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.

Effect of emergency general surgery on postoperative performance status in patients aged over 90 years.

Background: Functional deterioration following emergency general surgery (EGS) poses a significant challenge in super-elderly patients. However, limited research has focused on assessing the deterioration in postoperative performance status (PS). This study aimed to investigate the impact of EGS on PS deterioration in super-elderly patients, and the extent to which deteriorated PS is recovered. Methods: This historical cohort study comprised 77 super-elderly patients who underwent EGS between July 2015 and December 2020. Functional deterioration was evaluated by comparing preoperative and postoperative Eastern Cooperative Oncology Group Performance Status (ECOG-PS). The Emergency Surgical Score (ESS) was used as a risk-adjustment tool. Questionnaires were mailed to the patients and their families to assess post-discharge PS and obtain their impressions of EGS. Results: Postoperative PS deteriorated in 35/77 patients (45.5 %). Significant differences were observed between the groups in terms of sex, serum C-reactive protein (CRP) levels, ESS scores, preoperative ECOG-PS, duration of operation, and major complications. Multivariate analysis of preoperative factors showed that ESS ≥7 (OR: 3.7, 95 % CI: 1.0-13), preoperative ECOG-PS ≤2 (OR: 5.9, 95 % CI: 1.7-21), and female sex (OR: 5.8, 95 % CI: 1.6-21) were associated with postoperative ECOG-PS deterioration. According to the questionnaire results, PS recovery post-discharge was observed in 6/36 (17 %) patients, and 34/36 (94 %) patients and their families expressed positive impressions of EGS. Conclusions: EGS in super-elderly patients highly caused a deterioration in their PS, particularly in patients with maintained preoperative PS. PS hardly recovered; however, most patients and their families had positive impressions of the EGS. Key message: We assessed the pre- and postoperative performance status of super-elderly patients who underwent emergency general surgery. Surgery caused a marked deterioration in patients' functional performance, which seldom recovered postoperatively.

Diffusely infiltrative squamous cell carcinoma of the esophagus resembling scirrhous gastric cancer: a case report.

Diffusely infiltrative squamous cell carcinoma of the esophagus is rare and difficult to diagnose. Case presentation: The patient was a 75-year-old woman whose chief complaints were dysphagia and upper abdominal pain. Esophagogastroduodenoscopy and biopsy revealed squamous cell carcinoma at the abdominal esophagus. After neoadjuvant chemotherapy, esophagogastroduodenoscopy showed diffuse thickening and poor distensibility of the stomach wall. We suspected scirrhous gastric cancer and performed multiple biopsies, which revealed no evidence of malignancy. We then performed staging laparoscopy. There were no apparent changes in the serous membrane of the stomach, but peritoneal lavage cytology revealed squamous cell carcinoma. Thus, we made a diagnosis of squamous cell carcinoma of the esophagus with diffuse invasion of the stomach. Intraoperative pathological diagnosis revealed that there was greater diffuse submucosal invasion of the oral esophagus than we expected, and we had to resect the esophagus at the level of the middle thoracic esophagus. Despite multidisciplinary treatment (surgery, chemotherapy, and radiotherapy), the patient died 20 months after the initial diagnosis. Clinical discussion: In this case, although biopsy did not lead to a diagnosis, peritoneal lavage cytology led to the correct diagnosis. Moreover, it was impossible to preoperatively predict the exact extent of the expansion because of diffuse submucosal invasion. Conclusion: When diffusely infiltrative squamous cell carcinoma of the esophagus is suspected, peritoneal lavage cytology may be useful for confirming the diagnosis; however, it should be assumed that accurate preoperative evaluation of the range of diffusely infiltrative squamous cell carcinoma is difficult.

Emergency open drainage of massive hemoperitoneum and early stage left hepatectomy for abdominal compartment syndrome due to hepatocellular carcinoma rupture: a case report.

BACKGROUND: Spontaneous rupture is one of the most life-threatening complications of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) effectively achieves hemostasis in patients with hemodynamic instability. However, there have been no reports of abdominal compartment syndrome (ACS) caused by massive intra-abdominal hematoma after TAE. We report emergency open drainage of a massive hematoma for abdominal decompression and early stage left hepatectomy at the same time. CASE PRESENTATION: A 75-year-old woman was transported to our emergency department with hypovolemic shock. Dynamic contrast-enhanced computed tomography revealed extravasation of contrast medium from a HCC lesion in the medial segment of the liver and a large amount of high-density ascites. TAE was immediately performed to achieve hemostasis. Three hours after the first TAE, we decided to perform a second TAE for recurrent bleeding. After the second TAE, the patient's intra-abdominal pressure increased to 35 mmHg, her blood pressure gradually decreased, and she had anuria. Thus, she was diagnosed with ACS due to spontaneous HCC rupture. Twenty-seven hours after her arrival to the hospital, we decided to perform open drainage of the massive hematoma and left hepatectomy for ACS relief, prevention of re-bleeding, tumor resection, and intraperitoneal lavage. The operative duration was 225 min, and the blood loss volume was 4626 g. Postoperative complications included pleural effusion and grade B liver failure. She was discharged on postoperative day 33. The patient survived for more than 3 years without functional deterioration. CONCLUSIONS: Even after hemostasis is achieved by TAE for hemorrhagic shock due to spontaneous rupture of HCC, massive hemoperitoneum may lead to ACS, particularly in cases of re-bleeding. Considering the subsequent possibility of ACS and the recurrence of bleeding, early stage hepatectomy and removal of intra-abdominal hematoma after hemodynamic stabilization could be a treatment option for HCC rupture.

Evaluating the outcomes of primary anastomosis with hand-sewn full-circular reinforcement in managing perforated left-sided colonic diverticulitis.

Background: It is a challenge to avoid stoma formation in emergency surgery of perforated left-sided diverticulum. The hand-sewn full-circular reinforcement of the colorectal anastomosis is used during complete pelvic peritonectomy to avoid a diverting ileostomy. This study examined the effect of applying the reinforcement method to perforated left-sided colonic diverticulitis with respect to the permanent stoma rate and cost-effectiveness. Materials and methods: This historical cohort study examined all patients who underwent emergency surgery for perforation of a left-sided diverticulum at the Hyogo Prefectural Amagasaki General Medical Center between July 2015 and September 2019. The cohort was divided into two groups: those who underwent conventional method (Group F) and those for whom the hand-sewn full-circular reinforcement method was actively performed (Group L). Results: The number of patients who underwent emergency surgery which did not lead to an ostomy increased significantly from 12% (3/25) in Group F to 42% (11/26) in Group L (P = 0.0015). The rate of permanent stoma decreased from 80% in Group F to 27% in Group L (P < 0.001). Total treatment costs for patients under the age of 80 in Group L were significantly lower than those in Group F (2170000 ± 1020000 vs 3270000 ± 1960000 JPY; P = 0.018). Conclusions: In emergency surgery for left-sided perforated colonic diverticulitis, applying the hand-sewn full-circle reinforcement of the anastomotic site may reduce stoma formation at the initial surgery and consequently decrease permanent stoma rate and contribute to cost-effectiveness without increasing complications such as anastomotic leakage.

Clinical impact of bloodstream infection on acute cholecystitis indicated for emergency cholecystectomy.

BACKGROUND: The significance of blood culture for acute cholecystitis remains unclear. METHODS: A retrospective cohort study was conducted on patients who underwent emergency cholecystectomy at Hyogo Prefectural Amagasaki General Medical Center to examine the clinical impact of bloodstream infection (BSI), focusing on the association of BSI with bactibilia and severity grade based on the Tokyo guidelines 2018 (TG18). RESULTS: Among 177 patients included in the study, 32 had positive and 145 had negative BSI. Significant differences were observed between the positive and negative BSI in terms of age, body mass index (BMI), the American Society of Anesthesiologists physical status (ASA-PS) and TG18 severity score. The odds ratios of BSI for patients aged ≥72 years, with a BMI of ≤21.8, an ASA-PS of ≥3E, and grade III acute cholecystitis were 3.45, 3.23, 2.43 and 4.51, respectively. In the multivariate analysis, lower BMI and grade III were significantly associated with BSI with odds ratios of 2.53 (95% confidence interval: 1.07-6.21, P = .037) and 3.03 (95% confidence interval: 1.02-8.82, P = .041). Bacterial species that could not be isolated in the bile culture alone were identified in blood culture on 10 (38.5%) of 26 patients. CONCLUSIONS: Bloodstream infection is associated with grade III acute cholecystitis. Blood culture enables the identification of bacteria that cannot be isolated in bile culture. Blood culture should be obtained for patients with grade III acute cholecystitis who undergo emergency cholecystectomy.

Dissecting aneurysm of the proper hepatic artery after laparoscopic hepatectomy possibly related to the Pringle maneuver: A case report.

In hepatectomy, the Pringle maneuver is commonly used, but its association with iatrogenic injury is not yet well understood. This report presents a case of dissecting aneurysm of the proper hepatic artery (PHA) possibly associated with the Pringle maneuver during laparoscopic hepatectomy, that was successfully treated by transcatheter arterial embolization (TAE). The patient was a woman in her 70s, and repeat hepatectomy for liver metastasis of rectal neuroendocrine neoplasm was planned. She underwent hand-assisted laparoscopic hepatectomy with the Pringle maneuver. On postoperative day (POD) 7, enhanced computed tomography showed a dissecting aneurysm of the PHA. TAE of the PHA to prevent hemorrhage was performed on POD 9 with no complications. Even after TAE, intrahepatic arterial flow was provided by the peribiliary arteries. This case suggests the possibility that the Pringle maneuver can cause a dissecting aneurysm of the hepatic artery.

Endovascular repair using a covered stent for a ruptured infected aneurysm of the superior mesenteric artery after pancreaticoduodenectomy: a case report.

BACKGROUND: Delayed arterial hemorrhage after pancreaticoduodenectomy is a life-threatening complication. There are no reports about infected aneurysms of the superior mesenteric artery after pancreaticoduodenectomy without clinically relevant pancreatic fistula. CASE PRESENTATION: A 78-year-old woman with borderline resectable pancreatic ductal adenocarcinoma involving the superior mesenteric arterial nerve plexus underwent pancreaticoduodenectomy with en bloc resection of the superior mesenteric vein and the superior mesenteric arterial nerve plexus after neoadjuvant chemotherapy. On postoperative day 14, she had bacteremia and sudden fever with chills. During the postoperative course, macroscopic abscesses or distinct infectious signs, including pancreatic fistula or bile fistula, were not present, but pylephlebitis was observed. After the antimicrobial treatment course, the patient was discharged. After 17 days, she was hospitalized for melena. Contrast-enhanced computed tomography showed a ruptured aneurysm of the superior mesenteric artery into the small intestine without a major intraabdominal abscess. E. coli was isolated from blood cultures. The patient was diagnosed with a ruptured infected aneurysm of the superior mesenteric artery. She was treated successfully with a covered stent by the cardiology team. There was no recurrence of bleeding at the 4-month follow-up, and the stent was patent in all subsequent computed tomography scans. CONCLUSIONS: Endovascular repair using a covered stent was effective in palliating acute bleeding from an infected aneurysm of the superior mesenteric artery.