[An autopsy case of nasal-type primary gastric extranodal NK/T-cell lymphoma with early liver failure].

An 82-year-old woman was admitted to the hospital because of tiredness and fever. She was diagnosed with acute hepatitis. Although the cause of acute hepatitis was undetermined, her health condition and liver function improved, and she was discharged. Four weeks later, she was hospitalized again because of anorexia. Laboratory data revealed worsened anemia. Endoscopy results revealed a huge ulcerative lesion in the lesser curvature of the stomach. After 4 days, she vomited blood and died of hemorrhagic shock. The autopsy revealed a nasal-type primary gastric extranodal NK/T-cell lymphoma (ENKTL). Although no lymphoma cells were found in the liver biopsy collected during the first hospitalization, lymphoma cells and lymphocytes in the liver tissue were identified during autopsy because the lymphoma had infiltrated the liver. Primary gastric ENKTL is extremely rare and poorly understood. However, the general prognosis of progressive ENKTL is poor. Early diagnosis of liver metastasis of lymphoma cells is difficult;thus, in some cases, lymphoma metastases to the liver are diagnosed during autopsy. Although further experiments are required, we report a rare case of primary gastric ENKTL.

A case of recurrence of a solid pseudopapillary neoplasm of the pancreas effectively treated with proton beam radiotherapy.

We report a case of a male in his 50 s who underwent pancreaticoduodenectomy for solid pseudopapillary neoplasm (SPN) of the pancreas at 30 years. He developed a liver abscess 15 years after the surgery, and CT scan revealed a swollen retroperitoneum lymph node and a tumor in the liver. Symptoms, including abdominal distension, appetite loss, and epigastric pain, appeared due to lymph node metastasis. Endoscopic ultrasonography-guided fine-needle aspiration against the lymph node revealed SPN recurrence. The tumor had invaded the common hepatic artery, and surgery was not indicated. Chemotherapy of Gemcitabine/nab-Paclitaxel biweekly was performed 8 times; however, no reduction in tumor size was observed, and the patient's symptoms worsened. Proton beam therapy (67.5 GyE in 25 fractions) was subsequently performed for lymph node metastasis, and led to a gradual reduction in lymph node metastasis, and an improvement in symptoms. No re-expansion of lymph node metastasis has been observed 3 years after proton beam therapy. Since SPN is low malignancy and most cases can be expected to be cured by surgery, there is currently no standard treatment of unresectable SPN. This case is the first report of proton beam therapy for SPN, and was considered to be effective.

[Mesalazine-induced myocarditis].

A 30-year-old man presented with constipation and abdominal pain. He was suspected of having ulcerative colitis, and administration of 2400mg/day of oral mesalazine was initiated. After 10 days of treatment, he experienced fever and chest pain. Blood examination, electrocardiography, and cardiac ultrasonography revealed elevated cardiac enzymes, ST-segment elevation, and diffuse hypokinesis, respectively. Mesalazine-induced acute myocarditis was diagnosed based on a positive drug-induced lymphocyte stimulation test and the absence of other myocarditis-causing conditions. Prompt cessation of mesalazine quickly improved his heart function and test results. Although rare, clinicians should consider the possibility of cardiac adverse events caused by mesalazine.

Endoscopic ultrasonography-guided drainage of infected intracystic papillary adenocarcinoma of the liver.

We describe a case of effective use of endoscopic ultrasonography (EUS)-guided drainage of an infected intracystic papillary adenocarcinoma (ICPA) of the liver. The patient was an 84-year-old woman who was admitted with complaints of continuous epigastric pain and a slight fever. Laboratory data revealed severe inflammation. Computed tomography scanning showed a 110-mm cystic lesion with enhanced papillary tumors in the medial segment of the liver associated with a cyst in the right lobe and subcapsular cyst of the liver. Streptococcus species were detected in the culture of cystic fluid, and a diagnosis of infected ICPA was suspected. Although the patient was medicated by antibiotics, the fever did not resolve. EUS-guided transgastric drainage was performed for the abscess of the medial segment of the liver. Fourteen days after the endoscopic procedure, the plastic drainage tube was replaced with a metal stent. Inserting an endoscope into the liver cyst through the metal stent permitted observation and biopsy of an intracystic tumor, and the diagnosis of ICPA was confirmed. The patient was discharged with the internal metal stent still in place.

Extensive lanthanum deposition in the gastric mucosa: the first histopathological report.

Lanthanum carbonate is one of the new phosphate binders used for the treatment of hyperphosphatemia in patients with chronic kidney disease. It is poorly absorbed from the gastrointestinal tract, forms insoluble complexes within the lumen, and prevents the absorption of dietary phosphate. A 63-year-old female with a 7-year history of peritoneal dialysis, who was treated with lanthanum carbonate for four years, underwent endoscopic submucosal dissection for intramucosal gastric cancer. Resected specimens showed massive accumulation of macrophages containing fine, granular, brown material in the lamina propria. This was confirmed as lanthanum deposition by scanning electron microscopy with energy dispersive x-ray spectroscopy. Although lanthanum may be poorly absorbed, increased tissue accumulation of lanthanum, particularly in the liver and bone, has been reported in animals with chronic kidney disease. This report indicates enhanced gastrointestinal absorption of lanthanum in some patients or conditions, although its clinical significance awaits further studies.

ROS-generating oxidases Nox1 and Nox4 contribute to oncogenic Ras-induced premature senescence.

Activated oncogenes induce premature cellular senescence, a permanent state of proliferative arrest in primary rodent and human fibroblasts. Recent studies suggest that generation of reactive oxygen species (ROS) is involved in oncogenic Ras-induced premature senescence. However, the signaling mechanism controlling this oxidant-mediated irreversible growth arrest is not fully understood. Here, we show that through the Ras/MEK pathway, Ras oncogene up-regulated the expression of superoxide-generating oxidases, Nox1 in rat REF52 cells and Nox4 in primary human lung TIG-3 cells, leading to an increase in intracellular level of ROS. Ablation of Nox1 and Nox4 by small interfering RNAs (siRNAs) blocked the RasV12 senescent phenotype including ß-galactosidase activity, growth arrest and accumulation of tumor suppressors such as p53 and p16Ink4a. This suggests that Nox-generated ROS transduce senescence signals by activating the p53 and p16Ink4a pathway. Furthermore, Nox1 and Nox4 siRNAs inhibited both Ras-induced DNA damage response and p38MAPK activation, whereas overexpression of Nox1 and Nox4 alone was able to induce senescence. The involvement of Nox1 in Ras-induced senescence was also confirmed with embryonic fibroblasts derived from Nox1 knockout mice. Together, these findings suggest that Nox1- and Nox4-generated ROS play an important role in Ras-induced premature senescence, which may involve DNA damage response and p38MAPK signaling pathways.

[A case of unilocular serous cystic neoplasm mimicking mucinous cystic neoplasm].

A 40's woman had a cystic lesion in the tail of the pancreas that had grown over a 1.5-year period. Endoscopic ultrasound revealed a partition structure and "cyst-in-cyst" like lesion, and a diagnosis of mucinous cystic neoplasm was made. The patient underwent distal pancreatectomy with splenectomy. Following histological examination, our final diagnosis was revised to unilocular serous cystic neoplasm since the increase in cysts was due to hemorrhage and the partition structure was in fact granulation tissue. We here discuss this rare case with reference to previous published reports.

[Annular pancreas with high confluence of pancreaticobiliary ducts in an adult].

A man in his 80's was admitted complaining of epigastralgia, and acute pancreatitis was diagnosed. Abdominal CT and MRI showed enlargement of the pancreatic head encircling the descending part of the duodenum and a duodenal diverticulum. Endoscopic retrograde cholangio-pancreatography (ERCP) revealed annular pancreas and high confluence of pancreaticobiliary ducts. Annular pancreas had been reported to have associated with a broad spectrum of pancreatic anomalies, few cases of annular pancreas coexisting with high confluence of pancreaticobiliary ducts, or pancreaticobiliary maljunction have been reported. Combination of both anomalies was interesting from the view point of embryology. We report a rare case of annular pancreas with high confluence of pancreaticobiliary ducts.

Small bowel tissue concentration of rebamipide: study of two dosages in healthy subjects.

Non-steroidal anti-inflammatory drug (NSAID)-related small intestinal complications exist, since developed new diagnostic modalities, such as balloon and capsule endoscopies. Some experiments have shown rebamipide to protect from NSAID-induced small intestinal complications. The purpose of this study is to investigate whether the effective concentrations of rebamipide (COR) are present in the small intestine after taking an ordinary clinical dose and double dose of this drug. Twelve healthy male subjects were enrolled. After taking 100 or 200 mg of rebamipide, balloon enteroscopy was performed at 1 and 3 h, and biopsy samples were obtained from the jejunum and the stomach. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The mean COR in the jejunum was higher than 100 µM at 1 h and higher than 10 µM at 3 h in both the 100 and 200 mg groups. Mean COR in the stomach was less than 100 µM at 1 h in the 100 mg group; however it was higher than 100 µM in the 200 mg group. In conclusion, the COR level in the jejunum was sufficient to protect for NSAID-induced gastrointestinal complications.

Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND: To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens. METHODS: The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively. RESULTS: Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements. CONCLUSIONS: This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.

Abscess of the round ligament of the liver associated with acute obstructive cholangitis and septic thrombosis.

A man with abscess of the round ligament of the liver associated with acute obstructive suppurative cholangitis and portal thrombosis is reported. A 63-year-old man was admitted with epigastralgia and high fever. Blood tests showed elevation of hepato-biliary enzymes and coagulopathy consistent with acute obstructive suppurative cholangitis and disseminated intravascular coagulation. Computed tomography revealed a small abscess of the round ligament of the liver and left portal thrombosis. After endoscopic biliary stenting, antibiotics and thrombolytic therapy, the high fever, disseminated intravascular coagulation and portal thrombosis rapidly improved, and the round ligament abscess was also later resolved.

Pancreaticobiliary fistula associated with pancreatolithiasis.

We report here a case of pancreaticobiliary fistula associated with pancreatolithiasis. A 47-year-old female without a habit of alcohol drinking was admitted by her family physician after suffering from mild acute pancreatitis. Computed tomography revealed mild acute pancreatitis with pancreatolithiasis at the head of the pancreas. The pancreatolithiasis was exposed to the inner surface of the common bile duct and possibly compressed and narrowed the Wirsung and Santorini ducts, resulting in the pancreatitis attack. We used extracorporeal shock wave lithotripsy to treat the pancreatolithiasis. After complete elimination of stones by extracorporeal shock wave lithotripsy, endoscopic retrograde cholangiography showed an apparent pancreaticobiliary fistula between a branch of the Santorini duct and the lower portion of the common bile duct. There was no communication between the bile duct and the Wirsung duct or its branches; therefore, the diagnosis was not pancreaticobiliary maljunction. There have only been a few reports of pancreaticobiliary fistula without an association with pancreatic pseudocysts or intraductal papillary-mucinous pancreatic neoplasm, and there have only been few reports of pancreaticobiliary fistula with pancreatolithiasis.

Intestinal diffuse large B-cell lymphoma associated with celiac disease: a Japanese case.

Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well known to be associated with celiac disease (CD), an enteropathic disorder with a propensity for certain racial and genetic backgrounds. CD is typically characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies in the sera, and microscopical findings of the intestinal mucosa, which resolve with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD and the associated NHL have been supposed to be quite rare, and studies concerning the frequency of CD or its relationship with NHL are scarce. We describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma associated with CD. Following multi-combined chemotherapy, the patient's lymphoma has been in a state of complete response, and his GI symptoms have improved with a GFD. This case suggests that the possibility of CD and its association with intestinal NHL should be kept in mind, even in Asian populations.