Ai Sadatomo

Interaction of Neutrophils with Macrophages Promotes IL-1β Maturation and Contributes to Hepatic Ischemia–Reperfusion Injury

Accumulating evidence suggests that IL-1β plays a pivotal role in the pathophysiology of hepatic ischemia–reperfusion (I/R) injury; however, the mechanism by which I/R triggers IL-1β production in the liver remains unclear. Recent data have shown that neutrophils contribute to hepatic I/R injury independently of the inflammasomes regulating IL-1β maturation. Thus, we investigated the role of neutrophils in IL-1β maturation and tissue injury in a murine model of hepatic I/R. IL-1β was released from the I/R liver and its deficiency reduced reactive oxygen species generation, apoptosis, and inflammatory responses, such as inflammatory cell infiltration and cytokine expression, thereby resulting in reduced tissue injury. Depletion of either macrophages or neutrophils also attenuated IL-1β release and hepatic I/R injury. In vitro experiments revealed that neutrophil-derived proteinases process pro–IL-1β derived from macrophages into its mature form independently of caspase-1. Furthermore, pharmacological inhibition of serine proteases attenuated IL-1β release and hepatic I/R injury in vivo. Taken together, the interaction between neutrophils and macrophages promotes IL-1β maturation and causes IL-1β–driven inflammation in the I/R liver. Both neutrophils and macrophages are indispensable in this process. These findings suggest that neutrophil-macrophage interaction is a therapeutic target for hepatic I/R injury and may also provide new insights into the inflammasome-independent mechanism of IL-1β maturation in the liver.

Caspase-1 Deficiency Promotes High-Fat Diet-Induced Adipose Tissue Inflammation and the Development of Obesity

Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was stromal vascular fraction rather than adipocytes in the adipose tissue. These findings demonstrate a critical role of caspase-1 in macrophage-driven inflammation in the adipose tissue and the development of obesity. These data provide novel insights into the mechanisms underlying inflammation in the pathophysiology of obesity.

Hepatic portal venous gas after endoscopy in a patient with anastomotic obstruction

A 72-year-old male underwent a laparoscopic low anterior resection for advanced rectal cancer. A diverting loop ileostomy was constructed due to an anastomotic leak five days postoperatively. Nine months later, colonoscopy performed through the stoma showed complete anastomotic obstruction. The mucosa of the proximal sigmoid colon was atrophic and whitish. Ten days after the colonoscopy, the patient presented in shock with abdominal pain. Abdominal computed tomography scan showed hepatic portal venous gas (HPVG) and a dilated left colon. HPVG induced by obstructive colitis was diagnosed and a transverse colostomy performed emergently. His subsequent hospital course was unremarkable. Rectal anastomosis with diverting ileostomy is often performed in patients with low rectal cancers. In patients with anastomotic obstruction or severe stenosis, colonoscopy through diverting stoma should be avoided. Emergent operation to decompress the obstructed proximal colon is necessary in patients with a blind intestinal loop accompanied by HPVG.

Sigmoid volvulus after laparoscopic surgery for sigmoid colon cancer

We report the first case of sigmoid volvulus after laparoscopic surgery for sigmoid colon cancer. The patient is a 75‐year‐old man who presented with the sudden onset of severe abdominal pain. He had undergone laparoscopic sigmoidectomy for cancer 2 years before presentation. CT scan showed a distended sigmoid colon with a mesenteric twist, or “whirl sign.” Colonoscopy showed a mucosal spiral and luminal stenosis with dilated sigmoid colon distally and ischemic mucosa. The diagnosis of ischemic colonic necrosis due to sigmoid volvulus was established. Resection of the necrotic sigmoid colon was performed and a descending colon stoma was created. A long remnant sigmoid colon and chronic constipation may contribute to the development of sigmoid volvulus after laparoscopic sigmoidectomy. Prompt diagnosis is essential for adequate treatment, and colonoscopy aids in the diagnosis of ischemic changes in patients without definitive findings of a gangrenous colon.

Floating gallbladder strangulation caused by the lesser omentum: report of a case

Strangulation of the gallbladder by the omentum is extremely rare. We report what to our knowledge is only the second documented case of strangulation of a floating gallbladder by the lesser omentum. A 61-year-old Japanese woman presented to a local hospital after the sudden onset right upper quadrant pain. Her clinical features suggested a gallbladder volvulus, and the patient was referred to our hospital for investigation and treatment. Ultrasonography and computed tomography showed no cholecystolithiasis, but the fundus and body of the gallbladder were markedly swollen without wall thickening, whereas the neck of the gallbladder was normal. A narrowed, twisted area was seen between the body and neck of the gallbladder. Based on these findings, gallbladder volvulus was diagnosed and she underwent emergency laparoscopic cholecystectomy. The fundus and body of the gallbladder were grossly necrotic. The narrowest part of the gallbladder was tightly strangulated by the lesser omentum, but the gallbladder neck was normal. Histopathologic examination of the resected gallbladder showed ischemic changes in the wall of the fundus and body. This case highlights that the clinical features and imaging findings of a gallbladder strangulated by the lesser omentum are similar to those of gallbladder volvulus and that a positive outcome is dependent on a correct diagnosis and prompt surgical management.

Spontaneous Regression of Pulmonary Metastases from a Malignant Phyllodes Tumor

We report a case of spontaneous regression of pulmonary metastases from a malignant phyllodes tumor. A 50-year-old woman was diagnosed with a breast phyllodes tumor. Computed tomography and positron emission tomography revealed multiple lung metastases. She underwent a mastectomy to control the pain of the enlarging breast mass. Histopathologic examination diagnosed a malignant phyllodes tumor. Without the administration of any adjuvant therapy, the follow-up chest computed tomography scan and positron emission tomography scan showed disappearance of the lung metastases 2 months after surgery.

Adeno-associated Virus Vector-mediated Interleukin-10 Induction Prevents Vascular Inflammation in a Murine Model of Kawasaki Disease

Kawasaki disease (KD), which is the leading cause of pediatric heart disease, is characterized by coronary vasculitis and subsequent aneurysm formation. Although intravenous immunoglobulin therapy is effective for reducing aneurysm formation, a certain number of patients are resistant to this therapy. Because interleukin-10 (IL-10) was identified as a negative regulator of cardiac inflammation in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS), we investigated the effect of IL-10 supplementation in CAWS-induced vasculitis. Mice were injected intramuscularly with adeno-associated virus (AAV) vector encoding IL-10, then treated with CAWS. The induction of AAV-mediated IL-10 (AAV-IL-10) significantly attenuated the vascular inflammation and fibrosis in the aortic root and coronary artery, resulting in the improvement of cardiac dysfunction and lethality. The predominant infiltrating inflammatory cells in the vascular walls were Dectin-2+CD11b+ macrophages. In vitro experiments revealed that granulocyte/macrophage colony-stimulating factor (GM-CSF) induced Dectin-2 expression in bone marrow-derived macrophages and enhanced the CAWS-induced production of tumor necrosis factor-α (TNF-α) and IL-6. IL-10 had no effect on the Dectin-2 expression but significantly inhibited the production of cytokines. IL-10 also inhibited CAWS-induced phosphorylation of ERK1/2, but not Syk. Furthermore, the induction of AAV-IL-10 prevented the expression of TNF-α and IL-6, but not GM-CSF and Dectin-2 at the early phase of CAWS-induced vasculitis. These findings demonstrate that AAV-IL-10 may have therapeutic application in the prevention of coronary vasculitis and aneurysm formation, and provide new insights into the mechanism underlying the pathogenesis of KD.

Four-directional approach to the meso-transverse attachment combined with preoperative radiological vascular simulation facilitates short-term surgical outcomes in laparoscopic transverse colon cancer surgery: Creative lap transverse colon surgery

Transverse colon resection is one of the most difficult laparoscopic procedures because of anatomic hazards such as variations in the mesenteric vascular anatomy and the complex structure of organs and surrounding membranes.

Utility of preoperative 3-D simulation of laparoscopic lateral pelvic lymph node dissection for advanced rectal cancer: Surgical outcomes of 10 initial cases: 3-D simulation for pelvic node dissection

Laparoscopic lateral pelvic lymph node dissection (LPLD) is technically challenging because of the complicated anatomy of the pelvic wall. To overcome this difficulty, we introduced preoperative 3‐D simulation. The aim of the study is to investigate the usefulness of preoperative 3‐D simulation for the safe conduct of laparoscopic LPLD for rectal cancer.

Metachronous solitary metacarpal bone metastasis from rectal cancer

Abstract Metachronous solitary metacarpal bone metastasis from rectal cancer has not been reported previously. Here, we describe a 54-year-old woman who underwent abdominoperineal resection for rectal cancer following neoadjuvant chemoradiotherapy. The resected specimen contained adenocarcinoma with no lymph node metastases (Stage II, T3N0M0); no adjuvant chemotherapy was administered. Fifteen months after surgery, the patient presented with pain and swelling of the right thumb. Radiography revealed metacarpal bone destruction, and fluorine-18 fluorodeoxyglucose positron emission tomography showed uptake only in the metacarpal bone. Open biopsy revealed an adenocarcinoma, and a right thumb resection was performed. Histological examination indicated features of adenocarcinoma similar to the findings of a rectal lesion, leading to a diagnosis of metachronous solitary metacarpal bone metastasis from rectal cancer. The patient remains free of disease after 6 years of follow-up. Our findings suggest that surgical resection may lead to favorable outcomes in patients with resectable solitary bone metastases.