Jun Nagata

Inflammasome-mediated regulation of hepatic stellate cells

The inflammasome is a cytoplasmic multiprotein complex that has recently been identified in immune cells as an important sensor of signals released by cellular injury and death. Analogous to immune cells, hepatic stellate cells (HSC) also respond to cellular injury and death. Our aim was to establish whether inflammasome components were present in HSC and could regulate HSC functionality. Monosodium urate (MSU) crystals (100 microg/ml) were used to experimentally induce inflammasome activation in LX-2 and primary mouse HSC. Twenty-four hours later primary mouse HSC were stained with alpha-smooth muscle actin and visualized by confocal microscopy, and TGF-beta and collagen1 mRNA expression was quantified. LX-2 cells were further cultured with or without MSU crystals for 24 h in a transwell chemotaxis assay with PDGF as the chemoattractant. We also examined inhibition of calcium (Ca(2+)) signaling in LX-2 cells treated with or without MSU crystals using caged inositol 1,4,5-triphosphate (IP(3)). Finally, we confirmed an important role of the inflammasome in experimental liver fibrosis by the injection of carbon tetrachloride (CCl(4)) or thioacetamide (TAA) in wild-type mice and mice lacking components of the inflammasome. Components of the inflammasome are expressed in LX-2 cells and primary HSC. MSU crystals induced upregulation of TGF-beta and collagen1 mRNA and actin reorganization in HSCs from wild-type mice but not mice lacking inflammasome components. MSU crystals inhibited the release of Ca(2+) via IP(3) in LX-2 cells and also inhibited PDGF-induced chemotaxis. Mice lacking the inflammasome-sensing and adaptor molecules, NLRP3 and apoptosis-associated speck-like protein containing CARD, had reduced CCl(4) and TAA-induced liver fibrosis. We concluded that inflammasome components are present in HSC, can regulate a variety of HSC functions, and are required for the development of liver fibrosis.

The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma

The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca(2+) signaling in epithelia and regulates cellular functions such as secretion, apoptosis and cell proliferation. Loss of one or more InsP3R isoform has been implicated in disease processes such as cholestasis. Here we examined whether gain of expression of InsP3R isoforms also may be associated with development of disease. Expression of all three InsP3R isoforms was evaluated in tissue from colorectal carcinomas surgically resected from 116 patients. Type I and II InsP3Rs were seen in both normal colorectal mucosa and colorectal cancer, while type III InsP3R was observed only in colorectal cancer. Type III InsP3R expression in the advancing margins of tumors correlated with depth of invasion, lymph node metastasis, liver metastasis, and TNM stage. Heavier expression of type III InsP3R also was associated with decreased 5-year survival. shRNA knockdown of type III InsP3R in CACO-2 colon cancer cells enhanced apoptosis, while over-expression of the receptor decreased apoptosis. Thus, type III InsP3R becomes expressed in colon cancer, and its expression level is directly related to aggressiveness of the tumor, which may reflect inhibition of apoptosis by the receptor. These findings suggest a previously unrecognized role for Ca(2+) signaling via this InsP3R isoform in colon cancer.

Giant Adrenal Myelolipoma in a Patient without Endocrine Disorder: A Case Report and a Review of the Literature

We herein present a surgically treated case of huge adrenal myelolipoma. A 62-year-old woman presented to our surgical outpatient clinic with a retroperitoneal tumor. A clinical examination revealed an elastic soft, smooth-surfaced, painless, child-head-sized tumor with poor mobility, which was located in the left upper abdomen. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed an uneven tumor surrounding the stomach, spleen, pancreas, and left kidney, which was 20 × 18 × 10 cm in size. The retroperitoneal tumor was resected. The tumor was attached to the surrounding organs, including the pancreas, spleen, and left kidney, but had not directly invaded these organs. The tumor was yellow and elastic soft and covered with a thin film. The origin of the tumor was suggested to be the left adrenal gland. The weight of the excised tumor was 1500 g. The histopathological diagnosis was adrenal myelolipoma. The patient had an uneventful recovery and was discharged from the hospital on the thirteenth day after the operation. She has been followed up in our outpatient clinic.

Novel technique of abdominal wall nerve block for laparoscopic colostomy: Rectus sheath block with transperitoneal approach

A 62-year-old man who had acute rectal obstruction due to a large rectal cancer is presented. He underwent emergency laparoscopic colostomy. We used the laparoscopic puncture needle to inject analgesia with the novel transperitoneal approach. In this procedure, both ultrasound and laparoscopic images assisted with the accurate injection of analgesic to the correct layer. The combination of laparoscopic visualization and ultrasound imaging ensured infiltration of analgesic into the correct layer without causing damage to the bowel. Twenty-four hours postoperatively, the patient’s pain intensity as assessed by the numeric rating scale was 0-1 during coughing, and a continuous intravenous analgesic was not needed. Colostomy is often necessary in colon obstruction. Epidural anesthesia for postoperative pain cannot be used in patients with a coagulation disorder. We report the use of a novel laparoscopic rectus sheath block for colostomy. There has been no literature described about the nerve block with transperitoneal approach. The laparoscopic rectus sheath block was performed safely and had enough analgesic efficacy for postoperative pain. This technique could be considered as an optional anesthetic regimen in acute situations.

Perforated Jejunal Diverticulum Treated by Exteriorization in An Adult Patient with Alcoholic Psychosis: A Case Report

We herein describe a surgical case of perforated jejunal diverticulum in an adult patient with alcoholic psychosis and dementia. A 70-year-old Japanese male presented with vomiting and abdominal pain in a mental hospital. He had undergone a distal gastrectomy, the details of which are unclear. He entered the internal medicine ward of our hospital and was diagnosed with bowel obstruction and conservatively treated with a long tube. At the 4th hospital day, he suffered from severe abdominal pain with muscular defense. Computed tomography revealed a dilated small intestine and intra-abdominal free air and ascites. After laparotomy, a perforated jejunal diverticulum was identified at 30 cm along the anal side from the ligament of Treitz. Adhesiolysis and exteriorization of the perforated jejunal diverticulum using a tube were performed, as the status of the patient was too serious to tolerate resection of the small intestine including the perforated lesion. The patient eventually recovered and left the hospital on Day 37 after the operation. This report presents a rare surgical case of perforated jejunal diverticulum due to small bowel obstruction in an adult patient with alcoholic psychosis and dementia.

Transperitoneal rectus sheath block and transversus abdominis plane block for laparoscopic inguinal hernia repair: A novel approach

A laparoscopic approach for inguinal hernia repair is now considered the gold standard. Laparoscopic surgery is associated with a significant reduction in postoperative pain. Epidural analgesia cannot be used in patients with perioperative anticoagulant therapy because of complications such as epidural hematoma. As such, regional anesthetic techniques, such as ultrasound‐guided rectus sheath block and transversus abdominis plane block, have become increasingly popular. However, even these anesthetic techniques have potential complications, such as rectus sheath hematoma, if vessels are damaged. We report the use of a transperitoneal laparoscopic approach for rectus sheath block and transversus abdominis plane block as a novel anesthetic procedure.

Duodenal Gastrointestinal Stromal Tumor Treated by Wedge Resection: A Case Report

This report describes a patient with a duodenal gastrointestinal stromal tumor (GIST). A 77-year-old Japanese male presented with abdominal fullness and weight loss. Computed tomography (CT) of the abdomen demonstrated an enhanced mass, 4 × 3 cm in size, at the right side of the inferior vena cava. An endoscopic examination revealed a duodenal submucosal tumor. He was referred to the surgical outpatient clinic for surgical treatment of a duodenal submucosal tumor. Laparotomy allowed for the identification of a nut-sized extramural tumor at the second portion of the duodenum. Wedge resection of the duodenum including the tumor was performed. A histopathological examination revealed that the tumor was composed of a proliferation of spindle cells with spindle nuclei and eosinophilic fibrillar cytoplasm, arranged in fascicles with a hypercellular area. An immunohistochemical examination revealed that these tumor cells were positive for c-kit, CD34, and S-100 and were negative for SMA. The mitotic figures were less than 1 in 20 high-power fields. This duodenal tumor was diagnosed as a low-risk GIST. The patient had an uneventful recovery and was discharged from the hospital on Day 17 after the operation. This report presents a rare surgical case of duodenal GIST treated with wedge resection of the duodenum.

[A case of low grade ductal carcinoma in situ of the breast with difficulties in making the preoperative diagnosis after detection by FDG-PET].

A 56-year-old woman underwent FDG-PET screening, which demonstrated delayed-phase uptake in the lower part of the left breast. The findings of mammography, ultrasonography, MRI and cytological examination were compatible with ductal carcinoma in situ (DCIS), but core needle biopsy showed no evidence of malignancy. Therefore, partial resection of the left breast with sentinel lymph node biopsy was performed to make a definite diagnosis. Histological examination showed that this tumor was low grade DCIS. FDG-PET is a very useful examination to detect malignant diseases, but it is quite difficult to distinguish them from benign ones. It is suggested that delayed-phase uptake of FDG-PET is useful for diagnosis of DCIS.