Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high‐volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19‐9 independently indicated surgical response in pancreatic cancer. Patients with CA19‐9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19‐9 levels decreased postoperatively. CEA and CA125 in the presence of CA19‐9 ≥1000 U/mL could independently predict the non‐decrease of CA19‐9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA+/CA125+/CA19‐9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy.

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BACKGROUND.Lymphovascular invasion (LVI) and/or lymph node metastases (LNM) adversely influence the overall survival (OS) of patients with T1 esophageal adenocarcinoma. Although endoscopic therapy may be adequate for patients with T1a cancer, patients with T1b cancer require esophagectomy/lymphadenectomy. The authors hypothesized that LVI status would subclassify T1b cancers and facilitate new therapeutic strategies.METHODS.Ninety‐nine consecutive patients with T1 adenocarcinoma were analyzed after they underwent esophagectomy/lymphadenectomy. LNM was assessed in all patients, and LVI was assessed in 89 patients. OS was correlated with pathologic cancer stage in association with LVI and LNM.RESULTS.The 5‐year OS rate for patients with T1a tumors (88%) was superior to that for patients with T1b tumors (62%; P = .001). The 5‐year OS rate for patients who had cancers without LVI (85%) was superior to the rate for patients who had cancers with LVI (36%; P = .0001). It is noteworthy that, for cancers without LVI, the 5‐year OS rate for patients with T1b tumors (77%) was similar to the rate for patients with T1a tumors (90%; P = .08), but it was superior to the rate for patients with T1b tumors that had LVI (27%; P = .006). The presence of LVI and/or LNM resulted in worse 5‐year OS (≤37%) compared with the lack of LVI and/or LNM (88%; P < .001). The rate of LNM for patients who had T1b tumors without LVI still was 19%, and the relapse rate was 16%.CONCLUSIONS.The current results demonstrated that LVI distinguishes the biologic behavior of early esophageal cancer, and patients who have T1b cancer without LVI have a clinical biology similar to that of patients with T1a cancer. If LNM before surgery can be diagnosed with high sensitivity by better endoscopic techniques and/or molecular biomarkers, then a new therapeutic paradigm for T1b cancers could emerge. Further research is needed on patients with T1b esophageal adenocarcinoma. Cancer 2008. © 2008 American Cancer Society.

Background: Mipsagargin (G-202) is a thapsigargin-based prodrug with cytotoxic activity masked by a peptide that is cleaved by prostate-specific membrane antigen (PSMA), a protease expressed in prostate cancer cells and the endothelium of tumor vasculature. It was hypothesized that PSMA-mediated activation of mipsagargin would result in disruption of the tumor vasculature, leading to a decrease in blood flow, and in direct cytotoxic effects on tumor cells, resulting in anti-tumor activity. Method: In this open-label, Phase II study, mipsagargin was administered intravenously on Days 1, 2, and 3 of a 28-day cycle to patients with hepatocellular carcinoma (HCC) who progressed on or after treatment with sorafenib or intolerant of sorafenib. Assessments included time to disease progression (TTP), response rate, progression-free survival (PFS), overall survival (OS), and safety. Blood flow metrics in hepatic lesions were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results: Of 25 treated patients, 19 were evaluable for efficacy. None had an objective response, 12 (63.2%) had a best response of stable disease, and 12 (63.2%) showed radiologic progression; seven patients (36.8%) were censored. The median TTP was 134.0 days, median PFS was 129.0 days, and median OS was 205.0 days. Of five patients with DCE-MRI data for 11 HCC lesions, all demonstrated a reduced Ktrans (mean, 52%). The most common treatment-emergent AEs were Grade 1–2 and consisted of increased blood creatinine (68.0%), fatigue (56.0%), and nausea (44.0%). Conclusions: Mipsagargin is relatively well tolerated and promotes prolonged disease stabilization in patients with advanced HCC that had progressed on prior treatment with sorafenib. A significant decrease in Ktrans upon treatment suggests mipsagargin reduces blood flow in hepatic lesions.

CD44 is a transmembrane glycoprotein and surface receptor for hyaluronan that is involved in the response of cells to their microenvironment. CD44 splice variants play roles in carcinogenesis, differentiation, and lymph node metastasis and are predictive of the prognosis for various carcinomas, including gastric cancer. Current data suggest that gastric tissue stem cells and gastric cancer stem cells both express the splice variant, CD44v9. Overall, the data regarding the alterations that occur in CD44 and its splice variants in response to acute and chronic infection with Helicobacter pylori are scant and poorly elucidated in terms of possible changes in expression that occur in gastric cancer precursor lesions, such as chronic atrophic gastritis, pyloric metaplasia and intestinal metaplasia. In this study, we discuss the available data and suggest which new data would likely be useful in clinical practice. We also discuss the potential for CD44-targeted therapeutic strategies in gastric cancer. CD44 and its splice variants are positively associated with the initiation and progression of gastric cancer and may also play important roles in diagnosis, therapy and prognosis. CD44 research has been active but fragmented, and it may offer new therapeutic approaches to gastric cancer.