. Commun. 288, 975–980). In this study, we found that the amino acid sequence His-Gly-Lys (HGK) in D5H is the core motif for inhibition of adhesion and invasion of MDA-MB-231 cells in vitro. P-5m (484GHGKHKNK491, Gly484–Lys491), an octapeptide including the HGK motif derived from D5H, and HGK, a tripeptide, inhibited both cell adhesion and invasion in vitro. However, an octapeptide designated P-5m (K487R), in which Lys487 was changed to Arg, did not inhibit either cell adhesion or invasion, and peptides HGR and HGG also had no inhibitory effect. Recombinant GST-D5H expressed in Escherichia coli had a stronger inhibitory effect on cell adhesion and invasion in vitro than did GST-D5H (K487R) in which Lys487 was changed to Arg. Furthermore, P-5m (Gly484–Lys491) peptide clearly suppressed lung metastasis in mice experimentally induced by using B16-F10 cells, but P-5m (G487R) had no effect. These data strongly indicate that both the HGK motif and lysine residue (Lys487) play essential roles in inhibition of cell adhesion and invasion in vitro and in prevention of metastasis of cancer cells in vivo. We tried to identify the HGK motif binding protein on the surface of cancer cells. A 95-kDa surface biotin-labeled membrane protein was specifically detached from GST-D5H by P-5 (His479–Lys493) peptide but not by P-1 (Gly402–Lys420) peptide originating from the N-terminal region of D5H.