Search

Purpose: Laparoscopic sleeve gastrectomy (LSG) drastically affects body composition. However, studies focusing on the association between the changes in the pre-and postoperative muscle mass and postoperative results are limited. We evaluated the association between changes in the muscle mass and weight loss and fat reduction., Methods: This retrospective study included 29 consecutive patients who underwent both LSG and a bioelectrical impedance analysis (BIA) consecutively. We investigated changes in the body composition on the BIA and visceral fat area (VFA) on computed tomography and correlational changes in muscle mass with weight loss and fat reduction., Results: The total weight loss (%TWL) 12 months after surgery was 30.9%. The VFAs pre- and postoperatively were 224 and 71.0 cm 2 , respectively. The fat mass (FM), percentage of FM, appendicular skeletal muscle mass (ASM), and skeletal muscle mass index (SMI) decreased from pre- to postoperatively (54.8 vs. 32.2 kg; 49.0 vs. 41.2%, 26.7 vs. 23.9 kg, 9.24 vs. 8.27, respectively), whereas the percentage of ASM (%ASM) increased (22.1 vs. 28.0%). The rate of change in %ASM positively correlated with weight loss and fat reduction (%TWL, rs = 0.65; %VFA loss, rs = 0.62)., Conclusion: The rate of change in %ASM was positively correlated with weight loss and fat reduction., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Ethical approval: All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and the Helsinki Declaration of 1964 and later versions. This study was approved by the Ethics Committee of the Jikei University School of Medicine (30-175). Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

When a slightly soluble surfactant droplet is positioned at the tip of a capillary beneath the water surface, the surface tension begins to oscillate spontaneously─a phenomenon known as the spontaneous oscillation of surface tension (SOS). This behavior arises from transient Marangoni flows generated periodically by surfactant molecules. Our molecular-level observations reveal that this oscillatory behavior originates from periodic fluctuations in the surface pressure of the surfactant monolayer at the water surface, which are attributed to orientational changes in the surfactant molecules. We demonstrate that shortening the oscillation period requires increasing the diffusion and solubility of surfactants, while enhancing the amplitude depends on amplifying the momentum of the Marangoni flow produced by the surfactants. Furthermore, the elasticity of the surfactant monolayer critically determines the amplitude, while its dilational viscosity influences the time constant for surface tension recovery. These findings advance our understanding of SOS and offer insights into many-body systems driven by the Marangoni effect, such as cellular movement.

Osteopenia is a potential prognostic factor in patients with cancer. Occult vertebral fracture, the most common complication of osteopenia, has recently been associated with cancer. The present study aimed to investigate the prognostic value of occult vertebral fracture after gastrectomy in patients with gastric cancer. The current retrospective study included 222 patients who underwent gastrectomy for gastric cancer between October 2013 and February 2023. Occult vertebral fracture was quantitatively evaluated using preoperative sagittal computed tomography images from the 11th thoracic to 5th lumbar vertebrae. Multivariate analysis showed that occult vertebral fracture (P<0.01, P=0.02, respectively), stage II or III (P<0.01, P<0.01, respectively), and R1 or R2 curability (P<0.01, P=0.03, respectively) were independent and significant predictors of disease-free and overall survival rates. Additionally, patients with both occult vertebral fracture and osteopenia had significantly lower disease-free and overall survival rates than those with either osteopenia or occult vertebral fracture (P<0.01, P<0.01, respectively). In conclusion, occult vertebral fracture may be considered a strong predictor of poor clinical outcomes in patients undergoing gastrectomy for gastric cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2025, Spandidos Publications.)

The physiological functions of supersulfides, inorganic and organic sulfides with sulfur catenation, have been extensively studied. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulfide synthase. This study aimed to investigate the role of supersulfides in joint homeostasis and bone regeneration. Using Cars2 AINK/+ mutant mice, in which the KIIK motif of CARS2 essential for supersulfide production was replaced with AINK, we evaluated the role of supersulfides in fracture healing and cartilage homeostasis during osteoarthritis (OA). Tibial fracture surgery was performed on the wild-type (Cars2 +/+ ) and Cars2 AINK/+ mice littermates. Bulk RNA-seq analysis for the osteochondral regeneration in the fracture model showed increased inflammatory markers and reduced osteogenic factors, indicative of impaired bone regeneration, in Cars2 AINK/+ mice. Destabilization of the medial meniscus (DMM) surgery was performed to produce the mouse OA model. Histological analyses with Osteoarthritis Research Society International and synovitis scores revealed accelerated OA progression in Cars2 AINK/+ mice compared with that in Cars2 +/+ mice. To assess the effects of supersulfides on OA progression, glutathione trisulfide (GSSSG) or saline was periodically injected into the mouse knee joints after the DMM surgery. Thus, supersulfides derived from CARS2 and GSSSG exogenously administered significantly inhibited inflammation and lipid peroxidation of the joint cartilage, possibly through suppression of ferroptosis, during OA development. This study represents a significant advancement in understanding anti-inflammatory and anti-oxidant functions of supersulfides in skeletal tissues and may have a clinical relevance for the bone healing and OA therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Osteoarthritis (OA) shows various clinical manifestations depending on the status of its joint components. We aimed to identify the synovial cell subsets responsible for OA pathophysiology by comprehensive analyses of human synovium samples in single-cell resolution. Two distinct OA synovial tissue groups were classified by gene expression profiles in RNA-Seq: inflammatory and fibrotic. The inflammatory group exhibited high expression of inflammatory cytokines, histologically inflammatory infiltrate, and a more severe pain score. The fibrotic group showed higher expression of fibroblast growth factor (FGFs) and bone morphogenetic proteins (BMPs), showed histologically perivascular fibrosis, and showed a lower pain score. In single-cell RNA-Seq (scRNA-Seq) of synovial cells, MERTKloCD206lo macrophages and CD34hi fibroblasts were associated with the inflammatory and fibrotic groups, respectively. Among the 3 fibroblast subsets, CD34loTHY1lo and CD34loTHY1hi fibroblasts were influenced by synovial immune cells, whereas CD34hi fibroblasts were influenced by mural and endothelial cells. Particularly, in CD34hi fibroblast subsets, CD34hiCD70hi fibroblasts promoted proliferation of Tregs, potentially suppressing synovitis and protecting articular cartilage. Elucidation of the mechanisms underlying the regulation of these synovial cell subsets may lead to novel strategies for OA therapeutics.

Objectives: Temporomandibular joint osteoarthritis (TMJ-OA) with condylar resorption is a multifactorial condition involving hormonal imbalance and articular disk dysfunction, often leading to severe TMJ degeneration. This study investigated the combined effects of estrogen deficiency and anterior articular disk derangement (ADD) on condylar bone resorption in a mouse model., Methods: Female C57BL/6J mice underwent ovariectomy (OVX) to induce estrogen deficiency and ADD was surgically induced for stress. The animals were divided into the control, OVX, ADD, and OVX + ADD groups. Microcomputed tomography and histological analyses were conducted to evaluate condylar bone structure, trabecular architecture, and osteoclast activity., Results: OVX and ADD caused significant condylar bone loss, characterized by reduced bone volume fraction (BV/TV) and abnormal trabecular architecture. The OVX + ADD group exhibited exacerbated bone resorption, with decreased BV/TV and increased trabecular separation compared to OVX or ADD alone. Histological analyses revealed increased osteoclast activity in the OVX + ADD group, suggesting a synergistic effect of estrogen deficiency and ADD on condylar degradation., Conclusion: Estrogen deficiency amplifies the bone-resorptive and inflammatory effects of ADD, accelerates TMJ degeneration, and underscores the interplay between hormone imbalance and articular disk dysfunction in the pathophysiology of TMJ-OA. There is a need for integrated treatment strategies, such as effective hormone replacement therapy and articular disk repositioning, to effectively manage temporomandibular joint disorders, particularly in postmenopausal women or those with hormonal imbalances. Further research is required to elucidate these molecular pathways and evaluate long-term therapeutic interventions., (Copyright © 2025. Published by Elsevier B.V.)

Backgrounds: We previously reported poor vascularity of narrow gastric tube evaluated by thermography was associated with anastomotic leakage (AL) after esophagectomy. Meanwhile, the association between the fornix low perfusion on devascularized whole stomach (DWS) and the incidence of AL remains unclear. Therefore, this study aimed to clarify the impact of the fornix low perfusion on DWS., Methods: A total of 238 patients who underwent Mckeown esophagectomy with gastric tube reconstruction between 2008 and 2021 were analyzed. Patients were divided into non-AL and AL groups and their clinical outcomes including vascular factors of DWS and gastric tube were compared. Additionally, the logistic regression analysis was conducted to detect the risk factors of AL., Results: AL occurred in 31 patients (13.0%). Regarding vascular factors, avascular area temperature retain rate (Av-TRr) on DWS, right gastroepiploic artery length rate and anastomotic viability index (AVI) on gastric tube were significantly smaller in the AL group than in the non-AL group. In logistic regression model for AL, multivariate analysis showed that diabetes (Odds ratio [OR], 3.90; 95% confidence interval [CI], 1.32-11.60), hand-sewn anastomosis (OR, 4.42;95% CI, 1.05-18.60), Av-TRr on DWS<0.91 (OR, 4.67; 95% CI, 2.00-10.90), and AVI<0.64 (OR, 2.68; 95% CI, 1.12-6.39) were significant risk factors., Conclusions: Fornix low perfusion on DWS was a risk factor of AL as well as low AVI on gastric conduit. Additionally, fornix low perfusion on DWS was correlated with low AVI on gastric conduit., Competing Interests: The authors declare no conflicts of interest for this article., (© 2025 The Author(s). Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Introduction and Importance: The importance of preoperative tumor site marking has increased over the years, as the method of intraoperative primary lesion identification and determination of resection margins is one factor determining whether oncological safety and function-preserving gastrectomy are possible during surgery. We hypothesize that preoperative placement of the near-infrared fluorescent (NIRF) clip, ZEOCLIP FS, near the oral incision line of the gastric tumor will allow for Firefly recognition of the NIRF clip on da Vinci during surgery and easy determination of the tumor location and incision line. Hence, we report on two cases in which the procedure was performed., Case Presentation: Case 1: A 62-year-old woman was diagnosed with early gastric cancer of 35 mm in size located in the greater curvature of the gastric angle and underwent robot-assisted distal gastrectomy. NIRF clips were placed around the negative biopsy-confirmed area on the tumor's oral side by endoscopy on the day before surgery. The clips were identified intraoperatively in Firefly mode, and we performed gastrectomy without using an intraoperative endoscope. Case 2: A 60-year-old man was diagnosed with early gastric cancer 40 mm in size on the anterior wall of the gastric angle and underwent robot-assisted distal gastrectomy. Similarly, NIRF clips were placed around the site of negative biopsy confirmation the day before surgery. NIRF clips were identified, and we performed gastrectomy., Clinical Discussion: The time taken to mark the gastric resection line after activating the Firefly imaging system was 120 and 154 s, respectively, and intraoperative endoscopy was not required. The advantage of our two-step method is that a surgeon can mark the clips the day before the surgery, even if they are not endoscopists. Increasing the recognition rate of fluorescent clips and preventing their remains are future issues., Conclusion: Based on the results of the above two cases, ZEOCLIP FS is influential in determining the tumor's location and the resection line., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To compare the pathophysiology and surgical outcomes of emergency surgery for upper gastrointestinal tract perforation with and without fungal peritonitis and identify the risk factors for fungal peritonitis., Methods: The subjects of this retrospective study were patients with upper gastrointestinal perforation and peritonitis who underwent emergency surgery at a single medical center in Japan. The patients were allocated to two groups according to the presence or absence of fungal peritonitis: group F and group N, respectively., Results: At the time of surgery, ascitic fluid culture or serum β-D glucan levels were available for 54 patients: 29 from group F and 25 from group N, respectively. The stomach was perforated in 14 patients (25.9%) and the duodenum was perforated in 40 patients (74.1%). Group F had a higher proportion of patients with low preoperative prognostic nutritional index scores (≤ 40) and C-reactive protein levels and a higher postoperative complication rate. The time to initiate food intake and the postoperative hospital stay were also significantly longer in group F. Multivariate analysis identified that the perforation site of the stomach was a risk factor for fungal peritonitis., Conclusion: Patients with fungal peritonitis from upper gastrointestinal tract perforation had higher postoperative complication rates, delayed postoperative recovery, and a longer hospital stay. Gastric perforation was a risk factor for fungal peritonitis., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: The real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated., Methods: This multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors., Results: Among 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1 months and overall survival was 14 months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4 months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7 months., Conclusions: Our study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding., (© 2024. Japanese Society of Gastroenterology.)

Background: Metastatic gastric tumors are rare and malignant melanoma, breast cancer, lung cancer, and esophageal cancer are common as primary lesions. On the other hand, renal cell carcinoma is easy to metastasize hematogenously to the whole body. However, metastasis to the stomach is rare and the detailed treatment of gastric metastasis is not mentioned. In this study, we report an uncommon case of gastric metastasis from renal cell carcinoma that underwent surgical full-thickness resection and reviewed the literature for treatment options., Case Presentation: The patient was a female in her 60s and in January 2007, she underwent a transabdominal left nephrectomy for clear cell carcinoma of the left kidney. The pathological diagnosis was pT2N0M0 stage II. In October 2017, a total pancreatectomy with D2 dissection was performed for multiple pancreatic masses, in which the pathological diagnosis was pancreatic metastasis of renal cell cancer. In May 2019, an esophagogastroduodenoscopy for heartburn revealed redness and erosion in the greater curvature of the residual gastric body. The pathological diagnosis was gastric metastasis from renal cell carcinoma. No metastatic findings were observed and gastric wedge resection was performed. Pathological diagnosis of the resected specimen showed a 4-mm tumor, mainly within the mucosa and partly extended to the submucosal layer in 500 µm. The resected specimen had a clear resection margin., Conclusions: In this study, we report a case in which a full-thickness resection was performed for gastric metastasis 12 years after renal cancer surgery and 2 years after pancreatic metastasis surgery. The patient survived 4 years and 8 months after gastric wedge resection. Although gastric metastasis often takes the form of submucosal tumors, it is necessary to select full-thickness resection for R0 resection, even in small and flat lesions., (© 2024. The Author(s).)

Introduction: Obesity impairs patients' quality of life (QoL). Laparoscopic sleeve gastrectomy (LSG) is a common procedure for patients with severe obesity; however, studies reporting changes in obesity-related QoL are limited. The aim of this study was to assess changes in obesity-related QoL and food tolerance in the early postoperative period., Methods: We included 20 consecutive patients who underwent LSG between May 2021 and July 2023. We evaluated changes in obesity-related QoL 6 months after surgery using an obesity and weight loss QoL questionnaire (OWLQOL) and a weight related symptom measure (WRSM). Additionally, we assessed eating satisfaction and food tolerance after surgery., Results: The percentages of total weight loss and excess weight loss were 28.5% and 79.1%, respectively. OWLQOL scores and WRSM changed from 36.5 to 73.0 points and from 44.0 to 15.0 points (p = .007, .007), respectively. The food tolerance score decreased from 25 to 21.2 points (p < .001), while eating satisfaction showed no significant change (p = .25)., Conclusion: Obesity-related QoL is enhanced even in the early postoperative period, without sacrificing eating satisfaction. The findings of this study may provide valuable insights for patients when considering LSG., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Objective: Anastomotic leakage is one of the most severe complications after esophagectomy. However, a diagnostic gold standard for anastomotic leakage has not been established yet. This retrospective cohort study aimed to evaluate the potential use of routine postoperative contrast-enhanced computed tomography findings as an early predictor of anastomotic leakage in patients who underwent esophagectomy for esophageal cancer., Methods: This study included 75 patients who underwent Mckeown esophagectomy, of whom 22 developed anastomotic leakage after surgery. The computed tomography findings for this patient cohort were categorized into 3 grades based on mural enhancement patterns observed at the anastomotic site. Both semiquantitative and quantitative analyses were performed, and the interobserver agreement between the 2 experienced radiologists was assessed., Results: It was found that poor enhancement in both the early and portal venous phases (grade 2) had a robust association with the occurrence of anastomotic leakage. The computed tomography enhancement ratio that is used to estimate wall degeneration and ischemia was significantly higher in patients with anastomotic leakage., Conclusions: Routine postoperative contrast-enhanced computed tomography could be beneficial for the early detection of anastomotic leakage, even in asymptomatic patients, after esophagectomy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate combining a monoclonal antibody targeting nectin-4 with a highly potent microtubule disrupting agent. EV is expected to be a candidate for the third-line treatment for urothelial carcinoma previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Very few cases of patients experienced hyperglycemia of unknown cause., Case Presentation: We describe a 72-year-old Asian man with mild obesity, type 2 diabetes, hyperlipidemia, hypertension, and chemo-resistant metastatic urothelial carcinoma. He developed hyperglycemia and febrile neutropenia after 3 doses of EV. He had hyperglycemia of 489 mg/dL and was started on continuous intravenous insulin infusion (CVII). The patient's intravenous insulin requirements peaked at 316 units per day. He also developed febrile neutropenia and consequent sepsis caused acute kidney injury. Continuous hemodialysis filtration (CHDF) together with antibiotics were started to treat the septic condition. The blood glucose level gradually decreased after CHDF treatment and CHDF was continued for 14 days. The timing of liberation from CHDF correlated with the elimination half-life of EV of 3.4 days. CVII was treated for 26 days and the patient was finally released from the intensive care unit., Conclusion: This case indicates that the uncontrollable hyperglycemia induced by EV during metastatic urothelial carcinoma treatment is effectively managed with CVII and CHDF until the elimination of the adverse effect of EV., Competing Interests: All the authors declare no conflict of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Sarcopenia is a prognostic predictor in emergency surgery. However, there are no reports on the relationship between osteopenia and in-hospital mortality. This study clarified the effect of preoperative osteosarcopenia on patients with gastrointestinal perforation after emergency surgery., Methods: We included 216 patients with gastrointestinal perforations who underwent emergency surgery between January 2013 and December 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra. Sarcopenia was evaluated by measuring the area of the psoas muscle at the level of the third lumbar vertebra. Osteosarcopenia is defined as the combination of osteopenia and sarcopenia., Results: Osteosarcomas were identified in 42 patients. Among patients with osteosarcopenia, older and female patients and those with an American Society of Anesthesiologists Physical Status of ≥ 3 were significantly more common, and the body mass index, hemoglobin value, and albumin level were significantly lower in these patients than in patients without osteosarcopenia. Furthermore, the osteosarcopenia group presented with more postoperative complications than patients without osteosarcopenia (P < 0.01). In the multivariate analysis, age ≥ 74 years old (P = 0.04) and osteosarcopenia (P = 0.04) were independent and significant predictors of in-hospital mortality., Conclusion: Preoperative osteosarcopenia is a risk factor of in-hospital mortality in patients with gastrointestinal perforation after emergency surgery., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer., Methods: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 10 4 )., Results: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS., Conclusion: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller‑myotomy with Dor‑fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia., Methods: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course., Results: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01)., Conclusions: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established., Methods: This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival., Results: In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5-not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis., Conclusions: Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: Some prospective trials have demonstrated the feasibility of sentinel node (SN) biopsy in gastric cancer (GC) surgery. This study aimed to identify the appropriate concentration settings for the intraoperative injection of indocyanine green (ICG) for SN biopsy., Methods: Before the clinical studies, porcine model experiments explored the optimal concentration of ICG injected intraoperatively. Next, nine GC patients were enrolled in the clinical research. ICG (0.5 ml) was injected intraoperatively into four quadrants of the submucosa around the tumor at various concentrations (0.5, 0.25, and 0.1 mg/ml). The lymphatic basin dissection method was applied to the ICG-positive lymphatic areas. The number and location of the lymphatic basins and positive nodes were recorded intraoperatively., Results: In the porcine model, the visibility gradually became clear at an ICG concentration higher than 0.1 mg/ml. In the clinical study, the average number of detected lymphatic basins was 3.3, 1.7, and 1.7, respectively. The mean number of detected SNs was 14.7, 6.7, and 4.0, respectively., Conclusion: To improve the reproducibility of SN biopsy, it is essential to prepare the correct concentration setting of ICG. Under current conditions in which ICG is injected intraoperatively, a 0.1 mg/ml concentration setting of ICG may be necessary and sufficient for SN identification., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis., Methods: We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells., Results: Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1β and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia-astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells., Conclusions: Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain., (© 2024. The Author(s).)

Background/aim: The purpose of this study was to evaluate the outcomes of the sentinel node navigation surgery (SNNS) followed by limited gastrectomy for early gastric cancer (EGC) with Endoscopic Curability C-2 (eCuraC-2)., Patients and Methods: Between 2001 and 2018, 33 patients were included in this study. Following sentinel node (SN) biopsy using indocyanine green combined with an infrared ray laparoscopic system, limited gastrectomy (LG) [wedge resection (WR), or segmental gastrectomy (SG)] was performed without extended lymphadenectomy., Results: SN detection rate was 97% (32/33). The mean number of SNs per case was 7.8. Three patients (9.1%) with lymph node metastasis (LNM) had a positive SN identified by intraoperative pathological examination. When intraoperative pathologic examination showed SN to be LNM negative, 11 patients underwent WR, and seven were subjected to SG. Postoperative pathological examinations showed no false negatives for LNM, and four patients (12%) had residual cancer in their resected stomachs. Overall survival and disease-specific survival five years after SNNS were 87.9% and 100%, respectively., Conclusion: SNNS followed by LG with lymphatic basin resection may be one of the ideal procedures for patients with eCuraC-2 due to the accurate diagnosis of LNM and favorable disease-specific prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short-term outcomes, recent studies on the long-term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow-up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long-term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies., Competing Interests: The authors declare no conflicts of interest for this article., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in bariatric-metabolic surgery (BMS) worldwide, accounting for approximately 90% of BMS procedures in Japan. While numerous studies have reported on the safety and efficacy of LSG, gastroesophageal reflux disease (GERD) remains a major postoperative complication. Although Roux-en-Y gastric bypass (RYGB) is preferred for severe obesity with GERD, it is less suitable for Japanese patients who have a higher risk of gastric cancer due to the remnant stomach which is difficult to observe with esophago-gastro-duodenoscopy. To address de novo and exacerbation GERD after LSG, we conducted LSG with Toupet fundoplication (T-sleeve) for Japanese patients with severe obesity. In our first T-sleeve case, the patient demonstrated sufficient weight loss and improved GERD following surgery. Hence, we suggest that T-sleeve is a feasible option for Japanese patients with obesity and concurrent GERD., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Accumulating evidence suggests that expression levels of tumor-infiltrating (TI) cells may play a prognostic role in patients with esophageal cancer who have undergone esophagectomy. However, its effect on patients undergoing neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy followed by esophagectomy for esophageal squamous cell carcinoma (ESCC) remains unclear. Therefore, this study aimed to elucidate the prognostic impact of TI cells in patients who underwent esophagectomy following neoadjuvant DCF therapy., Methods: Overall, 81 patients with ESCC who underwent curative esophagectomy following neoadjuvant DCF therapy were included. The number of TI CD8+ cells was determined using light microscopy at ×400 in tumor invasive margins. Receiver operative characteristic curve was used to determine the cutoff values for mortality for continuous variables; the patients were separated into high and low TI CD8+ cell groups and their backgrounds and clinical outcomes were compared., Results: Overall and relapse-free survival were significantly worse in the TI CD8+-low group than that in the TI CD8+-high group (p < 0.01). Multivariate analysis revealed that positive ypN (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.08-9.02) and low TI CD8+ cell levels (HR, 2.77; 95% CI, 1.31-5.85) were independent prognostic factors for overall survival. Furthermore, positive venous invasion (HR, 2.63; 95% CI, 1.29-5.35) and low TI CD8+ cell levels (HR, 2.77; 95% CI, 1.70-5.46) were significant prognostic factors for relapse-free survival., Conclusions: Low TI CD8+ cell level was a prominent prognostic factor for patients with ESCC undergoing neoadjuvant DCF therapy followed by esophagectomy., (© 2023 Wiley Periodicals LLC.)

Background/aim: The Japan Society of Endoscopic Surgery (JSES) proctoring system was established to prevent serious pancreatic pressure injuries in Japan in 2019. To safely perform robotic gastrectomy (RG) in our hospital, which has no experience in robotic surgery, we conducted a clinical trial with the support of this proctoring system., Patients and Methods: The present study was a single-center clinical prospective study. The primary endpoint was morbidity determined using Clavien-Dindo classification (C-D) Grade IIIa or higher., Results: Ten patients, seven males and three females, were recruited in this study. RG was performed under the proctoring system of the JSES in the initial six cases and was completed independently for the remaining four patients. We successfully performed the initial ten cases without C-D classification grade IIIa or higher morbidities., Conclusion: This study underscores the significance of a proctoring system for introducing RG to facilities with limited experience in robotic surgery. Despite some limitations, this study demonstrated successful outcomes in the initial ten cases, emphasizing the benefits for both surgeons and patients. This study provides valuable insights into the safety of RG in small institutions and calls for further research in this area., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Although findings from both animal and clinical research indicate that the blood-brain barrier (BBB) contributes to the pathogenesis of various psychiatric disorders (including depression), the underlying mechanisms are unknown. We investigated the levels of the tight-junction proteins claudin-5 and aquaporin-4 (AQP-4) in astrocytes of learned helplessness (LH) rats (an animal model of depression) and non-LH rats (a model of resilience)., Methods: We administered inescapable mild electric shock to rats and then identified the LH and non-LH rats by a post-shock test. The expressions of claudin-5 and AQP-4 in several brain regions of the LH and non-LH rats were then evaluated by a western blot analysis., Results: The levels of both claudin-5 and AQP-4 in the CA-1 and CA-3 hippocampal areas of the LH group were significantly lower than those of the control group, whereas those of the non-LH rats were not significantly different from those of the control and LH rats., Conclusions: These results suggest that LH rats but not non-LH rats experienced down-regulations of claudin-5 and AQP-4 in the CA-1 and CA-3. It is possible that a region-specific modulation of claudin-5 and AQP-4 is involved in the mechanisms of vulnerability but not resilience in depression., Competing Interests: Declaration of competing interest On behalf of all the authors, the corresponding author states that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: While laparoscopic fundoplication is a standard surgical procedure for patients with esophageal hiatal hernias, the postoperative recurrence of esophageal hiatal hernias is a problem for patients with giant hernias, elderly patients, or obese patients. Although there are some reports indicating that reinforcement with mesh is effective, there are differing opinions regarding the use thereof. The aim of this study is to investigate whether mesh reinforcement is effective for laparoscopic fundoplication in patients with esophageal hiatus hernias., Methods: The subjects included 280 patients who underwent laparoscopic fundoplication as the initial surgery for giant esophageal hiatal hernias, elderly patients aged 75 years or older, and obese patients with a BMI of 28 or higher, who were considered at risk of recurrent hiatal hernias based on the previous reports. Of the subject patients, 91 cases without mesh and 86 cases following the stabilization of mesh use were extracted to compare the postoperative course including the pathology, symptom scores, surgical outcome, and recurrence of esophageal hiatus hernias., Results: The preoperative conditions indicated that the degree of esophageal hiatal hernias was high in the mesh group (p = 0.0001), while the preoperative symptoms indicated that the score of heartburn was high in the non-mesh group (p = 0.0287). Although the surgical results indicated that the mesh group underwent a longer operation time (p < 0.0001) and a higher frequency of intraoperative complications (p = 0.037), the rate of recurrence of esophageal hiatal hernia was significantly low (p = 0.049), with the rate of postoperative reflux esophagitis also tending to be low (p = 0.083)., Conclusions: Mesh reinforcement in laparoscopic fundoplication for esophageal hiatal hernias contributes to preventing the recurrence of esophageal hiatal hernias when it comes to patient options based on these criteria., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Cartilage is considered to be immune privileged in general. Clinically, live cells are removed from subcutaneously transplanted allogeneic cartilage mainly for preservation and for infection control. However, because maintaining cartilage feature requires live chondrocyte, it would be beneficial to subcutaneously transplant cartilage with live chondrocyte even if it was allogeneic. We harvested femoral head from 3-week-old male C57BL/6 mice, subcutaneously transplanted to 6-week-old male mice, BALB/c, BALB/c nu/nu , or C57BL/6-Tg (enhanced green fluorescent protein [EGFP] under the control of the CMV-IE enhancer, chicken beta-actin promoter, rabbit beta-globin genomic DNA [CAG promoter]), as allogeneic, allogeneic immunodeficient control, or syngeneic transplantation. We also transplanted cartilaginous particles from human induced pluripotent stem cells derived from human leukocyte antigen homozygous donor to 6-week-old male mice either BALB/c and BALB/c nu/nu as xenogeneic or xenogeneic immunodeficient control. The transplantation periods were 1, 2, 3, 4, 8, 12, and 24 weeks. As the result, we did not observe exposure of the transplant or apparent macroscopic inflammatory in all samples. Histological analysis suggested that the femoral head showed focal ossification and thinning in syngeneic transplantation. In allogeneic transplantation, slight invasion of CD3 (+) T cell and the denaturation of the cartilage were observed, suggesting immune reaction against allogeneic cartilage. In xenogeneic transplantation, slight invasion of CD3 (+) cell and CD4 (+) cell and the structure of the perichondrium-like tissue got unclear, suggesting slight immune reaction against xenogeneic cartilage. Our findings suggest that we should carefully investigate for appropriate procedure to control immune reaction against allogeneic cartilage with live chondrocyte and to maintain its cartilage feature for long time.

Background: Neoadjuvant chemotherapy followed by surgery is Japan's most effective treatment modality for advanced thoracic esophageal squamous cell carcinoma. However, the prognosis is not as expected. This study aimed to examine prognostic factors in patients with pathologically ineffective neoadjuvant chemotherapy followed by surgery for esophageal squamous cell carcinoma., Methods: We retrospectively analyzed patients who underwent neoadjuvant chemotherapy followed by curative esophagectomy for esophageal squamous cell carcinoma between December 2008 and July 2021. The patients were divided into the neoadjuvant chemotherapy effective group and the neoadjuvant chemotherapy ineffective group according to the pathological diagnosis. Clinicopathological data, prognosis, and recurrence were analyzed., Results: A total of 143 patients (121 males, 22 females; median age, 67 years) were included in this study. Of these, 34 patients were classified into the effective group and the remaining 109 patients were assigned to the ineffective group. The ineffective group had significantly worse overall survival and recurrence-free survival than the effective group (p = 0.0192 and p = 0.0070, respectively). In the ineffective group, multivariate analysis demonstrated that microscopic venous invasion was an independent prognostic factor for overall survival (hazard ratio 2.44; 95% confidence interval 1.13-5.30) and recurrence-free survival (hazard ratio 2.43; 95% confidence interval 1.24-4.73)., Conclusions: Microscopic venous invasion was associated with poor survival and cancer recurrence in the neoadjuvant chemotherapy ineffective group of patients who underwent esophagectomy for esophageal squamous cell carcinoma., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: Trastuzumab-based chemotherapy is a standard treatment regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. This is a case of a patient who has survived 12 years after being diagnosed with advanced gastric cancer with multiple liver and lung metastases., Case Presentation: A woman in her 70s underwent total gastrectomy, cholecystectomy, and left hepatic lobectomy for gastric cancer with liver metastasis. One month after the surgery, multiple liver metastases appeared. After two courses of S-1 + CDDP chemotherapy, the liver metastases disappeared, and new lung metastases occurred. Because the primary tumor was HER2 positive, S-1 + CDDP + trastuzumab chemotherapy was performed. After one course of chemotherapy, the blood test showed pancytopenia, and CDDP was discontinued. S-1 + trastuzumab chemotherapy was then initiated, and as a result, the lung metastases disappeared. The patient is alive without recurrence 12 years after the surgery., Conclusions: We encountered a case of long-term survival after multidisciplinary treatments for HER2-positive advanced gastric cancer with multiple liver and lung metastases., (© 2023. Japan Surgical Society.)

Background: Preoperative C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) are correlated with a poor prognosis of various cancers. The significance of postoperative systemic inflammation markers for prognostic stratification of patients with esophageal cancer (EC) has not been established. Therefore, this study aimed to elucidate the impact of postoperative CAR and NLR on survival in patients with EC for prognostic stratification., Methods: A total of 235 patients who received curative esophagectomy were analyzed. A Cox proportional hazard model was performed to detect prognostic factors., Results: Multivariate analysis revealed that postoperative CAR ≥ 0.05 (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.57) and NLR ≥ 3.0 (HR, 2.81; 95% CI, 1.79-4.40) were independent prognostic factors for overall survival. Meanwhile, postoperative CAR ≥ 0.05 (HR, 1.61; 95% CI, 1.07-2.41) and NLR ≥ 3.0 (HR, 1.92; 95% CI, 1.29-2.85) were also significant prognostic factors for relapse-free survival. In addition, the patient group with postoperative CAR ≥ 0.05 and NLR ≥ 3.0 had the worst survival., Conclusions: Postoperative CAR ≥ 0.05 and NLR ≥ 3.0 can predict the poor survival of patients who received curative esophagectomy for EC., (© 2023 Wiley Periodicals LLC.)

Background: In recent years, the number of patients requiring surgery for intra-thoracic stomach (ITS) has been increasing due to the effects of obesity and gibbus due to aging. The aim of this study is to assess the effects of the degree of hernia on the pathological conditions and surgical outcomes in ITS patients., Methods: ITS was defined as cases in which over 50% of the stomach had deviated into the mediastinum by esophagogastric fluoroscopy and/or computed tomography, with 65 patients who underwent laparoscopic surgery as the initial surgery included. We compared the pathological conditions and surgical outcomes by dividing the subjects into 3 groups: Group A: 50%- < 75%; Group B: 75%- < 100%; and Group C: 100% (upside-down stomach), depending on the degree of deviation into the mediastinum of the stomach., Results: The breakdown of patients was 33 in Group A, 21 in Group B, and 11 in Group C. Regarding the preoperative pathological conditions, Group C had a high body mass index (BMI) and a low score for factor V according to upper gastrointestinal endoscopy (p = 0.0109, p = 0.0062, respectively). While the surgical results indicated that the operation time was extended depending on the degree of hernia (p = 0.0051), there was no marked difference in other surgical outcomes or the postoperative course among the three groups, with a high degree of satisfaction., Conclusions: In the case of ITS, although the operation time was extended depending on the degree of the hernia, the surgical outcomes were the same, and overall good results were obtained., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background & Aims: The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET)., Methods: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%., Results: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected., Clinicaltrials: gov ID: NCT04813029., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Backgrounds: The optimal method for evaluating frailty grade in patients with cancer has not been established in patients undergoing esophagectomy for esophageal cancer. This study aimed to clarify the impact of cachexia index (CXI) and osteopenia on survival in esophagectomized patients for esophageal cancer to develop frailty grade for risk stratification of the prognosis., Methods: A total of 239 patients who underwent esophagectomy were analyzed. CXI was calculated as follows: skeletal muscle index × serum albumin/neutrophil-to-lymphocyte ratio. Meanwhile, osteopenia was defined as below the cutoff value of bone mineral density (BMD) calculated by the receiver operating characteristic curve. We evaluated the average Hounsfield unit within a circle in the lower midvertebral core of the 11th thoracic vertebra on preoperative computed tomography as BMD., Results: Multivariate analysis revealed that low CXI (Hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.25-3.04) and osteopenia (HR, 1.86; 95% CI, 1.19-2.93) were independent prognostic factors for overall survival. Meanwhile, low CXI (HR, 1.58; 95% CI, 1.06-2.34) and osteopenia (HR, 1.57; 95% CI, 1.05-2.36) were also significant prognostic factors for relapse-free survival. A frailty grade combined with CXI and osteopenia stratified into four groups by their prognosis., Conclusions: Low CXI and osteopenia predict poor survival in patients undergoing esophagectomy for esophageal cancer. Furthermore, a novel frailty grade combined with CXI and osteopenia stratified the patients into four groups according to their prognosis., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Risk prediction of anastomotic leakage using anatomical and vascular factors has not been well established. This study aimed to assess the anatomical and vascular factors affecting the hemodynamics of the gastric conduit and develop a novel risk stratification system in patients undergoing esophagectomy with retrosternal reconstruction., Methods: This retrospective cohort study analyzed 202 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube retrosternal reconstruction between January 2008 and December 2020. Risk factors for anastomotic leakage (AL), including the anatomical index (AI) and anastomotic viability index (AVI), were evaluated using a logistic regression model., Results: According to the logistic regression model, the independent risk factors for AL were preoperative body mass index ≥23.6 kg/m 2 (odds ratio [OR], 7.97; 95% confidence interval [CI], 2.44-26.00; P <  0.01), AI <1.4 (OR, 23.90; 95% CI, 5.02-114.00; P <  0.01), and AVI <0.62 (OR, 8.02; 95% CI, 2.57-25.00; P <  0.01). The patients were stratified into four AL risk groups using AI and AVI as follows: low-risk group (AI ≥1.4, AVI ≥0.62 [2/99, 2.0%]), intermediate low-risk group (AI ≥1.4, AVI <0.62 [2/29, 6.9%]), intermediate high-risk group (AI <1.4, AVI ≥0.62 [8/53, 15.1%]), and high-risk group (AI <1.4, AVI <0.62 [11/21, 52.4%])., Conclusion: The combination of AI and AVI strongly predicted AL. Additionally, the use of AI and AVI enabled the stratification of the risk of AL in patients who underwent esophagectomy with retrosternal reconstruction., Competing Interests: The Authors declare that they have no competing interests in relation to this study., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background/aim: The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events, such as febrile neutropenia (FN), is high. This study retrospectively examined whether pegfilgrastim treatment reduces FN development during DCF therapy., Patients and Methods: This study evaluated 52 patients who were diagnosed with esophageal cancer and underwent DCF therapy at Jikei Daisan Hospital, Tokyo, Japan, between 2016 and 2020. They were divided into non-pegfilgrastim and pegfilgrastim-treated groups, and side-effects of chemotherapy and cost-effectiveness of pegfilgrastim were examined., Results: Eighty-six cycles of DCF therapy were conducted (33 and 53 cycles, respectively). FN was observed in 20 (60.6%) and seven (13.2%) cases, respectively (p<0.001). The lowest absolute neutrophil count during chemotherapy was significantly lower in the non-pegfilgrastim group (p<0.001), and the number of days until improvement from nadir was significantly shorter in the pegfilgrastim group (9 vs. 11 days; p<0.001). No significant difference was found in the onset of grade 2 or more adverse events by Common Terminology Criteria for Adverse Events. However, renal dysfunction was significantly lower in the pegfilgrastim group (30.7% vs. 60.6%, p=0.038). Hospitalization costs were also significantly lower in this group (692,839 vs. 879,431 Japanese yen, p=0.028)., Conclusion: This study revealed the usefulness and cost-effectiveness of pegfilgrastim in prevention of FN in patients treated with DCF., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Iatrogenic diaphragmatic hernia (IDH) is a rare complication that has been reported after various interventions, including liver transplantation, liver resection and nephrectomy. A surgical procedure for IDH has not been optimized. A 56-year-old man presented to our hospital with a 1-week history of abdominal pain and nausea. His medical history included an open nephrectomy for renal cancer 8 years ago and open distal pancreatectomy for its recurrence 1.5 years ago. Enhanced computed tomography showed IDH with the fornix of the stomach herniating to the left pleural cavity, without radiographic signs of strangulation. His symptoms improved after gastric decompression with nasogastric tube placement, and he underwent elective surgery. The incarcerated stomach was repositioned, and the hernia orifice was closed and reinforced with expanded polytetrafluoroethylene mesh using a thoracoscopic procedure. The patient had an uneventful postoperative course. The operative procedure for IDH should be tailored depending on anatomical alternations after previous surgeries., Competing Interests: All authors have no conflict of interest regarding this paper., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)

Colorectal metastasis from gastric cancer is rare and may develop several years after gastric cancer surgery. Therefore, colonoscopic findings provide useful diagnostic information. The present report describes a case of gastric cancer colon metastasis diagnosed 8 years and 10 months after gastrectomy for advanced gastric cancer. A 64-year-old male patient underwent gastrectomy in December 2010 and received chemotherapy for 4 years and 10 months after the surgery. Subsequently, the patient was diagnosed as having colorectal cancer by computed tomography in February 2019. Colonoscopy revealed linitis plastica-like colon stenosis; however, biopsy pathology did not reveal any findings indicating malignancy. Right hemicolectomy was performed, and pathological examination revealed colon metastasis from gastric cancer. The patient received chemotherapy but died of peritoneal carcinomatosis 1 year and 8 months after the colectomy. According to literature, colorectal metastasis from gastric cancer is often attributed to hematogenous metastasis and often exhibits characteristic macroscopic features. Treatments, such as chemotherapy for gastric cancer and/or colorectal resection, are considered effective for gastric cancer colorectal metastasis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kohno et al.)

Background: Impaired gastric conduit perfusion during esophagectomy and reconstruction is considered a key risk factor of anastomotic leaks. The aim of this study is to evaluate the indication and feasibility of additional microvascular anastomosis (AMA) to the gastric conduit in esophageal cancer surgery., Patients and Methods: Patients who received an esophagectomy with gastric conduit reconstruction between July 2008 and July 2021 at a single center were reviewed. Patient characteristics, anastomotic viability index (AVI) of the gastric conduit measured with thermal imaging, and operative outcomes were analyzed using Fisher's exact test and Mann-Whitney U test. Two propensity score weighting methods (inverse probability of treatment weighting and overlap weighting) were applied to investigate whether AMA reduces anastomotic leaks., Results: Of the 293 patients who underwent an esophagectomy over the study period, 26 received AMA. AVI in the AMA group was significantly lower than that in the control group (0.64 vs. 0.74, p = 0.026). Overall anastomotic leak rates were 3.8% in the AMA group and 12.4% in the control group. Using two different propensity score weighting methods, the same conclusion was obtained that AMA significantly reduced anastomotic leaks after esophagectomy (both p < 0.001). The logistic regression model for estimating probability of anastomotic leaks provided AVI criteria for AMA application and revealed that AMA significantly reduced the estimated leak rates by a maximum of 49%., Conclusions: Additional microvascular anastomosis significantly reduced anastomotic leaks after esophagectomy. The proposed AVI criteria for AMA application can help guide surgeons as to when AMA is needed., (© 2022. Society of Surgical Oncology.)

Osteoblasts produce the receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin, the inducer and the suppressor of osteoclast differentiation and activation. We previously proposed that the degradation of osteoprotegerin by lysine-specific gingipain of Porphyromonas gingivalis and neutrophil elastase is one of the mechanisms of bone resorption associated with infection and inflammation. In the present study, we found that cathepsin K (CTSK) also degraded osteoprotegerin in an acidic milieu and the buffer with a pH of 7.4. The 37 k fragment of osteoprotegerin produced by the reaction with CTSK was further degraded into low molecular weight fragments, including a 13 k fragment, depending on the reaction time. The N-terminal amino acid sequence of the 37 k fragment matched that of the intact osteoprotegerin, indicating that CTSK preferentially hydrolyzes the death domain-like region of osteoprotegerin, not its RANKL-binding region. The 13 k fragment of osteoprotegerin was the C-terminal 13 k portion within the RANKL-binding region of the 37 k fragment. Finally, CTSK restored RANKL-dependent osteoclast differentiation that was suppressed by the addition of osteoprotegerin. Collectively, CTSK is a possible positive regulator of osteoclastogenesis., (© 2023. The Society for In Vitro Biology.)

Purpose: The Eckardt score (ES) is a famous scoring system used for assessing achalasia patients. We studied the correlation between our scoring system and the ES and examined the relationship between each score and the pathophysiology of achalasia., Methods: The subjects were 143 patients with diagnosed achalasia. We assessed the frequency and degree of dysphagia, regurgitation (vomiting), and chest pain on a 5-point scale from 0 to 4, with the product of the frequency and degree score defined as each symptom score (0-16). The sum of the three symptom scores was the Total Symptom Score (TSS). We then studied the correlation between the TSS and the ES, including whether these scores reflected the pathophysiology., Results: The median scores were 20 for TSS and 6 for the ES, indicating a high correlation between the two scores (r = 0.7280, p < 0.0001). A relationship was found between the morphologic type and both scores (TSS: p = 0.002, ES: p = 0.0036). On creating a receiver operating characteristic (ROC) curve for the Straight type and each score, the AUC was 0.6740 for TSS and 0.6628 for ES., Conclusions: A high positive correlation was found between the TSS and the ES. Both scoring systems reflected the morphologic type well, demonstrating that the TSS was a scoring system comparable to the ES., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Anastomotic stricture (AS) is one of the major complications after esophagectomy for esophageal cancer. We have previously reported that severe mucosal degeneration (MD) of the anastomotic site was associated with the incidence of AS. Meanwhile, there are few reports to correlate anastomotic internal circumference (AIC) with computed tomography (CT) with the incidence of AS. Therefore, this study was conducted to clarify the correlation of early postoperative endoscopic and CT findings with the incidence of AS. We assessed 205 patients who underwent esophagectomy. We then divided them into the non-AS group (n = 164) and the AS group (n = 41) and compared their background data and intraoperative and postoperative outcomes. We also evaluated the risk factors for AS using logistic regression model. Multivariate analysis revealed small AIC (P = 0.003; OR = 4.400; 95% CI = 1.650-11.700) and severe MD (P < 0.001; OR = 7.200; 95% CI = 2.650-19.600) as the independent risk factors for AS development. We also stratified the patients into the following four groups according to the incidence of AS: low-risk (normal AIC and intact or mild MD, 6.2%), intermediate-risk (small AIC and intact or mild MD, 29.4%), high-risk (normal AIC and severe MD, 42.9%), and very high-risk (small AIC and severe MD, 61.1%). Early postoperative endoscopic and CT findings were useful in predicting the development of AS after esophagectomy., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Aim: Osteopenia, characterized by low bone mineral density, is a potential prognostic factor for patients with cancer. The aim of this study was to clarify the impact of preoperative osteopenia in patients with gastric cancer (GC) after gastrectomy., Methods: We included 224 patients with GC who underwent gastrectomy between August 2013 and May 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra using computed tomography., Results: Osteopenia was identified in 68 patients (30%). The osteopenia group had significantly worse overall survival (OS) and disease-free survival (DFS) than the non-osteopenia group ( P  < .01, P  < .01, respectively). The postoperative hospital stay was significantly longer, and the occurrence of postoperative complications (Clavien-Dindo grade ≥ III) was significantly higher in the osteopenia group ( P  = .04, P  < .01, respectively). In multivariate analysis, osteopenia ( P  < .01), stage ≥II ( P  < .01), and R1 or R2 curability ( P  < .01) were independent and significant predictors of DFS. Additionally, osteopenia ( P  < .01), intraoperative blood loss ( P  = .04), stage ≥II ( P  < .01), and R1 or R2 curability ( P  < .01) were independent and significant predictors of OS., Conclusion: Preoperative osteopenia was independently associated with a poor prognosis and recurrence in patients who underwent gastrectomy for GC., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

The Runt-related transcription factor (Runx) family plays various roles in the homeostasis of cartilage. Here, we examined the role of Runx2 and Runx3 for osteoarthritis development in vivo and in vitro. Runx3-knockout mice exhibited accelerated osteoarthritis following surgical induction, accompanied by decreased expression of lubricin and aggrecan. Meanwhile, Runx2 conditional knockout mice showed biphasic phenotypes: heterozygous knockout inhibited osteoarthritis and decreased matrix metallopeptidase 13 (Mmp13) expression, while homozygous knockout of Runx2 accelerated osteoarthritis and reduced type II collagen (Col2a1) expression. Comprehensive transcriptional analyses revealed lubricin and aggrecan as transcriptional target genes of Runx3, and indicated that Runx2 sustained Col2a1 expression through an intron 6 enhancer when Sox9 was decreased. Intra-articular administration of Runx3 adenovirus ameliorated development of surgically induced osteoarthritis. Runx3 protects adult articular cartilage through extracellular matrix protein production under normal conditions, while Runx2 exerts both catabolic and anabolic effects under the inflammatory condition., (© 2022. The Author(s).)

Ectopic endochondral ossification in the tendon/ligament is caused by repetitive mechanical overload or inflammation. Tendon stem/progenitor cells (TSPCs) contribute to tissue repair, and some express lubricin [proteoglycan 4 (PRG4)]. However, the mechanisms of ectopic ossification and association of TSPCs are not yet known. Here, we investigated the characteristics of Prg4-positive ( + ) cells and identified that R-spondin 2 (RSPO2), a WNT activator, is specifically expressed in a distinct Prg4 + TSPC cluster. The Rspo2 + cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. RSPO2 expression levels in patients with ossification of the posterior longitudinal ligament were lower than those in spondylosis patients, and RSPO2 protein suppressed chondrogenic differentiation of human ligament cells. RSPO2 was induced by inflammatory stimulation and mechanical loading via nuclear factor κB. Rspo2 + cells may contribute to tendon/ligament homeostasis under pathogenic conditions.

Background: Jackhammer esophagus (JE) is a hypercontractile esophageal motility disorder diagnosed using high-resolution manometry (HRM). We sought to determine the clinical presentation and therapeutic data of patients with JE in Japan., Methods: The study included patients with JE, diagnosed through HRM performed for suspicious esophageal motility disorders. Demographics, esophagogastroduodenoscopy, radiology, and therapy data were collected from patient charts., Results: Among the 4,412 HRM tests performed, 89 patients (61.6 ± 13.4 years; 64 males, 25 females) were diagnosed with JE (2.0%). Dysphagia was the most frequent symptom (80%), followed by chest pain (40%) and heartburn (25%). Esophagogastroduodenoscopy showed abnormal findings in 32% of patients: corkscrew/rosary beads appearance in 26%, narrowing in 11%. Eosinophilic infiltration (> 15 eosinophils/high power field) was diagnosed in 21%. Esophagography showed abnormal findings in 9% of the patients. For the initial therapy, 47 patients received medical treatment followed by peroral endoscopic myotomy (21 patients) and laparoscopic myotomy (two patients). Thirteen patients did not receive any treatment and 10 of those (77%) reported spontaneous resolution of symptoms. Patients who required invasive treatment experienced severe disability in their quality of life and greater maximal distal contractile integral than those who did not., Conclusions: HRM showed that the prevalence of JE was very low (2%). Esophagogastroduodenoscopy revealed some characteristic features of JE in patients. Some patients showed improvement of symptoms without invasive treatments. Follow-up with/without medical treatment should be considered before performing invasive treatment in patients whose distal contractile integral is relatively low and the quality of life is not impaired., (© 2022. The Author(s).)

Background: The diagnosis and pathological evaluation of esophageal achalasia have been improved dramatically by the development of high-resolution manometry. It is currently known to be divided into three subtypes. However, the differences between subtypes in terms of esophageal clearance remain unclear., Aims: To compare the pathology of subtypes in patients with esophageal achalasia from the perspective of esophageal clearance., Methods: We classified the patients diagnosed with esophageal achalasia into three subtypes based on the high-resolution manometry findings and compared the patient background, esophagography findings, esophageal manometry findings, timed barium esophagogram (TBE) findings, and their symptoms. We also calculated the esophageal clearance rate from TBE to investigate the relationship with the subtypes., Results: There were 71 cases of Type I, 140 cases of Type II, and 10 cases of Type III. No differences by subtype were found in patient background or symptoms. Regarding the esophageal manometry findings, the integrated relaxation pressure was high in Type II (p = 0.0006). The esophagography revealed a mild degree of esophageal flexion in Type III (p = 0.0022) and a high degree of esophageal dilation in Type I and II (p = 0.0227). The esophageal clearance rate in descending order was: Type III, II, and I (height: p = 0.0302, width: p = 0.0008)., Conclusions: The subtypes by high-resolution manometry diagnosis had an association with the esophagography findings and best reflected the esophageal clearance, with no correlation to the patient backgrounds and symptoms., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)