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The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords “gastric cancer” and “tumor marker,” to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2–3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.

We reviewed our research concerning p53 molecules in esophageal squamous cell carcinoma by focusing on the p53 molecular diagnosis and treatment of esophageal squamous cell carcinoma. First, we developed diagnostic tools to analyze serum p53 autoantibodies to detect esophageal squamous cell carcinoma. Positive rate was around 25% to 30% in all patients and around 20% even in stage I patients. Presence of serum p53 antibodies was significantly associated with overexpression of p53 protein in tumor cells. Seropositive patients were more likely than seronegative patients to be resistant to chemotherapy. Monitoring of the titer of serum p53 autoantibodies was useful in predicting patients at high risk of recurrence and/or treatment response. Second, using Ad5CMV‐p53 for 10 patients with advanced esophageal squamous cell carcinoma, we carried out a phase I/II study of adenoviral‐mediated p53 gene therapy. Although no complete response was observed, local tumor was stabilized in nine patients. No serious adverse events related to Ad5CMV‐p53 were observed in these patients. One patient survived for over 5 years after the start of p53 gene therapy. Intratumoral injection of Ad5CMV‐p53 is therefore safe, feasible, and biologically active when given in multiple doses to patients with esophageal squamous cell carcinoma. Our observations from these clinical studies indicate that p53 is a useful molecular target both in the diagnosis and in the treatment of esophageal squamous cell carcinoma. Serum p53 autoantibodies were useful to detect early stage of esophageal cancer and useful to monitor during treatment. p53 gene therapy was feasible and safe for patients with esophageal cancer.

Because the production of tumor‐associated antibodies (TAA) is a humoral immune response in cancer patients, serum autoantibodies may be detected even in patients with early‐stage tumors. Seventeen recombinant proteins with tags in Escherichia coli (p53, RalA, p90, NY‐ESO‐1, HSP70, c‐myc, galectin‐1, Sui1, KN‐HN‐1, HSP40, PrxVI, p62, cyclin B1, HCC‐22‐5, annexin II, HCA25a, and HER2) were applied as capturing antigens in sandwich ELISA to measure serum IgG levels. Sera from 73 healthy donors and 386 patients with breast cancer, including 182 stage 0/I patients, were evaluated using cutoff values for each TAA equal to the mean +3 SD of the serum levels of healthy controls. The positive TAA rates were relatively high for p53 (10%) and RalA (10%). The positive rates of all TAA of stage 0/I were similar to those of all patients. Even in the stage 0/I patients, 24% showed that two or more TAA were positive, and the positive rate of a five‐TAA combination assay was 37%. The positivity rate was significantly higher for the non–luminal type than for the luminal type (P = .003). Logistic analysis showed that seropositivity (positive for one or more TAA) in breast cancer patients was independent from any TNM factor or disease stage and was significantly associated with histological grade in the multivariate analysis (P = .007). TAA in breast cancer patients may be useful for early detection. However, seropositivity of breast cancer reflects the tumor characteristics but not the disease stage. We performed 17 tumor‐associated antibody (TAA) panel assays in 386 breast cancer patients’ serum. The tumor factor associated with the tumorigenesis regulated a humoral immune reaction that resulted in a diversity of TAA seropositivity.

Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords “remnant,” “stomach,” and “cancer,” revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.

Purpose The impact of postoperative complications on survival after radical surgery for esophageal, gastric, and colorectal cancers remains controversial. We conducted a systematic review of recent publications to examine the effect of postoperative complications on oncological outcome. Methods A literature search of PubMed/MEDLINE was performed using the keywords “esophageal cancer,” “gastric cancer,” and “colorectal cancer,” obtaining 27 reports published online up until the end of April 2016. Articles focusing on (i) postoperative morbidity and oncological outcome; and (ii) body mass index (BMI), postoperative morbidity, and oncological outcome, were selected. Univariate and multivariate analyses (Cox proportional hazards model) were performed. Results Patients with postoperative complications had significantly poorer long‐term survival than those without complications. Complications were associated with impaired oncological outcomes. The hazard ratios for overall survival were 1.67 (95% confidence interval [CI], 1.31‐2.12), 1.59 (95% CI, 1.13‐2.24), and 1.55 (95% CI, 1.28‐1.87) in esophageal, gastric, and colorectal cancers, respectively. High BMI was associated with postoperative morbidity rate but not with poor oncological outcome. Low BMI was significantly associated with inferior oncological outcome. Conclusions Complications after radical surgery for esophageal, gastric, and colorectal cancers are associated with patient prognosis. Avoiding such complications might improve the outcomes. A systematic review of the impact of postoperative complications on long‐term survival of patients with gastrointestinal cancers showed that infectious complications, particularly pneumonia, were significant risk factors with negative impacts on patient survival.