Expression and Mutation of MAGE-A3 mRNA in Lung Cancer Tissues

Objective： To inwvetigate the expression of MAGE-A3 mRNA in tissue samples derived from lung cancers and to discuss the possibility of using MAGE-A3 antigens as a new peptide vaccine for inunotherapy for lung cancers. Methods： Tumor tissue samples of lung cancers and paired non-tumor tissues of the lung were obtaimed from 31 lung cancer patients. Total RNA was extracted and cDNA was synthesized. Nested polymernse chain reaction amplification using MAGE-A3 specific primer was performed to detect the expression of MAGE-A3. The 10 clones of 5 samples of MAGE-A3 mRNA positive PCR products were DNA sequenced by using DNAs sequencer （PE-377）. Results： Of 31 lung cancers, 26 （83.9%） expressed MACE-A3 mRNA. The expression of MAGE-A3 gene was not detectable in the adjacent lung tissues. The DNA sequencing confirmed that the target gene fragment in all 5 samples of PCR products was MACE-A3 cDNA. Point nmtations occurred in 4 samples （8 clones） detected （C^2773→T^2773; G^2807→A^2807） resulting in alternation of amino acid residue in one position （E^143→K）. Conclusion： （1） The MAGE-A3 gene was expressed exclusively in tumor tissues of the patients with lung cancer in China. This tumor rejection antigen may have potential to be used as a new peptide vaccine for immunotherapy for lung eancers. （2） There are two point mutations of MAGE-A3 gene sequence in some Chinese lung cancer patients.

mRNA Expression of the Cancer-testis Antigens SSX1 and SSX4 in Human Hepatocellular Carcinomas

Objective: To detect the mRNA expression of the cancer-testis antigens (CT) SSX1 and SSX4 gene in human hepatocellular carcinomas (HCCs) and to investigate the specificity of their expression in HCCs. Methods: The mRNA expression of SSX1 and SSX4 in HCC tissues and the corresponding nearby liver tissues in 35 cases was detected by using RT-PCR; Six positive RT-PCR products were randomly selected and sequenced. Results: In all 35 HCC tissues, SSX1 in 27 cases (81%) and SSX4 in 23 cases (73%) were detected, and their expression was negative in the liver tissues nearby HCC and the non-tumor liver tissues (12 cirrhotic tissues and 15 normal tissues). In all 6 cases selected randomly, the results of DNA sequencing were identical with the cDNA sequence of SSX1 and SSX4 genes. The SSX1, SSX4 mRNA expression was not significantly correlated with age, sex, the tumor size, the level of tumor differentiation, the serum AFP level and the infection rate of HBV and HCV respectively (P>0.05). Conclusion: The SSX1, SSX4 mRNA expression was greatly specific in HCCs, which would not only provide the ideal target molecular sites for HCC tumor vaccines, but also establish the potential value of the polyvalent tumor-antigen vaccines for HCC therapy and its theory bases.

Mechanisms of cell immortalization mediated by EB viral activation of telomerase in nasopharyngeal carcinoma

Nasopharyngeal carcinoma （NPC） is a common cancer in Southern China and Southeast Asia. The disease is a poorly differentiated carcinoma without effective cure, and the mechanism underlying its development remains largely unknown. Of several factors identified in NPC aetiology in recent years, Epstein-Barr virus （EBV） infection has emerged to be most important. In almost all NPC cells, EBV uses several intracellular mechanisms to cause oncogenic evolution of the infected cells. One such mechanism by which EBV infection induces cellular immortalization is believed to be through the activation of telomerase, an enzyme that is normally repressed but becomes activated during cancer development. Studies show that greater than 85% of primary NPC display high telomerase activity by mechanisms involving EBV infection, consistent with the notion that EBV is commonly involved in inducing cell immortalization. More recently, different EBV proteins have been shown to activate or inhibit the human telomerase reverse transcriptase gene, by modulating intracellular signalling pathways. These findings suggest a new model with a number of challenges towards our understanding, molecular targeting and therapeutic intervention in NPC.

Construction, expression and characterization of the engineered antibody against tumor surface antigen, p185^(c-erbB-2)

The c-erbB-2 proto-oncogene encodes a 185kDa protein p!85, which belongs to epidermal growth factor receptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis for certain cancer patients. The monoclonal antibody A21 which directed against p185 specifically inhibits proliferation of tumor cells overexpressing p185, hence allows it to be a candidate for targeted therapy. In order to overcome several drawbacks of murine MAb, we cloned its VH and VL genes and constructed the single-chain Fv (scFv) through a peptide linker. The recombinant scFvA21 was expressed in Escherichia coli and purified by the affinity column. Subsequently it was characterized by ELISA, Western blot, cell immunohistochemistry and FACS. All these assays showed the binding activity to extracellular domain (ECD) of p!85. Based on those properties of scFvA21, we further constructed the scFv-Fc fusion molecule with a homodimer form and the recombinant product was expressed in mammalian cells. In a series of subsequent analysis this fusion protein showed identical antigen binding site and activity with the parent antibody. These anti-p185 engineered antibodies have promised to be further modified as a tumor targeting drugs, with a view of application in the diagnosis and treatment of human breast cancer.

Cellular immunity augmentation in mainstream oncologic therapy

Anticancer immunotherapy has undergone a long evolving journey for decades, and has been dramatically applied to mainstream treatments in oncology in recent 5 years. This progress represents an advanced milestone following cytotoxic medicine and targeted therapy. Cellular immunity plays a pivotal role in the immune responses of hosts to tumor antigens. Such immunity is notably suppressed during neoplastic progression due to immuno-editing processes. Cellular immunity can also be selectively reactivated to combat malignancies while exploiting the advantages of contemporary scientific breakthroughs in molecular immunology and genetic engineering. The rapid advancement of cellular immunity-based therapeutic approaches has achieved high efficacy in certain cancer patients. Consequently, the landscape of oncologic medicine and pharmaceutical innovation has transformed recently. In this regard, we present a comprehensive update on clinically established anti-cancer treatments with cell immunity augmentation as the major mechanism of action.

Peripheral and mesenteric serum levels of CEA and cytokeratins,staging and histopathological variables in colorectal adenocarcinoma

AIM： To evaluate the differences that exist bet- ween peripheral and mesenteric serum levels of carcinoembryonic antigen （CEA） and cytokeratins in patients with colorectal adenocarcinoma. METHODS： One hundred and thirty-eight patients with colorectal adenocarcinoma who underwent surgery at Hospital Sao Paulo （Discipline of Surgical Gastroenterology of UNIFESP-EPM） between December 1993 and March 2000 were retrospectively analyzed. Differences between CEA and cytokeratin （TPA-M） levels in peripheral blood （P） and in mesenteric blood （M） were studied. Associations were investigated between peripheral and mesenteric levels and the staging and histopathological variables （degree of cell differentiation, macroscopic appearance, tumor dimensions and presence of lymphatic and venous invasion）. RESULTS： Differences were observed in the numerical values of the marker levels： CEA （M） （39.10 mg/1 ± 121.19 mg/L） vs CEA （P） （38.5 mg/L ± 122.55 mg/L）, P 〈 0.05; TPA-M （M） （325.06 U/L ±527.29 U/L） vs TPA-M （P） （279.48 U/L ±455.81 U/L）, P 〈 0.01. The mesenteric CEA levels were higher in more advanced tumors （P 〈 0.01）, in vegetating lesions （34.44 mg/L ± 93.07 mg/L） （P 〈 0.01） and with venous invasion （48.41 mg/L ± 129.86 mg/L） （P 〈 0.05）. Peripheral CEA was higher with more advanced staging （P 〈 0.01）and in lesions with venous invasion （53.23 mg/L ± 258.57 mg/L） （P 〈 0.05）. The patients demonstrated increased mesenteric and peripheral TPA-M levels with more advanced tumors （P 〈 0.01 and P 〈 0.01） and in non-ulcerated lesions [530.45 U/L =1= 997.46 U/L （P 〈 0.05） and 457.95 U/L ± 811.36 U/L （P 〈 0.01）]. CONCLUSION： The mesenteric levels of the tumor markers CEA and cytokeratins were higher than the peripheral levels in these colorectal adenocarcinoma patients, Higher levels of these biologic tumor markers are associated with an advanced state of cancerous dissemination

Receptor-binding cancer antigen expressed on SiSo cells can be detected in metastatic lymph nodes from gastrointestinal cancers

AIM： To investigate the expression of receptor-binding cancer antigen expressed on SiSo cells （RCAS1） in metastatic lymph nodes from gastrointestinal cancer. METHODS： Metastatic lymph nodes from gastrointestina cancer were detected for RCAS1 by immunohistochemica staining and mRNA in situ hybridization.RESULTS： A total of 102 metastatic lymph nodes from bile duct, gastric, colon, and pancreatic cancer were investigated for RCAS1 expression. The immunoreactivity of RCAS1 was identified in 100% of metastatic lymph nodes. Both local and distant metastatic lymph nodes showed RCAS1 expression. On the contrary, specimens of non-cancerous lymph nodes were negative for RCAS1. The result of mRNA in situ hybridization was also confirmed by the finding of immunohistochemical staining. RCAS1 mRNA was detected in all tumor cells that metastasized to lymph nodes. CONCLUSION： All metastatic lymph nodes express RCAS1 in tumor cells at both protein and mRNA levels, and RCAS1 should be used as a complementary factor for identification of metastatic lymph nodes from gastrointestinal cancers.

Significance of serum tumor markers CA50 and CEA in gastric cancer

AIMS The CAS0 and CEA are well-described human tumor-as- sociated antigens most useful clinically in gastrointestinal cancer. In this study we compared these markers in sera from patients with malignant and benign digestive tract diseases. METHODS Using a side-phase radioimmunoassay,CA50 and CEA serum levels were measured in 33 control subjects and 86 patients with gastric cancer(n=34),gastric ulcer(n=27)and chronic atrophic gastritis(n=25).Carcinoma of the stomach was found in the antrum(n=22),in the body(n=3),and the fundus(n=9),and histopathologically,was divided into adeno- carcinoma(n=21),squamous cancer(n=4)and not divided (n=9).Gastric ulcer,when present,appeared in the antrun(18 patients),the body(3)and the fundus(9)and chronic atrophic gastritis was all associated with intestinal metaplasia(IM). RESULTS The normal ranges established for CA50 and CEA in the control group were 16.26+6.14 kU/L and 3.12±1.03/μg/L respectively.In the patients with gastric cancer,serum levels of CA50(112.67±38.36 kU/L)and CEA(10.28±3.76μg/L) were elevated significantly(P<0.01,respectively),the former being>22 kU/L in 18 of 34 patients(53%;range,5-1 550 kU/ L),and the latter>5 μg/L in 19 of 34 patients(55.8%,range, 0.5-17.4 μg/L).A statistically significant correlation was found between the levels of CA50 and GEA(r=0.648,P<0.01). The serum levels of CA50(46.4±25.9 kU/L,P<0.01 )and CEA(6.85±2.43 μg/L,P<0.01)were much lower in patients with gastric ulcer or chronic atrophic gastritis(P>0.05). CONCLUSIONS Based on these results,it is concluded that CA50 and CEA are indicators for advanced gastric cancer,and af- ter surgery,their serum levels may decrease considerably. Overall,there is such a close correlation between them that in clinical practice they might be of great value to the diagnosis of gastric cancer.

New tumor-associated antigen SC6 in pancreatic cancer

AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb)in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal diseases.METHODS: Six hundred and ninety-five serum specimens obtained from 115 patients with pancreatic cancer, 154 patients with digestive cancer and 95patients with non-digestive cancer were used and classified in this study. Serum specimens obtained from 140 patients with benign digestive disease and 89 patients with non-benign digestive disease served as controls. Ascites was tapped from 16 pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV)of 41, 80, and 118 U/mL were used.RESULTS: The average intra- and interassay CV detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively. The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in most malignant and benign cases were within the normal upper limit. Among the 16 pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the normal range in 93.8% patients. There was no significant difference in the concentration of SC6-Ag.Decreased expression of SC6-Ag in sera was significantly related to tumor differentiation. The concentration of SC6-Ag was higher in patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9 was significantly higher than that of ultrasound and computer tomography (CT) in pancreatic cancer patients. Higher positive predictive values were indicated in 92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% CT.CONCLUSION: The combined test of SC6-Ag and CA19-9 may improve the diagnostic rate of primary cancer. The detection of SC6-Ag is valuable in the diagnosis of pancreatic cancer before and after surgery.

Comparison between surgical outcomes of colorectal cancer in younger and elderly patients

AIM:To compare the outcome of surgical treatment of colorectal adenocarcinoma in elderly and younger patients.METHODS:The outcomes of 122 patients with colorectal adenocarcinoma who underwent surgical treatment between January 2004 and June 2009 were analyzed.The clinicopathological and blood biochemistry data of the younger group(<75 years) and the elderly group (≥75 years) were compared.RESULTS:There were no significant differences between the two groups in operation time,intraoperative blood loss,hospital stay,time to resumption of oral intake,or morbidity.The elderly group had a significantly higher rate of hypertension and cardiovascular disease.The perioperative serum total protein and albumin levels were significantly lower in the elderly than in the younger group.The serum carcinoembryonic antigen level was lower in the elderly than in the younger group,and there was a significant decreasing trend after the operation in the elderly group.CONCLUSION:The short-term outcomes of surgical treatment in elderly patients with colorectal adenocarcinoma were acceptable.Surgical treatment in elderly patients was considered a selectively effective approach.

Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2

We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2.

Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells

Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma （NB）, the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.

Changes in tumor-antigen expression profile as human small-cell lung cancers progress

Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

Purification and characterization ofα-L-fucosidase from human primary hepatocarcinoma tissue

AIM: To purify and characterizeα-L-fucosidase from human liver cancer tissue and to detect the localization ofα-L-fucosidase in tumor tissue. METHODS: Cation exchange chromatography on CM-52 and ultrafiltration were used to separateα-Lfucosidase (AFU) from crude extract of liver cancer tissue. 4-methylumbelliferyl-α-L-fucopyranoside was used as a fluorescent substrate to quantify the purified AFU activity in each step. A polyclonal antibody (pAb) against the purified AFU was obtained by anion exchange chromatography on DEAE-52 after ammonium sulfate fractionation and ultrafiltration. Immuohistochemical staining was used to observe the expression of AFU in malignant and adjacent liver tissues. RESULTS: Humanα-L-fucosidase was purified 74-fold to apparent homogeneity with 15% yield. SDSPAGE indicated the presence of one subunit of molecular weight of 55 Ku. The specific activity of AFU in pooled fraction by chromatography was 10085 IU/mg. Western blot analysis indicated that the pAb could recognize one protein band of molecular weight of 55 Ku. The expression of AFU was observed in cytoplasm membrane of liver cancer tissue but not in that of adjacent tissue. CONCLUSION: The purifiedα-L-fucosidase from primary hepatocarcinoma (PHC) is different in its properties fromα-L-fucosidase in human other organs. The polyclonal antibody prepared in this experiment can be applied to the diagnosis of PHC.

Anti-tumor effect of CTLs activated by dendritic cells pulsed with K-ras mutant peptide and whole tumor antigen on pancreatic cancer

Objective： We studied the role of specific cytotoxic T lymphocytes （CTLs） activated by dendritic cells （DCs） presenting cationic nanoparticles with the K-ras （12-Val） mutant peptide and whole tumor antigen in the killing of different pancreatic cancer cell lines in vitro and in vitro. Methods： Peripheral blood DCs were induced by rhGM-CSF and IL-4 and cultured. DCs were sensitized by whole antigen of a pancreatic cancer cell line （PANC-1） with expression of K-ras mutant, K-ras mutant peptide （K-ras＋peptide） and cationic nanoparticles with K-ras mutant peptide （K-ras＋peptide-CNP）, respectively. Cell surface markers were measured by flow cytometry. Lymphocyte proliferation was detected by the 3H-TdR test, and ELISAwas performed to detect IFN-y secretion. 125I-UdR was used to measure the killing effect of CTLs. We also evaluated the antitumor activity of CTLs in vivo in a tumor-bearing nude mouse model prepared with the PANC-1 （K-ras＋） and SW1990 （K-ras-） cell lines. Results： Compared with K-ras＋peptide, low concentration K-ras＋pepUde-CNP can be effectively presented by DCs （P 〈 0.05）. CTLs induced by DCs pulsed with whole tumor antigen had significant greater killing effect （P 〈 0.05） on PANC-1 and SW1990 pancreatic cancer cells compared with K-ras＋peptide and K-ras＋peptide-CNP-induced CTLs. CTLs induced by DCs pulsed with K-ras＋peptide and K-ras＋peptide-CNP had a specific killing effect （P 〈 0.05） for PANC-1 and no effect （P 〉 0.05） on SW1990 cell lines （P 〉 0.05）. Conclusion： Cationic nanoparticles with K-ras （12-Val） mutant peptide can be effectively presented by DCs at a low concentration in a short time. CTLs induced by K-ras＋peptide-CNP had specific killing activity for the pancreatic cancer cell line with the K-ras （12-Val） mutant and could significantly inhibit tumor growth and increase the survival time of tumor-bearing nude mice.

Prediction of HLA-A2-restricted CTL epitope specific to HCC by SYFPEITHI combined with polynomial method

AIM: To predict the HLA-A2-restricted CTL epitopes of tumor antigens associated with hepatocellular carcinoma (HCC).METHODS: MAGE-1, MAGE-3, MAGE-8, P53 and AFP were selected as objective antigens in this study for the close association with HCC. The HLA-A*0201 restricted CTL epitopes of objective tumor antigens were predicted by SYFPEITHI prediction method combined with the polynomial quantitative motifs method. The threshold of polynomial scores was set to -24.RESULTS: The SYFPEITHI prediction values of all possible nonamers of a given protein sequence were added together and the ten high-scoring peptides of each protein were chosen for further analysis in primary prediction. Thirtyfive candidates of CTL epitopes (nonamers) derived from the primary prediction results were selected by analyzing with the polynomial method and compared with reported CTL epitopes.CONCLUSION: The combination of SYFPEITHI prediction method and polynomial method can improve the prediction efficiency and accuracy. These nonamers may be useful in the design of therapeutic peptide vaccine for HCC and as immunotherapeutic strategies against HCC after identified by immunology experiment.

The role of Langerhans cells in oral squamous cell carcinoma

During the initiation, promotion, and progression of multi-step carcinogenesis, changes in specific host immuno- logical factors have been observed. Although immunology of oral cancer has long been focused on antigens and lymphocytes, the fact remains that the antigen presenting cells, like the Langerhans cells （LCs） of the epithelium are initiators and modulators of the immune response. LCs as sentinels of immune response, have been investigated in several orai mucosal diseases, including cancer. Inadequate presentation of tumor antigens by host dendritic cells is one potential mechanism that allows tumor progression, tn this review, the role of LCs in OSCC is discussed. Elucidation of the role of APCs, in particular LCs, may help to better understand the mechanisms underlying anti-tumour immune responses and, improve the effectiveness of anti-cancer immunity in tumour-bearing hosts. This section focuses on the roles LCs in the immunity of cancer and how cancer bypasses the dendritic cell-mediated immune responses, are discussed. Subsequently, the effects of tumor microenviornment on LC＇s and their therapeutic implications are elaborated.

Clinical use of hepatic carcinoma associated membrane protein antigen (HAg18-1) as reagent of enzyme linked immunosorbent assay for detection of primary hepatocellular carcinoma

AIMS To evaluate the sensitivity,specificity and clinical value of hepatic carcinoma associated mem- brane protein antigen (HAg18-1) used as a reagent of serum quick enzyme linked immunosorbent assay (ELISA) for the detection of primary hepatocellular car- cinoma (PHCC). METHODS Serum quick enzyme linked immunosor- bent assay (ELISA) with HAg18-1 as reagent,which was prepared by monoclonal antibody against human hepatic carcinoma,was performed on 100 cases of pri- mary hepatocellular carcinoma (PHCC),5 cases of hepatic biliary carcinoma (HBC),10 cases of metastatic hepatic carcinoma (MHC),20 cases of hep- atitis B (HB),20 cases of liver cirrhosis (LC),20 cas- es of gastrointestinal malignant tumours and 20 cases of gastronintestinal inflammatory diseases (including ulcers). Alpha-fetoprotein (AFP) detection concurrent- ly for each case. Twenty samples of bank blood were tested as controls. RESULTS Positive rate of HAg18-1 ELISA and AFP detection were 81% and 68% in PHCC,20% and 40% in HBC,19% and 20% in MHC,10% and 20% in BH, 10% and 20% in LC,10% and 15% in gastrointestinal malignant tumors,and 5% and 10% in gastrointestinal inflammatory diseases. No positive result of HAg18-1 ELISA and AFP detection occurred in any sample of bank blood. CONCLUSIONS HAg18-1 ELISA has high sensitivity and specificity in the detection of PHCC. HAg18-1 ELISA and AFP detection,if used together,may be complementary to each other in the diagnosis of PHCC.

CT diagnosis of recurrence after pancreatic cancer:Is there a pattern?

AIM:To investigate predilection sites of recurrence of pancreatic cancer by computed tomography(CT)in follow-up after surgery. METHODS:Seventy seven patients with recurrence after pancreatic cancer surgery were retrospectively identified.The operative technique,R-status,T-stage and development of tumor markers were evaluated. Two radiologists analyzed CT scans with consensus readings.Location of local recurrence,lymph node recurrence and organ metastases were noted.Surgery and progression of findings on follow-up CT were con-sidered as reference standard. RESULTS:The mean follow-up interval was 3.9± 1.8 mo,with a mean relapse-free interval of 12.9± 10.4 mo.The predominant site of recurrence was local (65%),followed by lymph node(17%),liver metastasis (11%)and peritoneal carcinosis(7%).Local recurrence emerged at the superior mesenteric artery(n=28),the hepatic artery(n=8),in an area defined by the surrounding vessels:celiac trunk,portal vein,inferior vena cava(n=22),and in a space limited by the mesenteric artery,portal vein and inferior vena cava(n=17). Lymph node recurrence occurred in the mesenteric root and left lateral to the aorta.Recurrence was confirmed by surgery(n=22)and follow-up CT(n=55).Tumor markers[carbohydrate antigen 19-9(CA19-9),carcinoembryonic antigen(CEA)]increased in accordance with signs of recurrence in most cases(86%CA19-9;79.2% CEA). CONCLUSION:Specific changes of local and lymph node recurrence can be found in the course of the cardinal peripancreatic vessels.The superior mesenteric artery is the leading structure for recurrence.