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PURPOSE: The second planned interim analysis (median follow-up 12.5 months) in a phase III trial of postoperative adjuvant chemotherapy for stage III gastric cancer revealed significant improvement in relapse-free survival (RFS) for S-1 plus docetaxel over S-1 alone. Although enrollment was terminated on the recommendation of the independent data and safety monitoring committee, we continued follow-up and herein report on 3-year RFS, the primary endpoint. PATIENTS AND METHODS: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. In the S-1 plus docetaxel group, S-1 was given orally for 2 weeks followed by 1 week of rest for seven courses, and docetaxel was given intravenously on day 1 of the second to seventh courses. The combination therapy was followed by S-1 monotherapy for up to 1 year. RESULTS: The 3-year RFS rate of the S-1 plus docetaxel group was 67.7%. This was significantly superior to that of 57.4% in the S-1 group (hazard ratio [HR] 0.715, 95% CI 0.587-0.871, P = 0.0008). This translated into a significant benefit in the 3-year overall survival (OS) rate in the S-1 plus docetaxel group (77.7% versus 71.2%, HR 0.742, 95% CI 0.596-0.925, P = 0.0076). CONCLUSION: On 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel was confirmed to improve both RFS and OS and can be recommended as a standard of care for patients with stage III gastric cancer treated by D2 dissection.

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Gastric endocrine carcinoma is a comparatively rare type of gastric cancer, accounting for 0.6% of all gastric cancers. Six cases of gastric endocrine carcinomas that were identified from November 2011 to March 2017 were reviewed. The mean age of the patients was 73.3 years, and 1 patient had StageⅠA cancer, 1 had Stage ⅡB, 2 had Stage ⅢA, and 2 had Stage Ⅳ. Three patients had concomitant conventional adenocarcinoma. Four patients underwent total gastrectomy, 3 of whom showed liver metastases after surgery. The prognosis of gastric endocrine carcinoma is poor because it rapidly metastasizes to the liver and lymph nodes. When unresectable metastatic disease occurs, systemic therapy with cytotoxic chemotherapy can be introduced. Chemotherapy is performed in accordance with that for small cell lung cancer; however, the response rate of chemotherapy is very low, so further studies are needed to improve this treatment.

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BACKGROUND: Fournier's gangrene is a necrotizing fasciitis of the genital and perineal region. It may progress, affecting the groin, the thigh, or even the abdominal wall. Despite adequate treatment (debridement and antibiotics), the mortality rate is very high, reaching 20-35%. Fournier's gangrene caused by penetration of a rectal cancer followed by neoadjuvant chemotherapy is very rare. We report this case with a review of the literature. CASE PRESENTATION: A 68-year-old man visited the emergency room due to perineal pain during which he accepted the chemotherapy for locally advanced rectal cancer. Abdominal CT scan showed extensive emphysema in the scrotum and gluteus maximus muscle. We diagnosed as Fournier's gangrene caused by penetration of a rectal cancer. We performed debridement, left orchiectomy, transverse colostomy with double orifices. Post-operative day 30, we performed abdominoperineal resection. We performed CapeOX therapy eight courses as adjuvant chemotherapy. The patient had no recurrence for 1 year and 2 months after the operation. CONCLUSIONS: Going forward, knowledge gained from this case will increase the opportunity to perform neoadjuvant chemotherapy for locally advanced rectal cancer. In medical treatment, we must put the possibility of Fournier's gangrene in mind and treat as soon as possible.

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A 70-year-old man was diagnosed with advanced gastric cancer based on esophagogastroduodenoscopy(EGD). Abdominal computed tomography(CT)showed swelling of the lymph nodes and invasion to the liver and pancreas. The patient was treated using combined docetaxel, cisplatin, and S-1(DCS)chemotherapy. After 2 courses of treatment, the primary tumor and lymph node metastases continued to grow. The patient was treated using secondary chemotherapy with irinotecan (CPT-11). After 1 course of treatment, the primary tumor and regional lymph nodes reduced in size. We performed curative total gastrectomy with D2 lymph node dissection. There has been no recurrence for 15 months after adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Therefore, CPT-11 therapy is a possible option for the management of advanced gastric cancer after DCS therapy.

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A 52-year-old Japanese man presented for evaluation and treatment of rectal cancer. Screening computed tomography revealed pancreatic arteriovenous malformations (P-AVMs) and abnormally expanded inferior mesenteric vein (IMV) that resulted from P-AVMs. One-stage surgery for rectal cancer was dangerous so we first performed distal pancreatectomy to cure P-AVM and thus normalize the abnormally expanded IMV. After the operation, the IMV was occluded by the thrombi, and then the IMV became normal. We could perform safely radical laparoscopic surgery for rectal cancer. This is the first case report of P-AVMs combined with rectal cancer.

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BACKGROUND: The aim of this study was to compare the postoperative health-related quality of life (HRQOL) between open and laparoscopic distal gastrectomy. METHODS: A multi-institutional nonrandomized study was conducted. Patients with clinical T1 gastric cancer were prospectively enrolled and underwent distal gastrectomy by either the open or laparoscopic approach. HRQOL was measured using the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 and the site-specific module for gastric cancer. Questionnaires were completed at baseline and at 1, 3, 6, and 12 months postoperatively. Clinicopathological characteristics and short-term outcome including postoperative morbidity and HRQOL were compared between the approaches. RESULTS: A total of 145 patients (open, n = 72; laparoscopic, n = 73) were enrolled between September 2008 and January 2011 and analyzed. The laparoscopic approach was associated with longer operating time, less blood loss, and a similar incidence of postoperative complications. At each time point, the questionnaires were retrieved from more than 90 % of the patients. The worst scores for most of the scales were observed at 1 month postoperatively and improved thereafter. No statistically significant differences were observed regarding physical functioning, the primary endpoint. On the other hand, role, emotional, cognitive, and social functioning scores were superior in the laparoscopic group at 6 and 12 months postoperatively. Symptom scales including fatigue, pain, eating restriction, taste problems, and anxiety were better in the laparoscopic group before 6 months but not at 12 months. CONCLUSIONS: The study was considered to be negative because no benefit of the laparoscopic approach was observed in terms of physical functioning. However, more favorable scores for some of the symptom scales during the first 6 months and several functioning scales at 12 months after surgery suggest a potential benefit of the laparoscopic approach.

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A 63-year-old woman underwent surgery for Stage IV cancer of the ascending colon with multiple lymph node metastases. The pathological diagnosis was neuroendocrine carcinoma. Following first-line chemotherapy, the patient presented clinically with progressive disease (PD). Second-line chemotherapy with bevacizumab/Leucovorin and 5-fluorouracil with oxaliplatin (FOLFOX4) was effective and a partial response (PR) was achieved after 7 courses of therapy, as determined by computed tomography (CT) examination. Neuroendocrine carcinoma is known to be extremely malignant; however, this case suggests that chemotherapy with bevacizumab may improve the prognosis of this disease.

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This is an account of a case of primary adenocarcinoma of the small intestine successfully treated with chemotherapy. A 46-year-old man was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed bowel obstruction, and this was found at surgery to be due to a tumor at the jejunum 100 cm distal from the Treitz ligament. Pathological diagnosis of the resected specimen was adenocarcinoma. Although adjuvant chemotherapy with doxifluridine 800 mg/day was given, a recurrent lesion at the abdominal wall was detected 19 months after surgery. Colonoscopy simultaneously revealed stenosis at the descending colon. The patient was subsequently treated with resection of the mass at the abdominal wall, and colostomy was made at the transverse colon to circumvent the stenosis due to peritoneal carcinomatosis. It was not long before another recurrence developed at the abdominal wall with a subsequent rise in tumor markers. mFOLFOX6 (oxaliplatin 85 mg/m2, levofolinate calcium 200 mg/m2, 5-FU 400/2,400 mg/m2) was given, and the patient responded. Primary small intestinal adenocarcinoma is a rare disease with a dismal prognosis. Due to rarity of the disease, clinical trials have not been performed, and little is known about the effect of chemotherapy. The current patient survived for 4 years and 5 months after the diagnosis, owing at least partially to the mFOLFOX6 which was found to be the only active regimen.

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BACKGROUND: Although paclitaxel was given triweekly in phase II trials prior to its approval for gastric cancer in Japan, it is currently more often delivered by a weekly schedule in the second-line setting. PATIENTS AND METHODS: A phase II trial with response rate as the primary end-point was conducted. Patients with metastatic or unresectable gastric adenocarcinoma who had measurable lesions and had disease progression with the front-line chemotherapy were treated by weekly administration of paclitaxel at a dose of 80 mg/m2. RESULTS: Forty-five patients were accrued and 44 were assessable for response. Partial responses were observed in 7 patients (16%). Stable disease was documented in further 14 patients (48%). Median progression-free survival of all patients enrolled was 2.6 months and median overall survival was 7.8 months. Toxicity was mild and manageable, the most frequent > or = grade 3 toxicity being neutropenia occurring in 16% of the patients. CONCLUSION: With modest response rate, favorable toxicity profile, and progression-free or overall survival similar to those of more intense combination regimens, weekly paclitaxel remains a rational therapeutic option for gastric cancer refractory to the first-line chemotherapy.

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BACKGROUND/AIMS: PGP9.5 is a ubiquitin hydrolase widely expressed in neuronal tissue at all stages of neuronal differentiation and has been used as a neuroendocrine marker. Recently, it has been proved that PGP9.5 expression was highly observed in squamous cell carcinoma of lung cancer, suggesting that it might be a tumor marker for squamous cell carcinoma. To better characterize its role in digestive tract cancers, we examined PGP9.5 expression retrospectively in esophageal cancers. METHODOLOGY: We examined PGP9.5 expression retrospectively in 40 resected esophageal cancers (squamous cell carcinoma) and 10 gastric cancers (adenocarcinoma) using immunohistochemistry. RESULTS: Of 40 esophageal cancer specimens, 19 (48%) exhibited positive staining with PGP9.5 in most tumor cells, while no PGP9.5 expression was observed in any of the 10 gastric cancers. CONCLUSIONS: Although the precise mechanism underlying the effect of PGP9.5 on oncogenicity remains to be proven, it was confirmed that it may be a potential marker for esophageal squamous cell carcinoma.

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PURPOSE AND EXPERIMENTAL DESIGN: It has been proved recently that DeltaNp63 may play an oncogenic role in the tumorigenic pathway of squamous cell cancers. To gain additional insight into this pathway, we examined global patterns of gene expression in cancer cells after DeltaNp63 gene introduction using the oligonucleotide microarray approach. RESULTS: We found that S100A2 might be a target of the DeltaNp63 pathway. To confirm the data obtained from oligonucleotide microarray, we then examined the interaction of DeltaNp63 to S100A2. S100A2 induction was strictly dependent on DeltaNp63 expression by DeltaNp63 transgene and Northern analysis. DeltaNp63 transactivated the S100A2 promoter, and significantly more fold changes were seen in DeltaNp63-introduced cells than in p53-introduced cells, suggesting that DeltaNp63 may be a novel stimulator of the S100A2 promoter. CONCLUSION: Taken together, this evidence would seem to suggest that S100A2 is a novel downstream mediator of DeltaNp63.

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We previously proved that p16 promoter methylation present in the tumors of colorectal cancer patients can be detected in the serum of those same patients using methylation-specific PCR (MSP). To seek the possibility that this technique could be applied to the monitoring of cancer recurrence, we examined the p16 methylation using MSP. We detected tumor DNA in the serum of 31 of 45 (69%) patients with recurrent colorectal cancer. No methylation was found in serum DNA of 50 patients with colorectal cancers whose corresponding tumor DNA had no methylation in p16 promoter. These results suggested that MSP might be a sensitive and useful method to detect recurrent colorectal cancer in serum.

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Assays based on the molecular detection of genetic changes in serum have been shown as potential diagnostic tools for colorectal cancer. We examined the methylation status of p16 in colorectal cancers using methylation-specific PCR (MSP). Forty-four of 94 (47%) cancer DNA exhibited abnormal promoter methylation of p16 gene while no corresponding normal DNA exhibited such methylation. Subsequently, we examined whether aberrant methylation could be detected in corresponding serum DNA, and found that 13 of 44 (30%) patients with p16 promoter methylation in tumor DNA demonstrated abnormal methylation in their serum DNA. Moreover, abnormal methylation was found in the serum of patients in all clinical stages, suggesting that early colorectal cancer could be detected using the MSP method.

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PURPOSE AND EXPERIMENTAL DESIGN: We proved recently that PGP9.5-negative pancreatic cancer patients had significantly better survival rates compared with those who were PGP9.5 positive, and PGP9.5 may be a novel marker for indicating the prognosis of pancreatic cancer patients. In this study, we examined the expression of PGP9.5 in primary colorectal cancers using immunohistochemistry and correlated the result with the clinicopathological features. RESULTS: Of 74 colorectal cancer specimens examined, 33 cases (46%) showed positive staining with PGP9.5 in most tumor cells, whereas no PGP9.5 expression was detected in adjacent normal epithelium. Subsequently, we correlated PGP9.5 expression in tumors with the clinicopathological features of affected patients and found two significant differences in maximal tumor size and the extent of tumor (P = 0.035 and 0.019, respectively). CONCLUSION: This result suggests that PGP9.5 expression is related to tumor progression and may be useful as a marker for invasive colorectal cancer.

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