[A Case of Advanced Gastric Cancer with Multiple Bone Metastases, Virchow Lymph Node and Para-Aortic Lymph Node Metastases That Responded to Combined Modality Therapy and Underwent Conversion Surgery].

A 41-year-old woman with type 3 advanced gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple bone metastases was diagnosed with U-less cType 3 cT4aN3M1, cStage IV. We administered docetaxel, cisplatin, and S-1 (DCS)therapy for unresectable gastric cancer. After 11 courses of DCS, we confirmed that the distant lymph node metasta- ses were significantly reduced. We performed radiotherapy(30 Gy/10 Fr)on the thoracic lumber vertebrae. Because the patient was successfully downstaged, we performed total gastrectomy with Roux-en-Y reconstruction. The histopathological diagnosis was ypT3N2M0, ypStage III A. In this case, DCS therapy successfully treated gastric cancer with distant metastases, including multiple bone metastases.

Validity of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 for resectable locally advanced gastric cancer.

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.

Long-term comparison of boomerang-shaped jejunal interposition and Billroth-I reconstruction after distal gastrectomy.

BACKGROUND: Billroth-I (BI) is a simple, physiological method of reconstruction following distal gastrectomy. In actuality, postoperative QOL is by no means favorable due to the high incidence of post-gastrectomy syndrome. The aim of this study is to assess the safety and efficacy of boomerang-shaped jejunal interposition (BJI) after distal gastrectomy. METHODS: Sixty-six patients with early gastric cancer underwent the BI procedure (n = 33) or BJI (n = 33) after distal gastrectomy, following which they were compared for 5 years. Tumor characteristics, operative details, postoperative complications and complaints, number of meals, and body weight were analyzed. Patients were followed up by endoscopy every 12 months. RESULTS: There were no significant differences in the incidence of postoperative complications. The incidence of heartburn (30 vs. 0 %, P = 0.0009) and oral bitterness (33 vs. 6 %, P = 0.0112) were significantly lower in the BJI cases. Endoscopic findings revealed significantly lower incidences of reflux esophagitis (24 vs. 0 %, P = 0.0051) and remnant gastritis (70 vs. 3 %, P < 0.0001) in the BJI group. The incidence of food stasis was low in both groups (12 vs. 15 %). In the BJI group, 30 patients (90 %) were eating 3 meals/day within 12 months, whereas in the BI group, 16 patients (48 %) were still eating 5 meals/day at 12 months or later. CONCLUSIONS: BJI is as safe as BI, but is better in terms of improvement in bile reflux and food intake without stasis. This procedure, therefore, appears to be a useful method for reconstruction after distal gastrectomy.

Lipogenic gene expression profile in patients with gastric cancer.

Numerous types of cancer exhibit increased lipogenesis and expression of lipogenic enzymes and transcription factors, including sterol regulatory element-binding protein-1. Lipogenic gene expression is upregulated at the mRNA level, in concert with metabolic pathways associated with changes in expression and/or activity of lipogenic transcription factors. However, this expression pattern in human gastric carcinoma has not been elucidated. In this study, lipogenic gene expression in cancer tissues was investigated using quantitative PCR. In patients with gastric cancer, carnitine O-palmitoyltransferase type I mRNA and miR-33b were significantly downregulated, suggesting that miR-33b downregulation is mediated by conditions that also affect the expression and/or activity of transcription factors involved in lipogenic gene expression. Consequently, the association between miR-33b and gastric cancer may provide a novel strategy for the genetic diagnosis of gastric cancer. However, additional studies including a larger number of samples are required to confirm these results.

Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients.

BACKGROUND: Imatinib mesylate, a small-molecule tyrosine kinase inhibitor, is currently used for adjuvant therapy of patients who have undergone resection of high-risk gastrointestinal stromal tumors (GISTs). There are no data concerning the efficacy and safety of postoperative adjuvant therapy with imatinib for Japanese or East Asian patients with GIST. METHODS: A single-arm, open-label, multicenter trial was conducted in 17 hospitals in Japan. The eligibility criteria included histologically proven primary high-risk GISTs with macroscopic complete resection. Patients were treated with imatinib at a dose of 400 mg/day for 1 year after surgery. The primary endpoint was recurrence-free survival as assessed by Kaplan-Meier analysis. The secondary endpoints were overall survival and safety. This study was registered with ClinicalTrials.gov, number NCT00171977. RESULTS: A total of 64 patients were enrolled between September 2004 and July 2006. The median age of the patients was 59.5 years. Forty-nine (76.6%) patients completed the 1-year treatment, whereas 15 (23.4%) patients did not complete the treatment owing to recurrence, toxicities, and consent withdrawal. At the median follow-up period of 109 weeks, 20 patients had recurrence. The 3-year recurrence rate was 42.7% (95% confidence interval 29.2-56.3%), which exceeded the expected recurrence rate in this trial. The recurrence-free and overall survival rates at 2 years were 71.1 and 93.7%, respectively. The most frequent adverse drug reaction of any grade was eyelid edema (48.4%), followed by neutropenia (40.6%), leukopenia (39.1%), nausea (39.1%), rash (37.5%), and peripheral edema (37.5%), most of which were mild and manageable. CONCLUSIONS: Adjuvant therapy with imatinib at 400 mg/day for 1 year is well tolerated by Japanese patients and possibly reduces the risk of early recurrence of high-risk GISTs.

Comprehensive analysis of genes involved in the malignancy of gastrointestinal stromal tumors.

BACKGROUND: During tumorigenesis of gastrointestinal stromal tumors (GISTs), the most frequent changes are reported to be gain-of-function mutations in the C-KIT proto-oncogene. However, we speculated that additional genetic alterations are required for the progression of GISTs. PATIENTS AND METHODS: Using 15 cases diagnosed with GISTs, we searched for novel indicator genes by microarray analyses using an Oligo GEArray(R) PI3K-AKT Signaling Pathway Microarray Kit. In addition, we analyzed the mutational status of C-KIT and the proliferation status indicated by the Ki-67 index. RESULTS: The tumor localizations of the 15 GISTs were as follows: 8 in the stomach; 2 in the small intestine; 2 in the mesentery; 1 in the duodenum; 1 in the rectum; and 1 in liver. Regarding the C-KIT gene analysis, mutations in exon 11 were detected in 11 out of 13 patients. In 1 out of the 13 patients, mutations were detected in both exons 11 and 13. No genetic abnormalities were identified in 1 patient. The Ki-67 labeling indices were significantly lower for the low-risk and intermediate-risk groups than for the high-risk group (p=0.0440). No specific genes were overexpressed in the >1% Ki-67 group. Regarding the primary lesion sites, the following 6 genes were overexpressed in tumors in the stomach: RBL2, RHOA, SHC1, HSP90AB1, ACTB and BAS2C. CONCLUSION: Gene analysis is currently only useful for diagnostic assessment and predicting therapeutic effects. However, it may be possible for new malignancy-related factors to be identified by comparing and investigating gene expression levels and other factors using such analyses.

Successful endoscopic procedures for intraductal papillary neoplasm of the bile duct: a case report.

Attention has recently been focused on biliary papillary tumors as the novel disease entity intraductal papillary neoplasm of the bile duct (IPNB), which consists of papillary proliferation of dysplastic biliary epithelium. As even benign papillary tumors are considered as premalignant, some investigators recommend aggressive surgical therapy for IPNB, although no guidelines are available to manage this disease. Few reports have described long-term follow-up of patients with benign IPNB without radical resection. If patients with IPNB who are treated only with endoscopic procedures are noted, clinical profiles and alternative therapies other than resection may be recommended. We report the case of a patient who experienced repetitive cholangitis for 10 years and was finally diagnosed with IPNB. Radical resection could not be recommended because of the age of the patient, therefore, endoscopic sphincterotomy was performed. Although an endoscopic retrograde biliary drainage catheter was placed several times for repetitive cholangitis, the patient has done well during follow-up. Our case may offer insights into the natural course and management decisions for the novel disease entity of IPNB.

[A case of effective treatment of oral TS-1 and intravenous MMC administration for multiple metastases of gastric cancer].

A 49-year old man underwent distal gastrectomy (D3) for circumferential type 3 cancer at the gastric antrum and cholecystectomy in September 2002. During the surgery, multiple metastases were observed predominantly in the left lobe of the liver, and lateral segmentectomy was performed as non-curative (curability-C) resection leaving the small metastases in the right lobe of the liver. Based on the results of chemo-sensitivity tests (5-FU 15.0%, CDDP 34.0%, MMC 35.3%, TXT 0.0%), we started to administer TS-1 (100 mg/day for 4 weeks followed by a 2-week rest interval) and MMC (10 mg/body on day 1). Due to leukocytopenia, the regimen was changed to TS-1 (100 mg/day for 4 weeks followed by a 2-week rest interval) and MMC (4 mg/body every other week [day 1, 14]) from the second course. Levels of tumor markers dropped and liver metastatic lesions remarkably decreased in size by CT after the third course. In conclusion, a combination of TS-1/MMC may be regarded as one option for postoperative adjuvant chemotherapy for outpatients.

Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer.

BACKGROUND: Correlations between the malignant potential and prognosis of cancer and abnormal control mechanisms of apoptosis have been discovered in a variety of cancers. Survivin is a member of the inhibiting apoptosis protein family that is abundant in embryonic and carcinoma tissues. We measured the expression of survivin mRNA in gastric cancer to determine whether levels of survivin mRNA expression could serve as an index of malignancy. METHODS: Expression of survivin mRNA was measured in samples of both gastric cancer and noncancerous tissue from 107 patients. Survivin mRNA was detected by the real-time polymerase chain reaction (PCR) method, and then the relationship between the survivin mRNA level and histological diagnosis was analyzed. RESULTS: Expression of survivin mRNA was observed in 105 of 107 cancerous tissues and in 101 of 107 noncancerous tissues. The Mean value of survivin mRNA expression in cancerous tissue was 5.18 +/- 1.30, significantly higher ( P < 0.01) than that in noncancerous tissue, at 4.21 +/- 1.48. No significant differences were found in the values of survivin mRNA expression according to histological classification or according to increasing depth of tumor invasion. However, survivin mRNA expression was significantly higher ( P < 0.01) in patients displaying lymph node metastasis (5.48 +/- 1.01) than in patients without the metastasis (4.70 +/- 1.55). CONCLUSIONS: These results indicate that increased survivin mRNA expression begins in the early stages of gastric carcinogenesis. Moreover, the level of survivin mRNA expression may indicate the potential for lymph node metastasis in patients with gastric cancer. Correlations between the malignant potential and prognosis of cancer and abnormal control mechanisms of apoptosis have been discovered in a variety of cancers. Survivin is a member of the inhibiting apoptosis protein family that is abundant in embryonic and carcinoma tissues. We measured the expression of survivin mRNA in gastric cancer to determine whether levels of survivin mRNA expression could serve as an index of malignancy.