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The predictive roles of dihydropyrimidine dehydrogenase (DPD) in patients who undergo curative resection and adjuvant chemotherapy with S-1, which is the oral 5-fluorouracil prodrug tegafur combined with oteracil and gimeracil, remain unclear. In the present study, the clinical data from 66 consecutive patients who underwent curative resection and received adjuvant chemotherapy with S-1 for the treatment of pancreatic cancer at Kanagawa Cancer Center (Yokohama City, Japan) from April 2005 to March 2014 were retrospectively analyzed. The association between the DPD status and the survival and clinicopathological features were investigated. Of the 66 patients, 34 patients exhibited positive DPD expression (51.5%). Although a significant increase in DPD expression in male patients was observed, no significant differences were identified for other clinicopathological parameters, including tumor factor or node factor, between the DPD-positive expression group and the DPD-negative expression group. The median follow-up period of the present study was 29.2 months. There was no significant difference in the 3-year overall survival (OS) rates following surgery, which were 12.6 and 14.5% in the DPD-positive and DPD-negative expression groups, respectively (P=0.352). However, in a subgroup analysis, a significant difference in the 3-year OS rates following surgery was noted, which were 58.9 and 14.5% in the DPD-high and DPD-low expression groups, respectively (P=0.019). The intratumoral DPD expression in curatively resected pancreatic cancer patients treated with S-1 adjuvant chemotherapy was identified to not be useful as a predictive marker, whereas the level of DPD expression is a potential predictive marker. The results of the present study require confirmation in another cohort or in a prospective multicenter study.

Postoperative morbidity is high after pancreatic surgery. Recently, a simple and easy-to-use surgical complication prediction system, the surgical Apgar score (SAS), calculated using 3 intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate) has been proposed for general surgery. In this study, we evaluated the predictability of the SAS for severe complications after pancreatic surgery for pancreatic cancer. We investigated 189 patients who underwent pancreatic surgery at Kanagawa Cancer Center between 2005 and 2014. Clinicopathologic data, including the intraoperative parameters, were collected retrospectively. In this study, the patients with postoperative morbidities classified as Clavien-Dindo grade 2 or higher were classified as having severe complications. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for morbidity. Postoperative complications were identified in 73 patients, and the overall morbidity rate was 38.6%. The results of both univariate and multivariate analyses of various factors for overall operative morbidity showed that an SAS of 0 to 4 points and a body mass index ≥25 kg/m2 were significant independent risk factors for overall morbidity (P = 0.046 and P = 0.013). The SAS and body mass index were significant risk factors for surgical complications after pancreatic surgery for pancreatic cancer.

The safety and feasibility of administering S-1 adjuvant chemotherapy for pancreatic cancer has not yet been fully evaluated in elderly patients.This retrospective study selected patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II disease or lower or stage III disease with combined resection of the celiac artery, and received adjuvant S-1 at our institution. The patients were categorized into two groups: non-elderly patients (70 years of age: group A) and elderly patients (70 years of age: group B). The toxicity and S-1 continuation rates were compared between the two groups.A total of 76 patients were evaluated in the present study. There were no grade 4 toxicities. The incidences of grade 3 hematological and non-hematological toxicities were5 % in both groups, and the differences were not significantly different. The continuation rate at 6 months was 60.5 % in group A and 72.7 % in group B, which was also not significantly different.These results suggest that S-1 adjuvant chemotherapy for pancreatic cancer is safe and feasible, regardless of the age of the patient, especially for elderly patients who may be candidates for clinical trials.

Objective: This retrospective study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. Methods: Two cycles of a 3-week regimen of fluoropyrimidine S-1 (40 mg/m2, orally, twice daily), together with cisplatin (60 mg/m2, intravenously, day 8), were administered to patients, separated by a 2-week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n = 27). We retrospectively evaluated overall survival and prognostic factors in these patients. Results: Univariate analysis showed that positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after S-1 plus cisplatin chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. Conclusion: After S-1 plus cisplatin neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.

This study aimed to evaluate the safety and feasibility of pancreatic surgery for pancreatic cancer in elderly patients.In total, 9 patients underwent pancreatic surgery for pancreatic cancer between April 2005 and March 2014. The surgical complications were evaluated by Clavien-Dindo classification.The median operating time was 420(range: 354-503)min and the median blood loss was 640(range: 350-1,170)mL. Grade 2 or higher complications were observed in 3 patients. Pancreatic fistula(Grade 3b)was observed in 1 patient, delirium was observed(Grade 2)in 1 patient, and portal vein thrombosis(Grade 2)was observed in 1 patient. No surgical mortality was observed.Our results suggest that pancreatic surgery is a safe and feasible treatment for pancreatic cancer in elderly patients.

Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm. IMTs are found in a number of locations throughout the body, but splenic involvement is uncommon. One case of splenic IMT is described. A 42-year-old woman presented with anterior chest pain and was found to have a splenic mass by computed tomography(CT). Fluorine-18-FDG-PET showed no FDG accumulation in the spleen. Magnetic resonance imaging(MRI)at 6 months follow-up showed an increase in the size of the tumor. We performed splenectomy for a suspected malignant tumor. The surgical specimen was a gray-white mass in the spleen. The mass was histopathologically diagnosed as primary splenic IMT because it consisted of desmin- and SMA-positive spindle-shaped cells with various inflammatory cells. In Japan, only 6 cases(including this case)of primary splenic IMT have been reported. Surgery is the only curative approach, but recurrences occur in around 5% of cases of pulmonary IMT, and around 25% of cases of extrapulmonary IMT. This patient needs to be carefully followed up.

The factors which affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated in pancreatic cancer. The objective of this retrospective study was to clarify the risk factors for the discontinuation of S-1 adjuvant chemotherapy after 6 months of treatment. The study included patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II or III disease, had a serum creatinine level ≤1.2 mg/dl and received adjuvant S-1 between June 2007 and March 2014. Forty patients were eligible for the present study. A comparison of the 6-month continuation stratified by each clinical factor using the log-rank test revealed a significant difference in the creatinine clearance (CCr) between the patients who continued and discontinued the treatment. A CCr of 60 ml/min was regarded as a critical point. The uni- and multivariate Cox’s proportional hazard analyses demonstrated that the CCr was the only significant independent predictive factor. The 6-month continuation rate was 70.8 % in the patients with a CCr ≥60 ml/min and was 25.0 % in patients with a CCr

In surgical treatment of elderly patients, securing the safety of surgery and radical cure must be balanced. Our purpose was to verify the safety and validity of laparoscopic surgery for the treatment of colorectal cancer in elderly patients. Patients with cTis–T4a colorectal cancer who were 75 years or older were randomized to receive open or laparoscopic surgery. Exclusion criteria were patients who had a bulky tumor, rectal cancer that required pelvic side wall lymphadenectomy, and history of colon resection. Patients were divided according to tumor location (right colon, left colon, and rectum). The short-term outcomes were compared between the two groups. One hundred patients (right 43, left 28, and rectum 29) were registered in each group from August 2008 to August 2012. There were no differences in patient characteristics between the two groups. Three patients were converted from laparoscopic to open, because of bleeding, excision of peritoneum metastasis, and patient’s desire, respectively. In the short-term results (open:laparoscopic), there were significant differences in the rates of complications (36:23 %) and ileus (12:4 %), amount of blood loss (157:63 mL), and duration of surgery (150:172 min). There were no significant differences in the pathological margins, and the number of dissected lymph nodes. In the subgroup analysis according to the tumor location, there were significant differences in the rate of complications (39.4:22.5 %), amount of blood loss (135:42 mL), duration of surgery (139:160 min), and length of postoperative stay (13.0:10.0 days) in the colon cancer. There were no significant differences in short-term results in the rectal cancer. Laparoscopic surgery in elderly colorectal cancer patients did not result in a difference in radical cure compared with open surgery, and the short-term results except the duration of surgery were excellent. It is an effective procedure for elderly patients with colorectal cancer, especially colon cancer.

Purpose Despite numerous studies, the best postoperative therapy for Crohn’s disease is still undefined. We retrospectively evaluated the effects of postoperative maintenance therapy with daikenchuto, a traditional Japanese Kampo medicine, on the reoperation rate at 3 years in patients with Crohn’s disease. Methods A total of 258 patients who underwent surgery for Crohn’s disease were identified for the study. For the prevention of postoperative recurrence, patients were stratified to receive 5-aminosalicylic acid, azathioprine or daikenchuto, and their effects on preventing reoperation at 3 years were evaluated. Results Of the 258 patients, 44 required reoperation with intestinal resection within 3 years due to disease recurrence. The 3-year reoperation rate was significantly lower in the postoperative daikenchuto group than in the non-daikenchuto group (11.3 vs. 24.5 %, P = 0.01), and was similarly significantly lower in the postoperative 5-aminosalicylic acid group than in the non-5-aminosalicylic acid group (14.8 vs. 29.6 %, P = 0.0049). A multivariate Cox analysis showed that postoperative daikenchuto (P = 0.035) and postoperative 5-aminosalicylic acid (P = 0.022) were significantly and independently associated with the rate of reoperation at 3 years in patients with Crohn’s disease. Conclusion We propose that continuous daikenchuto therapy is a clinically useful and feasible maintenance therapy for the prevention of postoperative reoperation in patients with Crohn’s disease.

The aim of this study was to evaluate the safety and feasibility of the bioabsorbable staple line reinforcement in distal pancreatic resection.Thirteen patients underwent distal pancreatic resection using the bioabsorbable staple line reinforcement between May 2014 and December 2014. Surgical complications were evaluated by Clavien-Dindo classification.Median age was 64 years. Median operation time was 219 minutes and median blood loss was 490 mL. ComplicationsGrade 2 were observed in 3 patients. Among them, pancreatic fistula (Grade 2) was found in 2 patients and ileus (Grade 2) in 1. No surgical mortality was observed.Our results may suggest that the bioabsorbable staple line reinforcement is safe and feasible in distal pancreatic resection.

By remarkable progress of chemotherapy for pancreatic cancer, we sometimes achieve resection of initially unresectable pancreatic cancer after chemotherapy. Otherwise, the safety and feasibility of radical pancreatic resection after chemotherapy is not still clear. In this report, we evaluated the safety and feasibility of conversion surgery for initially unresectable pancreatic cancer in our center.Between 2009 and 2014, approximately 500 patients were diagnosed with unresectable pancreatic cancer and received chemotherapy, and after chemotherapy, 10 patients were found to have resectable tumors on computed tomography. We evaluated surgical complications using the Clavien-Dindo classification. Clinicopathological data were reviewed by using UICC, seventh edition, and the chemotherapeutic effect was measured by using Evans classification.The mean age of patients was 68 years, with 4 men and 6 women. The preoperative chemotherapy regimens were S-1 chemotherapy in 2 patients, gemcitabine in 5 patients, and gemcitabine plus S-1 chemotherapy in 3 patients. Nine patients underwent pancreatoduodenectomy, and 1 underwent distal pancreatosplenectomy. The mean operative time was 527.5 minutes, and the mean estimated blood loss was 875 mL. Surgery-related morbidity more than Grade 2 based on Clavien-Dindo classification occurred in 6 patients. Mortality was 0%.Our study suggests that conversion surgery for initially unresectable pancreatic cancer is safe and feasible.

BACKGROUND:Postoperative intra-abdominal septic complications are a serious concern with regard to postoperative morbidity and mortality in Crohn’s disease.OBJECTIVE:The aim of this study was to identify the clinical variables that potentially impact the risk of intra-abdominal septic complications

大腸癌根治切除例のうち，粘液癌を分化型腺癌と比較し臨床病理学検討を行うとともに，粘液癌を組織学的特徴により2群に分類し，臨床病理学的な検討と予後因子の検討を行った．粘液癌の発生頻度は5.1%で，高·中分化型腺癌と比較して，右側の発症率，腫瘍径の大きい症例，深達度T3以深の症例が有意に多かった．粘液癌の5年生存率は68.8%と高·中分化型腺癌と比較し有意に低かった．粘液癌の予後因子の検討では，由来組織，リンパ管侵襲，リンパ節転移が予後規定因子として有意差をもって選択され,因子の数が多い症例ほど5年生存率は有意に低かった．また，粘液癌をその由来組織により高分化型と低分化型に分類し検討すると，低分化型では5年生存率が40%と有意に低かった．粘液癌の中でもこれらの予後不良因子を有する症例の場合には高リスク大腸粘液癌として，高·中分化型腺癌とは異なる治療方針を考慮する必要性があると考えられた．

目的：下部直腸癌患者の低位前方切除術の際にdiverting stomaとしてileostomyを造設後にイレウスを発症した症例を分析し，イレウス発症の危険因子を明らかとする．対象·方法：下部直腸癌手術の際に同時にileostomyを造設した23人を対象とした．イレウス発症群，イレウス非発症群の2群に分け，術前因子，手術因子の各項目について比較検討した．結果：イレウス発症群は10例で，イレウス非発症群は13例であった．単変量解析では男性および腹直筋の厚さ≥10mmが危険因子として選択された（p＜0.05）．多変量解析では腹直筋の厚さ≥10mmが危険因子として選択された（p＜0.05）．考察：腹直筋の厚さ≥10mmの危険因子を有する症例に対しては，diverting stomaとして腹直筋以外の回腸挙上経路あるいは横行結腸人工肛門の造設なども考慮して手術を施行する必要があると考えられる．

目的：下部直腸癌に対する側方リンパ節郭清の適応の指標とする目的で，Air注腸CTでの下部直腸癌の深達度T3以深を示す所見を明らかとし，診断精度を評価した．対象・方法：当科での下部直腸癌167例中，術前にAir注腸CTを施行した113例を対象．病理学的深達度がT3以深とT2以浅の2群に分け，CT画像における，（1）腸管壁の辺縁凹凸不整，（2）腸管壁の肥厚，（3）ケバ立ち，（4）鋸歯状変化，（5）腫瘍径，（6）環周率の6項目を比較検討した．結果：病理学的深達度がT3以深63例，T2以浅50例であった．単変量および多変量解析では，（1）腸管壁の辺縁凹凸不整，（3）ケバ立ちの2項目が深達度T3以深を示す因子として選択された（p＜0.05）．（1），（3）の所見を有する症例のAir注腸CTにおける深達度T3以深の正診率は，87.6%，89.4%であった．結論：Air注腸CTは下部直腸癌の術前深達度診断に有用であることが示唆された．

目的:高齢者術後せん妄発生予測因子を明らかにする．方法:2006年1月からの2年間に当院で手術をした胃癌と大腸癌の症例で，改訂長谷川式簡易知能評価スケール（以下HDS-R）による評価を術前行った70歳以上の高齢者121例を対象とし，術前因子（年齢，性別，既往歴，ASA分類，PNI，PS，術前在院期間，HDS-R）と手術因子（病変部位，手術時間，出血量，アプローチ，手術難易度，ICU入室，白血球数，CRP，術後合併症，食事開始時期）を検討した1)．結果:術後せん妄発生率は19.0％（23/121）だった．単変量解析では，術後せん妄発生とPNI（p=0.007），HDS-R（p=0.001），CRP（p

This study was designed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for lateral pelvic lymph-node metastasis. Eighty-four patients with primary lower rectal cancer were examined by MRI and subsequently underwent radical surgery with lateral pelvic lymph-node dissection, without preoperative treatment. Lateral lymph-node metastases were assessed preoperatively by MRI, and the results were compared with the histopathological findings. The criterion for lateral lymph-node metastasis was any recognizable lymph node in the pelvic wall, regardless of diameter. Lateral pelvic lymph-node metastasis was diagnosed on preoperative MRI in 16 patients (19.9 %). The overall patient-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI were 75, 69.1, 36.4, 92.2, and 70.2 %, respectively. When a cut-off value of 10 mm was used for diagnosis, the corresponding values were 43.8, 98.5, 87.5, 88.1, and 88.1 %, respectively. The mean diameter of metastatic nodes (14.7 mm) was significantly larger than that of negative nodes (5.7 mm; P

The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, has been shown to predict the clinical outcomes of a variety of cancer types. The aim of this study was to determine whether the GPS predicts clinical outcomes of patients with pancreatic cancer treated with adjuvant chemotherapy after surgery.Forty patients resected for pancreatic cancer who underwent adjuvant gemcitabine monotherapy after curative surgery were included. The GPS was measured prior to adjuvant therapy and correlated with clinical outcomes.The disease-free survival (DFS) and overall survival (OS) in patients with an elevated GPS (GPS1 or GPS2) were significantly poorer (p=0.001 and p=0.035, respectively, by log-rank test) than patients with a GPS of 0. An elevated GPS was found to be independently associated with poor DFS (p=0.002, by Cox regression model).The pre-adjuvant GPS may predict clinical outcome in patients with pancreatic cancer undergoing adjuvant chemotherapy after surgery.

We investigated the impact of postoperative complications on survival and recurrence after curative surgery for pancreatic cancer.This study included 164 patients who underwent curative surgery for pancreatic cancer between 2005 and 2014. The patients were classified into those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified.Postoperative complications were found in 61 out of the 164 patients (37.2%). The RFS rate at five years after surgery was 10.6% in the C group and 21.0% in the NC group. The RFS tended to be worse in the C group than in the NC group (p=0.1756). The OS rate at five years after surgery was 7.4% in the C group and 22.8% in the NC group, which was significantly different (p=0.0189). The multivariate analysis demonstrated that the occurrence of postoperative complications was a significant independent risk factor for OS and a marginally significant risk factor for RFS.The development of postoperative complications was a risk factor for a decreased overall survival in the patients who underwent curative surgery for pancreatic cancer. The surgical procedure, perioperative care and the surgical strategy should be carefully planned to avoid complications.

A 64-year-old woman was diagnosed with Stage IV gastric cancer with lymph node and multiple liver metastases. She was treated with 6 courses of chemotherapy, in 3-week courses, with capecitabine (1,000 mg/m/(2)) plus cisplatin(80 mg/m(2)) administered for 2 weeks, followed by a drug-free week. She underwent curative total gastrectomy with D2 lymph node dissection and reconstruction by using the Roux-en-Y method. The postoperative pathological findings revealed a T3 (SE), N1M1, Stage II B tumor; the tumor was determined to be Grade 1b owing to the chemotherapeutic effect. Postoperatively, only S-1 therapy was administered, because of the development of Grade 3 hand-foot syndrome. The patient is alive 1 year and 8 months after the initial gastrectomy.

We report a case of gastric small cell carcinoma with liver and lymph node metastases responding to CPT-11 plus cisplatin (CDDP) chemotherapy. The patient was a 77-year-old woman with advanced gastric cancer, clinically diagnosed as P0H1M1CY0T4aN3. The immunostaining and pathological analysis of a biopsied specimen obtained during a gastrointestinal tract endoscopy indicated small cell carcinoma of the stomach. The patient received the following chemotherapy treatments: 11 courses of CPT-11 plus CDDP, 8 courses of docetaxel plus S-1, and 2 courses of paclitaxel. The patient is alive 2 years after the first chemotherapy treatment. We conclude that the combination of chemotherapy used was effective for treating the patient's small cell carcinoma of the stomach, which is considered to have a poor prognosis.

338 Background: Pancreaticoduodenectomy (PD) remains the mainstay of surgical treatment for hepatobiliary and pancreatic malignancy and offers the only chance of long term survival. However, the morbidity and mortality after PD has been reported to be high. Therefore, it is important to determine the most appropriate perioperative care. This study assessed whether enhanced recovery after surgery (ERAS) program is safe and feasible in patients who underwent pancreaticoduodenectomy Methods: The subjects were patients who underwent consecutive PD between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization and 30-day readmission rate. Key ERAS program targets were: nasogastric tube (NGT) removal [postoperative day (POD) 1]; resumption of oral fluids (POD 2); urinary catheter removal (POD 3); tolerating diet (POD 5); drain removal (POD 7). Results: A total of 109 patients were studied. The overall incidence of morbidity was 51.4%, the incidence of mortality was 1.8%, and the incidence of readmission was 1.8%. The median postoperative hospital stay was 23 days. The proportions of patients achieving key targets were: 93.6% for NGT removal; 94.5% for resumption of oral fluids; 31.2% for urinary catheter removal; 79.8% for tolerating diet; 80.7% for meeting mobility targets, and 37.6% for drain removal. Conclusions: ERAS program is safe and feasible in patients who undergo PD. However, achieving compliance on some targets, especially the removal of catcher and drain, were more challenging.

Hepatic resection has been regarded as the only curative treatment for colorectal liver metastases. After a first hepatectomy, 30% to 70% of patients develop intrahepatic recurrence. In this study, we retrospectively analyzed risk factors for intrahepatic recurrence.From April 1990 to December 2006, 86 patients with colorectal liver metastases underwent curative hepatic resection at Kanagawa Cancer Center. Clinicopathological characteristics of 35 patients in the intrahepatic recurrence group were compared with those of 30 patients in the no recurrence group.The 5-year survival rate was 18.7% for patients in the intrahepatic recurrence group. Lymph node metastases of primary colorectal cancer and synchronous liver metastases were found to be independently associated with intrahepatic recurrence.We suggest that neoadjuvant chemotherapy before hepatectomy should be considered as feasible treatment for reducing intrahepatic recurrence in two cases; One case is resectable synchronous liver metastases from colorectal cancer, and the other is resectable metachronous liver metastases with primary regional lymph node metastases from colorectal cancer.

The patient was a 54-year-old man. He was an HBV carrier, and hepatocellular carcinoma (HCC) was detected for the first time in 2000. An operation was performed, but HCC recurred. After repeating the operation and transarterial chemo-embolization (TACE) for the recurrent HCC, a tumor was found in January 2009 on the ventral side of the right kidney, and we thought it was a retroperitoneal metastasis of HCC or peritoneal dissemination. He was enrolled in a trial of systemic chemotherapy, called "S-1 monotherapy for extrahepatic metastasis of HCC", but the tumor seemed progressive. Since he showed no other lesion, he was indicated for surgical resection. Intraoperatively, the tumor was localized between the duodenum and the right kidney, and was covered by the retroperitoneum. Pathological examination of the resected specimen revealed retroperitoneal metastasis of HCC. Intrahepatic recurrence was detected 6 months after the resection. Therefore, he underwent TACE, and he is currently (1 year after surgery) alive without any extrahepatic metastasis. We describe herein this case because retroperitoneal metastasis of HCC is very rare.

Recent studies suggest that altered patterns of stanniocalcin 1 (STC1) gene expression have a role in human carcinogenesis. This study examined the relationship between the relative expression of the STC1 gene and clinicopathological factors in patients with colorectal cancer.Surgical specimens of cancer tissue and adjacent normal mucosa were obtained from 202 patients with colorectal carcinomas. The relative expression levels of STC1 mRNA in the cancer and the normal adjacent mucosa were measured by quantitative real-time, reverse-transcriptase polymerase chain reaction.The relative expression levels of the STC1 gene were higher in the cancer tissue than in the normal adjacent mucosa and high expression of STC1 correlated with poor postoperative survival.High expression of the STC1 gene might be a useful predictor of poor postoperative outcome in patients with colorectal cancer.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a major endogenous regulator of matrix metalloproteinases. This study examined the relation between TIMP-1 gene expression and postoperative mortality in patients with colorectal cancer (CRC). Specimens of CRC were obtained from 202 patients. The relative expression levels of TIMP-1 mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. The expression level of the TIMP-1 gene was categorized as low or high according to the median value. The TIMP-1 level did not correlate with any clinicopathological feature. On Kaplan-Meier analysis, the 5-year overall survival rate was significantly lower in patients with high TIMP-1 (62.6%) than in those with low TIMP-1 (80.6%; p=0.0113). High TIMP-1 mRNA expression was associated with significantly poorer overall survival on univariate Cox regression analysis (p=0.013) and multivariate analysis (p=0.019). [corrected]. Overexpression of TIMP-1 thus correlated with poor outcomes in patients with CRC. Our results suggest that the TIMP-1 gene expression level might be a useful, independent prognostic factor in CRC.

Background Matrix metalloproteinases are members of a large family of endopeptidases that participate in the extracellular-matrix degradation that accompanies cancer cell invasion, metastasis and angiogenesis. The membrane-type 1 matrix metalloproteinase (MT1-MMP) gene has been reported in various cancers and is associated with tumor invasion and metastasis. This study examined the relation of the relative expression of MT1-MMP gene to clinicopathological factors and outcomes in patients with colorectal cancer (CRC). Methods We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated CRC. The relative expression levels of MT1-MMP mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. Results MT1-MMP gene expression was higher in cancer tissue than in adjacent normal mucosa. The level of MT1-MMP gene expression was not related to any clinicopathological factor. Overall survival at 5 years differed significantly between patients with high MT1-MMP gene expression and those with low expression. Conclusions Overexpression of the MT1-MMP gene is considered a useful independent predictor of outcomes in patients with CRC. J. Surg. Oncol. 2010;102:571–575. © 2010 Wiley-Liss, Inc.

Matrix metalloproteinase-7 (MMP-7), MMP-9, MMP-13, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are considered to have important roles in the invasiveness and outcomes of colorectal cancer (CRC). This study examined the clinicopathological significance of the relative expression of these genes in patients with colorectal cancer, especially as related to liver metastasis. The study analysed surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. MMP-7, MMP-9, MMP-13, TIMP-1, and beta-actin mRNA of cancer tissue and adjacent normal mucosa were measured by quantitative real-time, reverse-transcriptase polymerase chain reaction. Expression levels of MMP-7, MMP-9, MMP-13 and TIMP-1 were higher in cancer tissue than in adjacent normal mucosa. On analysis of the relations between gene expression and clinicopathological factors, MMP-13 expression was found to correlate with liver metastasis. Moreover, MMP-13 expression levels were higher in tumour tissue with liver metastasis than in that without liver metastasis. It is concluded that MMP-13 gene expression is a useful predictor of liver metastasis in patients with CRC.

An 80-year-old man with no history of thoracic radiotherapy nor interstitial pneumonia was administered S-1 for gastric cancer in June 2007. Twenty-two days after starting S-1, he had dyspnea, and X-rays showed reticular shadows in both lung fields, yielding a diagnosis of interstitial pneumonia. Drug lymphocyte stimulating test (DLST) was positive against S-1. The total dose of S-1 was 2,200 mg to the symptom onset. We immediately started steroid pulse therapy after emergency hospitalization, and it revealed improved condition and he was able to leave the hospital. S-1 administration is becoming frequent because RCTs supported the efficacy of S-1 for gastric cancer. Interstitial pneumonia as a side effect of S-1 is not frequent, but it is necessary to pay attention to dyspnea throughout the duration of administration.

Background Some studies have found high incidences of intraoperative and postoperative complications for patients with gastric cancer. To determine the predictive factors for the surgical complications of laparoscopic gastric surgery, surgical outcomes were evaluated. Methods Between April 2002 and December 2007, 152 patients with preoperatively diagnosed early gastric cancer who underwent laparoscopy-assisted distal gastrectomy (LADG) were enrolled. Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan software. The predictive factors for surgical complications of LADG were evaluated by univariate and logistic regression analyses. Results Of 152 patients, conversion to open surgery due to uncontrollable bleeding was observed in nine male patients, and postoperative complications were detected in seven male and one female patient (four anastomotic leakage, two intraabdominal abscess, one pancreatic fistula, and one lymphorrhea). High body mass index (BMI) and high VFA independently predicted conversion to open surgery and postoperative complications. VFA was significantly higher, operation time was longer, blood loss was greater, and SFA was lower in male than in female patients, whereas no significant difference was observed in BMI between male and female patients. Conclusions High BMI and high VFA can predict technical difficulties during laparoscopic gastric surgery and postoperative complications. Particularly, LADG should be performed cautiously to prevent surgical complications for male patients with high VFA. Predictive impact of VFA should be further determined in a larger set of patients.

553 Background: Targeted therapies of monoclonal antibodies have changed the treatment of metastatic colorectal cancer (mCRC). A target therapy with chemotherapy regimen for mCRC was decided by KRAS mutation status (KRAS exon2 [codon12, codon13]). Currently, there are many reports suggesting that in addition to analysis of KRAS mutation status, the evaluation of EGFR gene copy number, levels of EGFR ligands, BRAF, NRAS, PIK3CA mutations could be helpful to have a more accurate selection of patients who may have a benefit from anti-EGFR targeted drugs. Methods: Mutation status of 50 oncogenes were analysed in 35 mCRC patients with all RAS wild type, using next-generation sequencing technology. The response for chemotherapy was classified response group (R group) and non-response group (N group) by RECIST. The relation between mutation status of 50 oncogenes and the response for chemotherapy was assessed. Results: There were 25 oncogene mutations in the 50 genes. Driver mutation associated with oncogenic mutation deeply were 5 oncogenes, which were PIK3CA, AKT1, BRAF, PDGFRA and TP53. Only BRAF mutation was significantly associated with poor chemo response in the 5 oncogenes. A case which had two driver mutations was only in the N group. One of the two driver mutations was tumor suppressor gene, TP53. Conclusions: BRAF mutation and the number of driver mutations are key predictors of chemosensitivity in the mCRC cases with all RAS wild type.

252 Background: The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established. The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established. Methods: We retrospectively analyzed clinical data from 143 consecutive patients who underwent macroscopically curative resection and received adjuvant gemcitabine or S-1 chemotherapy for pancreatic cancer from 2005 to 2014 in our institution. Correlations between CY status and survival and clinicopathological features were investigated. Results: Of the 143 patients, 21 patients were peritoneal washing cytology positive (CY+) (14.7%). Although significant difference was observed in the tumor size, no other correlation between cytology status and clinicopathological parameter existed (age, gender, histology, UICC T status, LN metastasis, lymphovascular invasion). The recurrence free survival (RFS) rates at 3 and 5 years after surgery were 5.1% and 0% in CY+ patients, respectively, and were 21.5% and 16.1% in peritoneal washing cytology negative (CY-) patients, respectively, which were significantly different (p

446 Background: We investigated the impact of postoperative complications on pancreatic cancer survival and recurrence after curative surgery. Methods: This study included 164 patients who underwent curative surgery for pancreatic cancer between 2005 and 2014. The patients were classified into those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: Postoperative complications were found in 61 of the 164 patients (37.2%). The RFS rate at five years after surgery was 10.6% in the C group patients and was 21.0% in the NC group patients. The RFS tended to be worse in the C group than in the NC group (p=0.1756). The OS rate at five years after surgery was 7.4% in the C group and 22.8% in the NC group, which was significantly different (p=0.0189). The multivariate analysis demonstrated that postoperative complications and lymphatic invasion were significant independent risk factors for the RFS and OS. Conclusions: The development of postoperative complications was a risk factor for a decreased overall survival and for disease recurrence in patients who underwent curative surgery for pancreatic cancer. The surgical procedure, perioperative care and the surgical strategy should be carefully planned to avoid complications.

419 Background: Postoperative morbidity is high after pancreatic surgery. Numerous studies have evaluated factors to predict the patients at risk. Recently, a simple and easy-to-use surgical complication prediction system, the surgical Apgar score (SAS) calculated using three intraoperative parameters (estimated blood loss, lowest mean arterial pressure and lowest heart rate) has been proposed for general surgery. In this study, we evaluated the predictability of the SAS for severe complications after pancreatic surgery for pancreatic cancer. Methods: We investigated 189 patients who underwent pancreatic surgery at Kanagawa Cancer Center between 2005 and 2014. Clinicopathological data, including the intraoperative parameters, were collected retrospectively. In this study, the patients with postoperative morbidities classified as Clavien-Dindo grade II or more were classified as having severe complications. Uni- and multivariate logistic regression analyses were performed to identify the risk factors for morbidity. Results: Postoperative complications were identified in 73 patients, and the overall morbidity rate was 38.6%. The results of both univariate and multivariate analyses of various factors for overall operative morbidity showed that a SAS of 0-4 points and a body mass index > 25 kg/m2 were significant independent risk factors for overall morbidity (P=0.024 and P=0.014, respectively). The rate of abdominal abscess formation was significantly higher in the patients with a SAS of 0-4 points, while the occurrence of a pancreatic fistula was significantly higher in the patients with a body mass index > 25 kg/m2. Conclusions: The SAS was a significant risk factor for surgical complications after pancreatic surgery for pancreatic cancer. Careful attention is required for these patients in order to help prevent complications and treat them as soon as they develop.

198 Background: This study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. Methods: Two cycles of a 3 week regime of the fluoropyrimidine, S-1 (40 mg/m2, orally, twice daily), with cisplatin (60 mg/m2, intravenously, day 8) were administered to patients, separated by a 2 week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n=27). We compared overall survival and prognostic factors in these patients with a non-neoadjuvant group (n=19). Results: For all patients, univariate analysis identified non-curative gastrectomy and positive lavage cytology as adverse prognostic factors; extended lymph node dissection was a positive prognostic factor. Multivariate analysis showed that non-curative resections independently influenced prognosis (hazard ratio=2.902, p=0.011). In the SP group, positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after SP chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. Conclusions: After SP neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.

486 Background: The safety and feasibility of starting S-1 adjuvant chemotherapy for pancreatic cancer has not been evaluated in elderly patients. Methods: The patients who underwent curative D2 surgery for pancreatic cancer were selected to this retrospective study. The patients were diagnosed within stage I to III disease, and received adjuvant S-1 at our hospital. Patients were categorized into two groups; non-elderly patients (age