A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma / 中华肝脏病杂志

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma / 中华肝脏病杂志

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

Research and exploration of salivary biological markers for hepatitis B-related hepatocellular carcinoma / 中华肝脏病杂志

Objective: To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods: Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results: 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion: Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.

Uptake of DNA by cancer cells without a transfection reagent

BACKGROUND: Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. METHODS: A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). RESULTS: The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. CONCLUSIONS: In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting reagent.

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

Clinicopathological Characteristics and Prognosis of Alpha-fetoprotein Producing Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: Several studies reported a subgroup of gastric cancer patients showing elevated serum alpha-fetoprotein (AFP) at the time of diagnosis. We investigated the clinicopathological characteristics and prognostic factors of AFP producing gastric cancer (AFPPGC) by comparing with AFP non-producing gastric cancer (AFPNPGC). METHODS: A total of 909 patients were diagnosed with gastric cancer from January 2005 to March 2013 at Gyeongsang National University Hospital and their AFP levels were measured at the time of diagnosis. After excluding 138 patients with underlying liver diseases, 34 patients with elevated serum AFP level over 10 mg/mL were assigned to AFPPGC group and the remaining 737 patients with serum level of AFP below 10 ng/mL were assigned to AFPNPGC group. RESULTS: The median survival length was shorter in AFPPGC group than AFPNPGC group (18.3+/-25.5 months vs. 30.0+/-22.0 months, p=0.004). The incidence of liver metastasis (47.1% vs. 3.3%, p<0.001) and lymph node metastasis (91.2% vs. 31.6%, p<0.001) was significantly higher in AFPPGC group. The probability of encountering metachronous liver metastasis after the operation was higher in AFPPGC group (44.4% vs. 2.0%, p<0.001). Multivariate analysis revealed that patients in the AFPPGC group who received chemotherapy (p=0.037) or underwent operation (p=0.001) had a better survival rate. CONCLUSIONS: AFPPGC behaves more aggressively and shows a worse prognosis. Therefore, serum AFP level should be routinely checked in all patients diagnosed with gastric cancer.

Clinicopathological Characteristics and Prognosis of Alpha-fetoprotein Producing Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: Several studies reported a subgroup of gastric cancer patients showing elevated serum alpha-fetoprotein (AFP) at the time of diagnosis. We investigated the clinicopathological characteristics and prognostic factors of AFP producing gastric cancer (AFPPGC) by comparing with AFP non-producing gastric cancer (AFPNPGC). METHODS: A total of 909 patients were diagnosed with gastric cancer from January 2005 to March 2013 at Gyeongsang National University Hospital and their AFP levels were measured at the time of diagnosis. After excluding 138 patients with underlying liver diseases, 34 patients with elevated serum AFP level over 10 mg/mL were assigned to AFPPGC group and the remaining 737 patients with serum level of AFP below 10 ng/mL were assigned to AFPNPGC group. RESULTS: The median survival length was shorter in AFPPGC group than AFPNPGC group (18.3+/-25.5 months vs. 30.0+/-22.0 months, p=0.004). The incidence of liver metastasis (47.1% vs. 3.3%, p<0.001) and lymph node metastasis (91.2% vs. 31.6%, p<0.001) was significantly higher in AFPPGC group. The probability of encountering metachronous liver metastasis after the operation was higher in AFPPGC group (44.4% vs. 2.0%, p<0.001). Multivariate analysis revealed that patients in the AFPPGC group who received chemotherapy (p=0.037) or underwent operation (p=0.001) had a better survival rate. CONCLUSIONS: AFPPGC behaves more aggressively and shows a worse prognosis. Therefore, serum AFP level should be routinely checked in all patients diagnosed with gastric cancer.

Evaluation of the UniCel(TM) DxI 800 Immunoassay Analyzer in Measuring Five Tumor Markers

PURPOSE: Tumor marker concentrations in a given specimen measured by different analyzers vary according to assay methods, epitopes for antibodies used, and reagent specificities. Although great effort in quality assessment has been instituted, discrepancies among results from different analyzers are still present. We evaluated the assay performance of the UniCel(TM) DxI 800 automated analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers. MATERIALS AND METHODS: The linearity and precision performance of the five tumor marker assays were evaluated, and concentrations of the respective markers as measured by DxI were compared to those measured by other conventional analyzers (ADVIA Centaur(TM) and Vitros(TM) ECi) using 200 specimens collected from 100 healthy persons and 100 patients with respective cancers. RESULTS: The linear fits for all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for all). The imprecision of each tumor marker assay was less than 5% coefficient of variation, except for low and high concentrations of AFP. The results from UniCel(TM) DxI 800 were highly correlated with those from other analyzers. CONCLUSION: Our results demonstrate that UniCel(TM) DxI 800 has good linearity and precision performance for the tumor markers assayed in this study. However, there were discrepancies between assaying methods. Efforts to standardize tumor marker assays should be undertaken, and the redetermination of cut-off levels is necessary when developing methods of analyzing tumor markers.

Unusual anatomic location of a primary intracranial yolk sac tumor

A nongerminomatous germ cell tumor occurring in the brain parenchyma is extremely rare. A 2-year-old boy presented with symptoms of abnormal movements in the hand and mouth. MRI scanning revealed a lesion occupying the left temporoparietal region. Craniotomy was performed and the tumor was removed by en bloc resection. Histological examination revealed that the tumor was arranged in a reticular pattern, and Schiller-Duval bodies were evident at the center of the tumor. Immunohistochemical study showed that the tumor cells were positive for alpha-fetoprotein and vimentin, but negative for glial fibril-lary acidic protein. The histological diagnosis was pure yolk sac tumor

Binding characteristics of sperm with recombinant human zona pellucida glycoprotein-3 coated beads.

Background & objectives: An inability or decreased ability of spermatozoa to bind to the zona pellucida (ZP), an extracellular glycoproteinaceous matrix surrounding egg, is one of the plausible causes of idiopathic infertility. It will be clinically useful to distinguish this condition from other causes of infertility. An assay system, investigating binding of human sperm with ZP glycoprotein may prove useful in this regard. We attempted to develop a simple assay system to analyse the binding of capacitated human spermatozoa to human zona pellucida glycoprotein-3 (ZP3) using baculovirus-expressed recombinant human ZP3 coated beads. Methods: Recombinant baculovirus-expressed ZP3 was purified, labelled with biotin and coated on streptavidin sepharose beads. An in vitro assay system was optimized to study binding of capacitated human sperm to ZP3 coated beads. Results: A higher percentage of baculovirus-expressed recombinant human ZP3 coated beads showed significant (P<0.05) binding of capacitated human sperm as compared to beads coated with fetuin. An inhibition in the binding of sperm to ZP3 coated beads was observed in presence of cold recombinant human ZP3. Further, prior incubation of ZP3 coated beads with monoclonal antibodies (MAbs) against ZP3 but not against ZP2 resulted in the decrease in number of sperm bound to bead. Interpretation & conclusion: An in vitro assay system to study the binding of human sperm to ZP3- primary sperm receptor was established, which may be useful to determine the functional competence of spermatozoa.

A case of liver metastasis of gastric hepatoid adenocarcinoma / 대한간학회지

We report herein a case of hepatoid adenocarcinoma of the stomach with liver metastasis. Gastric carcinoma generally presents as adenocarcinoma and rarely shows a hepatoid pattern, which can produce alpha-fetoprotein (AFP). The stomach is one of the common sites at which hepatoid adenocarcinoma has been detected. A 75-year-old female patient was admitted to the hospital with a symptom of epigastric discomfort. Gastrofibroscopy revealed a large tumor occupying the greater curvature of the stomach body. The level of serum AFP was markedly increased. Abdominal computed tomography revealed multiple liver masses. Biopsy samples of the gastric lesion and liver masses finally confirmed her case as hepatoid adenocarcinoma in the stomach with liver metastasis. The AFP-producing gastric carcinoma needs special attention because it often presents with early liver metastasis and has a poor prognosis.

Preoperative Radiologic and Postoperative Pathologic Risk Factors for Early Intra-Hepatic Recurrence in Hepatocellular Carcinoma Patients Who Underwent Curative Resection

PURPOSE: The risk of hepatocellular carcinoma (HCC) recurrence must be considered ahead of surgery. This study was undertaken to identify pre-operative risk factors for early intrahepatic recurrence of HCC after curative resection in a large-scale. MATERIALS AND METHODS: We retrospectively reviewed the preoperative three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who underwent curative resection; tumor size, number, gross shape, capsule integrity, distinctiveness of tumor margin, portal vein thrombosis (PVT), alpha-fetoprotein level (AFP), and protein induced by vitamin K absence-II (PIVKA-II) levels were assessed. Surgical pathology was reviewed; tumor differentiation, capsule, necrosis, and micro-vessel invasion were recorded. RESULTS: HCC recurred in 61 patients within six months (early recurrence group), but not in 179 patients (control group). In univariate analysis, large tumor size (p = 0.018), shape (p = 0.028), poor capsule integrity (p = 0.046), elevated AFP (p = 0.015), and PIVKA-II (p = 0.008) were significant preoperative risk factors. Among the pathologic features, PVT (p = 0.023), Glisson's capsule penetration (p = 0.033), microvascular invasion (p < 0.001), and poor differentiation (p = 0.001) showed statistical significance. In multivariate analysis, only the histopathologic parameters of microvascular invasion and poor differentiation achieved statistical significance. CONCLUSION: Preoperative CT and laboratory parameters showed limited value, while the presence of microscopic vascular tumor invasion and poorly differentiated HCC correlated with higher risk of early recurrence after curative resection.

Redifferentiation of human hepatoma cells (SMMC-7721) induced by two new highly oxygenated bisabolane-type sesquiterpenes.

Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl transferase activity. In addition,we found that HOBS inhibited the anchorage- independent growth of SMMC-7721 cells in a dose-dependent manner.Taken together,all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.

Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. In Egypt, HCC was reported to account for about 4.7% of chronic liver disease (CLD) patients. Squamous cell carcinoma antigen (SCCA) has been reported to be strongly expressed in HCC tissue hampering its extensive use in clinical practice. AIM: To evaluate the clinical usefulness of serum SCCA levels as a serological marker for early detection of HCC among high-risk patients compared to AFP. MATERIALS AND METHODS: The study comprised of three groups. Group A included 30 patients with CLD diagnosed based on clinical, laboratory, and ultrasonographical investigations; group B included 49 patients with HCC diagnostically confirmed by spiral CT, elevated alfafetoprotein (AFP), and/or liver biopsy; and group C, the control group, included 15 healthy subjects matched for age and sex. All groups were subjected to thorough history taking, full clinical examination, and laboratory investigations including liver functions, viral markers, and AFP and SCCA estimation using ELISA technique. RESULTS: This study revealed a highly significant difference between patients with HCC, CLD, and controls regarding serum SCCA levels (5.138 +/- 7.689, 1.133 +/- 0.516, and 0.787 +/- 0.432 ng/ml, respectively). SCCA level was persistently elevated in patients with HCC with normal AFP levels representing its useful role in early detection and follow-up of patients treated for HCC. The area under the curve (AUC) of SCCA was 0.869 (95% CI 0.783-0.929), the cut-off value was established at 1.5 ng/ml with sensitivity of 77.6% and specificity of 84.4%). The difference between AUC of SCCA and that of AFP was 0.09 which mounted statistical significance. CONCLUSIONS: SCCA could represent a useful tool as a marker for detection of HCC.

Hepatoid carcinoma of the gallbladder.

Hepatoid carcinoma is a special type of extrahepatic tumor associated with hepatic differentiation, and has the morphological and functional features of hepatocellular carcinoma. Hepatoid carcinoma of the gallbladder is very rarely reported in the literature. We report a case of hepatoid carcinoma of the gallbladder in a 71-year-old female who presented with abdominal pain and was first diagnosed as cholelithiasis with cholecystitis. The microscopic findings of the gallbladder after cholecystectomy showed an area of tumor with polygonal cells, eosinophilic cytoplasm, distinct cell borders, round vesicular nuclei and prominent nucleoli, arranged in trabecular pattern resembling hepatocellular carcinoma intermingled with areas of adenocarcinoma or cholangiocarcinoma. The specimen from the pancreas also showed the same type of tumor cells. Histochemically, some of tumor cells were positive for Victoria Blue, Stein, and PAS. The immunohistochemistry for alpha-fetoprotein (AFP) showed strong intra cytoplasmic positivity, both in tumor cells with hepatic differentiation and tumor cells with bile duct epithelium differentiation. Based on these findings, this case was diagnosed as hepatoid carcinoma of the gallbladder with metastasis to the pancreas. This is the first case that has been reported in our department.

Endodermal sinus tumour of stomach--a case report.

This is a case report of an endodermal sinus tumour arising in the stomach of a 1 1/2 years male child. The tumour occupied full thickness of fundus and part of the body of the stomach. H&E sections of the tumour tissue showed endodermal sinus tumour with predominantly reticular and endodermal sinus patterns. Elevated level of alpha-fetoprotien was detected in the serum of the patient and within the tumour tissue by immunohistochemical technique.