Background: The purpose of this study was to examine the efficacy of anticoagulant fondaparinux postoperatively for preventing recurrence after curative resection of colorectal cancer with lymphnode metastasis. Patients and Methods: The records of 279 patients who underwent curative resection of colorectal cancer with lymph-node metastasis between 2006 and 2013 were reviewed. Patients were divided into two groups based on the type of prophylaxis for postoperative venous thromboembolism: the FPX group, treated with subcutaneous fondaparinux plus intermittent pneumatic compression; and the IPC group, treated with intermittent pneumatic compression alone. Recurrence-free survival was compared using propensity score matching. Results: In the propensity score-matched cohort, the 3-year recurrence-free survival rate was 74.9% and 74.4% in the FPX (n=61) and IPC groups (n=61), respectively (p=0.830). Conclusion: Our results do not suggest that short-term postoperative anticoagulation as prophylaxis for venous thromboembolism prevents colorectal cancer recurrence after curative resection.
To evaluate clinical importance of the expression of sialyl Lewis-X (sLe(x)) and sialyl Lewis-a antigen (sLe(a)) in gastrointestinal cancers, we examined immunohistochemically expression of the two antigens in esophageal, gastric, colorectal, and pancreatic cancer. Expression of sLe(x) and sLe(a) were associated with several clinicopathologic features which reflect tumor aggressiveness in esophageal, gastric and colorectal cancer, but not in pancreatic cancer. In esophageal and colorectal cancer, survival rate of the patients with sLe(x) positive tumors was significantly poorer than that of the patients with sLe(x) negative tumors, while in gastric cancer that with sLe(a) positive tumors was significantly poorer than that with sLe(a) negative. Cox's multivariate analysis revealed that sLe(x) expression status was one of the significant discriminants of prognosis in colorectal cancer patients and sLe(a) status in gastric cancer patients. These results suggest that sLe(x) and sLe(a) expression could be involved in aggressiveness of gastrointestinal cancer and might prove to be a potent marker for prognosis in patients with gastric cancer and colorectal cancer.
Background. Rejection of pancreatic islet grafts is still a serious problem. We evaluated the effect of mitomycin C (MMC) on the survival of crude islets grafts after xenogeneic islet transplantation. Methods. WS (RT1k) rat islets pretreated with various concentrations of MMC (0, 1, 3.2, 10, 32, 50, 100, 320, and 1,000 μg/ml) were transplanted into C57BL/6 mice with streptozotocin-induced diabetes. In vivo graft function was assessed by a daily measurement of nonfasting blood glucose concentration in each animal. We also examined the separate effect of MMC on purified islets and contaminants present in the crude islet preparation. Results. MMC at doses of 10, 32, 50, and 100 μg/ml resulted in a significant prolongation of the mean graft survival time from a control of 12.4±2.5 days to 23±7.4, 17.5±5.4, 25.5±14.7, and 26.7±8.9 days, respectively. Deterioration of glucose metabolism was noted when the dose exceeded 32 μg/ml, whereas at 320 μg/ml, MMC failed to restore normoglycemia. Prolongation of survival time of crude islets was the result of its effect on islets and contaminant components of the crude islet preparation. In vitro study showed that MMC treatment at a higher concentration than 10 μg/ml reduces the stimulatory as well as proliferative capacity of lymph node cells. Conclusions. Pretreatment of pancreatic islets with MMC at 10 μg/ml prolongs xenograft survival without deterioration of in vivo graft function. This novel treatment modality represents a new strategy for the modulation of immunity of islets and contaminants in crude islet preparations.
Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined.VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells.Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification.The prognostic significance of VCP expression level in GC was demonstrated.
Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers' cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers' cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers' cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers.
Ten patients with malignant upper gastrointestinal obstruction caused by incurable gastric cancer underwent an endoscopic placement of self-expandable metallic stents for palliation. There were 6 male and 4 female patients aged 39-98 (median, 65.5). The site of obstruction was the cardia in 2, the pylorus in 4, the duodenum in 1, and surgical anastomosis in 3 patients. All the patients were unable to take food orally. Stent deployment was technically successful in all patients. After the stent insertion, 80% of patients resumed solid diet. The median survival time after the insertion was 129 days. The median length of home stay after the procedure was 54.5 days. Although chemotherapy was added in 5 patients after the insertion, there were no significant differences either in survival time or in home stay between the patients with and without chemotherapy. No procedure-related mortality was observed. Mediastinitis occurred in 1 patient, and the remaining 9 patients had no serious complications. Stent migration was observed in 2 patients, and stent occlusion due to tumor ingrowth occurred in 4 patients.
Recognition of metastatic tumor cells with distinct biochemical phenotypes predominant in the primary tumors should be useful not only for establishment of new therapeutic approaches but also for identification of high-risk or low-risk patients for relapse. We examined whether carbohydrate antigens, sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)) are involved in colorectal cancer metastasis.Metastatic abilities of human colon cancer cell variants that were selected for their high or low cell surface levels of sLe(x) (KM12-HX and KM12-LX, respectively) were analyzed. Also, immunohistochemical expressions of sLe(x) and sLe(a) in 159 primary colorectal cancers were examined to determine the clinical significance of increased expression of these antigens.KM12-HX cells adhered more readily to tumor necrosis factor-alpha activated endothelial cells than did KM12-LX cells. Increased adhesion of KM12-HX cells to activated endothelial cells was inhibited by antibodies against E-selectin and sLe(x) and by modification of cell surface carbohydrates. KM12-HX cells showed more invasive ability in vitro and more metastatic potential in the liver of nude mice than KM12-LX cells. Although no difference was seen in the expression of six messenger ribonucleic acids corresponding to progression or metastasis of colorectal cancer, expression of fucosyltransferase was found to be responsible for the higher expression of sLe(x) in KM12-HX cells. Clinical records of patients showed that disease-free survival rate of patients with sLe(x)-positive tumors was significantly poorer than that of those with sLe(x)-negative tumors. Cox's multivariate analysis revealed that the sLe(x) status was an independent predictive factor for disease recurrence (P = 0.004), depth of invasion (P = 0.0005), and histologic type (P = 0.037), but sLe(a) status, age, gender, tumor location, N stage, and vessel invasion were not.Increased expression of sLe(x) could be involved in establishment of colorectal cancer metastasis. It appears that examining sLe(x) expression may serve as a potent marker of the recurrence in patients with colorectal cancer.
CA 19-9, equivalent to Sialyl Lewis antigen, is a well-known tumor marker in pancreatic cancer. At the initial step of the biosynthesis of CA 19-9, N-acetylglucosamine-beta1,3-galactosyltransferase (beta3Gal-T) transfers galactose to N-acetylglucosamine (GlcNAc). Recently, beta3Gal-T5 has been presumed to be related to the formation of the type 1 chain in an in vitro experiment in terms of kinetic enzyme characterization. The purpose of this study was to investigate which beta3Gal-T is related to the synthesis of CA 19-9 in human pancreatic cancer tissues.We examined beta;3Gal-T1, T2, T3, T4, and beta;3Gal-T5 mRNA expressions in 13 noncancerous and cancerous tissues of the human pancreas using real-time polymerase chain reaction, and compared those gene expression levels with the immunoreactivity of CA 19-9 and its precursor DUPAN-2 in cancerous tissues.Beta;3Gal-T5 gene expression significantly augmented in cancerous tissues, when compared with the adjacent noncancerous tissues. Additionally, there was a good correlation between BETA;3GAL-T5 gene transcription levels and immunohistochemical grades of CA 19-9 or its precursor DUPAN-2 in cancerous tissues. However, no correlation was observed between beta;3Gal-T1, T2, T3, and beta;3Gal-T4 gene expression levels and CA 19-9 or DUPAN-2 immunoreactive grades in cancerous tissue.beta3Gal-T5 is presumed to be responsible for the synthesis of CA 19-9 in pancreatic cancer tissue.
