Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.

Correlation between relative dose intensity of adjuvant S-1 chemotherapy and psoas muscle mass volume and survival after resection of pancreatic ductal adenocarcinoma: A retrospective study.

This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: P = .023, 5-year relapse-free survival: P = .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.

Using the geriatric nutritional risk index to predict outcomes in older patients with remnant gastric cancer after gastrectomy: a retrospective multicenter study in Japan.

PURPOSE: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC). METHODS: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS. CONCLUSIONS: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC.

Preoperative low skeletal muscle volume can result in insufficient administration of S-1 adjuvant chemotherapy in older patients with stage II/III gastric cancer.

BACKGROUND AND PURPOSE: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. METHODS: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. RESULTS: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). CONCLUSION: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.

A gastroduodenal artery that branched from the celiac artery in gastrectomy: A rare case of an anatomical variant.

Understanding anatomical anomalies of the branch of the celiac artery for safe gastrectomy is important. We report a case of laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer with a vascular anatomical anomaly of the celiac artery. A 45-year-old woman was referred to our hospital because of early gastric cancer. Computed tomography showed an anatomical variation of the gastroduodenal artery, which branched from the celiac artery. The celiac artery also branched into the left gastric artery, the splenic artery, and the common hepatic artery. Preoperative understanding of an unusual branch of the celiac artery enabled a safe laparoscopic surgery. There were no postoperative complications. The Adachi classification or Michel classification is used for an anatomical anomaly of the celiac artery, but to the best of our knowledge, this case has not been previously classified and is the first reported case.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

Skeletal Muscle Mass Before Second-line Chemotherapy Correlates With Subsequent Prognosis and Rate of Late-line Chemotherapy in Patients With Unresectable Gastric Cancer.

BACKGROUND/AIM: Chemotherapy is the standard treatment for patients with unresectable gastric cancer (UGC); however, the survival outcomes are poor. This study investigated the predictive values of skeletal muscle mass (SMM) index (SMI) before second-line chemotherapy and the survival outcomes of patients with UGC. PATIENTS AND METHODS: A total of 79 patients diagnosed with UGC at our hospital who received at least second-line palliative chemotherapy were included. The cross-sectional SMM at the third lumbar vertebra was obtained before second-line chemotherapy. SMI was defined as the muscle area normalized by height squared (m2), and SMI before second-line chemotherapy was defined as 2ndSMI. RESULTS: Using 2ndSMI for men and women (35.4 and 31.7 cm2/m2, respectively) as the cutoff value, patients were divided into high (2ndSMIHigh; n=54) and low (2ndSMILow; n=25) 2ndSMI groups. The number of patients receiving fourth-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.039). The overall survival time after the start of second-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.008). The incidence of grade 3 or 4 side effects was significantly higher in the 2ndSMILow than in the 2ndSMIHigh group (p=0.028). The multivariate analysis identified 2ndSMI as independent prognostic factor after the start of second-line chemotherapy. CONCLUSION: The 2ndSMILow group had a significantly worse prognosis and significantly less conversion to fourth-line chemotherapy than the 2ndSMIHigh group. Moreover, 2ndSMILow was associated with grade 3 or 4 side effects of second-line chemotherapy.

Preoperative Osteopenia as Risk Factor for Death from Other Diseases After Gastrectomy in Elderly Patients.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density, is a prognostic factor in patients with digestive tract cancers, including gastric cancer (GC). However, the correlation between preoperative osteopenia and GC in elderly patients is unclear. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. Patients were classified into the non-elderly group (n=169) and the elderly group (n=82). Bone mineral density was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Although overall survival was significantly shorter in the elderly compared to the non-elderly group (p=0.0062), there was no significant difference in disease-specific survival between the two groups (p=0.71) because of the higher rate of death from other diseases. In addition, the elderly group had a significantly higher incidence of osteopenia (p<0.001) and a significantly lower prognostic nutritional index (p<0.001). Multivariate analysis revealed that preoperative osteopenia and a low preoperative prognostic nutritional index were significant risk factors for death from other diseases after gastrectomy in elderly patients. CONCLUSION: In elderly patients with GC, preoperative osteopenia is an important factor to consider in terms of both curability and death from other diseases.

Hepatectomy for massive hepatic necrosis after transcatheter arterial embolization hemostasis for hepatic hemorrhage following hepatic trauma: A case report.

Key Clinical Message: Although partial hepatic necrosis often occurs following endovascular treatment for bleeding associated with hepatic trauma, it is relatively rare that additional treatment is required. However, invasive procedures such as hepatic resection should sometimes be considered when infection occurs over massive hepatic necrosis. Abstract: Although partial hepatic necrosis following endovascular treatment for bleeding associated with hepatic trauma is occasionally experienced, it is relatively rare for the necrotic area of the liver to require additional treatment. However, invasive procedures such as hepatic resection should sometimes be considered when infection occurs over massive hepatic necrosis.

Surgical Outcomes of Robotic Distal Pancreatectomy Versus Laparoscopic Distal Pancreatectomy at a Hospital in a Sparsely Populated Area.

Background: Robotic distal pancreatectomy (RDP) has a better or comparable surgical outcome when compared with laparoscopic distal pancreatectomy (LDP). However, whether the surgical outcome for these procedures in local, low-volume hospitals are comparable with those of the typically larger centers described in published reports remains unclear. Methods: This study enrolled 48 patients who underwent either RDP or LDP between August 2012 and April 2023. Data were retrospectively analyzed to evaluate the short-term surgical outcomes of RDP versus LDP in our hospital, which is a low-volume center. Results: The use of stapling with reinforcement in RDP was significantly higher than in LDP, and the postoperative hospital stay for RDP was significantly shorter than for LDP. Except for these two variables, there were no statistically significant differences between RDP and LDP in preoperative, intraoperative, or postoperative patient characteristics. Conclusion: RDP can be performed as safely and effectively as LDP in a low-volume hospital located in a sparsely populated area.

Preoperative Osteopenia Is a Risk Factor for Death in Patients Undergoing Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density (BMD), has been reported as a prognostic factor in patients with digestive tract cancers. However, the correlation between preoperative osteopenia and the prognosis of gastric cancer (GC) remains unclear. The aim of this study was to reveal the importance of preoperative osteopenia as a prognostic factor in patients undergoing gastrectomy for GC. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. BMD was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Osteopenia had a high area under the curve and predictive value for both overall survival (OS) and disease-specific survival (DSS). The study cohort was categorized into an osteopenia group and non-osteopenia group based on the optimal BMD cutoff values for OS (157.5) and DSS (195) determined by receiver operating characteristic analysis. The multivariate analysis revealed that OS (hazard ratio=3.607, p<0.001) and DSS (hazard ratio=2.797, p=0.03) were significantly worse in patients with than without preoperative osteopenia. CONCLUSION: Preoperative osteopenia is associated with poor OS and DSS in patients undergoing gastrectomy for GC.

Perioperative Infusion Management for Adhesive Bowel Obstruction with Congenital Nephrogenic Diabetes Insipidus: A Case Report.

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disease that results in polyuria due to decreased responsiveness to the antidiuretic hormone in the collecting ducts of the kidney. Without compensation by drinking large amounts of water, dehydration and hypernatremia can rapidly develop. We present a case of a patient originally diagnosed with CNDI who required surgery and a fasting period due to adhesive bowel obstruction. The patient was a 46-year-old man who was originally diagnosed with CNDI. He was prescribed trichlormethiazide but self-discontinued treatment in the process. His normal urine output was about 7,000-8,000 mL/day. He underwent robot-assisted radical cystectomy and uretero-cutaneostomy for bladder cancer. Two years later, he was hospitalized due to adhesive bowel obstruction. A 5% glucose solution was infused, and the dose was adjusted according to the urine volume and electrolytes. An adhesiotomy was performed due to recurrent bowel obstruction in a short period of time. A 5% glucose solution was used as the main infusion during the perioperative period. Once drinking water was resumed after surgery, urinary output and electrolytes were easily controlled. In conclusion, patients with CNDI should be given a 5% glucose solution as the primary infusion, and the infusion volume should be adjusted by monitoring daily urine output, electrolytes, and blood glucose levels. Infusion management is easier if oral intake is initiated as early as possible.

Impact of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Short-Term Analysis.

Background: We compared short-term clinical outcomes between robotic-assisted minimally invasive esophagectomy (RAMIE) and video-assisted thoracic esophagectomy (VATS-E) using propensity score-matched analysis. Methods: We enrolled 114 patients with esophageal cancer who underwent esophagectomy at our institution from January 2013 to January 2022. Propensity score matching was performed to minimize selection bias between the RAMIE and VATS-E groups. Results: After propensity score matching, 72 patients (RAMIE group, n = 36; VATS-E group, n = 36) were selected for analysis. No significant differences in clinical variables were observed between the two groups. The RAMIE group had a significantly longer thoracic operation time (313 ± 40 vs. 295 ± 35 min, P = 0.048), a higher number of right recurrent laryngeal nerve lymph nodes (4.2 ± 2.7 vs. 2.9 ± 1.9, P = 0.039), and a shorter postoperative hospital stay (23.2 ± 12.8 vs. 30.4 ± 18.6 days, P = 0.018) than the VATS-E group. The RAMIE group tended to have a lower rate of anastomotic leakage (13.9% vs. 30.6%) than the VATS-E group, although the difference was not statistically significant (P = 0.089). No significant differences were found in recurrent laryngeal nerve paralysis (11.1% vs. 13.9%, P = 0.722) or pneumonia (13.9% vs. 13.9%, P = 1.000) between the RAMIE group and the VATS-E group. Conclusion: Although RAMIE for esophageal cancer requires a longer thoracic surgery time, it might be a feasible and safe alternative to VATS-E for treating esophageal cancer. Further analysis is needed to clarify the advantages of RAMIE over VATS-E, especially in terms of long-term surgical outcomes.

A low cumulative perioperative prognostic nutritional index predicts poor long-term outcomes in patients with gastric cancer: A single-center retrospective study in Japan.

PURPOSE: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC). METHODS: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method. RESULTS: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC. CONCLUSIONS: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC.

Right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes after esophagectomy.

Mediastinal lymph node recurrence is often observed following esophageal cancer surgery; however, no treatment has been established for the same. Surgical resection is often considered for cases of recurrence in a single lymph node region, although the procedures and approaches vary depending on the recurrence site. Right thoracoscopic resection is rarely opted for owing to its high surgical difficulty. Herein, we report a successful case of right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes following esophagectomy. The intraoperative findings revealed few adhesions around the recurrent lymph nodes due to the initial surgery, and the recurrent lymph nodes were safely resected within a short period. The patient was discharged on postoperative day 4 without any complications, and there was no recurrence after 20 months. Thus, right thoracoscopic resection may be a promising treatment option for recurrent pretracheal lymph nodes after esophagectomy.

Usefulness of the Modified Frailty Index for Predicting Pneumonia Occurrence After Esophagectomy.

Background: Esophagectomy is an invasive and complication-prone surgical procedure. Therefore, a tool that can predict the occurrence of postoperative complications may be useful for perioperative management. In this study, we investigated whether the modified frailty index (mFI) could be a useful tool for predicting the postoperative complications of esophagectomy. Methods: In this study, 162 patients who underwent curative esophagectomy for esophageal squamous cell carcinoma from 2004 to 2019 at our institution were included. The patients were divided into the high mFI (≥ 0.27) and low mFI (< 0.27) groups, and the short-term postoperative outcomes of each group were examined retrospectively. Results: Regarding background factors, age and the American Society of Anesthesiologists physical status classification were significantly higher in the high mFI group (P = 0.049 and P = 0.002, respectively); however, the other items were not significantly different between the two groups. Regarding surgical outcomes, no significant differences in operative time, blood loss, and hospital stay were observed between the two groups. Regarding postoperative complications, pneumonia was significantly more common in the high mFI group (P = 0.035). In multivariate analysis, high mFI (P = 0.034) was an independent predictor of pneumonia, along with operative time ≥ 613 min (P = 0.03) and preoperative BMI < 20.48 (P = 0.006). Conclusion: The mFI is useful for predicting pneumonia after esophagectomy.

TRPV4 channels promote vascular permeability in retinal vascular disease.

This study aimed to determine the role of transient receptor potential vanilloid 4 (TRPV4), a calcium (Ca2+)-permeable cation channel, in the pathophysiology of retinal vascular disease. The retinal vein occlusion (RVO) murine model was created by irradiating retinal veins using lasers. TRPV4 expression and localization were evaluated in RVO mice retinas. In addition, we examined the effects of TRPV4 antagonists (RQ-00317310, HC-067047, GSK2193874, and GSK2798745) on retinal edema, blood flow, and ischemic areas in RVO mice. Furthermore, changes in the retinal expression of tumor necrosis factor (TNF)-α and aquaporin4 (AQP4) by RQ-00317310 were analyzed using Western blot. We also assessed the barrier integrity of epithelial cell monolayers using trans-endothelial electrical resistance (TEER) in Human Retinal Microvascular Endothelial Cells (HRMECs). The expression of TRPV4 was significantly increased and co-localized with glutamine synthetase (GS), a Müller glial marker, in the ganglion cell layer (GCL) of the RVO mice. Moreover, RQ-00317310 administration ameliorated the development of retinal edema and ischemia in RVO mice. In addition, the up regulation of TNF-α and down-regulation of AQP4 were lessened by the treatment with RQ-00317310. Treatment with GSK1016790A, a TRPV4 agonist, increased vascular permeability, while RQ-00317310 treatment decreased vascular endothelial growth factor (VEGF)- or TRPV4-induced retinal vascular hyperpermeability in HRMECs. These findings suggest that TRPV4 plays a role in the development of retinal edema and ischemia. Thus, TRPV4 could be a new therapeutic target against the pathological symptoms of retinal vascular diseases.

The prognostic impact of the lymphocyte-to-C-reactive protein ratio in patients with unresectable or recurrent advanced gastric cancer treated with first- and second-line treatment.

PURPOSE: The goal of this study was to determine which markers are the most useful as first- and second-line pre-treatment markers in patients with unresectable or recurrent gastric cancer (URGC). METHODS: This study included 101 URGC patients who were treated with first- and second-line chemotherapy. Several prognostic scores based on nutrition and inflammation were analyzed using a receiver operating characteristic (ROC) analysis to determine the most useful prognostic marker. RESULTS: The lymphocyte-to-C-reactive protein ratio (LCR) had the highest area under the curve for both first- and second-line chemotherapy, according to an ROC analysis. An ROC analysis was used to determine the optimal LCR cut-off for the median survival time before first- and second-line chemotherapy, and patients were divided into high- and low-LCR groups. Patients with a high LCR had a significantly longer survival than those with a low LCR before first- and second-line chemotherapy (p = 0.004, p < 0.001, respectively). A low LCR before both first- and second-line chemotherapy was an independent poor prognostic factor in a multivariate analysis. CONCLUSIONS: URGC patients with a low LCR before both first- and second-line chemotherapy had a significantly worse prognosis than those with a high LCR in this study. Nutritional intervention during chemotherapy induction may lead to a better prognosis.

Impact of gastrectomy on body composition within 1 month in patients with gastric cancer.

PURPOSE: The present study examined the changes in and risk factors for body composition (BC) during the first postoperative month when dynamic biological reactions occur. METHODS: We retrospectively assessed 202 patients who underwent gastrectomy. The BC was assessed using a bioelectrical impedance analysis and evaluated within 1 month preoperatively, 1 week postoperatively, and 1 month postoperatively. Multiple regression analyses were performed to identify predictive factors for BC change. RESULTS: The mean reduction rate in BC at 1 month postoperatively was - 6.0, - 10.5, - 5.6, - 1.1, - 10.1, and + 1.2% for body weight, body fat, skeletal muscle, bone mineral, extracellular water/total body water, and the whole-body phase angle, respectively. A multiple regression analysis revealed that independent risk factors for weight loss were complications, operative time, and type of gastrectomy (P = 0.004, 0.011, 0.015, respectively), and those for skeletal muscle loss were complications and gastrectomy type (P = 0.002, 0.010, respectively). A segmental lean mass analysis revealed that the lower limbs were markedly reduced at 1 week postoperatively (- 8.0%), and these independent risk factors were the female sex and Stage II/III disease (P = 0.008, 0.036, respectively). CONCLUSION: Detailed analyses of BC might help elucidate the mechanisms underlying postoperative physical changes, which might be useful for perioperative management.

Simultaneous regulation of ferroptosis suppressor protein 1 and glutathione peroxidase 4 as a new therapeutic strategy of ferroptosis for esophageal squamous cell carcinoma.

BACKGROUND: Ferroptosis suppressor protein 1 and glutathione peroxidase 4 have been identified as key molecules in two independent pathways associated with ferroptosis inhibition. This study investigated the prognostic significance and clinical associations of FSP1 and GPX4 expression in esophageal squamous cell carcinoma (ESCC) and assessed the therapeutic potential of regulating these molecules in ESCC cells. METHODS: Immunohistochemical analysis was performed on surgical specimens of 97 patients with ESCC for FSP1 and GPX4 expression. To identify the change in ESCC cell viability, FSP1 and GPX4 inhibitors were administered to three cell lines. In addition, ferroptosis as the cause of reduced cell viability by FSP1 and GPX4 inhibition was confirmed. RESULTS: Prognosis was significantly worse for patients in the group positive for both FSP1 and GPX4 compared with the other groups (p < 0.001). In multivariate analysis, positivity for both FSP1 and GPX4 was an independent poor prognostic factor (p = 0.002). The combination of FSP1 and GPX4 inhibitors induced cell death more potently than each inhibitor did alone. Furthermore, the ferroptosis inhibitor markedly canceled this cell death. CONCLUSIONS: Overexpression of FSP1 and GPX4 is a poor prognostic factor for patients with ESCC. Simultaneous suppression of both FSP1 and GPX4 caused potent cell death, which was markedly abrogated by ferroptosis inhibitors. These findings indicate that simultaneous regulation of FSP1 and GPX4 may be a new therapeutic target in ESCC.