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.

[Locally Advanced Gastric Cancer Showing Marked Tumor Shrinkage after the First Dose of Nivolumab for Fourth-Line Chemotherapy].

We report a case of locally advanced gastric cancer, which showed marked tumor shrinkage after the first dose of nivolumab. A 75-year-old woman was diagnosed with locally advanced gastric cancer with pancreatic invasion and pyloric stenosis. We performed gastrojejunostomy before chemotherapy. The first-line, second-line, and third-line chemotherapies were not effective, resulting in tumor progression and necrosis with abdominal wall penetration. Her performance status was good, so we started nivolumab therapy as the fourth-line chemotherapy. Nine days after the first dose of nivolumab, she had a severe abdominal pain and a sense of fatigue. CT imaging showed a remarkable degree of tumor necrosis just beneath the skin. We diagnosed progressive disease and discontinued the chemotherapy. However, her general condition gradually improved and CT imaging 4 months after the first dose of nivolumab showed marked tumor shrinkage. We restarted nivolumab therapy and she has been alive for 2 years 10 months since the introduction of chemotherapy. It was suggested that a single dose of nivolumab only could lead to marked tumor shrinkage in chemotherapy for advanced gastric cancer.

Brachial plexus paralysis after thoracoscopic esophagectomy for esophageal cancer in the prone position: A thought-provoking case report of an unexpected complication.

INTRODUCTION: During prone esophagectomy, placement of a port in the third intercostal space for upper mediastinal dissection requires adequate axillary expansion. To facilitate this, the right arm is elevated cranially and simultaneously turned outward. Brachial plexus paralysis associated with esophagectomy in the prone position has not been documented. PRESENTATION OF CASE: A 58-year-old man diagnosed with middle intrathoracic esophageal cancer was referred to our department. Thoracoscopic esophagectomy in the prone position was performed following neoadjuvant chemotherapy. After surgery, he complained of difficulty moving his right arm. Physical examination revealed perceptual dysfunction and movement disorder in the territory of cervical spinal nerve 6. Magnetic resonance imaging indicated the injury in the right posterior cord of the brachial plexus at the costoclavicular space. Therefore, we diagnosed the patient with right brachial plexus injury caused by the intraoperative position. The postoperative course was uneventful other than the brachial plexus paralysis, and he was discharged on postoperative day 23. He underwent continuous rehabilitation as an outpatient, and the right brachial plexus paralysis had completely disappeared by 2 months after surgery. DISCUSSION: This is the first case of brachial plexus injury during thoracoscopic esophagectomy in the prone position. In prone esophagectomy, managing the patient's position, especially the head and arm positions, is so important to avoid brachial plexus injury due to intraoperative positioning. CONCLUSION: The clinicians should consider managing the patient's position with anatomical familiarity to avoid brachial plexus injury due to intraoperative positioning.

Internal Hernia Associated with Colostomy After Laparoscopic Surgery for Rectal Malignancy: A Report of 3 Thought-Provoking Cases.

BACKGROUND Colostomy creation via intraperitoneal route is often performed during laparoscopic Hartmann's operation or abdominoperineal resection (APR). Herein, we report 3 rare cases of internal hernia associated with colostomy (IHAC). CASE REPORT The first case involved a 70-year-old man with IHAC after laparoscopic APR. Laparoscopy revealed the small intestine passed through a defect between the lifted sigmoid colon and left lateral abdominal wall in a cranial-to-caudal direction. The dislocated bowel with ischemic change was restored to its normal position and the lateral defect was covered with lateral peritoneum and greater omentum. The second case involved a 75-year-old man with IHAC after laparoscopic APR. Intraperitoneal findings were similar to those in the first case, except for the size of the lateral defect. This defect was too large for primary closure or patching; therefore, no surgical repair was performed. Unfortunately, this led to IHAC recurrence and creation of a new colostomy via extraperitoneal route. The third case involved an 85-year-old man with acute peritonitis resulting from IHAC after laparoscopic Hartmann's operation. Surgery revealed incarcerated bowels forming a closed loop and a perforation in the lifted sigmoid colon. The perforated colon was compressed by the dilated herniated bowel. The resected sigmoid colon showed perforation at the ulcer, which was shown on pathology to be caused by ischemia. CONCLUSIONS IHAC can lead not only to ischemia of strangulated bowel, but also to secondary damage to the lifted colon. During laparoscopic Hartmann's operation or APR, the colostomy should be created via extraperitoneal route to avoid IHAC.

Successful Laparoscopic Cholecystectomy in Moderate to Severe Acute Cholecystitis: Visual Explanation with Video File.

BACKGROUND Experience alone is insufficient to ensure successful laparoscopic cholecystectomy (LC), although LC has become widespread worldwide. Iatrogenic biliary injuries occur beyond the learning curve. CASE REPORT Biliary injury during laparoscopic cholecystectomy results from anatomical misidentification. The use of a critical view of safety has been established, to identify the cystic artery and the cystic duct, as the cystic duct can be hidden by inflammation (infundibular cystic duct). Seven patients who underwent emergency laparoscopic cholecystectomy due to acute cholecystitis are presented who underwent a critical view of safety protocol during surgery. Five men and two women (mean age, 63.0±13.0 years) included five cases of acute severe cholecystitis and two cases of acute moderate cholecystitis. The mean operative time to complete the critical view of safety exposure was 54.0±17.4 minutes. No cases underwent conversion to open surgery. The mean postoperative duration to ambulation and normal diet was 0.7±0.5 days and 1.0±0.6 days, respectively. The mean time to postoperative patient discharge was 3.9±0.9 days. In all seven cases, the postoperative course was uneventful. The protocol for this surgical procedure is presented, with schematic figures and videos. CONCLUSIONS A case series of seven patients who presented with moderate-to-severe acute cholecystitis and who underwent laparoscopic cholecystectomy, showed good postoperative outcome without surgical complications, using a using a critical view of safety protocol.

Which Therapeutic Option Is Optimal for Surgery-Related Perineal Hernia After Abdominoperineal Excision in Patients with Advanced Rectal Cancer? A Report of 3 Thought-Provoking Cases.

BACKGROUND Although perineal hernia (PH) is considered a surgery-related complication after abdominoperineal excision, the optimal therapeutic option for PH remains controversial. CASE REPORT The first case involved a 72-year-old man in whom PH was diagnosed 6 months after surgery. Laparoscopic findings revealed moderate adhesion at the pelvic floor, and a perineal approach was added. The pelvic floor defect was repaired by composite mesh. Combined laparoscopic surgery with a perineal approach was effective. The second case involved a 71-year-old man in whom PH was diagnosed 7 months after surgery. Laparoscopic findings revealed severe adhesion of the pelvis, and a perineal approach was added. The pelvic floor defect was repaired by composite mesh. The seromuscular layers of the small intestine were injured, and the damaged small intestine was resected and anastomosed. Composite mesh did not cause postoperative infection even with simultaneous bowel resection. The third case involved a 76-year-old man in whom PH was observed 12 years after surgery. Combined laparoscopic surgery with a perineal approach was performed from the beginning of surgery. Laparoscopic findings clearly demonstrated an intractable adhesion. Unexpected injury of the small intestine caused intra-abdominal contamination; therefore, the pelvic floor defect was primarily closed by absorbable sutures. Combined laparoscopic surgery with a perineal approach was effective even in this patient with a huge PH and intractable adhesion. CONCLUSIONS The combination of laparoscopic surgery with a perineal approach is an adequate option for PH treatment, and the perineal approach should be added without hesitation if needed.

Feasibility of Extended Dissection of Lateral Pelvic Lymph Nodes During Laparoscopic Total Mesorectal Excision in Patients with Locally Advanced Lower Rectal Cancer: A Single-Center Pilot Study After Neoadjuvant Chemotherapy.

BACKGROUND The feasibility of additional dissection of the lateral pelvic lymph nodes (LPLNs) in patients undergoing total mesorectal excision (TME) combined with neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC) is controversial. The use of laparoscopic surgery is also debated. In the present study, we evaluated the utility of laparoscopic dissection of LPLNs during TME for patients with LARC and metastatic LPLNs after NAC, based on our experience with 19 cases. MATERIAL AND METHODS Twenty-five patients with LARC with swollen LPLNs who underwent laparoscopic TME and LPLN dissection were enrolled in this pilot study. The patients were divided into 2 groups: those patients with NAC (n=19) and without NAC (n=6). Our NAC regimen involved 4 to 6 courses of FOLFOX plus panitumumab, cetuximab, or bevacizumab. RESULTS The operative duration was significantly longer in the NAC group than in the non-NAC group (648 vs. 558 minutes, respectively; P=0.022). The rate of major complications, defined as grade ≥3 according to the Clavien-Dindo classification, was similar between the 2 groups (15.8% vs. 33.3%, respectively; P=0.4016). No conversion to conventional laparotomy occurred in either group. In the NAC group, a histopathological complete response was obtained in 2 patients (10.5%), and a nearly complete response (Tis N0 M0) was observed in one patient (5.3%). Although the operation time was prolonged in the NAC group, the other perioperative factors showed no differences between the 2 groups. CONCLUSIONS Laparoscopic LPLN dissection is feasible in patients with LARC and clinically swollen LPLNs, even after NAC.

Portal vein aneurysm associated with arterioportal fistula after hepatic anterior segmentectomy: Thought-provoking complication after hepatectomy.

BACKGROUND: Few cases of postoperative arterioportal fistula (APF) have been documented. APF after hepatectomy is a very rare surgery-related complication. CASE PRESENTATION: A 62-year-old man was diagnosed with hepatocellular carcinoma in segments 5 and 8, respectively. Anterior segmentectomy was performed as a curative surgery. Each branch of the hepatic artery, portal vein, and biliary duct for the anterior segment was ligated together as the Glissonean bundle. The patient was discharged on postoperative day 14. Three months later, dynamic magnetic resonance imaging showed an arterioportal fistula and portal vein aneurysm. Surprisingly, the patient did not have subtle symptoms. Although a perfect angiographic evaluation could not be ensured, we performed angiography with subsequent interventional radiology to avoid sudden rupture. Arteriography was immediately performed to create a portogram via the APF from the stump of the anterior hepatic artery, and portography clearly revealed hepatofugal portal vein flow. Portography also showed that the stump of the anterior portal vein had developed a 40-mm-diameter portal vein aneurysm. Selective embolization of the anterior hepatic artery was accomplished in the whole length of the stump of the anterior hepatic artery, and abnormal blood flow through the APF was drastically reduced. The portal vein aneurysm disappeared, and portal flow was normalized. Dynamic computed tomography after embolization clearly demonstrated perfect interruption of the APF. The patient maintained good health thereafter. CONCLUSIONS: Post-hepatectomy APFs are very rare, and some appear to be cryptogenic. Our thought-provoking case may help to provide a possible explanation of the causes of post-hepatectomy APF.

Surgical options for full-thickness rectal prolapse: current status and institutional choice.

Full-thickness rectal prolapse (FTRP) is generally believed to result from a sliding hernia through a pelvic fascial defect, or from rectal intussusception. The currently accepted cause is a pelvic floor disorder. Surgery is the only definitive treatment, although the ideal therapeutic option for FTRP has not been determined. Auffret reported the first FTRP surgery using a perineal approach in 1882, and rectopexy using conventional laparotomy was first described by Sudeck in 1922. Laparoscopy was first used by Bermann in 1992, and laparoscopic surgery is now used worldwide; robotic surgery was first described by Munz in 2004. Postoperative morbidity, mortality, and recurrence rates with FTRP surgery are an active research area and in this article we review previously documented surgeries and discuss the best approach for FTRP. We also introduce our institution's laparoscopic surgical technique for FTRP (laparoscopic rectopexy with posterior wrap and peritoneal closure). Therapeutic decisions must be individualized to each patient, while the surgeon's experience must also be considered.

Intentional Modulation of Portal Venous Pressure by Splenectomy Saves the Patient with Liver Failure and Portal Hypertension After Major Hepatectomy: Is Delayed Splenectomy an Acceptable Therapeutic Option for Secondary Portal Hypertension?

BACKGROUND Major or aggressively-extended hepatectomy (MAEH) may cause secondary portal hypertension (PH), and postoperative liver failure (POLF) and is often fatal. Challenges to prevent secondary PH and subsequent POLF, such as shunt creation and splenic arterial ligation, have been reported. However, these procedures have been performed simultaneously only during the initial MAEH. CASE REPORT A 58-year-old female with chronic hepatitis C developed a solitary hepatic cellular carcinoma with portal tumor thrombosis. Blood examination and imaging revealed a decreased platelet count and splenomegaly. Her liver viability was preserved, and collaterals did not develop, and her tumor thrombosis forced us to perform a right hepatectomy from an oncological standpoint. The estimated volume of her liver remnant was 51.8%. A large volume of ascites and pleural effusion were observed on post-operative day (POD) 3, and ascetic infection occurred on POD 14. Hepatic encephalopathy was observed on POD 16. According to the post-operative development of collaterals due to secondary PH, submucosal bleeding in the stomach occurred on POD 37. Though it is unclear whether delayed portal venous pressure (PVP) modulation after MAEH is effective, a therapeutic strategy for recovery from POLF may involve PVP modulation to resolve intractable PH. We performed a splenectomy on POD 41 to reduce PVP. The initial PVP value was 32 mm Hg, and splenectomy decreased PVP to 23 mm Hg. Thereafter, she had a complete recovery from POLF. CONCLUSIONS Our thought-provoking case is the first successfully-treated case of secondary PH and POLF after MAEH, achieved by delayed splenectomy for PVP modulation.

Laparoscopic appendectomy for acute appendicitis: How to discourage surgeons using inadequate therapy.

Acute appendicitis (AA) develops in a progressive and irreversible manner, even if the clinical course of AA can be temporarily modified by intentional medications. Reliable and real-time diagnosis of AA can be made based on findings of the white blood cell count and enhanced computed tomography. Emergent laparoscopic appendectomy (LA) is considered as the first therapeutic choice for AA. Interval/delayed appendectomy at 6-12 wk after disease onset is considered as unsafe with a high recurrent rate during the waiting time. However, this technique may have some advantages for avoiding unnecessary extended resection in patients with an appendiceal mass. Non-operative management of AA may be tolerated only in children. Postoperative complications increase according to the patient's factors, and temporal avoidance of emergent general anesthesia may be beneficial for high-risk patients. The surgeon's skill and cooperation of the hospital are important for successful LA. Delaying appendectomy for less than 24 h from diagnosis is safe. Additionally, a semi-elective manner (i.e., LA within 24 h after onset of symptoms) may be paradoxically acceptable, according to the factors of the patient, physician, and institution. Prompt LA is mandatory for AA. Fortunately, the Japanese government uses a universal health insurance system, which covers LA.

Postoperative Biliary Leak Treated with Chemical Bile Duct Ablation Using Absolute Ethanol: A Report of Two Cases.

BACKGROUND Postoperative bile duct leak following hepatobiliary and pancreatic surgery can be intractable, and the postoperative course can be prolonged. However, if the site of the leak is in the distal bile duct in the main biliary tract, the therapeutic options may be limited. Injection of absolute ethanol into the bile duct requires correct identification of the bile duct, and balloon occlusion is useful to avoid damage to the surrounding tissues, even in cases with non-communicating biliary fistula and bile leak. CASE REPORT Two cases of non-communicating biliary fistula and bile leak are presented; one case following pancreaticoduodenectomy (Whipple's procedure), and one case following laparoscopic cholecystectomy. Both cases were successfully managed by chemical bile duct ablation with absolute ethanol. In the first case, the biliary leak occurred from a fistula of the right posterior biliary tract following pancreaticoduodenectomy. Cannulation of the leaking bile duct and balloon occlusion were achieved via a percutaneous route, and seven ablation sessions using absolute ethanol were required. In the second case, perforation of the bile duct branch draining hepatic segment V occurred following laparoscopic cholecystectomy. Cannulation of the bile duct and balloon occlusion were achieved via a transhepatic route, and seven ablation sessions using absolute ethanol were required. CONCLUSIONS Chemical ablation of the bile duct using absolute ethanol is an effective treatment for biliary leak following hepatobiliary and pancreatic surgery, even in cases with non-communicating biliary fistula. Identification of the bile duct leak is required before ethanol injection to avoid damage to the surrounding tissues.

Impact of stepwise introduction of esophagojejunostomy during laparoscopic total gastrectomy: a single-center experience in Japan.

BACKGROUND: The number of laparoscopic gastrectomies performed in Japan is increasing with the development of laparoscopic and surgical instruments. However, laparoscopic total gastrectomy is developing relatively slowly because of technical difficulties, particularly in esophagojejunostomy. METHODS: We retrospectively reviewed 83 patients with early gastric cancer in the upper portion of the stomach who underwent laparoscopic total gastrectomy between April 2007 and March 2016. We classified the patients into three periods, mainly on the basis of the esophagojejunostomy procedures performed: first period, various conventional procedures based on the physicians' choice (n=14); second period, transoral method (n=51); and third period, fully intracorporeal technique (n=18). We evaluated the clinical impact of a stepwise introduction of unfamiliar new methods during laparoscopic total gastrectomy. RESULTS: Between the first and second periods, there were significant differences in the blood loss volume, number of harvested lymph nodes, frequency of conversion to open surgery, and postoperative hospital stay. The number of harvested lymph nodes was significantly higher in the third than in the second period, with no detriment to other intraoperative or postoperative factors. CONCLUSION: The use of a unified surgical method for esophagojejunostomy seems to be the key to a successful and advantageous laparoscopic total gastrectomy. Stepwise introduction of a well-established technique of esophagojejunostomy during laparoscopic total gastrectomy will benefit patients, as shown, for example, by the higher number of dissected lymph nodes in the present study. However, a protracted learning curve is required.

Outcome of a Modified Laparoscopic Suture Rectopexy for Rectal Prolapse with the Use of a Single or Double Suture: A Case Series of 15 Patients.

BACKGROUND Surgery is considered to be a mainstay of therapy for full-thickness rectal prolapse (FTRP). Surgical procedures for FTRP have been described, but optimal treatment is still controversial. The aim of this report is to evaluate the safety and feasibility of a simplified laparoscopic suture rectopexy (LSR) in a case series of 15 patients who presented with FTRP and who had postoperative follow-up for six months. CASE REPORT Fifteen patients who underwent a modified LSR at our surgical unit from September 2010 were retrospectively evaluated. The mean age of the patients was 72.5±10.9 years. All 15 patients underwent general anesthesia, with rectal mobilization performed according to the plane of the total mesorectal excision. By lifting the mobilized and dissected rectum cranially to the promontorium, the optimal point for subsequent suture fixation of the rectum was marked. The seromuscular layer of the anterior right wall was then sutured to the presacral fascia using only one or two interrupted nonabsorbable polypropylene sutures. The mean operative time was 176.2±35.2 minutes, with minimal blood loss. No moderate or severe postoperative complications were observed, and there was no postoperative mortality. One patient (6.7%) developed recurrence of rectal prolapse one month following surgery. CONCLUSIONS The advantages of this LSR procedure for the management of patients with FTRP are its simplicity, safety, efficacy, and practicality and the potential for its use in patients who can tolerate general anesthesia.