Murine xenogeneic immune responses to the human testis: a presumed immune-privileged tissue.

INTRODUCTION: Immune privilege provides a natural paradigm for potentially down-regulating allogeneic and xenogeneic inflammatory immune responses. Fas ligand has been suggested as a general underlying mechanism of immune privilege; the human Fas ligand has been shown to ligate murine Fas in vitro. METHODS: In this study, we examined whether the human testicular xenograft, a presumed immune-privileged tissue would have prolonged survival in mice. In addition, in vitro and in vivo murine xenogeneic immune responses to the human testicular xenografts were characterized using MHC class I, MHC class II, CD4, CD8, CD4/8 knockout mice. RESULTS: Unlike in rodent testis, Fas ligand mRNA is not expressed and Fas is highly expressed in human testis. Human testicular xenografts are immunogenic, and do not induce any preferential pattern of recipient systemic Th1 or Th2 cytokine bias. Interestingly, an indefinite survival of the human testicular xenografts is observed in murine MHC class II knockout mice, whereas the human skin xenografts were rejected without a delay. In vivo murine immune responses to human testicular xenografts require a recipient MHC class II-dependent CD4 T cell-mediated process that appears to depend on B7-1/B7-2 costimulatory signals. CONCLUSIONS: Our results demonstrate that the concept of immune privilege, as defined by the expression of Fas ligand and prolonged survival after transplantation, cannot be extended to human testis. The stringent restriction of murine xenogeneic immune responses to discordant human testicular xenografts to the indirect MHC class II-dependent CD4 T cell-mediated pathway suggests a potential venue for immune modulation to induce tolerance across a discordant species barrier.

Difference in prognostic value between sialyl Lewis(a) and sialyl lewis(x) antigens in blood samples obtained from the drainage veins of the colorectal tumors.

Subtraction values, (i.e. values obtained by subtracting the serum titer of sialyl Lewis(a) (CA19-9) and sialyl Lewis(x) (SLX) antigens in peripheral venous blood from the serum titer of the same antigen in the tumor's drainage venous blood) were determined in order to clarify whether or not such values for these specific antigens (d-CA19-9 and d-SLX) are prognostic factors after resection for colorectal cancer. The blood samples were obtained from 144 colorectal cancer patients during surgical excisions of the tumors. Univariate and multivariate analyses revealed that d-SLX level was an independent prognostic factor, separate from stage, while d-CA19-9 level did not have any additional prognostic value. In conclusion, a high d-SLX level is a predictor of poor outcome after surgery.

The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer.

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)a (CA19-9), sialyl Lex (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior.

Expression of blood group antigens A, B and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients.

The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy.

Increased serum level of sialyl Lewis(x) antigen in blood from the tumor drainage vein in patients with non-polypoid growth type of colorectal cancer.

Two types of colorectal cancer with distinct morphologies have been described in recent studies: polypoid growth type (PG-type) and non-polypoid growth type (NPG-type). We hypothesize that the morphologic differences may correspond to additional biological distinctions. Ratios of sialyl Lewisa (CA 19-9), sialyl Lewisx (SLX), or carcinoembryonic antigen (CEA) in the venous blood drainage from the tumor to that of the respective antigen in the peripheral venous blood (d/p ratio) was examined in order to ascertain whether or not the ratio is correlated with either the PG-type or NPG-type colorectal tumor growth pattern. Blood samples from 118 patients with colorectal cancer were obtained from a peripheral vein and from the tumor drainage vein during surgical excision of the tumor. Statistical tests were conducted by univariate and multivariate (logistic regression) analyses. Among the cancers examined there were 17 PG-type (14.4%) and 101 NPG-type (85.6%). NPG-type cancers had a higher frequency of moderately differentiated adenocarcinoma cells and T3/T4 tumors than PG-type cancers (P<0.0001 and P<0.0001, respectively). NPG-type cancers had a more advanced stage than PG-type cancers (P=0.0007). The d/p ratio of SLX in NPG-type cancers was significantly higher than that in PG-type cancers (P=0.028). Multivariate logistic regression analysis showed that three variables, namely histologic type, T factor, and d/p ratio of SLX, were independently related to tumor growth patterns. In conclusion, NPG-type cancers are characterized by a high SLX d/p ratio, which may be at least partly responsible for a different tumor progression pattern compared to other cancer types.

Congenital true diverticula of the esophagus: a case report.

Pseudodiverticulosis secondary to gastroesophageal reflux is a common disease in adults, but true esophageal diverticula are rare in infants and children. A 5-year-old boy was well until the age of 1 1/2 years when he started vomiting. An upper gastrointestinal series showed two diverticula bulging from the posterior right side of the middle esophagus associated with slight hiatal hernia and short esophagus. Diverticulectomy, the Collis-Nissen antireflux procedure, and pyloroplasty were performed simultaneously through a left thoracoabdominal incision. Histological examination of the diverticula showed that the wall of each diverticulum consisted of a full-thickness of esophageal wall. Because there was no tracheal remnant in the diverticula, this lesion is more likely to be a true diverticulum than a duplication.

Differences in release mechanisms and distributions for sialyl Le(a) and sialyl Le(x) antigens in colorectal cancer.

BACKGROUND: To investigate colorectal cancer-related carbohydrate antigen release and distribution, we evaluated serum levels of sialyl Le(a) (CA19-9) and sialyl Le(x) antigen (SLX) in blood samples obtained from both a peripheral vein and a tumor's draining vein. METHODS: Blood samples were obtained during surgery from 126 patients. Based on these samples, patients were placed into a high-antigen group, with a concentration above a selected cutoff value, or into a low-antigen group, with a tumor marker concentration below that same value. The blood samples obtained from peripheral veins were designated by the "p" prefix, and samples from drainage veins were designated by the "d." RESULTS: Serum d-SLX levels were significantly higher than p-SLX levels (P < .0001), although there was no difference between those of d-CA19-9 and p-CA19-9. Only 1 (3.6%) of 28 patients in the high d-CA19-9 group had a low p-CA19-9. In contrast, 6 (33.3%) of 18 patients in the high d-SLX group had low p-SLX levels (P = .0103). Correlations between pathological variables and either p-CA19-9 levels or d-CA19-9 levels were similar. However, both distant metastasis and venous invasion did prove to be independent variables related to d-SLX levels, as shown by logistic regression analysis. CONCLUSIONS: SLX may drain predominantly via the draining veins of colorectal tumors into portal circulation, whereas CA19-9 may drain via another route.

Surgical treatment and subsequent outcome of patients with carcinoma of the splenic flexure.

Extended resection, comprising extended right hemicolectomy, splenectomy, and distal pancreatectomy, has been advocated for carcinoma of the splenic flexure because the lymphatic drainage at this site is variable. The present study addresses the problems associated with selecting the most appropriate operative procedure to achieve cure of splenic flexure cancers. We conducted a retrospective review of 27 patients with splenic flexure cancer who underwent curative resection. Left partial colectomy was performed in 20 patients and partial resection of the transverse/descending colon was performed in 7 patients. The combined resection of adjacent organs due to tumor adherence was performed in three patients. The spleen and distal pancreas were the organs most frequently resected among a collective total of six adjacent organs. The median duration of follow-up was 60.9 months after resection for splenic flexure cancer. No patient developed local recurrence. There was no significant difference in 5-year survival between patients with splenic flexure cancers and those with colon cancers at other sites. In conclusion, splenic flexure cancer resected by left partial colectomy or partial resection of the transverse/descending colon without routine extended resection was not associated with a worse prognosis than colon cancers at other sites.

Prognostic value of serum sialyl Lewis(a), sialyl Lewis(x) and sialyl Tn antigens in blood from the tumor drainage vein of colorectal cancer patients.

The serum levels of sialyl Lewis(a) (CA19-9), sialyl Lewis(x) (SLX), sialyl Tn (STN) and carcinoembryonic antigen (CEA) in peripheral venous blood and tumor drainage venous blood of colorectal cancer patients were examined to determine their value as prognostic factors after surgery. Blood samples were obtained from the peripheral vein and from the tumor drainage vein from 124 colorectal cancer patients during surgical excision of the tumor. The patients were divided into high-antigen and low-antigen groups for each antigen in each location. Serum levels of SLX, STN and CEA in tumor drainage venous blood (d-SLX, d-STN and d-CEA, respectively) were significantly higher than in peripheral venous blood (p-SLX, p-STN and p-CEA, respectively). The survival time after surgery for patients with high d-SLX or d-CEA levels and low levels of the same antigen in peripheral venous blood was significantly shorter than the survival time for those patients with low levels of antigen at both sites (p = 0.0003 or p = 0.0406, respectively). Cox's regression analysis revealed that a high d-SLX or high d-CEA level was an independent prognostic variable for patient survival. In conclusion, determining d-SLX or d-CEA is more useful than p-SLX or p-CEA in predicting the outcome for colorectal cancer patients.