Hiroto Nishimata

Signet-ring cell carcinoma of the colon 7mm in size with peritonitis carcinomatosa.

A 72-year-old woman was admitted with a complaint of a sensation of abdominal fullness. Cytologic examination of ascites revealed many poorly differentiated adenocarcinoma cells. Barium enema study and colonoscopy revealed IIa+IIc-type carcinoma of the descending colon. Endoscopic mucosal resection was performed to determine the histological type and the depth of invasion. The resected tumor was 7 x 6 mm in size, and an amorphous pit pattern was observed in the depressed area by stereomicroscopy. Poorly differentiated adenocarcinoma with signet-ring cells had diffusely infiltrated into the deeper part of the submucosal layer. Immunohistochemical findings showed this tumor to have mucin derived from gastric foveolar epithelium, suggesting that the signet-ring cell carcinoma of the colon showed gastric differentiation. Primary signet-ring cell carcinoma of the colon and rectum is a rare form of adenocarcinoma of the large intestine and shows more malignant biological behavior than ordinary colorectal carcinoma. Early diagnosis and curative operation are important.

Angiopoietin-like protein 2 is a potential biomarker for gastric cancer.

Globally, gastric cancer is one of the most common types of cancer and is the second leading cause of cancer‑induced mortality. Early detection of gastric cancer is able to contribute to a reduction of its mortality. For early detection, more specific and sensitive biomarkers than the classic biomarkers, including carcinoembryonic antigen, carbohydrate antigen 19‑9 and C‑reactive protein, are required. The present study focused on the evaluation of the potential of angiopoietin‑like protein 2 (ANGPTL2) as a novel biomarker for gastric cancer. The expression levels of ANGPTL2 in undifferentiated and differentiated gastric cancer cell lines (HGC‑27 and MKN7, respectively) were therefore investigated. Additionally, ANGPTL2 levels in the serum of gastric cancer patients were compared with those of healthy individuals to evaluate the possibility of the protein as a predictive biomarker for gastric cancer. It was established that the expression levels of ANGPTL2 mRNA and protein were higher in undifferentiated HGC‑27 cells than those in differentiated MKN7 cells. In a patient study, it was indicated that the levels of ANGPTL2 in the serum of gastric cancer patients were higher than those in healthy controls. The diagnostic performance of ANGPTL2 was assessed by constructing a receiver operating characteristic (ROC) curve and was evaluated by calculating the area under each ROC curve (AUC). For the discrimination of patients with gastric cancer from healthy individuals, the AUC for ANGPTL2 was 0.774 (P=0.005) (95% confidence interval, 0.615‑0.933). These results suggested that ANGPTL2 was a potential biomarker for gastric cancer.

Necrotic regions are absent in fiber-shaped cell aggregates, approximately 100 μm in diameter

Microscopic, fiber-shaped cell aggregates, have been used as building blocks for fabricating macroscopic three-dimensional tissue architectures, in the field of tissue engineering. In this study, we examined the occurrence of necrotic regions in the most widely used, fiber-shaped cell aggregates, approximately 100 μm in diameter. Alginate hydrogel hollow microfibers were used as templates for the cell aggregates. We demonstrated negligible necrotic region formation occurred in the cell aggregates formed in the hollow microfibers. Furthermore, we improved on previously-reported methods for preparing the hollow microfibers to avoid common microfiber tangling during the fiber preparation process.

Combined assessment of serum folate and hemoglobin as biomarkers of brain amyloid ß accumulation.

A relationship between Alzheimers disease (AD) and folate has been reported. Amyloid positron emission tomography (PET) is currently one of the most reliable biomarkers for AD. We investigated the correlation between serum folate levels and amyloid imaging to clarify whether serum folate could be a biomarker for AD. We also examined the usefulness of a combined assessment of serum folate levels and red blood cell hemoglobin content. Apolipoprotein E (APOE) gene polymorphisms were also assessed. Serum folate levels and hemoglobin content were evaluated by receiver operating characteristic analysis for their diagnostic capability as AD biomarkers relating to brain amyloid β accumulation. The area under the ROC curve (AUC) for serum folate was 0.136 (95% confidence interval [CI]: 0.000–0.312; p = 0.016). The AUC for hemoglobin content was 0.848 (95% CI: 0.661–1.000; p = 0.021). Therefore, the folate deficiency with low folate levels or the non-anaemia with high hemoglobin content levels were found to have a high probability of also testing positive for amyloid. Furthermore, eight patients were found to be folate deficiency and non-anaemia, those who were consist of 7 amyloid positive patients (87.5%), and only one of the amyloid negative patients (12.5%). These results suggest that a deficiency of serum folate and high hemoglobin levels may reflect an increased risk of amyloid β accumulation in the brain. Additionally, we demonstrated that these biomarkers could enhance the effectiveness of APOE as an AD biomarker. This study reveals that the combined assessment of serum folate levels and red blood cell hemoglobin content may be a useful biomarker for amyloid β accumulation in the brain. We also found that the combination of serum folate levels and hemoglobin content is a more specific and sensitive blood biomarker for AD than APOE or folate alone. These findings may be used to support clinical diagnosis of AD using a simple blood test.

CASE REPORT: Successful Balloon-Occluded Retrograde Transvenous Obliteration for Ruptured Gastric Fundal Varices in a Patient with Child–Pugh C Cirrhosis: Case Report and Literature Review

The rupture of gastroesophageal varices is one of the leading causes of death in cirrhotic patients. Once gastric fundal varices bleed, the mortality rate is particular very high. Surgical procedures such as Hassab’s devascularization and transection have a limitation in urgent treatment of ruptured gastric varices because of poor underlying hepatic reserves. Endoscopic sclerotherapy, transjugular intrahepatic portsystemic shunt, and percutaneous transhepatic obliteration for ruptured gastric fundal varices can achieve temporary hemostasis but have unsatisfactory results and many complications. Child–Pugh C patients with bleeding from gastric fundal varices, in particular, have a higher mortality rate compared with Child A or B patients. Balloon-occluded retrograde obliteration with ethanolamine oleate–iopamidol is a promising treatment for ruptured gastric fundal varices. A case of successful balloon-occluded retrograde transvenous obliteration and the follow-up management for ruptured gastric fundal varices in a patient with Child–Pugh C cirrhosis is reported, and the literature reviewed.

Use of ANGPTL2 mRNA levels in formalin‑fixed paraffin‑embedded tissues as a biomarker to diagnose gastric cancer and to evaluate the extent of vascular invasion

With the recent advances in medical technologies, gastric cancer can often be removed with minimally invasive surgical techniques when identified early. Surgery must remove all gastric cancer, since residual cancerous tissue may lead to recurrence. Resected cancerous tissues are pathologically evaluated to determine whether all cancerous areas have been removed, but such assessments are rarely straightforward, and cancer markers could inform such pathological evaluations of cancer. An ideal marker would be identifiable in formalin-fixed paraffin-embedded (FFPE) tumor tissue. The first objective of the present study was to compare levels of angiopoietin-like protein 2 (ANGPTL2) in cancerous and noncancerous areas of FFPE tissues to determine whether ANGPTL2 is a marker relevant to the pathological diagnosis of cancer. The second objective was to evaluate whether ANGPTL2 mRNA is useful as a marker of the extent of vascular invasion of gastric cancer. Out of the 15 patients studied, 12 had a higher ANGPTL2 mRNA levels in cancerous areas compared with noncancerous areas. This finding indicated that ANGPTL2 mRNA is useful as a biomarker for identifying cancerous areas in FFPE tissues, at least for male patients. Spearmans rank correlation analysis showed a significant correlation between the ANGPTL2 mRNA level and the degree of vascular invasion of cancer (r=0.66; P=0.01). In receiver operating characteristic curve analysis of the association between the ANGPTL2 mRNA level and the degree of vascular invasion, the area under the curve was 0.92 (95% confidence interval, 0.78-1.00; P=0.01), indicating a significant association. The present study demonstrates that ANGPTL2 mRNA in FFPE tissues is a potential biomarker that informs the pathological diagnosis of gastric cancer and that ANGPTL2 mRNA may be predictive of vascular invasion, which is an indicator of metastasis in gastric cancer.

Minute carcinoma of the pancreas presenting as pancreatic pleural effusion.

A 70-year-old Japanese man with no history of pancreatitis visited his local practitioner, complaining of dyspnea on effort. Left massive pleural effusion was detected and he was then referred to our hospital. A plain chest film showed marked left pleural effusion. Thoracentesis yielded 2000 ml of bloody fluid with high amylase content (22 665 IU/l). Endoscopic retrograde pancreatography revealed a tapered occlusion of the main pancreatic duct. Pancreatic cancer was suspected, and a distal pancreatectomy and a splenectomy were performed. Histologically, the diagnosis was ductal adenocarcinoma of the pancreas, 5 × 6 mm in size, with regional lymph node metastasis. He has experienced no recurrence of cancer or pleural effusion since the operation.

Abstracts of selected papers presented at the 77th General Meeting of the Japanese Society of Gastroenterology

M E E T I N G OF T H E J A P A N E S E S O C I E T Y OF G A S T R O E N T E R O L O G Y March 28-30, 1991-Tokyo, Japan Chairman: Yutaka MATSUO, M.D.

Abnormality of serum immunoglobulins in chronic liver disease-immune complex like substances, abnormaly basic γ-globulin, secretory IgA and anti-DNA antibody

1) Serum secretory IgA was reduced in chronic liver disease while it was increased in obstructive jaundice. 2) Serum anti-dsDNA antibody was slightly increased in chronic liver disease, especially it was significantly increased in lupoid hepatitis in which its titer paralelled with the course of disease activity. 3) Serum Clq binding activity, Clq binding inhibition activity and polyclonal rheumatoid factor binding inhibition activity were increased in chronic liver disease and their disease activity was correlated with concentration of macromolecular immune complexes which were fractionated with sucrose density gradient ultracentrifugation. 4) Abnormally basic y-globulin which was dominantly found in chronic hepatitis B sera was determined to be monomeric IgG. I t was increased in aggravation of the disease but has no correlation with Clq binding monomeric IgG. 5) Liver membrane specific lipoprotein (LP-1), Espinosas liver specific antigen (LSA), Nerenbergs hepatorenal antigen (HRA) and Tamm-Horsfall glycoprotein (THGP) had positive charge, and LP-2 and F-antigen did negative charge. 6) Human liver cell membrane fraction could not be obtained by the method of Ray or aqueous two phase polymer system which have been used for rat liver.