ABSTRACT
Cholangiocarcinoma (CCA) is an aggressive malignant tumor of bile duct epithelia. Recent evidence suggests the impact of cancer stem cells (CSC) on the therapeutic resistance of CCA; however, the knowledge of CSC in CCA is limited due to the lack of a CSC model. In this study, we successfully established a stable sphere-forming CCA stem-like cell, KKU-055-CSC, from the original CCA cell line, KKU-055. The KKU-055-CSC exhibits CSC characteristics, including: (1) the ability to grow stably and withstand continuous passage for a long period of culture in the stem cell medium, (2) high expression of stem cell markers, (3) low responsiveness to standard chemotherapy drugs, (4) multilineage differentiation, and (5) faster and constant expansive tumor formation in xenograft mouse models. To identify the CCA-CSC-associated pathway, we have undertaken a global proteomics and functional cluster/network analysis. Proteomics identified the 5925 proteins in total, and the significantly upregulated proteins in CSC compared with FCS-induced differentiated CSC and its parental cells were extracted. Network analysis revealed that high mobility group A1 (HMGA1) and Aurora A signaling through the signal transducer and activator of transcription 3 pathways were enriched in KKU-055-CSC. Knockdown of HMGA1 in KKU-055-CSC suppressed the expression of stem cell markers, induced the differentiation followed by cell proliferation, and enhanced sensitivity to chemotherapy drugs including Aurora A inhibitors. In silico analysis indicated that the expression of HMGA1 was correlated with Aurora A expressions and poor survival of CCA patients. In conclusion, we have established a unique CCA stem-like cell model and identified the HMGA1-Aurora A signaling as an important pathway for CSC-CCA.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Mice , Animals , HMGA1a Protein , Cholangiocarcinoma/metabolism , Neoplastic Stem Cells/metabolism , Bile Ducts, Intrahepatic/metabolism , Bile Duct Neoplasms/metabolism , Cell Line, Tumor , Cell ProliferationABSTRACT
BACKGROUND: Paracecal hernias, also known as pericecal hernias, are an exceptionally rare type of internal hernia. We report a unique case of paracecal hernia due to membranous adhesion of the omentum to the right paracolic gutter. CASE PRESENTATION: An 86-year-old female was admitted to our hospital with vomiting and abdominal pain. Laboratory findings showed a slightly elevated C-reactive protein level. Computed tomography scan showed dilated loops of the small intestine in the right paracolic gutter with medial displacement of the cecum and ascending colon. Internal hernia around the cecum due to postoperative adhesion after appendectomy was suspected, and she underwent emergency laparotomy. Intraoperative findings revealed the adhesion between the omentum and right paracolic gutter forming a cavity with the small intestine incarcerated. No abnormal adhesion in the ileocecal region was seen. We transected the omental adhesion from the orifice to the far end of the cavity near the hepatic flexure of the colon to release strangulation and to prevent recurrence. The patient was discharged on postoperative day 14 without complications. CONCLUSIONS: Paracecal hernias have a type of membranous adhesion of the omentum to the right paracolic gutter. Surgeons should be aware of this paracecal hernia type, when they encounter the internal hernia.
ABSTRACT
BACKGROUND: The presence of a vitelline vascular remnant is rare, and definitive preoperative diagnosis is difficult. We herein describe a case of intestinal obstruction caused by a vitelline vascular remnant with mild chronic appendicitis successfully diagnosed and treated with laparoscopic surgery. CASE PRESENTATION: A 14-year-old male was admitted to our hospital with sudden-onset right lower abdominal pain and vomiting. A blood test on admission revealed slight leukocytosis. Computed tomography scan showed that the appendiceal wall was enhanced and thickened. Although the ileum was slightly dilated and ascites was present at the recto-vesical pouch, these were thought to be inflammatory changes secondary to appendicitis. Laparoscopic surgery was performed using three trocars. Strangulated small bowel obstruction caused by a band connecting the right medial umbilical fold to the ileal mesentery was found intraoperatively. After reduction, neither ischemic change of the small intestine nor Meckel's diverticulum was detected. The appendix was slightly inflamed, and serous ascites was present at the recto-vesical pouch; therefore, appendectomy was also performed. The patient was discharged on postoperative day 4 without complications. Pathological examination revealed that the band consisted of blood vessels, and it was diagnosed as a vitelline vascular remnant. The appendix included fecal stones and showed chronic inflammatory change histologically; the patient was thus diagnosed with chronic appendicitis. CONCLUSIONS: Definitive preoperative diagnosis of a vitelline vascular remnant, especially with coexisting appendicitis, might be difficult. Laparoscopic surgery might be useful for patients who demonstrate unusual symptoms because it allows for simultaneous diagnosis and treatment.
ABSTRACT
Clinicians generally suspect pulmonary tumor embolism (PTE) with uncontrolled carcinomas which often spread to lungs. We, however, experienced an autopsy case of diffuse microscopic PTE despite controlled liver metastases of transitional cell carcinoma (TCC). A 66-year-old man with progressing respiratory symptoms showed almost normal chest findings on computed tomography. Although liver metastases were successfully shrunk by chemotherapy, the patient died from aggressive respiratory failure. An autopsy revealed small pulmonary vessels showing diffuse tumor emboli. TCC can cause PTE even if liver metastases are controlled. We must therefore be aware that PTE can manifest as respiratory symptoms without any computed tomography findings.