Ferroptosis-related gene glutathione peroxidase 4 promotes reprogramming of glucose metabolism via Akt-mTOR axis in intrahepatic cholangiocarcinoma.

The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.

Hepatoid carcinoma and related entities of the extrahepatic bile duct: A clinicopathological study of four cases.

Hepatoid carcinoma or related entities (HPC/RTs) are extremely rare, especially in the extrahepatic bile duct (EHBD). Only a few case reports have been published. We analyzed the clinicopathological features of HPCs/RTs in EHBD. HPC/RT of extrahepatic cholangiocarcinoma (eCCA) cases were selected based on the histological characteristics and immunohistochemical detection of spalt-like transcription factor 4 (SALL4) and/or alpha-fetoprotein (AFP). Four HPC/RT cases arose in the distal but not in the perihilar EHBD. The four patients with HPC/RT included one female and three males with a median age of 77 years. There are various macroscopic types of HPC/RT. The predominant histological features were two solid-type carcinomas that mimicked hepatocellular carcinoma and two well-differentiated tubular adenocarcinomas. Immunohistochemically, SALL4 and glypican-3 were expressed in all cases, and AFP was expressed in one case. Cancer cell phenotypes included intestinal, pancreatobiliary, and mixed pancreatobiliary and intestinal types. Focal neuroendocrine differentiation and severe perineural and lymphovascular invasions were also observed. HPC/RT recurred in two patients within 2 years, and one patient died 13 months postoperatively. It is suggested that the HPC/RT of EHBD shares common characteristics with HPC/RT arising in various organs, and has some unique characteristics. HPC/RT of EHBD might be more aggressive than conventional eCCA.

Primary hepatic extranodal marginal zone B-cell mucosa-associated lymphoid tissue lymphoma treated by laparoscopic partial hepatectomy: a case report.

BACKGROUND: Primary hepatic extranodal marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphoma is very rare, so it is difficult to diagnose preoperatively. And there is no established treatment for hepatic MALT lymphoma. We report herein a case of primary hepatic MALT lymphoma treated by laparoscopic partial hepatectomy, and discuss the usefulness of laparoscopic hepatectomy for a rare liver tumor. CASE PRESENTATION: This patient was a woman in her 60s, who was diagnosed preoperatively as having synchronous liver metastasis from sigmoid colon cancer; therefore, laparoscopic partial hepatectomy was performed. She had a good course after the operation and was discharged on postoperative day 12. However, she was diagnosed pathologically as having primary hepatic MALT lymphoma. A bone marrow biopsy was also performed, and then she was finally diagnosed as having limited-stage primary hepatic MALT lymphoma. She received no postoperative treatment and showed no recurrence for 4 years postoperatively. CONCLUSIONS: We experienced the good result of the patient with limited-stage primary MALT lymphoma treated by laparoscopic partial hepatectomy. Liver tumors are sometimes misdiagnosed by imaging examinations alone. Laparoscopic hepatectomy has been widespread recently as a minimally invasive procedure, and it may be useful for both diagnosis and treatment.

Chronic inguinal pain after laparoscopic intraperitoneal onlay mesh (IPOM) repair for inguinal hernia treated successfully with laparoscopic selective neurectomy: A case report.

INTRODUCTION: Laparoscopic intraperitoneal onlay mesh (IPOM) repair is occasionally used for inguinal hernia repair. Here, we report a case of chronic neuropathic pain after laparoscopic IPOM repair for inguinal hernia, which was treated successfully with laparoscopic selective neurectomy. PRESENTATION OF CASE: A 59-year-old man with bilateral inguinal hernia underwent laparoscopic repair. Transabdominal preperitoneal repair was performed on the left side, whereas IPOM repair was performed on the right side due to a peritoneal defect. At postoperative month 1, he presented with severe pain and numbness distributed from the right inguinal region to the inner thigh region. The symptoms had persisted for 1year despite medical treatment. We diagnosed that the symptoms might be due to the entrapment of nerves in the contracted mesh, and performed a second surgery via laparoscopic approach 13 months after the first surgery. On laparoscopic exploration, the lateral side of the mesh was contracted and involved nerve branches. We ligated and cut off these nerve branches. His symptoms resolved immediately after the surgery. At postoperative month 12, he has passed without any pain, numbness, and hernia recurrence. DISCUSSION: Laparoscopic exploration would be useful to figure out chronic neuropathic pain after laparoscopic inguinal hernia repair. CONCLUSION: Laparoscopic IPOM repair for inguinal hernia should be avoided as much as possible because it may cause chronic neuropathic pain. Laparoscopic selective neurectomy is an option for patients with chronic neuropathic pain after laparoscopic hernia repair.