Gastric Lymph Research Articles

Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer

BackgroundThe putative tumor metastasis suppressor 1(MTSS1) is an actin-binding scaffold protein that has been implicated to play an important role in carcinogenesis and cancer metastasis, yet its role in the development of gastric cancer has not been well illustrated. In this study, we detected MTSS1 expression and explored its clinical significance in gastric cancer.MethodsImmunohistochemistry was performed using tissue microarrays containing gastric adenocarcinoma specimens from 1,072 Chinese patients with normal adjacent mucosa, primary gastric cancer and lymph node (LN) metastasis and specific antibody against MTSS1. MTSS1 mRNA and protein expression were detected by reverse transcription-polymerase chain reaction and Western blotting. The clinical follow-up was done in the 669 patients living in Shanghai that was chose from the 1072 cases.ResultsComplete loss of MTSS1 expression was observed in 751 cases (70.1%) of the 1,072 primary tumors and 103 (88%) of 117 nodal metastases; and loss of MTSS1 expression was significantly associated with poorly differentiated tumors, large tumor size, deep invasion level, the presence of nodal metastases and advanced disease stage. Moreover, multivariate analysis demonstrated that loss of MTSS1 expression correlated significantly with poor survival rates (RR = 0.194, 95% CI = 0.144-0.261, P < 0.001).ConclusionsMTSS1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting MTSS1 may serve as a useful biomarker for the prediction of outcome of gastric cancer.

Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes

Connexin 43(Cx43) and E-cadherin are concurrently expressed in many tumors and were ever classified as tumor suppressors in primary tumors (PT), whereas recent studies showed that these two proteins played specific roles in tumor metastasis. The aim of our study is to determine the expression of Cx43 and E-cadherin in primary gastric tumors (PTs) and matched metastatic lymph nodes (MLNs) and to explore the clinical and pathological implications of expression of these proteins. Immunohistochemical assay was conducted to detect the expression of Cx43 and E-cadherin in PTs and MLNs, and the clinical and pathological implications were analyzed by statistical methods. In PTs, the expression of Cx43 and E-cadherin was significantly reduced, compared to adjacent normal tissues (P < 0.01). The expression of Cx43 and E-cadherin was significantly increased in MLNs compared with PTs (P < 0.01 and P < 0.01, for Cx43 and E-cadherin, respectively), and some Cx43 and E-cadherin-negative PTs developed Cx43 and E-cadherin-positive MLNs. Furthermore, reduced expression of both Cx43 and E-cadherin significantly correlated with poor differentiation, advanced TNM stage, and lymph note metastasis of gastric cancers. Cx43 and E-cadherin expression significantly correlated with each other. We concluded that concurrent reduction in Cx43 and E-cadherin may contribute to the occurrence of gastric cancer. However, concurrent increased expression of Cx43 and E-cadherin may contribute to the efficient metastasis of gastric cancer to the lymph nodes.

Risk factors for lymph node metastasis in patients with early gastric cancer and signet ring cell histology

Early gastric cancer with signet ring cell histology has been reported as a favourable histological type. The aim of this study was to identify risk factors associated with lymph node metastasis in patients with this type of early gastric cancer. A cross-sectional study of patients with early gastric cancer with differentiated and signet ring cell histology undergoing surgery was conducted. Risk factors were evaluated using multiple logistic regression analysis with odds ratios and 95 per cent confidence intervals. In 1362 patients undergoing gastrectomy for early gastric cancer, the rate of lymph node metastasis was similar for tumours with signet ring cell and differentiated histological findings (10.7 versus 9.0 per cent respectively; P = 0.307). Logistic regression analysis showed that depth of tumour invasion was predictive of lymph node metastasis in patients with signet ring cell histology (P < 0.001). Tumour size was not associated with lymph node metastasis in either univariable or multivariable analysis. Lesions smaller than 2 cm were not uncommon in patients with signet ring cell gastric tumours and lymph node metastases (six of 48; 13 per cent). Patients with early gastric cancer with signet ring cell-type histology are probably best treated by gastrectomy with lymph node dissection.

A case of HIV-associated lymphoproliferative disease that was successfully treated with highly active antiretroviral therapy

We report a case of a 41-year-old male with human immunodeficiency virus (HIV)-associated lymphoproliferative disease (LPD) who was successfully treated with highly active antiretroviral therapy (HAART). He presented with epigastralgia, and an upper endoscopic examination revealed submucosal tumors and ulcerations in his stomach. Histopathologic examination of a biopsy specimen resulted in a diagnosis of diffuse large B-cell lymphoma. He also showed systemic lymphadenopathy; whereas, a concurrent inguinal lymph node biopsy produced a diagnosis of follicular hyperplasia. He was treated with CHOP chemotherapy but the response was poor. He demonstrated several immunological abnormalities, such as eosinophilia and bone marrow insufficiency, and was suspected to be in an immunocompromised state. He was examined for HIV infection and turned out to be positive. The gastric and inguinal lymph node specimens were re-evaluated and diagnoses of HIV-LPD and HIV lymphadenitis were made, respectively. He was treated with HAART and achieved complete remission and has remained tumor-free for 20 months. To the best of our knowledge, there is no previous report in which HIV-LPD was successfully treated with antiretroviral therapy alone. It is assumed that HAART resulted in the restoration of anti-tumor immunity in this case, which led to the eradication of LPD cells.

Cell cycle regulators, APC/β-catenin, NF-κB and Epstein-Barr virus in gastric carcinomas

To evaluate the clinicopathological value of cell cycle regulators, the Wnt pathway, the NF-betaB pathway and Epstein-Barr virus (EBV) and to assess their relationships in gastric carcinoma. We investigated cell cycle regulators (p53, p21, Rb), APC, beta-catenin and NF-kappaB using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma. p53 overexpression was more frequently observed in advanced gastric carcinoma and lymph node metastasis than in early carcinoma or in the absence of metastasis (p < 0.05). p21 loss was positively correlated with APC loss, but inversely correlated with beta-catenin nuclear accumulation and NF-kappaB positivity (p < 0.05). EBV positive gastric carcinomas were located in the upper third of the stomach, and more were of the diffuse or mixed types than the EBV negative group (p < 0.05). EBV infection was positively correlated with p21 loss and APC loss and inversely correlated with beta-catenin alteration (p < 0.05). In multivariate analysis, patient age, TNM stage and p53 were independent prognostic factors for gastric carcinoma. p53 status is a prognostic marker for gastric carcinoma. p21, APC, beta-catenin and NF-kappaB may be functionally interrelated in gastric carcinogenesis. Loss of p21 and APC may be involved in the carcinogenesis of EBV positive gastric carcinomas.

Clinical significance of Fas and FasL protein expression in gastric carcinoma and local lymph node tissues

To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of gastric carcinoma. Immunohistochemistry was used to detect Fas and FasL protein expression in 64 gastric carcinoma tissue samples and 20 normal gastric tissue samples. Relation between FasL and Fas expression, age and gender of gastric cancer patients, and pathological subtype and lymph node metastasis of gastric cancer was analyzed. The Fas expression level was significantly higher in normal gastric tissue samples than in gastric carcinoma tissue samples (85.0% vs 25.0%, P < 0.001), while the FasL expression level was significantly lower in normal gastric tissue samples than in gastric carcinoma tissue samples (30.0% vs 81.3%, P < 0.001). The Fas expression level was significantly higher in invasive lymph nodes than in non-invasive lymph nodes (82.9% vs 56.5%, P < 0.003) and in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated gastric carcinoma tissue samples (50.0% vs 18.0%, P = 0.015). The FasL expression level was significantly lower in well-differentiated gastric carcinoma tissue samples than in poorly- differentiated gastric carcinoma tissue samples (42.9% vs 84.0%, P = 0.021). The Fas and FasL expression levels (25.0% and 81.3%) were significantly different in gastric carcinoma tissue samples (P < 0.001), but had a non-linear correlation (P = 0.575). Abnormal Fas and FasL expressions in gastric carcinoma and lymph node tissues are involved in carcinogenesis and metastasis of gastric cancer.

Accuracy of Surgical Diagnosis in Detecting Early Gastric Cancer and Lymph Node Metastasis and Its Role in Determining Limited Surgery

Accuracy of Surgical Diagnosis in Detecting Early Gastric Cancer and Lymph Node Metastasis and Its Role in Determining Limited Surgery

Significance and relationship between Cripto-1 and p-STAT3 expression in gastric cancer and precancerous lesions

To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis. The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal metaplasia (IM) and 25 dysplasia (DYS). The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were significantly higher in GC with lymph node metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relationship between CR-1 and p-STAT3 expressions in GC (r(k) = 0.189, P = 0.002). The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.

Up-regulation of PIK3CA promotes metastasis in gastric carcinoma

To explore expressions of PIK3CA in the progression of gastric cancer from primary to metastasis and its effects on activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway. mRNA and protein levels of PIK3CA were assessed, respectively, by real-time quantitative polymerase chain reaction and immunohistochemistry in specimens of normal gastric mucosa, primary foci and lymph node and distant metastasis of gastric cancer. Akt and phosphorylated Akt protein were also examined by Western blotting in these tissues, in order to analyze the effect of PIK3CA expression level changes on the activation of PI3K/Akt signaling pathway. PIK3CA mRNA in lymph node metastasis were approximately 5 and 2 folds higher, respectively, than that in the corresponding normal gastric mucosa and primary gastric cancer tissues (P < 0.05), while no statistical significance was found compared with distant metastasis. Immunohistochemically, PIK3CA protein expression was discovered in 7 (35%) specimens of 20 primary foci vs 10 (67%) of 15 of lymph node metastasis or 11 (61%) of 18 of distant metastasis (35% vs 67%, P = 0.015; 35% vs 61%, P = 0.044). With the increased level of PIK3CA expression, the total Akt protein expression remained almost unchanged, but p-Akt protein was upregulated markedly. Increased expression of PIK3CA is expected to be a promising indicator of metastasis in gastric cancer. Up-regulation of PIK3CA may promote the metastasis of gastric cancer through aberrant activation of PI3K/Akt signaling.

Utility of Surgical Resection in the Management of Metachronous Krukenberg's Tumors of Gastric Origin

Purpose: The aim of this study was to determine the prognostic factors and the significance of metastatectomy for Krukenberg’s tumors of gastric origin. Materials and Methods: Among the patient who underwent gastric surgery from 1992 through 2005, 90 female patients with Krukenberg’s tumors of gastric origin were identified. We retrospectively reviewed the clinicopathologic characteristics, prognostic factors, and treatments for primary gastric cancer. We also investigated the prognostic risk factors for the onset of metachronous Krukenberg’s tumors and the survival time of patients who underwent an operation for metachronous Krukenberg’s tumors. Results: The presence of a synchronous Krukenberg’s tumor (mean survival time=17.6 months, P<0.01), peritoneal seeding (14.5 months, P<0.01), and non-curative resection (15.1 months, P<0.01), were statistically significant prognostic factors for survival time in female patients with gastric cancer. The stage of primary gastric cancer (P=0.049) and lymph node metastasis (P=0.011) were statistically significant risk factors for recurrence time of a metachronous Krukenberg’s tumor. In the metachronous Krukenberg’s tumor group (n=53), the mean survival time of the metastatectomy group (n=46, 43.2 months, P=0.012) was longer than that in the chemotherapy or conservative treatment groups (n=7 and 24 months, respectively). Metastatectomy, presense or abscence of residual tumor and extent of residual tumor were significant prognostic factors for survival time in female patients with metachronous Krukenberg's tumor of gastric origin. Conclusions: A close observation and evaluation with ultrasound or computed tomography is necessary in female patients with advanced gastric cancer to detect a metachronous Krukenberg’s tumor as soon as possible. The surgeon must operate more aggressively in patients with metachronous Krukenberg’s tumors.

The role of embolization in the management of tumour recurrence after radical nephrectomy

This article presents the case of a 56-year-old woman who developed a tumour recurrence following radical nephrectomy. This was invading the descending colon and causing severe gastrointestinal haemorrhage. Angiography revealed neovascularization from T11 and T12 intercostal arteries, which were successfully embolized percutaneously.

Gastric stromal tumors in Carney triad are different clinically, pathologically, and behaviorally from sporadic gastric gastrointestinal stromal tumors: findings in 104 cases.

Carney triad, as originally described in 1977, was the association of 3 tumors: gastric epithelioid leiomyosarcoma [later renamed gastrointestinal stromal tumor (GIST)], extra-adrenal paraganglioma, and pulmonary chondroma. The disorder affected mostly young women and was not familial. We studied the clinical and pathologic features of the gastric neoplasm in 104 patients with the syndrome. Most (88%) were young women (mean age, 22 y), and the usual presentation was gastric bleeding. The tumors, commonly antral-based (61%), were multifocal, and ranged from 0.2 to 18.0 cm in dimension. Most (86%) featured round and polygonal (epithelioid) cells. Metastasis occurred in 49 patients (47%): to gastric lymph nodes (29%), liver (25%), and peritoneum (13%). Immunopositivity was detected in the tumors tested as follows: KIT, 100%; CD34, 75%; PKCtheta, 21%; PDGFRA, 90%; and smooth muscle actin, 6%. Fourteen patients (13%) died of metastatic GIST at a mean age of 45 years (range, 30 to 69 y). Estimated 10 and 40-year survivals were 100% and 73%, respectively. Median survival time was 26.5 years (range, 16 to 60 y). There was no correlation between the National Institutes of Health tumor risk classification and the tumor behavior. Compared with sporadic gastric GISTs, the gastric stromal tumor in Carney triad showed distinctive features: female predilection, young patient age, epithelioid cell predominance, multifocality, frequent lymph node metastasis, serial tumor occurrence, and unpredictable behavior. Thus, the Carney triad gastric stromal tumor is different clinically, pathologically, and behaviorally from sporadic gastric GIST.

Colonic and gastric cancer metastatic lymph nodes: applications of autofluorescence-based techniques

Lymphadenectomy and extended lymphadenectomy are still controversial issues in surgical oncology. The detection methods for metastatic lymph nodes include lymphoscintigraphy and radiolabelled antibody, but immunohistochemical sentinel lymph node (SLN) identification is commonly used. The potential diagnostic use of cell and tissue autofluorescence (AF) is well known. Here we review our studies on the application of AF-based techniques for diagnosing metastatic lymph nodes. We had previously demonstrated that AF imaging allows discrimination between hyperplastic and primary neoplastic lymph nodes. Our more recent studies show that the combination of autofluorescence microspectroscopy and multispectral imaging autofluorescence microscopy can be applied to the diagnosis of secondary neoplastic lymph nodes in gastric and colorectal cancer. These techniques have been validated by histochemical and immunohistochemical methods. Studies are in progress to select the best dye tracer for SLN identification, to improve image quality and to develop a software for automatic analysis of tissue AF to help the decision-making process during surgery.

Study on the clinicopathological characteristics and pattern of lymph node metastasis in patients with gastric remnant cancer

To investigate clinicopathological characteristics and the pattern of lymph node metastasis of patients with gastric remnant cancer. The data of the clinicopathological characteristics and the pattern of lymph node metastasis in 56 patients with gastric remnant cancer treated from March 1994 to December 2008 was investigated and compared with those in 1171 patients with primary gastric cancer treated over the same period. Fifty-six patients (4.6%) with gastric remnant cancer were enrolled in this study during the period. Compared with patients with primary gastric cancer, the age of cancer onset was older [(64.3+/-9.0) vs. (58.3+/-12.6) yrs], lymph node metastasis rate was higher (31.8% vs. 25.5%), Borrmann's classification was later and neighbor organ resection rate was higher (57.1% vs. 26.4%) in patients with gastric remnant cancer; the differences were all significant (chi2=18.800, 11.679, 9.177, 25.190; P<0.05). Patients with gastric remnant cancer who underwent lymph node dissection tended to have a higher incidence of No.10 (splenic hilar lymph node) and No.11 (splenic artery lymph node) group lymph node metastasis than those in primary gastric cancer (chi2=5.558, 6.099; P<0.05). In contrast, patients with primary gastric cancer had a higher incidence of No. 2 (left cardiac lymph node), No.3 (lesser curvature lymph node) and No.8 (common hepatic artery lymph node) group lymph node metastasis than those in gastric remnant cancer (chi2=15.508, 6.003, 4.084; P<0.05). The jejunal mesentery lymph node metastasis was 24.0% (6/25) in patients with gastric remnant cancer and the peripheral connective tissue infiltration rate was 14.3% (8/56). It suggested that patients with gastric remnant cancer has different clinicopathologic characteristics and the pattern of lymph node metastasis from those with primary gastric cancer. D2 lymph node dissection of proximate gastric cancer and jejunal mesentery lymph node dissection should be the standard operation for these patients; but combined neighboring organ resection should be taken into consideration.

Prognostic impact of splenectomy on advanced proximal gastric cancer with No. 10 lymph node metastasis

Background This study evaluated the prognostic impact of D2 lymphadenectomy combined with splenectomy in patients with advanced proximal gastric cancer and lymph node metastasis at the splenic hilum (No. 10 lymph nodes). Methods The clinical records of 216 patients with advanced proximal gastric cancer and No. 10 lymph node metastasis who underwent D2 curative resection were retrospectively analyzed. Seventy-three patients underwent simultaneous splenectomy (splenectomy group), while 143 patients did not (spleen-preserving group). Five-year survival rates, mean numbers of dissected No. 10 lymph nodes and metastatic No. 10 lymph nodes, and operative morbidity and mortality were calculated and compared between the two groups. Potential prognostic factors were evaluated by univariate and multivariate analysis. Results The 5-year survival rate was 30.0% for the splenectomy group and 19.7% for the spleen-preserving group (χ2=14.73, P &lt;0.05). The mean numbers of dissected No. 10 lymph nodes and metastatic No. 10 lymph nodes in the splenectomy group were significantly greater than in the spleen-preserving group (P &lt;0.05). Multivariate analysis revealed that the depth of invasion, splenectomy, and type of gastrectomy were independent prognostic factors. The survival rate for T3 patients with and without splenectomy was 38.7% and 18.9%, respectively (χ2 =15.03, P &lt;0.05). For patients undergoing total gastrectomy, survival rates were 33.4% and 20.7%, respectively (χ2 =13.63, P&lt;0.05). Operative morbidity and mortality in splenectomy group was 24.7% and 4.1%, respectively, and in the spleen-preserving group was 17.5% and 3.5%, respectively. The differences were not statistically significant (P &gt;0.05). Conclusions Splenectomy is beneficial for No. 10 lymph node dissection in patients with advanced proximal gastric cancer. To improve patient prognosis, total gastrectomy with splenectomy is recommended for patients with T3 proximal gastric cancer who have No. 10 lymph node metastasis.

High-Level Expression of S100A4 Correlates with Lymph Node Metastasis and Poor Prognosis in Patients with Gastric Cancer

The present study investigated the clinical significance of S100 calcium binding protein A4 in the development, progression, and metastasis of gastric cancer. Tumor tissue, adjacent normal tissue, and lymph node and peritoneal metastases were obtained from patients with gastric cancer, and their gene expression profiles were analyzed by Affymetrix GeneChip HG-U133A2.0 array. The expression of S100A4 was detected by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) in gastric tumor tissue and lymph node and peritoneum metastasis. Immunohistochemistry was employed to analyze S100A4 expression in 436 clinicopathologically characterized gastric cancer cases and in corresponding distant metastases from 61 patients. A total of 434 genes and 169 expressed sequence tags were upregulated by at least twofold in the tumor tissue. The expression of S100A4 in lymph node and peritoneal metastases was significantly higher than that in gastric tumor tissue. The expression of S100A4 messenger RNA (mRNA) or protein differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph node and peritoneal metastases. Further multivariate analysis suggested that depth of invasion, lymph node and distant metastases, tumor-node-metastasis (TNM) stage, and upregulation of S100A4 were independent prognostic indicators for the disease. Gene expression profiles are a useful way to perform simultaneously large-scale analysis of the expression level of thousands of genes. Expression of S100A4 in gastric cancer is associated significantly with lymph node and distant metastases, and poor prognosis. S100A4 may be a useful marker to predict development, progression, and metastasis of gastric cancer.

An Aggressive MALT Lymphoma Despite Negative Helicobacter pylori Testing

Purpose: MALT lymphoma is a form of non-Hodgkin B cell lymphoma (NHL) involving the mucosa-associated lymphoid tissue (MALT); however, the occurrence of Helicobacter pylori-negative lymphoma of the stomach—a primary gastric lymphoma, is not very common. Methods: We report a case of a 49-year-old Hispanic female with complaints of intermittent gastric pain, nausea and occasional vomiting for 2 years. The patient stated her pain was dull and went away with food and admitted to weight loss. She denied any significant past medical history or any familial gastrointestinal issues. Her lab values were within normal limits, except for mild anemia. Her physical exam was notable for epigastric tenderness. Subsequently, the patient was scheduled for upper endoscopy which demonstrated superficial ulceration, limited distensibility and rigidity. Extensive biopsies of the antrum and proximal stomach revealed necrotic debris with acute leucocytic exudation and extranodal marginal zone B cell lymphoma. Giemsa staining and serology for H. pylori was negative. The patient was then empirically started on triple antibiotic therapy (Amox/clav/PPI) for H. pylori eradication, and scheduled for endoscopic ultrasound (EUS). The EUS demonstrated excellent 5 layer echopattern throughout the stomach. The MALT lymphoma appeared to be confined to the superficial antral mucosa without peri gastric lymph node involvement. The patient underwent repeat endoscopy with multiple biopsies 4 weeks later which showed histologic persistence of MALT lymphoma. She was therefore referred to an oncologist for systemic chemotherapy. Results: Presently, 12 clinical studies with almost 400 patients and case reports have shown that a cure of H. pylori infection is associated with complete remission in approximately 80% of patients with low-grade MALT lymphoma in an early clinical stage. However, what can be done if the patient is found to be H. pylori negative? Rates of about 7-15% of H. pylori-negative gastric MALT lymphoma patients have been reported. The reason for the occurrence of a maltoma without the evidence of H. pylori is unknown. Perhaps multiple etiological factors are at fault for the pathogenesis of MALT lymphoma. Conclusion: Eradication strategies may not entirely preclude the risk for neoplastic transformation. H. pylori negative associated MALT may indeed represent a different clinical entity with more aggressive characteristics. Though rates are low, they remain significant. Despite directed HP treatment, our patient demonstrated persistent malignacy and ultimately needed systemic chemotherapy.

Kinetics of the local immune response in the gastric lymph of lambs after primary and challenge infection withTeladorsagia circumcincta

Groups of 5-month-old lambs which had been trickle infected with Teladorsagia circumcincta for 8 weeks then drenched, and worm-free control lambs were challenged with 50 000 T. circumcincta L3s. From 10 days later fewer parasites were recovered from the previously infected sheep, and secondary cellular and humoral responses were observed in the gastric lymph. Increases in CD4+ and CD25+ T lymphoblast traffic on day 3, followed by CD21+ and IgA+ lymphoblasts on day 5, and an increase in total and parasite specific IgA concentrations peaking on day 6 were observed in previously infected lambs. Similar peaks in lymphoblast output were not observed until days 10-12 in the control lambs. This data was highly comparable with that obtained recently from yearling sheep subjected to an identical infection-challenge regime, and contrasted with that obtained from similar experiments in the 1980s when 4(1/2)-month-old previously infected lambs were more susceptible to and had much weaker immune responses to challenge than 10-month-old sheep. The fact that 40% fewer larvae were given during the trickle infection regime in the four recent trials is offered as an explanation for this difference.

A long-time survivor of alpha-fetoprotein-producing gastric cancer successfully treated by fluoropyrimidine-based chemotherapy: a case study.

A 67-year-old male with advanced gastric cancer and lymph node metastasis as well as a tumor embolus in the portal vein was treated by S-1/cisplatin therapy. The serum alpha-fetoprotein levels were elevated to 836ng/ml at the first visit. After one course of chemotherapy, the patient showed stable disease; the serum level of alpha-fetoprotein also decreased to 626ng/ml after a transient increase, and therefore reduction surgery was performed. A total gastrectomy with a distal pancreatectomy, splenectomy, and regional lymph node dissection was performed. The resected specimen was diagnosed to be alpha-fetoprotein-producing gastric cancer. There were no metastatic foci in the resected lymph nodes, presumably due to the preoperative chemotherapy. S-1/cisplatin therapy was continued after the operation to treat the remaining tumor embolus in the portal vein. After one course of this therapy, the tumor embolus disappeared. However, a lymph node measuring 1.5cm in diameter appeared in the hepatoduodenal ligament. Therefore, the chemotherapy was changed to paclitaxel monotherapy. After 2 courses of paclitaxel monotherapy, the lymph node swelled, and thus 5'-deoxy-5-fluorouridine was added to the paclitaxel regimen. After 5 courses of this regimen, the lymph node swelling disappeared without any other new lesions and a total of 21 courses were performed. The patient remained stable for over 8years without recurrence. The expression of chemoresistance-related proteins was retrospectively analyzed by immunohistochemistry to evaluate the chemoresistance. The ortate phosphoribosyltransferase expression was strongly positive, and the good outcome in this case may have been associated with this result.

Accuracy of Surgical Diagnosis in Detecting Early Gastric Cancer and Lymph Node Metastasis and Its Role in Determining Limited Surgery

The aim of this study was to evaluate the accuracy of surgical diagnosis of early gastric cancer (EGC) and lymph node metastasis, and elucidate its role in determining limited surgery for EGC. We reviewed 369 patients undergoing gastrectomy for primary gastric carcinoma. Surgical diagnosis was evaluated by determining its sensitivity, specificity, and accuracy, and was compared with preoperative examinations. Sensitivity, specificity, and accuracy of intraoperative diagnosis for EGC were 74.5%, 95.7%, and 83.7%, respectively. The predictive value for EGC by intraoperative diagnosis was 95.7%. Surgical diagnosis of EGC showed higher specificity and predictive value than preoperative examinations did, which significantly reduced the risk of underestimating advanced gastric cancer (AGC) to EGC. The sensitivity, specificity, and accuracy for lymph node metastasis by surgical diagnosis were 73.2%, 78.1%, and 76.4%, respectively. In 70 patients with a discrepancy in the diagnosis of EGC between pre- and intraoperative diagnoses, surgical diagnosis was correct in 63 (90%) patients, but preoperative examination was correct in only 7 (10%) patients. Surgical diagnosis shows better accuracy than preoperative examinations do in detecting EGC and lymph node metastasis. Our results suggest that the decision to perform limited surgery based on surgical diagnosis might reduce the risk of undertreatment of AGC to EGC better than preoperative examinations.