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Multidetector-row CT (MDCT) may provide accurate preoperative staging of resectable gastric cancer. However, the standard methods and criteria to diagnose the T and N stages to select the patients who are good candidates for neoadjuvant chemotherapy have not been established yet.The aim of this prospective study was to evaluate the accuracy of MDCT to diagnose the serosal invasion and nodal metastases of gastric cancer. Patients who had gastric adenocarcinoma underwent MDCT scanning using a standardized method. The T and N stage were diagnosed by prespecified criteria. The analyses were performed in the patients who had cN0-2 and M0 tumors and underwent curative gastrectomy as a primary treatment. The accuracy was calculated by comparing the results of MDCT with the histopathological findings.A total of 315 patients were analyzed. The overall diagnostic accuracy (95 % confidence interval) of T staging was 71.4 % (225 of 315, 66.2-76.1). The accuracy, sensitivity, and specificity for serosal invasion were 85.7 % (81.4-89.1), 54.5 % (42.6-66.0), and 94.0 % (90.3-96.3), respectively. The false-positive rate for serosal invasion was 6.0 % (2.9-7.7). The overall diagnostic accuracy of N staging was 75.9 % (239 of 315, 70.9-80.3). The accuracy, sensitivity, and specificity for nodal metastases were 81.3 % (76.6-85.2), 46.4 % (36.8-56.3), and 96.8 % (93.5-98.4), respectively. The false-positive rate for nodal metastases was 3.2 % (1.6-6.5 %).These results suggest that MDCT provides an accurate diagnosis with high specificity and a low false-positive rate and can be used to select the patients who are candidates for preoperative chemotherapy.

Adjuvant chemotherapy aims to eradicate micrometastatic tumor cells before and after curative surgery. Many Phase III trials have been conducted to study the efficacy of postoperative adjuvant chemotherapy; however, most trials have failed to show any survival benefit because of their low statistical power and/or poor patient compliance. Since 2000, two pivotal Phase III trials, the ACTS-GC and the CLASSIC, have demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. Although treatment with S-1 for 1 year or combination therapy with capecitabine and oxaliplatin for 6 months is effective, more intensive chemotherapy is necessary to further improve the survival rates. In Europe, two Phase III trials, the MAGIC and the FNCLCC/FFCD, have produced results that strongly suggest that neoadjuvant chemotherapy is beneficial. The advantages of neoadjuvant chemotherapy include a high rate of R0 resection, tumor regression, high compliance and the avoidance of unnecessary surgery. The disadvantage of neoadjuvant chemotherapy is over-diagnosis. In Japan, the Japan Clinical Oncology Group has conducted several clinical trials using neoadjuvant chemotherapy to target extensive nodal disease and/or scirrhous carcinomas. The optimal courses and regimens of neoadjuvant chemotherapy should, therefore, be clarified in the future.

Background The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies. Methods 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed. Results Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology. Conclusions Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

Compliance of S-1 adjuvant chemotherapy is not high. The aim of the present study is to clarify risk factors for continuation of S-1 after gastrectomy. This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2/3 disease, creatinine clearance more than 60 ml/min, and received adjuvant S-1 at our institution between June of 2002 and December of 2011. Time to S-1 treatment failure (TTF) was calculated. A total of 103 patients were selected for the present study. When TTF curve stratified by each clinical factor was compared by the log-rank test, body weight loss (BWL) of 15 % was regarded as a critical point. Both univariate and multivariate Cox proportional hazard analyses demonstrated that BWL was the significant independent risk factor. Moreover, BWL remained a significant factor in both the univariate and multivariate analyses in the subset excluding 8 patients who discontinued S-1 because of recurrence. The 6-month continuation rate was 66.4 % in the patients with BWL

We report a case of gallbladder hernia into the lesser sac through the foramen of Winslow. The patient was a 90-year-old woman, admitted to hospital with obstructive jaundice. Computed tomography (CT) showed a left-deviated and remarkably enlarged gallbladder dragging the liver, and a dilated intrahepatic bile duct. The deviated gallbladder was thought to compress the common bile duct, causing the obstruction. Laparoscopic examination revealed gallbladder herniation into the lesser sac without a floating gallbladder; thus, we performed laparoscopic cholecystectomy. Herniation of the gallbladder is the rarest of all internal hernias and most reported cases have involved a floating gallbladder. The case we report here is therefore considered especially unusual.

The cost of laparoscopic gastrectomy (LG) has not been fully clarified yet.The actual cost for the instruments used for surgery was examined between LG and conventional open gastrectomy( OG) by separating distant (l D-) and total (l T-) gastrectomy in a total of 20 patients(5 for each)during Oct 2010 and Feb 2011. The profit was defined as the difference of the actual cost and the operation fee including the instruments determined by the insurance and compared.The fee for D-OG, T-OG, D-LG, and T-LG were 708, 700 yen, 856 , 400 yen, 783 , 600 yen and 922 , 300 yen, respectively. The mean profits of D-OG, T-OG, D-LG, and T-LG were 408 , 297 yen, 475 , 812 yen, 308, 681 yen and 269 , 478 yen, respectively.Appropriate surgical and instrumental fees should be determined considering the actual cost.

Survival and clinical course were unknown in patients with recurrence of para-aortic lymph node after curative D2 gastrectomy and adjuvant S-1 chemotherapy.The study examined clinical characteristics and prognosis of 3 patients who had para-aortic nodal recurrence after curative D2 gastrectomy and S-1 adjuvant chemotherapy.Initial stage was III C in all of the patients. Median treatment interval of S-1 was 8 . 8 months. Para-aortic nodal metastasis was single in 2 and multiple in 1 patient. Median survival time was 14 .3 months. Other recurrent sites than para- aortic node were not seen in all of the patients.In the times of S-1 adjuvant chemotherapy, it is valuable to know whether para-aortic node should be resected prophylactically, or be treated after recurrence, or be treated by locally or systemically.

S-1 mono-therapy for advanced gastric cancer is hard to continue in some patients due to adverse events. We retrospectively examined the patients who received S-1/Krestin( PSK) immunochemotherapy for advanced gastric cancer.During September 2006 to August 2008, 3 patients had received S-1/PSK. S-1 was given for 6-week schedule or 3-week schedule, and PSK was for everyday during the S-1 treatment.Cases 1 and 2 had lymph node metastases after surgery. Case 3 had peritoneal metastasis. The median treatment duration was 112 days. The median overall survival was 552 days. All patients stopped the treatment due to progression of disease. There were no patients who stopped the treatment due to adverse events.PSK may increase the compliance of S-1.

BackgroundWe conducted a pilot phase II study to evaluate the efficacy and safety of S-1 as a first-line, S-1 plus cisplatin as a second-line, and weekly paclitaxel as a third-line therapy for advanced gastric cancer.Patients and MethodsBetween 2002 and 2005, 19 patients were enrolled in this study. Chemotherapy consisted of either 60 mg/m2of S-1 for 4 weeks at 6 weeks interval, a combination of 60 mg/m2S-1 for 3 weeks and 60 mg/m2cisplatin on day 8 at 5 weeks interval, or 60 mg/m2paclitaxel at day 1, 8, 15, at 4 weeks interval. The regimen was repeated until the occurrence of unacceptable toxicities, disease progression, or patient refusal. The primary end point was the overall survival.ResultsThe response rates were 33.3%, 12.5%, and 0% after the first, second, and third line chemotherapy, respectively. The mean overall survival time was 994 days. The median survival time could not be calculated because 12 out of 19 patients were still alive when the study was concluded. Regarding hematological toxicity, the major adverse effect was leukopenia, which reached grades 3–4 in all lines of chemotherapy investigated. In addition, regarding non-hematological toxicities, the major adverse effect was anorexia, which reached grade 3–4 in the second line chemotherapy, and no deaths were attributable to the adverse effects of the drugs.ConclusionThis sequential therapy was an effective treatment for advanced gastric cancer with acceptable toxic side-effects. We considered this sequential therapy to be effective because of the smooth switch to the next regimen.

Nowadays, patients with chronic hepatitis C in all countries are generally treated with interferon (IFN), and more than 50% of patients become HCV-RNA negative following PEG-IFN plus ribavirin therapy, but unfortunately, the IFN therapy is not effective in about 70% of patients with HCV-associated LC. In Japan, HCC actually develops in about 7% of those patients every year. A strategy for preventing HCC development other than IFN therapy is, therefore, urgently needed for those patients. We reported that the recurrence rate and the development of HCC was more rapid in the high serum ALT level (>80 IU) patients with HCV-associated LC. Sho-saiko-to, Juzen-taiho-to, and stronger-neo minophagen C are herbal medicines used in Japan to treat chronic viral liver diseases, and they work by reducing inflammatory processes and controlling ALT levels. Aggressive reduction therapy for ALT levels in HCV-LC patients could significantly prevent HCC development.

The clinical efficacy and safety of CPT-11+CDDP therapy were studied retrospectively in 34 patients with advanced and recurrent gastric cancer. The overall response rate was 5. 9%; MST was 209 days. The adverse effects observed were grade 3 in 7 patients(20. 6%). CPT-11+CDDP therapy could be useful and safe as third-line chemotherapy.

Expression and presence of the carbohydrate antigens CA19-9, SLX and STN, and CEA in tissues and serum were examined in 132 patients with early or propria muscle invaded gastric cancer. The seropositive rate was not different in patients with cancer or gastritis. In tumor tissue, the positive rate for these antigens was 28.8% in CA19-9, 9.1% in SLX, 47.0% in STN and 72.9% in CEA. Results showed that gastric cancers, even at an early stage, produce abnormal carbohydrate antigens not detected in normal tissues. However, transfer of antigens into the circulation was not observed in patients with early gastric cancer, suggesting the possibility that number of carcinoma cells may be involved in the transfer of antigens into blood.

A 59-year-old man visited our hospital. After examination he was diagnosed with advanced gastric cancer with multiple liver metastases. At first, chemotherapy of S-1/CDDP was administered. After two weeks, he had severe diarrhea and anorexia, so the therapy was discontinued. Weekly paclitaxel was selected as the next therapy. Depending on the leukocytopenia, doses and intervals were controlled. After 4 courses, CT and MRI revealed that the liver metastases had disappeared, while the primary lesion remained. Seven months after beginning treatment, distal gastrectomy was performed. After the operation, 6 courses of paclitaxel therapy were given at the same doses and the same intervals as before the operation. Two years have passed since the operation, and no recurrence was seen on CT and MRI. Because of the relatively low frequency of adverse events in the digestive system, continued treatment with paclitaxel is possible. These findings show that paclitaxel is an effective drug for advanced gastric cancer with liver metastasis.

Serum adiponectin concentrations are negatively correlated with body fat percentage and with the risk of colorectal cancer. However, few studies have examined the relationship between adiponectin receptor expression and colorectal cancer. We measured the expression levels of the AdipoR1 and AdipoR2 genes by quantitative real-time reverse-transcription polymerase chain reaction in 202 paired specimens of cancer tissue and adjacent normal mucosa obtained from patients with colorectal cancer. To evaluate the clinical significance of AdipoR1 and AdipoR2, correlations between the expression of these genes and clinicopathological features were examined. Both genes were expressed in colorectal cancer and in adjacent normal mucosa. The expression levels of the genes were significantly higher in cancer tissue than in normal mucosa (P

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.

We report three cases of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel (DOC). We administered S-1 orally at 80 mg/m² on days 1 to 7 and days 15 to 21, and DOC intravenously at 40 mg/m² on day 1 and 15, and evaluation was conducted every two courses. Case 1: A 73-year-old man with gastric cancer of cT4a, accompanied with bulky N2 lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by total gastrectomy, which revealed his histological grade to be 1b. Case 2: A 65-year-old man with gastric cancer of cT4a, accompanied with bulky lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by distal gastrectomy, which revealed his histological grade to be 1b. Case 3: A 76-year-old woman with gastric cancer of cT4b (panc), was treated with four courses of S-1 and DOC. After that, the main tumor was judged to be cT4a, followed by total gastrectomy, which revealed her histological grade to be 1b. Combined S-1 and DOC chemotherapy is an effective regimen for the treatment of unresectable gastric cancer.

Cetuximab, a monoclonal antibody used to target the epidermal growth factor receptor(EGFR), was approved for refractory and metastatic colon cancer expressing EGFR, and the EGFR expression must be confirmed. But the EGFR expression may become false negative by immunohistochemistry. When we used a past operation specimen for a search in particular, a correct evaluation may be difficult for prolonged formalin fixation. We report a case successfully treated by cetuximab, who was diagnosed as EGFR-negative by the past operation specimen, but as EGFR-positive by the liver biopsy specimen. A 51- year old woman with multiple organ metastases, who had experienced failure with prior oxaliplatin, irinotecan(CPT-11), 5- FU and bevacizumab regimens, was administered cetuximab plus CPT-11 because it was EGFR-positive by liver biopsy, and the tumor was obviously reduced. It is useful to obtain another specimen such as by liver biopsy, when the EGFR expression is negative by a past operation specimen.

Background We developed a skin-level jejunostomy tube (SLJT) procedure for patients undergoing esophagectomy using a skin-level gastrostomy tube (G-tube) (Entristar™; Tyco Healthcare, Mansfield, Mass), in order to improve their nutrition status and quality of life (QOL). We describe the procedure and the adverse effects of SLJT in patients with esophageal cancer (EC). Methods Over a 24-month period (March 2008 to March 2010), there were 16 patients (mean age: 61.8 years; age range: 49-75 years; 15 men, 1 woman) who had Stage II or III EC. Primary jejunostomy was performed under general anesthesia during esophagectomy. The technical success and the immediate and delayed complications of the procedure were recorded. Jejunostomy techniques SLJT placement using the G-tube (20Fr) was performed 20 cm from the Treitz ligament on the side opposing the jejunal mesenterium. The internal retention bolster was exteriorized through an incision in the abdominal wall. A single purse string suture using a 4-0 absorbable suture was performed. The internal retention bolster was then inserted into the jejunal lumen via the small incision. The intestine adjacent to the tube was anchored to the peritoneum using a single stitch. Results The SLJT was successfully inserted in all 16 patients. No early complications were documented. Follow-up for a median of 107 days (range, 26-320 days) revealed leakage to the skin in four patients, including superficial wound infections in two patients. There were no cases of obstruction of the tube or procedure-related death. Conclusions This SLJT placement technique using the G-tube is a safe procedure in patients with EC and allows the creation of a long-term feeding jejunostomy.

A 21-year-old man was referred to our hospital because of a right thoracic mass detected on a medical checkup. He was asymptomatic. There was no history of trauma or Gardner syndrome. Computed tomography revealed that the chest wall tumor involved the right first and second ribs (Figure 1A). The tumor occupied the right hemithorax and displaced the mediastinum to the left (Figure 1B). A combined clamshell incision and median sternotomy were performed. The tumor was resected en bloc with portions of the first rib, second rib, sternum, musculus pectoralis major, and clavicle. The chest wall was reconstructed with a 1-mm composite mesh (polypropylene/polytetrafluoroethylene). Mechanical ventilation was required for 2 weeks postoperatively because of respiratory failure. However, the patient recovered without any functional deficit. Histopathological examination confirmed a desmoid tumor measuring 23.5 18 11 cm and weighing 2800 g. The specimen showed proliferations of spindle-shaped cells with slight atypia in a collagenous stroma. The surgical margins were free of tumor (Figure 2). Desmoid tumors are relatively rare tumors derived from fascial or musculoaponeurotic structures. Pathologically they are benign but grow locally aggressive. If feasible, surgical resection of the tumor is the treatment of choice, but a high incidence of local recurrence has been reported.1,2 Reoperation and positive margins are associated with a high risk of local recurrence.1 Therefore, it is essential to achieve local control by wide resection with tumor-free margins on initial treatment.

ヒト胃癌細胞株STKM-1を用いてCis-diamminedichloroplatinum (以下CDDP) とカフェイソとの併用抗腫瘍効果と染色体におよぼす影響について検討した.CDDP (2μg/ml) 3時間接触で57%の増殖率であったが, CDDP接触後カフェイソ1mM持続接触にて23%に, 2mMにて9.3%に低下し, 抗腫瘍効果の増強が認められた.CDDP (2μg/ml) 処理後の染色体におけるgap/breakの出現頻度は1.816±1.509/Cell, exchangeの出現頻度は0.184±0-565/Ce11であった.CDDP処理直後からカフェイン1mMを24時間接触させるとgap/breakの出現頻度は4-206±3.162/Cell, exchangeは0.760±0.938/Cellと増加した.CDDP処理後24, 48時間後にカフェインを接触させても同様の結果が得られた.以上より, カフェインはDNA修復阻害作用を有し, 胃癌に対する化学療法において, CDDPとの併用で抗腫瘍効果の増強が期待された.

Recently a case of multiple gastric carcinoma occurring 19 years after gastrojejunostomy was experienced. A 59-year-old man was referred to the hospital under a diagnosis of multiple gastric carcinoma resulting from X-ray examination, endoscopy and biopsy of the stomach at nearly hospital, to where he visited because of hematemesis in November 1987. There was a history of undergoing freeing of intestinal adhesions and gastrojejunostomy for intestinal obstruction when he was 40 years old. After admission to the hospital, operation was carried out in March 1988. Intraopertive findings included P0H0N0S2 and subtotal gastrectomy including a part of the anastomosed small intestine was radically performed. The resected specimen revealed 4 different lesions, namely, Borrmann type 2 (tub1, ss) in the pylorus vestibule, Borrmann type 1 (por, pm) in the anastomosed site of the stomach and jejunum, IIc (por, sm) in greater cuavature of the body of the stomach, and IIc (tub1, sm) in lesser cuavature of lower body of the stomach. Occurrence of gastric carcinoma following gastrojejunostomy, especially multiple type, has been rarely reported in Japan. This case which was accompanied by a change of extensive gastritis cystica polyposa in the submucosal layer ranging from the anastomosed site to greater cuavature of the body of the stomach was very interesting. Some literature notes are also presented here.

Circadian rhythms are daily oscillations in various biological processes, generated by the feedback loops of eight core circadian genes: Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Clock, Bmal1 and Casein Kinase I e (CKIe). Recent studies have suggested that circadian genes participate in the growth and development of various cancers. This study examined the relations of circadian gene expression to clinicopathological factors and outcomes in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. The relative expression levels of the circadian genes in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. Expression of the Clock gene and the CKIe gene in cancer tissue were significantly higher compared to that in adjacent normal mucosa. Expression of the Per1 and Per3 genes in cancer tissue was significantly lower compared to that in adjacent normal mucosa. Analysis of the relations between clinicopathological features and expression of the eight circadian genes in cancer tissue showed that high expression of the Bmal1 gene and low expression of the Per1 gene correlated with liver metastasis. On analysis of the relations between outcomes and gene expression, high expression of the Per2 gene was associated with significantly better outcomes than low expression of the Per2 gene. Overexpression of the Bmal1 gene and reduced expression of the Per1 gene may thus be useful predictors of liver metastasis. Moreover, reduced expression of the Per2 gene may be a predictor of outcomes in patients with colorectal cancer.

CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p

Regenerating islet-derived family members (Reg) are superfamily of calcium-dependant lectins that are expressed in the proximal gastrointestinal tract and ectopically at other sites in the setting of tissue injury. The regenerating islet-derived family member 4 (RegIV) gene has been reported in various cancers, associating with diverse functions. This study examined the relation of the relative expression of RegIV gene to clinicopathological factors and outcomes in patients with colorectal cancer (CRC).We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated CRC. The relative expression levels of RegIV mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction.RegIV gene expression was higher in cancer tissue than in adjacent normal mucosa. The multivariate analysis of clinicopathological factors for 5-year overall survival showed a higher level of RegIV gene expression was a significant independent predictor. Overall survival at 5 years differed significantly between patients with high RegIV gene expression and those with low expression.Overexpression of the RegIV gene is considered a useful independent predictor of outcomes in patients with CRC.

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.

Pseudomembranous colitis, an antibiotic-associated diarrhea, needs early diagnosis and treatment for the high fatality rate in severe cases. We report a case of pseudomembranous colitis following the use of antibiotics in febrile neutropenia (FN). A 74-year-old man with non-curative resected sigmoid colon cancer was treated with cefepime in FN induced by chemotherapy. Complications of diarrhea were seen on day 2. Paralytic ileus and disseminated intravascular coagulation were also complications. He was diagnosed as pseudomembranous colitis for Clostridium difficile toxin-positive. Vancomycin enemas were administered because oral administrations were impossible, and the effect was provided. Vancomycin enemas are an effective therapy for patients with severe pseudomembranous colitis unable to tolerate oral medications because of ileus.

We investigated whether or not there are cancer cells in the blue node (BN) and the sentinel lymphaticus (SL), which is detected using sentinel node biopsy (SNB).Patent blue (1%) is injected submucosally into 4 to 5 different sites at 1 mL per site around the primary tumor. Blue-stained lymphatics and lymph nodes can be seen by turning over the greater omentum and lesser omentum extraperitoneally. If blue nodes or lymphaticus are found, biopsy is performed at this point. The study was conducted in 14 patients (11 males and 3 females, mean age 65.7 y/o) with a preoperative diagnosis of T1 tumor invasion and NO that there is no lymph node metastasis. Informed consent was obtained from the patients for SNB after patent blue staining and investigation of CEAmRNA and CK20mRNA.Of the 14 patients in whom BN and SL were identified, 1 (7.1%) had positive CEAmRNA and positive CK20mRNA of SL.Our present study shows the possibility for the existence of cancer cells in the lymphaticus from the tumor to BN. We should avoid the cut of lymphaticus when we perform gastrectomy.

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.

As a project of the Kanagawa Colorectal Cancer Study Group, we performed this study to analyze the efficacy and the safety of modified FOLFIRI (irinotecan: 150 mg/m2) therapy for Japanese patients with metastatic colorectal cancer.We treated PS 0-1 Japanese patients with measurable or assessable colorectal cancer who either had not received preliminary treatment, or were postoperative with metastasis and had undergone radiation therapy or adjuvant chemotherapy before more than four weeks, and further had provided written acceptance of our proposed procedures. Twenty patients received modified FOLFIRI therapy as a 2-hour infusion of CPT-11 150 mg/m/2 and l-LV 200 mg/m2 followed by a bolus 5-FU 400 mg/m/2 and 46-hour infusion 5-FU 2, 400 mg/m2. Tumor response was assessed by RECIST and toxicity by NCI-CTC.Thirty males and seven females underwent an average 10 courses of treatment. This therapy achieved a 50% response rate, 80%disease-control rate, and 316+/-40 days PHS. Regarding hematological toxicity, 11 patients (55%) experienced leukemia, which developed to grade 3/4 in 5 (25%) of them. Twelve patients (65%) experienced neutropenia, which developed to grade 3/4 in 10 (50%) of them. Digestive toxicity was observed in 16 patients (80%), which developed to grade 3/4 in only one patient (5%) with gastric ulcer. Six patients (30%) experienced alopecia, which was grade 1/2 only.This clinical study was safely carried out. The efficacy was as good as in previous reports using a regular dose of CPT-11.

Extraskeletal osteosarcoma is an uncommon high-grade malignant soft tissue sarcoma. Well-differentiated extraskeletal osteosarcoma is thought to have a better prognosis than classical extraskeletal osteosarcoma, but dedifferentiation after recurrence has also been reported. We present a case of a primary retroperitoneal extraskeletal osteosarcoma in a 62-year-old Japanese woman. Abdominal CT revealed a large mass with diffuse calcification in the right retroperitoneal space and tumor resection was performed. The histopathological diagnosis was well-differentiated retroperitoneal extraskeletal osteosarcoma. She was followed up by CT every 6 months without adjuvant radiotherapy and chemotherapy for 31 months until anaplastic high-grade spindle cell sarcoma recurred in the retroperitoneum. Our case is the seventh reported description of well-differentiated extraskeletal sarcoma, and the first to arise in the retroperitoneum and recur as an entirely dedifferentiated spindle cell sarcoma.

Paraneoplastic neurological syndromes (PNSs) are a heterogeneous group of neurological disorders caused by immune-mediated mechanisms. The incidence of PNS is much less than 1% for solid tumors, except for small-cell lung cancer and thymoma. We report a rare case of gastric cancer that presented with primary clinical findings of PNS. The patient was a 63-year-old woman who was admitted for worsening neuropathy. Laboratory and neurological tests excluded a nutritional deficit, diabetes mellitus, and connective tissue disease as causes of her neuropathy. Computed tomography (CT) of the abdomen, positron emission tomography (PET)-CT, and endoscopy of the stomach revealed gastric cancer with lymph node swelling. Distal gastrectomy was performed and pathological and immunohistochemical examinations indicated endocrine cell carcinoma. The gastrectomy stopped the exacerbation of her symptoms and recurrence was not observed, but the neurological disorders were irreversible. This case suggests that early diagnosis of the primary tumor is required to improve the outcome in patients with PNS.

Extrahepatic portal vein aneurysm is a rare disorder. From 1956 to 2008, we found only 43 published English-language reports, including 67 cases, using Pub Med. We report a case of a 77-year-old woman who had complaints of lower abdominal fullness and residual urine. We performed ultrasonography (US), which demonstrated a congenital extrahepatic portal vein aneurysm. She had no obvious symptoms of the extrahepatic portal vein aneurysm. She had undergone gastrectomy without blood transfusion for gastric ulcer more than 20 years ago. Physical examination revealed no abnormal findings. US revealed a2.2×1.8 cm, round shaped hypoechogenic lesion at the hepatic hilum. Color Doppler US showed bidirectional colors due to circular flow within this lesion. 3D-CT and CT angiography demonstrated that the saccular aneurysm at the hepatic hilum was 3.0 cm in diameter and was enhanced equal to that of portal vein.Twenty-six months after the diagnosis, the aneurysm had not grown in size. Since our patient had no serious complaints or liver disease, surgical procedures had not been employed. US and 3D-CT are noninvasive diagnostic techniques and are helpful in the diagnosis and follow-up of extrahepatic portal vein aneurysms.

幽門輪と胃癌の進行度・予後との関係を調べる目的で, 下部胃癌症例162例を対象にし, 幽門輪に接した, または幽門輪を越えて十二指腸へ進展した胃癌 (幽門輪群) と, 幽門輪から離れた胃癌 (非幽門輪群) との間で臨床病理学的成績を比較・検討した.その結果, 幽門輪群は非幽門輪群に比べて進行癌の頻度が有意に高かった.リンパ節転移率も幽門輪群で有意に高率であった.しかし予後的漿膜面因子PS (+) 例のみの比較では両群間に差がなかった.組織学的分化度では両群間に有意な差を認めなかったが, 十二指腸進展例では, 組織型が分化型のものは限局性に, 未分化型は浸潤性に進展する傾向が認められた.治療成績では治癒切除例の5年生存率は幽門輪群40.7%, 非幽門輪群69.3%で, 幽門輪群で不良であった.しかしps (+) 症例のみに限定すると生存率による差はなかった.

Claudin-7 is a tight junction protein that plays an important role in tumorigenesis, tumor invasion and metastasis. We examined the clinical significance of claudin-7 expression in 75 postsurgical non-small cell lung cancer (NSCLC) patients. Claudin-7 expression was measured immunohistochemically and was found to be high in 25 patients (33.3%) and low in 50 (66.7%). Survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high NSCLCs (P=0.024). In particular, survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high squamous cell carcinomas (P=0.011). A reduced expression of claudin-7 was associated with poor outcome in NSCLCs. Claudin-7 may thus be a useful biomarker and a potential therapeutic target in patients with NSCLC.

Herein, we report two extremely rare cases of differentiated thyroid carcinoma (DTC) with extended tumor thrombus or mediastinum lymph node metastasis (LNM) involving the superior vena cava (SVC), causing SVC syndrome. Both of these patients were successfully treated with radical resection and reconstruction of the SVC using autologous tissue instead of an expanded polytetrafluoroethylene (ePTFE) graft. The left brachiocephalic vein was used to reconstruct the SVC in a papillary thyroid carcinoma patient with mediastinum LNM and a pericardial patch was used in a follicular thyroid carcinoma patient with tumor thrombus. Our search of the English-language literature found sporadic reports of SVC resection with reconstruction by vascular graft (ePTFE), interposed between the brachiocephalic vein and the right atrium. However, SVC reconstruction using autologous tissue in thyroid carcinoma has not been reported to date. To our knowledge, this is the first report describing such an unusual technique in DTC patients.

A 52-year-old woman visited our hospital with epigastralgia. Detailed examination revealed a duodenal cancer of the ascending limbs. Since she refused the resection, the administration of S-1 alone was commenced. After one course of this treatment, oral intake became impossible. Duodenography and endoscopy showed duodenal obstruction, and she underwent surgery. The tumor proved to be unresectable due to direct invasion of the inferior vena cava. Duodenojejunostomy was performed. After surgery, she was treated by S-1 and survived 2 years and 11 months, which resulted in 3 years and 2 months' long survival from her first visit. The intervals of the intake and home stay, after the operation, were 2 years and 8 months and 2 years and 5 months, respectively. The combination of S-1 administration and bypass operation provides a useful alternative for the treatment of unresectable duodenal cancer with stenosis.

A 73-year-old man with gastric cancer of Borrmann type 3 accompanied with N3 was treated by combination therapy of S-1 and docetaxel (DOC). He received DOC intravenously at 45 mg/m/2 on day 1 and 15, and S-1 orally at 120 mg/body on day 1 to 7 and day 15 to 21. This treatment was repeated every 28 days as one course. After 4 courses of treatment, a CT scan revealed partial response of the lymph node metastases, and imaging modalities showed complete response of the primary lesion. The serum CEA value normalized after 4 courses of treatment. Toxicities included leukocytopenia (grade 3-4) and neutropenia (grade 3-4). Chemotherapy in the outpatient setting was possible by reduction of dose (DOC 45--40--35 mg/m2). Total gastrectomy was performed after 4 courses of treatment. The histological effect of primary lesion was judged to be Grade 2.

Background To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. Methods We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Results Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Conclusion Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.

In May 2006, a 79-year-old man underwent left colectomy and D2 lymphadenectomy for descending colon cancer (fStage II , Cur A). No adjuvant chemotherapy was done. Eighteen months after surgery, the serum tumor marker level was increased (CA19-9 526 U/mL), and multiple liver metastases (H2) and peritoneal dissemination were detected using abdominal CT. He was treated with S-1 plus CPT-11 therapy, because mFOLFOX6 as a standard chemotherapy for advanced colorectal cancer was rejected. After 4 courses, tumor markers normalized and abdominal CT revealed a partial response. At present, progression-free survival (PFS) is 240 days. In our case, this regimen was found to be convenient and safe in an outpatient compared with FOLFIRI and FOLFOX. This case suggested that S-1 plus CPT-11 therapy could well be a promising systemic chemotherapy for patients with advanced colorectal cancer.

We report a patient who long had a complete response by chemotherapy with imatinib mesilate(IM)for locally recurrent gastrointestinal stromal tumor(GIST)of the stomach. On July 2000, a 58-year-old woman was pointed out to have anemia in the course of surveillance for malignant melanoma of skin. Endoscopic examination revealed continuous bleeding from a submucosal tumor with ulceration on the posterior wall of the stomach. After endoscopic homeostasis failed, emergency laparotomy was performed and a biopsy was also done. The diagnosis made was GIST from immunohistological findings of positive c-kit, positive CD34, negative HMB45, and negative S100. After diagnosis, total gastrectomy, distal pancreatectomy, and splenectomy were performed. On September 2003, a local recurrence was recognized, and then chemotherapy by 400 mg IM daily was started. After beginning with a dose of IM 400 mg daily, the reduction of the tumor was monitored. The IM dose then had to be reduced to 300 mg daily. Because of the adverse side effects of IM, systemic edema and body weight increased. After reduction of IM, the adverse reactions resolved promptly, and a complete response of the primary tumor has been maintained for 4 years 3 months.

There are several reports describing [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) findings in patients with lymphomatoid granulomatosis (LYG). We report a case of grade I LYG that showed increased uptake of FDG. The patient was a 63-year-old Japanese male who underwent an FDG-PET/computed tomography (CT) scan in screening for a malignant lesion. Increased uptake of FDG [maximum standard uptake value (SUV(max)), 3.7] was observed in the right hilar region in FDG-PET and enhanced CT revealed a round, abnormal mass that also showed increased FDG uptake. The patient had no previous symptoms. A tumor biopsy was performed and the histological diagnosis was grade I LYG. Therefore, increased SUV(max) in FDG-PET might be useful for diagnosing of LYG.

Background We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection. Methods Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex- and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations. Results Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma. Conclusion Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

We report a case of small cell carcinoma of the esophagus(SCEC)treated by chemotherapy with 5-fluorouracil(5- FU)plus cisplatin(CDDP)and operation. A 60-year-old man was seen at the hospital because of a sensation of food sticking in his throat at meals. Gastrointestinal endoscopy revealed a type 2 tumor in the middle portion of the esophagus, which was pathologically diagnosed as small cell carcinoma. With a diagnosis of SCEC, preoperative chemotherapy with 5-FU plus CDDP was given. Primary lesion showed complete response. After chemotherapy, an operation was performed. The tumor had histopathologically disappeared, and the patient has been free of any signs of recurrence, as of 6 years 2 months after the operation. Primary small cell carcinoma of the esophagus is a rare disease with early systemic metastasis, and the prognosis remains poor. In a review of the literature, all patients with SCEC who had survived for 2 years or more had undergone combined therapies including operation, chemotherapy and radiotherapy. This study deals with a long-term surviving patient without any signs of recurrence after excision of the foci followed by chemotherapy.

A 74-year old man was treated with first-cycle chemotherapy of paclitaxel (70 mg/m2=110 mg day 1, 8, 15) and carboplatin (AUC5=500 mg day 1) for lung cancer (c-T3N2M0, stage III A). On day 6 abdominal pain appeared, while on day 7 abdominal CT showed a perforation of the digestive tract. Thirty-three hours after the onset he underwent Hartmann operation during which we recognized a perforation 1.7 cm in size in the rectum. Although the cause of the perforation was unknown from the pathological findings, anticancer agents were suspected to be involved. Perforation should be taken into consideration in connection with acute abdominal disease after chemotherapy.