Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach.

Gastric cancer is one of the most common malignancies worldwide. In this study, we screened for genes upregulated in gastric cancer by comparing gene expression profiles from serial analysis of gene expression and microarray and identified the palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) gene. Immunostaining for PLUNC in 140 gastric cancer cases revealed strong and extensive staining of PLUNC in hepatoid adenocarcinoma of the stomach, whereas 7% of conventional gastric cancer cases showed focal immunostaining of PLUNC. Gastric hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphologic similarities to hepatocellular carcinoma. To investigate the utility of PLUNC immunostaining in the diagnosis of gastric hepatoid adenocarcinoma, six cases of gastric hepatoid adenocarcinoma (six primary tumors and two associated liver metastases) were studied further. PLUNC staining was observed in all six primary hepatoid adenocarcinomas. PLUNC staining was observed in both the hepatoid adenocarcinoma and tubular/papillary adenocarcinoma components of primary tumors, although PLUNC staining was preferentially localized in tubular/papillary adenocarcinoma components. Staining of PLUNC was also detected in both liver metastases. PLUNC staining was not observed in 52 cases of primary hepatocellular carcinoma or in normal adult or fetal liver. These results indicate that PLUNC is a novel marker that distinguishes gastric hepatoid adenocarcinoma from primary hepatocellular carcinoma.     

Mitochondrial abnormalities of muscle tissue in mice with juvenile visceral steatosis associated with systemic carnitine deficiency

A mouse with juvenile visceral steatosis (the JVS mouse) has been recognized as a novel animal model for systemic carnitine deficiency. We examined cardiac, skeletal and smooth muscle cells in JVS and control mice by light and electron microscopy. Cardiac and skeletal muscle cells of these mice at 4 weeks of age exhibited a ragged-red appearance after trichrome staining. Electron microscopy, demonstrated increased numbers of mitochondria and lipid droplets in the cells. Compression or distortion of the myofibril bundles, primarily due to the increased number of mitochondria, suggests the possible existence of a functional disturbance of the cardiac and skeletal muscle. In the urinary bladder, only one or two large lipid droplets and slightly increased number of mitochondria were recognized in the perinuclear region of the smooth muscle cells. At 8 weeks of age, the mouse enzyme histochemistry specific for mitochondria, such as cytochrome c oxidase and succinic dehydrogenase, and oil red O staining, confirmed further increases in the number of mitochondria and lipid droplets in the heart. However, the accumulation of these organelles in the skeletal and smooth muscle cells was no greater than that noted in JVS mice at 4 weeks of age. In the cardiac muscle cells, autolysosomes or autophagic vacuoles containing electron-dense membranous, lamellar or whorled structures closely associated with mitochondria and pseudoinclusion bodies in the nucleus were recognized, and bundles of myofibrils were buried under numerous mitochondria, suggesting the existence of disturbed contractile function in the heart of JVS mice. These results indicate that this murine strain associated with systemic carnitine deficiency exhibits a generalized mitochondrial abnormality in the muscle system especially in the heart.     

Closure method for thick pancreas stump after distal pancreatectomy: soft coagulation and polyglycolic acid felt with fibrin glue

Purpose

Pancreatic fistula (PF) remains an obstacle to safe distal pancreatectomy (DP). A thick pancreatic parenchyma is a major risk factor for PF. In this paper, we elucidate the feasibility of the new closure method using soft coagulation and polyglycolic acid felt with fibrin glue.

Methods

In 2009–2013, 96 patients underwent DP with a novel closure method for pancreatic stump that utilized soft coagulation and polyglycolic acid felt with fibrin glue. We evaluated amylase levels in drainage fluid on postoperative days (POD) 1 and 3 and the incidence of postoperative PF according to International Study Group of Pancreatic Fistula (ISGPF) definitions.

Results

Drain amylase levels on POD1 and POD3 were 275 and 241 U/L, respectively, and ISGPF-defined Grade B/C PF rates were 16.7 %. No clinical factors were significantly associated with PF. Average pancreatic parenchymal thicknesses were similar in PF-positive and PF-negative patients (10.4?±?2.6 mm vs. 10.1?±?2.2 mm, P?=?0.639). There was no significant difference in the postoperative PF rate between patients with thick (≥12 mm) and thin (<12 mm) pancreas (11.1 vs. 18.8 %, P?=?0.544).

Conclusion

Our novel pancreatic stump closure method appears to be simple and effective, particularly in patients with thick pancreas.

     

Serum Levels of Intact Parathyroid Hormone Is a Prognostic Indicator of Dialyzed Patients: The Nishinomiya Study

Patients with chronic kidney disease on dialysis are at higher risk for cardiovascular disease (CVD), which is the greatest cause of mortality. The target range of serum intact parathyroid hormone (iPTH) for prognosis, 60 to 240 pg/mL, was recommended by the Japanese Society for Dialysis Therapy guidelines. To investigate the impact of this iPTH target on CVD, dialysis patients were enrolled. A total 287 participants were observed. At the start of the study, serum iPTH levels, routine laboratory parameters, and certain factors related to CVD were evaluated. A survival analysis (Kaplan–Meier curve) was used. After 10 years of follow‐up, 19.2% of patients had CVD. The subjects were divided into three groups according to their iPTH level at baseline based on the target range of 60 to 240 pg/mL: Low, Middle, and High groups. CVD was more common in the High and Low groups compared to the Middle group. A lower risk of CVD was evident in the extended dialysis patients with a range of 60 to 240 pg/mL iPTH. Further studies are needed to evaluate the impact of the iPTH level on poor outcome.     

Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac effectively prevent colon cancer in humans and rodent models. However, their cellular targets and underlying mechanisms have remained elusive. We found that dietary sulindac induced apoptosis to remove the intestinal stem cells with nuclear or phosphorylated β-catenin in APC(Min/+) mice. NSAIDs also induced apoptosis in human colonic polyps and effectively removed cells with aberrant Wnt signaling. Furthermore, deficiency in SMAC, a mitochondrial apoptogenic protein, attenuated the tumor-suppressive effect of sulindac in APC(Min/+) mice by blocking apoptosis and removal of stem cells with nuclear or phosphorylated β-catenin. These results suggest that effective chemoprevention of colon cancer by NSAIDs lies in the elimination of stem cells that are inappropriately activated by oncogenic events through induction of apoptosis.     

Alpha-fetoprotein-producing clear cell carcinoma of the gallbladder with neuroendocrine differentiation

An uncommon case of alpha-fetoprotein (AFP) producing clear cell carcinoma of the gallbladder with neuroendocrine differentiation in a 78-year-old Japanese woman, who complained of epigastralgia, is reported. Macroscopically, the nodular infiltrative type of tumor, measuring approximately 4.5 × 3.5 cm in size, was located in the fundus of the gallbladder. Histologically, the tumor was composed of clear cell carcinoma with AFP production, non-clear cell adenocarcinoma with neuroendocrine differentiation, and poorly or undifferentiated carcinoma with extensive ulceration. Carcinoma in situ was found in the surrounding gallbladder epithelium. Her postoperative laboratory tests showed a decrease in AFP levels to normal. The clinical and pathologic significance of AFP production or neuroendocrine differentiation in the gallbladder carcinomas have thus far remained completely obscure. However, we should recognize the entity of this tumor because the accurate diagnosis of primary clear cell carcinoma of the gallbladder may have important therapeutic implications.